Lecture notes-Tania UnitsI and IV by xusuqin

VIEWS: 52 PAGES: 156

									                   CLINICAL PATHOPHYSIOLOGY
                              PT 711
                             OT 619
                           Spring, 2011

Course Content

Course Director:         Dr. K. Jackson Thomas
                         Office: 341 CHP Building B
                         Phone: (843) 792-4426
                         E-mail: thomaskj@musc.edu

Course Co-Instructor:    Dr. David O. Sword
                         Assistant Professor
                         Office: 304 CHP Building B
                         Phone: (843) 792-o315
                         E-mail: Sworddo@musc.edu



Acknowledgements and many thanks go to Ms. Tania McElveen of the MUSC Division of
Occupational Therapy for her efforts in editing and expanding the Unit I text contained in
this document.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Injury, Inflammation, and Healing
Reference: Goodman and Fuller Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

Definition:     “Altered     function    resulting    in    disease,    injury,   or     death.”
What can cause altered function? Pathologic processes, such as ischemia, infections (viruses,
bacteria, and fungi), tissue degeneration, exposure to toxins, trauma, thermal affect, radiation,
exposure to radiation, electrical shock, and genetic abnormalities may be involved.

Cellular Aging

As cells in various tissues age, they become less able to function and to replace themselves.
Telomere dysfunction, for example, has been associated with aging and cancer in human cells, as
are changes in the mitochondria, cell membrane, and ribosomes. When mitochondrial DNA
undergoes age related changes, the ability of the cell to properly replicate itself is affected.

Aging cells tend to accumulate foreign substances within their cytoplasm, which in turns
hampers function. Lipofuscin, for example, is a well-known pigment that often develops in aging
cells, and is thought to encroach on the cell nucleus and affect function, such as wound healing.
Lipofuscin accumulation might be a symptom of cellular membrane, mitochondrial and/or
lysosomal damage. Lipofuscin is a product of the oxidation of unsaturated fatty acids.
This pigment is associated with aging through ‘wear and tear’ that can accumulate not only in the
skin, but also in nerve cells, heart, muscle, kidney, liver, ganglion cells and adrenals. Lipofuscin
deposits in the skin causing an “Age Spots”.

Beta Amyloid formation
As person ages, some soluble proteins can spontaneously undergo structural and conformational
changes. Such process leads to their aggregation into amyloid fibrils. Even though, there are
enzymes that can possibly partially reverse the damage, amyloid accumulation may contribute to
further damage in various organs and tissues, such as heart and brain. (Lowenson JD, Roher AE,
Clarke S, 1994). In Alzheimer's disease, for example, beta-amyloid accumulates in the brain and
causes nerve cells to weaken and die. Neurofibrillary tangles are pathological protein aggregates
found within neurons in cases of Alzheimer's disease.

How amyloid beta-protein forms? Aβ-protein is formed after sequential cleavage of the amyloid
precursor protein (APP). APP can be processed by α-, β- and γ-secretases; Aβ protein is
generated by successive action of the β and γ secretases. (See the slide).

Free radicals
Once of the most popular theories of aging has to do with the accumulation of free      radicals
secondary to metabolism. Free radicals are oxygen molecules that have given up a pair of
electrons. As these “deprived” oxygen molecules try to replace their lost electrons, they
“borrow” from other tissue molecules, resulting in DNA and tissue damage, thus accelerating the
aging process.

Telomere aging clock theory
Some believe that the telomere aging clock theory is valid, and suggests that structural changes
in the telomere signals the onset of cell senescence. A telomere is a region of repetitive DNA at
the end of chromosomes, which protects the end of the chromosome from destruction. Certainly,
genetics likely plays a role in aging, as does nutrition, exposure to chemicals (i.e. smoking), and
a sedentary lifestyle.

How long we live depends on genes we inherited. In other words, person’s potential lifespan
predetermined at the moment of conception. Some genes are beneficial: for example the gene
that helps effectively metabolize cholesterol would reduce person’s risk of death from heart
conditions. Other genes can be harmful: for example the genes which increase the risk of cancer.
Some gene mutations can happen after conception and after birth. Exposure to radiation, toxins
and free radicals may increase the chance of harmful mutations.
Progeria (Greek-prematurely old) is very rare genetic condition (1 per 8 million live births), that
is not inherited, but occurred as a new mutation. Child with such disorder has symptoms that
resemble aging process which started at an early age. They have small, fragile bodies and they
develop wrinkled skin, loss of hair and loss of eye sight Children with progeria usually live to
their mid teens and they die from typical age related conditions, such as atherosclerosis leading
to heart failure and kidney failure.
Ultimately, an individual will age along with his/her cellular make-up, and even though specific
pathologic changes may differ from one person to the next, observers should see a decrease in
strength and functional reserve for activity, a decline in resistance to infection, and an increase in
the tendency to develop common conditions such as atherosclerosis.

Signs of Aging
•    Decrease in strength and functional reserve for activity
•    Decline in resistance to infection
•    Prone to develop diseases, atherosclerosis

Cell Injury
Cells and tissue may be injured by a number of mechanisms. Often, injuries are reversible and
sub-lethal, so that cells can repair themselves through regeneration. However, if the injury is
severe and of great magnitude, then cells may actually die and repair has to occur via
replacement with non-functional, or scar tissue. Examples of ways that cells and tissue can

become injured include: infectious agents, immune reactions, genetic factors, nutritional
factors, physical factors, and chemical factors.

Apoptosis is a form of programmed death in multicellular organisms. It is one of the main types
of programmed cell death (PCD) and involves a series of biochemical events leading to a
characteristic cell morphology and death, which in more specific terms, implies a series of
biochemical events result in a variety of morphological changes, including blebbing, or changes
to the cell membrane such as loss of membrane asymmetry and attachment, cell shrinkage,
nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation.
Processes of disposal of cellular debris whose results do not damage the organism differentiate
apoptosis      from     necrosis,     which      results    from      injury     and/or    disease.
In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular
injury, apoptosis, in general, confers advantages during an organism's life cycle. For example,
the differentiation of fingers and toes in a developing human embryo occurs because cells
between the fingers undergo apoptosis with the result being that the digits end up being separate.
Current estimates are that between 50 billion and 70 billion cells die each day due to apoptosis in
the average human adult. For an average child between the ages of 8 and 14, approximately 20
billion to 30 billion cells die a day. In a year, this amounts to the proliferation and subsequent
destruction of a mass of cells equal to an individual's body weight!
http://en.wikipedia.org/wiki/Apoptosis.Accessed 1/2/08

Inhibition of apoptosis can result in a number of cancers, autoimmune diseases, inflammatory
diseases, and viral infections.

A. Reversible cell injury. When the magnitude and nature of an injury is not sufficient to result
in actual tissue death, then cellular adaptations to the injury may take place, and eventually
healing without actual tissue loss may occur. The hydropic change noted typifies this adaptive
- Hydropic change, or cloudy swelling, is the accumulation of fluid inside the cell due to failure
of the Na+K+pump. Because of injury to the cell membrane, the enzyme systems, which drive
the pump, are not available. Since Na+ is more heavily concentrated in the extracellular fluid
(ECF) that in the intracellular fluid (ICF), the Na+ ions begin to passively diffuse across the cell
membrane into the ICR. Water travels with the Na+ ions into the ICF, and thus causes cellular
edema and swelling. During the hydropic change, the cell reverts to anaerobic metabolism,
which results in production of excess amount of lactic acid. The resulting drop in pH further
slows down cellular metabolism and impedes active transport mechanisms. During this time,
ribosomes may detach from the endoplasmic reticulum, resulting in decreased protein synthesis.
However, if the cell nucleus remains intact and the toxic stimulus is removed, recovery is quite
possible and the injury to the cell is reversible.
- Intracellular accumulations are common in liver disease. Such accumulations are called a fatty
change. In fatty change, hepatocytes (liver cells) become infiltrated with fat and form fatty
inclusion bodies. This disease process occurs in liver degeneration, or cirrhosis, which is
associated with chronic alcohol abuse, chronic hepatitis, and other liver diseases that will be
presented and discussed later.

Irreversible Cell Injury and Necrosis
If an injurious or stressful stimulus is of sufficient duration or magnitude, or if cells are unable to
adapt, then they will be irreversibly damaged. Irreversible damage implies that cells will die, and
undergo necrosis.
Microscopic changes in necrosis include:
a. The nucleus undergoes fragmentation (karyorrhexis), and may disappear
altogether (karyolysis).
b. The cytoplasm stains red (eosinophilic).
c. The mitochondria become enlarged and develop calcium deposits, and are unable to generate
energy in the form of ATP.
d. Lysosomes release enzymes to begin breaking down and dissolving cells.

General gross changes
Trophic Response: early, general decrease in blood supply to a body part (Occlusive Arterial
Disease- OAD). Symptoms of trophic problems may include scaly, cold and shiny skin, alopecia
(hair loss), subcutaneous tissue “puffy,” and decreased/absent pedal pulse.

 Types of necrosis
a. Fibrinoid necrosis – occurs on the endothelial lining of blood vessels, and is caused by an
accumulation of proteins in the plasma and cellular debris that form deposits.
b. Coagulative necrosis - generally involves a small area of severe ischemia. The tissue is firm,
and resembles egg white after boiling, because the protein undergoes denaturation. Example -
decubitus ulcer
c. Colliquative (Liquefactive) necrosis - lysosomes liberate enzymes; results in tissue breakdown
and liquefaction.
d. Caseation necrosis - type of tissue destruction that is only partial and incomplete. Grossly,
there is a “cheesy” appearance, and is best typified by tuberculosis (caused by the organism
Mycobacterium tuberculosis).
e. Fatty necrosis - type of issue destruction in which normal functioning tissue is replaced by fat
(non-functional). The fatty tissue then binds calcium salts from the body fluid, which gives the
tissue a “chalk” appearance.

Outcomes of necrosis
Pathologic Tissue (Dystrophic) calcification - necrotic tissue binds calcium from the body fluids
to form histoliths (stones embedded in tissues). Myositis ossificans is a common example.
Myositis ossificans may occur in injuries to the thigh muscles, especially the quadriceps. Also,
pathologic tissue calcification occurs in tuberculosis and in atherosclerosis.

Outcomes of necrosis depend on many factors, such as

a)       The type of tissue affected
b)       The size of lesion
c)       Location of lesion

Necrosis can heal or can lead to permanent damage, and can be local or systemic.

The Inflammatory Process.
The body’s response to injury is a natural process called inflammation. Inflammation occurs as
the body attempts to wall off, dilute, and eventually kill an invading foreign body. The natural
cycle of the inflammatory process is as follows: cellular injury, followed by acute inflammation,
then followed by chronic inflammation with granuloma (accumulation of macrophages and
connective tissue) formation. Healing can potentially occur at any stage of the cycle.
A Granuloma is a spherical mass that contains different immune cells. Granuloma occurs when
the immune system attempts to wall off substances, which perceived by the body as foreign
(exp.: bacteria, fungi, foreign bodies, suture fragments), but unable to fully eliminate them.

The inflammatory process has two main phases: dilution and demolition phases.

Dilution phase depends in large on Mast cells

Role of mast cells in inflammation:
Mast cells can be found in any tissues and they appear to play a key role in the initiation of
inflammation. The cytoplasm of mast cells is full of granules, which contain mediators of
inflammation. The outer membrane of mast cells has many receptors, which when activated
trigger exocytose (release) of granules with mediators.

Mast Cells release inflammatory mediators and they initiate the inflammatory process.
Vasoactive Amines-cause vasodilatation and increase vessel permeability
a.     Histamine. Histamine increases the blood flow to the area and the leakage of fluid and
proteins from the blood into the tissue space. Thus the quick release of histamine produces the
redness and swelling associated with inflammation.
b.     Platelet Activation Factor is an important activator and mediator of many leukocyte
functions, including platelet aggregation and inflammatory reactions. It is also involved in
changes to vascular permeability, the oxidative burst (production of various highly reactive
oxygen derivatives by certain cells), chemotaxis of leukocytes, as well as augmentation of
arachidonic acid metabolism in phagocytes.

Cytokines: a category of signaling molecules that are used in cellular communication, similar to
neurotransmitters and hormones. Cytokines help to recruit to white blood cells such as
lymphocytes (T- and B-cells, NK cells), monocytes (that will turn into macrophages when they
leave the vessels and enter the tissues), neutrophils and eosinophils.

a.      Interleukins (1-35)
Interleukin-1 is responsible for triggering the blood clotting cascade, helps to activate T-cells,
decreases blood pressure and induces fever. It causes fever by stimulating the release of
prostaglandins, the chemicals which affect the temperature center in hypothalamus.
b.      Eosinophil chemotactic factor. Eosinophil chemotactic factor: stimulates chemotaxis
(movements according to certain chemicals in their environment) of eosinophils; may be
responsible for accumulation of eosinophils at sites of inflammation and allergic reactions.
c.     Neutrophil chemotactic factor. Neutrophil chemotactic factor: stimulate chemotaxis of

d.     Tumor necrotic factor. All the cells involved in inflammation have receptors for TNF and
are activated by TNF to synthesize more on their own. This positive feedback quickly amplifies
the response.
e.     Bradykinin helps to relax the smooth muscle walls of the arterioles lowering blood
pressure and increasing blood flow to the tissue and makes the capillaries leakier, allowing blood
components to enter the tissue space. These effects (like those of histamine) produce the redness,
warmth, and swelling of inflammation

Derivatives of arachidonic acid (AA):
a.      Thromboxane is a vasoconstrictor and a potent hypertensive agent, and it facilitates
platelet aggregation.
b.       Prostaglandins and leukotrienes have many functions. They make it easier for the WBC
to get to the site of inflammation. Prostaglandins stimulate nerves to send pain message

Mast cell inflammatory mediators increase local vasodilatation, increase vascular permeability
and facilitate an exudate formation.
Exudate is a protein rich fluid that has leaked out of a tissue or its capillaries because of injury or
inflammation (Specific gravity >1.012 and a protein content >2 gm/100mL (2 gm%).

Why Dilution phase is important? Fluid exudate dilutes ECF and fibrin from the exudates
isolates the inflamed area.

The mediator molecules make changes in blood vessels to permit the migration of neutrophils
outside of the blood vessels into the extracellular space . The neutrophils move along a
chemotactic gradient created by the local cells to reach the site of injury.

Non-cellular biochemical reaction on inflammation are activated by bacteria and/or necrosis
include a) complement system, b) coagulation system c) and fibrinolysis system

The acute inflammatory response requires constant stimulation to be sustained. Inflammatory
mediators have short half lives and are quickly degraded in the tissue. Hence, acute inflammation
ceases once the stimulus has been removed.

Cardinal Signs of Inflammation (Dilution phase):

Redness (erythema) - capillary dilatation happens because of the action of histamine and other
vasoactive amine released from the mast cells. Vasoactive amines cause the pre-capillary
sphincters to relax, which allows increased blood flow to the capillary. Vasodilatation then
follows. The caliber of the arteriole and pre-capillary sphincter controls the volume flow into a
capillary bed. In the normal state, the flow is such that some capillaries appear collapsed and
others extremely narrow. With arteriolar dilation and pre-capillary sphincter relaxation, the
increased volume flowing into the capillaries distends them and produces the gross red-purple
discoloration of tissue. Blood flow becomes sluggish and stasis of flow occurs in the affected
capillary segments.

Swelling - increased permeability to fluid due to histamine and vasoactive amine release that
forms a fluid exudate which the venous end cannot handle. Accumulation of protein increases
osmotic pressure and pulls fluid into the tissue space. Swelling also caused by increased ECF
colloid osmotic pressure - osmotic pressure generated by plasma proteins.

Heat - due to increase in blood volume to the involved area. Vasodilation and its resulting
increased blood flow causes the redness and increased heat

Pain – can be caused by several factors such as pressure on sensory nerve endings from leakage
of fluid into the tissue space and bradykinin, a plasma protein found in the fluid exudates.
Plasma, the fluid portion of blood, is high in protein (5.5-7.5 grams/100 ml); bradykinin is one
protein in the total protein found in plasma. Other chemicals, such as histamine and
prostaglandins and lowered pH in ECF (accumulation of CO2) also can cause pain.

Loss of function - the area is painful, swollen, and difficult to use. The loss of function is
probably the result of a neurological reflex in response to pain.

Formation of a Cellular Exudate (Demolition phase)

a.      White blood cell (WBC) pavementation (margination) occurs because of loss of laminar
flow due to stasis of blood flow. In laminar flow, blood has its highest flow velocity at the center
of the blood vessel, with flow decreasing incrementally toward the edges of the blood vessel. In
laminar flow, most white blood cells (and red blood cells) are traveling in the area of highest
velocity, i.e. the center of the blood vessel. As the velocity of blood flow decreases, more and
more white and red blood cells migrate to the edges of the blood vessel, thereby positioning them
to marginate at the edges.
b.      Spaces between the endothelial cells enlarge and granulocytic WBC’s called neutrophils
(polymorphonucleocytes – PMN’s) squeeze through, which defines a process called diapedesis.
Leukocytes immigrate to the site of injury by a process called chemotaxis. Chemotactic factors
can be both endogenous and exogenous. Bacterial products are the most common exogenous
factors. Endogenous agents include components of compliment, leukotrienes and cytokines
Chemotaxis causes the PMN's to migrate toward the foreign body. Various chemical factors
mediate this process, examples of which are cytokines (produced and secreted by white blood
cells), namely eosinophil chemotactic factor (ECF), neutrophil chemotactic factor (NCT) for
mediating chemotaxis. Interleukin-1 (Il-1) increases blood flow, tumor necrosis factor (TNF),
which enhances the effects of Il-1, platelet activating factor (PAF), which enhances the action of
both platelets and white blood cells, and arachidonic acid derivatives (prostaglandins,
thromboxane, and leukotrienes), all of which increase platelet and white blood cell activity and
enhance vascular permeability.
c.      Phagocytosis of necrotic tissue, bacteria and other irritants causes white cell death and
causes suppuration, or pus. Phagocytosis is the ability of the WBC to recognize the pathogen,
form an attachment, engulf it and kill it. Various chemical mediators are important in this
function. Bacterial killing is accomplished mostly by an oxygen-dependent mechanism. Killing
can also occur by the release of granules from the lysosomes. Neutrophils ingest particles by
flowing their cytoplasm around the objects and internalizing them in an envelope of cell
membrane, the phagosome. The digestive enzymes of the lysosomes are then released into the
d.      Fluid dilutes the offending substance, and fibrin in the plasma limits spread of the
Acute vs. Chronic Inflammation

Acute inflammation is an inflammatory episode lasting less than 2 weeks. For inflammation to
end during this time period, the offending agent either has to be removed or destroyed by the
body's defense mechanisms. The hematologic status for an episode of acute inflammation
Leukocytosis -WBC counts above normal. (Normal = 4000-8000 WBC’s/mm3)
PMN’s are elevated and dominate the white blood cell count. PMN's normally comprise about
70% of the total white blood cell count, but in acute inflammation the percentage of PMN's may
go to >90% of the white blood cell count, otherwise known as a “shift to the left” of these white
blood cells.

Stages of acute inflammation
When injury occurs:
Reflex vasoconstriction
Momentarily inhibits bleeding
Vasoactive amine/Cytokine release
Vasodilatation and Bleeding

Chronic inflammation is an inflammatory episode lasting more than 2 weeks. In chronic
inflammation, the offender or irritant remains present and viable. For the episode to end, the
offender must be removed or destroyed by the body's defense mechanisms (i.e. the immune
system). Because the body is fighting to rid itself of the offender or irritant, chronic
inflammatory episodes place tremendous stress on energy resources. Many individuals with long
term inflammation show weight loss, fatigue, decreased cognitive abilities, and other signs of
stress. Development of a malignancy may also be an outcome of chronic inflammation. The
hematologic status in chronic inflammation includes:
Return of PMN's to normal (shift to the right) or depressed levels and subsequent elevation of
other white blood cells, i.e. monocytes (also known as a macrophages when they appear in the
cellular exudate) and lymphocytes (known as agranulocytes).
There may be a mild leukocytosis or even a leukocytopenia (decreased overall white blood cell

Inflammation is a homeostatic mechanism that allows the body to defend itself against a foreign
Thus, inflammation produces several outcomes that may be regarded as desirable. Examples
1) inflammation walls off an invading foreign body due to fibrin in the fluid exudate;
2) the fluid exudate produced by inflammation dilutes the concentration of the foreign body, and;
3) white blood cells in the cellular exudate kill foreign bodies by phagocytizing them
While inflammation is recognized as an important homeostatic mechanism of defense, an
episode may produce undesirable side effects. These include:
1) lassitude (fatigue and loss of energy);
2) loss of appetite (anorexia);
3) fever;
4) varying other disabilities, such as prostration, and;
5) acute phase reaction or synthesis of acute phase proteins,
 Acute phase reactions are likely mediated by cytokines that are produced by white blood cells
involved in the inflammatory reaction.
Fever during inflammation is likely caused by the action of such cytokines on the temperature
regulating areas of the hypothalamus. Also, cytokine mediated stimulation of the bone marrow
results in increase release of white blood cells into the circulation.
Acute phase proteins are synthesized by the liver, and include C-reactive protein, serum amyloid
associated protein (SAAP), and others involved with blood coagulation and the immune
response. These proteins may attach to erythrocytes (red blood cells) and increase viscosity of
the blood and cause an increased erythrocyte sedimentation rate (ESR).
Increased ESR's, when present, generally typify the presence of inflammation.
Positive APPs ( acute phase proteins) are proteins that are increased during acute phase response.
Positive acute-phase proteins serve different physiological functions in the immune response
a.       act to destroy or inhibit growth of microbes, (C-reactive protein, Mannose-binding
protein, complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin.
b.        give negative feedback on the inflammatory response, e.g. serum protease inhibitors or
c.       Affect coagulation by stimulating it, e.g. alpha 2-macroglobulin and coagulation factors
This effect may limit infection by trapping pathogens in local blood clots.
d.       contribute to the innate immune system by their ability to increase vascular permeability
and act as chemotactic agents for phagocytic cells.

Negative APPs are proteins that are decreased during acute phase response
Examples include albumin, transferrin, transthyretin, retinol-binding protein, anti-thrombin, and
transcortin. The decrease of such proteins may be used as markers of inflammation. The
physiological role of decreased synthesis of such proteins is generally to provide amino acids in
order to produce "positive" acute-phase proteins more efficiently

Tests for inflammation
Acute-phase proteins-APP (from the Liver)
C-reactive protein (CRP)
The CRP blood test is a non-specific marker of inflammation in the arteries. A CRP level of less
than 1.0 milligrams per liter of blood classifies as low risk for cardiovascular disease, 1.0 to 2.9
milligrams is intermediate risk and more than 3.0 milligrams is high risk.

Serum amyloid associated protein (SAAP) or Acute-phase serum amyloid A proteins are secreted
during the acute phase of inflammation.

Increased erythrocyte sedimentation rate (ESR)
Elevated ESR is associated with processes such as protein attachment to red blood cells and
increased blood viscosity.
Inflammation changes the proteins in red blood cells causing them to bind to one another in
clumps, making them denser than normal red blood cells. An ESR test simply notes the speed at
which blood cells sink to the bottom of a test tube. The faster the blood cells fall, the more
inflammation is in your body.
ESR normal values:

                 Age   20            55           90
                 Men   12            14           19
                 Women 18            21           23

Outcomes of necrosis and cell death
Healing-Resolution (Minimal Damage)
Healing-Replacement of Tissue (metaplasia)
Dystrophic Calcification - Myositis Ossificans
Super-infection forming Gangrene

Necrotic tissue may be replaced by regenerating normal tissue, and may bind calcium from the
body fluids to cause dystrophic calcification. Areas of necrosis may become superinfected with
bacteria, of which a common outcome is gangrene (genus Clostridium). Gangrene may be
described as “dry”, “wet”, or “gas” gangrene (see lecture slides for examples).
“Dry” gangrene – ischemia with a line of demarcation;
“Wet” gangrene - moist, progressive, infected with Clostridium;
“Gas” gangrene - edema, foul odor from H2, N2 and CO2 gas-Infected with Clostridium.

Tissue Healing

When discussing healing and repair, the following tissue types should be considered. There are
four morphologically different tissue types: nerve, muscle, epidermal, connective ( including
bone and cartilage) and three types of regeneration processes:
1. Labile, also called Vegetative Intermitotics.
Examples: Bone marrow, epidermal lining of the GI tract, and skin. These cells normally
replace themselves on a periodic basis.
2. Stable, also called Vegetative post-mitotics.
Example: liver. These cells normally replace themselves only following injury.
3. Permanent, also called Fixed post-mitotics.
Examples: Central nervous system, cardiac muscle, and kidney. Cells will hypertrophy to take
the place of lost cells.

The process of tissue healing begins soon after tissue injury or tissue death has   occurred, and
takes place either by regeneration (resolution-regrowth of original tissue)      or   by    repair
(replacement of original tissue with a connective tissue scar).

1. Regeneration/Resolution:
In healing by regeneration, there must be irreversible injury to tissue cells, and no actual
destruction of tissue. The offending agent is removed and inflamed tissue is left or replaced
exactly as it was before the injury. Characteristics:
Minimum tissue destruction
Offender removed
Original tissue replaced
No Scarring
Different tissue replaced than original is called Metaplasia
2. Repair: Depending on the degree of tissue necrosis, healing can proceed in one of two ways,
i.e. either by primary intention or by secondary intention. In either case, necrotic tissue must be
removed from the injured site before healing can occur.

a. Primary intention: In healing by primary intention, the edges of a wound are in close
approximation to each other. Repair occurs with a minor degree of scarring and loss of function.
To heal by primary intention, a wound must progress in the following manner:
- Edges of the wound are bound together by a blood clot.
- Inflammatory reaction causes WBC’s to enter the blood clot and break down as they attack and
kill bacteria and other foreign bodies.
- Organization - fibroblast synthesis of fibronectin, proteoglycans, elastin, and several kinds of
collagen (granulation tissue), which matures as a scar.
-Re-epithelialization must occur over an organized clot.
-Rapid healing (7-10 days)

b. Secondary intention: In healing by secondary intention, wound edges are not close together.
Healing follows the same order as primary intention, except:
-The wound takes much longer to heal;
-A larger scar is formed;
-A cicatrix (scar) is formed with wound contracture, causing more potential for permanent
In some individuals (young women, African Americans, and persons of Mediterranean descent),
scarring on the skin can be severe, due to deposition of Type III collagen (granulation tissue)
rather than Type I Collagen. Collagen is one of the long, fibrous structural proteins whose
functions are quite different from those of globular proteins such as enzymes. This is referred to
as keloid formation, or hypertrophic scarring. There are more than 28 types of collagen
described in the literature; however, over 90% of the collagen in the body is of type I, II, III, and


      c. Webster.com dictionary entry
      d. Kerr, JF. (1965). "A histochemical study of hypertrophy and ischaemic injury of rat
         liver with special reference to changes in lysosomes". Journal of Pathology and
         Bacteriology 90 (90): 419–35. doi:10.1002/path.1700900210.
      e. Agency for Science, Technology and Research. "Prof Andrew H. Wyllie - Lecture
         Abstract". Retrieved on 2007-03-30.
      f. Kerr JF, Wyllie AH, Currie AR (Aug 1972). "Apoptosis: a basic biological
         phenomenon with wide-ranging implications in tissue kinetics". Br. J. Cancer 26 (4):
         239–57. PMID 4561027.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

The Immune System: Function and Immunopathology
Reference: Goodman and Fuller, et al. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunters/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

Definition: “Physiologic mechanism which allows a person to recognize foreign invaders
and inactivate them without injury to the host tissue.”

Types of the Immunity

Innate and Acquired Immunity.
Innate immunity acts as the body’s first line of defense to prevent entry of pathogens, and
consists of 2 basic systems: first, the skin and mucosal barriers, and second, the inflammatory
response that occurs when a foreign substance is introduced and cells are injured. Natural Killer
cells play the crucial role. Acquired immunity is defined by the ability of the body’s immune
system to specifically recognize and inactivate foreign substances without injury to other host
tissue. Acquired immunity occurs after exposure to a foreign substance after birth.

Innate Immunity

In addition to natural barriers and the inflammatory response, which is induced by white blood
cells ( i.e. monocytes, neutrophils) and other cells (i.e. macrophages and mast cells, innate
immunity also utilizes natural killer (NK) lymphocytes to protect an individual from disease. NK
lymphocytes were discovered in the early 1970’s, and are not “thymic educated” (see below) and
thus operate independently of the thymus gland. They do not have to be sensitized to become
operative, and are the lymphocytes that perform the surveillance function of seeking out and
destroying abnormally developing tissue and cells, i.e. cancer cells or other abnormally mutated
cells. They destroy these cells by producing perforins and/or proteases (both called granenzymes,
which penetrate the abnormal cell’s membrane and cause it to fragment and die.
Even thought NK cells appear to have natural killing ability, there are certain conditions and
factors that have been shown to activate them.
Cytokines (IFNα/β, IFNγ, IL-2) play a crucial role in NK-cell activation. As these are stress-
molecules released by presence of a foreign agent, they serve to signal to the NK cell the
presence of such. NK cells express the FcR molecule, an activating receptor which binds the Fc
portion of antibodies. This allows Natural Killer cells to target and attack foreign bodies that
have been immobilized by antibodies. Aside from the FcR receptor, Natural Killer cells express a
variety of receptors which serve to either activate or suppress cytolytic activity. These have an
important role in regulating the NK-cell response.

Acquired Immunity: Active and Passive Immunity

   A. Passive immunity is resistance to a foreign body that is acquired by receiving antibodies
from another person. Passive immunity occurs in infants who are breast fed, and in fetuses, as
they receive IgG from the maternal circulation. Passive immunity is also induced by vaccination
with previously formed antibodies (smallpox, rabies, measles, and tetanus). These forms of
acquired immunity are very quick and effective, but, unfortunately, are only temporary in their
    B. Active immunity is resistance to a foreign body that occurs as a result of contact with
the foreign body itself. Contact may occur via infection, immunization with a live or attenuated
antigen, or via transplantation of foreign cells or organs. In active immunity, the individual
actively produces antibodies and sensitized lymphocytes in response to the antigen. In such
exposure, the active immunity acquired is long term, but typically has a slow onset.

The Immune Response

When activated, the immune response goes through the following phases:
1. Recognition of a foreign material (induction, or the afferent limb of the reaction);
2. Elimination of the foreign invader (the efferent limb of the reaction);
3. Resolution of the immune reaction with sparring of injury to normal host tissue.

Phase 1: Recognition and elimination are served by the basic immune functions of: 1) defense,
which implies protection against foreign invaders such as bacteria and viruses, and 2)
surveillance, which implies protection against abnormal and potentially harmful tissue such as
malignant tumors. Any foreign body of this nature is referred to as an antigen, because it has a
different cell make up than the body’s own tissue. Once the body’s immune system attacks and
destroys the antigen, lack of injury to normal host tissue is served by the basic immune function
of maintenance of homeostasis. Homeostasis is the body’s normal functioning environment.
Induction phase, or recognition of foreign material. Induction begins with the introduction of an
antigen into the host’s system. Antigenic substances are determined by their major
histocompatibility complex (MHC), which is a group of genetically determined molecules located
in the chromosomes (in humans, MCH has been found to exist on the 6th chromosome). MHC’s
were originally found on leukocytes, and were thus referred to as human leukocytic antigens
(HLA’s). The MHC serves as a “cell marker,” and is unique among individuals. MHC thus
varies from one individual to the next, and allows one’s own body makeup to exist and to be
recognized by his/her immune system as being endemic and non-foreign. To become antigenic,
a tissue cell has genetically determined epitopes on its outer surface. The epitopes are
determined by the MHC, and are the portion of the cell that is recognized by the immune system
as being “foreign”. Generally, antigens have a high molecular weight (greater than 100,000
Daltons), and are proteins. Small molecular weight substances generally do not provoke an
immune response on their own, are, thus, non-allergenic. However, certain small molecular
weight substances can act as antigens by becoming haptens. Haptens are small molecular weight
substances that bind to a large protein carrier in the plasma proteins and become antigenic.
The Major Histocompatibility Complex (MHC) is a set of molecules displayed on cell surfaces
that are responsible for lymphocyte recognition and "antigen presentation". The MHC molecules
control the immune response through recognition of "self" and "non-self" and, consequently,
serve as targets in transplantation rejection.
The MHC is encoded by several genes located on human chromosome 6.
Antigen vector-
Antigen dissemination in the body can take two different routes: through lymphatic system
(lymphogenous) and through blood vascular system (hematogenous)
When antigen entered the lymphatic system following will occur:
-Antigen is taken to the Lymph nodes
-Antigens Stimulate “Naïve” Lymphocytes
-Release Transfer Factor (TF)
-“Sensitized” Memory Lymphocytes Produced. Memory Lymphocytes are responsible for Initiate
Immune Response and they also Accelerate Immune Response in the case of Next Exposure.
In the blood vascular system:
-Naïve Lymphocytes are Stimulated
-Information Transferred to Lymph Nodes
-“Sensitized “Memory Lymphocytes Released

Phase 2: or elimination of the foreign invader. Elimination of foreign material occurs via two
different systems, the cell mediated response and the humeral response.
The cell mediated response works from T lymphocytes (CD4, CD8 lymphocytes), whereas the
humeral response works from B-lymphocytes.

Humeral Immunity. B-lymphocytes are produced in the bone marrow, and each has a receptor
for recognizing a specific antigen. When the antigen interacts with the B-lymphocyte, the result
is the production of antibodies. The following schematic explains this function:

Antigen → reacts with the receptor site of a B-lymphocyte and **CD4 helper T lymphocytes are
activated and release lymphokines. At this point, the antigen may become structurally altered,
so that B-lymphocytes are stimulated. B-lymphocytes then form plasma cells, which produce
antibodies to the antigen.
An antigen-antibody complex is thus formed, which, in turn, activates the immune complement
system. Immune complements are produced in a cascade fashion, resulting in the ultimate
distraction of the foreign invader. The immune complement system is also known as a soluble
mediator. The complement system consists of small proteins found in the blood, mostly
produced by the liver, and normally circulating as inactive molecules. Several triggers can
stimulate complement system and cause the cascade of reactions. The main functions of
complement reactions are: lysis of foreign bodies, enhance opsonisation, increase chemotaxis by
attracting leucocytes. (An opsonin is any molecule that “coats” and acts as binding enhancers for
the process of destruction and ultimate phagocytosis of an antigen).

     Activation of the Immune Complement Cascade

Destruction of a foreign body following formation of an antigen-antibody complex and activation
of the immune complement system

When a foreign substance enters the body causing the formation of antibodies, the event is called
a primary immune response. Appearance of specific antibodies usually then occurs after about 7-
10 days, reflecting a clone of B-lymphocytes that form plasma cells. The first antibodies that are
formed are IgM, followed by IgG and IgA (see below). Months and/or years after initial
exposure, when a second exposure occurs, the sensitized person has a secondary immune
response. This response occurs more rapidly than the primary immune response, because of the
presence of memory cells left over from the first contact with the foreign body. The memory
cells rapidly proliferated to form a large clone of B cells capable of producing IgM as during
the primary immune response. The resulting production of IgG, however, is much larger, and
tends to persist much longer. In addition, the IgG tends to bind with the foreign body more
tightly and inactivate or clear it from the body more quickly and effectively.
Antibodies. Antibodies are proteins produced by plasma cells to combat a specific foreign agent.
The proteins are called immunoglobulins. Immunoglobulins are high molecular weight proteins
that are composed of 2 heavy (H) polypeptide chains and 2 light (L) polypeptide chains.

Antibody Schematic Structure showing H chains and L chains and disulfide bonds

Shows 2 reactive binding sites - most antibodies are bivalent with variable and constant portions

H chains - classification of antibodies depends upon the amino acid sequence in its construction,
and there are 5 known antibody classes:
1.      IgG 80% of total circulating body fluids, There are four IgG subclasses (IgG1, 2, 3
and 4) in humans, named in order of their abundance in serum (IgG1 being the most abundant-
about 67%)).
2.      IgM is usually first immunoglobulin to be produced, and may be an lgG precursor. IgM is
a basic antibody that is present on B lymphocytes. It is the primary antibody against A and B
antigens on red blood cells, and is by far the physically largest antibody in the human circulatory
3.      IgA is attached to mucosal surfaces. More IgA is produced in mucosal linings than all
other types of antibody combined. In its secretory form, IgA is the main immunoglobulin found
in mucous secretions, including tears, saliva, colostrum, intestinal secretions, vaginal fluid and
secretions from the prostate and respiratory epithelium. It is also found in small amounts in
blood. Because it is resistant to degradation by enzymes, IgA can survive in harsh environments
such as the digestive and respiratory tracts, to provide protection against microbes that multiply
in body secretions.
4.      IgE was discovered as recently as 1966 and is attached to mast cells and is capable of
triggering the strongest immune reactions. It plays an important role in allergy, and is especially
associated with type 1 hypersensitivity. IgE has also been implicated in immune system
responses to most parasitic worms like and may be important during immune defense against
certain protozoan parasites
5.        IgD is an antibody that makes up about 1% of proteins in the plasma membranes of
immature B-lymphocytes where it is usually co expressed with another cell surface antibody
called IgM. IgD is also produced in a secreted form that is found in very small amounts in blood

serum. IgD's function is to signal when the young B cells in the spleen are ready to be activated.
By being activated, they are ready to take part in the defense of the body in the immune system.

L chains – these also depend upon amino acid sequence, but are not considered in classifying the
antibody. L chains exist as two basic structural types, i.e. a kappa segment and a lambda

                        Kappa segment (black)
                               Lambda segment (gray)

L chains may appear in the urine as Bence Jones protein (BJP) in myelodysplastic          diseases,
such as multiple myeloma (BJP may also be present in other diseases as well, such as renal
failure, lytic bone disease, or anemia). L chains in urine precipitate at 50-60° centigrade, and re-
dissolve upon heating to 90-100° C, so that their identity may be established in this fashion.

Multiple myeloma can also be diagnosed with protein electrophoresis, which shows the
formation of a monoclonal peak.
Multiple myeloma is a malignant disease of the bone marrow and is associated with an
overproduction of plasma cells, thus it may be referred to as a plasma cell dyscrasia. The
plasma cells cause overproduction of immunoglobulins, which increase blood viscosity and
overload the circulation system. Red blood cell counts and platelet counts fall, leaving the
individual anemic and at risk to bleed internally. Calcium releases from the bones and it will be
possible to see “punched out “ lesions on the X-rays of the bones. Calcium/uric acid kidney
stone may form. Patients may also have symptoms of gout. As the bone marrow breaks down,
pathologic fractures may occur and calcium is released excessively into the blood resulting in
actual stone formation. Also, due to loss of bone integrity, the patient may be in severe pain.
Mean survival in multiple myeloma is 2-4 years (American Cancer Society). Diagnosis can be
based on: presence of Bence-Jones protein in the patient’s urine, bone marrow biopsy, X ray
(punched out lesions), and plasma protein electrophoresis (monoclonal peak)

       Normal protein electrophoresis                     Protein electrophoresis of
                                           serum and of urine showing
                                        a monoclonal peak

Another plasma cell dyscrasia is Waldenstrom’s macroglobulenemia. In this disease, B-
lymphocytes and plasma cells infiltrate the bone marrow. Destruction of bone marrow is rare, but
the infiltrating cells produce large amounts of IgM, which causes increased plasma volume and
severe plasma hyper-viscosity. Usually patients do not have any bone destraction. Symptoms of
WM include weakness, fatigue, weight loss and chronic oozing of blood from the nose and
gums. Lymphadenopathy, splenomegaly, and hepatomegaly may be seen. The laboratory
diagnosis of Waldenström macroglobulinemia is contingent on demonstrating a significant

monoclonal IgM spike and identifying malignant cells consistent with Waldenström
macroglobulinemia (usually found in bone marrow biopsy samples and aspirates).
The progress of the disease is much like non-Hodgkin’s lymphoma, and the median survival rate
is about 4 years.

Cell Mediated Immunity. T-lymphocytes are “thymic educated,” i.e. they are programmed by the
thymus gland during the first years of life for their immune function. The following pathway
explains their activation and function.

Antigen → reacts with the **CD4 helper T lymphocytes, which are activated and release
lymphokines. The lymphokines in turn activate the CD8 (cytotoxic) lymphocytes, which in turn
become macrophages and release perforins. Perforins cause the antigen to break down.

Please note that the double asterisks (**) in both the above pathways for humeral and cell
mediated immunity indicates that the CD4 helper cells are the white blood cell population that is
attacked by the AIDS virus, i.e. HIV. Destruction of this population of cells causes a block in the
pathway, leading to immunodeficiency. Also, a subset of CD8 cells exists that are regulatory in
nature. These are the T-lymphocytes that have a suppressor function, in that they modulate or
"turn off" the CD4 and cytotoxic CD8 T cells so as to act as an antagonist to their action.

Another type of “cell mediated” immunity comes from the NK lymphocytes. These white blood
cells are not “thymic educated,” and thus operate innately and independently of the thymus. NK
cells do not have to be sensitized to become operative, and are the lymphocytes that perform the
surveillance function of seeking out and destroying abnormally developing tissue and cells, i.e.
cancer cells and cells with MHC variations. They have similarities to T lymphocytes, and
destroy antigens in the same manner as cytotoxic CD8 lymphocytes, that is, by producing
perforins from target oriented granules, which penetrate the antigen’s cell membrane. The figure
below gives a diagrammatic representation of their action against foreign bodies.

NK Cell Activation and Interaction with Antibodies
FcR receptor
        -NK cells express the FcR molecule, an activating receptor which binds the Fc portion
of antibodies.
        -This allows Natural Killer cells to target and attack foreign bodies that have been
immobilized by antibodies.

Cell Mediated Response
T Lymphocytes:
CD4 T Cells (Helper)
CD8 T Cells (Regulatory)
Cytotoxic T Cells
Memory T Cells
Natural Killer T Cells
Gamma Delta T Cells

Immune system and Aging process

A. Changes in innate immunity that are associated with aging include thinning of the skin,
decreased GI tract acidity, shallow breathing, less acidic urine, and a less elastic bladder that may
result in urine retention. White blood cells lose motility and function, immune complement
levels may increase, and NK cell function may decrease.
B. Changes in acquired immunity that are associated with aging include involution
of the thymus, with a subsequent decline in the numbers of T-lymphocytes. In addition to
diminished T-lymphocytes, antibody production declines as B-lymphocyte function ages. Also,
the tendency to form autoantibodies increases, and thus facilitates development of various
autoimmune diseases (rheumatoid arthritis, regional enteritis, autoimmune thyroiditis,
scleroderma, etc.). Genetic mutations of cells are also more frequent with advancing age, and the
tendency of mutated cells to self-destruct (apoptosis) declines.
C. As individuals and their immune systems age, problems may present to occupational and
physical therapists that have important implications for treatment. For example, autoimmune
diseases can affect joints and soft tissue, and have dramatic consequences for movement,
mobility, and quality of life. Thinning of the skin may cause older individuals to be less resistant
to pressure sores, whereas changes in the GI system may negatively affect nutrition. Elderly
person might have decreased appetite and decreased absorption. Decreased elasticity of the
urinary tract may lead to incontinence and urine retention, which in term may provoke urinary
tract infections. Loss of immune competence among T-lymphocytes and B-lymphocytes causes
potential decreased ability of older individuals for fight infection. Finally, increased tendency to
develop autoantibodies may cause a number of diseases that are primary diagnostic reasons for
referral to physical therapy, especially if they affect mobility and/or cause chronic pain.

Frequency of autoimmune diseases can rise (Rheumatoid Arthritis). Person can be less resistant
to pressure sores because of thinner skin.

Interactions between the immune and central nervous system (CNS)

A. The immune system and the CNS communicate bi-directionally, i.e. one can influence the
other and vice versa. Psychogenic stress, for example, can influence the white blood cell count in
a negative fashion and reduce the effectiveness of both B-lymphocytes and T-lymphocytes. Also,
white blood cells my travel to the CNS, where they secrete cytokines (leukotrienes,
prostaglandins, for example) in order to fight infection by foreign agents.
B. Glial cells may also play an immune role, and secrete various neurocytokines, which promote
healing when there has been an injury to the CNS; however, they may affect personality in a
negative way, and cause memory loss, sleep disturbance, confusion, and dementia.

Exercise and Immunology

A. Exercise may have some significant effects on the immune system. Following a bout of acute
exercise, the white blood cell population in the blood rises, as does the NK cell population
(however, these populations tend to return to baseline or below baseline after exercise).
Strenuous exercise done for long periods of time may actually reduce the white blood cell
population and promote the release of cytokines that activate the immune complement system
and cause an acute phase reaction. Exercise generally increases apoptosis.
B. Persons with mild signs of infection may exercise in a light to moderate fashion (i.e. an
upper respiratory infections). In cases of more severe symptoms (i.e. fever), exercise should
probably be avoided entirely.

Immunodeficiency Diseases-Primary vs. Secondary Immunodeficiency

A. In primary immunodeficiency, an individual is born with a poorly functioning immune
system. Examples of primary immunodeficiency include:
1. X-linked agammaglobulinemia (Bruton’s agammaglobulinemia)– immunological deficiency,
first described in 1952, which manifests from late infancy and typically results in frequent
bacterial infections commencing in the second half of the first year of life: tonsils and lymph
nodes are very small; marked decrease of serum immunoglobulins of all types (maternal IgG
gives some protection in early infancy) Bruton’s is a congenital B cell deficiency, which results
in recurrent or chronic infections such as Haemophilus influenza, Streptococcus pneumoniae,
and various strains of staphylococci. http://atlasgeneticsoncology.org/Kprones/BrutonAgammaID10023.html

2. DiGeorge’s syndrome – DiGeorge syndrome (also called 22q11 deletion syndrome, congenital
thymic hypoplasia, or third and fourth pharyngeal pouch syndrome) is a birth defect that is
caused by an abnormality in chromosome 22 and affects the baby's immune system. The disorder
is marked by absence or underdevelopment of the thymus and parathyroid glands. The disorder
is named for Angelo DiGeorge, the pediatrician who first described it in 1965. Some researchers
prefer to call it DiGeorgeanomaly, or DGA, rather than DiGeorge syndrome, on the grounds that
the defects associated with the disorder represent the failure of a part of the human embryo to
develop normally rather than a collection of symptoms caused by a single disease. Please see the

following web site.     http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?requestURI=/healthat
   oz/Atoz/ency/digeorge_syndrome.jsp. Accessed 1/3/08

3. Severe combined immune deficiency syndrome (SCIDS)–severe combined immunodeficiency,
or SCID, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune
system are deficient, due to a defect in one of several possible genes. SCID is a severe form of
heritable immunodeficiency. It is also known as the "bubble boy" disease because its victims are
extremely vulnerable to infectious diseases. The most famous case is the boy David Vetter. SCID
affects about 1 in 100,000 live births. These babies, if untreated, usually die within 1 year due to
severe, recurrent infections. Chronic diarrhea, ear infections, recurrent Pneumocystis carinii
pneumonia, and profuse oral candidiasis commonly occur. Treatment options are much improved
since David Vetter, and living in a bubble is no longer necessary. This congenital disorder was
the subject of a “made for TV” movie of years past entitled “The Boy in a Bubble”. In the
movie, David Vetter (played by a young John Travolta), who was born with SCID S was kept in
total isolation, and a glass room was developed for him, with filtered air, and a communication
system to try and make his life as normal as possible. He eventually, however, developed an
opportunistic infection (EBV) and died from complications. Most often, children born with
SCIDS die within their first year, due to overwhelming bacterial, fungal, and viral infections.

B. In secondary immunodeficiency, an individual acquires immune dysfunction either by
disease, by medication, or other secondary cause.

1. Acquired immunodeficiency syndrome (AIDS). In this disease, the human immunodeficiency
virus (HIV) is introduced via sexual contact, infected needles or through infected blood
transfusions. Two types of HIV have been identified, i.e. HIV-1 and HIV-2, with HIV-1 being
the most common cause of AIDS in the US. The virus attacks the CD-4 cell population, which
deactivates the immune system. Opportunistic infections, cancer (Kaposi’s sarcoma, non-
Hodgkin’s lymphoma) then affect the host, causing illness and, ultimately, death. One of the
opportunistic infections commonly suffered by AIDS patients is due to pneumocystis carinii.,
which causes pneumonia and is often a terminal event. Many individuals with AIDS have
hepatitis C as well, although all systems may be affected (CNS, PNS, GI tract, skin,
cardiopulmonary, etc.). AIDS patients typically experience severe diarrhea, neurologic deficits
and dementia, and marked weight loss. In 1992, the Centers for Disease Control (CDC) defined
the definition of active AIDS to include individuals who are infected with HIV-1 (viral load) and
have a CD4 cell count below 200/ml (normal 600-1200 ml). Please read carefully Goodman
and Fuller pp 257-274 for more information on this important disease.

2. Pharmacologically induced immunodeficiency – occurs secondary to medicines used to reduce
the graft – host reaction following organ transplants. Examples:
Cyclosporin-inhibit T cells
Azathioprine (Imuran)-inhibits wbc proliferation
as well as with corticosteroids used to treat inflammatory conditions.

3. Chronic Fatigue Syndrome (CFS) and Immune Dysfunction Syndrome. Chronic fatigue
syndrome (CFS) was identified as a disease entity in the
late 1970’s. Symptoms include extreme loss of energy and endurance for activity, non-specific
constitutional symptoms, and painful muscular areas. CFS likely has several etiologies, including
a recent infection as well as behavioral factors. Formerly, the disorder was thought to be
specifically due to infection with the Epstein-Barr virus, (EBC-which has been linked to
infectious mononucleosis), but specific evidence to support this belief is lacking. Presently, the
overarching view of CFS is that it may be the result of increased production of certain cytokines.
Other theories also exist, but none are conclusive at this time. Symptoms include: severe fatigue
lasting 6 months or longer that is not improved by rest, difficulty with memory and
concentration, muscle pain, and flu-like symptoms. Patients with CFS typically suffer
depression, and may become much unmotivated to re-achieve their function. They must be
given empathy and understanding, as they are still regarded by some as “symptom magnifiers.”
Presently, there are no specific markers for CFS.

4. Please consult the following list for diseases causing hypo-immunity. Use your text, another
pathology book, or perform a search on line to learn more about these diseases and ways that that
affect a person having such a disorder.

                 Ataxia-telangiectasia
                 Chediak-Higashi syndrome
                 Combined immunodeficiency disease
                 Complement deficiencies
                 DiGeorge syndrome
                 Hypogammaglobulinemia
                 Job syndrome
                 Leukocyte adhesion defects
                 Panhypogammaglobulinemia
                 Bruton’s disease
                 Congenital agammaglobulinemia
                 Selective deficiency of IgA
                 Wiscott-Aldrich syndrome

Autoimmune Diseases

An autoimmune disease develops when the body forms antibodies to its own protein. At this
point, some 56 autoimmune diseases have been identified (see table 7-5 p 280 in Goodman and
Fuller for a partial list of autoimmune diseases).
Autoimmune diseases can be systemic or organ specific. General manifestations are:
constitutional symptoms (loss of appetite, fatigue, mild fever) migratory joint pain, leukopenia,
thrombocytopenia, and anemia. Persons with an autoimmune disease will usually have an
increased erythrocyte sedimentation rate (ESR).
Examples of autoimmune disease
1. Lupus Erythematosus (LE). LE is a disease that occurs primarily in
women, and can be localized to the skin (discoid lupus) or systemic (SLE), which involves
multiple organ systems. One of the most common signs of lupus is a butterfly rash (about 80%
of individuals with LE have this), which occurs over the nose and extends onto the cheeks and
face. Little patches of dilated capillaries (telangiectasias) are also common. Also, in SLE, a
common complication occurs in the kidneys, as the disease affects the renal vasculature and
results in hypertension and renal failure.
2. Fibromyalgia. Fibromyalgia is a chronic muscle pain syndrome, and for a specific diagnosis,
the affected person must have 11-18 painful, tender points (see Figure 7-28, p 292 in Goodman
and Fuller). Presently, fibromyalgia is the most common musculoskeletal condition in the US,
and is characterized by muscle pain on both sides of the body in various muscle groups, i.e. neck,
back, arms, legs, jaw, feet, and hands. For a complete of symptoms of fibromyalgia, see Table 7-
6 on p 293 in Goodman and Fuller. The etiology of fibromyalgia is not known, but there is
suspicion that thyroid dysfunction or release of pro-inflammatory cytokines (interleukin-,
interferon-) be the cause.

Hypersensitivity Disorders

Type I – anaphylaxis, or allergy. This immune reaction is IgE mediated. If the reaction occurs in
the bronchial smooth muscle, it may cause the muscle to spasmodically contract, i.e. bronchial
asthma. Anaphylaxis results in widespread fluid leakage into the tissues, and, as a result, wide
spread edema. The affected person may go into circulatory shock with rapid decline in blood
pressure, as well as respiratory failure.
Pathogenesis of a Type I (anaphylactic) hyper-immune reaction

Type II - Cytotoxic – hemolytic. This immune hypersensitivity reaction occurs when
incompatible blood types are mixed, and would thus constitute an adverse reaction to a blood
transfusion. In Type II reactions, circulating IgG or IgM unites with epitopes on the surface of
the antigen. This outcome results in accelerated phagocytosis and/or lysis of the target cell after
activation of the complement cascade. If the target cell is a bacterium, then this outcome is
beneficial. If, however, the target cell is one of the body's own cell (such as an erythrocyte), then
hemolysis occurs. In ABO incompatibility resulting from transfusion of mismatched blood,
massive hemolysis occurs, with subsequent intravascular clotting, loss of circulation, and shock.

Pathogenesis of a Type II (hemolytic) hyper-immune reaction

Type III - Increased accumulations of immune complexes. In this reaction, antigens combine with
antibodies in the circulation to form circulating immune complexes, which are then deposited
into various tissues and organ sites (such as the kidneys). Organs risk damage and malfunction
subsequent to this event. Certain disease states can cause Type III immune reactions, i.e.
rheumatoid arthritis and glomerulonephritis. In these diseases, immune complexes are formed
that activate the complement cascade resulting in damage to joints, skin, and kidneys.

Pathogenesis of a Type III (circulating immune complexes) hyper-immune reaction

Antigens Combine With Antibodies to form circulating immune complexes
– Immune Complex Precipitation
– Immune Compliment System is Activated
– Small Blood Vessel Inflammation
– Potential Multiple Organ Involvement

– Lupus erythematosus
– Polyarteritis nodosa
– Immune complex mediated serum sickness

Type IV – Delayed reactions (takes 24-72 hours to develop)
Cellular – graft vs. host reaction. This immune complex reaction occurs following an organ or
tissue transplant between individuals (i.e. a homograft)). Other examples of the reaction are
those seen with allergic contact dermatitis (i.e. poison ivy), and tuberculosis (the reaction on the
skin forms the basis for the tuberculosis skin test, or PPD). The reaction is T – cell mediated, so
that considerable time is required for the lymphocytes to become sensitized and the reaction to
Type IV reaction-positive PPD test for Tuberculosis exposure

1. S Fagarasan and T Honjo (2003). "Intestinal IgA Synthesis: Regulation of         Front-line
Body Defenses". Nat. Rev. Immunology 3: 63–72. doi:10.1038/nri982. PMID 12511876
2. Gould H et al. (2003). "The biology of IGE and the basis of allergic disease". 2         Annu
Rev Immunol 21: 579–628.             doi:10.1146/annurev.immunol.21.120601.141103.           PMID
3. Erb KJ (2007). "Helminths, allergic disorders and IgE-mediated immune            responses:
where do we stand?". Eur J Immunol 37 (5): 1170–1173. doi:10.1002/eji.200737314. PMID
4. Fitzsimmons C, McBeath R, Joseph S, Jones F, Walter K, Hoffmann K, Kariuki               H,
Mwatha J, Kimani G, Kabatereine N, Vennervald B, Ouma J, Dunne D            (2007).        "Factors
affecting human IgE and IgG responses to allergen-like        Schistosoma mansoni antigens:
Molecular structure and patterns of in vivo exposure". Int. Arch. Allergy Immunol. 142 (1): 40–
50. doi:10.1159/000095997.           PMID 17019080.
5. Watanabe N, Bruschi F, Korenaga M (2005). "IgE: a question of protective immunity in
Trichinella spiralis infection". Trends Parasitol. 21 (4): 175–8.    doi:10.1016/j.pt.2005.02.010.
PMID 15780839
6. Pfister K, Turner K, Currie A, Hall E, Jarrett EE (1983). "IgE production in rat
    fascioliasis". Parasite Immunol 5 (6): 587–593. doi:10.1111/j.1365- 3024.1983.tb00775.x.
PMID 6657297
7. Duarte J, Deshpande P, Guiyedi V, Mécheri S, Fesel C, Cazenave P, Mishra G,
    Kombila M, Pied S (2007). "Total and functional parasite specific IgE responses         in
Plasmodium falciparum-infected patients exhibiting different clinical status".      Malar. J. 6: 1.
doi:10.1186/1475-2875-6-1. PMID 17204149.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Infectious Diseases: Overview of Common Causes and Outcomes
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunters/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

Signs and Symptoms of Infectious Disease

a. Numerous symptoms and signs, none of which are necessarily specific for any certain disease,
signal the onset and progression of infection. These symptoms and signs may involve one or
more organ systems, but almost invariably present with fever, chills, malaise and local
enlargement of lymph nodes. Other symptoms and signs include arthralgia, myalgia, headaches,
and nausea and vomiting. Please see Goodman and Fuller, Table 8-1, p 299 for a complete list
of organ systems and how they may be affected by infectious agents.
b. Infections may be caused by either viruses or bacteria. Some infectious diseases may cause
fever that routinely does not exceed 102 degrees F (tuberculosis, hepatitis), while others cause
fever that routinely exceeds 102 degrees (peritonitis, HIV infection)-please Goodman and
Fuller Table 8-2, p 299 for a complete list of disorders that may fall into one of these two
categories among hospitalized patients. Generally, fever below 102 degrees F is treated as a
benign, non-emergency situation, whereas fever about 102 degrees F is looked at as needing
immediate attention. Fever above 102 degrees F may cause delirium and convulsions, especially
in children. Fever arising secondary to infections is due to toxins released from bacteria and/or
the impact of the bacteria or virus on the hypothalamus, which regulates body temperature.
Sometimes, a specific cause for fever may not be able to be identified, known as FUO (fever of
unknown origin). In such cases an autoimmune disease or cancer should be suspected.

The Chain of Transmission of Infectious Disease

A. Before an infection can occur, there must be a reservoir (another human, soil, food) that is
friendly to a pathogen . There must then be a portal of exit from the reservoir (urine, semen,
feces, respiratory secretions). Next, a mode of transmission must occur, so that the infection may
be delivered to the new host. Example modes of e transmission include: contact (skin-to-skin,
mucous membrane to mucous membrane), airborne (fine particles from sneezing or coughing),
droplet (also sneezing or coughing), (vehicle contaminated food/water), and vector born (insects
or other animals).
B. List some examples of diseases that are spread by each of these modes of transmission. Of
course, exposure to known infectious agents should kept to a minimum, and all therapists (as
well as other health care workers), should also use universal precautions, avoidance measures,
and hand washing. For more on control of disease transmission, please the box 8-6 in Goodman
and Fuller, p. 318.

Clinical manifestations of Common Infectious Diseases

A. Infections may develop from various sources, but overall come from one of 3 broad
categories: 1) bacteria, 2) viruses, or 3) parasites. These pathogens may be obtained in many
ways, and knowledge of their transmission pathways helps in prevention. Please see Goodman
and Fuller box 8-6 on p 314 for additional information on tips for preventing infection.
1. Bacterial Infections: Several will be mentioned (Staphylococcus, Streptococcus, Clostridium,
and Pseudomonas)-for more information, please see Goodman and Fuller p 319.
a. Staphylococcus aureus is a common pathogen residing in the skin, and is spread by direct
contact. Penetration into the deeper layers of the skin (such as via a hair follicle) cause an
abscess and suppurative drainage. It is the most common cause of both community and
nosocomial (hospital acquired) infections, and may cause infection in virtually any part of the
body (septic arthritis, infective endocarditic, osteomyelitis)-see Goodman and Fuller for a more
complete summary of S. Aureus infections, Table 8-7 on p 319.
*MRSA. Methicillin Resistant Staphylococcus Aureus or "MRSA," is a very serious infection.
MRSA is a powerful Staph infection that is resistant to many antibiotic medicines. A MRSA
infection can be more serious than infections caused by other Staph bacteria, and is becoming
more and more common both in and out of the hospital. Many healthy people, including
caregivers, have MRSA in or on their bodies without knowing it. The bacteria may be on their
skin or in the nose. This is called colonization, and is different from infection. Colonized means
that a healthy person can carry the Staph bacteria and can possibly infect others. With
colonization, the colonized persons are not sick, but are at risk to become infected with their own
MRSA. Sick people in the hospital and older or weakened people are at a greater risk to get
MRSA. Also at risk are persons that have had surgery or other procedures. Diabetics are also
more likely to get MRSA, as are those with HIV or kidney failure. Being in the hospital a long
time or having a burn or lung infection can increase the risk of getting MRSA, as can the use of
IV street drugs. Review the following information about MRSA.

Causes: Staph aureus may be found in the nose or other hairy or moist areas of the body. MRSA bacteria may also
be found on objects, like the telephone, side rails of a hospital bed, or tray tables. One can also get MRSA from the
hands of another person who is colonized.
A MRSA infection may cause redness, swelling, or tenderness where you have the infection, like a wound or a burn.
If MRSA is in their blood, individuals may become febrile.
The skin may be red if MRSA is an integumentary infection.
If MRSA infects the heart, the affected person will have chest pains, trouble breathing, or palpitations. A palpitation
is a pounding or racing feeling in the heart.
One will likely not have any symptoms if only colonized with MRSA.

B. Streptococcus pyogenes (Group A Streptococcus) is also a common bacterial pathogen, and
infection results in diseases such as: streptococcal pharyngitis (strep throat), impetigo, and
rheumatic fever (see Goodman and Fuller Table 8-7 p 319 for a more complete list).
Transmission can be airborne or by direct contact. S. pyogenes (Group A Beta hemolytic) can
also cause a rare form of gangrene, and may result in sepsis and death. Necrotizing fasciitis and
streptococcal myositis are also very serious diseases with high mortality rates that are caused by
S. Pyogenes. Other forms of streptococcal bacteria include: S. Agalactiae (Group B
streptococcus), which is the leading cause of neonatal pneumonia, meningitis, and sepsis, and S.
pneumoniae, which is the most common cause of bacterial pneumonia and bacterial meningitis in
children and adults.

C. Clostridium myonecrosis, C. perfringens; 2) C. septicum; 3) C. sporogenes, and; 4) C. welchi
are common causes of infection following circulatory interruption, a condition known as
gangrene. Of the various bacteria involved, C. perfringens is the classic offender. Gangrene
often affects the lower limbs because the vascular supply is poor. The infected area may turn
black, and the skin may slough, and show a line of demarcation between normal and infected
tissue (“dry gangrene) or may become moist (“wet”) gangrene and include infection. Sometimes
the infected tissue may become distended and give off a foul odor (“gas” gangrene). With
improved oxygen to the affected area healing may occur (remember, Clostridium is anaerobic).
Hyperbaric oxygenation can facilitate this process, especially with dry gangrene. However, in
cases of wet or gas gangrene, the limb will likely have to be amputated to stop the spread of the
infection into the trunk and bloodstream. In gas      gangrene, the disease may spread rapidly to
adjacent tissues and cause sepsis, and can be fatal within a few hours of onset.
d. Pseudomonas aeroginosa is a major opportunistic pathogen and is one of the most common
nosocomial infections. P. aeroginosa may colonize humans, but is often associated with
pneumonia, wound infections, urinary tract infections, and sepsis in debilitated and older
individuals. Whirlpool tanks, respiratory equipments, and liquid soap dispensers are prime
targets for growth. The pathogen releases strong, necrotizing enzymes, and is responsible for the
green-pigmented discharge seen in suppurative infections. Common sites of infection include the
CNS (pseudomonas meningitis), skin (erythema gangrenosum), and bones and joints
(osteomyelitis and osteochondritis).

D.      Viral Infections. Perhaps the most significant blood borne viral pathogens (other than
HIV) are Hepatitis B (HBV) and Hepatitis C (HCV). Both of these viruses may result in
significant illness, with fever, jaundice, nausea, and abdominal swelling, and general malaise.
Incubation periods are relatively long for both diseases (approxi,ate;y2-3 months on the average),
and transmission may be by percutaneous contact (needle stick or cut), blood transfusion, or
unprotected sexual contact. Vaccine currently exists for HBV; however, none is currently
available for HCV. At least 10% of individuals with HBV run the risk of developing chronic
hepatitis. The risk is greater with HCV- more than 80% of those affected may develop chronic
hepatitis, with another 30% developing cirrhosis. Some may develop liver cancer and
hepatocellular failure, which without heroic measures such as liver transplantation, is uniformly

E. Other viral diseases: Herpes viruses. Basically, there are 8 types of herpes viruses (see Box 8-
9 in Goodman and Fuller p 328.)

Herpes Simplex1 (HSV-1) and Herpes Simplex2 (HSV-2). HSV-1 are the viral pathogens
responsible for “cold sores” and mouth sores, and HSV-2 causes genital herpes, with lesions
affecting the genitalia and urinary tract. Both HSV-1 and HSV-2 are highly contagious, and can
be transmitted via direct contact with a break in the skin or mucus membranes of the eye, mouth,
throat, or urogenital tract. Infection is life long, and may migrate to sensory nerve roots and
cause pain or blindness. Encephalitis and meningitis may also be caused by HSV. The pathogens
may lie dormant at time with the infected person being asymptomatic; periods of stress may
reactivate them and produce symptoms (usually flu-like along with mucocutaneous lesions).

Varicella-Zoster virus (VZV) or Herpes Zoster is responsible for chicken pox, and is transmitted
via respiratory secretions. VZV has the ability to migrate to sensory nerve ganglia (i.e. the dorsal
root ganglia) and remain latent for many years. If reactivated, the VZV may migrate along the
nerve root and cause inflammation, i.e. shingles. Shingles is a very painful condition, and may
take several weeks to resolve. Vaccine is available for VZV.

Cytomegalovirus (CMV) a cytomegalic inclusion disease, and is a type of herpes virus that is
transmitted through blood or secretions (vaginal, semen, breast milk, urine, etc.) and may affect
multiple organ systems (although the virus often affects the salivary glands. CMV may occur
congenitally, or in the prenatal or postnatal state. Four of five adults over 35 have antibodies for
CMV, having contracted the virus either during childhood or early adulthood. CMV in healthy
individuals is usually asymptomatic and self-limiting; however, immune compromised persons
or neonates may develop more serious diseases (CMV hepatitis, CMV pneumonitis, CMV
chorioretinitis and blindness, and CMV gastroenteritis).

Infectious mononucleosis is caused by Epstein-Barr virus (EBV), which is a member of the
herpes virus group. The virus is spread through saliva, but may also be transmitted via blood
transfusion. Some individuals develop a maculopapillary rash, there may be both liver and spleen
enlargement. Body temperature fluctuates, but usually peaks at 101-102 degrees F. In healthy
individuals, the disease is self-limiting and subsides in a few weeks with relatively few
complications. The disease is diagnosed with a positive Monospot test. See the following
website and read about the Monospot test at: http://en.wikipedia.org/wiki/Monospot_test

Respiratory viral infections include influenza viruses and respiratory syncitial virus (RSV)
Influenza viruses are classified as A, B, or C, with A and B causing serious influenza outbreak
and illness-these are the only types included in flu vaccine. influenza viruses are transmitted via
respiratory droplets, and infection results in fever, chills, headache, malaise, sore throat, nausea
and vomiting, and diarrhea. Healthy individuals generally see the disease resolve in 7-10 days,
but complications include viral pneumonia, bronchitis, and sinusitis. RSV may be transmitted via
direct contact or via respiratory droplets, and may cause pneumonia, bronchiolitis, and
tracheobronchitis in young children (the prime candidates for development of the disease.
Healthy adults usually experience a mild tracheobronchitis when infected. Serious pulmonary
RSV may develop in older adults and immune compromised individuals, with bone marrow
transplant patients and pediatric liver transplant patients being at particular risk. Symptoms and
signs include low-grade fever, wheezing, and an increased respiratory rate (tachypnea).
Occasionally, recurrent infections with RSV occur, and may cause the development of asthma or

IV. Miscellaneous Infectious Diseases

A. Please read the text Goodman and Fuller pp 339 on infections and joint prostheses and

B. Please read the text Goodman and Fuller pp 339--342 on Lyme disease.

C. Please read the text Goodman and Fuller pp 343-346 on sexually transmitted

D. Please read the text Goodman and Fuller pp 346-347 on infections in drug user.
Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Oncology: General Overview, Terminology, and Clinical Expectations
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

What is neoplasia?

Neoplasia: New growth – tumor; “A neoplasm is an abnormal mass of tissue, the growth of
which exceeds and is uncoordinated with that of the normal tissues and persists in the same
excessive manner after cessation of stimuli which evoke the change.” –Willis. The term
“neoplasia” encompasses both malignancies (a.k.a. “cancers”) and benign conditions. Malignant
tumors result in about 500,000 deaths in the U.S. annually. This number amounts to more than
20% of all deaths, and ranks cancer as the second overall cause of death among all age groups.

Lung cancer is, by far, the most common fatal cancer in men (31%), followed by colon & rectum
(10%), and prostate (9%). In women, lung (26%), breast (15%), and colon & rectum (10%) are
the leading sites of cancer death.

Survival rate for Cancers
It tells you the percentage of people who survive a certain type of cancer for a specific amount of
time. Cancer statistics often use an overall five-year survival rate. For instance, the overall five-
year survival rate for bladder cancer is 80 percent. That means that of all people diagnosed with
bladder cancer, 80 of every 100 were living five years after diagnosis. Conversely, 20 out of
every 100 died within five years of a bladder cancer diagnosis.
Relative 5 year : 64.7 percent (All Sites)
Pancreas: 5 percent (5 year)
Lung: 15 percent (5 year)

                                View details for:
All Sites   Colon and Rectum   Lung and Bronchus     Female Breast       Prostate

                  Place cursor over symbol or line to view data


Five-year absolute survival rates describe the percentage of patients that are alive five years after
their disease is diagnosed.

Five-year relative survival rates describe the percentage of patients with a disease that are alive
five years after their disease is diagnosed divided by the percentage of the general population of
corresponding sex and age that are alive after five years. Typically, cancer five-year relative

survival rates are well below 100%, reflecting excess mortality among cancer patients compared
to the general population. In contrast to five-year absolute survival rates, five-year relative
survival rates may also equal or even exceed 100% if cancer patients have the same or even
higher survival rates than the general population. This pattern may occur if cancer patients can
generally be cured, or if patients diagnosed with cancer are otherwise more privileged (e.g., in
terms of socioeconomic factors or access to medical care) than the general population.

5year relative survival rates:
Group with cancer: 55/100 are alive after 5 years
General Population Group: 85/100 are alive after 5 years
55/85=64.7% 5 year relative survival rate
Classification of Tumors

Benign: Benign tumors have a capsule and push surrounding tissue aside but do not invade
surrounding tissue. They instead present as hyperplastic masses and are named from the type of
tissue they arise from (– add suffix –oma).

    Epithelium        Connective Tissue       Muscle                Nerve

Papilloma           Chondroma             Myoma                Glioma
Adenoma             Fibroma                                    Neuroma
*please see Goodman and Fuller Table 98-1, p 349 for more examples

Malignant (cancer): Malignant tumors have several distinct features that differ from benign
tumors, several of which are as follows:

*   Have ill defined edges, no capsule, and are locally invasive by direct extension;
*   Are usually larger than benign tumors because of autonomous growth;
*   Metastasize, which means that cells break off from the parent tumor and move to a distant
    organ or tissue site. Mechanisms include:
a.        Hematogenous spread, i.e. via the blood-vascular system;
b.        Lymphogenous spread, i.e. via the lymphatic system.
* Malignant tumors are named from the type tissue they arise from. Just add the suffix –
carcinoma if epithelial; -sarcoma if connective tissue, -glioma if a tumor in the CNS, and –
blastoma if a peripheral nerve tumor. Tumors are graded as I – IV, with the higher grades having
the greatest ability to invade and metastasize.

    Epithelium            Connective Tissue      Muscle                     Nerve

    Carcinoma             Sarcoma                Sarcoma                    Glioblastoma
    Adenocarcinoma        Fibrosarcoma           Rhabdomyosarcoma           Blastoma
                                                 Leiomyosarcoma             Neuroblastoma
*please see Goodman and Fuller Table 9-1, p 349 for more examples

Can also be classified by the
A) Morphologic qualities of malignant cells
B) Stages (Describes the extent of disease or spread of cancer from the site of origin)

Factors contributing to the metastatic quality of malignant cells

       Lack of adhesiveness, which means that cells do not adhere to each other;
       Increased motility, which means that cells are very active and mobile;
       Autonomous Growth;
       Lack of contact guidance, which means that cells' growth is independent of
       surrounding cells;
       Lack of contact inhibition, which means that cells' behavior is not governed by
        surrounding cells.

Morphologic qualities of malignant cells

Cancerous cells have several microstructural features that readily distinguish them from normal
cells. These microstructural changes are well known, and when present in a tissue biopsy
specimen, verify the presence of a malignancy. The microstructural cellular changes are:

* Dysplasia, which means that the cells have an abnormal appearance, such as an irregular
shape or an abnormal nucleus. An early form of dysplasia is called metaplasia. Metaplasia is a
benign and potentially reversible change in which an adult cell changes from one type into
* Pleomorphism, which means that the cells have different sizes and shapes.
* Anaplasia, which means that the cells resemble embryonic cells, lack differentiation, and
have a high reproductive rate). Anaplasia the most advanced from of metaplasia, and is
characteristic of malignant cells only.

Cancer Staging

Cancer staging is the process of describing the extent of the disease or the spread of cancer from
the site of origin. Staging is essential in determining the choice of therapy and assessing
prognosis. A cancer’s stage is based on information about the primary tumor’s size and location
in the body, and whether or not it has spread to other areas of the body. A number of different
staging systems are currently being used to classify tumors. For example, summary staging has
been useful for descriptive and statistical analysis of tumor registry data. The different levels of
summary staging are:
A. Summary Staging – Ann Arbor Method
1. In situ, which means that cancer cells are present only in the layer of cells
they developed in and have not spread to other parts of that organ or
 elsewhere in the body;
2. Invasion of local tissue means that cancer cells have spread beyond the
     original layer of tissue;
3. Invasion of regional lymph nodes;
4. Distant metastasis, which means that cancer cells have spread to other
    organs in the body.

 B. The TMN staging system is another classification system that assesses tumors
in 3 ways: extent of the primary tumor (T); absence or presence of regional
lymph node involvement; and, absence or presence of distance metastasis (M).
Once the T, N, and M are determined, a “stage” of I, II, III, or IV is assigned,
with stage I being early stage and IV being advanced stage.
•    Used for all other cancers except:
•    Brain
•    Blood

C. Staging by Cell Type of Origin (Grading)
1. Low grade (localized)-cell types resemble normal, fully differentiated cells.
2. High grade (metastatic)-cell types are poorly differentiated and tend to
       metastasize early to distant organ sites.

Etiology, Risk Factors, and Pathogenesis for/of Cancer

A. Endogenous cancers are those that tend to show a familial, or hereditary
pattern. Examples include: breast cancer, colon cancer, and certain forms of ovarian and prostate
cancer. In breast cancer, specific protooncogenes have been isolated and identified (BRCA1 and
BRCA2). In colon cancer, a hereditary condition known as multiple familial polyposis may exist,
in which benign polyps develop in the mucosa of the colon, and eventually become malignant.
Certainly, aging is the most common genetic (and unavoidable) condition that
underlies cancer occurrence.
B. Exogenous cancers are those that may be attributed to some external cause,
such as environmental factors or behavioral factors that cause malignant mutations in cells.
Exposure to environmental factors that can cause cancer (i.e. carcinogens) may be accidental or
self-induced, and can produce a wide variety of cancerous outcomes. Examples of carcinogens
include: tobacco use, certain viruses (Human papillomavirus), chemicals (tar, soot, alcohol
consumption), and physical agents (radiation, asbestos). Please see Goodman and Fuller Box 9-
3 p 353 for a more complete list of cancer risk factors.
C.     Pathogenesis: Tumors form when there is an increased mitotic rate, DNA
mutation with chromosomal abnormalities, and hyperplasia with accumulation. Also, tumor cells
live longer than normal cells, making them more durable and allowing them to accumulate into a
mass. Recently, tumor activators have been discovered and written about extensively in the
literature; the most commonly studied activators are tumor viruses and oncogenes. Proto-
oncogenes are normal genes that can became oncogenes due to mutation. Oncogenes are have
mutations and cause an individual to develop a particular kind of cancer.“Suppressor”
oncogenes, or anti-oncogenes have also been studied, i.e. genes that would block cancer cells
from forming. Anti-oncogenes such as BRCA1 and BRCA2 for breast cancer-and maybe ovarian
cancer-help prevent DNA damage during cell replication.
p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans
is encoded by the TP53 gene. p53 is important in multicellular organisms, where it regulates the
cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As
such, p53 has been described as "the guardian of the genome", the "guardian angel gene", and the
"master watchman", referring to its role in conserving stability by preventing genome mutation.
p53 has many mechanisms of anticancer function, and plays a role in apoptosis, genomic
stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works through several

       It can activate DNA repair proteins when DNA has sustained damage.
       It can induce growth arrest by holding the cell cycle at the G1/S regulation point on DNA
damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have
time to fix the damage and the cell will be allowed to continue the cell cycle).
       It can initiate apoptosis, the programmed cell death, if DNA damage proves to be
irreparable. http://en.wikipedia.org/wiki/P53

Invasion and Metastasis
Because of their lack of adhesiveness and increased motility, cancer cells can spread to local
tissue by direct extension. Direct extension into blood and lymphatic vessels may then allow
cells to break off from each other and travel to distant organ sites, a process known as metastasis.
Metastatic tumor cells usually deposit in highly vascular organs, a process called seeding. In this
process, the cells float in body fluids until they find a solid spot to latch on to (i.e. filter organs).
Good filters include brain, liver, lungs, and bone, and lymph nodes, all of which may imply
multiple tumor site metastases.

Clinical Manifestations of Cancer

While the clinical presentation of cancer may vary from one individual to the next, most patients
will present with several recognizable symptoms and signs. Also, malignant neoplasms will
often cause symptoms and signs of disease well in advance before they are formally diagnosed.
Such symptoms and/or signs may be noted either by the patient or the patient’s family or
friends. Some of the symptoms/signs of a malignant neoplasm are as follows:
* Exertion of pressure on tissue to cause obstruction;
* Erosion of normal tissue/replacement with a mass;
* Bleeding – tissue eroded may be a blood vessel;
* Infection – may be due to ulceration or obstruction;
* Anemia – blood loss, vitamin B12 malabsorption, bone marrow depression (metastatic cancer
to bone, treatment from chemotherapeutic agents);
* Metabolic disturbances:
– Hormones may be produced in increased amounts: Pheochromocytoma (tumor of adrenal
gland tissue) causes increased production of Catecholamines, which in turn cause blood sugar
elevation, blood pressure and heart rate elevation
In case of lung cancer, human chorionic gonadotropin may be produced
Metabolic disturbances may cause other symptoms i.e. cancer arthritis, vasculitis. These
conditions are called paraneoplastic syndromes;
* Cachexia – as a result of anorexia, liver damage, or metabolic drag;
* A palpable enlargement (lump, mass, or swelling) may be present;
* Migratory thrombophlebitis. Blood clots form in different and varying vascular areas of the

VIII. Cancer Pain and Cancer Related Fatigue
A. Cancer Pain is a multifaceted phenomenon, and may be associated with several factors,
including pressure on nerves and/or displacement of nerves. Microscopic infiltration of nerves
by cancer cells can also induce pain, as can interference with the blood supply to organs or tumor
blockage of hollow organs (bile duct, pancreatic duct, for example). Metastasis to bone is
particularly painful, as pressure may be placed on the sensory endings of the periosteum,
accompanied by bone destruction. Often, bone metastasis is followed by pathologic fractures, in
which the involved bone breaks spontaneously or when a routine force is applied.
B. Cancer-related fatigue may occur as a result of the catabolic effects of the disease, or may be
due to treatment. Patients receiving radiation therapy, chemotherapy, and bone marrow
transplant routinely report extreme fatigue, and about 30% claim that the fatigue is permanent
and lasts for years after cessation of treatment.

Ways to Prevent Cancer
By far the best way to manage cancer is to prevent its occurrence, and the American Cancer
Society has estimated that most cancers can be prevented. Three tiers of prevention have been
A. Primary Prevention: Primary prevention includes screening for risk factors and subsequent
elimination of those that are modifiable. Examples include: smoking cessation, increase dietary
fiber, increase physical activity, reduce exposure to sunlight).
B. Secondary Prevention: Secondary prevention utilizes early detection and prompt treatment of
local malignancies before they become invasive and spread. Sometimes, treatments are instituted
for individuals having a high risk for certain cancers, i.e. women known to have a high risk for
breast cancer may be placed on a drug called tamoxifen.
C. Tertiary Prevention: Tertiary prevention focuses on managing symptoms of individuals
diagnosed with cancer, as well as limited complications and preventing disability associated with
cancer and/or its treatment.

Diagnosis and Management of Cancer
Eliminate risk factors. Understanding which environmental, chemical, and infectious agents have
been implicated in cancer may do much to reduce the incidence of cancer. Some of these risk
factors are listed below. To see a more comprehensive list of risk factors for various
malignancies, please see Cancer Facts & Figures, which is published annually by the American
Cancer Society.
The publication may be accessed online at:
http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf or may be obtained by
contacting the local chapter of the ACS. Avoidance measures listed include:
     Eliminate smoking and chewing tobacco; also avoid exposure to “secondhand” smoke;
     Reduce intake of smoked foods. Reduce low roughage diets (red meats) and substitute
        high fiber diets (fruits and vegetables);
     Avoid overexposure to sunlight.

Screening procedures for early detection of cancer (secondary prevention)
    Pap smears to detect uterine cancer cells and dysplasia;
    Digital exam, hemocult test, sigmoidoscopy and or full colonoscopy to detect colorectal
    Mammogram, self-exam to detect breast cancer;
      Self exam of testes in men to detect testicular lumps;
      Digital exam and prostate-specific antigen (PSA) blood test to detect early prostate
      Carcinoembryonic Antigen (CEA): Colorectal, gastric, pancreatic, lung, breast, and
       thyroid cancer;
      Alpha Fetoprotein (AFP)-Liver cancer;
      CA-125-Ovarian cancer.

Treatments for cancer are numerous, and may either be indicated or contra-indicated, depending
on the location, staging, and nature of the primary tumor. Examples of common treatments are:
     Radiation therapy – kills cancer cells because they tend to be more susceptible to
        radiation; there is less of an effect to the individual’s normal cells;
     Adjuvant Chemotherapy – toxic to tumor cells, but are less toxic to the individual’s
        normal cells. Some cells, however, such as the hematopoetic cells in the bone marrow,
        are destroyed by chemotherapeutic agents, thus rendering the patient anemic and
        susceptible to infection;
     Surgical excision of the primary tumor or regional lymph nodes.
     A fairly recent development combining surgery and chemotherapy is called neoadjuvant
        chemotherapy, in which the neoplasm is reduced in size by administration of
        chemotherapy, and then surgically excised.
     Immunotherapy, a new experimental approach, tries to stimulate the patient’s immune
        system to combat and eliminate the cancer;
     Angiostasis, another new and experimental approach that seeks to eliminate the cancer by
        interrupting its blood supply;
     Rehabilitation – Physical/Occupational/Speech Therapy. Speech pathologists are
        especially valuable in rehabilitating patients with oropharyngeal and laryngeal cancers.
        Physical and occupational therapists are widely utilized to help patients regain functional
        mobility, strength, and independent activities of daily living as they recover from surgery,
        undergo chemotherapy, and learn to adjust to the limitations of their disease.

Cancer Statistics and Summary
Five-year relative survival rates are commonly used to monitor progress in the early detection
and treatment of cancer. The relative survival rate is the survival rate observed for a group of
cancer patients compared to the survival rate for persons in the general population who are
similar to the patient group with respect to age, gender, race, and calendar year of observation.
Relative survival adjusts for normal life expectancy (factors such as dying of heart disease,
accidents, and diseases of old age). Five-year relative survival rates include persons who are
living five years after diagnosis, whether in remission, disease-free, or under treatment. While
these rates provide some indication about the average survival experience of cancer patients in a
given population, they are less informative when used to predict individual prognosis and should
be interpreted with caution for the following reasons: First, 5-year relative survival rates are
based on patients who were diagnosed and treated at least 8 years ago, and do not reflect recent
advances in treatment. Second, information about detection methods, treatment protocols,
additional illnesses, and behaviors that influence survival are not taken into account in the
estimation of survival rates. The five-year relative survival rate for all cancers combined is
64.7% (American Cancer Society, 2011). Additional statistics include:

   A.     1 out of 3 persons will develop cancer;
   B.     Pancreatic cancer 5 year relative survival rate is only 4% (all stages);
   C.     Lung and bronchial cancer relative 5 year survival rate is only 14% (all stages)
   D.     This year about 522, 200 Americans are expected to die of cancer, making it the second
          leading cause of death in the US;
    E. In the US, 1 in every 4 deaths is from cancer;
    F. Note in the graph below the longitudinal history of death rates of colon cancer, lung
cancer, uterine cancer, and breast cancer. Also, note the cancer cases by site in males and
females, then note the cancer deaths by site in males and females-see the graphs (see slides) In
particular, observe the rankings by frequency of the different types of cancers as they newly
occur in males and females; observe also the rankings by frequency of the different cancer
deaths by site and sex.

Diagnosis of specific neoplastic disease-skin cancers
1.        Basal cell carcinoma: a nodule that appears on the skin as a "pearly" nodule with
peripheral telangietatic blood vessels. Basal cell carcinomas are generally slow growing and may
be observed well ahead of their becoming invasive.
2.        Squamous cell carcinoma: generally larger and more invasive that basal cell carcinoma.
The area of the skin affected presents as an ulcerated, verrucous area showing a thickened, scaly
nodule. Squamous cell carcinomas usually appear in older individuals, and, like basal cell
carcinomas, there is a high correlation with exposure to sunlight. The incidence of both
squamous cell and basal cell carcinoma is highest in Caucasians with fair skin, and are lowest in
African Americans.
3.        Melanoma: malignant melanoma makes up only about 3% of primary skin cancers, but
is responsible for virtually all skin cancer deaths. There is a strong relationship to sun exposure,
and most melanomas occur in fair skinned individuals. Melanomas may be quite aggressive, and
become invasive into the surrounding tissue very quickly. Once melanoma cells become invasive
they may spread to distant organ sites, and form metastatic tumors in vital structures, such as the
brain, the liver, and the lungs. The prognosis for individuals with metastatic melanoma remains
discouraging. Melanoma should be suspected when a mole-like structure is observed on a patient
that is asymmetrical, has irregular borders, has a dark blue-black color, and is greater than the
diameter of a pencil eraser. Knowledge of the ABCD’s for melanoma empowers health
professionals of virtually any discipline to screen for its potential presence in-patients. If such a
mole is discovered, then the patient should be followed up very soon by a dermatologist for

diagnosis to rule out/rule in the presence of malignant melanoma. These characteristics have led
to the acronym ABDC’s for melanoma screening, namely:

         B=borders are irregular

Knowledge of the ABCD’s for melanoma empowers health professionals of virtually any
discipline to screen for its potential presence in-patients. If such a mole is discovered, then the
patient should be followed up very soon by a dermatologist for diagnosis to rule out/rule in the
presence of malignant melanoma.

                                        End-Unit I
                                    Study Tips for Unit I
Be sure you can:

1. Discuss the different types of necroses, including giving specific examples/criteria of cellular
   injury and death. Also, the five major headings in Goodman and Fuller, Chap 1, along with
   the general points made in Goodman and Fuller Chaps 2-4.

2. Describe how an inflammatory reaction is initiated, develops step by step, and use correct
   terminology and key pathophysiological concepts.

3. Outline the steps involved in tissue healing, both in wounds with opposed edges and those
   with separated edges. What is healing by resolution? What are the stages of necrosis?

4. Explain, in a sequential fashion, how the immune system is currently thought to “recognize
   and eliminate offenders, without injury to the host tissue.”

5. Give some examples of diseases involving the immune system. What are some symptoms
   and signs? Some diagnostic criteria?

6. Differentiate active vs. passive immunity.

7. List the 4 kinds of immune hypersensitivity, (i.e. Types I-IV), reactions in terms of function,
   and give specific examples of each. (See Text – Chaps. 5 and 12).

8. Discuss and evaluate different kinds of infectious diseases, noting correctly for each the
   causative organism and patient symptoms and signs.

9. Discuss how tumors are classified, according to tissue criteria, and ways that benign and
   malignant tumors differ.

10. List ways malignant tumors spread; also define specific terms, which generally apply to
    malignant tumors, such as “dysplasia”, “anaplasia”, “contact inhibition”, etc.

11. Review statistics on incidence, survival, etc. of certain significant neoplasms, such as lung,
    breast, etc. No need, however, to “memorize” numbers – just look at relationships of
    different cancers to each other, those most common, etc.

12. Define and explain basic lab values, such as arterial blood gases, acid/base disorders,
    complete blood count, serum enzymes (CK and LDH), blood coagulation,
    electrolytes, and liver functions tests-see appendix A.

                                      FORMATIVE EXAM

You see now see how you can do on these questions, which generally follow the form on the
Unit I exam. Answers are attached. You will see some questions that require you to do clinical
problem solving as will be expected on the exam.

 1.                 Concerning a patient’s response to acute bacterial infection:

                    a.     White blood cell counts become greatly reduced.
                    b.     White blood cell counts are usually normal range (5000-
                    c.     Neutrophilic reactions are generally most common.
                    d.     May be a forerunner to acute granulocytic leukemia.
                    e.     Often accompanied by thrombocytopenia and bleeding.

2.                  Congenital absence of the thymus would likely compromise
                    immunity BECAUSE:

                    a.   The thymus controls plasma cell synthesis of antibodies
                    b.   T Lymphocyte regulation and production is initiated by the thymus.
                    c.   The complement protein group would be suppressed.
                    d.   Both the B and T lymphocyte population would be reduced.
                    e.   The bone marrow would be depressed.

3.                  When stimulated by an antigen, sensitized T-lymphocytes release:

                    a.   IgM
                    b.   Secretory IgA
                    c.   Lymphokines
                    d.   IgG
                    e.   IgE

4.                  Lung cancer:

                    a. Is now ahead of breast cancer in frequency of occurrence in
                    b. Prognosis for survival in terms of 5-year survival rate is quite
                    c. Is highly correlated with smoking history in both males and
                    d. has decreased in incidence over the past 50 years.
                    e. occurs routinely in children with DiGeorge’s syndrome.
                    In gangrene secondary to ischemic necrosis:

5.                  a.   So called “gas gangrene” usually responds best to hyperbaric
                    b.   The clostridium organism may multiply secondary to tissue
                    c.   An amputation almost inevitably results.
     d.   The upper extremities are most often involved.
     e.   Superficial lesions heal poorest, because healing is via second

6.   In allergic asthma:

     a.      Antigen attachment to IgA promotes mast cell degranulation.
     b.      Classification would best suit a Type I hypersensitivity
     c.      Allergic response is manifested as multiple blood clots.
     d.      The disorder is primarily caused by aging.
     e.      The disorder commonly predisposes those affected to lung cancer.


1.    Answer is C. In a bacterial infection, WBC’s are generally high (normals are 5,000 –
      10,000/ul). The clinical picture shows a disproportionate increase in neutrophils
      (PMN’s). Platelets remain within normal range.

2.    Answer is B. T-lymphocytes are “cloned” by the thymus, thus one must have a thymus
      in order to have T-lymphocytes, and subsequently, immune competency. The thymus
      does not seem to have an effect on production of antibodies, complement proteins, or B
      cells (choices a, c, d).

3.    Answer is C. When “primed” or “sensitized”, T-lymphocytes release a group of
      mediators called lymphokines. One of these lymphokines is macrophage immobilizing
      factor (MIF). Do you know any others? The MIF tends to keep macrophages from
      migrating to other sites, and keeps them sequestered at the site most needed for
      eliminating a foreign invader. IgM, secretory IgA, IgG, bradykinin are secreted from
      other sources-mucous membranes, mast cells, granulocytes, etc. (choices a, b, d, e).

 4.   Answer is C. There is virtually no doubt that smoking and lung cancer go hand in hand.
      Although significant in females, lung cancer is still behind cancer of the breast in females
      in terms of frequency (although latest stats put lung cancer first in the death rate).
      Although treatment techniques abound, lung cancer still has a poor prognosis, and
      survival rates in the long run are still not good (about 13%) (choice b).

5.    Answer is B. Clostridium perfringens, which is implicated in gangrene, thrives in an
      anaerobic environment. Therefore, in a lesion with poor circulation, organisms might
      well flourish. Gangrene most often is seen in the lower extremities; however, depending
      on the depth of the lesion, the degree of circulation impairment, etc., amputations may
      be avoided with treatment. Healing may take time, but the more superficial the lesion,
      generally the more satisfactory the healing. In “gas gangrene”, the lesion is deep and
      does not typically respond well to treatment of any sort (save amputation) – hyperbaric

6.    Answer is E. A Type I hypersensitivity (of anaphylaxis) best describes the mechanism of
      antigen – antibody formation with mast cell degranulation, histamine release, etc., which
      is essential to the allergic response (choice b).
      Clinically, asthma is manifested by bronchoconstriction, mucosal swelling, and increased
      bronchial secretions. All this restricts flow of air in the pulmonary airways, leading to
      wheezing, shortness of breath, etc. IgA is attached to mucosal surfaces and forms a
      barrier of defense. IgE is attached to mast cells, and complexes with the antigen
      (allergen) to cause mast cell degranulation. Thus, choice A is false.

                   UNIT II


                            Medical University of South Carolina
                                 College of Health Professions
                       Divisions of Occupational and Physical Therapy

Cardiovascular Pathophysiology-Overview and General Concepts
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
David O. Sword DPT, PT

Overview: Cardiovascular disease or cardiovascular diseases refers to the class of diseases
that involve the heart or blood vessels (arteries and veins). While the term technically refers to
any disease that affects the cardiovascular system, it is usually used to refer to those related to
atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and
treatments. Most countries face high and increasing rates of cardiovascular disease. Each year, in
fact, heart disease kills more Americans than cancer. Heart disease is the number one cause of
death and disability in the United States and most European countries (data available through
2005). A large histological study showed vascular injury accumulates from adolescence, making
primary prevention efforts necessary from childhood.

Signs and Symptoms of Cardiovascular Disease include the following:
           Pain
           Palpitations
           Fatigue
           Syncope
           Cough
           Cyanosis
           Peripheral edema
           Claudication
                                Structure of a normal artery

       I. Discussion of Signs and Symptoms of Cardiovascular Disease

       -Pain: Classical angina (chest pain of a cardiac origin) often presents as substernal chest
       pain, and may be expressed as “Pressure”, “tightness”, “squeezing”, “heaviness.” Angina
       may manifest itself in many ways, and does not always fit the classical description.
       Angina and Myocardial Infarction (MI) may produce similar symptoms; however, the
       symptoms associated with MI tend to be much more severe.

Note: the heart is supplied by the C5-C6 spinal segments. Thus, visceral pain of cardiac
origin may be referred to the corresponding somatic region, i.e. “the shoulder”.

-Palpitations may indicate underlying heart disease that is resulting in an abnormal heart
rhythm (“arrhythmia”). Some arrhythmias are benign, while others are life threatening.

-Dyspnea may occur in response to activity, and may be due to:
-Cardiac disease –”sudden onset” or “unusual onset;”
-Pulmonary disease;
-Deconditioning; and/or
-Other causes.

-Syncope: An inadequate cardiac output may lead to syncope, or lightheadedness and
even fainting. Cardiac causes for syncope include:
-Cardiac valvular dysfunction;
-Cardiac arrhythmias;
-Heart failure.

-Fatigue: Some individuals, especially women, experience profound fatigue as their
major symptom of angina/MI. Moreover, any individual with an impaired cardiac output
is likely to report fatigue.

-Cough: Cough is a possible indicator of left-sided heart failure with resulting “back-up”
into the lungs resulting in “pulmonary congestion.”

-Cyanosis: Cyanosis is a blue coloration of the skin and mucous membranes due to the
presence of deoxygenated hemoglobin in blood vessels near the skin surface. Cyanosis
occurs when the oxygen saturation of arterial blood falls below 85-90% (1.5g/dl
deoxyhemoglobin), as may happen when blood pools in the lungs as a result of heart
failure. The reason why cyanosis occurs is that deoxygenated hemoglobin is more prone
to optical bluish discoloration, and also produces vasoconstriction that makes the
discoloration more evident. The scattering of color that produces the blue hue of veins
and cyanosis is similar to the process that makes the sky appear blue, i.e. some colors are
refracted and absorbed more than others. During cyanosis, tissues are uncharacteristically
low on oxygen, and therefore tissues that would normally be filled with bright
oxygenated blood are instead filled with darker, deoxygenated blood. Darker blood is
much more prone to the blue-shifting optical effects[2], and thus oxygen deficiency -
hypoxia - leads to blue discoloration of the lips and other mucous membranes.

-Peripheral edema (or tissue swelling) occurs commonly in the presence of congestive
heart failure (CHF). The reasons for this will be discussed later in this section.

-Claudication (“leg pain”): Claudiacation may occur as a result of severe atherosclerotic
disease affecting the arteries that supply the LE’s.

II. Aging and the Cardiovascular System

   A. Disease-Independent Changes:
    Reduced # of myocytes and cells within the conduction system
    Development of cardiac fibrosis
    Reduced calcium transport across the membrane
    Reduced capillary density
    Reduced responsiveness to beta-adrenergic stimulation
    Impaired autonomic reflex control of HR
   B. Additional age associated changes in the cardiovascular system include:
    Thickening of the left ventricular wall (“especially in the face of underlying
    Stiffening/calcification of the ventricles, valves, and arteries
    Increased likelihood of clinically significant atherosclerotic heart disease
       Note: Age is a non-modifiable risk factor for heart disease.

   C. Functional Changes in the Cardiovascular System with Aging
    Decrease in maximal HR
    Decrease in cardiac output (Q)
    Decrease in VO2 max (“aerobic fitness”)
    Increase in the incidence of various arrhythmias

       Note: Cardiac function can be improved at any age. Active older adults can
slow down, or even reverse some of the age associated declines in cardiac function.

III. Gender Differences and the Cardiovascular System

    A. Several factors may be cited when comparing/contrasting the          cardiovascular
system of males and females. Please note the following:
     Increased incidence of Mitral Valve Prolapse (MVP) in females
     Increase in LV mass with aging (remains constant in men)
     Increased risk of dangerous arrhythmias
     Decreased responsiveness to anticoagulants and thrombolytics, but a higher
       incidence of bleeding.
     CAD in Women
     CAD is the leading cause of death in women (250,000/yr)
     Risk of CAD rises sharply with menopause
     Historically women have not been treated as aggressively as men
     Hormonal Influence
       -Estrogen appears to be “cardioprotective”
       -Increased HDL levels
       -Reduces clotting risks
       -Both estrogen and estradiol have a dilating effect on blood vessels (helps
       maintain normal BP and blood flow)

       Note: Hormone Replacement Therapy has not been shown to provide
       “cardioprotective” benefits, and thus remains a controversial subject.

      Oral contraceptives, on the other hand, may increase the risk of blood clots
      and subsequent MI/stroke. This is especially true in women over 35 who are

IV. Atherosclerosis: Definition and Pathogenesis

   A.   Theories, of which each of the following will be discussed.
       Response to Injury (“the most widely accepted theory”)
       Monoclonal
       Lipid Insudation
       Response to Injury Theory
       Damage to endothelial lining
       Platelets and monocytes adhere to injured area
       Platelets release Platelet-derived growth factor (PDGF), promoting infiltration
        of smooth muscle cells from media to intima
       Plaque composed of smooth muscle cells, connective tissue, and cellular debris
       Lipids (LDL’s) are deposited in the plaque

   B. Risk Factors for CAD
    Non-modifiable
    Modifiable
      -BP (HTN = SBP > 140 or DBP > 90 mmHg)
      -Cholesterol (Total chol. > 200 mg/dl)
      -Smoking (There is no safe amount)
      -Inactivity (Increases risk for many chronic disease conditions)
      -Obesity (BMI > 30 kg/m2)
      -Diabetes (fasting glucose level > 126 mg/dl)
      -Stress (“Can you say Type A?”)
                Emerging Risk Factors
                 -C-reactive Protein – marker for inflammation. Elevated levels increase   risk of
              -Homocysteine – AA formed as body metabolizes methionine (“another AA”).
       Elevated levels increase risk of MI. B vitamins can help moderate homocysteine levels.

V. Clinical Manifestations of CAD
    Angina – chest discomfort/other symptoms resulting from myocardial ischemia.
    Infarction – “heart attack” with permanent tissue damage
    Sudden Cardiac Death – death within 60 min of onset of symptoms
    Congestive Heart Failure – inability of the heart to effectively pump blood

Classification of Angina
    Stable- predictably induced with a given level of exertion (same RPP). Treat with rest
       and/or medications
    Unstable- may or may not be brought on by exertion. Characterized by increasing
       frequency, duration, and intensity of ischemia, and/or a reduced “ischemic threshold”.
    Prinzmetal/ Variant- caused by coronary spasm. Anginal episodes may be cyclical,
       often occurring at the same time each day. Often occurs in the presence of underlying
       CAD. Treated with calcium channel blocker medications.
    Asymptomatic “Silent Ischemia”- up to 70% of ischemic episodes. Common in

Cardiovascular Diseases – Acute Myocardial Infarction (AMI)
    Factors that precipitate angina pectoris
         – Stress – may increase HR, BP, and myocardial oxygen demand (mVO2)
         – Exposure to Cold – causes vasoconstriction which can increase the workload of
             the heart
         – Exercise – increases mVO2

Diagnosis of Myocardial Ischemia
    Patient Hx: symptoms, risk factors, family hx
    Patient Exam: HR, BP, auscultation - S3 or S4 audible?
    Clinical Tests: EKG, GXT, Radionuclide tests, Echocardiography, Cardiac

Treatment of Myocardial Ischemia
    Rest
    Medications – meds to help decrease mVO2
    Cardiac Rehab – once the individual is stable
    Percutaneous Transluminal Coronary Angioplasty (PTCA) – procedure in which a
      balloon tipped catheter is inserted into a narrowed coronary artery and the balloon is
      inflated in order to compress the arterial plaque against the wall of the artery, thus
      allowing for increased blood flow. This procedure commonly involves placing a
      meshlike “stent” in the artery to prevent re-occlusion.

    Coronary Artery Bypass Graft (CABG) – procedure in which an artery(ies) or vein(s)
     from another part of the body is used to direct blood around an obstructed/narrowed area
     in a coronary artery.
         – Commonly used bypass vessels:
                 Internal mammary (LIM is preferred bypass vessel for blockages in the
                 Radial artery
                 Saphenous vein

Myocardial Infarction (MI)
   MI - permanent damage to myocardial tissue due to interrupted blood flow
         – transmural - full thickness
         – subendocardial - partial thickness

Note: Most MI’s occur near the apex of the heart. The most common site of blockage is the
(1) left anterior descending artery (LAD), followed by the (2)left circumflex (LCX), and finally
the (3) right coronary artery (RCA).

Diagnosis of MI
    Symptoms and HX
    EKG evidence – “ST segment elevation”
    Elevated blood levels of specific enzymes

MI - Symptoms
    Similar to angina but much more profound
    Nausea
    Diaphoresis

Serum Markers of Cardiac Damage
    CPK-MB
    LDH (“flipped ratio”) – LDH1 > LDH2 (“not normal”)
    Troponin (cTnT)
    AST (formerly known as SGOT)
    Myoglobin (a “heme” protein)

Acute Myocardial Infarction (AMI)
    Definition: “Disruption of blood supply and ischemia to the                 myocardium
      with resulting necrosis and replacement of muscle fibers with scarring.”
         – Prodrome: Angina pectoris (80%)
         – Cardiovascular Diseases - AMI
                   Plaque forms inside an artery
                   A thrombus forms around the plaque
                   Vessel occlusion occurs
                   Ischemia to the myocardium results
                   Degeneration of myocardial fibers
                   Heart’s ability to pump is compromised
    Major complications of AMI
       – Dysrhythmias – abnormal heart rhythms
       – Heart Failure (HF) – reduced pumping ability = decreased cardiac output. Over
           90% of deaths post-MI are due to HF
       – Sudden Death Syndrome
       – Mural thrombus / CVA – clot in ventricle that can lead to stroke
       – Ventricular aneurysm – weakened (“ballooned”) area due to infarction
       – Ventricular rupture with tamponade – pericardial sac fills with blood and
           compresses the heart, limiting its ability to pump blood

     Dysrhythmias (“Arrhythmias”) – examples:
          – Ventricular Fibrillation ( V-fib)– life threatening, no effective cardiac output,
             need to defibrillate ASAP!!
          – Ventricular Tachycardia (V-tach) – sustained, rapid ventricular rhythm, life
             threatening, will severly limit cardiac output, demands immediate attention
          – Multiple PVC’s – impairs cardiac output and may progress to V-tach or V-fib,
             can usually be managed with meds
For examples of the above listed arrhythmias, refer to ECG Library.com

       V. Medical and Surgical Management of MI

               Treat symptoms – rest, O2, specific medications
               Limit damage – medications, surgical intervention (PTCA, CABG)
               Secondary Prevention – lifestyle changes, medications, cardiac rehabilitation
                (there is a 20% reduction in risk of subsequent fatal MI among individuals who
                participate in formal programs post MI)

       VI. Rehabilitation Management of MI

           A.   General considerations
               CABG: PT/OT Implications
               Sternal Precautions
               No lifting, pulling, pushing (10# limit) for 6 wks
               Log roll technique in/out bed
               No driving (4-8 wks)
               ROM exercises – neck, shoulders, torso (“caution with sternectomy”)
               Scar mobilization when incision is healed
               Be conservative if the patient has osteoporosis, diabetes, or advanced age

           B. Cardiac Rehabilitation
            Phases
              -I = Inpatient phase
              -II = Acute outpatient (may last up to 12 weeks)

       -III = Follows phase II (may last 6 months or more)

       Note: monitor vital signs pre, during, and post exercise. Be aware of
       contraindications to exercise in the cardiac patient – Box 11.6, page 406

   C. Orthostatic Hypotension. Orthostatic hypotension is defined as a drop in
    (SBP) systolic blood pressure > 20 mmHg and/or drop in diastolic blood
    pressure (DBP) > 10mmHg, with reflexive increase in heart rate (10-20%)
    as individual transitions from supine or sitting to a standing position.
   Several causes of orthostatic hypotension have beeen identified:
    Autonomic dysfunction
    Volume depletion
    Prolonged immobility
    Venous pooling
    Various medications
    Starvation/malnutrition

VII. Myocarditis. Myocarditis is defined as generalized inflammation of the
myocardium, and is usually the result of viral or bacterial infection.
However, other causes may also be contributory, such as:
    Ischemic heart disease
    Radiation therapy (Women treated for breast cancer??)
    Drugs (lithium, cocaine)
    Systemic Lupus Erythmatosus (SLE)

VIII.Cardiomyopathy. Cardiomyopathy is defined as an impaired ability of the
     cardiac muscle fibers to contract and relax. The specific pathogensis of
     cardiomyopathy is unknown. Cardiomyopathy may be classified as follows:
    Dilated (most common)
    Hypertrophic
    Restrictive
   Partial list of risk factors for developing cardiomyopathy include:
    Radiation therapy
    Chemotherapeutic agents
    Rheumatic fever
    Alcohol abuse
    Sarcoidosis (this is a disease of unknown etiology that will be discussed in the
       section on pulmonary diseases)
    Obesity
    Hypertension (HTN)
    Smoking

IX. Congenital Heart Disease. Congenital heart disease implies an anatomic
    defect in the heart that is present at birth. The incidence of congenital heart
    disease is about 8 per 1000 babies, i.e. babies that are born with some form of
    congenital heart disease or defect.
      Symptoms of congenital heart disease: commonly include cyanosis and CHF
      Classification: the congenital disorders of the heart are broadly classified as
       cyanotic, and acyanotic.

X. Arrhythmias. Arrhythmias (also called dysrhythmias) implies that an
   individual has an irregular heart rhythm.
     Implications: Ranges from totally benign to potentially life threatening.
     Cause of is often unknown, but myocardial ischemia, MI, and CHF all increase
       the risk of arrhythmia.
     Certain arrhythmias occur more frequently in older individuals (“atrial–

XI. Valvular Dysfunction. Several factors contribute to valvular dysfunction:
     Stenosis – stiffening/calcification of a heart valve
     Regurgitation – “incompetent heart valve” – may allow retrograde blood flow
     Prolapse – “MVP” - valve leaflets billow back into the atrial chamber during
       systole and allow retrograde blood flow
     Valve dysfunction can impair cardiac output and increase the workload of the
       heart. Eventually signs of heart failure may develop.
     Rheumatic Heart Disease, which can be associated with valvular damage due to
       Group A beta hemolytic streptococcus induced infective endocarditis

XII. Pericarditis. Pericarditis is inflammation of the pericardium (“membranous
     sack surrounding the heart”).
    Cause: Idiopathic (85%), infections, MI, cardiac trauma, other causes
    Treatment: - correct underlying cause if known (antibiotics). May need to drain
       fluid (“pericardiocentesis”). If untreated, may lead to cardiac tamponade, with
       resulting cardiac failure.

XIII.Aneurysm. An aneurysm is an abnormal stretching of the wall of an artery,
     vein, or the heart, with the diameter being at least 50% greater than normal.
     The following should be noted regarding aneurysms:
    Aneurysm risk increases with age
    Atherosclerosis is a major contributing risk factor for aneurysm development
    Treated surgically if threshold size is reached
    Rupture is often catastrophic due to hemorrhage

XIV. Peripheral vascular disease (PVD). PVD may be caused by several
     pathologic conditions of blood vessels supplying the extremities and major
     abdominal organs. There are a wide variety of PVD’s (inflammatory,
     occlusive, vasomotor). PVD affects the LE’s more frequently than the UE’s
     Atherosclerosis is a common underlying cause for PVD affecting the LE’s,
     and can result in ischemic pain referred to as “claudication”.

A. Intermittent Claudication

Intermittent claudication implies a condition in which a “cramping” pain develops
in the calves of the legs during exercise. An episode may precipitated by walking,
and implies arterial insufficiency of blood flow to the gastrocnemius/soleus
muscles. The cause of the arterial insufficiency may be due to vessel spasm in the
posterior tibial artery and its branches, which feed the calf muscles, and/or the
posterior tibial artery may have partial occlusion due to atherosclerotic plaque,
fibroelastic disease, and localized thrombi. Intermittent claudication can occur with
any of the various forms of arteriosclerosis, and implies widespread arterial
vascular disease.

                             Medical University of South Carolina
                                  College of Health Professions
                        Divisions of Occupational and Physical Therapy

Cardiovascular Pathophysiology-Disorders of the Pump
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
David O. Sword DPT, PT

I. Heart Failure (HF)

      With HF the heart is unable to pump enough blood to meet the body’s metabolic
      demands. It is often the end result of various types of cardiovascular diseases, including
      coronary artery disease (CAD) and hypertension (HTN). It is generally a progressive
      disorder characterized by weakening and dilation of the heart. A decline in pump function
      as measured by the ejection fraction (EF) leads to a reduced functional capacity (FC),
      sometimes so severe that simple activities of daily living (ADL’s) become exhausting to
      the individual. Serial tracking of EF can be accomplished via electrocardiography. A
      normal EF (“percentage of blood emptied from the left or right ventricle with each beat
      of the heart”) is greater than 50%.

             Common Causes of HF:
              -Decrease in myocardial capacity:
              a.      Post myocardial infarction (MI). As the result of an MI (“heart
              attack”), the heart muscle (“myocardium”) may become damaged
              or scarred. This in turn can result in reduced myocardial pumping
              b.     Intrinsic muscle disease – myocarditis (“inflammation of the heart
               muscle”) and cardiomyopathy (“impaired ability of the heart’s
      muscle fibers to contract and/or relax”) are examples of intrinsic
      muscle diseases. These conditions may be the result of:
                      -Coxsackie virus – a virus that frequently attacks and damages the
      heart. It closely resembles the virus responsible for poliomyelitis.
                      -Bacterial infections, including staphyloccus and streptococcus.
                      -Genetic disorders - Paget’s Disease and acromegaly are examples
      of genetic disorders that may increase the risk of HF
                      -Idiopathic – when the underlying cause of intrinsic muscle disease
              (“or any disease for that matter”) is unknown, it is referred to as
              being “idiopathic” in origin.

              -Increased pressure/volume load
              a.      Hypertensive cardiovascular disease, which results in increased
              resistance to blood flow. Causes include:
                      -Fluid retention
                      -Increased resistance to blood flow
              b.      Biophysics of increased pressure/volume load:
                       -Driving Pressure=BP
                       -Driving Pressure=Flow (volume/min.) x Resistance
                       -BP = Flow x Resistance
              c.        Valvular disease, and examples include:
                       -Acquired (Rheumatic fever, valvular stenosis)
                       -Congenital (Mitral Valve Prolapse, stenosis of the aorta and/or
              pulmonary artery)
                       -Basic definitions of valvular disease:
                       1.       Stenosis – characterized by a restricted or narrowed
                       opening. An aortic stenosis would result in an increased
                       myocardial workload as the heart works to pump blood
                       through the narrowed aorta. A heart valve that becomes
                       stiff and non-compliant, perhaps due to calcification, is
                       often referred to as a “stenotic valve”.
                       2.      Insufficiency – often used to describe a valve that does not
                       close properly and allows blood to flow in a retrograde
              (“backward”) direction. Mitral valve prolapse (MVP) is a
              fairly common disorder that may result in insufficiency.
              d.       Rheumatic Heart Disease – typically occurs in childhood, and is
              caused by group A beta hemolytic streptococcus bacteria. May
              result in damage to the heart valves, whereby they become scarred
              and stiff, and no longer function normally.
              e.       Mitral Valve Prolapse – congenital disorder characterized a
              tendency for the mitral valve leaflets buckle up (“prolapsed”) into
              the left atrium as the ventricle contracts. If this prolapsed allows
              retrograde blood flow, then we would refer to this as an
              insufficiency. MVP is more common in women, and may result in
              one or more of the following signs/symptoms:

           General symptoms and signs associated with HF
            -Murmur – an abnormal heart sound heard during auscultation of the heart.
            -Palpitations – individual may report that there heart is “racing” or that they feel
      “pounding” in their chest”.
            -Tachycardia – rapid heart rate (> 100 bpm)
            -Shortness of Breath (“dyspnea”) with minimal or no activity.

II. Pathophysiology of HF

              Initial Ventricular Hypertrophy
               Starling Curve: Starlings Law of the Heart states that with increased filling
      (EDV) of the heart, the heart muscle (“myocardium”) fibers are stretched allowing for a
      more optimal arrangement of the contractile myofilaments within the sarcomeres. This
      results in increased contractility and thus a greater cardiac stroke volume (“blood ejected
      per beat of the heart”).
               In HF, there is an initial cardiac hypertrophy as the heart adapts to an
               increasing pressure/volume load. Over time, the heart will become dilated,
      resulting in impaired myofilament arrangement (“impaired myosin and actin linkage”),
       and a subsequent decline in contractility. The end result is a decline in the hearts ability
       to pump blood.

              “Dilated Cardiomyopathy” – used to describe the impaired
               contraction/relaxation of the myocardial muscle fibers secondary to significant
               dilation of the ventricle. The underlying cause of the cardiomyopathy is often
               times unknown (“idiopathic”). Black men between the ages of 40-60 years
               appear to be at greatest risk. Some known causes of dilated cardiomyopathy
               include long-term alcohol abuse, rheumatic fever, progressive muscular
               dystrophy, and sarcoidosis.

III. Contributing Pathologic Conditions to HF
            Myocarditis. This condition implies chronic myocardial inflammation usually
              due to a viral or bacterial infection. May also be caused by chest radiation for
              treatment of malignancies (‘cancer”), sarcoidosis, and drugs (lithium, cocaine).
              Systemic lupus erythmatosus (SLE), a type of collagen vascular disease may
              result in a type of myocarditis.

              Myocardial Ischemia. This condition implies long standing myocardial ischemia
               (“lack of oxygen to the heart muscle”) with or without MI can increase the risk of

       IV. HF – Pathophysiologic Biophysical Concepts
            Progressive Ventricular Dilatation
            Law of LaPlace: T= P x R
              -The law of LaPlace can be used to help understand factors that contribute to the
       decline in pump function that is so characteristic of HF.
              T=Wall Tension, or the amount of force that it takes to squeeze the
              blood out when the heart contracts.
              P=Distending Pressure, or the amount of force caused by the blood
              pushing out on the sides of the heart muscle.
              R=Radius of the heart chamber (ventricle), or the distance from the
              center of the ventricle to the heart muscle.
       An increased filling pressure (P) and/or increased chamber diameter (R) will result in
       the heart having to work harder (T) to pump blood, and over time results in declining
       V. HF - Classified
            Left versus Right
            Forward = Decreased Perfusion
            Backward = Passive Congestion

       VI. HF - Clinical Picture
            Left - Sided Heart Failure
             a.      AMI
             b.      Systemic HTN
             c.      Mitral/Aortic Valve Disease
    d.     Coarctation of the Aorta
    e.     HF – “Fun Facts”
                  -Most common Hosp. Discharge Dx.
                  -Incidence is increasing due to better management of MI’s
                   (decreased mortality) and HTN
                  -> 30 billion in costs annually
                  ->5 million patients
                  -500,000 new diagnoses/yr
                  -12-15 million office visits/yr

    Systems Affected by left – sided heart failure:
    a.    Lungs
          1.     Passive congestion
          2.     Pulmonary edema
          3.     Orthopnea
          4.     Paroxysmal Nocturnal Dyspnea
    b.    Kidneys
          1.     Decreased renal perfusion due to reduced cardiac output
          2.     Sodium and Water Retention leading to volume overload

    -Left - Sided Heart Failure – Additional Characteristics
    a.      Anasarca - a generalized, massive edema. More common in right
    sided heart failure, but also seen in left-sided heart failure.
    b.      Pedal edema (Pitting)
    c.      Facial edema
    d.      Vasoconstriction – this occurs due to reduced renal perfusion with
    subsequent increase in renin release and formation angiotensin II, a
    potent vasoconstrictor. Aldosterone secretion from the adrenal
    glands also is triggered by renin, leading to reabsorption of sodium
    and water in the renal tubules and further exacerbating “volume
    e.      Hypertension/Hypotension – hypertension is usually seen earlier
    on, with hypotension occurring as the CHF worsens and pump
    function deteriorates.
    f.      Pulsus Alterans (alternating strong and weak pulse beats)
    g.      Fever & Pallor
    h.      Cardiac Cachexia – weakness and emaciation secondary to
    progressive debilitating HF.
    i.      Third Heart Sound, i.e. “lub-dub-dub”

   Right - Sided Heart Failure. 85% of those patients diagnosed with right sided
    failure have chronic obstructive pulmonary disease (COPD), which will be
    discussed in the section on respiratory disorders.
    a.      Acute myocardial infarction (AMI)
    b.      Pulmonary HTN
    c.      Tricuspid/Pulmonic Valve Disease
d.       Pulmonary Artery Stenosis
-Discussion of etiologic factors for right – sided heart failure.
a.       AMI – An MI that affects the right side of the heart will
potentially impair its pumping function. This would lead to a
“back-up” of fluid, as the cardiac output could not keep up with the
venous return to the right side of the heart.
b.       Pulmonary Hypertension - elevated pressures in the pulmonary
vasculature. A normal pulmonary arterial BP is about 20/10
mmHg. Elevated pulmonary pressures mean the right side of the
hard has to work harder to pump blood to the lungs. The major
cause of pulmonary HTN is COPD, and the leading cause of
COPD is smoking! – “Don’t Smoke!!
c.       Tricuspid/Pulmonic Valve Disease – stenotic and/or insufficient
valves leading to an increased workload on the right side of the
d.       Pulmonary Artery Stenosis – a narrowed pulmonary artery would
result in the right side of the heart having to generate more
pressure (“work harder”) in order to pump blood through a smaller
opening (“the narrowed vessel”).

-Systems affected by right – sided heart failure
a.      Lungs
        1.      Increased pulmonary vascular resistance
        2.      No Pulmonary Edema
        3.      No Passive Pulmonary Congestion
b.      Spleen & Liver
        1.      Passive Congestion
        2.      Splenomegaly & Hepatomegaly
        3.      Ascites
c.      Kidneys
        1.      Decreased perfusion – unlike with left-sided failure, the
        decreased perfusion is due passive back-up of blood/fluid
due to the failing right ventricle. The end result is the same
                i.e. sodium/water retention caused by increase in
        aldosterone secretion.

       2.      Anasarca – a generalized, massive edema
       3.      Pedal Edema/Pitting
       4.      Facial Edema

                             Medical University of South Carolina
                                  College of Health Professions
                        Divisions of Occupational and Physical Therapy

Cardiovascular Pathophysiology-Non-Atherosclerotic causes of Arteriosclerosis; Venous
and Lymphatic Disorders
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
David O. Sword DPT, PT

        Not all cardiovascular arterial diseases are caused by atherosclerosis, and several
may be attributed to other etiologic factors.

        A.       Cystic Medial Necrosis (Monckeburg’s Arteriosclerosis)

                This form of arteriosclerosis involves the tunica media (rather than the tunica
                intima). It is comparatively rare when compared to atherosclerosis, and
                commonly occurs in Marfan’s syndrome. Marfan’s syndrome is a genetic
                disorder, involving connective tissue. Individuals with the disorder are typically
                tall, thin, and lanky, with abnormally long limbs. They frequently develop
                cardiovascular disease, because of the involvement of the connective tissue in
                their arteries.

        B.     Thromboangiitis obliterans (Buerger’s disease)

                This form of arteriosclerosis is caused by an inflammatory reaction of unknown
                origin, which causes proliferation of fibroelasitic tissue within the arterial wall.
                The fibroelastic tissue gradually replaces the tunica intima, resulting in narrowing
                of the lumen, along with the formation of multiple thrombi. Statistically, the
                disease affects men about 5 times more than it affects women, and has its highest
                incidence in smokers. The disease is progressive, gradually resulting in ischemia
                with infarction at affected sites. The disease has no known relationship to the
                presence of hyperlipoproteinemia, and thus, bears no specific tie with


       A. Raynaud’s Disease

             Raynaud’s disorder (or syndrome) presents as a sudden, dramatic spasm of the small
             arteries in the digits. Patients with Raynaud’s disease are usually female, and may
             have a smoking history. Precipitating factors are cold temperatures and/or emotional
             stress, and patients having the disorder should be advised to stop smoking (if
             applicable). The disease has a high correlation with collagen vascular disease (i.e.
             rheumatoid arthritis, lupus erythematosus), but may often occur as a single entity in
            otherwise healthy individuals. Generally, patients respond favorably to cold
            avoidance and techniques for stress management.


       The diseases that follow are not directly related to the arterial system, but rather   involve
pathologic processes of the venous and lymphatic systems.

       A. Phlebothrombosis (or deep venous thrombus – DVT). DVT’s are the most
          commonly occurring acute disorder of veins. DVT’s most often occur in the deep
          veins of the calf muscles, but may also occur in the pelvic veins and even in the upper
          extremity deep veins. Symptoms and signs of a DVT are generally those of acute
          localized inflammation, i.e. pain, swelling, increased temperature, and redness around
          the area of the clot. In addition, passive dorsiflexion of the ankle and foot with an
          extended knee may exacerbate the pain around the affected area; such a finding is
          called Homan’s sign. DVT’s can occur in any age group, but are most common in
          the elderly and in immobilized patients.
          Causes of DVT’s include:
          1. Phlebitis, which is caused by localized irritation to a vein, such as seen in
               individuals receiving intravenous therapy, or in intravenous drug users.
          2. Venous stasis, in which venous blood flow becomes sluggish, with subsequent
               formation of clots. Venous stasis is a significant risk factor in:
          3. Post – surgical patients, especially in orthopedic surgery, in which a limb
               may be immobilized or in a cast;
          4. Spinal cord patients, since they have immobility from paralysis;
          5. Obese patients;
          6. Immobilized patients, especially those hospitalized who are over 50 years of
          7. Patients with CHF;
          8. Patients with blood dyscrasias, or with hypercoagulation syndromes,
               such as disseminated intravascular coagulation (also shows paradoxical
               bleeding, or DIC);
          9. Patients with varicose veins;
          10. Patients taking oral contraceptives.
          11. Patients taking the drug tamoxifen, for prevention or treatment of breast

        B. Chronic Venous Insufficiency (CVI)

               -CVI is an ongoing disorder, which can also produce DVT’s. This disorder is
               often seen in persons with right-sided CHF, or with limb paralysis following a
               stroke or other neuromuscular disease (such as multiple sclerosis). Besides
               DVT’s, persons with CVI may develop:
               1.      stasis ulcers, which is a large area of skin breakdown over the medial side
               of the leg, just above the ankle (these are generally relatively painless, as
               compared to arterial ulcers – which develop as a result of arterial insufficiency);
               2.      cyanotic pedal edema, which decreases overnight with elevation.
            3.      a generalized discomfort and feeling of “tightness” and “fullness” in the
            legs, ankles, and feet.

    C. Major Worries Associated with DVT’s

       1. Pulmonary embolism, in which a portion of the DVT breaks off and travels to the
           heart, passes through the right atrium and right ventricle, and lodges in a small
           vessel of the pulmonary infarct. If the embolus is large enough (i.e. a “saddle”
           embolus), a fatal episode can be the result. Many emboli are small (or very small,
           so as to be “microemboli”), and may break off as a “shower” of clots to the lungs.
           Patients may often survive these episodes, but still experience a rapid onset of
           dyspnea and generalized respiratory distress. NOTE: rarely, patients with a septal
           defect in the heart may develop a “paradoxical embolus”, in which the embolus,
           once entering the heart, will pass through the septal defect and travel to a systemic
           site (i.e. brain, kidneys) and cause an infarct;
        2. Osteoporosis, since patients may become non-weight bearing for extended
            periods of time;
        3. Stasis ulcers, associated with poor venous circulation in the skin.


     Lymph is removed from capillaries as part of the fluid which diffuses into the        tissue
spaces. Lymph is, therefore, an ultra filtrate, which is largely devoid of         protein, and is
     absorbed into the lymphatic vessels, which terminate as blind         endings in the tissue
spaces. Lymph is then re-circulated back into the venous           system, after flowing through
lymph nodes and lymphatic vessels. If occlusion of          the lymphatic vessels occurs
(lymphedema), then swelling occurs, the tissue becomes hard and firm, and the skin turns
yellow – orange (peau d’orange).
     Lymphedema – happens when a stasis of flow occurs in the lymphatic vessels,
     causing lymph to leak into the tissue spaces and cause swelling.

     A. Primary lymphedema – lymphedema with no specific cause. It may be
  present at birth (lymphedema congenita), occur later in life (lymphedema
  praecox), or develop after age 35 (lymphedema tarda). Primary lymphedema                     is
  more common in females than in males, and occurs most frequently in the
  lower limbs.
     B. Secondary lymphedema – lymphedema which occurs secondary to a disease
  or a surgical procedure. The most common example of secondary
  lymphedema is seen in post mastectomy patients, because the axillary lymph
  nodes (which allow upper limb lymphatic drainage) have been removed.
  Extreme forms of secondary lymphedema, producing trunk–like extremities
  (elephantiasis) and severe genital swelling is seen in tropical environments,
  and is caused by parasitic infestation of the lymphatics.
     C. Treatment for Lymphedema
             -Exercise – swimming, which activates the muscular pump;
             -Exercise – active movement, such as pedaling an imaginary bicycle;
             -Wearing an elastic garment, which simulates the muscular pump;

-Use of a forced action compression sleeve (such as a Jobst pump).

                           Medical University of South Carolina
                                College of Health Professions
                      Divisions of Occupational and Physical Therapy

The Hematological System and Hematological Diseases
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

    5. Name and explain at least 5 considerations that Physical and Occupational
       Therapists should give in planning and carrying out treatments for patients with
    heart and/or blood vascular disorders. For a summary of normal blood values,
    please see Appendix B on pp 152-153.

I. Signs and Symptoms of Hematological (or Blood Vascular) Disorders

   A. Symptoms and signs of blood vascular disorders are many and varied, but often include:
      1.      Edema and congestion, in which edema is the accumulation of excessive
      fluid with the interstitial tissues or within body cavities, whereas
      congestion implies the accumulation of excessive blood within the blood
      vessels of an organ or tissue (see under the congestive heart failure portion of this unit).
      2.      Thrombus and embolus, in which a thrombus is a blood clot that has
      formed either in a blood vessel or in the heart that has remained
      stationary, whereas an embolus is a blood clot that has broken
      off from its original location and has moved through a vessel to
      lodge at a distant site (see under the peripheral vascular diseases portion of this unit).
      3.       Infarction, which is cell death and tissue necrosis that is caused by a
      disruption in the blood supply (see under myocardial infarction portion of this unit).
      4.      Lymphedema, which is chronic swelling of an area due to accumulation
      of interstitial fluid secondary to obstruction of lymphatic vessels or lymph
      nodes (see under lymphatic disorders in this unit).
      5.      Shock (hypovolemic, cardiogenic, obstructive, septic, neurogenic), in
      which blood pressure falls so low that perfusion of the organs cannot
      occur (followed in some cases by organ failure). Blood moves according to a pressure
      gradient (delta P=Q (flow) x R (vessel resistance).
      6.      Anemia, in which the red blood cell count falls significantly, thus
      resulting in reduction in hemoglobin and the ability of the blood to carry
      oxygen to the organs and the tissues.
      7.      Polycythemia, in which too many red blood cells cause viscosity increase
      of the blood and congestion.
      8.      Leukocytopenia and leukocytosis, in which leukocytopenia means a
      significant reduction in the total white blood cell count (the person is then
      vulnerable to infection), whereas leukocytosis implies a blood disorder in
      which immature white blood cells accumulate (such as leukemia).

II.    Aging and the Hematopoietic System

        Aging affects the bone marrow, with the percentage of non-blood cell producing
        marrow being approximately equal to age, and reaching a plateau at round age 50.
        Red marrow, which produces both red and white blood cells, may be found in the
        vertebral bodies, sternum, pelvis, and skull. Non-blood cell producing marrow is called
yellow marrow (consists of fat), and is found in the long bones of the      extremities. A number
of other changes in the hematopoietic system occur with aging, such as:
        1.     Decrease in total serum iron, iron-binding capacity, and intestinal absorption of
        2.     Increased fragility of red blood cell membranes;
        3.     A rise in plasma fibrinogen and platelet adhesiveness;
        4.     Decreased hemoglobin (12-15 gms/100 ml) and hematocrit (36%-45%); Decrease
               in Vitamin B12 absorption, which can cause pernicious anemia;
        5.     Decreased number and size of lymph nodes, and;
        6.     Decline in cellular immunity due to altered T-cell function.

III.   Blood Transfusions

       A.      Patients receiving physical/occupational therapy who have undergone prolonged
       surgical procedures that have been accompanied by bleeding and patients
       who have been subjected to trauma are among likely candidates for
       transfusion. Patients who have undergone elective surgery may very well
       receive autologous blood transfusions (i.e. transfusions with one’s own
       blood), which minimizes the risk of a negative reaction. Also, the
       development of recombinant human erythropoietin (rHuEpo) has
       decreased the need for transfusion in many cases.***

***Erythropoietin is the active form of renal erythropoietic factor, which is produced by the
kidneys. Activated erythropoietin stimulates the bone marrow, thus promoting hematopoiesis.

       B.      Complications of blood transfusions are usually related to ABO
       incompatibility, and come about as a result of a Type II hyperimmune
       reaction, resulting in the destruction of red blood cells and intravascular
       clotting. Symptoms of an adverse transfusion reaction include: chills
       and fever, rash, jaundice, and blood stained urine. Occasionally,
       transfusion-related acute lung injury may result, which resembles adult
       respiratory distress syndrome.

       C.      Other negative outcomes of blood transfusion include: transmission of
       disease (Hepatitis B and C, HIV, air embolism, and circulatory overload.
       Sometimes, a blood transfusion reaction may not occur for several days,
       leading to a delayed transfusion reaction (usually the result of an
       undetected RBC antibody).

IV.   Specific Blood Disorders (Blood Dyscrasias)

      A.      Hemochromatosis is an autosomal recessive disorder caused by excessive
      iron absorption from the small intestine. The disorder favors men over
      women in a ratio of 8:1, and symptoms rarely appear until the individual
      reaches his 50’s or 60’s. In this disease, the affected individual is unable to
      remove iron that is absorbed in excess, so that iron begins to accumulate in
      the various organs and tissues (i.e. heart, pancreas, liver, skin, etc.). Iron
      accumulation in large amounts causes tissue damage, and may result in
      diseases such as arthropathy (which may be one of the first signs of the
      disease), liver damage and cirrhosis, cardiomyopathy, diabetes
      mellitus, pulmonary disease, and sterility. Symptoms include abdominal
      pain, weakness, fatigue, arthralgia, hepatomegaly, and abnormally
      darkened skin.
      B.      Porphyria is a disease in which there is a genetic error causing deficiency
              any of the enzymes along the hemoglobin synthesis pathway. The “heme”
              portion of hemoglobin is formed from porphyrins, so if the synthetic
              pathway is interrupted due to enzymatic deficieny, the porphyrins will
              accumulate and produce porphyria in the affected person
      C.      Descriptive measurements (indices) of blood are as follows:
              1.      Complete blood count (CBC): consists of a total red blood cell (rbc)
                      count/mm3, total white blood cell count/mm3, a differential white cell
                      count (i.e. the percentage of granulocytes-PMN’s, eosinophils, basophils-
                      and agranulocytes-monocytes, lymphocytes), a total platelet
                      count/mm3, a hemoglobin total/100ml blood, and a hematocrit (packed
                      cell volume). Other indices that are included: reticulocyte count
                      (immature rbc’s, mean corpuscular volume (MCV), mean corpuscular
                      hemoglobin concentration (MCHC-30%), and mean corpuscular
                      hemoglobin (MCH~30 pg). MCV, MCHC, and MCH are measurements
                      describing the volume of the rbc, the proportion of the rbc that is actually
                      hemoglobin, and the amount of hemoglobin per rbc, respectively
              2.      Hemoglobin exists in several forms (over 300 variants have been
                      identified). However, most variants that are actually observed in
                      the population are as follows: HbA-normal adult hemoglobin;
                      HbF-fetal hemoglobin; HbS-hemoglobin found in sickle cell
                      disease, and; Hb-Memphis type hemoglobin (an aberrant sickle
                      cell type).
      D.      The Anemias. Anemia is a reduction in the oxygen-carrying capacity of the blood
              due to an abnormality in the quantity and quality of red blood cells (hemoglobin
              <14 gms/100 ml in males and <12gms/100 ml in females). Anemia may be
              attributed to a variety of causes, including disease processes that result in
              excessive blood loss, destruction of erythrocytes, and decreased production of
              erythrocytes. In general, anemias have the following in common: 1) pallor,
              which is caused by decreased blood volume, decreased hemoglobin, and
              vasoconstriction to maximize oxygen delivery to major organs (see nail beds,
              mucous membranes of the mouth, and palmar creases); 2) tachycardia; cardiac
       murmurs (caused by increased velocity of blood flow); angina (chest pain),
       dyspnea, fatigue, headache, dizziness, syncope, tinnitus (ringing in the ears),
       anorexia, constipation/diarrhea, and stomatitis (sore tongue/oral mucous
       membranes). Persons with anemia generally have low rbc counts (< 5.4 million/
       mm3 in males; <4.5million/ mm3 in females).
       1.     Anemias caused from excessive blood loss: This form of
              anemia is the most common, and can be caused from
              chronic blood loss associated with cancer, long term use of
              aspirin or non-steroidal anti-inflammatory agents, or
              excessive bleeding from menstruation. This form of anemia is also
              known as normocytic, normochromic: rbc’s are of normal size
              and shape, and have normal Hgb concentration (MCH, MCV,
              MCHC are all normal).
       2.     Anemias caused by destruction on red blood cells: These anemias may
              be congenital or acquired. Congenital types include: sickle cell disease;
              acquired types include: autoimmune hemolytic anemia, malaria,
       3.     Anemias caused by decreased production of erythrocytes: In
              this scenario, two types of are possible:
              a.      Macrocytic, normochronic: rbc’s are enlarged but the
                      hemoglobin concentration is normal (MCH, MCHC are normal;
                      MCV is increased). This type of anemia occurs when DNA
                      synthesis has been interfered with, and is seen in vitamin B12
                      and/or folic acid deficiency states, or during cancer chemotherapy.
                      Pernicious anemia, which occurs dues to vitamin B12 deficiency,
                      is a type of macrocytic, normochromic anemia.
              b.      Microcytic, hypochromic: rbc’s are smaller than normal, and
                      hemoglobin concentration per rbc is below normal (MCH, MCHC,
                      MCV are all decreased). This type of anemia reflects insufficient
                      heme synthesis (iron deficient states), insufficient globin synthesis
       4.     Aplastic Anemia. Aplastic anemia is a life-threatening illness, in
              which the bone marrow is suppressed, thus resulting in an
              insufficient number of production of all blood cells (rbc’s , wbc’s,
              and platelets). The cause of aplastic anemia may be congenital,
              idiopathic, or acquired (viruses, antibiotics, certain chemicals have
              been blamed). Depending on the severity of the bone marrow
              depression, patients having aplastic anemia may survive long-term
              on supportive therapy, with gradual recover as the bone marrow
              recovers. Severe aplastic anemia with marked pancytopenia
              usually results in death quickly, due to internal bleeding and

E.      Polycythemia. Polycythemia is a myeloproliferative disorder in which
there are too many red blood cells. The condition results in increased
blood volume and increased blood viscosity. In polycythemia, an

increased number of white blood cells and platelets may also exist. There
are 2 basic types of polycythemias:

       a.     Primary polycythemia, or polycythemia vera. In this disease, the bone
              marrow overproduces blood cells. The disease mainly affects older men,
              and is progressive. The patient’s skin is rust-colored, eyes are blood-shot,
              and the patient may complain of headache with “fullness in the head”,
              dizziness, and fatigue. Because of the increased number of blood cells,
              vessel thrombosis is common. The bone marrow eventually exhausts itself
              due to over activity, or may convert to acute myelogenous leukemia.
       b.     Secondary polycythemia. Secondary polycythemia is an acquired form of
              the disease, and occurs when either: 1) the circulating volume of plasma is
              decreases (as in dehydration), or 2) the number of red blood cells increases
              due to some external cause (smoking, for example, causes CO2 build up in
              the blood, which in turn stimulates the bone marrow to increase rbc
              production). For treatment of secondary polycythemia, removal of the
              underlying cause usually corrects the condition.

F.    White Blood Cell Disorders
      1.     Neutrophilia-known as a “shift to the left,” implies an increased number
             of these neutrophils (PMN’s), and occurs during periods of stress, after
             violent exercise, and infection. Other WBC’s can also increase in response
             to certain disorders. For example, monocytosis occurs during chronic
             inflammation, eosinophilia occurs in allergy, basophilia may be present
             in certain malignancies, and lymphocytosis may occur in hepatitis,
             mumps, malignant lymphomas, and infectious mononucleosis.
      2.     Leukocytopenia and agranulocytopenia occur in certain viral infections
             and in bone marrow depression. Depending on the severity of wbc
             decrease, these can be very serious, if not fatal conditions.
      3.     Leukemia. Leukemia is a malignancy of the red bone marrow, in which
             massive amounts of immature and ineffective white blood cells are
             produced. The most common way of classifying leukemia is via the
             French-American-British (FAB) method, i.e. acute leukemia and chronic
             a.       Acute Leukemia. There are 2 basis types of acute leukemia, i.e.
                     acute lymphoblastic (ALL) and acute myeloblastic (AML).
                     AML accounts for about 80% of acute leukemia in adults, whereas
                     ALL is more common in children,
                     1.      Clinical manifestations of acute leukemia. In AML,
                             patients present with infection and/or bleeding, fever/chills,
                             tachycardia and tachypnea. Wbc counts are usually very
                             high, with the cytoplasm containing Auer rods (WBC
                             counts often > than 200000/mm3). RBC and platelet counts
                             may be very low. Since wbc’s are immature, individuals
                             with AML are at great risk for infection. Bleeding (gums,
                             subcutaneous, and internal) also is problematic, since
                             platelet counts are low. Without treatment, AML is fatal in
             3-6 months; combination chemotherapy produces remission
             in 70% of patients with the disease, and about 25% achieve
             5- year survival.
             In ALL, signs and symptoms are similar to AML, although,
             on occasion, WBC counts may be normal or low, but with a
             high lymphocyte count. Lymph nodes are enlarged in ALL,
             and patients generally have hepatosplenomegaly, and
             experience weight loss and night sweats. In addition,
             children with ALL are more likely to experience bone and
             joint pain than adults, as well as CNS effects (headaches,
             seizures, for example).
     2.      Both AML and ALL have rapid onset and have a high
             fatality rate, although with improved treatment, children
             with ALL have about a 90-95% chance of achieving
             remission (adults’ chances are about 80%). Along with
             chemotherapy, physical and occupational therapy, bone
             marrow transplantation is considered to be an important
             option for long-term survival.
b.   Chronic leukemia. Chronic myelogenous (granulocytic)
     leukemia (CML) has a slow onset, accounts for 15% of
     leukemias, and is most common in middle age adults. Granulocyte
     counts are high, and may be greater than 30000/mm3. In most
     cases, a chromosome abnormally called the Philadelphia
     chromosome is present translocation from C22 to C9). Persons
     with CML present with fatigue, weight loss, diaphoresis
     (sweating), heat intolerance, and hypersplenism. Stabilization can
     usually be achieve via numerous chemotherapies, but the disease
     generally progresses to an acute myeloblastic stage, with death
     occurring shortly thereafter. Median survival with CML is about 5-
     6 years. The other type of chronic leukemia in the FAB
     classification is Chronic lymphocytic leukemia (CLL). CLL
     usually occurs in older adults, and is characterized by the
     proliferation of small, immature lymphocytes (counts are usually
     around 100000/mm3. In most cases, the B-lymphocytes are the
     ones involved, leading to a decrease in antibody production. Signs
     and symptoms are similar to CML, with progression to
     hepatomegaly and lymphoadenopathy. Platelet counts fall,
     resulting in bleeding, and because of the effective WBC reduction,
     patients are prone to pneumonia and various infections. Some
     patients may survive 10 years or longer with CLL, others who
     develop aggressive formation of immature lymphocytes and severe
     thrombocytopenia may expect a much shorter survival rate; some
     of these may also develop autoimmune hemolytic anemia. A
     variant of B cell leukemia is Hairy cell leukemia, which has a 5:1
     adult male predominance.

G.   Disorders of Hemostasis
     Coagulation refers to a series of steps that form a platelet and fibrin clot
     for the purpose of limiting hemorrhage. Three major steps are needed: 1)
     transient vasoconstriction; 2) platelet aggregation, and 3) stepwise
     activation of the clotting factors. Clotting occurs through activation of
     an extrinsic pathway (initiated via the vascular endothelium) and an
     intrinsic pathway, which is initiated by factors in the plasma. Clot
     resolution is provided by plasminogen, which, in its active form (plasmin)
     breaks down and dissolves the fibrin in the clot. Plasminogen
     proactivators act to convert plasminogen to plasmin.

     Several disorders of hemostatis exist.
     1.     Vasculitis, in which small blood vessels are destroyed, results in
            purpura. Purpura can be caused by several diseases, as well as
            aging (Senile purpura). Other types of purpura are hereditary
            hemorrhagic purpura (Osler-Weber-Rendu), Erlos Danlos
            syndrome, and allergic purpura.
     2.     Several hereditary forms of purpura exist.
            a.      Hemophilia-a bleeding disorder that usually occurs in
            males, as it is a sex-linked recessive disorder. People with
            hemophilia A are missing clotting factor VIII; whereas
            Hemophilia B lacks clotting factor IX (Christmas factor).
            b.      von Willebrand’s disease-the most commonly inherited
                    coagulation disorder, and occurs equally in males and
                    females. In von Willebrand’s disease, platelets do not
                    adhere to collagen in the blood vessels, thus the patient has
                    a tendency to bleed very easily. A plasma protein called
                    von Willebrand’s factor facilitates platelet adherence to
                    vessels walls, and in von Willebrand’s disease, this factor is
                    low or missing.
     3.     Thrombocytopenia (platelet count <150,000/mm3 of blood) also causes
            purpura and internal hemorrhage. Thrombocytopenia is often a side effect
            of cancer that has metastasized to the bone marrow, of cancer treatment,
            and of aplastic anemia. Idiopaththic thrombocytopenia (ITP) is an
            autoimmune disorder that can also cause purpura and hemorrhage. On the
            other hand, thrombosis can occur, which can cause intravascular
            clumping and clotting. Two kinds of thrombosis occur: Primary
            thrombosis, which is a myeloproliferative disorder resulting over-
            production of platelets, and secondary thrombosis, caused by removal of
            the spleen, inflammation, and malignancy. Thrombotic
            thrombocytopenic purpura (TTP) disease in which multiple blood clots
            are formed in the circulation and the platelet count drops. The cause of
            TTP is thought to be due to a defect in the degradation of von
            Willebrand’s factor, thus platelets adhere easily to endothelium and
            intravascular clot formation is facilitated.
     4.     Disseminated Intravascular Coagulation (DIC). DIC is a
            hypercoagulation disorder that occurs sometime in cancer, following
                     trauma, in obstetrical situations (i.e. premature birth), following sepsis,
                     and in severe burns. In this disorder, the clotting mechanism is stimulated
                     by release of cytokines, and widespread clotting occurs in the small blood
                     vessels. The clotting is paradoxical in nature, as the clotting factors are
                     used at such a fast rate that none are available-thus massive hemorrhage

V.    Splenomegaly

      Many diseases can result in splenomegaly, including cysts, primary tumors, and vascular
      occlusion of the venous system. Tumors occurring at other sites (such as Hodgkin’s
      disease) also can cause splenic enlargement; persons with anemia also may have an
      enlarged spleen. Often removable of the spleen (splenectomy) will be of benefit to the
      patient having one of these conditions.

VI.   Please read in Goodman and Fuller pp 701-709 on malignant lymphomas (Hodgkin’s
      Disease and non-Hodgkins lymphoma), and pp 709-713 on multiple myeloma.
                                          End-Unit II

                                      Study Tips for Unit II
Be sure you can discuss/describe the following:

       a. Congestive heart failure (CHF) – both right and left pump failure and associated
       b. Various disorders of the heart and pericardium, including valvular disorders,
          myocarditis, pericarditis, and other pertinent problems as discussed in this unit.

       c. Acute myocardial infarction (AMI) – symptoms, signs, complications;

       d. Peripheral vascular diseases (PVD’s) – atherosclerotic disease vs. nonartherosclerotic
          diseases, venous disorders (superficial and DVTs), risk factors;

       e. Hematologic diseases, and state the pathology in terms of hematologic laboratory

Also, be sure that you can:

1.     Discuss/differentiate signs/symptoms of right ventricular pump vs. left ventricular
     pump failure, and name some potential causes of each.

2.     Differentiate between different general etiologies of CHF – (i.e. primary myocardial
       disease vs. increased pressure volume load).

3.     Define angina pectoris, acute myocardial infarction and their etiologies. Which vascular
       structures of the heart are usually involved?

4.     List and discuss various sequelae/complications associated with AMI. What is a

5.     Discuss valvular lesions and how they can affect cardiac efficiency. What is a heart
       “murmur”? Review EKG’s and enzymes as they relate to myocardial infarction.

6.     Define “arteriosclerosis”. Relate to “arteriolar sclerosis” and “atherosclerosis”, “non-
       atherosclerosis disorders”.

7.     Outline the parts of a “typical” artery.

8.     List and describe the types of atherosclerotic lesions. Where/when do they appear? How
       can they affect the individual?

9.     Outline the different risk factors for developing atherosclerosis.

10. Discuss hypertensive cardiovascular disease (high blood pressure). What are some
    pathologic complications of high blood pressure? What is “essential” hypertension? What
      is “renal hypertension”? What physiologic mechanisms must occur in producing “renal
      hypertension”? (i.e. the angiotensin-aldosterone sequence and effect).

11. Compare/contrast “atherosclerotic disease” vs. “non-atherosclerotic disease” and
    give specific examples of the latter.

12. Discuss phlebothrombosis, risk factors, and potential causes, and potential outcomes
   (i.e. pulmonary embolism).

13. Describe mechanisms for the formation of lymphedema and classify types (i.e.
   primary vs. secondary).


                             FORMATIVE EXAM (answers included)

    For each of the following, select the most appropriate answer.

    1. Which of the following is NOT considered to be a statistical risk for

       a.   being an elderly male
       b.   inheritance of hyperlipoproteinemia
       c.   being a diabetic
       d.   smoking habit
       e.   type B personality

  2. Symptoms and signs usually associated with right ventricular pump failure include
     all the following EXCEPT:

     a.   ascites
     b.   hepatomegaly
     c.   lower extremity venous distension/edema
     d.   pulmonary edema
     e.   splenomegaly

Answer questions 3-8 based on the patient presented in question 3

3.   A patient recovering from Hodgkin’s lymphoma missed his next appointment with you.
     After several days, you hear from his wife that he has been coughing and has become short
     of breath, and that he has been hospitalized with pericarditis and reduced left ventricular
     function. If this report is true, then which of the following should you expect regarding his

     a.     there will likely be permanent damage to his lungs and bronchial airways.
     b.     he almost certainly now has von Willebrand’s disease.
     c.     he likely has neurological paralysis of the diaphragm.
     d.     Hodgkin’s lymphoma increases his risk of developing systemic lupus
     e.     accumulation of the fluid in the lungs likely caused him to be short of breath.

4.   After the follow-up, you learn that the patient has been diagnosed with pulmonary edema.
     The most likely causative etiology was:

     a.     passive congestion in the pulmonary venous system
     b.     right ventricular failure with elevated hepatic portal vein pressure
     c.     increased urine output by the kidneys
     d.     systemic hypotension
     e.     extreme abdominal obesity that interferes with diaphragmatic function

  5. For pulmonary edema, his prognosis is best described by which of the following?

     a. he will have permanent loss of functional lung tissue.
     b. if the fluid volume overload is decreased, he will like have improved breathing.
     c. he will develop chronic obstructive pulmonary disease.
     d. he will develop cor pulmonale.
     e. he will develop a pulmonary blood clot, that will be passed through the heart
  and travel to the brain.

6.    As an inpatient with pulmonary edema, the biggest risk that he faces (of the
following) is:

     a. internal bleeding due to lack of prothrombin production.

      b. progressive left ventricular failure due to increased fluid retention and volume
      c. re-occurrence of his lymph node cancer due to the deconditioning effects of bed
      d. anaphylactic shock due to depletion of body fluids.
      e. sudden weight gain due to inactivity.

7.   After two weeks of hospitalization, you learn that he has developed
     a blood clot in his right leg. Which of the following most likely best explains the
     cause of the clot formation?

      a.   hypercoalgulation of blood caused by the toxins given off from lymphoma.
      b.   venous stasis in the deep veins of the legs as a result of hospitalization and inactivity.
      c.   arterial hypoxemia caused by hypoxemia due to left ventricular failure.
      d.   decreased arterial blood flow to the legs.
      e.   an increase in blood IgE levels secondary to the body’s immune response to combat

8.    The greatest risk for additional morbidity in this patient in association with the blood clot

       a. development of the disease thromboangiitis obliterans.
       b. development of a cerebral embolus and subsequent stroke.
       c. development of a pulmonary embolus.
       d. myocardial infarction, due to migration of the clot into the coronary circulation.
       e. development of gastrointestinal dysfunction, due to concurrent blood clots formed in
          the pancreas.

  9. Arteriosclerosis involving the renal tissue:

     a.    results in the kidneys releasing aldosterone
     b.    results in angiotensinogen release from the kidneys
     c.    ultimately causes water retention and diffuse vasoconstriction
     d.    causes the kidneys to convert angiotensin I to angiotensin II
     e.    activates angiotensin converting enzyme (ACE)

  10. Cor pulmonale is a natural consequence of:

     a. Chronic obstructive lung disease
     b. Systemic hypertension
     c. Anterior descending artery thrombus
     d. All of the above
     e. B and c only


1.    ANSWER IS E. Choice “a” is not considered to be statistically as at risk as being male
      (obviously, one has to be something!) Female sex hormones (i.e. estrogens) may actually
      have inhibitory effect on the lipid receptors of the vessel walls, whereas male sex
      hormones (i.e. androgens) may facilitate these receptors to take up and attach lipids.
      Generally, risk for atherosclerosis may increase after menopause, but the men are already
      ahead of the game. People with inherited hyperlipoproteinemia (i.e. increased blood
      lipids) are certainly at greater risk, and may often have very high serum cholesterol
      and/or triglycerides, and diabetes mellitus seems to alter metabolism to the extent that
      lipids in the body become mobilized, thus allowing their accumulation in the blood.

2.   ANSWER IS D. Choices a, b, c, and e are more directly in line with right pump failure,
     as they occur when the right ventricle dilates and fails, allowing venous pressure in the
     systemic circulation to rise. This can result in liver/spleen enlargement, fluid
     accumulation in the abdominal cavity, venous distension/edema in the lower extremities,
     etc. Right pump failure alone is not generally associated with pulmonary edema, since
     the problem of congestion tends to appear on the venous side rather than the arterial side
     of the pump. Pulmonary edema is more likely to be a complication of left pump.

3.   ANSWER IS E. Pulmonary edema is caused in this case by left ventricular failure. The
     fluid will occupy the pulmonary interstitial spaces, and compress and infiltrate the
     alveolar spaces, making breathing difficult. There is no known relationship between
     pulmonary edema and diaphragmatic paralysis, or systemic lupus erythematosus (a
     collagen vascular disease to be discussed in the next unit).

4.   ANSWER IS A. With left ventricular failure, the pulmonary veins become overloaded
     with fluid congestion, which filters through the pulmonary capillaries and causes
     pulmonary edema. None of the other choices are directly related.

5.   ANSWER IS B. If the fluid volume overload is removed, the he should show improved
     breathing. None of the other choices are relevant.

6.   ANSWER IS B. Prothrombin is important in blood clotting, but is produced by the liver
     (Choice a). Pneumonia has no know relationship to lymph node cancer (Choice c) or
     anaphylactic shock (Choice d).

7.   ANSWER IS B. Hospitalization and inactivity increases the risk of venous stasis,
     especially in older patients. Venous stasis many times results in formation of thrombi in
     the deep veins of the legs (most common site). All the other choices in this question are
     purely distracters-none has any bearing on the case.

8.   ANSWER IS C. Pulmonary embolus is always the main worry in a venous thrombus. If
     the clot, or piece(s) of the clot break(s) off, the piece(s) can be swept thought the
     circulation, through the right side of the heart, and into the pulmonary circulation. Once
     in the pulmonary circulation, it(they) can occlude pulmonary vessel(s) and cause
     blockage of flow. The outcome can range from shortness of breath and chest pains to
     instant death. Choice c is a true statement, but does not pertain to the question that is
     implied in this item. In Choice b, the embolus would have to bypass the lungs and enter
     the systemic circulation for a CVA to occur. Such an event would be rare, and would
     typify a “paradoxical embolus,” in which a clot passes through a defect in the septum of
     the heart, and thus bypasses the lungs. If such an event occurred, then the migrating clot
     could potentially affect any organ, i.e. the brain (Choice b), heart, via the coronary
     circulation (Choice d), etc. Choice a is false because thromboangiitis obliterans is an
     arterial disease associated with smoking in males-the present case involves venous
     thrombi. Choice e is a distracter.

9.   ANSWER IS C. Arteriosclerosis involving the renal tissue (or arterionephrosclerosis)
     tends to cause the kidney to increase the secretion of the hormone renin, which triggers
       the progressive activation of angiotensinogen, aldosterone, etc. This is actually a
       homeostatic mechanism gone astray, in which the kidney is “fooled” into thinking that
       the individual needs to retain water and increase the peripheral resistance from impending
       shock due to excessive fluid loss, vascular collapse, etc. The whole process results in the
       activation of Angiotensin II in the plasma protein fraction, which causes blood vessels to
       constrict and raises the peripheral resistance, as well as the increased secretion of
       aldosterone by the adrenal cortex. Aldosterone promotes retention of sodium and water
       by the renal tubules. A is false because the adrenal, not the kidneys, produce aldosterone.
       B is false because angiotensinogen is a plasma protein, not produced by the kidneys. D is
       false because Angiotensin I is converted to Angiotensin II in the lungs by the enzyme
       ACE. E is false because activated angiotensinogen (Angiotensin I) seems to activate
       ACE, not renal arteriosclerosis. See Price and Wilson, p. 671.

10.    ANSWER IS A. Cor pulmonale refers to right ventricular heart disease secondary to
       pulmonary disease of a long standing nature. As the lung forms shunts, loses arterial and
       vascular integrity, etc., and increased working load is placed on the right ventricle,
       resulting eventually in hypertrophy, dilatation, and potential CHF. COPD often causes
       this disorder, because of the long standing nature of the disease. Systemic hypertension
       would most likely affect the left ventricle (i.e. a primary myocardial disease).

                                            UNIT III


     Medical University of South Carolina
          College of Health Professions
Divisions of Occupational and Physical Therapy

Respiratory Pathophysiology-Overview of Chronic Pulmonary Disorders and Bronchial
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
David O. Sword DPT, PT

Chronic Pulmonary Diseases
There are two broad categories of chronic pulmonary disease:
I. Common Conditions Resulting From Pulmonary Disease
      Hypoxemia – reduced O2 content in the blood due to respiratory alterations/disease.
      Hypoxia – lack of O2 availability to the body’s tissues. May be due to hypoxemia or
      other non-respiratory causes.
      Hypercapnia – increased CO2 content in the blood due to respiratory
      Pulmonary Edema – fluid accumulation in the lung tissue. May be due to pulmonary
      disease, heart failure, and other systemic conditions.

II. Pulmonary Disease: Signs and Symptoms
       Abnormal Sputum
       Chest Pain
       Digital Clubbing
       Altered Breathing Patterns

III. Altered Breathing Patterns
        Apneustic – gasping inspiration followed by short or absent expiration. “Sleep Apnea”
        Biot’s – Irregular pattern of deep and shallow breaths interspersed with abrupt pauses
        in breathing.
        Cheyne-Stokes – Repeated cycles of deep breathing followed by shallow breaths or
        cessation of breathing.
        Hyperventilation – increased alveolar ventilation, relative to metabolic demands.
        Typically due to increased frequency of breaths, rather than increased depth of breathing.
        May result in a drop in PaCO2 (“hypocapnia”).
        Hypoventilation – decreased ventilation, relative to metabolic demands. Shallow
        and/or infrequent breaths. May result in a rise in PaCO2 (“hypercapnia”).
        Kussmaul’s – abnormally deep and rapid respirations, characteristic of diabetic coma.
        Stridor – high pitched sound created by an obstruction to airflow, especially an
        obstruction at the level of the trachea or larynx.
        Wheezing – high pitched sounds created as air passes through narrowed
        tracheobronchial airways. Commonly heard in individuals with asthma.
IV. Pulmonary Diseases:

      A.       Chronic Obstructive Pulmonary Disease (COPD)
              Airway Obstructed during Exhalation
              Abnormal Pulmonary Function Flow Curve
              General Characteristics-COPD
               -Pulmonary Functions Testing: Airflow Decrease- Reduced FEV1
               -Hypoxemia, Hypercapnia
               -Air Retention
               -Diffusion Block
               -Shunt effect with V / Q imbalance
               -COPD – Blood Gases
               1.     Arterial Blood Gases (ABGs)
                      a.      Arterial pO2 (80-100 mm Hg)
                      b.      Arterial pCO2 (35-45 mm Hg)
                      c.      Hemoglobin O2 saturation: SaO2 (95-100%)
               2,     Respiratory acidosis
                      a.      ↓ ph of body fluids: Normal = 7.35-7.45
                      b.      Hypoventilation
                      c.      Excess carbonic acid in the blood (H2CO3)

      B.       Specific Diseases resulting in COPD
              Bronchial Asthma-characteristics
               -Hyperactive Airway Disease
               -Wheezing – Rhonchus
               -Asthma Stats:
               1.     5000 Deaths/year
               2.     10,000,000 individuals in the US with asthma
               -Asthma-common triggers:
               1.     House Dust Mites
               2.     Cigarette Smoke
               3.     Cockroaches
               4.     Hyperthyroidism
               5.     Exercise, i.e. Exercise Induced Asthma (EIA)
               6.     Emotional Distress
               7.     Cold Air
               8.     Allergens (Mold spores, Pollen)
               9.     Idiopathic
               -Asthma Pathophysiology
               1.     Bronchial smooth muscle spasm
               2.     Bronchial mucosal edema
               3.     Increased bronchial secretions
               -Asthma-Symptoms and Signs
                     Perspiration
      Flared nostrils
      wheezing
      Cyanosis
      Flushing
      Cough
      Respiratory distress
      Dyspnea
      Use of accessory respiratory muscles
      Apprehension
      Tachycardia
      Diminished breath sounds

-Types of Bronchial Asthma
1.     Intrinsic (Adult Onset)
2.     Extrinsic
3.     Mixed
-Description of Bronchial Asthma Types
1.     Intrinsic Asthma
       a.      No Childhood History
       b.      Not IgE Induced-No Allergens
       c.      Chronic Sinusitis, Nasal Polyps
       d.      Exercise Induced
       e.      No Family History
       f.      Possible contributor: Gastroesophageal Reflux Disease
2.     Extrinsic Asthma
       a.      Allergen Provoked (may be inhaled or ingested)
       b.      IgE Mediated
       c.      Exercise Induced
       d.      Cold Temperature Induced
       e.      Pathophysiologic mechanism-Extrinsic asthma is a Type I
       Hyperimmune reaction (anaphylactic) that involves
       immune complexes formed between the allergen and IGE.
       The immune complex formed results in degranulation of
       the mast cells and subsequent release of inflammatory
       substances that cause: 1) bronchial constriction; 2)
       increased bronchial secretions, and; 3) bronchial mucosal

3.     Mixed Asthma
       a.    Intrinsic component
       b.    Extrinsic component
       c.    Same symptoms

-Status Asthmaticus-a profound and severe, potentially life-threatening
1.     Severe

            2.    Intractable
            3.    Rapid Breathing-pCO2 Falls
            4.    Hypocapnea
            5.    Fatigue and Exhaustion
            6.    Breathing Slows-pCO2 Rises
            7.    Hypercapea

                        Medical University of South Carolina
                             College of Health Professions
                   Divisions of Occupational and Physical Therapy

Respiratory Pathophysiology-Pulmonary Disorders: Pneumonia and COPD
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
David O. Sword DPT, PT

I. Common Signs and Symptoms of Pulmonary Disease
       Chest Pain
       Digital clubbing
       Altered breathing patterns
   -Discussion of Signs and Symptoms of Pulmonary Disease
     Cough
       Dry cough
       –Hypersensative airways
       Productive cough
       –Purulent sputum indicates infection
       –Non-purulent sputum indicates non-specific irritation
       –Hemoptysis indicates pathologic condition
    Dyspnea
       Hallmark feature of pulmonary disease
       Occurs secondary to inadequate ventilation and/or lack of O2 in the circulating blood
       Occurs mainly with diffuse, rather than localized disease

    Orthopnea – dyspnea when lying down, secondary to fluid shifts and decreased
       efficiency of the respiratory muscles.

    Chest Pain
       Usually substernal, or over the involved lung field
       May mimic angina, including radiation to the neck or UE
       Pleural irritation may result in sharp pain that is reduced by lying on the affected side,
       thus limiting movement (“autosplinting”)

      Cyanosis
       Noted as bluish coloring of the skin and mucous membranes.
       Occurs secondary to reduced oxygen saturation of the blood and/or reduced
       hemoglobin content

      Digital Clubbing
       A loss of the normal angle between the nail and nail-bed on the fingers and toes.
       Results in a club-like appearance
       Thought to be caused by a chronic perfusion deficit secondary to pulmonary disease.
       May also occur with certain cardiac, liver, and GI disorders
      Altered Breathing Patterns
       Change in the normal rate, depth, regularity and effort of breathing
II. Pulmonary Changes with Aging
        respiratory muscle strength and endurance
        in # of elastic fibers in the lung tissue
        chest-wall stiffness
        in overall lung function (FVC, FEV1)
        work of breathing (WOB)
        susceptibility to respiratory infections
        complications during anesthesia

III. Pulmonary Changes with Aging-PT/OT Implications
               –Expect reduced exercise capacities in older adults
        –Be aware of signs/symptoms of pulmonary disease, including abnormal
         breathing patterns
        –Monitor vital signs at rest and during activity, including pulse oximetry if
        –Educate on importance of regular aerobic exercise to reduce the age-related
         changes in cardiorespiratory function

IV. Acute Pulmonary Diseases

      Pneumonia
       Acute lung tissue inflammation
             –chills / fever
             –elevated WBCs
             –respiratory distress
             –sputum changes
             –cloudy areas on chest x-ray
      Pneumonia - Etiology
      Bacteria / Virus
              -Diplococcus pneumoniae (pneumococcal) >50%
              -Klebsiella pneumoniae (“Friedlander’s”) – typically seen in middle-aged
      Hypostasis
       Aspiration
       Fungus
       Virus
               -50% of All Types
               -Influenza A, B, C
       Pneumonia - Types
        1.     Lobar Pneumonia
              Self-limiting
              Involves an Entire Lobe
              Produces an intra-alveolar exudates
              Follows a 10 Day Course
              Pneumococcus and Klebsiella are common causes
              Consolidation of the affected lobe
              Occurs mainly in healthy Adults

        2.     Bronchopneumonia
              May cause pleural effusion and hydrothorax
              May result in atelectasis (“collapsed lung”)
              Diffuse patchy consolidation pattern
              Usually Bilateral
              Occludes small airways
              Longer Recovery; permanent damage
              Elderly and infants
              May result in pleurisy
              Staphylococcus and Streptococcus are common causes

    V. Respiratory Diseases-Other types of COPD
       Chronic Bronchitis
       Chronic Bronchitis
        –Progressive Disease
        –May have a hyperactive airway component
        –High incidence in England
        –Smoking history
       Emphysema
        Progressive destruction:
        –Of Distal Airways
        –Of Alveoli
              Irreversible and progressive
              Pulmonary Infections are common
              “End Stage” Lung Disease
              Males > Females

            Types of Emphysema
        1.      Centrilobular
        2.      Panlobular
        3.      Mixture

       Discussion of Emphysema Types

        1.     Centrilobular Emphysema
                     Destruction of respiratory bronchioles
                     Affects the central acinus of the lung
                     Poor ventilation causes V/Q imbalance
                     Cyanosis, bradypnea, well-nourished
                     Cor pulmonale

        2.     Panlobular Emphysema
                    Affects all of the Alveoli of an Acinus
                    Increased Pulmonary Dead Space
                    Diffusion Block
                    Compensation by Tachypnea
                    Spontaneous Pneumothorax-Blebs
                    Bullae Formation

   Other Types of Obstructive Pulmonary Diseases
    Carcinoma of the Lung
    Cystic fibrosis
   Discussion of other types of Obstructive Pulmonary Diseases
     Bronchiectasis
       -Common Causes:
       1.     Pertusis (Whooping cough)
       2.     Measles
       3.     Bronchopneumonia
       4.     Chronic Bronchitis

       Carcinoma of the Lung
        -Airway Blockage

   Cystic Fibrosis (CF)
    -Early mortality: 80% over the first 2 decades
    -Recessive Trait
    -“Much Mucus,” which is produced by both the lungs and the pancreas
    -GI malabsorption
    -Intestinal Blockage

   Cystic Fibrosis: Clinical Picture
    -Thin, Asthenic
    -Barrel Chest
    -Protruding abdomen
    -Elevated shoulders

   Cystic Fibrosis Treatment Options
    -Postural Drainage
    -Exercise; Breathing Exercises
    -Pursed-lip Breathing
    -Antibiotics & O2
    -Laryngeal Control

                           Medical University of South Carolina
                                College of Health Professions
                      Divisions of Occupational and Physical Therapy

Respiratory Pathophysiology-Pulmonary Disorders: Restrictive Disease
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
David O. Sword DPT, PT

I. Chronic Restrictive Pulmonary Disease
     Implies respiratory depth restriction
     No blockage of air flow
     Pulmonary volume reduction
     Pulmonary under inflation
     Pulmonary functions testing (PFT)
     Terms that define PFT:
      -Tidal Volume (TV)
      -Inspiratory Reserve Volume (IRV)
      -Expiratory Reserve Volume (ERV)
      -Residual Volume (RV)
      -Total Lung Capacity (TLC)
     PFT’s in chronic restrictive pulmonary disease
      -Flow normal
      -Volume reduced

II. Chronic Restrictive Pulmonary Disease affects the lung parenchyma. Specific
    diseases that cause chronic restrictive pulmonary disease include:

      Pneumoconiosis – this disease is an inflammatory fibrosis of the lungs that occurs as a
       result of occupational or environmental exposure to dust particles, usually mineral dust.
       The outcomes of pneumoconiosis are:
       »chronic irritation/inflammation
       »extensive fibrosis
       »Specific named diseases that represent examples of pneumoconiosis include:
               1.      Silicosis – long-term exposure to silica dust (“mining”)
               2.      Anthracosis – long-term exposure to coal dust (“black lung”)
               3.      Asbestosis – exposure to asbestos fibers

      Other causes of Chronic Restrictive Pulmonary Disease
          »   Orthopaedic Disorders
          »  Thoracic Deformities Restricting Ventilation (these included deformities such as
             pectus excavatum (hollow chest) and pectus carinatum (pigeon breast).
      Other causes of Chronic Restrictive Pulmonary Disease (continued)

   »   Obesity, which may cause Pickwickian Syndrome
   »   Sarcoidosis (which has an unknown etiology, but carries the following
       1.     High incidence in African-Americans
       2.     Deposits of gamma globulins
       3.     Increased B lymphocytes
       4.     Decreased T lymphocytes
   »   Neurologic causes, including:
       1.    Quadriplegia
       2.    Guillain-Barre Syndrome

   »   Muscular
       1.    Muscular Dystrophy

7. Pleural disorders – numerous disorders of the pleural membranes can cause
   restriction of lung expansion. Examples are:

   a. fibrosis of the pleurae, secondary to chronic pleuritis. Pleural fibrosis and
       calcification can be either post inflammatory or asbestos related. Pleural
      inflammation commonly causes acute pleural thickening due to fibrosis. In
       most cases, the thickening resolves almost completely. Some patients are
       left with minor degrees of pleural thickening, which usually produces no
      symptoms or impairment of lung function. Exposure to asbestos can also lead to
      focal, plaque like pleural fibrosis, at times with calcification,
      occurring up to ≥ 20 years after the initial exposure;
    b fluid in the pleural space (hydrothorax, pleural effusion from an exudate
      or transudate), which can compress the lungs and cause restriction to
   c. air in the pleural space (pneumothorax – see below), and hemothorax
      (bleeding into the pleural space – trauma or bleeding disorder).

8. Empyema – an empyema is a lung abscess, secondary to pulmonary infection, can
   occupy a large portion of a lung and cause a restricted pattern of breathing.

9. Pneumothorax – as mentioned above in #7, a pneumothorax occurs when there is air
   in the pleural space. Pneumothorax may occur secondary to chest trauma, or, in some
   cases, it may occur spontaneously. Each is explained as follows:
   a. traumatic pneumothorax – may be open or closed. Open pneumothorax
       occurs when a puncture wound penetrates the thorax and enters the pleural
       space, and there is no tissue flap covering the wound. Closed
       pneumothorax occurs when a puncture wound enters the pleural cavity,
       but a tissue flap covers the
       wound. Since the pressure in the pleural space is negative (-2 to –6 mm
       Hg), air is pulled into the plural space with each inhalation. The air is not
       pushed back out with exhalation, so air accumulates in the pleural space.

              Since air is non-compressible, air accumulation in the plural space rapidly
              compresses the lung. This condition is called a tension pneumothorax,
              and constitutes a serious, life- threatening emergency. The tissue left in
              closed pneumothorax, if it seals and does not act like a "one way" valve,
              may partially prevent this process from happening.
          b. spontaneous pneumothorax – occurs when a fissure occurs
          spontaneously, or without known cause, in the pleural sac. This condition
              allows air from the lung to leak into the pleural space. Spontaneous
          pneumothorax has symptoms of sudden onset of chest pain and pain with
          respiration. The occurrence generally is self-limiting, and heals within
              several days. Episodes of spontaneous peumothorax are highest in
          smokers, and there is a statistical incidence of higher
              than usual occurrence in blond males.

    10. Scar tissue formation in the lung parenchyma, due to collagen vascular
        Disease (such as rheumatoid arthritis). Collagen vascular disease is an
        autoimmune disease that generally affects joints. However, the autoimmune
        process may affect other organs as well (i.e. lungs, pleural, liver, heart, CNS).

    11. Amyloidosis – amyloid is glycoprotein, which when present in the blood, can
        be deposited in the lungs. The deposits cause inflammation and scarring,
        which restricts breathing. The cause for formation of amyloid is unknown, but
        it appears to be associated in some way with aging.

 B. Respiratory Distress Syndrome of the Newborn (RDS)

    RDS, or Hyaline Membrane Disease occurs in premature infants born before 7 months
    gestation. The disorder is caused by absence of surfactant on the mucosal surfaces of
    alveoli and small airways. Since mucosal surfaces are moist, they create a surface tension,
    which in turn, causes collapse of the alveoli and small airways. After 7 months gestation,
    lung maturity is usually complete, and enough surfactant is present to avoid airway/alveolar
    collapse. Surfactant is a lipid based substance, and, when present, coats mucosal surfaces
    and reduces surface tension. Surfactant consists of the lipid substances lethicin and
    sphingomyelin. Lung maturity is considered to be sufficient to allow normal breathing in
    infants when the lethicin/sphingomyelin ratio reaches 2:1. Lethicin/sphingomyelin ratios
    can be determined from a sample of amniotic fluid, obtained via amniocentesis. RDS can
    be treated with oxygen and life support, which may sustain the life of the infant until
    surfactant forms and the lung reaches maturity. Extracoporeal membrane oxygenation
    (ECMO) has been used successfully, and has improved the prognosis for premature infant
    survival. A side effect of oxygen therapy in premature infants is O2 induced blindness, a
    condition which is permanent. Oxygen is toxic to the retina of premature infants, and
    causes loss of photoreceptors and retinal scarring. The condition is called retrolental

 C. Adult Respiratory Distress Syndrome (ARDS). ARDS was first reported in the      late
1960’s as a severe form of respiratory distress of unknown origin. ARDS was noted to
happen sometimes in adults following recovery from trauma. The cause of     the onset of
ARDS has been poorly understood, and until recently, it has been almost uniformly fatal.
     While ARDS is still associated with high mortality, better understanding on itpossible
etiology has made treatments more effective. The pathophysiologic mechanism of ARDS is not
clear. Research on ARDS has suggested that the characteristic alveolar edema seems to involve
injury to the alveolar capillary membrane with the production of a capillary leak. The alveolo-
capillary membrane is normally impermeable to particles. However, with injury this
impermeability is weakened, and an influx of blood proteins, leukocytes, erythrocytes, and fluid
occurs. The fluid first accumulates in the interstitium; when the capacity of the interstitium is
exceeded, the fluid moves into the alveolus, causing congestive atelectasis. Also, alterations in
the surfactant may play a part in diffuse atelectasis, and the proteinaceous material of the
alveolus may become organized into hyaline membranes. Thus, the pathologic picture is similar
to that of RDS of the newborn. Since ARDS appears to be part of an inflammation-induced
systemic state, the course of the illness can evolve into multiple organ failure as well as
respiratory failure. ARDS is generally treated with positive end expiratory pressure (PEEP) to
expand alveoli, oxygen therapy, and with rehabilitation, i.e. physical and occupational therapy.
Patients recovering from ARDS may also require speech therapy if laryngeal damage has
occurred. Research on ARDS has focused on the mechanisms leading to inflammation, particular
the role of PMN's, platelets, and clotting factors.

        ARDS: Note fluid that has moved into the alveolus preventing gas exchange

                            Medical University of South Carolina
                                 College of Health Professions
                       Divisions of Occupational and Physical Therapy

Collagen Vascular Diseases and Arthopathies
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

    Collagen vascular diseases (CVD’s) represent a group of diseases affecting collagen, which
    is the protein component of connective tissue. CVD’s develop when autoantibodies form
    which react with the protein in collagen. The antigen – antibody complex which is formed
    causes a localized inflammatory response, resulting in pain, tissue damage, and ultimately,

I. Common Features of CVD’s

   All the collagen vascular diseases have the following in common with each other:

  A. They all affect blood vessels via the collagen in the vessel wall;
   B. They are all chronic diseases, and patients typically experience remissions and
   C. They are all autoimmune diseases, and are caused by the formation of autoantibodies
      which form antigen – antibody complexes with collagen in joints, blood vessels, and
      internal organs.
   D. They affect more females than males in varying ratios, an exception being the CVD
      Polyarteritis Nodosa (and its variants), which is more prevalent in males (see subheading
      F in the following text).
  Common Signs and Symptoms of CVD’s

  A. Weight loss and poor appetite;
  B. Anemia, which is generally a normochromic, normocytic type; (hypochromic – below
     normal hemoglobin concentration in each red blood cell; microcytic – small red blood cell
     size and appearance). This is characteristic of “iron deficiency anemia.”
  C. Fatigue;
  D. Fever;
  E. Joint and musculoskeletal pain, due to localized inflammation;
  F. Joint deformities (see below);
  G. Elevated erythrocyte sedimentation rate (ESR). This feature is often used as a
     diagnostic point, but may also occur in other febrile illnesses (i.e. colds, infections). ESR
     is demonstrated by allowing a blood sample to stand for an hour, then measuring (in mm)
     the distance of sedimentation that the red blood cells undergo due to gravity. This
     measurement, in mm/hr, is reported as the ESR. In CVD’s, circulating autoantibodies
     attach to erythrocytes, causing them to become heavier, and thus, settle faster (therefore,
     the ESR is “elevated”).
  H. Raynaud’s syndrome may be present. Since the blood vessels have inflamed walls, they
     may tend to go into spasm. When small vessels in the digits have spasm, the lumen is
   occluded, producing reduced blood flow. As in classical Raynaud’s, emotional distress,
   exposure to cold, and smoking tend to exacerbate the spasm.

II. Specific CVD’s

   a. Rheumatoid Arthritis (RA). Rheumatoid arthritis is the most common and probably
      the most well – known of the CVD’s. RA has been shown, through large sample
      studies, to be more common in females than in males, with a female to male ratio of
      5:2. Peak years of incidence for RA are in individuals 40 – 60 years of age. An
      aggressive form of the disease also occurs in children, and is known as juvenile
      rheumatoid arthritis (JRA). In RA, autoantibodies attach to collagen in the synovial
      lining of joints, causing inflammation. Redness, pain, and swelling cause dysfunction,
      and, over time, the joint structure breaks down. Within the joint cavity, there is
      formation of rheumatoid pannus. Rheumatoid pannus is an inflammatory exudate
      which collects around and over the synovial lining of affected joints.

      Clinical features associated with RA are:
      1. Constitutional symptoms, i.e. loss of appetite, fever, and fatigue;
      2. Peripheral distal polyarthritis, as the disease usually affects multiple distal joints,
          i.e. hands/finger, feet, elbow, knees;
      3. Morning stiffness/pain, generally lasting more than 1 hour;
      4. Joint erosion and breakdown with pannus formation, which is visible on X-ray.
          As a result, joint deformities form ulnar drift, boutonniere deformity flexion at the
          PIP, and hyperextension at the DIP), and swan neck deformity (hyperextension of
          the PIP and flexion of the DIP).
      5. Rheumatoid nodules may be observed, which are subcutaneous granulomas. A
          common place to find a rheumatoid nodule is just below the elbow, as the nodule
          has formed in the olecranon bursa.
      6. Extra-articular manifestations that may develop, in which other areas in addition
          to joints may be affected. In such cases, the same autoantibodies which react with
          collagen in synovial lining also react with collagen elsewhere in the body. The
          table below gives examples of extra – articular manifestation sites, along with
          pathologic outcomes produced.

                      Extra-articular Manifestations of Rheumatoid Arthritis

Skin                                             Subcutaneous nodules
                                                 Vasculitis, causing brown spots
                                                 Ecchymotic lesions

Heart                                            Pericarditis
                                                 Pericardial tamponade (rare)
                                                 Inflammatory lesions in the myocardium
                                                 and the valves
Lungs                                            Pleurisy, with or without effusion
                                                 Pulmonary inflammatory lesions

Eye                                              Scleritis

Nervous System                                   Peripheral neuropathy
                                                 Peripheral compression syndromes,
                                                 including carpal tunnel, ulnar nerve
                                                 neuropathy, peroneal palsy, and cervical
                                                 spine abnormalities

Systemic                                         Anemia (common)
                                                 Generalized osteoporosis
                                                 Felty’s syndrome
                                                 Sjogren’s syndrome (kerato-conjunctivitis
                                                 sicca)-Anti Ro/SS-A is a blood marker
                                                 present in about 70% of cases
                                                 Amyloidosis (rare)

   b. When working with patients suspected of having RA, the following assessment criteria
      should be noted:

        1.       In almost every case, signs of RA (i.e. redness, swelling, pain) will be
                 present in at least 3 or more joints;
        2.      Affected joints generally follow a symmetrical pattern, i.e. bilateral hands
                and feet, bilateral knees, etc. in adults. In juvenile rheumatoid arthritis
                (JRA), however, monoarthopathies are often noted;
           3.    Rheumatoid nodules are often present, especially at the olecranon bursa (as noted
           4.    Patients may complain of morning stiffness, which lasts for a long time (at least 1
                 hour is considered to be significant) (see above);
           5.    Bony erosion in joints is generally visible on X-ray (see above);
           6.    Rheumatoid factor (IgM) may be measured in the blood. Rheumatoid factor is
                 present in nearly all persons (about 80 – 90%) with RA, and is considered to be one
                 of the most specific criteria suggesting the presence of the disease. Another blood
                 marker that has been recently associated with rheumatoid arthritis is Anti-CCP,

           which stands for anti-cyclic citrullinated peptide antibody. A directed against one or
           more of the individual’s own proteins)

c. Osteoarthritis (OA – DJD) vs. RA. Both persons with osteoarthritis, or degenerative joint
   disease, and RA share some commonalties, i.e. early morning stiffness, sore, inflamed
   joints, and loss of ADL’s. However, when compared, distinct differences exist between the
   two diseases. Firstly, OA is NOT a CVD! Close attention to the differences between the
   diseases allows better understanding, and appropriate treatment can be offered to the
   patient. Several of these important differences may be noted as follows:

        1 OA affects, mainly the weight bearing joints and/or proximal joints (hips,
        knees, shoulders) whereas RA affects mainly the distal joints (although
        proximal joints may also be affected);
        2. DIP’s are almost always affected (Heberden’s nodes) in OA, whereas the
           PIP’s are more often affected in RA;
        3. The PIP’s are sometimes affected in OA (Bouchard’s nodes);
        4. In OA, morning stiffness is generally of shorter duration than RA, but pain
           progresses throughout the day in OA.
        5. There are no seronegative findings in OA, i.e. there are no diagnostic markers in
           the blood, as there is Rheumatoid factor in RA.

d. Lupus Erythematosus. Lupus Erythematosus is a CVD which has a very high female
   prevalence (8:1), and is most common during the 2nd and 3rd decades of life. However, it is
   not uncommon to see middle aged as well as elderly females develop the disease. Lupus
   Erythematosus exists as discoid type, which is localized to skin, and systemic type, which
   involves skin as well as internal organs. In discoid lupus erythematosus (DLE), scaly
   discoid lesions form on the skin, usually on the face, scalp, neck, and upper trunk. When
   the scalp is involved, DLE causes alopecia. DLE may cause scarring as the lesions heal,
   and typically the lesions are made worse by exposure to sunlight. Systemic lupus
   erythematosus (SLE), on the other hand, may involve multiple organ systems, and 30% of
   affected persons may have rheumatoid factor in the blood. Skin lesions tend to resemble
   DLE, but patients may have accompanying pulmonary disease, cardiovascular disease,
   and/or renal disease. When renal disease is present, patients will likely have an
   accompanying renal hypertension. Specific clinical features of SLE (by organ systems)

  Skin: There is usually a discoid rash on the face, neck, scalp, and upper trunk. The rash is
    photosensitive, and patients should be advised to avoid direct sunlight. In about 80% of
    affected patients, there is a butterfly shaped rash, which covers the bridge of the nose
    and cheeks. The presence of a butterfly shaped rash is generally considered to be highly
    suggestive of Lupus Erythematosus in a patient. Patients with SLE also have alopecia
    along with scalp lesions. Patients also develop areas of capillary dilatations, which may
    be seen on the skin. The areas of capillary dilatations are called telangiectasias.

  Joints: Patients with SLE often have an accompanying polyarthritis. The arthritis may
    assume an asymmetrical pattern (unlike RA). However, a pattern of joint deformities
    similar to that of RA may develop.
  Kidneys: Involvement of the renal vessels is one of the most common sites of pathology
    in SLE. The involvement typically produces a nephritis, and there is usually a renal
    induced hypertension, which is caused by reduced blood flow through the renal vessels
    and activation of the renin – angiotensin mechanism (review this mechanism in Unit II).

  Mucous membranes: Involvement of the mucus membranes occurs often in SLE, and
    implies that autoantibodies have affected collagen in the submucosa, causing an
    inflammatory response with nodule and ulcer formation.

  CNS/PNS: Involvement of the CNS can produce localized nodules and result in memory
    loss, dementia, and seizures. Involvement of the PNS can cause both sensory and motor

  Liver: SLE often affects the liver, and hepatic nodules with scarring can decrease liver
    function. Extensive involvement can ultimately lead to liver failure, which without organ
    transplantation, is uniformly fatal.

  Lungs and pleurae: as in RA, SLE can cause nodule formation with subsequent scarring
    and fibrosis in both the lungs and pleural membranes. Depending on the extent, such
    involvement can cause chronic restrictive lung disease, with limited respiration due to a
    restrictive breathing pattern.

  Cardiovascular system: the cardiovascular system is another common site for SLE
    involvement. There can be an SLE induced myocarditis, and valvular disease can occur
    if autoantibodies form complexes with the valvular collagen. There is almost always
    widespread associated vascular disease, and vascular scarring can potentially produce
    occlusions and aneurysms.

  Specific criteria exist for assessing the presence of SLE. Also, in SLE, there may be
an associated blood disorder. Features of the disorder include: 1) a normochromic,
normocytic anemia; 2) a thrombocytopenia (low platelet count), which causes easy
bruising; 3) a generalized leukocytopenia (low white blood cell count).

 There are also usually skin lesions and a rash in SLE. The rash often assumes a butterfly
 appearance on the face (review previous description in this unit).

 Like RA, arthralgia is a common complaint heard from patients with SLE. The arthralgia is
 due to arthritis – like inflammation of multiple joints.

 A specific diagnostic marker, the antinuclear antibody (ANA) is present in 90 – 95% of
 persons with SLE. ANA is an autoantibody which occurs in SLE, and represents an immune
 response to the contents of the cell nucleus of the affected person. Another marker that is
 seen in about 33% of patients with SLE is anti-cardiolipin, which is antibody to cell
 membranes. Anti-DNA is another marker that is highly specific for SLE. Anti-DNA is an
 immunoglobulin specific against native (double-stranded) DNA. Estimates are that sixty to
 eighty percent of patients with active SLE have a positive anti-DNA test. Another marker
     seen in some SLE patients is anti-Sm antibodies. SM is a ribonucleoprotein found in the cell

     LE cells – LE cells are able to be demonstrated in SLE, and represent a neutrophil (PMN)
     which has engulfed another leukocyte that has had its nucleus destroyed by ANA. The
     nucleus is pushed to one side and flattened against the cell membrane of the PMN, giving the
     LE cell its characteristic appearance.

e.    Systemic Sclerosis (Scleroderma). Systemic sclerosis is a CVD that causes the skin and
     subcutaneous tissue to become dense, fibrous, thickened, and tight. As with the previous
     CVD’s discussed, systemic sclerosis may be localized and affect only the skin (morphea
     type), or it may be generalized and affect other organ systems (systemic sclerosis). The
     disease affects primarily females, and the female to male ratio is 3:1. In scleroderma of both
     types, there is usually Raynaud’s syndrome, with the triggers for episodes being emotional
     distress, exposure to cold, and smoking. Persons with scleroderma may appear as thin and
     undernourished, and their skin has a shiny, tight and drawn appearance. The facial features
     may appear as sharp and accentuated, due to the tightly drawn skin (mauskopf faces).
     Systemic sclerosis form of scleroderma may present with the CREST variant, which is an
     acronym for the following clinical signs: 1) calcinosis, or subcutaneous areas of
     calcification; 2) Raynaud’s syndrome; 3) esophageal dysmotility, which leads to
     swallowing and feeding difficulty; 4) sclerodactyly, which is hardening of the skin around
     the digits, causing “sausage-like” appearance of the digits and interphalangeal joints, and; 5)
     telangiectasias, usually about the head, neck, face, and upper trunk. Thus, individuals with
     systemic sclerosis may show the following as noted by therapists:

        Physical appearance: Patients with Scleroderma may present with drawn pursed lips,
         shiny skin over the cheeks and forehead, and atrophy of the muscles of the face, temple,
         neck, and upper trunk. Raynaud’s syndrome is common in most persons with

        Rheumatoid factor may be identified by the clinical laboratory in some persons,
         as may ANA. However, the incidence of such findings in both cases is
           probably less than 10%.

f. Dermatomyositis. Dermatomyositis (if the disease affects the muscles but does not
  affect the skin, then it is called Polymyositis) is a CVD that is generally seen in older
  females, with autoantibodies forming antigen – antibody complexes with skin and
  subcutaneous tissue, and skeletal muscles. The disease affects about twice as many
  females as men. Clinical features include a scaly rash over the trunk and proximal
  extremities, proximal muscle weakness (myasthenia), and proximal muscle atrophy
  with calcinosis. Dermatomyositis is a chronic disease, which generally is progressive
  and gradually causes physical limitation and debilitation. Positive diagnosis of the
  disease is usually made via muscle biopsy, Other markers that help in diagnosing the
  disease are blood CK levels, 24 hour creatinine excretion levels, and elevated ESR.
  Presence of dermatomyositis in persons older than 40 years of age suggests a 20%
  chance of a hidden, or occult, malignant tumor existing concurrently.
  Dermatomyositis, in this case, may be referred to as a paraneoplastic syndrome.
An autoimmune response to nuclear and cytoplasmic autoantigens is detected in about 60-80%
of patients with polymyositis and dermatomyositis. Some serum autoantibodies are shared with
other autoimmune diseases (ie, myositis-associated antibodies [MAA]), and some are unique to
myositis (i.e, myositis-specific antibodies [MSA]). The MSA are found in approximately 40%
of patients with polymyositis and dermatomyositis, whereas MAA are found in 20-50%. The
identified MSA targets include 3 distinct groups of proteins: aminoacyl–transfer RNA (tRNA)
synthetases (anti-Jo-1), nuclear Mi-2 protein, components of the signal-recognition particle
(SRP). Most of the anti-tRNA synthetase antibodies are directed toward functional and highly
conserved domains of the enzyme. As many as 6 of 20 aminoacyl-tRNA synthetases have been
described, but anti-histidyl-tRNA synthetase (Jo-1) is most common (20- 30%). Autoantibodies
directed toward the other synthetases specific for alanine (anti-PL12), glycine (anti-EJ),
isoleucine (anti-OJ), threonine (anti-PL7), and asparagine (anti-KS) have been reported in only
about 1% of patients. Anti-Jo-1 autoantibodies were originally described as precipitating
autoantibodies in sera of patients with polymyositis. Later, the anti-Jo-1 antibodies were
recognized to be specific for patients with polymyositis. The target for the anti-Jo-1 antibodies
was one of a family of distinct cellular enzymes: the aminoacyl-tRNA synthetases.

The Jo-1 antigen is histidyl-tRNA synthetase. This enzyme is partially responsible for
attaching tRNA to their cognate ribosomal RNA (rRNA). The Jo-1 antigen migrates as a 53-kd
protein on sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE).

g. Mixed Collagen Vascular Disease (MCVD). Mixed connective tissue disease (MCTD) was
   first described as a distinct entity in 1972. The original condition was identified among a
   group of patients who had overlapping clinical features of systemic lupus erythematosus
   (SLE), scleroderma and myositis.1 It has been further defined as a condition in which there is
   an undifferentiated connective tissue disorder in the presence of anti-U1-ribonucleoprotein
   antibody (anti-U1-RNP Ab) and Raynaud's phenomenon. As a condition it usually evolves to
   become one of several other connective tissue disorders or an overlap syndrome and because
   of this property it remains a controversial diagnosis.
h. Polyarteritis Nodosa. Polyarteritis Nodosa is a CVD which, somewhat
 unusually, affects men more than women (male to female ratio is 3:1).
 Numerous variants of the disease exist, with temporal arteritis (also called
 giant cell arteritis) being one of the most common examples. The peak age of
 onset for polyarteritis nodosa is in the 7th decade of life, and the disease may be
 focused on specific arteries (i.e. the temporal artery in temporal arteritis);
 however, there is always the potential for progressive involvement of other
 areas. Generally, the disease eventually becomes systemic, and
 involves multiple organ systems. It most often affects the medium and small
 arteries, and the pathological scenario for arterial destruction is: autoantibodies
 form antigen – antibody complexes with the collagen in the arterial wall,
 resulting in tissue destruction and necrosis. As the vessel heals, non–elastic scar
 tissue results in aneurysm formation, which may rupture and bleed. Also,
 healing may cause the vessel wall to thicken, with formation of fibrous tissue.
 The fibrous tissue causes occlusion of the lumen of the vessel, resulting in
 increased resistance to blood flow and tissue ischemia. Generalized

polyarteritis nodosa is regarded as a progressive, debilitating disease, and is
potentially fatal in the long run. Other variants of polyarteritis nodosa include
Wegener's granulomatosis and pulse less disease. Wegener's
granulomatosis is characterized by arterial lesions in the lungs and upper
respiratory tract, and is associated with granuloma formation. Chronic
sinusitis, nasopharyngeal ulcers, and pulmonary cavities are frequent findings.
Focal necrotizing lesions may also be found in the kidneys, and death often
occurs due to renal failure. Pulse less disease affects the proximal branches
of the aortic arch, and is chiefly manifested by ischemia to the head, neck, and
upper extremities. The disease man resemble atherosclerosis, vascular syphilis,
or temporal arteritis. However, in this variant of polyarteritis nodosa, there is a
marked female predominance.

  Clinical features of polyarteritis nodosa include:

    1.     Renal failure and hematuria, due to renal vascular and glomerular
    2.     Constitutional symptoms (i.e. loss of appetite, fever, and fatigue);
    3.     Dysphagia, due to pharyngeal and esophageal dysmotility, as the vasculature of the
    4.     pharynx and esophagus are some of the most common areas affected
    5.     Pulmonary failure, due to involvement of the pulmonary vasculature (producing
    6.     hemoptysis, cor pulmonale, respiratory arrest).
    7.     Hypertension, due to narrowing of blood vessels and loss of blood vessel
    8.     In temporal arteritis (see above), patients may also have headaches, sudden visual
    9.     disturbances, and redness and tenderness over the involved blood vessels. They
    10.    may also experience a condition known as polymyalgia rheumatica,
    11.    characterized by pain and stiffness of the head, neck, and shoulders.
    12.    Patients with polyarteritis often show presence of the blood marker perinuclear
           antineutrophil cytoplasmic antibodies (P-ANCA), which is the antibody to
           white cells. P-ANCA is most seen in necrotizing, crescentic glomerulonephritis and
           polyarteritis nodosa. P-ANCA is found in some lupus patients.

i. Other Diseases with Similar Symptoms

  Several other diseases will be mentioned and briefly discussed, i.e. seronegative
  spondyloarthopathies, particularly ankylosing spondylitis,
  psoriasis, gouty arthritis with tophi , Reiter’s syndrome (a
  venereal disease), and enteropathic arthritis, usually caused by
  Crohn's disease, which will be discussed in Unit IV.

j. Fibromyalgia is a non-specific disorder that bears a resemblance to CVD’s, but
   has none of the specific clinical signs. It’s etiology is unknown, and was not a
   specific diagnosis until 1990. Symptoms include 1) aches and pains; 2)
   stiffness; 3) swelling in soft tissue; 4) tender points, and; 5) muscle spasms or
   nodules. Patients complain of stiffness, but do not show evidence of specific
   joint pathology, although sometimes swelling may be noted in articular and/or
   periarticular tissue. Patients may complain that they “hurt all over”, but may not
   be able to give a specific history. Fibromyalgia’s diagnostic criteria requires a
   history of widespread pain in 11 or more out 18 specified, bilateral tender points
   in the muscular tissue. Therapeutic exercise, massage, and soft tissue
   manipulation is often successful in treating the symptoms.

  k. Gout. Gout causes a particularly painful intermittent arthritis, which most
     commonly involves the tarsometatarsal joint of the great toe. Gout is most often
     seen in adult males. Gout is caused by deposition of uric acid crystals from the
     blood into the joint, which irritates the joint capsule and joint structures and causes
     an inflammatory response. All patients with gout have elevated blood levels of uric
     acid, or hyperuricemia. There are 2 types of gout: primary gout and secondary

    In primary gout, the patient metabolically overproduces or does not adequately
excrete uric acid in the urine. Secondary gout occurs when the overproduction or
decreased excretion is due to another disease process or medication. For example,
individuals with leukemia or multiple myeloma often develop gout, because large
numbers of cells are being destroyed and uric acid is being liberated. Persons with
kidney disease often develop gout as a result of their kidneys not being able to
excrete uric acid. Often, persons with gout develop visible deposits of urate on the
skin and superficial areas of the body called tophi.

                                            End-Unit III

                                   Study Tips for Unit III

Be sure you can discuss/describe the following:

1. Pulmonary diseases – restrictive disease and specific examples, RDS of the newborn, ARDS;
   and obstructive disease, and pneumonia.

2. Discuss COPD. Symptoms, signs, different specific named diseases, and pathophysiology;

3. Diseases of the Pleural Membranes;

4. Collagen vascular diseases (CVD’s);

5. Liver diseases – symptoms, signs, generalities, complications (cirrhosis, hepatitis, etc.), and;

6. Gall bladder disease (gall stones) – explanation of dysfunction, symptoms.

7. Pancreatic Diseases – give examples and explain dysfunction and symptoms

Be sure you can:

1) Discuss symptoms, signs and pathophysiology of emphysema, asthma and chronic
   bronchitis. What is bronchiectasis? How do these conditions contribute to COPD?

2) Discuss what is meant by a “restrictive lung disorder,” and give specific examples and

3) Discuss different pathologies involving the pleural membranes and pleural space-pleuritis,
   hydrothorax, pneumothorax, hemothorax, etc.

4) Define atelectasis. Relate to different pathologies, i.e. RDS of the newborn;

5) Define/discuss ARDS and give some potential etiologies;

6) Identify by name specific CVD’s and give specific symptoms, signs, and characteristics
   exclusive to each;

7) Define/differentiate the different forms of arthritis – name, show specific pathologic changes
   exclusive to each, give specific symptoms and signs of each;

Formative Exam

I. Provide the ONE best answer:

 1. Rheumatoid factor:

      a. is an IgM autoantibody
     b.   may appear in CVD’s other than rheumatoid arthritis
     c.   when present, may be isolated from the patient’s serum
     d.   all of the above
     e.   b and c only

2. Raynaud’s Syndrome (which is FALSE):

     a.   is a vasospastic arterial episode involving the hands and fingers
     b.   is frequently associated with scleroderma
     c.   is generally provoked by cold or emotional stress
     d.   is most common in adult males
     e.   in extreme cases, may cause digital necrosis and need for subsequent digital amputation

3. “Discoid” type of lupus erythematosus:

    a.    is more likely to occur in males than in females
    b.    generally results in rapid death due to renal failure
    c.    seldom presents with skin rash
    d.    seldom demonstrates presence of DNA antinuclear antibodies (ANA) in blood
    e.    may present with alopecia

4. Symptom(s) of cholelithiasis include:
     a. pain in the left lower abdomen
     b. pain radiating to back and right shoulder
     c. nausea and vomiting
     d. all of the above
     e. b and c only

5. Possible reasons for bleeding in persons with liver disease include(s)
     which of the following:
     a. acidosis with increased blood levels of ammonia
     b. decreased hepatic utilization of Vitamin K to form prothrombin
     c. rupture of esophageal varices
     d. all of the above
     e. b and c only

6. Which of the following is/are associated with systemic lupus
    erythematosus (SLE):

     a.   telangiectasias
     b.   renal vasculature destruction and occlusion
     c.   pleural and pulmonary fibrosis
     d.   all of the above
     e.   b and c only

7.    A patient with gouty arthritis:

       a.   would likely have elevated uric acid in the blood
       b.   would show Bouchard’s nodes
       c.   would likely have little discomfort
       d.   would probably be a young female
       e.   would probably have an accompanying systemic sclerosis

 8.    Cor pulmonale is a natural consequence of :

       a.   COPD
       b.   systemic hypertension
       c.   anterior descending artery
       d.   all of the above
       e.   b and c only

 9.    “Panlobular emphysema” differs from “centrilobular emphysema” in that:

       a.   panlobular involves the small airways; centrilobular involves the alveoli
       b.   centrilobular is more diffuse
       c.   panlobular is a reversible pulmonary disease, whereas centrilobular is not
       d.   centrilobular associated with cyanosis and hypoventilation

10.   A 60 year old patient missed his next appointment with you. After several days, you hear
      from his wife that he has been coughing and has become short of breath, and that he has
      been hospitalized with “lobar pneumonia.” If this report is true, then which of the following
      should you expect regarding his status?

      a.     there will likely be permanent damage to his lungs and bronchial airways.
      b.     he almost certainly now has “oat cell carcinoma” of the lungs.
      c.     he likely has neurological paralysis of the diaphragm.
      d.     lobar pneumonia increases risk of developing systemic lupus erythematosus.
      e.     accumulation of the fluid in the lungs likely caused him to be short of breath.

11.   After the follow-up, you learn that the patient in #10 has been diagnosed with bacterial
      lobar pneumonia. The most likely causative etiology was:

      a.     Streptococcus pneumoniae (pneumococcus)
      b.     Klebsiella pneumoniae
      c.     Pseudomonas aeruginosa
      d.     Eschericia coli
      e.     Pneumocystis carinii

12.   For lobar pneumonia, the above prognosis is best described by which of the

      a.    he will have permanent loss of functional lung tissue.
      b.    he will have complete recovery with restoration of normal lung tissue.
      c.   he will develop chronic obstructive pulmonary disease.
      d.    he will develop cor pulmonale.
      e.   he will develop a pulmonary blood clot, that will be passed through the heart
           and travel to the brain.

Answers to Unit III Formative Exam

 1. Answer is D. Rheumatoid factor is an IgM autoantibody and has been observed in
    several CVD’s (i.e. lupus erythematosus). Isolation from the serum is the way
    Rheumatoid factor is identified.

 2. Answer is D. Raynaud’s may be seen in CVD’s, especially scleroderma. The
    syndrome is defined as a vasospastic episode of the hands/fingers, and may sometimes
    result in ulcers and necrosis. Cold and emotional stress are common precipitators.
    Raynaud’s is more common in females than in males.

 3. Answer is E. Alopecia, or spotty loss of hair, quite often accompanies Discoid LE.

 4. Answer is E. From Chapter 27, general symptoms of gall stones are pain radiating to
    the back and shoulder, along with nausea and vomiting.

 5. Answer is E. Liver disease may progress to hepatic failure, with resultant increased
    blood levels of ammonia – however, this is not associated with bleeding. Decreased
    conversion of Vitamin K to prothrombin is a likely cause, as well as rupture of
    esophageal varices.

 6. Answer is D. In systemic LE, skin involvement with telangiectasias typically occurs.
    Also, the renal vessels are typically involved, along with the lungs and pleura.

 7. Answer is A. Since uric acid crystals are responsible for tophi (not Bouchard’s nodes)
    in gout, the blood levels will be elevated. Gout occurs generally in males; tophi are
    usually quite painful.

 8. ANSWER IS A. Cor pulmonale refers to right ventricular heart disease secondary to
    pulmonary disease of a long-standing nature. As the lung forms shunts, loses atrial and
    vascular integrity, etc., and increased working load is placed on the right ventricle,
    resulting eventually in hypertrophy, dilation, and potential CHF. COPD often causes
    this disorder, because of the long-standing nature of the disease. Systemic hypertension
    would most likely affect the left ventricle (i.e. a primary myocardial disease).

 9. ANSWER IS D. Generally centrilobular emphysema involves the small distal airways,
    which makes it difficult to compensate for ventilation/perfusion discrepancies. Since
    the patient traps air into his lungs and has a “shunt” disorder, he is likely to develop
    hypoventilation and cyanosis (i.e. blue bloater).

10. ANSWER IS E. Pneumonia is an inflammatory process of the lungs, and
    inflammation, fluid is produced. The fluid will occupy the pulmonary interstitial
    spaces, and compress and infiltrate the alveolar spaces, making breathing difficult.
    Lobar pneumonia typically is a self-limiting disease, and healing is usually complete
    with no residual damage. There is no known relationship between lobar pneumonia and

      diaphragmatic paralysis, oat cell carcinoma, or systemic lupus erythematosus (a
      collagen vascular disease to be discussed in the next unit).

11.     ANSWER IS A. Pneumococcal pneumonia makes up about 50% of all bacteria
        pneumonias. Klebsiella (also known as Friedlander’s pneumonia)       occurs more
        often in middle aged alcoholics, but is comparatively rare. Pneumocystis may be
        seen as a terminal event in AIDS. E. coli is more associated with GI infections, and
        Pseudomonas is often a problem in hospitalized patients who are terminally ill or
        have significant immunosuppression.

12.     ANSWER IS B. There is usually complete recovery in lobar pneumonia. Cor
        pulmonale usually occurs in chronic lung conditions.

                   UNIT IV


Acknowledgements and many thanks go to Ms. Tania McElveen of the MUSC Division of
Occupational Therapy for her efforts in editing and expanding the Unit IV text contained
in this document.

                             Medical University of South Carolina
                                  College of Health Professions
                        Divisions of Occupational and Physical Therapy

Diseases of the Liver, Gall Bladder, and Pancreas
Reference: Reference: Goodman and Fuller. Pathology: Implications for the Physical
Therapist (edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

Clinical Signs of Liver Disease

 A. Hepatomegaly
 -enlarged liver, due to swelling within the hepatic parenchymal tissue
 -nonspecific sign of different liver conditions such as
                               -direct toxicity
                               -disorders of metabolism

 -how to diagnose it?
                              -Palpation: the mass
                              -CT Scan
                              -often accompanied by jaundice

 B. Elevation of the enzymes in the blood due to necrosis or inflammation and damage to the
 hepatic cells membranes. Normally, hepatic enzymes are contained within the hepatic cells.
 Cell damage causes the leak of the enzymes into the circulation. Such damage can occur
 because of different reasons: infections, alcohol excess, cirrhosis, incorrect diet, neoplastic
 disorders, hepatotoxic substances: long term antibiotics, oral pain killers, oral hormone
 replacement medications, insecticides, pesticides, etc.
 Good news: liver cells have good capacity to regenerate and proper diet and supplements can
 help in some cases.
 Hepatic (liver) Enzimes:
 aspartate aminotransferase (AST),
 lactic dehydrogenase (LDH),
 gamma glutamyl-transferase (GGT), and
 alanine aminotransferase (ALT).
 alkaline phosphatase will also be elevated if there is biliary obstruction (i.e. obstruction to bile

C. Caval obstruction with pedal edema
-inferior vena cava obstruction due to occlusion of the venous drainage from the liver via the
hepatic veins into the inferior vena cava
 -causes passive congestion in the lower extremities

D. Portal hypertension and splenomegaly
- hypertension (elevated blood pressure) in the portal vein.
- due to occlusion of the venous drainage from the liver via the hepatic veins into the inferior
      vena cava.
- occlusion causes passive congestion in the hepatic portal vein and splenic vein, resulting in
      fluid back up and swelling in the associated organs.
- a portal pressure gradient (the difference in pressure between the portal vein and the hepatic
      veins) of 10 mmHg or greater.
- conditions that can be caused by portal hypertension due to congestion: splenomegalia,
      ascites, hepatic encephalopathy, dilated abdominal wall veins.

E. Esophageal Varices from Portal Hypertension
-It is the life-threatening complication
-caused by the block of the blood flow through the liver

The sequence of events:
-obstruction of portal venous blood flow
-portal hypertension
-collateral circulation develops in order to detour the blood flow to the systemic veins from the
obstructed area. The most significant portosystemic collaterals(anastomoses) are the
gastroesophageal which presented by the development of large, swollen veins (varices) within
the esophagus and stomach.Esophageal varices drain the blood to the azygos vein and are
responsible for upper gastrointestinal hemorrhage.
-symptoms of upper gastrointestinal hemorrhage
                     -vomiting of blood
                     -rapid heart rate
                     -low blood pressure
                     -black stool
                     -in very severe cases - shock

  F. Depression of the clotting mechanism,
            -any liver disorder is associated with coagulation problems, because liver plays a
             very significant role in this process:
            -hepatic damage
 The liver plays a central role in the clotting process, and acute and chronic liver diseases are
invariably associated with coagulation disorders due to multiple causes: decreased synthesis of
clotting and inhibitor factors, decreased clearance of activated factors, quantitative and
qualitative platelet defects, hyperfibrinolysis, and accelerated intravascular coagulation. The
bleeding tendency accounts for increased risk of morbidity and mortality in patients with liver
disease undergoing diagnostic or therapeutic invasive procedures. Peculiar coagulation
disorders are prevalent in patients with acute fatty liver of pregnancy or undergoing liver
transplantation. Emerging evidence shows that sepsis further impairs hemostasis in patients
with liver cirrhosis bleeding from esophageal varices. Thrombotic events, even if rare in
cirrhotic patients, occur mainly in the portal and mesenteric veins. The therapeutic approach to
coagulative disorders is also discussed.
Converting Vitamin K to prothrombin is impaired (prothrombin is necessary for clotting), and
may be measured with a laboratory blood test.
Prothrombin time normal=11-15 seconds and is reduced with decreased prothrombin synthesis
in liver disease);

G. Total circulating plasma (or serum) protein is decreased.
Albumin and globulin are two plasma proteins that used to assess liver function. Normal values
for total serum protein range from 6-8 g/dl, which in total makes 7% of total body weight.
Facts about albumin:
-synthesized in the liver
- represent the major fraction of circulating proteins.
- main function is to maintain oncotic pressure in the vessels. If oncotic pressure is low, fluid
will leak out to the interstitial spaces causing localized (pedal edema) or generalized edema
(anasarka). When liquid leaks from the interstitial spaces into the peritoneal cavity it causes
-another function of albumin is to bound and transport different chemical substances
(hormones, lipids, drugs, toxins) to the liver. In the liver substance detaches from albumin.
-low level is the sign of poor liver function, serious, chronic condition
-low level is not typical for the acute conditions
-most common reason for a low level is a chronic liver failure as a result of hepatic cirrhosis
-low albumin level can be a symptom of other conditions, not related to liver disorders (kidney
diseases, serious malnutrition, starvation, severe burns)

H. Anasarca (generalized edema) is due to hypoproteinemia, which occurs because the liver’s
ability to synthesize plasma proteins is impaired. The hypoproteinemia decreases vessel
osmotic pressure, causing fluid to leak into the extracellular tissue space. Also, compression of
the inferior vena cava and its venous tributaries by an enlarged liver will cause passive
congestion, which increases venous hydrostatic pressure in the veins of the lower extremities,
pelvis , and abdomen, and causes fluid to leak into the extracellular tissue space.

I. Ascites, which as discussed previously, is a collection of serous fluid, high in protein
content, in the abdominal cavity. Ascites results from increased production and flow of hepatic
lymph, as well as compression of abdominal lymphatics; passive congestion in the spleen and
abdominal viscera secondary to hepatic portal hypertension; hypoalbuminemia; sodium
retention, and; impaired water excretion. The passive congestion raises the venous hydrostatic
pressure and causes the organs to “weep” fluid into the abdominal cavity.

J. Elevated plasma bilirubin with jaundice (icterus).
Bilirubin comes from erythrocytes. Old erythrocytes undergo destruction. Bilirubin is a
chemical that comes from the hemoglobin of destroyed RBC and remained in the blood as a
product of this elimination process. Bilirubin is a waste product.Liver utilizes bilirubin and
produces and secretes bile into the gallbladder and intestines to help digest fats. Liver also
remove bilirubin products from the blood. In the liver cells, the cells attaching (conjugate)
 glucuronic acid to the bilirubin, and then secrete the complex into bile and then conjugated
 bilirubin is eliminated in the feces. Since the hepatic mechanism for excreting bilirubin is
 impaired due to swelling and occlusion of the bile ducts, the bilirubin produced from
 hemoglobin of dead rbc’s is backed up into the circulation.

  K. Pruitus (Ithing)
 -found in people with advanced liver disease and cirrhosis.
 -may be localized to a specific part of the body (hands and feet)
 -can also be a generalized itching all over the body. (“Everything itches even my insides!..”)
 -usually worse at night and causes sleeping problems
 -the exact cause is unknown
 -can be related to elevated bilirubin level, side effects of treatment

 L. Breast enlargement (Gynecomastia)
 Causes are unclear
 One of the liver functions is lipid metabolism and sex hormones utilize lipids. Possibly:
 Deficiency in testosterone metabolism
 Increased level of estrogens

 Model for End-Stage Liver Disease, or MELD-scoring system for stages of liver failure

 MELD uses the patient's values for serum bilirubin, serum creatinine, and the international
 normalized ratio for prothrombin time (INR) to predict survival
 The values are simply added
 MELD Score in hospitalized patients, the 3 month mortality is:

      40 or more — 71.3% mortality
      30–39 — 52.6% mortality
      20–29 — 19.6% mortality
      10–19 — 6.0% mortality
      <9 — 1.9% mortality

What are the causes of liver disease?

 Inflamation/infection (hepatitis)
 Obstruction to the bile flow (cholestasis)
 Accumulation of cholesterol or triglycerides (steatosis)
 Compromized blood flow through liver
 Damage by chemicals, minerals
 Infiltration by abnormal cells

The term "hepatitis" means inflammation, and liver cells can become inflamed because of

Hepatitis A (Infectious Hepatitis) – Type A hepatitis is a disease which primarily affects lower
socio – economic groups and individuals with impaired immunity. The disease is caused by the
Type A Hepatitis virus (HAV), which has an oral mode of entry. HAV may occupy uncooked
seafood, or any ingestible items which are contaminated by human waste. Upon entering the
body, HAV requires an average incubation period of 28 days. The usual course of the disease is
about 4 – 6 weeks, and is generally self – limiting with mild to moderate symptoms and signs of
liver dysfunction. HAV has been treated successfully with gamma globulins, which often abates
symptoms considerably when known exposure has occurred. Recently, HAV antibody has been
isolated in the blood of exposed individuals, making for identification of a specific serologic
marker to help assess HAV presence. Signs and symptoms of Hepatitis A include:
Constitutional symptoms, similar to “flu-like” symptoms;
Nausea and diarrhea;
Jaundice with pruritus (itching – which occurs because the bilirubin irritates the skin) – NOTE:
the jaundice is most obvious in the sclera of the eyes, which have an orange–brown color.

Hepatitis B (Serum Hepatitis).

Hepatitis B is caused by infection with the Hepatitis B virus (HBV), and is potentially a more
serious disease than Hepatitis A. Formerly, HBV was thought to enter the body only by
inoculation; however, more recent evidence suggests that the virus can be transmitted sexually
(STD) and via the oral route. Consequently, HBV is often identified in persons having multiple
sex partners (or even in monogamous relationships, if one partner is a “carrier”, i.e. one who
harbors HBV without symptoms or signs of active disease). HBV has, for many years, had a
high incidence in drug abuse subcultures, presumably due to use of contaminated needles. HBV
has a longer incubation period than HAV, with an average of 120 days between contraction of
the virus and development of active hepatitis. The disease has a variable course, and symptoms
may range from mild to severe. Hepatitis B generally has a longer clinical course than Hepatitis
A. Although Hepatitis B can be regarded as a self-limiting disease, infection with HBV can, for
a small percentage of cases, have potentially dire outcomes. About 10% of persons with HBV
infection develop a chronic form of hepatitis, in which there is progressive destruction of hepatic
tissue extending over several months to several years. As liver parenchyma is gradually lost,
there is worsening of clinical signs of liver disease (see previous list), and, eventually, end stage
liver disease is reached. In end–stage liver disease, patients become comatose and reach
hepatocellular failure. Death uniformly follows. Patients with end – stage liver disease have
achieved some degree of notoriety by having liver transplants, and some have survived well
beyond the post – operative stage (example; Larry Hageman). Others (i.e. Mickey Mantle)
having not been so fortunate. Clinical signs are similar to Hepatitis A (see above); however,
potential for severity is greater in Hepatitis B. A blood born marker for Hepatitis B exists and
has been identified; the HBV antibody can be isolated, and the antigen itself was isolated several
years ago. The antigen is called hepatitis associated antigen (HAA), (the older name was
"Australian antigen". HBV is a very durable virus, and consists of DNA that is protected by a
triple protein layer (HbsAG, HbeAG, and HbcAG.

Hepatitis C, Hepatitis D, and Hepatitis E (Non-A, Non B Hepatitis):

Type C Hepatitis (HCV) Hepatitis C is caused by the Hepatitis C virus (HCV). HCV is a
particularly virulent strain, and 50% of persons infected with HCV develop chronic hepatitis, and
20% develop cirrhosis of the liver and/or hepatic cancer. Symptoms of HCV are similar to HBV
and HAV, but are generally less severe in the acute phase of the disease. HCV is transmitted via
infected blood transfusions, but may potentially be transmitted whenever the skin is breeched by
an infected needle, such as from contaminated instruments used in tattoo parlors. Recently, the
HCV antibody was isolated, so that a specific marker for the disease can be identified.

Alcohol abuse
Alcohol abuse is the most common cause of liver disease in North America. Alcohol is directly
toxic to liver cells and can cause liver inflammation, referred to as alcoholic hepatitis. In chronic
alcohol abuse, fatty accumulation (steatosis) occurs in liver cells causing the cells to

Cirrhosis of the liver implies that liver parenchyma has been destroyed and replaced with fat. In
advanced cirrhosis, the liver may become small and constricted due to massive scar tissue
formation, and the surface of the liver may resemble a cobblestone street. In cirrhosis, the liver
becomes progressively non-functional, and end stage liver disease with hepatocellular failure
eventually occurs. Without heroic measures (i.e. liver transplantation), end stage liver disease is
a uniformly fatal event. Patients with cirrhosis of the liver may hemorrhage easily and become
toxic due to failure to properly metabolize certain substances, such as ammonia, which is derived
from protein metabolism. Such an outcome results in hepatic encephalopathy, with associated
neurological signs and symptoms.

       Several types of cirrhosis have been identified:

Laennec’s–most common (50%), and is the type of cirrhosis associated with long term alcohol
abuse. Scarring of the liver and loss of functioning liver cells cause the liver to fail.

Postnecrotic (35%)–associated with exposure to substances toxic to the liver;
Liver cells may become temporarily inflamed or permanently damaged by exposure to
medications or drugs. Some medications or drugs require an overdose to cause liver injury while
others may cause the damage even when taken in the appropriately prescribed dosage.
Taking excess amounts of acetaminophen (Tylenol, Panadol) can cause liver failure that is

Biliary (post-hepatic obstructive) (15%)–usually a congenital disorder in which there is atresia
and blockage of the hepatic ducts. Biliary cirrhosis can also develop in adults from progressive
sclerosis of the biliary system (sclerosing cholangiitis).

In cirrhosis, clinical signs and symptoms usually result from hepatic insufficiency and portal
hypertension effects. For an illustration of specifics related to hepatic insufficiency and portal
hypertension effects, please see associated power point slide in this lecture series.

Cirrhosis Progression:
Development of a Fatty Liver
Replacement with nodular scar tissue
End stage liver disease (ESLD)
Hepatocellular failure

Hepatocellular Failure and End Stage Liver Disease
Without heroic measures (i.e. liver transplantation), end stage liver disease is a uniformly fatal
event. Contributing events to morbidity and ultimate mortality include:
Hemorrhage, due to low prothrombin levels, and poor clotting. The hemorrhage often occurs
from ruptured esophageal varices, due to venous overload of the azygos vein (review anatomy);
Failure to detoxify nitrogen (produced during protein metabolism). This results in the formation
of ammonia, which is toxic (causes hepatic encephalopathy) and acts as an acid that lowers body
pH to marked levels (pH = 7.35 – 7.45 is normal);
In addition to the changes noted above, hepatic encephalopathy develops secondary to ammonia
toxicity. Behavioral and psychomotor changes in hepatic encephalopathy include:
          Stage 1: Personality changes
          Stage 2: Abnormal muscle involvement i.e. fasciculations, asterixis (flapping
          Stage 3: violence, aggressiveness;
          Stage 4: Coma (unresponsive to external stimuli, pain, etc.), and hepatic fetor
                (musty odor, due to the liver’s inability to metabolize amino acids, i.e. arginine).
                Please go on the web to
                http://www.medicinenet.com/coma/article.htm and see the Glasgow
                Coma Scale, which gives a numerical scale for rating coma depth.

Pancreatic and Gall Bladder Disease

Acute vs. Chronic Pancreatitis and Cholelithiasis

Acute pancreatitis can be caused by a number of factors (see Box 17-4, p. 913 in Goodman and
     Fuller), but alcohol use is the most common cause, especially in large cities. Symptoms
     include abdominal pain (mild to severe), which usually refers to the back. The condition
     results from acute inflammation of the pancreatic tissue, and may lead to auto-digestion of
     the pancreas by its own enzymes (trypsin, chymotrypsin).
Chronic pancreatitis develops in a small percentage of patients with acute pancreatitis, but the
     most common cause in adults in alcohol overuse, whereas the most common cause in
     children is cystic fibrosis. In chronic pancreatitis, there is gradual loss of pancreatic tissue,
     which is then replaced by scar tissue. Chronic pancreatitis is a serious disease, and can
     result in significant long term disability and even death from complications of diabetes
     mellitus and pulmonary failure.
Pancreatic Neoplasia can be in the form of benign cists a tumors or malignant tumors. 5 years
     survival rate for pancreatic cancer is < 5%. Risk factors include gender (male), race
     (African American), age (> 60), smoking, diet (low in fruits and vegitables, high in red
     meat, and high in sugar-sweetened drinks), diabetes, obesity.
Cholelithiasis (gall stones) use to be considered primarily as a disorder of middle              aged
     Caucasian females (fat, fair, fertile, flatulent, forty, female). More recently, however, this
     descriptor has become less accurate, and the disease appears to have its greatest
     representation in both males and females who are elders (females, however, are in the
     majority). Most gallstones consist of biliary cholesterol and bile pigments that have
precipitated. Etiologic factors include: elevated estrogen levels (causes stasis of bile) and
inflammation of the gall bladder and/or biliary duct system. Due to occlusion of the biliary
duct system, the hallmark for cholelithiasis is right upper quadrant colicky pain that often
refers to the mid upper back. Often, patients have a “relief-pain” food pattern, in which the
pain is made worse by eating a meal.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Diseases of the Gastrointestinal System
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

I. Signs and Symptoms of Gastrointestinal (GI) Disease

    Clinical manifestations of GI disease can be caused by a variety of underlying
    conditions or disorders, and some may be so non-specific that they are
    representative of other systemic conditions. In the latter case, such symptoms are
    referred to as constitutional symptoms. Examples of constitutional symptoms include
    nausea and vomiting, diarrhea, malaise, fatigue, fever, dizziness, and appetite loss.
    Some symptoms of GI distress may also appear during or after strenuous exercise,
    such as abdominal cramps and diarrhea. For more on symptoms and signs of this
    nature, please see Goodman and Fuller, Table 16-1 on p 829.

II. Aging and the GI System

 A.      Age related changes in the GI tract begin to take place in a subtle manner before the age
 of 50 in many individuals, with constipation, incontinence, and diverticular disease comprising
 the most complaints. Other age related problems include decrease in GI motility (ileus),
 absorption, and gastric acidity.
 1. Atrophic Gastritis. Atrophic gastritis is a disease prevalent in older persons in which
 there is atrophy of the gastric mucosa. In addition, in a chronic type of gastritis, there is reduced
 intrinsic factor, which is produced by the gastric mucosa and is necessary for the absorption of
 Vitamin B12, or extrinsic factor (see diagram below).

        Extrinsic Factor …..………...combines with……………..Intrinsic Factor
        (Vitamin B12

                                Absorption through the
                            Gastric Mucosa into the Circulation

                                         Vitamin B12

                              Hematopoiesis, Axon Myelinization

Loss of the ability to absorb extrinsic factor has serious implications, primarily on the ability to
produce red blood cells and upon maintenance of myelin in the nervous system. The disorders
may be characterized as:
Pernicious anemia, which is a macrocytic, normochromic anemia;
Peripheral neuropathy, with loss of sensation, weakness, and reduced deep tendon reflexes;
Subacute combined degeneration, which results in demyelinization of the lateral white columns
of the spinal cord (causing upper motor neuron disease and spasticity) and of the dorsal white
columns, causing loss of the fine tactile senses.
Dementia or “megaloblastic madness,” due to demyelinization of pathways in the cerebral

2. Diverticulosis
Many people have small pouches in the lining of the colon, or large intestine, that bulge
outward through weak spots. Each pouch is called a diverticulum. Multiple pouches are called
diverticula. The condition of having diverticula is called diverticulosis. About 10 percent of
Americans older than 40 have diverticulosis.1 The condition becomes more common as people
age. About half of all people older than 60 have diverticulosis. (retrived from:

III.   Pathological Processes and Clinical Manifestations of the Esophagus, the Stomach,
the Intestines, and the Abdominal Cavity.

A. The Esophagus.
Symptoms of esophageal disease include:
             1. Dysphagia, or difficulty in swallowing (i.e. as seen in scleroderma);
             2. Pyrosis, or “heartburn”, due to gastric reflux or acid;
             3. Odynophagia, or pain with swallowing;
             4. Waterbrash, or reflex salivary hypersecretion in response to peptic esophagitis
Examples of esophageal disease include:
 1. Esophagitis, non-specified, which produces pyrosis and often reflux. The disorder is
 usually acute, is due to eating spicy food, and resolves in a few days. Some individuals may
   have a chronic form of esophagitis, known as gastroesophageal reflux disease (GERD). In this
   disorder, acid from the stomach is regurgitated past the lower esophageal sphincter into the
   lower esophagus, causing chronic irritation. Over time, this may cause metaplasia of the lower
   esophagus (known as Barrett’s esophagitis), which becomes a potential risk for esophageal
   Please see and read Box 16-3 in Goodman and Fuller, p 835. Note also that hiatal hernia (i.e.
   herniation of the esophagus up through the diaphragm can also cause esophagitis.
   2. Scleroderma-the collagen in the esophagus and esophageal vessels is affected,       causing
   esophageal dysmotility and dysphagia;
   3. Esophageal Tumor–cancer of the lower esophagus has a higher than usual incidence along
   coastal South Carolina, especially among African Americans living on the barrier islands. The
   cause for this occurrence is unknown. Esophageal tumors cause obstruction, bleeding, and
   difficulty in swallowing. Other signs of esophageal disease (see above) may also be present.
   The overall 5 year survival rate is approximately 17%, with most patients dying within the first
   year of diagnosis.

5. Hiatal hernia - a condition in which a portion of the stomach protrudes upward into the chest,
   through an opening in the diaphragm. There are two magor types: sliding and rolling. Sliding
   hiatal hernia characterized by the movement of the gastroesophageal junction above the
   diaphragm together with some of the stomach. In rolling hernia part of the stomach herniates
   through the hiatus and lies beside the esophagus, without movement of the gastroesophageal
6. Achalasia–Dilatation of the lower esophagus, due to loss of the muscle tone and failure of the
   lower esophageal sphincter to relax. The loss is likely due to loss of muscle innervation
   (Auerbach’s plexus in the esophageal wall), and causes stricture. The dilatation is caused by
   accumulation of food in the lower esophagus.
   5. Mallory-Weiss Syndrome-MWS implies lower esophageal bleeding due to a mucosal
   lesion. Several reasons for developing MWS exist, such as alcohol abuse, certain viral illness,
   bulimia, and some antibiotics.
7. Tracheoesophageal fistula is the most common congenital disease of the esophagus. In this
   disorder, there is a communication between the trachea and esophagus, with the trachea often
   ending in a blind pouch. The infant will cough, choke, and have cyanosis (3 C’s of
   tracheoesophageal fistula, and without surgical intervention, death usually occurs due to
   aspiration pneumonia.

   B. The Stomach and Duodenum

   1. Gastritis. Acute gastritis implies a sudden onset of diffuse gastric inflammation,
   accompanied by epigastric pain, which follows a pain relief food pattern (i.e. pain is relieved by
   eating, which differentiates from gall bladder disease, which usually has a relief–pain pattern),
   and resolves in a few hours to a few days. Acute gastritis may develop subsequent to over-
   indulgence in eating and/or drinking, taking NSAIDs, or in GI viral infection. Please see and
   read Box 16-6 “Special Implications for the Therapist” in Goodman and Fuller, p 842.

    2. Peptic Ulcer. Numerous theories have existed over the years regarding the etiology of
    peptic ulcer disease. The latest thinking has revolved around the bacteria Helicobacter pylori,
    which has been identified in the gastric secretions of samples of most subjects (~90%) with the
disorder. While there may still be other factors involved (i.e. drugs such as NSAIDS) the
concept of a bacterial cause has gained both credibility and following. H. Pylori has also been
implicated ad a major factor in stomach cancer.
Peptic ulcer disease affects both males and females equally. Most (80%) peptic ulcers occur in
the duodenal bulb, while only 20% are       found in the stomach (most are found in the pyloric
region on the posterior wall). Peptic ulcers generally have a pain–relief food pattern (i.e.
relieved by food), and pain is often worse at night. Many individuals with peptic ulcers
experience seasonal exacerbations, i.e.     during the spring and fall their symptoms and pain
may be worse. Peptic ulcers may be stubborn to treat, and may show little response to various
interventions (relaxation techniques are often useful). Unfortunate complications of peptic
ulcers include: 1)gastroduodenal hemorrhage; 2) perforation, with leakage of gastroduodenal
contents into the peritoneal cavity, causing peritonitis, and; 3) obstruction, due to scarring and
stricture. Please see and read Box 16-7 “Special Implications for the Therapist” in Goodman
and Fuller, p 845.

3. Stress Ulcers. Stress ulcers may occur following major trauma, and are frequently seen in
spinal cord injuries and other traumatic injuries. Stress ulcers are thought to occur secondary to
ischemia to the GI tract, which may be caused by shunting of blood to other areas of the body
away from the stomach and intestines. The paucity of blood causes gastrointestinal infarcts,
which then ulcerate and bleed. Stress ulcers usually heal, but may recur from time to time
during the rehabilitation process.
4. Stomach Cancer. Most stomach cancers are adenocarcinomas, and occur more frequently
in males than in females. Fortunately in the US, the disease is decreasing in frequency for
reasons that are unclear). Stomach cancer has a statistical predilection for persons with H.
pylori, and mostly affects lower socioeconomic groups. Chronic gastritis is regarded as a risk
factor for the disease, and once tumors become apparent, the 5-year survival rate is only about
10%. One type of gastric cancer that has a particularly poor prognosis due to its aggressive
nature is linitis plastica (leather bottle stomach). Survival times for this type of stomach cancer
are short, and metastasis occurs early in the course of the disease. Please see and read Box 16-8
“Special Implications for the Therapist” in Goodman and Fuller, p 847.

C. The Small Intestine

Small Bowel (duodenum, jejunum, and ileum). Diseases of the small bowel fall into one of
two categories, depending on the clinical symptoms       and signs that are seen in the patient.
The two categories are: 1) Malabsorption syndrome, and 2) Obstructive syndrome. Both
will be discussed below, along with their symptoms and signs, and examples of each.
 1. Malabsorption Syndrome. Malabsorption syndrome is present when nutritional levels fall,
and the patient experiences sudden weight loss with a decrease in body mass. Malabsorption
syndrome may occur because the individual has reduced his (her) food intake, or because the
small bowel is unable to adequately absorb nutrients from its contents. Specific causes of
malabsorption syndrome include: 1) GI surgery; 2) Hepatobiliary/pancreatic disease; 3)
regional enteritis, or Crohn's disease; 4) GI Lymphoma; 5) Lactase deficiency, 6) infections
(bacterial, parasitic), and; 6) Sprue (Celiac Disease).

Crohn’s disease is an autoimmune inflammation of Ileum (usually) that affect full thickness
of the intestinal wall. People with Crohn’s may have variety of symptoms, including abdominal
pain, diarrhea (may contain blood), vomiting, weight loss, skin rashes, arthritis and fatigue.
Celiac disease is an autoimmune condition that damages the lining of the small intestine and
prevents it from absorbing parts of food. The damage is due to a reaction to eating gluten,
which is found in wheat, barley, rye, and possibly oats. Inflammation process leads to intestinal
villi loss.

Specific signs and symptoms of malabsorption are very obvious and may be observed
clinically. Although not all patients have all symptoms and signs, the following are more or
less present:
1) Marked, sudden weight loss; 2) Protracted diarrhea; 3) Steatorrhea, or fat in the stools
(generally due to loss of pancreatic enzyme and / or bile from the liver); 4) Flatulence, due to
formation of intestinal gas; 5) Nocturia, due to nocturnal absorption of intestinal fluid; 6)
Fatigue, due to nutritional deficit; 7) Anemia, due to malabsorption of Vitamin B12, folic acid,
and iron; 8) Neuropathy, due to demyelinization as a result of Vitamin B12 malabsorption,
and; 9) Easy bruising, due to subcutaneous tissue loss    and capillary fragility. Please see and
read Box 16-9 “Special Implications for the Therapist” in Goodman and Fuller, p 644.
2. Obstruction syndrome. Obstruction syndrome implies that there is a blockage in the bowel,
due to loss of peristalsis, presence of a tumor, or a volvulus, in which the bowel twists upon
itself and results in blockage. Examples of causes of obstruction syndrome are: 1)
Hirschsprung’s diseas (congenital megacolon) or senile ileus (dysmotility of the bowel due
to age). In Hirschsprung's disease, the nerves are not properly developed in the part of the
colon. Those areas cannot push material through. This leads to blockage. Bowel’s contents
build up behind the blockage. This process causes the colon to enlarge. 2) Paralytic ileus,
which occurs with parasympathetic loss to the lower colon. 3) Mechanical obstruction, such as
occurs in a volvulus and intestinal neoplasia, 4) Intussuception, in which a segment of the
bowel "telescopes" upon itself, and 5) “Organic” obstructive diseases can be caused by
dehydration and fecal impaction. 6)Post-surgical adhesions. For more about the implications
for obstructive disease of the bowel, please see and read Box 16-18 “Special Implications for
the Therapist” in Goodman and Fuller, p 869.

Signs and symptoms of obstruction include: 1) “cramping” abdominal pain; 2) abdominal
distention and bloating; 3) vomiting, and; 4) alternating pattern of constipation/diarrhea.

D. The Colon, or Large Intestine

Disorders can be diagnosed using Barium (contrast) study, and colonoscopy.
Colon (Large Bowel). Disorders of the colon generally cause the following set of symptoms
and signs: 1) Constipation; 2) Diarrhea; 3) Altered stool size/color; 4) Hematochezia, or blood
in the stool, and; 5) “cramping”, colicky pain.
Common diseases of the colon include:

1. Appendicitis occurs in all age groups. It may occur spontaneously with an unknown
etiology, or it may be caused by fecaliths, which are bits of dried stool that work their way into
the lumen of the appendix and cause obstruction. Symptoms of appendicitis include: 1) a
marked leukocytosis, with a large shift to the left (large number of PMN’s). There is pain and
severe rebound pain (Blumberg’s sign) over McBurney’s point, there may be nausea and
vomiting, and the patient usually spikes a temperature. Appendicitis is a medical emergency,
and suspicious cases should be referred immediately for follow-up and possible appendectomy.
If the inflamed appendix is not removed, then there is danger that the appendix will rupture,
causing contamination of the peritoneum with intestinal bacteria (E. Coli, for example), and,
ultimately, peritonitis. For more about the implications for appendicitis and peritonitis, please
see and read Box 16-21 “Special Implications for the Therapist” in Goodman and Fuller, p
878 and Box 16-22 “Special Implications for the Therapist” in Goodman and Fuller, p 879.

2. Diverticulosis, which implies outpocketings along the large bowel. Diverticulosis is usually
seen in elderly people, and occurs due to weakness of the intestinal wall as a consequence to
aging. The hydrostatic pressure inside the bowel causes the weakened area of the wall to bulge,
creating a diverticulum. Most diverticuli (90%) occur in the sigmoid colon. An acute
condition, diverticulitis, occurs when the diverticuli become inflamed. Patients with
diverticulitis have fever, abdominal pain, and hematochezia. Occasionally, an inflamed
diverticulum may rupture, causing leakage of intestinal contents into the abdominal cavity,
and, subsequently, peritonitis.

 3. Idiopathic ulcerative colitis (IUC). IUC is one of the most common bowel diseases in the
US, and primarily affects young adult females of Jewish ancestry. The disease has an etiology,
and generally affects the mucosa only (compare to regional enteritis discussed previously,
which affects the full thickness of the bowel). Cases exist where regional enteritis and IUC
coexist in the same patient. Patients       with IUC often notice a sudden onset of abdominal
cramping pain and rectal bleeding. The bowel may then become spastic and cause symptoms
and signs of obstruction (as discussed previously) to develop (Toxic megacolon).

4. Carcinoma of the colon. Most examples (65%) of colon cancer occur in the rectosigmoid
colon. Cancers in this region can often be detected early, either by digital exam of the rectum
or by the observation of blood in the patient’s stool. Prognosis, therefore, is usually better for
rectosigmoid cancer than for cancer of the ascending colon (35% of cases). In cancer of the
ascending or transverse colon, early detection is not often possible, for the tumor is “silent” and
without symptoms until metastasis to the liver and pancreas has occurred. Signs and sumptoms
may include hematochezia (occult), colicky pain, weight loss, anemia, alternating
diarrhea/constipation, abdominal distention. Carcinoma of the colon is the 3rd most common
cause of death from cancer, and occurs mostly in older men and women.

5. The most common bowel disorder in the US is spastic colon, or irritable bowel syndrome
(IBS). In IBS, the colon may alternate between hyperactivity and sluggishness. Abdominal
discomfort and alternating constipation/diarrhea are common complaints. Rarely is there
intestinal bleeding or hematochezia. There is no specific tissue pathology associated with IBS,
and even though the bowel may become distended            during a constipation phase, there is
usually a return to normal within a few hours to a few days. Relaxation techniques, exercise,
and counseling are often used in treating IBS. For more about implications for IBS, please see
and read Box 16-14 “Special Implications for the Therapist” in Goodman and Fuller.
Read about rectal abscesses, rectoanal fistulas, and hemorrhoids in Goodman and Fuller, pp

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Diseases of the Kidney and Urinary Bladder
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

Diseases of urinary tract can affect kidney, urinary tract, urinary bladder, and/or urethra.
Renal (kidney) disease can affect following structures: renal cortex, pyramids of medulla, renal
pelvis and/or ureter. Nephron is a structural unit of kidney. Diseases can affect different parts of
nephrons such as glomerulus, bowman capsule, and tubules. Also interstitial space can be

Renal disease constitutes a syndrome of disorders that range from vascular to traumatic. Also,
inflammatory conditions constitute a large category of renal pathology. Common outcomes of
renal disease include: renal toxicity, osteoporosis, acid/base imbalance, and cardiovascular
disease. Causes contributing to renal disease, along with systemic changes associated with such
causes, are presented first in the discussion which follows. NOTE: Review renal
anatomy/physiology from any source to help with understanding renal disease.

When substances such as electrolytes (i.e. sodium-Na+; potassium-K+, etc.) are transported from
the renal tubule (after filtration by the glomeruli) back into the renal interstitial vasculature, the
transport is called reabsorption. By reabsorbing certain substances, the kidney is able replenish
them, as needed, back into the circulation. On the other hand, when electrolytes are transported
across the renal tubular walls and into the renal tubule directly from the interstitial vasculature,
the process is known as secretion. Thus, secretion, which travels in the opposite direction from
reabsorption, allows electrolytes to be carried off in the urine (or excreted) without being filtered
by the glomeruli. These processes-reabsorption, secretion, and excretion-allow the kidney to
carry out one of its most important functions, and that is to regulate and maintain the proper
concentrations of electrolytes in the blood.

I. Trauma, Burns
A traumatic incident (burn, injury) in which the circulating blood volume is reduced causes the
renal vessels to constrict, resulting in renal ischemia. Since the renal tissue is deprived of blood,
renal damage occurs in the form of acute tubular necrosis (ATN). Recovery may be complete
or only partial, depending upon the degree of ischemia.
Crush injury: Muscle damage may result in release of myoglobin (which binds O2 in muscles)
into the circulation. Since myoglobin is a large protein molecule, it may occlude the small renal
vessels, producing a renal ischemia with tissue damage.

II. Renal Vascular Disease can be associated with renal arterionephrosclerosis collagen
vascular diseases such as SLE and scleroderma. The ultimate result of renal vascular disease is
that a decreased amount of blood passes through the kidney to be filtered, and the following
outcomes occur. The patient becomes hypertensive, since the juxtaglomerular apparatus, which
monitors blood flood in the kidney, allows renin to be secreted in large amounts. Renin then
activates angiotensinogen in the blood, which, in turn, activates angiotensin I and then
anigiotensin II, causing vessel constriction and aldosterone release, which causes fluid retention.
Renal vascular disease is a common form of renal pathology, and is usually produced by
hardening of the small renal arteries, i.e. renal arterionephrosclerosis. Please see the schematic
for the renin-angiotensin-aldostersone mechanism below.

            Renin-Angiotensin System
                          Renin + Angiotensinogen

                              Angiotension I

                              Angiotensin II (conversion via ACE)

           vasoconstriction                    Aldosterone secretion

                                              Na +, H20 retention

                                       Increased plasma volume

                   Increased blood pressure

Renal hypertension produced from presence of a collagen vascular disease: i.e. systemic lupus
erythematosus, scleroderma (systemic sclerosis), systemic polyarteritis nodosa. In this case,
sclerosis of the renal vessels due to scarring and collagen replacement causes occlusion, resulting
in reduced blood flow. The renin-angiotensin mechanism becomes activated, and blood pressure

III. Pyelonephritis: Inflammation of the renal pelvis, and may involve the renal
interstitial tissue.
Pyelonephritis is usually caused by spread of bacteria into the kidneys from the urinary bladder,
secondary to bladder infection (cystitis). Other causes include renal obstruction via urinary
calculus (kidney stone) or enlarged prostate in elderly men. Persons with neurogenic bladder
secondary to spinal cord injury also frequently develop pyelonephritis, due to reflux of bacteria
inhabited urine into the renal pelvis. Hematogenous spread from another infected area of the
body, or from systemic sepsis, also occurs, especially in immune compromised individuals
(HIV, for example). Pyelonephritis in healthy individuals occurs mostly in females, and may be
acute or chronic, with some individuals having repeated episodes of inflammation. Patients with
pyelonephritis develop high fever and chills, and become debilitated and immobile very quickly.
The disease is treated with antibiotics and increased fluid intake and strengthening during
Patients with severe bouts of pyelonephritis may require rehabilitation due to its physically
potentially disabling effects. Patients requiring dialysis may become confused, disoriented, and
speech impaired, a condition called dialysis dementia. Symptoms of dialysis dementia may
include confusion, disorientation, speech impairment, and fatigue.

IV. Acute Glomerulonephritis: Inflammation of the glomeruli.

A. Approximately 70% of cases of acute glomerulonephritis (AGN) follow an upper
respiratory infection with beta hemolytic streptococcus, which causes “strep throat.” The
disease is the result of a Type III hyperimmune reaction (review under the section on
Immunology in Unit I), and causes antigen–antibody complexes to form in the blood, which
settle in the glomeruli. Glomeruli then become inflamed, and renal function is impaired. AGN
occurs mostly in children (>50%), and affects boys about twice as much as girls. Of children
with AGN, 80 – 90% completely recover after 4 – 6 weeks. AGN also occurs in adults, although
less frequently than in children. Approximately 50% of adults with AGN completely recover;
however, those who do not recover may proceed to a much more serious stage of disease, i.e.
progressive glomerulonephritis (PGN) or chronic glomerulonephritis (CGN) (both are
presented in the following discussion). Glomerulonephritis may also be proliferative (increased
number of cells in the glomerulis) or non-proliferative (lack of glomerular increase in cells).
Generally, proliferative glomerulonephritis has a poor prognosis, with patients having this form
of the disease progressing to end stage renal disease and renal failure.

B. Symptoms and Signs of AGN:

1. About 50% of persons with AGN develop renal hypertension, due to activation of the
renin–angiotensin mechanism;

2. Most develop mild edema, secondary to fluid retention associated with activation of the
renin – angiotensin mechanism;

3. Urine becomes dark or “coke bottle” colored, due to the presence of erythrocytes and tissue
casts, which are excreted because of tissue damage in the glomeruli;

4.   Hematuria–due to glomerular filtration breakdown and loss of rbc’s in the urine;

5. Proteinuria, which is mainly albumen, and is low molecular weight, so that it is easily
filtered and lost in the urine. Normally, only a trace of protein, known as Tam –Horsfall protein
should appear in the urine over a 24 hour period (although “isolated” protein may appear in the
urine of some persons with no evidence of renal disease, and generally appears following a bout
of exercise).

6. Headache, as well as nausea and vomiting are common in AGN. Causes for these
symptoms are probably due to electrolyte imbalance (sodium and potassium) in the circulation,
which occurs commonly in renal disease;

7. An initial oliguric phase, associated with restriction of glomerular blood flow, is followed
by several weeks of polyuria, as the renal tubular system breaks down and starts to heal.

V. Rapidly Progressive Glomerulonephritis (PGN)

A. A small percentage of persons who have AGN will not recover, but will instead develop
PGN. PGN is a rapidly progressive form of glomerulonephritis, which causes fulminating loss
of the glomeruli. Fibrin accumulates in the glomeruli, which prevents filtration. Patients with
PGN rapidly develop marked renal failure and uremia, and the disease has a mean mortality rate
of 2 years. Persons tolerant of hemodialysis may live considerably longer; persons receiving a
renal transplant may recover.

B. Goodpasture’s syndrome occurs in some individuals with PGN having the Goodpasture
antigen (antiglomerular basement membrane antibody), and represents a potentially lethal
variant. In Goodpasture’s syndrome, renal failure appears rapidly due to loss of glomeruli, and
patients also develop pulmonary lesions. Hemoptysis occurs, respiratory failure ensues, and the
patient may dies from respiratory arrest. Because of the pulmonary component, survival of
Goodpasture’s syndrome is poor, and treatments do not often yield encouraging results.

VI. Chronic Glomerulonephritis (CGN) and Diabetic Kidney

A. A small percentage of persons that have AGN develop a chronic form of glomerulonephritis
called chronic glomerulonephritis (CG). CG is slowly progressive, with slow, gradual loss of
glomeruli, progressing over several years. When enough glomeruli are lost that filtration of
plasma is impaired, renal failure and uremic syndrome, or “end stage kidney” result.
B. Diabetic nephropathy (diffuse diabetic glomerulosclerosis and nodular diabetic
glomerulosclerosis (Kimmelstiel–Wilson disease).           These conditions are very common
contributors to renal disease and, ultimately, renal failure. In diabetes mellitus, the blood sugar
becomes elevated, with numerous pathophysiological outcomes. One of these outcomes is renal
disease, caused by thickening of the basement membrane of the glomerulus, causing loss of the
plasma filtering mechanism. The disease is progressive, and amounts to 25–30% of all cases of
renal failure. As the kidneys fail, the signs of uremic toxicity develop (see below), and the
patient will not survive long term without dialysis and/or renal transplantation. Diffuse diabetic
glomerulosclerosis is the most common lesion renal lesion in diabetes mellitus, whereas
Kimmelstiel-Wilson disease consists of nodular accumulations of eosinophilic material located
in the periphery of the glomerulus.

GN can also be classified as non-proliferating (with lack of glomerular hypercellularity) and
proliferating (with glomerular hypercellularity). Proliferating type usually progress to end stage
renal failure over weeks or years.

VII.    End Stage Renal Disease

A. End stage organ disease occurs when organ(s) such as the kidneys permanently fail to
function. In end stage renal disease, there is a complete or near complete failure of the kidneys to
function to excrete wastes, concentrate urine, and regulate electrolytes. Patients with end stage
renal failure will display some (if not all) of the following signs and symptoms:
1. Metabolic acidosis with confusion and lethargy.
2. Electrolyte Imbalance (heart dysrhythmia, nausea & vomiting, diarrhea, muscle cramps) due
to a Na+ vs. K+ inverse renal relationship. For a summary of normal blood electrolyte values,
please see Appendix B on pp 152-153.
 3. Renal Osteodystrophy- Renal osteodystrophy is thought to be the result of
hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia, both of
which are due to decreased excretion of phosphate by the damaged kidney. Low activated
vitamin D3 levels are a result of the damaged kidneys' inability to convert vitamin D3 into its
active form, calcitriol, and result in further hypocalcemia and hyperphosphatemia.
 4. Azotemia-Retention of nitrogenous metabolic waste products, i.e. urea, creatinine, and uric
acid. Patients will usually display elevated blood urea nitrogen (BUN), and due to elevated uric
acid, develop gout.
5. Renal Hypertension, due to activation of the rennin-angiotensin system (please see ppt slides
6. Renal induced anemia-caused by a lack of erythropoietin (EPO), a protein produced in the
kidneys that helps to create red blood cells.

b.   Without treatment, end stage renal disease is uniformly fatal. Treatment options include:
            1.      Hemodialysis
            2.      Peritoneal dialysis
            3.      Renal transplant
            4.      Physical rehabilitation

VII. Acute vs. Chronic Renal Disease

Renal disease affects one or more of the following: the nephron, the renal interstitial tissue, the
renal vasculature, or the renal pelvis. Some renal diseases are short-lived and self-limiting in
nature, whereas others are long standing and progressive.

A. Acute renal failure (ARF)– may be defined as an abrupt, frequently reversible decline in
renal function, with recovery expected in about 6 – 8 weeks. Some causes of ARF are:
1. Acute tubular necrosis, in which a marked loss of blood flow to the        kidney results in loss
of renal tubules. Causes of such an event include: acute fluid depletion from burns, hemorrhage,
salt depletion, or post-operative shock.
2. Acute obstruction, such as a large kidney stone, prostatic hypertrophy, or a bladder tumor.
3. Nephrotoxin consumption (organic solvents, heavy metals, antibiotics, X-ray contrast media).
Long-term consumption of nephrotoxins can contribute to CRF.
4. Acute interstitial nephritis-general inflammation of the renal interstitial tissue, and may be in
response to drug reaction or allergy.
5. Pigments, such as accumulation of hemoglobin secondary to disseminated intravascular
coagulation (DIC), or myoglobin secondary to trauma and “crush” injuries)

B. Chronic renal failure (CRF) may be defined as a progressive, relentless decline in the
nephron population. Some causes of CRF are:
1. Chronic pyelonephritis (see previous discussion);
2. Glomerulonephritis (see previous discussion);
3. Chronic hypertensive vascular disease;
4. Collagen vascular disease (systemic lupus erythematosus, polyarteritis nodosa, progressive
sclerosis or scleroderma):
5. Polycystic kidney disease-an inherited disease in which bilateral, multiple, expanding cysts
encroach on and destroy normal renal tissue by compression;
6. Renal tubular acidosis-hereditary inability of the renal tubules to handle acid and/or
7. Diabetes mellitus-damages the filtration mechanism and causes diabetic nephropathy;
8. Gout-causes the formation of urate stones in the kidney;
9. Hyperparathyroidism-causes hypercalcemia, which results in excess accumulation of
calcium in the renal tubules and formation of kidney         stones;
10. Amyloidosis-formation of the glycoprotein amyloid, which deposits in renal tissue and
gradually destroys renal function;
11. Toxins–lead or analgesics, which are toxic to renal tissue, and;
12. Obstructions (prostatic hypertrophy, kidney stones, neurogenic bladder resulting from spinal
cord injury, renal tumors).

VIII.    Common Renal Diagnostic Procedures

      The following diagnostic tests are very common for assessing renal function:

 Blood urea nitrogen (BUN) (15 – 25 mg%)
 Blood creatinine (<1.5 mg%)
 % of PSP given should be eliminated in the urine by the kidneys in 15 minutes.
 24 hour urine volume (1200 to 1500 ml)
 Intravenous pyelography (IVP). IVP is a popular radiological method for assessing the
kidneys. A radiopaque dye is given via IV. The dye is filtered and excreted by the kidneys,
giving an x-ray view of the kidneys, ureters, and urinary bladder.

IX.       Urinary Bladder Disease

Major diseases of the urinary bladder include bladder epithelial carcinoma (which can be occult
and metastatic), and may be related to smoking or exposure to other airborne carcinogens. Such
tumors may occur in urinary bladder, the ureters, or the urethra and cause bleeding and
obstruction to urine flow. Please see Goodman and Fuller Box 18-3 p951 for risk factors in
bladder cancer.      Commonly, urinary bladder incontinence may occur, and is most prevalent
in older individuals (females more than males). Causes may be neurogenic, reduced volume
capacity, or a hyperactive detrusor muscle.

Symptoms of Cystitis typically include dysuria, polyuria, nocturia, and abnormal urine color.
Urinary bladder incontinence may be caused by cystitis, neurogenic bladder, reduced bladder
volume capacity, hyperactive detrusor, and reduced pelvic floor support.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Diseases of the Endocrine System: Diabetes Mellitus
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD


   Diabetes mellitus is one of the most common diseases in the US, and is currently the 3 rd
leading cause of death in the country as well as being the leading cause of blindness. Each year,
there are 600,000 new cases reported in the US, and there is currently an estimated 10 million
cases in existence. Diabetes mellitus is the leading cause of lower extremity amputations, and
places anyone who has the disease at risk, especially if injuries of any kind are sustained to the
feet. Diabetes mellitus is a leading cause of kidney disease (Diabetic Nephropathy)

In diabetes mellitus, blood glucose levels become elevated beyond normal ranges (70 – 110
mg%), producing a condition called hyperglycemia. Normally, blood sugar regulation comes
under the control of insulin, which facilitates transport of glucose from the blood and
extracellular fluid across cell membranes to the intracellular fluid and lowers the blood sugar.
Insulin is produced and secreted by the islet cells (the beta cells) of the pancreas. Various
possible etiologies of diabetes mellitus exist, including heredity, environmental causes (viruses,
chemicals), autoimmune considerations, and elevated glucagon production and secretion from
the alpha cells, (the other type of pancreatic Islet cell group). The most common type of
diabetes mellitus is caused by decreased sensitivity to insulin, and appears to be related to
obesity. It is not completely clear why obesity contributes to diabetes mellitus, but it has been
speculated that increased fat may cause a decrease in the number of tissue insulin receptor sites,
and also may cause decreased intracellular breakdown of glucose.

Metabolic syndrome
 Central obesity (excessive fat tissue in and around the abdomen)
Atherogenic dyslipidemia (blood fat disorders — mainly high cholesterol & triglycerides and low
HDL cholesterol — that foster plaque buildups in artery walls)
 Raised blood pressure (130/85 mmHg or higher)
Insulin resistance or glucose intolerance (the body can’t properly use insulin or blood sugar)
Prothrombotic state (e.g. high fibrinogen or plasminogen activator inhibitor in the blood)
Proinflammatory state (e.g. elevated high-sensitivity C-reactive protein in the blood)

For a summary of normal glucose blood values, please see Appendix B on pp 152-153.

A. Classification of diabetes mellitus types

1. Type I (Juvenile Onset). Type I diabetes mellitus occurs mainly in children and young adults,
and is characterized by a marked decrease in production of insulin by the pancreatic islet cells.
Persons with Type I diabetes mellitus invariably become insulin dependent, requiring that they
receive insulin exogenously via injection each day.

2. Type II (Maturity Onset). Type II diabetes mellitus occurs mainly in middle – aged to older
adults, and is the most common form of diabetes. Persons with Type II diabetes mellitus likely
do not have an insulin deficit, but rather show poor physiologic response to insulin at normal
secretion levels. Some patients with Type II diabetes mellitus require extra amounts of insulin
be given to them exogenously, while others are able to control their blood glucose by taking oral
hypoglycemics, or by diet. New therapeutic pharmacology increases sensitivity to receptor sites
and allows the patient’s own insulin to be more effective.

B. Clinical Commonalties of Types I & II diabetes Mellitus

1. Both types have hyperglycemia. Without insulin, Type I diabetes mellitus becomes severe,
and the patient can become unconscious due to hyperosmolar coma. In hyperosmolar coma, the
osmotic pressure of the blood becomes elevated due to presence of high glucose levels, causing
water from the extracellular fluid to be pulled out of neurons. As neurons dehydrate, their
function becomes impaired, and hyperosmolar coma ensues. Hyperosmolar coma is uncommon
in Type II diabetes mellitus, since blood glucose levels rarely rise to high enough levels to cause
its development.

2. Glucosuria is seen in both types of diabetes, and occurs when glucose from the blood spills
over into the urine. Glucosuria generally occurs when the level of blood glucose contained in the
plasma being filtered by the kidneys exceeds the ability of the renal tubules to reabsorb (the
glucose). This level, called the glucose renal t-max, may vary within the population, but is
generally reached when the blood glucose exceeds 180 mg%. Glucosuria is a hallmark sign of
diabetes mellitus, and may be the first clinical indication of the presence of the disease.

3. Polyphagia, polydipsia, polyuria often occur in both types of diabetes mellitus. Since glucose
is being transported poorly across cell membranes, the body’s appetite may go unabated.
Polyuria occurs because of glucose being filtered into the renal tubules, which causes an osmotic
gradient that holds water in the tubules and increases renal output (called an osmotic diuresis).
Dehydration may result, causing excessive thirst, or polydipsia.

4. Elevated blood lipids are one of the more common complications of both types of diabetes
mellitus. Since glucose is not readily available for metabolism, the body’s energy system results
to an alternative energy source, i.e. fats. As fats are mobilized from the natural body stores, they
are absorbed into the circulation, increasing the blood lipids. Subsequent to elevation of the
blood lipids, plaque forms on the walls of large arteries, causing the eventual development of

5. Poor wound healing is common in diabetics (Type I & II). This is due to changes in
circulation, subsequent to vascular disease and atherosclerosis.

6. Peripheral neuropathy almost always develops in both Type I and Type II diabetes mellitus.
Peripheral neuropathy develops due to the formation of insoluble deposits of glucose side
products that settle into peripheral nerves. Patients with diabetes mellitus induced peripheral
neuropathy may experience burning pain in affected sensory nerve cutaneous distribution sites,
or may have anesthesia to such areas. Motor axons may also be involved, and patients display
weakness, muscle atrophy, and loss of deep tendon reflexes (DTR's). Peripheral neuropathy
represents a significant hazard to patients with diabetes mellitus, since sensation in weight
bearing areas becomes impaired. Injuries caused by tight shoes and repeated pressure can cause
open sores to develop, and since these areas will likely have poor circulation, they heal poorly
and may become infected. Such a scenario explains the high frequency of lower extremity
amputations often seen in diabetics.

7. Diabetes mellitus is best assessed in all diabetics by the glucose tolerance test (GTT). The
GTT is administered by having the patient fast overnight, then, before eating in the morning,
drink a solution of 100 gms of glucose. Blood samples are then taken just before administration
of the 100 gms of glucose, and at selected intervals thereafter each 30 min for several hours.
Concentration of glucose in the blood is determined for each sample taken, and the
concentrations are graphed. In a GTT, fasting blood glucose can be assessed, as well as the
patient’s ability to metabolize glucose over an extended period of time. Persons with normal
insulin output show early peaks in blood glucose, followed by prompt decline back to normal
levels. Persons with insufficient insulin output show early peaks in blood glucose levels that
remain elevated. Other tests:Fasting blood glucose test ( should be < 100mg%), Random blood
glucose test (should be < 200mg%), and urine glucose (should be no trace).

8. Elevated Glycated hemoglobin (A1C). Measures the average amount of glucose to which a red
blood cell has been exposed during its life cycle (~120 days) Under 7% Glycated hemoglobin is
the desired value.

9. Insulin shock happens when administered more insulin than needed, which leads to severe
hypoglycemia. When brain cells get very little glucose insulin shock can occur. Person can lose
his/her consciousness and die.

C. Clinical Differences between Type I and Type II Diabetes Mellitus

1. Type I–since the islet cells of the pancreas have stopped producing insulin, insulin must be
replaced via an exogenous source. If the insulin is not supplied regularly, then blood glucose
soars, and the patient may go into hypersomolar coma and die. On the other hand, if too much
insulin is given, blood glucose will fall to very low levels and severe hypoglycemia will result.
Since the brain requires satisfactory levels of glucose to maintain consciousness, the patient will
lose consciousness and lapse into a coma–like state, called insulin shock. Insulin shock is a very
serious event, and requires the administration of glucose via parenteral means to raise blood
levels back to functional status.

2. Type I–because blood glucose levels can become so highly elevated, and the body is forced to
generate energy entirely from fat, ketoacidosis can result. Ketoacidsosis is a credible potential
problem in Type I diabetes mellitus, but is rarely observed in Type II diabetes mellitus. To
develop ketoacidosis, the body must use fat for energy to the extent that fatty acids begin to
accumulate faster than they can be metabolized. Accumulated fatty acids then begin to break
down into their chemical components, i.e. acetic acid, butyric acid, and acetone. The subsequent
aggregation of these by products in the blood causes a drop in pH, and ketoacidosis exists.
Patients with ketoacidosis are generally lethargic, due to the depressive effects of acid pH on the
CNS. Patients with ketoacidosis typically have “acetone” breath, and the presence of ketone
bodies can be demonstrated in the urine by routine urinalysis.

3. Type II–unlike Type I diabetes mellitus, Type II diabetes mellitus will likely respond to oral
hypoglycemics. Older oral hypoglycemics acted on the islet cells to stimulate the production of
more endogenous insulin; more recent oral hypoglycemics increase the body’s sensitivity to
endogenous insulin. Some Type II diabetics require exogenous insulin on a regular basis;
apparently, they require an insulin “boost” to overcome their inability to use their own insulin.

4. Type II–obesity is a common problem seen in Type II diabetics. The obesity appears to
facilitate the onset of Type II diabetes mellitus, and is regarded as an important risk factor for
developing the disease. Obesity likely impairs the ability of glucose to attach to cellular receptors
for uptake; obesity may also interfere with the intracellular breakdown of glucose.

5. Type I – Ketoacidosis. When there is not enough insulin body switches to burning fatty acids
in order to create energy. Such process results in production of acidic ketone bodies, that are
toxic and cause variety of symptoms and complications.

6. Complications of Diabetes Mellitus.

   A. One of the most unfortunate complications of Diabetes Mellitus is that of diabetic kidney,
or diabetic nephropathy. Diabetic kidney can be a long term outcome of both Type I and Type
II diabetes mellitus; however, it most often occurs as a consequence to Type I. Estimates have
suggested that about 50% of Type I (insulin-dependent) diabetics develop chronic renal failure
within 15-25 years after the onset of their disease. Consequently, diabetes mellitus is a common
cause of renal failure. There are several different types of diabetic nephropathies: 1) diffuse
diabetic glomerulosclerosis; 2) nodular diabetic glomerulosclerosis, or Kimmelstiel-Wilson

disease, and; 3) the various non-glomerular diabetic nephropathies, including chronic
interstitial nephritis, papillary necrosis, and hyalinosis of the afferent and efferent arterioles.
   B. Blindness due to diabetic retinopathy is also a common complication of diabetes mellitus,
and constitutes the leading cause of blindness in the US. Diabetic retinopathy occurs in both
types of diabetes mellitus, and is due to destruction of the walls of the retinal blood vessels. The
vessels form microaneurysms and microhemorrhages, resulting in disruption of blood flow to
the retina. Loss of retinal cells occurs, with subsequent loss of vision.
   C. Diabetic gastroplegia, or loss of gastric and GI motility may accompany diabetes mellitus.
Appetite diminishes and patients may show signs of ileus and obstruction.

6.     Diabetes Insipidus. Diabetes insipidus (DI) is another type of diabetes that is unrelated to
DM. This disorder can come about due to defective secretion of ADH from the posterior
pituitary or may be the result of the malfunctioning kidneys. Nephrogenic DI, which may be
hereditary or medication induced, occurs when the disorder is renal in nature. Central DI occurs
when there is insufficient ADH, and may be caused by damage to the hypothalamus and/or the
pituitary gland as a result of: head injury, infection, surgery, and tumor.

Patients’ biggest risks are becoming dehydrated and having an electrolyte imbalance. Treatment
involves keeping the patient adequately hydrated and monitoring electrolytes.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Diseases of the Endocrine System: Adrenal Pathology and Clinical Presentations
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD


  Adrenocortical Dysfunction

   In dysfunction of the adrenal cortex, steroid hormones are either under-secreted
  (adrenocortical hyposecretion disorder), or are over-secreted (adrenocortical hypersecretion
  disorder). The objective of the following text will be to describe specific manifestations of
  hypo – and hypersecretion disorders, along with a brief review of the physiology of the
  adrenal cortex.

Adrenal Cortex and Medulla

A. The adrenal medulla secretes catecholamines called epinephrine and norepinephrine.
Catecholamines regulate the sympathetic response by causing the heart rate to increase, by
raising the blood pressure, and by elevating the blood sugar. Abnormal elevation of
catecholamines can be caused by pheochromocytoma, which is a catecholamine secreting tumor
of the adrenal cortex, causing elevated blood pressure, tachycardia, elevated blood sugar.
B. The adrenal cortex secretes hormones called steroids. Steroids all have the same basic
structure as cholesterol, and are, in fact synthesized biochemically from the cholesterol nucleus
(see Price and Wilson, p 946, fig. 61-18.      The adrenal cortex produces and secretes the
following steroid hormones:
Mineralocorticoids, i.e.,Aldosteron. Regulation of aldosterone secretion is via renin (from the
juxtaglomerular apparatus of the kidney, which monitors renal blood flow). The physiologic
effects of aldosterone are as follows:

1. Promotes renal reabsorption of sodium, thus preventing sodium loss and dehydration;
2. Promotes secretion of potassium and hydrogen into the renal tubules, thus, preventing the
development of hyperkalemia and metabolic acidosis (see Appendix B for discussion and
definitions of this disorder).

Glucocorticoids, i.e.,Cortisol. Regulation of cortisol is via adrenocorticotropic hormone
(ACTH), which is secreted from the anterior portion of the pituitary gland. The physiologic
effects of cortisol are as follows:
1. Elevates the blood sugar (glucose) by the following physiologic mechanisms:
a. Decreases transport of glucose across cell membranes
b. Increases gluconeogenesis by the liver – this means that the liver uses amino acids from
proteins to synthesize more glucose.

2. Reduces the body protein stores, thus creating a negative nitrogen balance. In this case,
protein from the muscles, bones, other protein stores is being used to make glucose. Obvious
effects of a negative nitrogen balance are: 1) muscle wasting and 2) osteoporosis

3. Mobilizes and redistributes fat, causing the circulating level of blood lipids to rise. Also, at
high levels, glucocorticoids can have a mineralocorticoid effect and cause an electrolyte
imbalance. This means that the effects would be similar to aldosterone (see Mineralocorticoids

4. Suppresses the immune system. This is the main reason for therapeutic administration of
glucocorticoids in diseases presented previously with a hyperimmune etiology, such as the
collagen vascular diseases (RA, SLE, etc.), bronchial asthma, and glomerulonephritis.

Sex hormones , i.e., Androgens (and to some degree even estrogens). Androgens cause a
masculinizing of secondary sex characteristics, increase muscle mass, cause acne, and increase
body hair. Estrogens cause feminizing effects, and result in breast enlargement and other
development of other female gender effects.

Disorders of the Adrenal Cortex. These disorders are described below in terms of whether they
are of a hypersecretion or hyposecretion nature.

1. Hypersecretion disorders of the adrenal cortex may be described as follows:
a. Hyperaldosteronism is a hypersecretion disorder that implies that the adrenal cortex is
oversecreting aldosterone. The cause for the oversecretion may be primary (Conn syndrome), as
in an aldosterone secreting tumor of the adrenal cortex, or it may be secondary, as in activation
of the renin–angiotensin mechanism due to associated renal disease.

Primary hyperaldosteronism (Conn’s Syndrome). In Conn’s syndrome, hypersecretion of
aldosterone is produced from hyperplasia of aldosterone secreting cells in the adrenal cortex.
Conn’s syndrome usually implies neoplasia of the adrenal cortex, which may be malignant.

Secondary hyperaldosteronism implies over activation of the renin – angiotensin system because
of decreased blood flow through the renal vessels ( as in renal disease and CHF). The effects of
hypersecretion of aldosterone may be observed as:

-Hypernatremia, due to retention of sodium by the kidneys. Retention of sodium results in
concurrent retention of fluid, so that the patient has edema and becomes hypertensive.
-Hypokalemia, since retention of sodium results in loss of potassium in the urine. Hypokalemia
results in myocardial hyper excitability and muscle cramps. Since potassium and hydrogen both
move in the same direction across the renal tubule, hydrogen would also be lost in excess in the
urine. Due to the loss of hydrogen in the urine, an acid-base disorder will result, and the patient
will have a metabolic alkalosis and hyper acidic urine.
b.    Cushing’s Syndrome, in which glucocorticoids such as cortisol are secreted in excess
amounts. Cushing’s Syndrome may be caused by the following:
1. cortisol secreting tumor, which results in primary Cushing’s Syndrome;
2. administration of exogenous glucocorticoids, such as prednisone, for an inflammatory
condition (rheumatoid arthritis or other collagen vascular diseases, asthma, glomerulonephritis,
3. The clinical presentation of Cushing’s Syndrome includes the
- fat pads
- moon face
- red cheeks
- pendulous abdomen
- bruising with ecchymoses
- striae over the abdominal region
- poor muscle development
- poor wound healing
- increased blood sugar leading to diabetes mellitus
- osteoporosis – with fractures and vertebral compression/collapse

c.    Adrenogenital Syndrome, which results from an increased level of androgens secreted from
the adrenal cortex. Causes of the adrenogenital syndrome are as follows:
Primary, which may be due to the presence in the adrenal cortex of an androgen secreting tumor,
or from congenital adrenal hyperplasia;
 Secondary, which may be due to exogenous androgens, i.e. “steroids”, such as used by some
body builders and athletes to increase strength, build muscle mass, etc. Unfortunately, exogenous
androgens have may side effects, including psychiatric manifestations.
The clinical presentation of adrenogenital syndrome includes the following:
- baldness/receding hairline
- hirsutism (excessive hair growth)
- androgenic flush
- small breasts in females
- male escutcheon (male distribution of pubic hair)
-   enlarged clitoris in females
-   - “heavy,” muscular extremities

2. Hyposecretion Disorders of the Adrenal Cortex

a. Addison’s Disease, which is usually an autoimmune disease of the aldosterone secreting cells
of the adrenal cortex, but may also be caused by disseminated adrenal tuberculosis. In Addison's
disease, aldosterone is significantly under secreted. The following changes occur in Addison’s

1. Hyponatremia, due to sodium loss. Since aldosterone causes sodium to be retained by the
kidneys, its absence causes sodium to be lost in the urine, taking water with it. Patients develop
polyuria with large urine volume, which results in loss of body water and hypotension, and,
ultimately, hypovolemic shock.
2. Hyperkalemia, due to sodium loss and potassium retention. Hyperkalemia has a profound
effect on heart muscle, causing slowing and weakening of the myocardial contraction. Also,
since hydrogen and potassium move in the same direction across the renal tubules, hydrogen ions
will be retained in excess
3. Metabolic acidosis
4. Hypermelaninsosis, which is caused by elevated ACTH from the anterior pituitary gland.
Since the adrenal cortex has atrophied, there is no feedback on the anterior pituitary;
consequently ACTH mobilizes the pigment in the skin, causing hypermelaninsosis, or darkening
of the skin in light skinned persons. Persons with Addison's disease may have alternating dark
and light patches on the skin caused from mobilization of pigment–this condition is called
vitelligo, and may be commonly seen in patients with the disease.

Medical University of South Carolina
College of Health Professions
Divisions of Occupational and Physical Therapy

Diseases of the Endocrine System: Other Endocrine Disorders
Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009
K. Jackson Thomas PT, EdD

At the conclusion of this section and after the chapter readings, you should be able to:

1. Explain the pathology of the following endocrine diseases and describe their
      symptomatic presentations:
       -hyper-hyposecretion disorders of the pituitary gland;
       -hyper-hyposecretion disorders of the thyroid and parathyroid glands;
       -disorders of the male and female genitourinary/reproductive systems.
2. Discuss estrogen insufficiency in post-menopausal females and estrogen induced
   osteoporosis; differentiate between post-menopausal osteoporosis and senile osteoporosis.
3. List at least 5 considerations that Physical and Occupational Therapist should
   consider when planning treatment protocols for patients with: a) osteoporosis; b)
   pituitary disease; c) thyroid and parathyroid disease; adrenal disease, and; diseases of
   the male and female reproductive system.


Pituitary disorders.

A. Acromegaly. Acromegaly implies a growth hormone (GH or somatotropin) secreting tumor
of the anterior pituitary gland. GH promotes increase in soft tissue mass increased in diameter
of long bones. The clinical presentations of acromegaly are:
- visual field changes (bitemporal hemianopsia) due to pressure on the optic chiasm, which is
located immediately rostral to the pituitary gland;
- osteoarthritic vertebral changes;
- prognathism and acromegalic faces;
- hirsutism;
- gynecomastia (enlarged breasts) and lactation;
- enlarged hands and feet.

Sometimes a hypersecretion of GH occurs before the epiphyseal growth plates close. In this case,
long bones can grow abnormally in length, resulting in a condition called gigantism. If a
hyposecretion of GH should occur, however, then long bone growth is stunted, resulting in
pituitary dwarfism.

Thyroid disorders.

Thyroxin controls the rate of metabolic processes in the body and influences physical
development. Physiologic effects of thyroxin include: increase metabolic rate, increase cardiac
excitability, increase blood pressure, increase GI motility, hyperactive deep tendon reflexes,
weight loss.

B. Hypothyroidism (Myxedema). Hypothyroidism may occur secondary to lack of iodine in
the diet, or it may be due to autoimmune thyroiditis (Hashimoto’s thyroiditis). In
hypothyroidism, the thyroid is unable to make and synthesize thyroxin, a hormone that is
dependent upon iodine for its synthesis and helps govern the body’s basal metabolic rate. The
clinical picture of hypothyroidism is:

-   myxedematous faces
-   decreased basal metabolic rate (BMR)
-   bradycardia with decreased myocardial excitability
-   low blood pressure
-   slow deep tendon reflex (DTR) reaction time
-   reduced gastrointestinal motility with constipation
-   enlarged thyroid gland, or goiter
-   weight gain

If the baby was born with hypothyroidism or if it develops soon after birth and not treated
properly, child will develop cretinism. Cretinism characterized by severely stunted growth and
mental retardation.

C. Hyperthyroidism (Grave’s Disease). Hyperthyroidism generally implies hyperplasia of the
thyroid gland, and/or palpable tumor. In hyperthyroidism, there is increased thyroxin production
and secretion, so that the patient’s metabolic rate is increased. The clinical picture of
hyperthyroidism is exactly opposite to hypothyroidism, and consists of:
- increased basal metabolic rate
- tachycardia, with increased cardiac excitability
- increased GI motility with diarrhea
- increased DTR reaction time
- weight loss
- fine tremor, upon extension of the fingers
- exophthalmus, or bulging eyes, caused by increase in retro-orbital fat

All the above clinical signs can be reversed with therapy to reduce thyroxin output;
exophthalmia, however, often remains as a permanent change in the facial appearance. Thyroid
cancer (thyroid papillary carcinoma) is one of the fastest growing cancers in the USA, which an
especially alarming increase in women. Although carcinoma of the thyroid papillary carcinoma
is rarely fatal when treated, distant metastasis to the bone and lungs harbors a less optimistic
prognosis. Overall, this cancer has a high cure rate with ten year survival rates for all patients
with papillary thyroid cancer estimated at 80-90%. Associated anatomically with the thyroid
gland are the parathyroid glands. The parathyroid glands secrete a hormone called parathyroid
hormone (PTH). PTH regulates blood calcium levels, with hyposecretion resulting in low blood
calcium (normal value in adults=9.0–10.5 mg/100 ml blood). Low blood calcium can cause
tetany, a condition in which muscles go into a spasm. The muscles of the wrist and hand are
notably affected, as well as the muscles of the ankle and feet. The facial muscles also show
spasms, with the patient often exhibiting a “risorial grin” (spasm of the risorius muscle). Also
affected are the muscles of the trunk, including the muscles used for respiration (diaphragm,
intercostals, etc.). Thus, an individual with hypocalcemia induced tetany may have difficulty
breathing as a result of respiratory muscle involvement. On the other hand, if the parathyroids
oversecrete PTH, the calcium in the blood will be elevated above normal levels, resulting in
possible calcium composed kidney stones and osteoporosis, as the elevated PTH caused calcium
release from bones and resulting bone demineralization.

D. Menopause. The climacteric occurs when regression of ovarian function takes place.
Menopause, which implies the cessation of uterine bleeding, is one event of the climacteric, and
usually occurs in females between the ages of 45 and 52. As ovarian function decreases,
estrogen levels decline, which in turn causes several different signs and symptoms, all of which
are quite common in post – menopausal individuals. Clinical symptoms and signs of menopause
1. hot flushes (very common)
2. palpitations
3. headaches
4. cold hands and feet
5. irritability
6. vertigo
7. anxiety
8. nervousness
9. depression
10. insomnia
11. night sweats
12. forgetfulness
13. inability to concentrate
14. fatigue
15. weight gain
16. osteoporosis (brittle bone disease)

E. Osteoporosis. Osteoporosis is a common contributor to fractures, especially broken hips.
Patients with hip fractures due to osteoporosis often must be cared for in nursing homes, and
there is a 12 – 20 percent mortality rate among such individuals.

1. Post–menopausal osteoporosis–generally affects women and may show up initially as
fractures of the wrist and/or the vertebrae. Many women with post–menopausal osteoporosis
develop kyphosis and show a characteristic dowager’s hump.

2.   Senile osteoporosis–develops as a result of aging and affects twice as many women as men.
3.   Major risk factors for osteoporosis are:
a.   advanced age
b.   female gender
c.   Caucasian or Asian race
d.   being thin and having small bones
e.   premature or surgically induced menopause
f.   family history of osteoporosis
g.   heavy alcohol use
h.   limited physical exercise
i.   inadequate calcium intake
j.   chronic use of corticosteroids
k.   tobacco use, specifically smoking

                                Dowager’s Hump seen in osteoporosis

             OSTEOPOROSIS POINTS TO CONSIDER (see assigned reading)

 1. Offer a simple definition of osteoporosis.

 2. List and describe briefly the two types of osteoporosis.

 3. Describe the population most often affected by osteoporosis.

 4. What is a “dowager’s hump?”

 5. List some major risk factors thought to be important in osteoporosis.

 6. At about what age does bone mass reach a peak? Name some factors that tend to enhance
    bone mass.

 7. Name some current therapeutic regimens for treating (and possibly preventing)

                                           End-Unit IV

                                      Study Tips for Unit IV
The following is a brief review of the objectives for the upcoming exam, also with a few practice
questions. All are intended to help you in focusing on the important items, as well as give you
some practice on these kinds of questions that you will be asked.

Please see or contact me for any questions that you might have.

Be sure to read carefully the attached article on Osteoporosis and do the study
questions attached under Osteoporosis Points to Consider. Questions on these topics will be
in terms of the following:

 1. Review of pathological interactions of the GI, hepatobiliary, renal, and endocrine systems.

 2. Gastric dysfunction -gastritis (chronic vs. acute), stress vs. peptic ulcers, cancer.

 3. Esophageal disorders - review the esophageal hiatus of the diaphragm, hiatal hernia
    (symptoms), achalasia, MWS, and esophageal cancer.

 4. Malabsorption syndrome vs. obstructive syndrome (causes, symptoms and signs, specific

 5. Diseases and pathophysiology of the large bowel, appendix, etc.

 6. Review of normal renal function, with key concepts and terms to include;

      a)   nephron (definition, parts, physiological concepts)
      b)   general anatomy of the kidney
      c)   key terms-filtration, secretion, reabsorption, and excretion
      d)   excretory vs. non-excretory functions

 7. Renal failure-review and define acute vs. chronic and be able to list some contributing
    factors to each (as per the handout).

8. Renal diseases as per Goodman and Fuller and lecture (i.e. glomerulonephritis
   -acute, progressive, chronic), acute tubular necrosis (ATN), etc.

All the signs and symptoms of uremia, or "uremic syndrome", along with explanation of
rationale for occurrence.

10. Pathophysiologic conditions of the endocrine glands, including diabetes mellitus
    (IDDM vs. NIDDM).

11.        Adrenal hypersecretion vs. hypersecretion disorders, same for thyroid and pituitary,
           estrogen and osteoporosis (read notes on this topic).



     1. Concerning pyelonephritis (Which is/are true?):

        a.   is often a result of obstruction to urine flow
        b.   is often spread to the kidneys via the bloodstream
        c.   is inflammation revolving the renal pelvis and/or renal interstitial tissue
        d.   all of the above
        e.   b and c only

     2. The condition most likely associated with inadequate levels of thyroxine
        would be:

        a.   osteoporosis
        b.   exophthalmia
        c.   hirsutism
        d.   lethargy
        e.   tachycardia

    3. Which of the following typify/typifies symptoms which might be manifest from
a malignancy of the lower large bowel?

        a.   anemia
        b.   diarrhea
        c.   weight loss
        d.   all of the above
        e.   b and c only

    4. Which of the following typify / typifies symptoms which might be manifest from
a malignancy of the lower esophagus?

        a.   dysphagia
        b.   rebound pain at McBurney's point
        c.   weight gain
        d.   all of the above
        e.   b and c only


         a.    Diverticulitis
         b.    Idiopathic ulcerative colitis
         c.    Both a and b
         d.    Neither a nor b

              5.   generally occurs in females more than males
              6.   generally occurs subsequent to irritable bowel syndrome (IBS)
              7    .occurs primarily in older patients
              8.   occurs more frequently in individuals with Jewish ancestry
              9.   hematochezia sometimes present

III. T/F (10-11)

   10.   The most common site for colorectal carcinoma to occur is the transverse colon.

   11.   Diverticulosis typically occurs in middle-age males, and is considered to be caused by
         the presence of hereditary polyps in the large bowel.

                           ANSWERS TO FORMATIVE EXAM


   1. Answer is D. Pyelonephritis was discussed in the lecture on renal diseases. The 3 items
  given which categorize this disease (which, incidentally, is what is   generally meant by
  the term "kidney infection") make up this question. For further explanation, if needed, please
  see me.

   2. Answer is D. Inadequate levels of thyroxine in the adult characterize the condition
      myxedema. In this condition, patients typically lack energy, and are quite lethargic.
      Also, tend to be overweight and have bradycardia.

   3. Answer is D. Lower colon malignancies may cause anemia due to bleeding.
      Diarrhea may be associated with blockage and weight loss, due to general nutritional

   4. Answer is A. A malignant tumor of the lower esophagus will likely cause an
      obstruction, thus causing difficulty in swallowing, dysphagia. Rebound pain at
      McBurney's point is usually indicative of appendicitis, and weight gain with
      esophageal cancer would be highly unlikely.

PART 11.

  5. Answer is B. Idiopathic ulcerative colitis is typically a mucosal disease of the      large
  bowel in young females.

  6. Answer is D. Neither diverticulitis or idiopathic ulcerative colitis is necessarily
     associated with irritable bowel syndrome ("spastic colon").

  7. Answer is A. Diverticulitis, or an inflammation of a diverticulum, is usually
     experienced by older individuals.

  8. Answer is B. IUC has a higher frequency in young women with Jewish ancestry.

   9. Answer is C. GI bleeding (hematochezia) generally is manifested in both diseases.

PART 111.

10. FALSE. The most common site for colorectal carcinoma is the sigmoid and/or             rectal
colon (along with the descending).

11. FALSE. Diverticulosis is primarily a disease of elderly individuals. There is no
  specific correlation with hereditary polyps.

                                      Appendix A

                              Clinical Laboratory Values

Reference: Goodman and Fuller. Pathology: Implications for the Physical Therapist
(edition 3). St. Louis: Saunders/Elsevier (USA), 2009: Chap 40.

                                                                 Appendix B

Laboratory   Reason                  Normal            Abnormalities                             Implications for Treatment
Value                                Ranges
RBC’s                                Male: 4.7-5.5
                                     Female: 4.1-4.9
White        Indicates the           5,000-            Leukocytosis (high WBC count)             Symptoms of elevation include fever,
Blood Cell   functional status of    10,000/ccm        may be due to acute/chronic               weakness and aches. Patients with levels >
Count        the immune system.                        infection or malignancy. Leukopenia       11,000 may have decreased exercise
(WBC)        WBC protect the                           (low WBC count) may be caused by          tolerance due to infection. Consider
             body against                              a disease of the immune system or         postponing exercise with levels <5,000 with
             infection and aid in                      radiation/chemotherapy.                   fever due to risk of infection.
             the immune
Hematocrit   Volume of red           Male 42-52%       Increased Hct may be due to tobacco       Patients with low levels may have weakness,
(Hct)        blood cells in whole    Female 37-47%     use, severe lung disease,                 fatigue, dyspnea on exertion, and tachycardia.
             blood; used to                            polycythemia vera. Decreased Hct          Modify treatment with Hct 25-30% and
             evaluate anemia and                       may be due to anemia or                   consider postponing exercise with Hct <25%.
             abnormal states of                        hemodilution.                             Frequent vital signs monitoring and rest
             hydration.                                                                          periods recommended with low levels.
Hemoglobi    Hb reflects the         Male 14-          Increased Hb can be seen in smokers       Modify treatment with Hb 8-10 due to
n (Hb)       oxygen carrying         18g/dL            and people with lung disease.             reduced exercise capacity. Consider
             component of the        Female 12-        Decreased Hb is found in anemia.          postponing exercise if Hb<8.
             red blood cell,         16g/dL
             indicates severity of
Platelets    Play primary role in    150-400,000/uL    Thrombocytosis (high platelet count)      With low platelet levels, bleeding can occur
(Plts)       clotting process. As                      may be caused by iron deficiency,         from mucosal surfaces and with minor
             a result of platelet                      neoplasm, inflammation, infection.        trauma. Patients are at higher risk for bruising
             activity, bleeding is                     Thrombocytopenia (low platelet            and bleeding under the skin. Prolonged
             stopped and wound                         count) can be caused by liver             bleeding can occur after surgery or trauma
             healing begins.                           disease. DIC, platelet disorders, viral   with levels less than 40,000. PT guidelines:
                                                       infection.                                No exercise < 20,000, light exercise (AROM
                                                                                                 and ambulation) 20,000-50,000, no resistive
                                                                                                 exercise <50,000.
Sodium       Na is an electrolyte    136-145 mEg/L     Changes in sodium can cause cells to      Be aware of potential symptoms when Na is
(Na)         that is important in                      shrink or swell. Levels are affected      low- weakness, confusion, stupor,
             nerve conduction,                         by diuretics, diarrhea, CHF. Brain        hypotension, seizures, edema and weight
             contraction of                            cells are susceptible and mental          gain.
             muscles,                                  status changes may be noted with
             functioning of cells.                     abnormal levels.
Potassium    K is an electrolyte     3.5-5.0 mEq/L     Increased K (hyperkalemia) can be         Minor changes in K can have significant
(K)          found inside the                          due to kidney disease or certain          consequences for cardiac function. Patients
             cells in the body                         medications. Hyperkalemia can             with abnormal K levels should be seen for
             that is important for                     produce ECG changes, nausea,              exercise after the level has been corrected.
             muscle and nerve                          diarrhea. Hypokalemia can be
             function.                                 caused by diarrhea, vomiting and
                                                       dehydration. Low K levels can lead
                                                       to dangerous ventricular
                                                       arrhythmias, cardiac instability,
                                                       dizziness, and hypotension.
Carbon       Measure of CO2 in       23-30 mEq/L       When CO2 levels are abnormal, it          Abnormal levels may be due to a wide range
Dioxide      blood, ordered as a                       suggests that the body is having          of dysfunctions: blood gases may be ordered
Content      part of the                               problems with acid/base balance or        to evaluate severity of imbalance and
(CO2)        electrolyte panel.                        an electrolyte to imbalance               determine if imbalance is respiratory or
Blood Urea   Waste product of        10-20 mg/dL       Increased levels seen in renal and        No specific activity guidelines but it is
Nitrogen     protein metabolism.                       liver disease. When kidneys are not       important to be aware that patients with renal
(BUN)        Directly related to                       functioning properly, high values         dysfunction may experience fatigue, muscle
             metabolic function                        can occur. Decreased values are           weakness, and decreased mental status as
             of the liver and                          caused by inadequate protein intake,      these levels rise.
             excretory function                        malabsorption, and liver damage.
             of the kidneys.
Creatinine   By product of           0.6-1.2 mg/dL     High levels are reflective of             No specific activity guidelines but it is
             normal muscle                             worsening kidney function. Low            important to be aware that patients with renal
             metabolism.                               levels seen with inadequate protein       dysfunction may experience fatigue, muscle
             Regulated and                             intake, liver disease and kidney          weakness, and decreased mental status as
             excreted by the                           damage.                                   these levels rise.
Blood          Measure of the         Fasting test 70-   Hypoglycemia (low levels) can lead       Symptoms of hypoglycemia include:
Glucose        sugar content in the   99mg/dL            to low activity tolerance;               sweating, hunger, trembling, anxiety, blurred
               blood; used to                            overexertion can cause                   vision, and confusion. Hold exercise if level
               detect hyper and       Pre-Diabetes       hypoglycemia reaction.                   is < 60 until level has been corrected.
               hypoglycemia and       100-125 mg/dl      Hyperglycemia (high levels) can          Symptoms of hyperglycemia include:
               to diagnose                               lead to diabetic ketoacidosis.           increased thirst, fatigue, blurred vision. Hold
               diabetes.              Diabetes > 126                                              exercise if level is > 350. Ideal pre-exercise
                                                                                                  glucose levels are in the range of 100-
                                                                                                  250/300 mg/dL.
Chloride       Electrolyte            98-106 mEq/L       Elevated levels seen with                If an electrolyte imbalance is detected, it may
               controlled by the                         dehydration. Decreased levels seen       lead to further tests. No specific activity
               kidneys. Involved in                      with diarrhea, infection, or diabetes.   guidelines.
               acid/base balance
               and in regulating
               blood volume.
Prothrombi     Measures the           May vary           An abnormal prothrombin time is          Patient receiving anticoagulant therapy may
n time (PT     clotting time of       depending on       often caused by liver disease/injury     have levels that are 2-3 times the laboratory
or Pro         plasma and is used     lab. 11-12.5 sec   or by treatment with anticoagulant       control values. With abnormally high levels,
Time)          to screen for                             drugs.                                   exercise may be held due to increased risk of
               bleeding                                                                           bleeding.
               abnormalities. PT is
               also used to monitor
               effectiveness of
               blood thinning
               drugs such as
Partial        Test that measures     May vary           Prolonged PTT may be seen with           Patients receiving anticoagulant therapy may
Thrombopla     clotting time in       depending on       chronic liver disease, DIC,              have levels that are 1.5 to 2.5 times the
stin Time      plasma. It is useful   lab. 30-40 sec     hemophilia, and the treatment of         laboratory control values. With abnormally
(PTT)          in the evaluation of                      medications to prevent or treat blood    high levels, exercise may be held due to
               disorders of both                         clots.                                   increased risk of bleeding.
               excessive clotting
               and excessive
               bleeding. Used to
               monitor the
               effectiveness of
Internationa   Standardization        0.9-1.1            Patients may have increased INR if       The therapeutic range is determined by the
l              technique used to                         they are taking anticoagulants for       MD, normally it is 2-3. At very high levels
Normalized     correct for                               medical reasons such as AF, DVT,         (>5), patient may be at increased risk for
Ratio (INR)    variations in                             prophylaxis, LVAD, and MI.               bleeding and it may be appropriate to avoid
               Prothrombin time                                                                   exercise. Patient may be on bedrest at levels
               between labs; used                                                                 >5. Consult with MD.
               to monitor warfarin

Appendix C

                                          Appendix D

                                     Postmortem Changes

An ongoing issue in the pathological examination of a deceased person (especially in forensic
cases) lies in understanding the natural changes in the body that follow death. Besides the
cessation of respiration, circulation, and metabolic processes, other changes begin to occur that
not only explain the observed physical changes that follow a person’s death, but also are helpful
in fixing the time of death within the limits of probability. In taking into account the physical
changes following death, one should also be aware that the onset (and subsiding) of the physical
changes can be considerably influenced by several factors, including environmental
circumstances (i.e. temperature and humidity), as well as muscular development and pre-mortem
muscular activity, pre-mortem nutritional status, and even age, to give examples.

A.     Many physio-chemical changes occur in the body immediately or shortly after death.
       These changes then progress in a generally predictable fashion all the way to
       decomposition and eventually, disintegration of soft tissue and depending on surrounding
       environment, even bone. However, changes that are associated with death that may be
       observed rather easily include:
       1. Algor mortis, or body cooling-a very useful indicator of the time of death, at least
          during the first 24 hours post-mortem. At death, all metabolic processes cease
          functioning, and since metabolism generates heat, body temperature cannot be
          intrinsically maintained. Thus, temperature, after an initial plateau, falls in a linear
          fashion. The length of the plateau and the subsequent fall, however, can be influenced
          by environmental temperature, with the plateau lasting much longer if the temperature
          of the deceased person is close to the environmental temperature.
       2. Livor mortis, or post-mortem lividity-a “purple-ish” discoloration that results from
          the gravitational pooling of blood in veins and capillaries and occurs in the gravity
          dependent portions of the body. Since circulation of blood has stopped with death, the
          red cell elements begin to settle out of suspension and accumulate in areas that are
          gravity dependent-hence, the discoloration. Lividity develops because blood remains
          in a liquid state immediately after death, and then after approximately a half hour to
          an hour post-mortem, become permanently liquid and cannot coagulate. This is due to
          release of fibrinolysins, which is antagonistic to clot formation. Exceptions to this
          general rule may occur in death that is associated with infection or wasting (i.e.
          cachexia), in which the fibrinolysins may fail to develop. In bodies embalmed with
          formaldehyde, clots are generally numerous in the heart and throughout the vascular
          system, as formaldehyde as a preservative denatures protein, thus causing blood to
          clot. Lividity usually is apparent as early as 20-30 minutes after death, but may be
          delayed in individuals who have marked anemia or massive bleeding.
       3. Rigor mortis, or post-mortem muscular (voluntary and involuntary)
          contraction/stiffening-general and gradual contraction of usually the small muscles of
          the eyelids, face and neck, then followed by contraction of muscles of the limb (feet
          and hands first, then those of the wrist/ankle, then knee/elbow, and finally
          shoulder/hip. Finally, the muscles of the truck are usually last to become rigid (thus
          small muscles first, and lastly large muscles).


To top