Physiology 2nd SCT- 1st semester
Body fluid compartments-homeostasis
Homeostasis is the process through witch bodily equilibrium is maintained. The body is designed to
maintain a constant „internal milleu“ with regard to the body´s:
Blood glucose levels...ect.
The body as an open system:
The body exchanges material and energy with it´s surroundings, meanwhile the amount of body
fluids are kept constant. Fluid intake must be matched tp prevent body fluids from increasing or
decreasing. So the body must balance the net gain or net loss.
The human body is about 55-60% in adult males and 50-55% in adult females, due to higher
proportion of body fat.
Aprox 42 L in a 70 kg man.
Drinks, food and metabolism of CO2 and H20 (oxidation of carbohydrates). Around 2300ml
per day, although it varies.
Evaporation from the respiratory tract and skin surface (not sweat which is sensible)
At room temp it´s ~25% of heat loss, it decreases in cold and increases in heat & exercise.
Bleeding, vomiting, diarrhea.
Any substance containing free ions that behaves as an electrically conductive medium. Because they
generally consist of ions in solution, electrolytes are also known as ionic solutions. They must be
consumed and eliminated in equal quantities.
In physiology, the primary ions of electrolytes are sodium (Na+), potassium (K+), calcium (Ca2+),
magnesium (Mg2+), chloride (Cl−), hydrogen phosphate (HPO42−), and hydrogen carbonate (HCO3−).
The electric charge symbols of plus (+) and minus (−) indicate that the substance in question is ionic
in nature and has an imbalanced distribution of electrons, which is the result of chemical
Na+ and K+ , usually by ingestion of food.
Clinically theu enter the body parenterally, through i.v. solution.
Abnormal routes e.g. vomit and diarrhea
Substances that are chemically altered must also be in balance BUT the amount consumed will not
have a simple one to one relationship to the eliminated amount. There must be a chemical
conservation btw substrates and end-products.
The distribution of various substances within the body in NOT homogeneous!!
Body fluid compartments
A region of the body with different chemical
compostion or unique behavior. Usually separated
from each other either by membranes or by whole cells
forming a epithelial (or endothelial) lining.
The total body fluid is distributed mainly btw 2
compartments; the intra- and extracellular fluid. The
extracellular fluid is divided to interstitial fluid and
1. Intracellular fluid
Aprox 36% of body weight, so ~ 25L in a 70 kg
The fluid of each cell contains it´s mixture of
different constituents but the concentration of these substances are similar from one cell to
2. Extracellular fluid
Aprox 24% of body weight.
Plasma: blood without red and white blood cells. It exchanges substances
continuously with the interstitial fluid through pores in the capillary
membranes, soluble to all solutes except proteins. So plasma and interstital
fluid have the same compsition except for protein.
3L in 70 kg man = about 4.5% of body weight
Interstitial space: Space btw the cells that makes up the organs.
8L in 70 kg man = about 11,5% of body weight
Also there is EC fluid in bone, dense CT and transcellular water in secretions
such as digestive secretions, intraocular fluid, CSF, sweat and synovial fluid.
The remaining 6 L is in these minor compartments.
Blood contains both extracellular fluid (plasma) and intracellular fluid (fluid in RBC), BUT blood is
considered to be a separated fluid compartment because it´s contained in a chamber of it´s own.
Plasma volume : Blood volume x (1-hematocrit)
The plasma water is the initial wate access point for ingested nutrients, and the exit point for the
body´s waste. Access to ALL the cells of the body, except RBC, is by the interstitial space.
The ionic compsition:
Different btw body compartments BUT
the total osmotic concentartions of EC
and IC fluid is similar (despite the
differece in total ionic concentration).
Main EC cation: Na+
anion: Cl- and HCO3-
Main IC cation: K+
anion: phosphates (inorganic,
HPO4 & H2PO4- AND organic, ATP ect.)
The EC fluid production in pathological conditions: differs btw
extravascular fluid with low protein content any fluid that filters from the circulatory system
into lesions or areas of inflammation
High BP Inflammation
Clean-water like fluid Turbid
No protein (-Rivalto reaction) Protein (+Rivalto reaction)
Low density High density
EXPRESSING FLUID COMPOSITION:
1. Molality: Concentration as moles solute per kg of solvent.
2. Molarity(M): Concentration expressed as moles solute per L of solution. M means
moles/liter! Physiological concentrations are low so they are often expressed in units of
millimolar (mM)=10-3M, micromolar (µM)=10-6M, nanomolar (nM)=10-9, or
3. Electrochemical equivalence (Eq): The weight in grams of an ionic substance that replaces or
combines with one gram (mole) of monovalent H+ ions.
For monovalent ions like Na+ and Cl- one Eq is equal to one GMW.
For monovalent ions like Ca++ and Mg++ one Eq is equal to one-half GMW.
Physiological concentrations are small and often measures in mEq/L= 10-3 Eq/L.
These units are useful in concidering how much of a substance is needed to maintain
4. Complications in determining plasma concentration: Not all ionic substances from freely-
diccociated, freely-dissolved species.
a. Many bind proteins
b. Plasma is 97% water. The 3% is protein and lipids. So ionic concentrations are
somewhat underestimated when expressed in terms of whole plasma.
Osmosis is the net diffusion of water accross a
semipermeable membrane from a region of high water
concentration to one of lower concentration. The
semipermeable membrane separates 2 compartments,
solute particles cannot go through BUT water will cross untill
solute concentration on both sides is equal. The force
generated: osmotic pressure (q).
Particles which dissociate to form ions exert an osmaotic
force in proportion to the number of osmotic particles
formed. For example: 1 mol NaCl if dissolved completely
formes a 2 osmolar solution and CaCl2 formes a 3 osmolar solution and so on. At physiological
conditions milliosmolar concentrations units are most appropriate (1mOSM= 10-3 osmoles/L).
But biological membranes are not impermaeble to all solutes so solutes can exert effcive osmotic
forces btw body compartments.
Except plasma proteins (all solutes can cross capillaries except proteins, ↑protein
concentration in plasma) so the exert an important net osmotic force across the capillary barrier.
↑plasma protein=↑water moves to plasma from interstitial space.
Membrane pumps effectively keep Na+ from entering cells= ↑EC *Na++ so water moves out
of cells into EC space. The osmotic force generated by a decrease in EC [Na+] causes EC water to go
The Donnan equilibrium
Proteins are large, osmotically active, negatively charged ions. They cannot move btw compartments
so the distribution of other ions is influenced in an attempt to maintain electoneutrality and osmotic
equilibrium on both sides of the membrane.
Diffusable cation concentration is higher in the compartment with non-diffusable anionic
proteins and diffusable anion concentration is lower.
↑total osmotic forces exerted by diffusable ions in the proteins free compartment ; there
are more diffusable ion particles in the protein-containing compartment.
The end result of the Gibbs-Donnan effect is that more water moves into the protein
containing compartment than would be predicted on the basis of the protein concentrations.
Measurement of body fluid compartments
Based on the definition of concentration in a well mixed compartment:
Concentration = Amount injected / Volume distribution
Needed to correct for any substance excreted during the time it takes for the injected substance to
distribute itself in the compartment. Equation for volume distribution:
Vd = (Amount injected-Amount excreted) / Concentration after equilibrium
The measure the volume of a compatment one must have a substance that distributes itself only in
the compartment of interest. Volumes for compartments where no such substance exists can be
determined by substraction.
Total body water: Deuterated water (D2O), titrated water(THO) and antipyrine are used.
EC-fluid volume: Labeled inulin, succrose, mannitol and sulfate.
Plasma volume: Radiolabeled albumin or Evans blue dye (binds to albumin)
IC-fluid volume: By substraction [ICF=TBW-ECFV]
Interstitial fluid volume: By substraction [ISFV=ECFV-PV]
Osmolarity is the same in all compartments, calculate:
Initial total body solute: (Plasma osmolarity) x (TBW)
Initial EC solute: (plasma osmolarity) x (ECV)
New total body solute: previous Amt. + Added Amt.
New TBW: Old TBW + Added body water
New total body osmolarity: New total body solute / New TBW
New EC solute: Old EC solute + Added EC solute
New ECV: New EC solute / New Total body osmolarity
New ICV: New TBW – New ECV
If desired, estimate New [Na+]p as: New body osmolarity / 2
Calculations! Initial conditions: ICF= 25L, ECF=17L, [Na+]p=140mEq/L
o Ingestion of 420 mEq NaCl.
ICF=23,3 L, ECF= 18,7L, [Na+]p= 150mEq/L
o Inhibiting and absorbing 1,5 L H20
ICF=25,9L, ECF=17,6L ,[Na+]p=135mEq/L
o Infusing 1,5 L isotonic saline
ICF=25L , ECF=18,5 L, [Na+]p=140 mEq/L
↑*Na++ in blood = ↓IC fluid volume . Cell shrinkage with brains cells being of particular significance.
Necessary to rule out: hypoproteinemia and hypolipidemia.
Increases EC osmolarity (cell shrinkage), if water is freely accesible the hypernatremia may be
prevented. It´s often seen in coma patients or infants without access to free water. Conditions:
Increased insensible water loss
Exessive sweat loss.
Central or nephrogenic diabetes isipidus (↓ADH secretion/response)
↓*Na++ in blood = ↑IC fluid volume. Cell swelling. Necessary to rule out hyperproteinemia and
Decrease EC osmolarity (cell swelling). Conditions:
Large water ingestion.
Syndrome of inapropriate ADH secretion (SIADH). ↑↑ADH = water retention and
↑*Glucose+ in blood= Glucose act as an effective osmole and can induce hyponatremia and cell
shrinkage. Cell shrinking needs correcting, NOT the hyponatremia.
Increased ECF volume:
↑central venous pressure (bulging of jugular veins) in conjunction with edem is often a indicative if
increased ECFV. If osmolarity is normal the IC fluid is probably normal.
Decreased ECF volume:
The main danger is hypovolemia which ultimately decreases tissue perfusion. Clinical presentation:
dry mucus membranes, lack of urination, tenting of skin, slow capillary refill. The conditions tening to
cause isotonic decreases in ECFV have little direct effect on cell volume, NOTE that the fluid lost has
the same osmolarity as ECF. Volume loss stimulates thirst and ADH secretion. This results in water
retention and occationally, 2° hyponatremia. Causes:
Vomiting, diarrhea, bleeding, burns (direct loss if interstitial fluid, also protein loss so plamsa
Solutions used clinically for volume replacement
The osmotic concentration depends on the gram molecular weight of the solute and it´s
Isotonic solutions: Same osmotic concentration as plasma
Hypertonic solutions: ↑osmitic concentration than plasma. Will decrese IC volume.
Hypotonic solutions: ↓osmotic concentrations than plasma. Expands IC volume.
General categories if IV solutions:
Dextrose solutions: Glucose is rapidly meatbolised to CO2 and H20. The volume is distibuted
IC and EC.
o Hypotonic (eg. 0.2%)
o Isotonic (0.9%)
o Hypertonic (eg. 5%)
Dextrose in saline. Has also various concentrations. Gives ↑volume and ↑calories.
Plasma expanders: E.g. Dextran with long chain polysaccharide, these solutions are confined
to the vascular compartment and preferentially expand this portion of ECF.
Flattened disk like fragments that are ~ 1µm x 4 µm.
Act as participants in the vascular clotting system. They are continuously being replaced, each
platelet circulates 9-12 days before being removed by splenic phagocyets.
They transport of chemicals important to the clotting process. By releasing enzymes and other
factors, they help initiate the clotting process.
Formation of a temorary patch (platelet plug) in the wall of the damaged blood vessel.
Prevents blood loss through the walls of damaged blodd vessels, also establishes a framework for
further tissue repairs.
3 main phases:
1. Vascular phase
Lasts 30 min.
Endothelial cells at injury site undergo changes:
- Contract and expose their basement membrane
- Release chemical factors and local hormones (ADP, tissue factor and prostacyclin)
- Endithelial cell membranes become „sticky“
2. Platelet phase
Within 15 sec of the injury.
Platelets begin to attach to sticky endothelial cells, the basement membrane and exposed
collagen fibres. Platelets attach to collagen in the tissue and a protein called von Willebrand
factor that leaks into traumatized tissue from plasma.
As platelets „stick“ they become „activated“. Activated platelets release:
- ADP → 1° stimulus for platelet aggregation (positive feedback)
-Thromboxane A2 → causes platelet aggregation and local vasoconstriction
-Serotonin → Causes local vaso constriction
The aggregation of platelets eventually leads to a platelet plug: A temporary mass of
platelets that stops blood loss and forms a framework for the clot.
3. Coagulation phase
Begins 30 sec + after injury (unlike first 2 that begin almost immediatly)
A sequence of steps leading to the conversion of fibrinogen (a circulating plasma protein) to
insoluble protein fibrin.
A network of fibrin grows and covers the surface of the platelet plug. RBC´s and additional
platelets are trapped in this tangle forming a blood clot that seals the damaged vessel wall.
Requiers clotting factors:
11 different proteins, most synthesized by the liver.
Many are pro-enzymes (inactive) that activate in the in the clotting process.
The synthesis of some requiers VIT K.
- Extrinsic pathway
A certain activator factor will be produced by
the tissue, it activates the clotting factor
„tissue thormoplastin activator“.
Begins with the release of tissue factor or by
damaged endothelial cells or peripheral tissue.
The greater the dagmage the more tissue
factor released and faster clotting will occur.
Tissue factor combines with ca++ and another
procoagulant (factor VII) to form an enzyme
called tissue thromboplastin (Factor III).
- Intrinsic pathway
Exposure of platelets to collagen activating the whole system via „contact factor“.
Begins with the activation of proenzymes exposed to collagen fibres at the site of injury.
Eventually, several activated proenzymes, Ca++ and Platelet factor-3 (PF-3) interact to form a
complex called platelet prothomboplastin.
- Common pathway
Begins when thromboplastin from either intrinsic or extrinsic pathway appear in the plasma.
Thromboplastin and activated Factor X form = Prothombin activator.
Prothrombin activator catalyzes the conversion of prothrombin into thrombin (involves 2 sparate
proteolytic cleavages by serine protease).
Thrombin catalyszes the conversion of the plasma protein fibrinogen to insoluble fibrin.
Interaction among the pathways:
Damage to the blood vessel enacts both the intrinsic and extrinsic pathways about 15 sec.
Ex. Pathway is short and fast and produces a small amount of thrombin very quickly. The speed
allows for a quick clot formation.
The Ex. Products are reinforced by a larger amount of thrombin made by the somewhat slower
Once the fibrin meshwork has appeared, RBC and platelets stick to it. Platelets than contract and
the clot undergoes clot retraction :
- Pulls torn vessel egdes together, reducing residual
bleeding at stabilizing the injury.
- Reduces the size of the injuerd area, making it
easier for fibriblasts, smooth muscle ceææs and
endothelial cells to complete repairs.
As repairs proceed, the clot gradually dissolved (fibrinolysis). The process begins with the activation
of the proenzyme plasminogen by 2 enzymes:
- Thrombin: activated in common pathway
- Tissue plasminogen activator: Released by damaged tissue
- Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the production of
circulating fragments that are cleared by other proteases or by the kidney and liver.
Plasminogen is converted into plasmin which digests the fibrin strands and erodes the foundation of
Manipulating Hemostasis: Antocoagulant drugs
Heparin : Inactivates thrombin
Caumadin : Block activation of Vitamin K
Streptokinase : Converts plasminogen to plasmin
Aspirin : Inhibits platelet aggregation
Citarte : Chelate calcium
Hemophilia: several different hereditary disorders with similar signs / symptoms.
Lack of Factor VIII. Most common type (83%). X-linked.
Less common. Deficiency of Factor IX. X-linked.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells—such as
nutrients and oxygen—and transports waste products away from those same cells. Blood accounts
for 7% of the human body weight, with an average density of approximately 1060 kg/m³, very close
to pure water's density of 1000 kg/m3. The average adult has a blood volume of roughly 5 L,
composed of plasma and several kinds of cells.
1. Fomed elements: 37-54%
2. Palsma : 46-63% = 92% water
The river that cells flow in, which by itself is straw-yellow in color. Carries blood cells, nutrients,
waste, Ab, clot proteins, chemical messengers e.g. hormones, and proteins that help maintain the
The term serum refers to plasma from which the clotting proteins have been removed. Most of the
proteins remaining are albumin and immunoglobulins.
The normal pH of human arterial blood is approximately 7.40 (normal range is 7.36-7.44), a weak
alkaline solution. Blood that has a pH below 7.35 is too acidic, while blood pH above 7.45 is too
Most important proteins:
Albumin (60%): Plasma osmotic(oncotic) pressure, transport lipids, steriod hormones
Globulin (35%): Transports ions, hormones, lipids. Immune function
Fibrinogen (4%): Hemostasis, blood clotting.
Regulatory proteins (<1%): Enzymes, Hormones.
Electrolytes: Physiological range
Functions of blood
1. Blood and transportation
RBC are packed with Hb
CO2 can be carried by 3 different mechanisms
2. Blood and Regulation
Blood absobes heat from active skeletal muscle and distributes it to
other tissues, aslo carries hormones. Core temp. is the highest.
The blood absorbes and and neutralizes the acid generated by active tissue(e.g. lactic acid in muscle).
The blood acts as both a conduit and resevoir for important electolytes and it´s volume is regulated
in responce to body water levels.
3. Blood and Protection
WBC can migrate to peripheral tissue and fight infection and remove debris.
Blood delivers Antibodies.
Blood contains blodd clotting enzymes and protein.
Red Blood Cells (Erythrocytes)
Lack nucleus and mitochondria.
Cannot reproduce, average lifespan is btw 90 & 120 days.
Each has about 280 million Hb molecules.
Typical concentration is 4-6 million/cubic mm.
OR hemtocrit 42% for females and 45% for males.
Their number is the most frequently determined
Their doughnut shape allows for shape changes so they can go through narrow gaps on capillaries
AND gives a big surface for O2 entry/exit. After their lifespan of ~120 days they go to spleen, there
they loose their biconcave shape and their volume increases, thus loosing their flexilbility and so they
cant go out of splenic capillaries. Their membrane lipids also get oxidized, and they are not replaced
due to lack of nuclei. They are finally destroyed by spleic macrophages.
The O2 binding and transporting protein found in extreme abundance in RBC. Hb levels are reported
in grams of Hb per 1L of whole blood (g/L).
140-180 g/L male adult
120-160 g/L female adult
140-200 g/L in infants
Hb has 4 subunits (2α,2β polypeptide chains), each subunit has it´s own heme group and an iron
containing pigment. The center is iron (Fe2+ [Fe3+ has less oxygen binding affinity]). The iron ion in
heme can reversably bind to O2 molecule, binds in the lungs and released in the tissues.
One Hb can carry max. 4 oxygen molecules. NOT BY COVALENT BINDING.
Oxygen is physically dissolved in water and bound to Hb.
Hb can bind CO2, and does so with higher affinity than to O2 BUT it´s concentration is normally so
low in inspired air that it´s not harmful.
Formation of RBC, this usually occurs within the bone marrow. In the early fetus, erythropoiesis takes
place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to
the spleen and liver. In humans with certain diseases and in some animals, erythropoiesis also occurs
outside the bone marrow, within the spleen or liver. This is termed extramedullary erythropoiesis.
All of the cells in the blood are made in the bone marrow. This happen primarily in the flat bones
such as skull, sternum and pelvis.
All the cells differentiate from one group of „master cells“ called stem cells. The stem cells can
become any kind of blood cell depending on need. They come under influence factors in their
environment to become RBC, WBC or platelets.
The bone marrow, in microscopic view, has mature and immature white cells, the cells that produce
platelets and both mature and immature red cells.
The number of RBC produced every sec must be 2.5 millions in adults, the are the fastest producing
cells in the body. They are very sensitive to toxins and pathological anormalies, making them a good
parameter in clinical measurements.
The rate of production is regulated by:
Hypoxia, detected by kidney cells.
o Decresed O2 intake
o Slow blood flow
Histotoxic effect (cobalt)
↑O2 requirement (T4,T3)
A glycoprotein hormone released by kidney cells, it´s target is the stem cells in red bone
marrow, stimulating erythropoiesis. Secretion of Epo increses in hypoxia. A feedback loop
involving EPO helps regulate the process of erythropoiesis so that, in non-disease states, the
production of red blood cells is equal to the destruction of red blood cells and the red blood
cell number is sufficient to sustain adequate tissue oxygen levels. It is produced mainly in the
kidney but 10% in the liver.
↓iron = ↓hemoglobin synthesis= hypochromic anemia. Hemoglobin sythesis is regulated
independantly from RBC so they can diverge.
Iron comes from food, it´s bound to Gastroferrin in the intestine to keep it in soluble form.
It´s taken up by the intestinal epithelium (if the stores are not full) and stored in the liver,
predominantly. If there is need for iron it´s transported in blood by Transferrin. APO ferritin is
important for the storage of iron. It´s able to combine with iron, which will produce ferritin.
This takes place in the intestinal epithelium.
Most of the iron is in the following form:
- Hemoglobin (50%)
- Myoglobin (25%)
- Respiratory enzymes (25%)
Vitamin B12 and folic acid.
B12 is essentail for cell division of all cells BUT since RBC are fast dividing B12 deficiency first
effects RBC. It´s necessary for methylation of DNA in cell differentiation.
Absorbtion of B12 requiers the intreinsic factor which is produced by parietal cells in the
stomach. Needed since VitB12 is a very large molecule and cannot cross the membrane
alone. The intrinsic factor binds to B12 and the complex travels to the terminal ileum, where
there are receptors which initiate mediated endocytosis.
With lack of B12 the RBC will grow for a longer time (cannot divide) resulting in megaloblasts
with large Hb content (pernicious anemia).
Lack og vitamin B12 causes problems with the nervous system, since the myelin sheath is
built up of this vitamin. Resulting in problems with defication, urination, paralysis, muscle
The usual reason for pernicious anemia is lack of Intrinsic factor (something wrong with
gastric mucosa). Treatment is intramuscular injection of Vitamin B12, bypassing the
1st sign :↑↑ Reticulocytes within 48 hrs.
2nd sign : ↑ RBC within weeks.
Application of Folic acid may also treat the anemia but NOT the nervos symptoms.
Complete blood count
Determination of the number of RBC and WBC per ml of blood.
% of whole blood occupied by packed by cells, but RBC are 99% of all cells thus other cells are
Male: 46% (40-54)
Female: 42% (37-47)
Higher % in males due to androgens (e.g. testosterone) taht
stimulate RBC synthesis. Estrogens do NOT.
Low Hct values may indicate anemias whereas high values may
% value for Hb divided by % of RBC, physiological conditions = 1
A number without a unit, determines the reason for anemia.
The ratio btw relative Hb and RBC count, when compared to normal value.
Reduced number of RBC due to decreased erythropoesis (iron or B12 deficiency), increased
erythrolysis (heamolysis or hepatosplenomegalia) or bleeding (acute/chronic, menstruation or birth)
Hyperchromic megaloblastic anemia (pernicious anemia)
Origin: Vit B12 (IF) or Folic acid (intake) deficiency.
1. ↓RBC number → stimulated erythropoiesis→no RBC→LEFT SHIFT (towards immature
cells-reticulocytes)in peripheric blood→megaloblast in peropheric blood.
2. ↑Hb per RBC, hyperchromia
3. Hipacidity/ anacidity with stomcah cell atrophy
Symptoms: Neurological problems, sore tongue, weight loss, pale skin, often with lemon tint,
Therapy: Vit B12 (i.m.), Folic acid (p.o.), Iron (p.o.)
Iron deficiencey anemia, the most common form. Aprox. 20% of women, 50% of pregnant
women and 3% of men are iron defiecient.
Origin: Lack of iron due to bleeding (acute or chronic) or increased requirement for iron
(pregnant or lactating women, adolescents in rapid growth)
1. ↓Hct & Hb
2. Small RBC
3. ↓serum *ferritin+ and *iron+
4. ↑Iron binding capacity (TIBC) in blood
5. Blood in stool
Therapy: Iron (p.o.). This anemia is more problematic since it´s hard to keep iron in solble
form. It´s possible to increase serum levels but not normalyse.
Blood loss (RBC loss), can be acute or chronic.
Sickle cell anemia
A single mutation in the gene for the β chain of globin resulting in abnormal hemoglobin. Β-
chains link together and become stiff rods under low O2 conditions. This pathological form
makes it impssible for RBC to pass through capillary walls or can block them. RBC become
sickle shaped and are more resistant to malaria. High frequency of gene is due ti positive
selection in centrain places of the world.
Hb chain is normal but decreased. Often seen in people of Mediterranean origin. One of the
globin genes is abcent or faulty.
↑Hemolysis = Jaundice
↑number of RBC, elevated Hct with normal blood volume. High blood viscocity, more work for the
heart. Blood may become 2-3 times more viscous and thus hard for heart to maintain CO.
Treatment is cytostatic therapy- inhibiting RBC production in red bone marrow.
A blood type is a classification of blood based on the presence or absence of inherited antigenic
substances on the surface of RBCs. These antigens may be proteins, carbohydrates, glycoproteins, or
glycolipids, depending on the blood group system, and some of these antigens are also present on
the surface of other types of cells of various tissues
The ABO system is the most important blood group system in human blood transfusion. The
associated anti-A antibodies and anti-B antibodies are usually "Immunoglobulin M". ABO IgM
antibodies are produced in the first years of life by sensitization to environmental substances such as
food, bacteria and viruses.
A AA or AO
B BB or BO
The Rhesus system is the second most significant blood group system in human blood transfusion.
The most significant Rhesus antigen is the RhD antigen because it is the most immunogenic of the
five main rhesus antigens.
A type of hemolytic anemia.
It is an alloimmune condition that develops in a fetus, when the IgG antibodies that have been
produced by the mother and have passed through the placenta include ones which attack the red
blood cells in the fetal circulation. The red cells are broken down and the fetus can develop
reticulocytosis and anaemia.
The mother sensitizes againts the 1st childs Rh antigen (being that it´s oposite to hers) after labor, or
after the placenta has broken, mixing the blood types. The problem starts at the 2nd pregnancy
when the mothers anti-Rh antibodies will cross the placenta (small molecules) and attack the fetal
RBCs. Resluts in amenia and hypoxia of the fetus. With each pregnancy the reaction is stronger
leaving a the child in danger for brain damage and death if blood transfusion is not performed.
White blood cells (leukocytes)
Cells of the immune system defending the body against both infectious disease and foreign materials
(toxins and pathogens). All WBC types are produced and derived from a multipotent cell in the bone
marrow known as a hematopoietic stem cell. Leukocytes are found throughout the body, including
the blood and lymphatic system.Different disorders can cause characteristic changes in circulating
population of WBC. Leukopenia=↓WBC.
A typical µL of blood contains 6000-9000 WBC, just a fraction of the total ans much less than
circulating RBC. Most of the WBCs at a given moment are in the CT or organs of the lyphatic tissue.
Types of WBC are clssified on
the appearance of granules in
50-70% of circulating WBC. Cytoplasm has pale neutral colored granules that contain
bactericidal compounds. They are polymorphonuclear. 12µm in diameter. First to arrive at
injury site, their activity and death in large numbers forms pus. Attack and digest bacteria
that have been surface marked for destruction. Survive in blood stream for ~ 10 hrs.
2-4% of circulating WBC. Reddish granules and a bilobular nucleus. Move into tissue after
several hours and survive from minutes to days. Phagocytose Ab-coated bacteria, protozoa
and cell debris. By exocytosis of toxic compunds onto target surface. Predominant in
parasitic infectiona and allergic reaction, then they increase in number.
Less than 1%. Small, only 8µm in diameter. Granules appear dark blue. Migrate to injury site
and discharge the content of the granules:
Histamine a vasodilator. ↑permeability of capillaries.
Heparin an anticoagulant.
This incraeses inflammation and attrackts other WBCs.
20-30% of circulating WBC. Large spherical basophilic nucleus and little cytoplasm.
Continuously migrate from the blood stream through peipheral tissue and back into the
blood stream, they are B, T and NK cells.
2-8% of circulating WBC. Almost twice the size of RBC. Large kidney shaped nucleus.
Individual monocytes use the circulation as a highway, they stay there for ~24hrs before
entering the tissue. In tissue they become: Macrophages.
Never Let Monkey Eat Banana
60 + 30 +6 +3 +3
A RBC lives btw 90-120 days. It dies in the spleen, due to rupture of rigid cell membrane, which
doesnt regenerate due to lack of cytoplasmic organelles. After hemolysis the Hb will be excreted by
The catabolism of heme yields bile pigments (from hemolysis, from RBC prcurosr in red bone marrow
and heme proteins of liver and other tissues). There is no evidence for the direct synthesis of biliruv-
bin from heme precursors.
Bilirubin is a pigmented organic anion waste product closely related to porphyrins and other
tetrapyrroles, it´s insoluble in water.
Hemoglobin→ verdoglobin→ biliverdine→ bilirubin→ urobilinogen→ urobiline→ stercobilinugen→
250-350 mg bilirubin forms daily. 70-80% is derived from the breakdown of RBCs. 20-30% comes
from heme proteins primarily from bone marrow.
The heme mioety is degreded to iron and biliverdin by heme oxygenase. Bilirubin reductase converts
biliverdin to bilirubin this occurs primarily in cells of the reticuloendothelial (mononuclear phagocyte)
Because of internal hydrogen bonding, bilirubin is not water soluble. Unconjugated (indirect)
bilirubin is transported in plasma via Albumins and CANNOT pass through glomerular membrane-
does NOT appear in urine due to it´s large size. The binding may get weaker in certain conditions.
A + B = AB AB: indirect bilirubin
B: direct bilirubin
The indirect bilirubin travels to the liver where hepatocytes will take up the bilirubin. The uptake is
via active transport and is rapid, but does´nt include uptake of serum albumin.
Free bilirubin concentrated in the liver is conjugated with Glucoronic Acid to form Bilirubin
Diglucoronide, or conjugated bilirubin. Catalysed by Glucoronyl transferase. Yields a reletively small
Conjugated bilirubin is secreted into the bile canaliculus with other
bile constituents. It reaches the GI-track where it is deconjugated and
reduced to Strereobilinogens (gives color of stool) and UBG by
bacteria. A substantial amount are absorbed back by the portal vein
and reabsorbed by Na+ couples 2° active transport to the liver where
it is turned back to bilirubin and excreted back to GI-tract, this is the
ENTEROHEPATIC CIRCULATION OF BILE.
Or it can reach the kidney via the systemic circulation (from the
lowest part of the GI tract, past the portal vein), where it will be
filtered and disappears with urine (and gives it´s color). The kidneys can excretes bilirubin
diglucoronide but NOT unconjugated bilirubin.
2 forms of hemoglobin:
Unconjugated (indirect) bilirubin Conjugated (direct) bilirubin
Albumin bound Conjugated to UDP, not albumin bound
Lipid soluble Water soluble
Cannot filtrate through glomeruli Filtrates through glomeruli
Cannot give positive reaction in diazol probe Gives a positive reaction in diazol probe
There are 3 forms of Jaundice:
Generally is a yellowish discoloration of the skin, sclerae (whites of the eyes) and mucous
membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This
hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids.
Treatment is UV-light which break down the double bonds of bilirubin or blood transfusion e.g. in
fetal jaundice, where fetal bilirubin (2α2γ) is replaced by adult bilirubin (2α2β). Fetal hemoglobin has
less, 2,3 bisPglycerate.
Normal serum bilirubin :10-20 µmol/L
1. Pre-Hepatic (hemolytic)
To many RBC are broken down, increased bilirubin. Each bilirubin needs to be bound to
albumin in plasma: ↑indirect bilirubin in plasma (CANNOT ENTER URINE). There will be
increased uptake by hepatocytes and thus increased production of conjugated bilirubin and
UBG. Darker stools and urine. E.g. neonatal jaundice.
2. Hepatic (heaptocellular)
There are 2 populations of hepatocytes: healthy and those affacted by a disease. The healthy
cells do their job- so UBG is in the urine and strereobilinogen in the feces. BUT the sick
hepatocytes will release their conjugated bilirubin into the blood stream, via weak liver
sinusoids. The conjugated bilirubin will appear in both plasma and urine. A small amount of
UBG may be in urine. Is due to hepatitis, virus or alchoholism.
3. Post- Hepatic (obstructive)
Obstruction on the bile duct (common and/or above the cystic) and conjugated bilirubin
cannot enter GI-tract. NO UBG is produced resulting in light colored urine and feces. Even
bile itself cannot enter GI, and it´s very importnant to absorbtion and digeation of lipids,
resulting in high amount of fat in feces. The patient may develp hemorrhage since VitK is not
Conjugated bilirubin and bile are continuously produced and pressure will increase. It may
rupture the bile duct membrane releasing conjugated bilirubin into blood stream (NEVER
happens normally). It will be excreted via urine, making urine very dark.
Aorta: Has the highest pressure, and a fluctuation pressure due to systole and diastole.
Arterioles: Provide the largest proportion to the TPR, there is huge resistance. Fluctuation diaspears
and pulastile pressure exists.
Capillaries: Further decresed pressure
Big veins: The pressure decreases even further.
The pressure must continuously decrease from aorta to big veins, this is the driving force of
The velocity profile:
The flow rate depends on the total cross section size of the vessels.
↑ total cross section = ↓ velocity
Capillaries [smallest velocity] > Veins > Aorta [biggest velocity]
At the end of the big veins the actual cross section is still larger than the aorta since there are 2 large
veins and only 1 aorta. The least velocity of flow is the the capillaries where exchange takes place.
This gives time for perfusion.
The total resistance of vessels in a series is the sum af the individual ones: R=R1+R2+R3...
In the vascular system the total resistance is greater than any of the individual ones. This is valid for
a series: Aorta→Arteries→Capillaries→Veins
BUT if the resistor is connected paralell, to calculate the total resistance: 1/R=1/R1+1/R2+1/R3... This
makes sure that the total resistance is always smaller than individual ones and blood vessels of the
sam type are connected paralell.
Layers inside the blood vessel with different velocities,
but same direction. The closer to the wall the slower,
with the highest velocity in the middle. NO SOUND.
Flow in different directions, much less effective and
Reynolds number, Rn. Gives probability of getting turbulent flow. ↑Rn = ↑prob. of turbulent flow.
Directly proportional to the velocity
Directly proportional to the diameter
Directly proportional to the density of the fluid
Invertly proportional to the viscosity of the fluid
The pressure difference btw the proximal and distal end in a vessel is the driving force of blood flow.
The pressure differecne equals the resistance of the tube times intesity of flow.
The mean arterial pressure is a term used in medicine to describe a notional average blood pressure
in an individual. It is defined as the average arterial pressure during a single cardiac cycle. Its not
equal to the avergate of systolic and diastolic because the arterial pressure remains nearer to the
diatolic pressure during most of the cardiac cycle.
The pressure in the aorta is continuously changing btw 2 extremes btw systole and diastole, thats
why an average point is needed.
1/3(SP-DP) is the pulse pressure; the change in blood pressure seen during the contraction of the
Total peripheral resistance is the sum of the resistance of all peripheral vasculature in the systemic
circulation. This should not be confused with Pulmonary Vascular Resistance, which is the resistance
in the pulmonary vasculature.
Directly proportional to length of tube :L
Directly proportional to viscocity: n
Directly proportional to a constant : 8/pi
Inversly proportional to the 4th power of the radius, The radius is the only parameter that
can be regulated. The most important vessel type in TPR are the arterioles, provide 60% of
Thus in vasoconstriction ↓radius and ↑resistance & ↑MAP, because TPRxCO=MAP
Law of LaPlace
T=rxPt Tension of wall equals to radius times transmural pressure
The transmural pressure difference btw intravascular pressure and extravascular pressure. This
applies to capillaries; despite that capillaries have relatively large pressue and very this wall they do
not burst, the transmural pressure is high but radius is SO small- so effective tension will be low
enough for the single cell layer to withstand the tension.
Big arteries with elastic distensable walls. Volume can easily be increased.
Pressure of the aorta as a function of the volume decrease:
↑Volume =↑Pressure in the aorta. The compliance decreses with age and it gradually become more
difficult to distend the aorta and it results in greater pressure increase with volume increase.
During ejection of blood, only 1/3 will drain towards the peripheral blood, 2/3 will remain in the
aorta. The pressure increaes in ejection but at the end of systole the aortic wall will recoil. The recoil
gives a continuous perfusion of blood. The remaining blood in aorta after ejection will then flow
towards peripheral blood. Befor complete emptying of the aorta the next ejection will occur.
Determination of pulse pressure:
pulse pressure=systolic pressure – diastolic pressure
Velocity of ejection
Inversly proportional to compliance
The pressure increses due to ejection, reaches max
value at the peak of the ejection and then decreases.
„incisura“ a sudden increase in pressure again, due to
closure of aortic valves, as they close blood wants to
reenter the heart, but cant. In peripheral blood vessels the incisura is not so sharp.May appear as a
The aortic pulse wave is shorter than in peropheal vessels BUT the velocity of the pressure wave has
nothing to do with velocity of blood itself. The ONLY thing that determines the velocity of the
pressure wave is the COMPLIANCE OF THE AORTA.
Parameters of the pulse pressure wave:
Amplitude (difference btw sys and dia pressures, high/low)
Rate of rise (how fast is the upstroke, fast/slow)
Equality (all pressure waves are identical)
3 important diseases that change the pressure wave:
Systolic murrmurr due to pathological ventricular emptying, btw S1 and S2. Amplitude and
rate of rise are affected: Slower and Lower waves.
Diastolic murrmurr btw S2 and S1, due to pathological ventricular filling. Bigger preload due
to 2 sources of blood; left atria and aorta. Results in larger diameter of left ventricule and
hypertrophy. Contractile force and rate of rise will increase, fast upstroke with high
amplitude. Can be so strong as to move the head of the patient.
Rigid aortic wall due to ca++ desosit. Less compliance and thus ↑ pressure. Normal diastoloic
pressure BUT higher systolic pressure. Fast and low waves.
- Systolic pressure:
↑Stroke volume= ↑ SP
↑Rate of ejection= ↑ SP
- Diastolic pressure:
↑TPR = ↑DP
↓compliance= ↑DP (not as muc as SP)
- Pulse pressure:
↑Stroke volume = ↑ SP = DP→ == ↑PP
↑TPR = ↑DP = SP → == ↑PP
↓Compliance = ↑DP = ↑↑ SP == ↑PP
Arterioles that accout for 60% of TPR. An arteriole is a small diameter blood vessel that extends and
branches out from an artery and leads to capillaries. 
Arterioles have thin, slim and skinny muscular walls (usually only one to two layers of smooth
Capillaries are the smallest of a body's blood vessels, measuring 5-10 μm in diameter, which connect
arterioles and venules. They exchange matabolites btw plasma and interstitial space, via:
Passive diffusion (O2 and CO2)
Fused vesicle channel
Clefts (btw adjacent endothelial cells, not in all tissue)
Bulk flow (filtration of water through the endothelial cells)
1. Hydrostatic pressure if the capillary Pc
Expels water out FROM plasma (filtration)
2. Hydrostatic pressure of the interstitial space Pi
Backwark movement of water TO plasma (reabsorbtion)
3. Oncontic pressure of the plasma πc
Most important are the albumins. Support movement of water TO plasma.(reabsorbtion)
4. Oncotic pressure of the interstitial space πi
Molecules FROM plasma (filtration)
The Starling equation is an equation that illustrates
the role of hydrostatic and oncotic forces (the so-
called Starling forces) in the movement of fluid across
If the effective pressure is zero there will be no filtration or absorbtion.
Peff= positive= Net Filtration
Peff=0= NO net fluid movement
The net oncotic pressure is more or less the
same along the whole length. The net
hydrostatic pressure of interstitial space
decreases from arterial to venous end. The
difference btw the 2 will decrease along the
length of the capillary.
ΔP is greater than Δπ = Net filtration
ΔP is lower than Δπ= Net absorbtion
Arterial end filttrates and venous end absorbes, the remains will go to lymph ~10%.
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. ↑water
in interstitial fluid of the connective tissue. Is because filtration exceeds absorbtion OR the lymphatic
passage is obscured.
1. ↑hydrostatic pressure at arterial end = ↑filtration.
Most usual reason is hypertension.
2. ↑hydrostatic pressur at venous end = ↓absorbtion because of obstructed veins. May lead to
ventricular failure and either systemic (RV) or pulmonary (LV) edema.
3. ↓oncontic pressure of plasma=↑filtration. Plasma albumins are responsable for 80% of total
oncotic pressure, may be caused by hypoproteinemia (liver disease, kidney disease or
4. Lymphatic obstruction, fluid in interstitial space cannot leave. Wucheria bancrofti and
Elefantiasis OR amputation.
5. ↑Capillary permeability=↑filtration. E.g. due to bee sting, with histamin secretion which
causes vasodilation and ↑ permeability.
NOTE that normally there is filtration at arterial end and absorbtion at venous end EXCEPT:
There is only absorbtion in the lungs (very low hydrostatic pressure)
There is only filtration in the kidney (very large hydrostatic pressure)
Veins carry low-oxygen blood from the tissues back to the heart; the exceptions being the pulmonary
and umbilical veins which both carry oxygenated blood. They store up to 60% of the blood. They are
in the low pressure area of the circulatory system.
Factors that effect the venous blood pressure:
Amount of blood in circulatory system
SNS activity (can cause venoconstriction = ↑VR=↑CO)
Compliance. Usually very high.
Respiration. Inspiration=↑VR due to high pressure gradient
Expiration=↓VR with decreasing pressure gradient
Muscle pump of the veins & peripheral valves should always be mentioned together. They have no
function on their own.
Deep vein thrombosis is the formation of a blood clot ("thrombus") in a deep vein. The problem
occurs when the clot becomes detached from the venous wall. It travels towards heart and then
lungs, where it can obstruct blood flow due to small diameter blood vessels. A small enbolism may be
unnoticed BUT large „riding“ embolism blocks 2 large vessels abd may cause death.
Pressure waves in big arteries- 3 types
1st grade changes in pressure: have the greates frequency and greatest amplitude. ↑ in systole,↓in
2nd grade changes in pressure: Due to respiration, Inspiration = ↑VR=↑EDV=↑SV. So in inspiration
the systole is a bit higher and lower in expiration, note that respiration is MUCH less frequent than
3rd grade changes in pressure: Traube-Hering waves, Smooth muscle cells in arteriole walls show
slow waves due to a continuous depolarization of the smooth muscle cells. As they contract the
radius of the vessel decreases and TPR will increase slightly. Note that it is a very slow process and
causes low changes in amplitude.
The continuous and passive partial contraction of the muscles. 3 types:
1. Resting myogenic tone
Intrinsic ability of smooth muscle of blood vessels to maintain continuous contracting. Doen
NOT depend on innervation or hormones.
2. Resting vasocontriction tone
The synpathetic innervation of the great majority of our blood vessels. There will be a
continuous discharge rate. It results in continuous stimulation of the appropriate smooth
muscle cells, maintaining a contraction on top of the reting myogenic tone.
3. Reflex vasocontriction
In a pressor response, ↑SNS activity, results in more contraction of smooth muscles.
Regulation of circulation
The neural regulation:
Allow for voluntary movements- skeletal muscles. Only one
motor neuron needed from spine to target muscle.
Receptor: N-cholinergic Receptor
A division of the Autonomic nervous sysytem. 2 neurons are
needed, one long preganglionic- the ganglion lies on or in the target organ- and one shorter
postganglionic neuron. Its target cells are Smooth muscle, Cardiac muscle and glands.
1st synapse: ACH + N-cholinergic Receptor
2nd synapse: ACH + M-cholinergic Receptor
3. Sympathetic: 3 types
2 neurons; one short pregenglionic –
ganglion far from innervated organ – long
postganglionic neuron. Effector organs are
Smooth muscle, Cardiac muscle and Glands.
1st synapse: ACH + N-cholinergic receptor
2nd synapse: NOR + adrenergic receptor
Sympathetic cholinergic fibres, innervate sweat glands, arrector pili m, some arterioles of
skeletal muscle (vasodilation). Like parasympathtic EXCEPT that the ganglia are
postitioned far from target organ AND the are activated in sympathetic activation.
1st synapse: ACH + N-colinergic Receptor
2nd synapse: ACH + M- cholinergic Receptor
c. A single preganglionic neuron.
The synapse: ACH + N-colinergic Receptor
The target cells a chromaffine cells of adrenal medulla which are modified sympathetic
neurons producing hormones (NOR-EPI & EPI).
The adrenergic receptors are a class of G protein-coupled receptors that are targets of the
catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines
adrenaline and noradrenaline, and are activated by these.
Coupled to Gs protein → ↑cAMP → positive tropic effects (↑HR)
Agonists: ISOPROTERENOL & ADRENALINE (physiological)
Antagonist: PROPRANOLOL & PINDOLOL
Coupled to Gs protein →↑cAMP→
- Smooth muscle in airwaves, skeleatl muscle arterioles, coronaries and bladder = RELAX!
Bronchodilation and Vasodilation.
Agonist: ISOPROTERENOL, ADRENALINE AND SALBUTAMOL (asthma medication)
Antagonist: POPRANOLOL (non-selective β-blocker, ↓HR and bronchoconstiction)
Coupled to Gp protein→↑ IP3 → ↑*Ca+++i
- Smooth muscle in most arterioles
- Smooth muscle CONTRACTION.
- Systemic vasoconstriction → ↑TPR → ↑MAP
- Mediate resting contrictor tone
Agonists: NOREPI AND PHENYLEPHRINE (in nosespray, vasocontricts)
Antagonists: PHENOXYBENZAMINE AND PRAZOSIN (α1 blocker=↓MAP)
Muscarinic acetylcholine receptors belong to a class of metabotropic receptors which use G proteins
as their signalling mechanism.
Agonist: ACH and muscarine
There are 5 subtypes
M1: Brain – IG3 pathway
M2: Heart - ↓cAMP - ↓HR to normal sinus rythm after SNS activation
M3: Brain and smooth muscle – IG3 pathway
Ionotropic (i.e. ligand-gated) receptors, nAChRs are directly linked to an ion channel and do not make
use of a second messenger like metabotropic receptors do. Nicotinic acetylcholine receptors are
present in many tissues in the body, and are the best-studied of the ionotropic receptors. The
neuronal receptors are found in the central nervous system and the peripheral nervous system. The
neuromuscular receptors are found in the neuromuscular junctions of somatic (voluntary) muscles;
stimulation of these receptors causes muscular contraction.
There are 2 major kinds of control mechanism:
Local control mechanism (Autoregulation)
Only is a limited number of arterioles in a certain body area affected, so there is no significant
cahnge in TPR, and MAP is NOT be greatly affected.
There will be an effect of perfusion of a particular organ, the local contol mechanism will control local
prefusion without cahngin MAP. This is via local HUMORAL vasodilators and vasocontictors by
modifying the basal myogenic tone *Vasodilation = ↓Tone = ↑Flow and vice versa+. These are
„mostly“ locally acting factors.
2 important mechanisms:
1. Bayliss effect
When pressure is increased in blood vessels the flow will not increase BUT the vessel wall will
be streched, and thus the smooth mucsle cells. When smooth muscle cells are streched
strech-activated non-specific cation channels open. ↑Ca++ ions enter the smooth muscle
cells → Contraction (vasoconstriction).
The ratio of R and P will change but Q will remain unchanged, thus flow will remain the same.
Bayliss works only in the „autoregulatory range“ ~ btw 60-140 (not concrete)
The mechanism: ↑MAP = ↑Stretch of wall= ↑Stretch activated channels = Depolarization
and ↑*Ca+++i = Vasoconstriction =↑R BUT Q WILL REMAIN THE SAME!!!
2. Local meatbolites.
Explaines the increased perfusion in tissue with increses activity.
Vasodilator metabolites (produced in all working Hypoxya*
tissue= use dependent production) Hypercapnia*
*different in pulm.
Vasodilator vasoactive substances EPI (β2-r)
Histamine * (with intact endithelium)
Nitric Oxide (NO)
ACH (with intact endothelium)
Serotonin* (with intact endothelium)
*different in pulm.
Vasoconstrictor vasoactive substances NOREPI (α1-r)
Histamine (without endothelium)
ACH (without endothelium)
Serotonin (without endothlium)
Systemic control mechanism
A large number of arterioles are affected. So there will be a large change in TPR and thus also MAP.
The aim is to adjust MAP through great change in TPR.
2 important mechanism:
1. Nervous control / SNS!
Most blood vessels are innervated by SNS, they maintain the resting vasocontrictor tone.
Vasocontriction in through increses activity of the SNS. Vasodilation is possible through
decrease in SN-activity, passively.
NOTE! The parasympathtic nervous system has very little to do with blood vessels, and is
NOT an important regulator of TPR. Except at local control where only a part of an organ is
affected: Active vasodilator mechanism. Active because the nerve fibres are activated to
cause vasodilation, this is NOT in systemic control of TPR.
The locally acting active vasodilator meachanisms are:
a. Parasympathetic vasodilator fibres.
The ONLY situation where PNS has anything to do with blood vessels. Result in
vasodilation at (TPR is not affected) :
b. Sympathetic cholinergic fibres
Vasodilation of certain skeletal muscle arterioles, a concious activation, preparing
muscler for increased activity.
c. Axon relex
Pain receptors in skin send information to CNS. At the same time it has collateral
branches to local blood vessels of skin. Substance P is secreted,causing the release of
nitric oxide from the endothelium.
2. Humoral control
„Mostly“ systemically acting factors: Epinephrine and Norepinephrine. They are synthesized
in adrenal medulla (modified sympathetic ganglion).
Almost 100% of circulating Epinephrine (75-85% of total released) is produced in
Adrenal medulla due to the presence on PNMT (Phenylethanolamine N-
methyltransferase) that converts Norepi to Epi.
Almost 100% of Norepinephrine is produced in sympathetic postganglionic fibres
that release NOREPI onto synapses, that what is not reabsorbed or destroyed
diffuses into circulation. Produced to a smaller extent in Adrenal medulla.
WHEN THEY ACT AS HUMORAL AGENTS!!!!
1. Application of low concentration of epinephrine.
The β receptor is most sensitive to Epinephrine.
- HEART (β1): positive chrontropic (↑HR) and inotropic effect (↑contractile force) which
results in ↑SV, more blood ejected. With more blood going to aorta the systolic pressure
- ARTERIES (β2): most importantly coronary arteries. There will be vasodilation, relaxation of
smooth muscle; ↓TPR resulting in decresed dialstolic pressure , easier for blood to leave the
aorta (less resistance). More blood will go to tissues.
Pulse pressure (difference btw SP and DP) will increase BUT MAP will remain as it was.
This is a kick start for circulation, with more blood going to circulation and more blood giong
2. Application of low concentration of norepinephrine.
The α receptor is most sensitive to norepinephrine, most importantly α1.
- ARTERIES & VEINS (α1):
Vasoconstriction: ↑TPR →↑DP, because it´s more difficult for blood to leave the aorta due
to high resistance. More blood will be in aorta and less blodd will go to tissues.
Vasocontriction & Venoconstriction: Systolic pressure will increse due to Frans-Starling law,
in ↑TPR the SV ↓ but is restored by frank-starling law. →↑CO → ↑SP.
BUT Diastolic pressure increases more than systolic pressure = pulse pressure will drop with
less start to circulation.
Since ↑TPR and ↑CO = ↑↑↑ MAP.
BUT this rise in MAP will initiate the depressor reflex evoking the classcail depressor
responce = ↓↓ HR = ↓↓ CO = ↓↓ Blood to circulation
So the net effect of norepinephrine doen NOT stimulate heart rate.
Reflex control of the cardiovascular system; central regulation of MAP.
Two important centers of regulation located in the Medulla oblongata.
The pressor center in the ventro-rostro-lateral nuclei
The depressor center in the postero-caudo-lateral nuclei and functionally
including the CIA (Cardiac inhibitory area).
The pressor center neurons have spontaneous activity and can produce spontaneous action
portentials. Their activity is adjusted by inputs from:
Chemoreceptors (CCR & PCR)
Low-pressure baroreceptors of the right atrium and vena cavas
Pain receptors of the skin
Receptors of the cerebral vessels
INPUT Location Activation Signal transmission Significance
Central Medulla ↑pCO2/↓pH of Intrinsic activity
chemoreceptor oblongata –in blood and CSF. of pressor center
pressor center. (not by ↓pO2!!)
Peripheral Aortic & carotid ↓pO2 of blood, CN IX & X
chemoreceptors bodies and severe to pressor center
Low pressure Wall of right Stretch; ↑VR CN X (sensory part)
baroreceptors atrium and vena
Pain receptors of Nociceptors in Pain Somatosenory
skin various layers of nerves
Receptors of Baroreceptors in Stretch; change in Viscerosensory
brain vessels the walls of brain ICP. nerves
They will stimulate the activity of the pressor center. The axons of the pressor center go downwards
and stimulate preganglionic neurons of the sympathetic nervous system. The postganglionic neurons
innervate the most important organ of the cardiovascular system (heart, arterioles and veins). These
are the effector organs of the cardiovascular reflex mechanism.
Limits the pressor center, by way of inhibition. The neurons of the depressor center have NO
spontaneous activity. Its inputs are:
High pressure baroreceptors of the carotid sinus and aortic arch
Low pressure baroreceptors of the pulmonary arteries
Mechanoreceptors of the abdominal wall
INPUT Location Signal transmission Activation
High pressure Carotid sinus CN IX & X Stretch-↑MAP
baroreceptors Aortic arch Not the same as PCR Phasic nature: not
[Most important] In the arterial walls contant fireing
Activation range: btw
Low pressure Wall of pulmonary Viscerosensory nerves Stretch - ↑Pulm.
baroreceptors arteries arterial pressure
Mechanoreceptors Abdominal wall Somatosensory nerves STRONG mechanical
The nerve fibres conducting the action potential from the baroreceptors to depressor center are
BUFFER NERVES. There are 4 buffer nerves in the body: left/right vagus & left/right glossopharyngeal.
If they were to be cut there would be no spontaneous activity of depressor center, and MAP would
rise to 220mmHg.
Decending pathways travel in the spinal cord, inhibiting neurotransmission of pressor fibres, at
The Depressor center blocks the pressor center activity:
1. Within the medulla oblongata, directly at pressor center.
2. Within the SNS preganglionic neurons, in the thoracolumbar part of spine.
3. At the heart, the CIA works through the vagus (not sensory) mediating parasympathetic
activity to SA-NODE= Negative tropic effect.
The „Classic“ Pressor & Depressor responses.
Pressor response Depressor response
HEART β1-adrR. Direct: via vagus (PNS):
↑SV & ↑HR = ↑CO = ↑MAP ↓HR=↓CO=↓MAP
Indirect: through resting
vasoconstricor tone; inhibition
of pressor center
↓HR & ↓SV=↓CO=↓MAP
ARTERIES α1-adrR mostly Indirect:
Vasoconstriction=↑TPR=↑MAP Vasodilation = ↓TPR =↓MAP
BUT β2 cause vasodialtion in
arteries of working muscle and
VEINS α1-adrR Indirect:
Venoconstriction: ↓Storage of Venodilation: ↑Storgae of
blood in veins= ↑VR = blood in veins = ↓VR = ↓SV=
↑Starling = ↑SV = ↑CO= ↓CO = ↓MAP
ADRENAL MEDULLA ↑Epinephrine release ↓Epinephrine release
There is equilibrium btw the 2, since the pressor center cannot decrease MAP and depressor center
cannot increase MAP.
The pressor reflexes – there are 4
1. Chemoreceptor reflex
2. Bainbridge reflex
3. Loven reflex
4. Cushing reflex
1. Chemoreceptor reflex
Activated by hypoxia or severe hypercapnia/acidosis (e.g. in physical exercise) sensed by
receptors in carotid and aortic bodies. Increased activity of pressor center (through CN IX, X).
↑SNS activity resulting in the „classical“ pressor response.
Senses the chemical composition of the blood and CSF, sensitive to hypercapnia and acidosis.
Sensation and response is within the medulla oblongata. Results in incresed SNS avtivity and
the „classical“ pressor response.
Both PCR and CCR increase MAP. They have a working range, mostly under 70-80 mmHg MAP. The
most important is to activate respiration during physical exercise. Special features are the double
target of ↑pCO2 and single target of ↓pO2.
2. Bainbridge reflex
The reflex involves a innervated heart, with intact nerve fibres. The reflex activated is the
VASO-VAGAL REFLEX, which means that both effernt and afferent pathways are found in
vagus. The aim is to match the amount of blood entering the ventricle and the amount of
blood ejected = VR and CO.
The reflex is initiated ↑VR – stretch of the atrium sensed by the low pressure baroreceptors.
They start the vaso-vagal reflex:
Baroreceptors → CN X → Pressor center → inhibited CN X (at CIA ) & activated SNS at SA-
The effects are at the Heart, especially the SA-NODE and HR will increase big time resulting in
increased CO (SVxHR=CO) and increased MAP (TPRxCO=MAP).
The reflex works as a frequency buffer fluctuating around a set point:
↑VR = Bainbride reflex =↑HR = Decreased diastolic time = ↓VR = De-activated bainbridge =
↓ HR = Increased diastolic time = ↑VR......
The reflex depends on the initial HR and is NOT to be confused with Frank-Starling
Machanism which is noly for de-ineervated heart!
Bainbridge Reflex is involved in Respiratory Sinus Arrhythmia. During inhalation intrathoracic
pressure decreases. It triggers increased venous return which is registered by baroreceptors,
which via Bainbridge Reflex constantly activates sympathetic nervous system within each
inhalation of each respiratory cycle.
3. Loven reflex
Intiated by a painful stimulus to the skin, which will initiate general vasoconstriction and
increase MAP. It´s sensed by the nociceptors of the skin. There are 2 responses:
i. Pressor reflex: systemic vasoconstriction and ↑ MAP = fight or flight
ii. Local axon reflex: Local vasodilation and ↑local flow = tissue repair
4. Cushing reflex comes later.
Depressor reflexes- there are 3
1. Baroreceptor reflex
2. Pulmonary baroreceptor reflex
3. Goltz reflex
1. Baroreceptor reflex
High pressure baroreceptors in aortic arch and carotic sinus. Sense ↑MAP and stimulate the
depressor center through CN IX, X. Response:
- CIA: ↑PNS activity on SA-NODE via vagus nerve (direct)
- Inhibition of SNS fibres via inhibition of pressor center
This results in the „classical“ depressor response, resulting in ↓MAP.
- Most important reflex to regulate MAP
- The MAP buffer reflex of circulation, it provides a negative feedback loop in which an
elevated blood pressure reflexively causes blood pressure to decrease; similarly, decreased
blood pressure depresses the baroreflex, causing blood pressure to rise.
Experiment 1: Occlusion a carotid artery below carotid sinus, there will be less flow to carotid
sinus and LESS depressor reflex= ↑MAP
Experiment 2: Occlusion of both carotic arteries above the carotid sinus. There will be increased
pressure at the carotid sinus increasing the activity of the depressor center = ↓MAP
2. Pulmonary baroreceptor reflex
Baaroreceptors in pulmonary artries, low pressure 25/8 mmHg. The sense ↑MAP-PULM. It
will inhibit SNS fibres (not affecting CIA at all) causing dilation of arteries and veins , more
blood will be ratained in venous circulation: ↓MAP = ↓MAP-PULM.
- Protective factor against high MAP-PULM that causes EDEMA.
- Camplementary role to the funtcion of the high pressure baroreceptor reflex. Little brother.
3. Goltz reflex
A storng mechanichal stimuli to the abdomen is sensed by machanoreceptors in abdominal
wall, that activate splanchnic nerves. They give ascending pathways to the spinal cord and
collateral braches to the depressor center. CIA will be activated, vagus is stimulates causing
increased PNS activity on SA-NODE = ↓HR, Sinus arrest, ↓MAP.
Functions of the endothelium:
Matrix / Barrier
Mitogenic (production of growth factors for vasculature growth)
Regulation of vascular tone
ANTI-coagulant in intact endothelium
o Non-Wetteble surface
o Plasminogen Activator
PRO-coagulant in damaged endothelium
o Wetteble surface
o Von Willebrand factor
o Thromboxane A2
o Factors V, IX, X
o Plasminogen activator inhibitor
Regulation of vascular tone:
- Mechanoreceptors : sense blood flow, sheer stress forces, they are always present as long as
there is blood flow.
- Ligand receptors: All stimuli
They signal endothelium. Endothelium releases products that cause:
- Vasoconstriction (ACE, Thromboxane A2, Leukotriens, Endothelins)
- Vasodilation (Prostacylins, Nitric oxide!!!)
Nitric oxide (NO)
Nitric oxide or nitrogen monoxide is a chemical compound known as the 'endothelium-derived
relaxing factor', or 'EDRF'. This gas is an important signaling molecule in the body of mammals,
including humans, and is an extremely important intermediate in the chemical industry. It is also a
toxic air pollutant produced by cigarette smoke automobile engines and power plants.
NO is an important messenger molecule involved in many physiological and pathological processes
within the mammalian body both beneficial and detrimental. Appropriate levels of NO production
are important in protecting an organ such as the liver from ischemic damage. However sustained
levels of NO production result in direct tissue toxicity and contribute to the vascular collapse
associated with septic shock.
Ach binds to M-achR, Serotonin to 5-HT or
mechanoreceptors react to sheer stress, ON ENDOTHELIAL
CELLS. NO is biosynthesised endogenously from L-arginine
and oxygen by various nitric oxide synthase (NOS) enzymes
and by reduction of inorganic nitrate. The endothelium
(inner lining) of blood vessels use nitric oxide to signal the
surrounding smooth muscle to relax by ↑cGMP, thus
resulting in vasodilation and increasing blood flow. Nitric
oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes.
These attributes make nitric oxide ideal for a transient signal molecule between adjacent cells and
within cells. Bayliss effect works against it; to keep flow constant.
Viagra: inhibits the enzyme that degrades the cGMP, that way sustaining vasodilation.
Ach, Serotonin or NORepinephrine binding directly on the smooth mucle cell (with damaged
endothelium) causes vasoconstricion. Bypass endothelium lining of the vessel.
1. Pulmonary circulation
The blood pressure is much lower, 25/8.
The pulmonary arteries are short and wide (↓R *resistanse+) and the CO (Q) is the same as in the
systemic circulation. As a consequense (Q=P/R) the MAP-pulm is much lower.
AND acording to the Hagen-Pouisille law, the resistanse of a tube is directly proportional to a
constant, divided by pi. The resistance is also directly proportional to the length, viscocity and
inversly proportional of the RADIUS in the power of 4.
Amount of blood is the same, length of circulation is shorter. Radius is larger = ↓Resistance
Low hydrostatic pressure (PC-pulm) while other starling forces are the same. Net filtration pressure is
less than 0! Reabsorbtion dominates over filtarion. No water molecules leave the capillaries, no
water goes into the alveoli, this keeps the lungs are dry as possible. Prevents pulmonary edema,
where alveoli get filled up with water and no proper gas exchange is present. Lifethreatning.
a. Toxic edema due to increased capillary permeability
b. Edema due to pulmonary arterial hypertension (fibrosis) → ↑Pc-pulm
c. Edema due to pulmonary venous hypertension (LV failure, mitral stenosis) → ↑Pc-pulm
→↑NFP →Filtration dominates over resorbtion.
Direct effect of SNS is negligible! BUT theter is indirect systemic SNS activation
(e.g. in the pressor reflex). →↑CO→↑Pulmonary Flow.
Acidosis - VASOCONTRICTION → Ventilation perfusion matching
(cause vasodilation systemically)
Ventilation perfusion matching: guarantees that good blood will be matched with good air; normal
ventilation. Hypoventilation with vasoconstriction will occur in the case of ↓pO2 and ↑pCO2.
2. Coronary circulation
There is a very strick correlation btw the cardiac cycle and the coronary circulation.
Ohm´s law: R=u/I R: resistance, u: potential difference, I: current
This applies to a hydrodynamic situation aswell: intensity of perfusion of the coronary system equals
the driving force, which is the pressure gradients divided by the resistance of a vessel. This pressure
gradient in the coronary circulation is the pressure difference btw the aorta and the coronary system.
The flow is phasic (discontinous)
Phasic driving force (MAP fluctuates)
Compression – Decompression
Subendocardial vs. Subepicardial.
1st stage of cardiac cycle: isovolumetric contraction (aortic valve is closed),
resistance of the coronary arteries is large due to contraction of the ventricular wall – vessels are
This is just prior to ejection, lowest pressure in aorta = very low pressure gradient. Thus; with low
pressure gradient and high resistance there is low perfusion of blood through the coronary
circulation. It´s worst period.
There may be retrograde perfusion, blood flows towards aorta due to much compression, but only in
the left ventricle.
2nd stage of cardiac cycle: Isotonic contraction (valves open blood flow out). In ejection there is high
pressure in aorta, increases the driving force. Here there is still considerable compression and high
resistance (ventricular myocytes are contracted) BUT the driving force has increased.
3rd stage: Diastole. Relaxation of the ventricular wall. Blood vessels are no longer compressed,
decreasing resistance greatly AND high pressure in aorta (especially in the beginning of diastole)
making the driving force high. High driving force + low resistance + no compression = ↑↑perfusion.
The best period for coronary perfusion. At rest diastole is 2x longer that systole. IMPORTANT!!
With ↑HR the diastole shortens, decreasing coronary perfusion and ventricular filling. Heart attack
may occur if HR goes above 220. But since CO= SVxHR, in heavy physical burden muscles require
more perfusion and thus CO is increased, which results in ↑HR. The heart performs greater work,
metabolic demand increases, greater perfusion demanded BUT diastole is shorter here. To
compensate: The caranary vessels have an extremely large resting myogenic tone(like the brain). In
this case the heart preforms greater work but there is not enough blood supply to meet the
demands. Hypoxia acts upon the resting myogenic tone causing powerful vasodilation. It makes
sure that there will be an increased perfusion in the coronary system in the shortened diastole. 4x
greater perfusion can be achieved.
The resting vasoconstriction is negligible.
There is NO continuous discharge of SNS on coronary blood vessels (SNS affects indirectly via ↑work
resulting in ↑FLOW due to local metabolites).
The coronary blood vessels will NOT participate in the depressor resonce.
The resting vasoconstriction tone is also negligible.
= in a pressor response there will not be vasoconstriction!
The smooth muscle cells of the coronary system have β2 receptors, their stimulation by SNS results
The most important adjustment of the coronary system is USE DEPENDENT HUMORAL
AUTOREGULATION by the persence/absence of local metabolites (use dependent) – due to the very
large resting myogenic tone. The most powerful vasodilators are HYPOXIA AND ADENOSINE
(byproduct of ATP). Adenosine binds to receptors in the coronary vessel walls and is later washed
away by blood. But the Bayliss effect works againt it (myogenic control).
Humoral control : Dominates in ↑MAP
Myogenic control (Bayliss): Dominates in ↓MAP
Arteriovenous oxygen difference is very large in the cardiac muscle. The cardiac muscle is very
effective in using and utilizing the oxygen. The heart is aerobic and needs oxygen.
3. Cerbral circulation
In the brain there is a very high resting myogenic tone (++++). This means that
smooth muscle cells in the walls of the blood vessels are continously contracted.
The magninitude is controlled by local metabolites :hypoxia, hypercapnia, acidosis (rather in CSF),
↑temperature, adenosine, ↑*K++. Prodiuced in the working tissue. They result in a decreased
myogenic tone → Local vasodilators. The single most powerful vasodialtor in the brain is
HYPERCAPNIA. Cause increased perfusion in the cerebral circulation.
There is no resting vasocontrictor tone (no continous SNS-no pressor effect) thus there will be no
depressor effect since there is no SNS activity to repress. The reflex vasoconstriction is also negligble
in the brain. So the humoral contol always dominates over the myogenic bayliss reciprocal effect.
The brain has a special compartment. The cranium containing blood, brain and CSF.
Vbrain+Vblood+VCSF = Constant.
The volume inside the cranium cannot be changed, there is no way to expand the skull. If the volume
of something is increasing the volume other things are decreasing. E.g. in the case of tumor healthy
brain tissue dies and disapears to make room. Also intracranial pressure will increase and perfusion
will be badly affected. Because the perfusion is determined by the transmural pressure, the pressure
difference btw the 2 sides of the vessel.
TMP = MAP – ICP
The transmural pressure is the driving force of the brain circulation. So, decreased transmural
pressure e.g. due to a brain tumor the ICP will increase; the pressure difference will be smaller. With
decreased TMP the radius of the blood vessel will decrease; contriction of the cerebral blood vessels;
↑↑ resistance! Which means impaired perfusion. Results in hypoxia and dieing neurons. The
mechanism that will try and keep the TMP constant is the Cushings reflex.
The Cushings Reflex
The aim is to maintain or restore the transmural pressure.
Baroreceptors in the walls of the brain vessels sense ↓TMP due to ↑ICP
Direct action due to extreme ↓MAP, ischemia or blood loss.
They send stimuli to the pressor center in the medulla oblongata. The pressor center sends stimuli
alnog the spinal cord to systemic arteries (not coronary or cerebral), heart and veins.
The result is a positive tropic effect, vaso and venoconstriction (↑TPR). And since MAP = COxTPR
there will be ↑↑↑MAP. This increases the pressure inside brain vessels and by increasing the
intravascular pressure you increase the extravascular pressure.
↑MAP = ↑ICP = ↑TMP
The high MAP causes hypertension. Baroreceptors in carotid sinus and aortic arch will sense it and
activate the depressor center. There are 3 possible outputs:
Inhibiting the pressor center directly BUT it cant since the pressor center is continously
Inhibition of synaptic transmission btw the pressor center and the preganglionic synpathtic
neurons BUT it cant due to the continous stimulation of the pressor center. Cannot override.
Increased vagal activity will decrease the heart rate.
This is a strange situation: ↑↑↑ MAP and ↓HR. Sign of raised ICP and brain tumor.
The ICP will eventually press the brain out through the foramen magnum, this will compress the
medulla where cardiovascular, vasomotor and respiratory centers are. This is called „coning“. The
treatment for this high ICP is diuretics to decrease blood volume.
4. Skeletal muscle
Moderate resting myogenic tone and resting vasocontrictor tone.
Humoral control: Mainly by humoral vasodilators
-Exercise →Use dependent production → vasodilation→↑FLOW
-Epinephrine→β2 receptors→ vasodilation →↑FLOW
-Sympathetic cholinergic (M-achR) → Vasodilation
-Sympathetic adrenergic (β2) →Vasodilation
-Sympathetic adrenergic (α1) →Vasoconstriction
WORK will determine the actual diameter of a skeletal muscle artery.
↑ Sympathetic cholinergic
↑Production of metabolites -------------------------> PRESSOR CENTER
Increases EPI secretion and sympathetic activity
↑Epinephrine to β2 <----------------------------------- systemically.
= Vasodilation = ↑FLOW
↑Sympathetic adrenergic to α1
-not coronary aa. and brain aa.
=Vasoconstriction = ↓FLOW
This is called redistribution.
There is an extensive capillary network and AV anatomosis. Large amounts of blood stored. It has a
role in thermoregulation; countercurrent flow.
There is NO resting myogenic tone but HIGH resting vasoconstriction; pressor & depressor reflex. The
receptor is α1 adrenergic in A & V. But in sweat glands there are M-AchR for sympathetic cholinergic
Cold: ↑SNS → Vasoconstriction→↓Q to store heat
Heat: Bradykinin mechanism: Sympathetic cholinergic nerve fibres stimulate sweat glands. They
produce sweat and Bradykinin-forming enzyme, as a result Bradykinin is formed which is one of the
strongest vasodilators. →↑G to lose heat.
First: ↑SNS vasoconsriction (redistribution of blood to workin muscle)
Then: Vasodilation due to bradykinin mechanism to lose heat.
Both vasodilation and vasoconstriction are mediated by the SNS depending on temperature and
timing of exercise.
2 arterioles, 2 capillary networks, 1 vein. There is resting myogenic tone (not as significant as in the
brain). There is no resting vasoconstrictor tone: no depressor effect BUT there is a strong reflex
vasocontrictor tone: vasoconstriction in pressor reflex, in redistribution.
Regulation of flow is to maintain a constant flow and is
Myogenic autoregulation: predominantly done by the Bayliss effect (VERY IMPORTNAT IN THE
Nervous: ↑SNS (pressor relflex) → Vasoconstriction → Redistribution
Humoral: both vasocontricion and vasodilation agents.
The Bayliss effect importance: Plot the renal plasma flow as a function of MAP.
Renal plasma flow is the amount of plasma which protrudes the kidneys through 1 minute. This gives
the intensisty of blood perfusion. Since the bayliss effect only works under a regulatory zone of the
kidney, at first at low pressure, if you increase the MAP you increase the renal plasma flow. BUT the
bayliss effect switches on (at ~60 mmHg) and as you increase the MAP you increase the resistance of
the blood vessel aswell. It will keep the level of renal plasma flow at a constant level. When you
reach a certain MAP (~140 mmHg) the Bayliss cant compensate anymore. This shows that the
production of primary ultrafiltartion is dependent on the MAP.
7. Splanchnic area
In general nervous control dominates over humoral control. A certain resting myogenic tone is
present, not very significant, BUT a large reflex vasoconstriction. Storng vasoconstriction in a pressor
response; redistribution in physical activity.
Circulatory shock, commonly known as just shock, is a serious, life-threatening medical condition
where insufficient blood flow reaches the body tissues. As the blood carries oxygen and nutrients
around the body, reduced flow hinders the delivery of these components to the tissues, and can stop
the tissues from functioning properly. The process of blood entering the tissues is called perfusion, so
when perfusion is not occurring properly this is called a hypoperfusional state. The causes can be:
Hypovolemic: This is the most common type of shock and based on insufficient circulating
volume. Its primary cause is loss of fluid from the circulation from either an internal or
external source. Hemorrhage, dehydration, trauma (contusion)
Cardiogenic: This type of shock is caused by the failure of the heart to pump effectively. This
can be due to damage to the heart muscle, most often from a large myocardial infarction.
↓CO (heart attack), ↓VR (heart tamponade)
Vasodilative: or Distributive shock - As in hypovolaemic shock there is an insufficient
intravascular volume of blood. This form of "relative" hypovolaemia is the result of dilation of
blood vessels which diminishes systemic vascular resistance. Neurogenic, anaphyactic shock,
I. Non-progressive – Compensated.
characterised by the body employing
physiological mechanisms, including
neural, hormonal and bio-chemical
mechanisms in an attempt to reverse
II. Progressive – Decompensated. The
shock will proceed to the progressive
stage and the compensatory
mechanisms begin to fail.
III. Irreversable. The vital organs have failed and the shock can no longer be reversed. Brain
damage and cell death have occurred. Death will occur imminently.
Hemorrhagic – symptoms:
↓MAP, due to decrease in circulatory volume.
↑HR, weak, thready pulse due to decreased blood flow combined with tachycardia.
↓Body temperature (↓MR), due to decreased perfusion and evaporation of sweat.
Pale, cold, wet skin
↑Respiratory efforts, due to sympathetic nervous system stimulation and acidosis.
Depressed mental function. Anxiety, restlessness, altered mental state due to decreased
cerebral perfusion and subsequent hypoxia , often with pupils dilated.
Stage I: The degree of symptoms/mechanism depends on the amount of blood loss. The key
response of the body is the negative feedback systems: Generally ↑SNS to maintain MAP!
Baroreceptor Depressor reflex ↓*
Chemoreceptor Pressor reflex ↑*
Cushings reflex ↑*
Stage II: Positive feedback.
Tissue damage , heart, kidney, CNS, lysosomes, acidosis, ↓ATP
Blood. ↑thormobosis, endothelial collapse.
Stage III: Exessive tissue damage, therapy is no help.
Regardless of the cause, the restoration of the circulating volume is priority. As soon as the airway is
maintained and oxygen administered the next step is to commence replacement of fluids via the
intravenous route. It is to be noted that NO plain water should be given to the patient at any point,
as the patient's low electrolyte levels would easily cause water intoxication, leading to premature
death. An isotonic or solution high in electrolytes should be administered if intravenous delivery of
recommended fluids is unavailable.
Inotropic agents in cardiogenic shock. Which enhance the heart's pumping capabilities, are used to
improve the contractility and correct the hypotension.
Corticosteroids (↑SV, stabilize lysosome membrane) reduce inflammatory responce.
The goal of respiration is to provide oxygen and remove carbon dioxide from tissues. There are 4
1. Pulmonary ventilation; inflow and outflow of air.
2. Gas exchange. Diffusion of O2 and CO2 btw alveoli and blood.
3. Transport of O2 and CO2 in the blood and body fluids.
4. Peripheral gas exchange.
Note that ventilation and gas transport require energy to power a mechanical pump (the heart) and
the muscles of respitation, mainly the diaphragm. In heavy breathing, energy is also required to
power additional respiatory muscles such as the intercostal muscles. The energy requirement for
ventiliation and gas transport is in contrast to the passive diffusion taking place in the gas exchange
The function of the airway is to clean, warm and moisten the air.
To understand breathing we must understand various pressure changes.
We have 3 different pressures:
1. The atmospheric pressure (0 in pysio)
2. Intrapulmonary pressure, pressure measured inside the alveoli. If there is no air movement,
they will be tha same. Thus at rest the intrapulmonary pressure is 0. To cause flow of air into
the alveoli during inspirationm the pressure must fall to a value slightly below atm. or 0. And
in expiration the oposite happens, the alveolar pressure rises above 0.
3. Intrapleural pressure, it is always lower (negative) than the atmospheric, -4mmHg.
The transmural pressures will decide if the compartments tend to be bigger or smaller.
1. Transpulmonary pressure: difference btw intrapulmonary pressure (0 at rest) and
intrapleural pressure (-4). It is a measure of the elastic forces in the lungs thant tend to
collapse - recoil pressure. The transpulmonary pressure works againts it trying to streach the
lung. So at rest the lung will not move.
2. Transthoracic pressure: btw the intrapleural and atmospheric. Its in equilibrium at FRC
(functional residual capacity)+1. Than the chest alone will have no tendency to move. The
volume within the thorax decides its tendency.
a. Maximum expiration: thorax has a tendency to be bigger.
b. Maximum inspiration: thorax has a tendency to be smaller.
3. Chest & lung : btw intrapulmonary pressure and atmospheric pressure. Is in equilibrium at
FRC or at the end of passive expiration:
Plot the pressure volume diagram:
At the beginning the intrapulmonary pressure is 0 and intrapleural pressure is -4. Then the
diaphragma (80% of work) and external IC muscles contract. Increasing the interthoracic space. The
intrapleural pressure will become more neg (~-6) creating an even bigger transpulmonary pressure
difference, that expands the lungs. As the lungs expand their volume
increases, acording to Boyles law „Forcing the volume V of the fixed
quantity of gas to increase, keeping the gas at the initially measured
temperature, the pressure p must decrease proportionally. Conversely,
reducing the volume of the gas increases the pressure“. Intrapulmonary
pressure decreases below 0 creating a pressure gradient via the
airways – air moves into the lungs.
At the end of inspiration the intrapulmonary pressure will go back to 0 again and their is no
movement of air. The intrapleural pressure remains -6, this is important because as we expand the
lungs there will be an even greater recoil.
A totally passive process (under normal conditions). Transpulmonary pressure is no longer
maintained and the elastic coil of the lung causes a decreased volume of the lung – increased
pressure inside and air will move out. At the end of expiration the pressure returns to 0 again, and
intrepleural pressure to -4. In forced expiration, using the internal IC muscles, the intrapleural
pressure will return to -4 quicker and may for a short time be more positive.
Compliance of the lungs:
How easy it is to inflate the lungs, depends on resistance. We have 2 elements, the lungs and thorax
their compliance can be measured separately.
There are 2 forces of the lung recoil: of the elastic forces of the lung tissue itself (collagen and elastic
fibres) and the elastic force caused by the surface tension of the fluid that lines the inside walls of the
alveoli. Tissue elastic forces tend to collapse the air-filled lung represent ~1/3 of the total lung
elasticity, but the fluid-air surface tension in alveoli is ~2/3. Increases when surfactant is not present.
Since water molecules tend to decrease the surface which they act upon (decreasing the radius of
the alveolus, forcing air out), thus surface tension is the force provided by water molecules that try to
decrease the radius of the alveoli, due to strong attraction to one another. If it wasnt there there
would be very large surface tension and tendency to collapse.
Law of Laplace: Pressure = 2x surface tension
Radius of alveolus
Surfactant is a phospholipid produced by pneumocytes type II (10% of alveolar surface), it greatly
decreases the surface tension of water. They are wetting agents that lower the surface tension of a
liquid, allowing easier spreading, and lower the interfacial tension between two liquids, dissolving
uncontinously in the fluid lining of the alveoli.
Respiratory distress syndrome: Surfactant is not produced properly. Seen in premature babies,
which dont have working pneumocytes type II. The lungs will collapse exhausting the inspiratoy
muscles. Treatment is to insert a tube into the airway (artificial breathing) or treat the mother with
cortisol (steroid hormone) wich increases the maturation of the pneumocytes type II.
Atelectasis: is a collapse of lung tissue affecting part or all of one lung. It is a condition where the
alveoli are deflated, as distinct from pulmonary consolidation. Infant respiratory distress syndrome is
another distinct type of atelectasis.
Surfactant will stabilize the alveoli of various sizes! Alveoli with different radii. Laplace law states that
the surface tension equals the readius times the TMP. In order to keep small alveoli open we need a
larger pressure difference (TMP btw alveoli). BUT then all the alveoli would eventually fuse to form
one large radius. So we have the same pressure in all. To keep them open surfactant produces a thick
layer on the small alveoli, decreasing their surface tension greatly, that way we stabilize alveoli of
Emphysema: a diorder with too big lung compliance. Elastic fibres are damaged and are NOT
replaced by collagen fibres. Decreaes the elastic recoil. Inflating is easy but expiration requires much
-Total lung capacity: 5-7 L, increases first 20
years of life. Less in older ppl due to less
lung elasticity. VC+RV
-Tidal volume: Volume of air inspired or
expired in normal breathing. Aprox 0.5 L in
-Inspiratory reserve volume (IRV): extra
volume of air that can be inspired over and
above the tidal volume with full force,
aprox 2,5 – 3 L.
-Expiratory reserve volume(ERV): the maximum extra volume that can be expired by forceful
expiration, after the normal tidal expiraion, aprox 1,1 L.
-Functional residual capacity (FRC): ERV + RV, aprox 2,5 L.
-Residual volume: volume of air remaining in the lungs after the most forceful expiration, aprox 1,2-
-Vital capacity: Maximum inspiration after maximum expiration, aprox 4.0 L.
Increase in total crossection as they descend. They have smooth muscle
surrouning the bronchi and bronchioles. The smooth muscle fibres are innervated
by the autonomic nervous system, it can make the total crosssection larger or
smaller. Changing the resistance of the airways.
Factors that will effect the radius of the airways:
1. Mechanical effect: Transmural pressure, the continous force that tries to stretch the lungs,
doing so it streched the elastic fibres aswell keeping the airways open. This is called lateral-
traction, which is a sort of pullin effect.
2. Nervous factor: The autonomic nervous system:
- SNS: Causes BRONCHODILATION (↓resistance and ↑crosssection). They act via Epinephrine
- PNS: Cause BRONCHOCONSTRICTION (↑resistance and ↓crosssection). Via Ach on M-achR.
Atropin is a specific inhibitor of bronchoconstriction.
3. Humoral factor:
- Achetylcholine: acts on M-achR and cause bronchocontriction.
- Epinephrine: acts on β2 causing bronchodilation.
- Histamine: very powerful bronchocontrictor, released from mast cells (asthma and
anaphylactic shock), also stimulates mucous production, that can ostruct small airways.
- CO2: Hypercapnia is the single most powerful bronchodilator. Useful is „ventilation-perfusion
Measurement of airway capacity is with a Tiffeneau test or Spirometry (meaning the measuring of
breath) is the most common of the Pulmonary Function Tests (PFTs), measuring lung function,
specifically the measurement of the amount (volume) and/or speed (flow) of air that can be inhaled
and exhaled. Spirometry is an important tool used for generating pneumotachographs which are
helpful in assessing conditions such as asthma, pulmonary fibrosis, cystic fibrosis, and COPD.
- FVC (Forced Vital Capacity). This is the total amount of air that can forcibly be blown out after full
inspiration, measured in liters.
-FEV1 (Forced Expiratory Volume). This is the amount of air that you can forcibly blow out in one
second, measured in liters. Along with FVC it is considered one of the primary indicators of lung
function. Should be around 80%, in healthy people. Decreases in bronchial asthma, 20-30%, highly
The muscles of respiration:
Predoninantly the diaphragma.
IC muscles and accessory muscles.
Neuromuscular junction: Somatomotor fibres come from pons or
medulla. Ach is the neurotransmitter acting on N-achR. They cause the
opening of cationic channels that depolarize the membrane and starting
an action portential propagation. Inhibitors are curare and artificial
curare derivatives used in surgical anathesia, with breathing machines.
Work of breathing:
1. Resistive work
2. Compliance work
They make up the total work of breathing: W=Wr+Wc
The compliance is proportional to the tidal volume. If you increase the tidal volume, it will stretch the
fibres in the alveoli more; more compliance work.
Resistive work ; friction as air particles hit the walls of the airways. Thats why you need work to move
the air through the airways. The resisitive work is proportional to rate of breathing. ↑rate
=↑columns of air must be moved faster =↑friction.
How the total work of breathing will change the frequency.
Minute volume of respiration: MVR=TVxRF (tidal volume x respiratory fequency).
It is the volume of air which can be inhaled (inhaled minute volume) or exhaled (exhaled minute
volume) from a person's lungs in one minute. The higher the minute volume the more carbon dioxide
(CO2) the person is releasing, the converse is the lower the minute volume the lower the amount of
carbon dioxide the person is releasing. The aim of the body is to maintain a constant MVR, by proper
Work of breathing as a function of respiratory frequency.
As we increase the frequency we increase the resistive work. If we maintain the
sam MVR and increase the frequency the tidal volume must decrease. So- if you
plot the compliance as a function of frequencym you will see that if you increase
the tidal volume you decrease the compliance work. The total work of breathing
is the sum of these 2 graphs and gives the most effective breathing – smallest
amount of work. Hering-Breuer reflex works to maintain this optimal frequency.
1. Anatomical dead space: Total volume of the conductive elements of airways. About 150 ml.
2. Physiological dead space: Anatomical dead space + non-perfused alveoli.
Gas transport in the blood:
In the pulmonary circulation arteries have venous blood and veins have
oxygenated arterial blood.
Alveolar gas exchange
What keeps O2 and CO2 moving trough the alveolar membrane is the partial
pressure. In the plasma we have greater partial pressure of CO2, that is why it leaves the blood going
to the alveolar space. And in the alveolar space the partial pressure of O2 is higher, forcing into the
plasma. This is by diffusion.
The rate of mobility of CO2 is greater BUT it´s partial pressure is less to compensate. So during the
sam amount of time, roughly tha same amount of O2 and CO2 will move through the alveolar
membrane and endothelium. Because, eventhough the driving force is different their permeability is
Oxygen - O2
- Physically dissovled [small amounts 1%]
determined by partial pressure (hypoxia & hypercapnia is the physicallys dissolved)
- Chemically combined to Hb [large amounts 99%]
determined by: concentration of Hb and saturation of Hb.
Each Hemoglobin has 4 heme groups, each heme can bind 1 O2 molecule. So 1 Hb can bind 4 O2,
with NONCOVALENT binding. Covalent binding formes methHb, which is pathological.
Oxygen-Hemoglobin saturation curve=
Maximal value is, theoretically, 100% and 100 mmHg pO2 in the
alveolar space is enough to saturate Hb.
The curve is sigmoid shaped. Due to the Positive cooperativity of Hb.
Binding of the first 02 molecule is the hardest, that causes a conformational change in the Hb,
facilitating the binding og the next and so on. So the binding of the 4th is the easiest.
Oxygen-Myglobin saturation curve=
It´s an oxygen binding molecule in skeletal msucle, role is to store
oxygen, in order to provide it during physical activity. 1 O2 can bind to
1 myoglobin, shows simple saturation with NO positive cooperativity. It
has a left shift compared to Hb, meaning it has greater O2 affinity and
in lack of O2 myoglobin can take over.
Hb releases the oxygen into the working tissue. Factor that effect it are:
- Partial pressure : btw plasma and interstitial space of working tissue, which has lower pO2.
- ↓ pH. Decreased pH (acidity) = decreased Hb affinity to O2, shifts the saturation curve to the
right, it can still reach 100%. With less affinity O2 will be released in to the working acidic
- ↑ Temperature. Shifts the saturation curve to the right, same as pH.
- ↑pCO2, hypercapnia. Shifts the curve to the right.
- 2,3 bis-phospho-glycerate. Binds to the β subunit of Hb, makes a conformational change
and decreases oxygen affinity. ↑2,3-BPG = ↓O2 affinity. Shifts the curve to the right.
BUT!!! Fetal Hb has no β subunit, 2α & 2δ. So 2,3-BPG cannot decrease oxygen affinity in
fetal Hb. So fetal Hb has higher O2 affinity than adult. There will be a left shift in the curve,
because since the mothers Hb cannot bind O2 as well with high 2,3-BPG it is released to the
2,3-BPG also plays a role in high altitudes, anemia, hypoxia (↑) and stored blood (↓).
CO bound to Hb formes carboxyhemoglobin. Binds on the heme group competeing with O2 for
binding but with x200 more affinity, it is a very effective blocker, patient will suffocate. To treat it you
need to get the patient to fresh air (first aid) or apply pure high pressure oxygen, it is the only
situation in medical practice where pure oxygen is allowed.
- Chemically dissoved in plasma as HCO3- (70%) [438 ml CO2/l in arterial blood]
- Physically dissovled (10%) [26 ml]
About 20x higher than O2. The only form that is transported in plasma alone.
- Bound to Hb (20%) [26 ml]
Hb-CO2: This is carbaminohemoglobin and is normal. CO2 binds to the globin part of Hb, to N-
terminus. Transported in plasma with RBC.
HCO3- production: Requiers RBC. So the importance of the RBC is not only to transport O2 but
also 90% of CO2 are transported via RBC!!!
In working tissue CO2 is produced, it enters the RBC. There is reacts with water, this need an
enzyme called cabonic acid anhydrid (CAA) which is why the process only takes place within RBC.
The end product is H2CO3 (hydrocarbonate) which will then dissociate from H+ forming HCO3-.
Bicarbonate is transported out of the RBC with a
BAND III transport protein in a HCO3-/Cl-
exchanger, by facilitated diffusion.
The H+ is neutrlized by a buffer, which is Hb. Hb
binds to the H+ (binding is stonger e-if Hb is
reduced) and causes a conformational change
making Hb have less affinity to bind O2 (right
ward shift of ↓pH). Also the CO2 (physically
dissolved) will bind to the globin part of Hb, causin a conformational change, also making Hb´s
affinity for O2 less (right ward shift of hypercapnia).
Hb is bound to a positively chanrged K+, as it binds H+ it releases K+. This causes an increase in
intracellular osmolarity – water enters RBS, and it will swell slightly.
The hematocrit value for venous blood is higher than arterial blood due to this swelling.
This whole process is the „Chloride shift“ or „Hamburger shift“.
Bore-effect: how ↑pCO2 results in less Hb O2 affinity.
Haldain-effect: ↑pO2 results in less Hb CO2 affinity.
Is only physically dissolved and the amount is linearly proportional to partial pressure in air.
Regulation of respiration
2 importanat regions in the brain have respiatory centers: PONS & MEDULLA OBLONGATA.
Pons centers (fine tuning of respiration):
1. Inspiration center (dorsal respiratoy group)
2. Expiration center (ventral respiratory group)
There is a certain interaction btw these centers, there are inputs and outputs.
The inspiratoy RAMP signal: Freq. of
Frequency of action potential againts time. Shows the slowly potential
rising discharge rate in time which abrubtly decreases. The
gradual increase of activity in the inspiratoy center stimulates the
motorneurons that innervate the muscles of inspiration (mainly
daiphragm). Meaning that the inspiration is a gradual process, not a Time
sudden muscle contraction.
The inspiratory center has similar function as the pressor center. It has spontaneous intrinsic
pacemaker activity and generates respiratory rythm. It is responsible for appropriating responses
to sensory information from chemoreceptors and mechanoreceptors in humans. Control length
and amplitude of inspiration.
CCR: central chemoreceptors stimulate inspiratory motorneurons. They are found in the
brainstem. They are stimulated by hypercapnia (mostly) and low pH. Hypoxia does NOT
stimulate the CCR, in case of hypoxia the neurons will be paralysed since the require O2 to
PCR: are in carotid body and aortic body (locations are called glomuses), particularly sensitive
btw 60 – 30 mmHG, stimulated by hypotension. They send info viia CN IX, X. They are sensitive to
hypoxia (mostly), hypercapnia and lox pH.
Under normal conditions pO2 does not control breathing since O2 saturation rearly decreases
and pCO2 changes earlier. But low pO2 multiplies the ↓pCO2 effect. And ↑pH facilitates the
Apart from stimulating the inspiratory center both CCR and PCR stimulate the Apneustic center
in the Pons. The apneustic center stimulates the
inspiratory center with several positive inputs. The
result is inspiration via decsending pathways (n.
Tractus Solitarius) that originate in the inspratory
center and terminate on motor neurons, most
importantly the phrenic nerve (C3-C5, mainly C4).
There will be a converge of the various stimulatory
inputs increasing the activity of the muscle,
The inspiratory center outputs will stimulate the
activity of the expiratory center & pneumotaxic
- The pneumotaxic center inhibits the inspiratory AND apneustic centers via n. parabrachialis. It
shortens the inspiratory ramp signal by decreasing length and increasing frequency of
- The expiratory center will inhibit the inspiratory center via n. ambiguus. This center is inactive
in resting respiration but can tribute to increased ventilation. Overdirve mechanism for
inspiration and expiration, little known about mechanism.
By inhibiting these 2 centers there will be no activity in the decsending pathways to the
inspiratory muscles → relaxation → expiration.
The decreased activity of the inspiratory center pCO2 will slowly increase, this activates CCR and
PCR which starts the next phase of inspiration.
There is one more input to these centers: inhibitory inputs. Fibres originating from stretch in the
walls of the BRONCHIOLI receptors will inhibit the inspiratory and apneustic centers. They travel
via the vagus nerve. In inspiration the bronchioli will be stretched, that will inhibit the inspiratory
center and apneustic center. This will also help in terminating inspiration.
Nervous cuts at various levels:
VAGUS INTACT VAGUS CUT
I. Above No change in Inhibition from stretch receptors is not
pneumotaxic breathing pattern, noavailable, more difficult to terminate
center centers affected. inspiration. Tidal volume increases and, to
maintain the minute volume of respiration,
the frequency decreases. MVR=↑TVx↓BR
II. Btw pneumotaxic Center needed for 2 mechanisms for terminating inspirations are
and apneutic termination of gone, weak inhibition from expiration center
inspiration has been is left. Long deep inspiration and short sudden
removed. ↑TV &↓BR expiration. APNEUSTIC BREATHING.
III. Btw Pons and Precise control of Irregular breathing, TV and BR change from
Medulla respiration is lost time to time. Average TV will be greater and
(pons). Irregular average BR will be lower. GASPING
breathing TV & BR BREATHING.
IV. Btw inspiratory Descending pathways No breathing.
and expiratory from inspiratory
centers center will not reach
C4 is very important! Damage in the spinal cord btw medulla and C4, decending pathway btw
them is lost – the patient will die, if phrenic nerve will not receive stimulus from motorneurons.
Below C4 the connection will be intact and patient will survive.
Like every other reflex it has receptors,
afferent pathway, efferent pathway and
effector of the reflex.
Receptors are stretch sensitive in the
BRONCHIOLI. Activated by stretch in
inspiration. Inforation is sent via vagus to the
inspiratory center. Resulting in inhibition of
the phrenic nerve, affacting the diaphragma.
The inhibition means lack of motorneuron
stimulation. The aim of the reflex is to set the tidal volume and breathing frequency to a
maximum effective breathing – with smallest effort. It is an efficiency-modulator.
Kussmaul breathing: high amplitude high frequnecy breathing due to acidosis. Acidosis will
stimulate the CCR and PCR which will cause increased activity of the inspiratory centers. Most
importnat cause is uncontrolled diabetes mellitus.
Cheyne-Stokes breathing: Periodic breathing; cretain stage of
activity followed by apnoe, or lack of breathing movement. A period of respiration is followed by
a long period of no respiration. 2 explination:
1. Hypersensitivity of CCR, this is pathological. A certain level of pCO2 will overexcite the CCR
which will overstimulate ther inspiratory center. This results in hyperventilation. The too
much O2 is inhaled, pCO2 greatly decreases (hypocapnia & hyperoxia) and none of the
chemoreceptors are activated. Resulting in no respiratory activity, untill pCO2 reaches the
activation threshold of CCR, this oocurs in patients
with brain hemorrhage.
2. Hyperventilation, voluntary.
Note that intoxications by alcholhol, morphine and heroine are powerful inhibitors of the
inspiratory center, resulting in hypoventilation and hypoxia. DO NOT GIVE OXYGEN. Because the
hypoxia stimulates the PCR and may be the only reason the patient is breathing at all.
Form of hypoxia:
1. Hypoxic hypoxia
Improper diffusion of O2 into blood, not enough O2 reaches the plasma. Reasons:
a. High altitudes.
b. Weakness of respiratory muscles.
c. Thickening of the alveolar wall. O2 cannot diffuse easily.
Treated with oxygen therapy.
2. Anemic hypoxia
There is enough O2 but not enough Hb. ↓RBC = ↓O2
3. Stagnation hypoxia
Impaired perfusion of a particular tissue or organ, local restriction in the flow of otherwise
well-oxygenated blood. Treatment involves impovement of the tissue perfusion
4. Histotoxic hypoxia
Enzymes responsable for utilisation of O2 are inhibited. Blocked respiratory enzymes, e.g.
due to cyanide poisoning. Instant death.
Decompression sickness (DCS), the diver’s disease, the bends, caisson disease is the name given to a
variety of symptoms suffered by a person exposed to a decrease (nearly always after a big increase)
in the pressure around the body. The body must adapt to the pressure following a rapid ascent. It is a
type of diving hazard and dysbarism (changes in ambient pressure). In order to maintain respiration
oxygen must be provided by high pressure from a tank. By increasing the alveoli you increase partial
pressure of nitrogen aswell, and more nitrogen will be dissolved in the plasma and by that is will be
easily disposed in the adipose tissue. If the pressure comes to a sudden drop the adipose tissue
cannot dissolve as much nitrogen as before and it tries to enter the plasma in an amount so bubbles
will be formed. They will obstruct the walls of small blood vessels mainly in the brain and big joints,
impairing blood perfusion in the brain, may cause death. To prevent it pressure must return to
normal slowly, so nitrogen can be exhaled.