Mechanisms of Disease
Session 1 – Cell Injury
Cell injury is part of a continuum. Degree of injury is a function of
M Injury: type, duration and severity
M Cell: Type, status, adaptability
Type of insult: Hypoxia, chemical, infections, physical, immune, Nutritional.
Cell damage occurs at plasma membranes, organellar membranes, DNA, structural proteins,
enzymes and can affect oxidative phosphorylation.
Pathogenesis of cell injury – ischemic hypoxia
Reversible: - loss of ATP Failure of Na/K pump morphological change = cell cytoplasm and
organelles swell with water.
- Anaerobic metabolism increased lactate and phosphate (low pH) morphological
change: chromatin clumps
- Reduced protein synthesis altered metabolism morphological change: intracellular
accumulations e.g. proteins and/or lipid.
Irreversible: - Massive intra-cytoplasmic [Ca2+] activates multiple degradative enzymes lethal
Reduced ATP synthesis/mitochondrial damage; loss of Ca homeostasis; disrupted membrane
permeability; free radicals.
Associated with cell injury in many settings... there generation occurs by
- Absorption of irradiation: e.g. H2O OHo and Ho
- Endogenous normal metabolic reactions: e.g. O2-•, and H2O2
- Transition metals: e.g. Fe3+ (receive an donate electrons freely)
- Exogenous toxins: e.g. carbon tetrachloride (highlights key concept: liver metabolism often
required to generate substance from inert substrate)
Removed by... spontaneous decay, anti-oxidants, storage proteins and enzymes.
Injure cells by... membrane lipid peroxidation, interaction with proteins (fragmentation and cross-
linkage), lastly by DNA damage.
Cytosolic free calcium is a potent destructive agent
Calcium is usually rapidly removed form the cytosol by ATP-dependent calcium pumps. In normal
cells, calcium is bound to buffering proteins, such as calbindin or parvalbumin, and is contained in
the ER, as well as in mitochondria. If there is abnormal permeability of calcium-ion channels, direct
damage to membranes, depletion of ATP, or damage to mitochondria, calcium increases in
concentration. If this happens activation of protein kinases causes phophorylation of protein. And
activation of phopholipases causes membrane damage and activation of proteases causes
Also cell injury by reactive oxygen metabolites that are extremely harmful to cells and are produced
on reperfusion after ischemia. Also ATP loss causes failure of biosynthesis and membrane pumps.
Cell injury morphology
Nuclear chromatin: shrinkage
(pyknosis), break-up (karyorrhexis);
Abnormal accumulations - due to
It is the death of groups of
contiguous cells in tissue or organ.
Necrosis is a dynamic process so
not always likely to see the characteristic cell death.
What you see depends on:
Degree of enzyme release: (more of this favours liquefactive necrosis)
o From lysosomes in dying cells (autolysis)
o And/or infiltrating inflammatory cells (heterolysis)
Degree of protein denaturation (favours coagulative necrosis)
Extent to which necrotic debris have been cleared away.
Protein denaturation > enzymatic digestion
Cells dead but basic shape endues
Most common form of necrosis
Affected tissue maintains solid consistency.
Enzymatic digestion > protein denaturation
Complete dissolution of necrotic tissue
Typically seen: Massive infiltration by neutrophils and ischaemic
necrosis in the brain
Accumulation of amorphous debris, tissue architecture is abolished
Characteristic in certain infections such as TB
Occurs in adipose tissue – typically following acute pancreatitis or trauma to fatty tissue
Pancreatitis lipase release digest adipocyte membranes and fat vacuoles fat necrosis
release of fatty acids react with Ca chalky calcified deposits.
Gangrene (not a separate kind of necrosis)
Clinical term for necrosis that is advanced and visible grossly
If mostly coagulative = dry gangrene
If mostly liquefactive necrosis = wet gangrene.
Not a specific pattern of necrosis but it refers to the cause of necrosis therefore infarct = ischaemic
necrosis. It can be coagulative (myocardial and liquefactive (brain).
White: occlusion of end artery
Red: venous occlusion, dual blood supply, loose tissues, previously congested tissues.
Apoptosis Vs Necrosis
Patterns of death Single cells Groups
Cell size Shrinkage; fragmentation Swelling
Plasma membrane Preserved continuity Early lysis
Mitochondria Increased membrane permeability Swelling; disordered structure
cytochrome c release
Organelle shape Contracted Swelling; disruption
Nuclei Chromatin: clumped & Pyknosis; karryhexis; karyolysis
DNA degradation Internucleosomal cleavage Diffuse & random
Cell degradation Phagocytosis; no inflammation Inflammation; macrophage
Physiological or pathological Both Always pathological
Active or passive Active – cells expend energy in Passive.
order to die
Physiological apoptosis – some examples
Involution during embryonic development e.g. interdigital space in humans
Hormone withdrawal e.g. endometrial cells at end of menstrual cycle.
Removal of auto-reactive immune cells
Pathological apoptosis – some examples
Removal of cells with DNA damage (mediated by p53)
Removal of virus-infected cells
Graft versus host disease.
Apoptosis – triggers
Intrinsic: mitochondria activate apoptosis
Release cytochrome c
Cytochrome c + APAF1 – apoptosome activates procaspase 9
Caspase 9 activates downstream caspases e.g. caspase 3
Extrinsic – Death ligands and receptors activate apoptosis
Bind respective TRAIL or FAS receptors activate procaspase 8
Caspase 8 activates downstream caspases
DNA ladder on a gel: due to DNA cleavage between nucleosomes
Altered membrane structure: phosphatidylserine on outside of cell membrane
Abnormal permeability: e.g. to dyes such as propidium iodide.
Chronic, excessive alcohol intake:
Alcohol is a hepatoxin and live damage is related to its intake. Toxicity is probably due to generation
of acetaldehyde in breakdown. Alcohol causes fatty liver, acute hepatitis and cirrhosis.
Acute hepatitis: ingestion of large amounts of alcohol causes a true hepatitis, with focal necrosis of
liver cells. Function tests show raised levels of transaminases.
With abstinence the inflammation resolves without harm. But with continues ingestion of alcohol,
fibrosis develops around the central veins, and in response to continues heptocyte necrosis. The
end-result is hepatic fibrosis that may progress to cirrhosis. Cirrhosis is characterized by the
replacement of normal tissue with fibrous tissue and the loss of functional liver cells.
A reduction in the capacity of liver cells to take up and conjugate bilirubin leads to
hyperbilirubinaemia that may produce jaundice. A reduction in the capacity to produce urea may
lead to hyperammonaemia. Reduction in protein synthesis so decreased levels of albumin,
lipoproteins and clotting factors these lead to oedema, fatty liver and decreased blood clotting
Acute Hepatic necrosis – Paracetamol
Acute hepatic necrosis is characterized by a markedly raised plasma levels of alanine transaminase
and aspartate transaminase, which are released from damaged hepatocytes.
In cases of paracetamol toxicity, the sulphate and glucuronide pathways become saturated, and
more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result,
hepatocellular supplies of glutathione become exhausted and NAPQI is free to react with cellular
membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute
The earliest visible sign of Sublethal damage is ultrastructual damage to mitochondria
Later damage can be seen as swelling to cellular organelles
Fatty change is a manifestation of Sublethal impairment of metabolism and is common in
Intense eosinophilia of the dead cell is due to loss of RNA and coagulation of proteins
Nuclei undergo phases of pyknosis, karyorrhexis and karyolysis, leaving a shrunken cell
devoid of nucleus.’
Proteins may be liberated from the dead cells and be detected in the blood in diagnosis.
Session 2 - Acute Inflammation
Acute: describing a disease of rapid onset, severe symptoms and brief duration. “Response of living
tissue to injury”
It is innate, immediate and early and has a short duration.
1. Vascular reaction – accumulation of fluid exudates and neutrophils in tissues
2. Controlled by a variety of chemical mediators derived from plasma cells
3. Protective, but can lead to local complication and systemic effects.
Causes: Microbial infections, hypersensitivity reaction (acute phase), physical agents, chemical,
Clinical signs: Rubor, tumor, calor, dolor which is redness, swelling, heat, pain (& loss of function)
Changes in vascular flow and calibre
1. Transient vasoconstriction of arterioles (few secs)
2. Vasodilatation of arterioles and then capillaries increase in blood flow (Histamine,
prostaglandins, nitric oxide)
3. Increased permeability of blood vessels. This causes exudation of protein, and slowing of
circulation. (Histamine, bradykinin,
4. [RBCs] increases in small vessels and
increases viscosity of blood (stasis).
Migration of neutrophils
5. Stasis causes neutrophils to line up
at the edge of blood vessels along
the endothelium called margination.
6. Neutrophils then roll along
endothelium, sticking to it
intermittently called rolling.
7. Then stick more avidly called
8. Followed by emigration of
neutrophils through blood vessel
wall. (C5a, leukotriene B4, bacterial
Neutrophils chemotaxis and phagocytosis
9. Neutrophils migrate to site of injury
down a concentration gradient of
10. Neutrophils phagocytose
11. Activated neutrophils may release toxic metabolites and enzymes causing damage to the
Histamine - vascular dilatation and the immediate transient phase of increased vascular permeability
Prostaglandins - potentiate the increase in vascular permeability caused by other mediators, some
cause platelet aggregation
Leukotrienes – has vasoactive properties
Cytokines (interleukins ie.IL-1, IL-6, IL-8; TNF-α, type 1 interferons, chemokines, TGF- α, TGF-β) -
Cytokines that affect the inflammatory response generally up-regulate innate immunity.
Fluid flow across vessel walls is determined by the balance of hydrostatic pressure within the vessel
and the difference in colloid osmotic pressure between the plasma and interstitial fluid:-
Increased hydrostatic pressure increase fluid flow out of vessel
Increase colloid osmotic pressure of interstitium increase fluid flow out of vessel
There is a net flow of fluid out of vessel.
Exudate – is fluid loss in inflammation which has a high protein content, specific gravity above 1.02
Transudate – Fluid loss due to hydrostatic pressure imbalance only, low protein content, specific
gravity less than 1.012 (e.g. venous outflow obstruction)
Oedema – excess of fluid in interstitium, can be Transudate or exudate
Pus – a purulent exudate, rich in neutrophils and cell debris.
How does it all work
Exudation of fluid – Delivers plasma proteins to area of injury, such as immunoglobulins,
inflammatory mediators and fibrinogen. It also dilutes toxins and increases lymphatic
drainage. This works to deliver microorganisms to phagocytes and antigens to immune
Infiltration of cells – removes pathogenic organisms and necrotic debris
Vasodilatation – increases delivery and temperature
Pain and loss of function – this enforces rest, reduces chance of further traumatic damage.
Mechanisms – chemical mediators of each step, these incite complex inter-reactions
Proteases – kinins, coagulation/fibrinolytic system
Prostaglandins/Leukotrienes – metabolites of arachidonic acid, synthesis blocked by NSAIDS
Cytokines/chemokines (produced by wbc’s) – many but some are PAF, TNF alpha, PDGF, TGF beta.
From platelets: 5-HT, Histamine, ADP
From neutrophils: Lysosomal constituents
Products released on neutrophil death
From endothelium: Prostacyclin, Nitric oxide
Plasminogen activators / inhibitors
1. Immediate early response (1/2 hour):
a. Histamine is released from masts cells, basophils and platelets. These in response to
many stimuli: physical damage, immunologic reactions C3a, C5a, IL1, factors from
neutrophils and platelets.
b. Results in vascular dilatation, transient increase in vascular permeability, pain but
2. Immediate sustained response – not always seen. Due to direct damage to endothelial cells.
3. Delayed response: (peaks about 3 hours)
a. Many and varied chemical mediators, interlinked and of varying importance.
Important because of possibility of therapeutic intervention.
Mechanisms of vascular leakage
Endothelial contraction -->gaps –histamine, leukotrienes
Cytoskeletal reorganisation --> gaps –Cytokines IL-1 and TNF, hypoxia
Direct injury -toxic burns, chemicals
Leukocyte dependent injury –toxic oxygen species and enzymes from leucocytes (pulmonary and
Increased transcytosis -channels across endothelial cytoplasm–VEGF
They phagocytose, recognition is facilitated by opsonins. Phagosomes fuse with lysosomes to
produce secondary lysosomes.
Mechanisms of neutrophil migration
Neutrophil adhesion and emigration is due to binding of complementary adhesion molecules on
endothelial and neutrophil surfaces. Chemical mediators change surface expression or avidity of
adhesion molecules. Selectins, immunoglobulins and integrins.
They can escape from vessels because of the relaxation of inter-endothelial cell junctions, the
digestion of vascular basement membrane and of course movement.
Movement is due to chemotaxis – movement along concentration gradients of chemoattractants –
involving receptor-ligand binding, rearrangement of cytoskeleton and production of pseudopod.
Produces superoxide and H2O2.
H2O2-Myeloperodidase-halide system – produces HOCl-
Myeloperoxidase independent killing is less efficient.
Lysozyme & hydrolases
Bactericidal permeability increasing protein (BPI
Major basic protein (MBP, Eosinophils)
Complication of acute inflammation
Swelling causes blockage of tubes e.g. bile duct, intestine
Exudate causes compression e.g. cardiac tamponade and serositis which is inflammation of a serous
membrane, such as the lining of the thoracic cavity.
Fever –‘endogenous pyrogens’ produced: IL1 and TNF alpha. Prostaglandins, therefore NSAIDS
Leukocytosis – IL1 and TNF alpha produce an accelerated release from marrow. Macrophages, T
lymphocytes produce colon-stimulating factors. Bacterial infections – neutrophils, viral –
Acute phase response – decreased appetite, altered sleep pattern and changes in plasma
concentrations of acute phase proteins such as C-reactive protein
Spread of microorganisms and toxins
What happens after...
1. Complete resolution
2. Continued acute inflammation with chronic inflammation; chronic suppuration
3. Chronic inflammation and fibrous repair, probably with tissue regeneration
Resolution – changes gradually reverse, vascular changes stop:
Neutrophils no longer marginate
Vessel permeability returns to normal
Vessel calibre returns to normal
This results in exudate drainage into lymphatics, fibrin is degraded by plasmin and other proteases,
neutrophils die, break up and are carried away or are phagoctosed. Lastly damaged tissue might be
able to regenerate.
If tissue architecture has been destroyed, complete resolution is not possible.
Mechanisms of resolution
All mediators of acute inflammation have short half lives. So they may be inactivated by degradation,
inhibitors may bind, they may be unstable, they may be diluted in the exudate and lastly specific
inhibitors of acute inflammatory changes.
Lobar pneumonia – caused by streptococcus pneumoniae which mainly infects young adults in
confined conditions such as alcoholics. Its clinical course is worsening fever, prostration,
hypoxaemia over. Fairly sudden improvement when antibodies appear.
Skin blister – caused by heat, sunlight or chemicals. Its predominant features are pain and exudate
which collects as fluid strips in the overlying epithelium.
Abscess – are solid tissues, inflammatory exudate forces the tissue apart. Liquefactive necrosis
occurs in the centre, this may cause high pressure therefore pain, may cause tissue damage and may
squash adjacent structures.
Inherited disorder Hereditary Angio-oedema bradykinin formation is caused by continuous
activation of the complement system due to a deficiency in one of its prime inhibitors, C1-esterase
inhibitor (C1INH). So bradykinin (peptide) is made in excess leading to excessive inflammation.
Session 3 – Chronic Inflammation
Chronic – a disease of long duration involving very slow change.
May take over from acute inflammation if damage is too severe to be resolved within a few days
May arise de novo from some autoimmune conditions (e.g. rheumatoid arthritis) some chronic
infections (viral hepatitis). Chronic low-level irritation.
May develop alongside acute inflammation in some severe persistent or repeated irritation.
It is characterised by the microscopic appearances.
They are derived from blood monocytes. Also they accumulate in chronic inflammation due to:
1. Recruitment from blood
2. Mitotic division
3. Immobilisation by cytokines (macrophage inhibitory factor)
May undergo activation once extravasated.
Function phagocytosis of debris & bacteria. This works by recognition, engulfment into a phagosome
and then formation of phagolysosome and killing.
They control other cells by cytokine release: TNF-alpha and IL-1.
They control other leukocytes – which in turn promotes other cytokine secretion, reciprocal
relationship with the lymphocytes. On endothelial cells they promote leukocyte adherence and on
fibroblasts, proliferation and collagen synthesis.
They produce blood clotting factors, growth factors and proteases.
They control processing and presentation of antigen to immune system by T-cell activation.
They secrete growth factors PDGF, EGF, FGF. These stimulate the growth of blood vessels, and
division and migration of fibroblasts.
Lymphocytes – B lymphocytes differentiate to produce antibodies and T lymphocytes are involved in
control & some cytotoxic functions
Plasma cells – differentiated antibody producing B lymphocytes
Eosinophils – allergic reactions, parasite infestations, some tumours
Fibroblasts/myofibroblasts – recruited by macrophages; make collagen
Giant cells – multinucleate cells made by fusion of macrophages. There are several types.
Morphology of most reactions is not specific, but proportions of each cell type may vary in different
Effects of Chronic Inflammation
Fibrosis: found in Chronic Cholecystitis
This causes repeated obstruction by gall stones, repeated inflammation leads to chronic, fibrosis of
gall bladder wall then occurs.
Found in gastric ulceration. This is due to imbalance of acid production and mucosal defence.
Inflammatory bowel disease
Ulcerative colitis is superficial – diarrhoea and bleeding
Crohn’s disease is transmural – strictures, fistulae
Rheumatoid Arthritis – is an autoimmune disease which consists of localised and systemic immune
response and localised chronic inflammation of synovium leads to joint destruction – can also affect
blood vessels, skin and lung.
Atrophy – gastric mucosa and adrenal glands
Stimulation of immune response – macrophage – lymphocyte interactions.
Chronic inflammation and immune responses overlap. This is due to immune diseases causes
pathology by chronic inflammation. Chronic inflammatory processes can stimulate immune
Is chronic inflammation with granulomas
They occur with persistent, low-grade antigenic stimulation and hypersensitivity.
Causes of granulomatous inflammation:
Mildly irritant ‘foreign’ material – common materials include keratin, urate crystals (such as
gout), degenerated altered collagen, and degenerated altered elastin.
Mycobacteria: TB, leprosy
Other rare infections
Unknown causes such as Sarcoid, Wegener’s granulomatosis and Crohn’s disease
Tuberculosis - Caused by mycobacteria, it produces no toxins or lytic enzymes, causes disease by
persistence and induction of cell-mediated immunity. Destruction of tissues occurs by caseating
granulomas. In TB granulomas, Langhans’ type giant cell, caseous necrosis, epithelioid histocytes and
lymphocytes are all present.
Primary TB – non-sensitized individual
Outcome: usually heals with some scarring & persistent bacteria in lung
Secondary TB – previously exposed individual
Usually starts in apex of lung and the outcome is varied
Arrest, fibrosis scarring erosion into bronchus tuberculous empyema Erosion into blood
Sarcoidosis is a chronic granulomatous disease of unknown cause, in which many tissues are
infiltrated by non-caseating granulomas. Common systems involved ate the lymphoreticular system,
lungs, skin, eyes and brain.
Syphilis the organism gains access to the body and then forms a primary lesion. The organism then
disseminated throughout many organs from this site. An immune response develops and the
primary infection heals but, thereafter, the disease becomes a chronic inflammatory condition,
affecting many organs.
Session 4- Regeneration and Fibrous repair
Regeneration – replacement of functional, differentiated cells
Repair – production of a fibrous scar
Stem cells – capable of indefinite division, though slowly
Labile cells – normal state is active cell division and usually rapid regeneration
Stable cells – Not normally dividing at significant rate, so the speed and regeneration is variable.
Permanent cells – unable to divide or regenerated
This is a discrete series of cell types but in fact it is more of a continuum.
Complex and poorly understood.
Growth factors – GF< PDGF, FGF,
IGF, and hormones ACTH,
oestrogen and growth hormone.
Contact with basement
membrane & adjacent cells
signalling through integrins
Growth factors act differently in different tissues.
Totipotent Multipotent – extent unknown
Only from embryos Available from bone marrow
Hard to obtain Syngenetic source easily available
Syngenetic source required therapeutic cloning Much studied – bone marrow transplantation
Ethical problems -
Proliferate locally to replace parenchymal cells
Respond to local environment and cytokines
May sometimes colonise tissues from the bloodstream
The theoretical potential for manipulating regeneration is enormous.
Formation and healing of granulation tissue.
1. Blood clot forms (haemorrhage and exudate)
2. Acute inflammation around the edges (neutrophils)
3. Chronic inflammation: macrophages infiltrate the clot and digest it
4. Capillaries and lymphatics sprout and infiltrate
5. Myofibroblasts infiltrate and differentiate
6. They glycoproteins and collagen are produced
7. Cell population falls, vessels differentiate and are reduced in number
8. Collagen matures contracts and remodels.
Features of fibrous collagens- triple helical fibrils arrange in ‘quarter stagger’ mode to form insoluble
fibres these are relatively resistant to general proteases; slow remodelling by specific collagenases.
Platelets are activated when brought into contact with collagen (which is exposed when the
endothelial blood vessel lining is damaged), thrombin (primarily through PAR-1), ADP receptors
(P2Y1 and P2Y12) expressed on platelets, a negatively charged surface (e.g. glass), or several other
activating factors. Once activated, they release a number of different coagulation factors and
platelet activating factors.
Extrinsic pathway: coagulation is initiated by a substance generated from damaged tissues called
Tissue Factor by interaction with factor VII
Intrinsic Pathway: coagulation is initiated by contact with surface agents such as collagen or by
proteases such as kallikrein, acting through factor XII
Healing by primary intention
A clean sutured wound
Dermis undergoes fibrous repair
Sutures out at 5-10 days
Maturation of scar continues up to 2 years
Minimal scarring, good strength
Risk of trapping infection under skin – produces abscess.
Healing by secondary intention
Clot dries to form a scab or eschar
Epidermis regenerates beneath
Repair process produces granulation tissue
It takes longer
Produces a larger scar; not necessarily weaker.
Produces more late contraction
Factors influencing wound healing
o Type, size, location of the wound
o Apposition lack of movement
o Infection: suppuration, gangrene, tetanus
o Blood supply: arterial, venous
o Foreign material: dirt, glass, sutures, necrotic tissues
o Radiation damage. (slows healing)
o Age, general state of health
o General cardiovascular status
o Dietary deficiencies e.g. protein, vitamin C, sulphur containing amino acids
Complications of repair
Insufficient fibrosis: wound dehiscence; hernia; ulceration
Excessive fibrosis cosmetic scarring; hypertrophic scars; keloid
Excessive contraction = limitation of joint movement obstruction of tubes & channels.
Healing in tissues
Cardiac muscle - No regeneration just scarring, as myocytes can’t divided they are differentiated to
such a degree they can’t proliferate. Convert contractile muscle into inflexible collagen which affects
the contraction. This results in arrhythmias or cardiac failure which results in fluid accumulation.
Brain - Liquefactive necrosis left with cystic space – no scarring because wouldn’t have any
Bone - Can repair completely from haematoma inflammatory reaction capillary grow stem
cell develop a callus which supported the framework
Liver - Hepatocytes are very differentiated but can still proliferate. You can remove 70% of the liver
and it can still regenerate.
Peripheral nerves - (wallerian degeneration) where damage is distal, regeneration begins at 3/4
days, regrow down previous channels
Wallerian nerve degeneration - nerves regenerate to previous node of Ranvier and then axon
regrows down the path it took previously, no cell division actually occurs - nerve growth only
requires cytoplasm and membrane.
Cartilage – can regenerate
Kidney – epithelium regenerates, architecture cannot, produces glomerular scarring and loss of
Muscle – replaced by scar tissue
Voluntary muscle – limited regenerative capacity from satellite cells
Session 5 – Haemostasis, Thrombosis and Embolism
Haemostasis is the arrest of bleeding, involving the physiological processes of blood coagulation and
the contraction of damaged blood vessels.
Successful haemostasis depends on
Constriction on blood vessels to limit blood loss.
Platelets to adhere to the damaged vessel wall and each other, to form a plug, and the
platelet release reaction.
o ATP ADP
o ADP, thromboxane A2 cause platelet aggregation, 5HT also realised.
o Platelets coalesce after aggregation.
Coagulation – cascade, series of inactive components converted to active components.
Prothrombin thrombin which activates fibrinogen fibrin.
Fibrinolysis – plasminogen plasmin via plasminogen activators
This is aided by endothelium, which is anti-thrombotic. On it there are plasminogen activators,
prostacyclin, nitric oxide and thrombomodulin.
It is the formation of a solid mass of blood within the circulatory system during life.
It is not a normal physiological process.
Occurrence is due to...
Abnormalities of the vessel wall such as
o Direct injury
Abnormalities of blood flow
o Stagnation or turbulence
Abnormalities of blood components
o Smokers, post-partum, post-op
Arterial – they are pale, granular, lines of Zahn and have lower cell content than venous.
Venous – soft, gelatinous, deep red and have a higher cell content.
o Complete dissolution of thrombus, the fibrinolytic system active, blood flow is re-
established, this is most likely when thrombi are small
o Progressive spread of thrombosis
o Distally in arteries and proximally in veins.
o Reparative process due to ingrowth of fibroblasts and capillaries and lumen remains
o Blood flow re-established but usually incompletely
o One or more channels formed through organising thrombus.
o This is an unlikely outcome
o Part of thrombus breaks off, travels through bloodstream and lodges at distant site
Effects of thrombosis
Arterial – it causes ischaemia, infarction though this depends on site and collateral circulation – if
other vessels are supplying the same tissue.
Venous – it causes congestion, oedema, ischaemia and infarction.
Embolism is the blockage of a blood vessel by solid, liquid or gas at a site distant from its origin.
More than 90% of emboli are thrombo-emboli. Other types include air, amniotic fluid, nitrogen,
medical equipment and tumour cells.
From systemic veins pass to the lungs = pulmonary emboli
From the heart, they pass via the aorta to renal, mesenteric and other arteries
From atheromatous carotid arteries pass to the brain
From atheromatous abdominal aorta pass to arteries of the legs
Deep vein thrombosis
Predisposing factors include – immobility, post-op, pregnancy and post-partum, oral contraceptives,
severe burns, cardiac failure and disseminated cancer.
High risk patients must be identified and offered prophylaxis.
Leg compression during surgery, Thrombo emboli disorder stockings.
Treatment intravenous heparin and oral Warfarin anticoagulant prevents propagation but does
not dissolve embolism.
Effects of pulmonary embolism
Massive PE > 60% reduction in blood flow rapidly fatal
Major PE – medium sized vessels blocked = shortness of breath +/- cough and blood stained sputum
Minor PE – small peripheral pulmonary arteries blocked. Asymptomatic or minor shortness of breath
Recurrent minor PEs lead to pulmonary hypertension.
Nitrogen embolism required rapid decompression, gaseous nitrogen in blood. This is the bends.
Fat embolism - can occur whenever there is a chance for fat to enter the circulatory system, such as
during surgery. So due to laceration of adipose tissue or fractures of long bones. One of the more
common scenarios is the fatty marrow entering the circulation after a fracture to a large long bone,
such as the femur, or after surgery on this bone, which then lodges in the lung, causing inflammation
of the lung and pulmonary failure.
Disorders of coagulation
Idiopathic Thrombocytopenia –is due to autoimmune destruction of platelets, which are coated
with anti-platelet antibodies. Can be acute of chronic, acute seen in children after viral infection
which generally recovers. Chronic occurs in adults and platelet destruction occurs in the spleen, a
spenectomy is a good treatment as it prolongs survival.
Disseminated intravascular coagulation – results from activation of the coagulation system in small
vessels throughout the body. This has several main effects:
Platelets are consumed, so low count.
Fibrin thrombi are deposited in small vessels in the brain, kidney, lung and other organs,
causing ischemic changes.
Coagulation factors are consumed and there is activation of the fibrinolytic system; fibrin-
degradation products acting as inhibitors of coagulation are generated.
Red cells are fragmented by passage through vessels occluded by thrombi, and there is
destruction of red cells.
Thrombophilia – the term describes an inherited or acquired tendency to make thrombi.
Haemophilia – the level of factor VII is reduced.
Session 6- Atheroma
Atheroma is the accumulation of intracellular and extracellular lipid in the intima and media of large
and medium sized arteries.
Atherosclerosis is the thickening and hardening of arterial wall as a consequence of atheroma.
Arteriosclerosis is the thickening of the walls of arteries and arterioles usually as a result of
hypertension or diabetes mellitus.
Macroscopic features of Atheroma
o Lipid deposits in intima, yellow slightly raised. Relationship to atheroma is debateable.
The simple plaque
o Raised yellow/white with an irregular outline widely distributed, enlarged and
The complicated plaque
o Haemorrhage into plaque
o Aneurysm formation
Common sites – Aorta – especially abdominal, coronary arteries, carotid arteries, cerebral arteries
and leg arteries.
Microscopic features - Early changes – proliferation of smooth muscle cells, accumulation of foam
cells and extracellular lipid
Later changes – fibrosis, necrosis, cholesterol clefts and maybe inflammatory cells.
Also disruption of internal elastic lamina, damage extends into media, ingrowth of blood vessels and
Ischaemic heart disease
o Sudden death
o Myocardial infarction
o Angina pectoris
o Cardiac failure
o Transient ischaemic attack
o Cerebral infarction
o Multi-infarct dementia.
o Ischaemic colitis
o Intestinal infarction
Peripheral vascular disease
o Intermittent claudication – exercise incapability
o Leriche syndrome - is atherosclerotic occlusive disease involving the abdominal
aorta and/or both of the iliac arteries.
o Ischaemic rest pain
o Slow progressive throughout adult life – risk factors operate over years
o Women protected relatively before menopause – presumed hormonal basis
o High plasma cholesterol associated with atheroma
o LDL most significant, adversely HDL protective
o Mode of action uncertain but changes coagulation system reduced PG12 and
increased platelet aggregation.
o Strong link between IHD and high blood pressure
o The mechanism is uncertain but it is suggested that endothelial damage is caused by
o DM doubles IHD risk, and furthers risk of cerebrovascular and peripheral vascular
disease. The protective effect in premenopausal women is also lost.
o >5 units/day increases risk of IHD
o Smaller amounts of alcohol may be protective
Infection - such as Chlamydia pneumoniae, helicobacter pylori and cytomegalovirus.
Lack of exercise, obesity, soft water oral contraceptive and stress.
Lipoprotein Class Transport Function
Chylomicrons Dietary Triacylglycerols from the intestine to tissues such as adipose tissue
VLDL Triacylglycerols synthesised in the liver to adipose for storage
LDL Cholesterol synthesised in the liver to tissues
HDL Excess tissue cholesterol to the liver for disposal as bile salts
Genetic variations in apolipoprotein E are associated with changes in LDL levels. Polymorphisms
involved lead to at least 6 Apo E phenotypes. Polymorphisms can be used as risk markers for
Familial Hyperlipidaemia –genetically determined abnormalities of lipoproteins lead to earl
development of atheroma. Physical signs arcus, tendon xanthomas, xanthelasma
How it occurs – just a hypothesis
Atheroma involves thrombosis, lipid accumulation, production of intercellular matrix and
interactions between cell types. Cells involved: endothelial, platelets, smooth muscle, macrophages,
Endothelial – key to haemostasis, alter permeability to lipoproteins, secretion of collagen,
stimulation of proliferation and migration of smooth muscle cells.
Platelets – key to haemostasis, stimulate proliferation and
migration of smooth muscle cells (PDGF)
Smooth muscle cells – take up LDL to become foam cells, synthesise
Macrophages – oxidise LDL, take up lipids to become foam cells,
secrete proteases which modify matrix, stimulate proliferation and
migration of smooth muscle cells
Lymphocytes – stimulate proliferation and migration of smooth
Neutrophils – secrete proteases leading to continued local damage
Endothelial injury due to LDL/toxins/hypertension, causes platelet adhesion, PDGF release = SMC
proliferation and migration, LDL oxidation, uptake of lipid by SMC and macrophages, SMC produce
matrix, foam cells produce cytokines causing further SMC stimulation and increased recruitment of
Session 7 – Cellular Adaptations
Control of Cell Growth
Cells in multicellular organisms communicate through chemical signals. Hormones act over a long
range and local mediators are secreted into the local environment and some cells communicate
through direct contact.
Cells are stimulated when extracellular signalling molecules bind to a receptor, each receptor
recognises specific ligand then act as transducers that convert the signal from one form to another.
Signalling molecules such as hormones and local mediators – epidermal growth factor (EGF), platelet
derived growth factor (PDGF), Fibroblast growth factor (FGF), TGF-beta, cytokines.
There are two main types of receptors that are important in cell growth; these are G-protein-linked
receptors and enzyme-linked receptors.
G-protein-linked receptors activate GTP-binding proteins (G-proteins) these are molecules switches,
they are turned on for brief periods while bound to GTP. Then they switch themselves off by
hydrolysing GTP to GDP.
Enzyme linked receptors have intracellular domains with enzyme function. Most are receptor
tyrosine-kinases these are activated by growth factors, thus being important in cell proliferation.
Also some activate a small GTP-binding protein, Ras (important in cancer).
The Cell Cycle
Cell cycle machinery is subordinate to a control system this consists mainly of protein complexes
which in turn consist of a cyclin subunit and a CdK subunit. The cyclin has regulatory function, the
Cdk catalytic function.
Different cyclin-Cdk complexes trigger different cell
cycle steps. The cell cycle control system has in-built
molecular breaks (checkpoints). These ensure that
the next step does not begin until the previous one is
The G1 checkpoint – the retinoblastoma protein plays
a key role, the RB protein function is determined by
its phosphorylation status, S phase cyclin-Cdk
complexes phosphorylate Rb.
Cellular proliferative capacity
Labile cell populations contain cells that move
rapidly form one cell cycle to the next
Stable cell populations dismantle their cell
cycle control machinery and exit the cell cycle, but re-enter it when stimulated
Permanent cell populations have left the cell cycle and cannot re-enter it.
The regeneration in labile and stable cell populations correlates with stem cell activation.
Regeneration: increase in cell number in a tissue or organ to replace losses.
Mammals can replace cells and tissues but not whole organs.
Hyperplasia: increase in cell number in a tissue or organ above normal
Only occurs in labile or stable cells it may occur pathologically or physiologically (e.g. hormonal
action on endometrium). Pathological occurs in several situations, hyperplasia and hypertrophy
often occur together, association with increased risk of caner.
Hypertrophy: acquired increase in size of a cell, tissue or organ
Occurs in permanent cells due to synthesis of more cellular structural components it is again due to
physiological or pathological causes. Physiological reasons such as increased functional demand e.g.
skeletal muscle, and hormonal e.g. uterus in pregnancy. Pathological increased functional demand
e.g. cardiac muscle due to valvular disease or hypertension.
Atrophy: acquired decrease in size of cell, tissue or organ
Atrophy of whole organs is often due to reduction in cell size and apoptosis. Causes reduced
workload, loss of innervation (Alzheimer’s) , reduced blood supply, inadequate nutrition, loss of
endocrine stimulation and ageing.
Metaplasia: change of one differentiated cell type to another.
Direct = cell A cell B
Indirect: stem cell to either differentiated cell A or differentiated cell B
Causes: an adaptive response to various stimuli, new cell type is better than old, the stimulus that
induced metaplasia may, later, induce cancer e.g. squamous cell carcinoma of the bronchus.
Hypoplasia: incomplete development of an organ with reduced cell numbers.
A tumour is a swelling of any nature:
Inflammatory, traumatic (e.g. haematoma), Neoplasm
Neoplasm – Abnormal growth of cells which persists after initiating stimulus has been removed.
Benign Neoplasm – cells grow as a compact mass and remain at their site of origin.
Malignant Neoplasm – Growth of cells is uncontrolled. Cells can spread into surrounding tissue and
spread to distant sites. CANCER = a malignant neoplasm.
Development change to DNA which must cause an alteration in cell growth and behaviour
oncogenes & tumour suppressor genes
Change must be non-lethal and be passed onto daughter cells monoclonal population.
Difference in Neoplastic cells – Alteration in growth control, factors regulating growth (receptors).
Alterations in cellular interaction.
Growth control: Increased cell proliferation, due to more cells entering cell cycle. Or cell cycle is
“sped up”. Cells have a changed life span; there are alterations in cell death-decreased apoptosis.
Modification of cell metabolism and angiogenesis can occur.
Increased or decreased growth factor receptors or altered receptors. Synthesis of growth factors
increases – autocrine or paracrine effect. Excess/modified growth control proteins.
Nuclear variation in size and shape Nuclear variation in size and shape minimal to
minimal marked, often variable
Diploid Range of ploidy
Low mitotic count, normal mitosis Low to high mitotic count, abnormal mitosis
Structural differentiation retained structural differentiation shows wide range of
organised Not organised
Functional Some failure of differentiation
Retention of specialisation Loss of specialisation.
Dysplasia – premalignant condition, increased cell growth, cellular atypia, altered differentiation,
can range from mild to severe. It occurs in the cervix, bladder, breast and others.
Smooth muscle: Leiomyoma Smooth muscle: Leiomyosarcoma
Fibrous tissue: Fibroma Bone: Osteosarcoma
Bone: Osteoma Fibrous tissue: Fibrosarcoma
Cartilage: Chondroma Cartilage: Chondrosarcoma
Fat: Lipoma Fat: Liposarcoma
Nerve: Neurofibroma Nerve: Neurofibrosarcoma
Nerve sheath: Neurilemmoma Nerve sheath: Neurilemmosarcoma
Glial cells: Glioma Glial cells: Malignant glioma
Lymphoid – malignant lymphoma – Hodgkin’s disease/non-Hodgkins (Reed Sternberg cell/ not reed
Bone Marrow – acute and chronic leukaemia
Germ Cell – Testis – teratoma, seminoma
Ovary - dermoid cyst/mature cystic teratoma.
Invasion and Metastasis
Is the ability of cells to break through basement membrane and then spread through the stroma.
Either into surrounding tissue or lymphatic/vascular channels.
It involves many factors:
1. Malignant cells do not adhere to the same extent as normal cells
Cadherins are Ca2+ dependent glycoproteins present at cells membrane. They
interact homotypically between cells that link them together. Linked to the actin
cytoskeleton by cadherins. Reduced expression occurs in cancer cells allowing cells
to move apart.
Integrins are cell surface glycoproteins composed of two subunits alpha, beta.
Reduced expression, in malignant cell means less contact with stroma allowing
2. Altered cell synthesis of enzymes that breakdown basement membrane and stroma.
Different enzymes can modify stroma allowing cells to break through basement
membrane and spread. Matrix metalloproteinases (MMP2 MMP 9 break type 4
collagen and MMP 1 breaks down type 1 collagen).
3. Factors produced that help cells become motile.
Cells propelled though the degraded basement membrane and lysed stromal matrix
Mediated by cell derived motility factors – autocrine signalling factors
AND cleavage products of matrix proteins
AND other ligands
AND Increased expression of receptors for motility factors.
Metastasis is the ability of malignant cells to invade into lymphatics, blood vessels and cavities and
spread to distant sites. Cells must be able to invade out of channels and colonise a different site.
Cancer cells are selective at where they grow.
They are selective because
Failure of angiogenesis formation of blood vessels. Growth factors produced by cancer
cells e.g. VEGF, can aid invasion. Angiogenic inhibitors try and stop this.
Primary – The site where the malignant neoplasm arises
Secondary – Metastasis, where the carcinoma has come from another organ.
Routes: Lymphatics, blood vessels, coelemic spaces (pleural cavity, peritoneal cavity)
Spread to local and distant lymph nodes, frequent spread of carcinomas.
Spread though capillaries and veins to various organs, common sites are lung, liver, bone and brain.
High occurrence, many malignant neoplasms can metastasise here. Sarcomas e.g. osteosarcomes
and carcinomas e.g. breast, stomach, large intestine, kidney and testis.
Blood travels there twice in the system, systemic and pulmonary.
Common site for carcinomas of large intestine (linked to hepatic portal), bronchial carcinoma, breast
Can cause destruction to bone: bronchial carcinoma, breast carcinoma, thyroid carcinoma, renal
carcinoma. Also brain, thyroid, kidney, prostate and liver Pneumonic: British transport keeps people late
Can cause production of dense bone: prostate.
Can cause problems within the brain and the meninges. From bronchial carcinoma, breast
carcinoma, testicular carcinoma, malignant melanoma. Pneumonic: Bridget Bordeaux, kinky cool
Effects of Tumours
In certain sites a small tumour can have devastating effects. Adversely people can survive a long
time with very extensive metastatic spread.
Local effects of benign neoplasms.
Cause compression – pressure atrophy, altered function
In a hollow viscus cause partial or complete obstruction. Ulceration of surface mucosa and bleeding.
Local effects of malignant neoplasms
Tend to destroy surrounding tissue. In a hollow viscus cause partial or complete obstruction and
constriction. Ulceration occurs. Infiltration around and into nerves, blood vessels and lymphatics.
Haematological – anaemia – due to ulceration, infiltration of bone marrow, haemolysis
-Low white cell and platelets - infiltration of bone marrow, treatment
-Thrombosis – carcinoma of pancreas
Endocrine – Excessive secretion of hormones- neoplasms of endocrine glands
Ectopic hormone secretion – E.g. ACTH, PTH, ADH by small cell carcinoma of bronchus
Cutaneous: Increased pigmentation – gastic, others
Herpes zoster – lymphoma, others
Pruritis (itching) – Jaundice, hodgkin’s
Dermatomyositis – Bronchial carcinoma
Neuromuscular – Sensory/sensorimotor neuropathies
- Myopathy and Myasthenia
- Progressive multifocal leucoencephalopathy
- May mimic metastasis to brain
- Problems with balance.
Cachexia – severe wasting
Malaise – weary
Pyrexia – fever.
How and why do Tumours occurs
Intrinsic factors: Inherited susceptibility, age, immune status and hormones
Extrinsic factors: radiation, chemicals, parasites and viruses
Inherited conditions which predispose to the development of tumours – relate to DNA repair.
Inherited susceptibility to development of a tumour or a group of tumours due to alteration of one
or more genes.
Defects in DNA repair mechanisms
Retinitis pigmentosa photosensitivity susceptible to skin cancer
Ataxia telangiectasia defective response to radiation damage presents in childhood
Fanconi’s anaemia sensitivity to DNA cross-linking agents results in impaired ability to make
Alteration in Gene
Name Gene Where Other
Polyposis coli APC 5q21 High risk in developing colon cancer
Hereditary non Mismatch repair eg. 2p21-22 No polyps but causes colon cancer
Li Fraumeni syndrome p52 17p causes many cancers
Familial breast/ovarian BRCA1/BRCA2 17q21/13q12
Retinoblastoma Rb 13q14
Radiation: Causes a wide range of different types of damage to DNA: Single and double stranded
breaks or base damage. Effects depend on quality of radiation and dose, DNA repair mechanisms
important, incorrect repair of DNA damage mutation.
Chemicals: carcinogenic interacts with DNA in one of a number of ways. For example, it can cause
specific base damage or single strand breaks. Damage repaired but may be imperfect.
Also some act directly, others are changed due to metabolism. If enzymes are required, tumours
occur in that organ, if not then at point of entry.
Polycyclic aromatic hydrocarbons: in coal tar and cigarette smoke
o 3,4-benzpyrene most important converted to active form by hydroxylation aryl
o Causes: lung cancer, bladder cancer and skin cancer
o Beta-napthylamine hydroxylated in liver to 1, hydroxy- 2napthylamine, which is
conjugated with glucuronic acid. deconjugated to active form in urinary tract
o Found in rubber and dye workers forming bladder cancer.
Nitrosamines nitrates/nitrites to nitrosamines by gut bacteria cause GI cancer.
Alkylating Agents bind directly to DNA, nitrogen mustard
Asbestos mesothelioma (cancer in a protective covering of most of the body’s organs)
Aflatoxins liver cancer
Hepatitis B heptatocellular carcinoma
Epstein Barr Burkitt’s lymphoma, nasopharyngeal carcinoma
Human papilloma virus (HPV) cervical carcinoma
Helicobacter gastric cancer and lymphoma
Parasite: Schistosoma bladder cancer
Malaria Burkitt’s lymphoma.
Geographical variation in cancer
Genetic, viruses present or not, parasites present or not, diet (high fibre stops GI cancers),
reproduction and breast cancer (early first pregnancy).
Age: incidence of cancer increases because:
Cumulative exposure to carcinogens
Accumulating genetic lesions
The function of the genes which are modified by radiation/chemicals/viruses is critical for the
development of neoplasms.
Proto-oncogenes: present in all normal cells, involved in normal growth and differentiation. DNA
sequence identical to viral oncogenes. ALTERATION (mutation, amplification, translocation)
C-myc binds to DNA stimulates synthesis this is amplified in neuroblastoma and breast
cancer. Translocation 8 to 14, adjacent to immunoglobulin (inappropriate transcription) in
Ras intracellular signalling mutation, causes colon and lung cancer
C-erbB-2 (HER-2) growth factor receptor, amplification, adenocarcinoma. (Herceptin,
stops agents which cause this).
Ret thyroid carcinoma in children
Tumour suppressor genes: in normal cells the protein encoded by the gene suppresses growth.
Loss/alteration to the gene results in loss of growth suppression. E.g. retinoblastoma/P53.
P53 gene encodes a nuclear protein which binds to and modulates expression of genes important
for DNA repair, cell division and cell death by apoptosis. Found in many cancers.
Carcinogenesis: Long period of time elapses between exposure to stimulus and the emergence of a
Initiating stimulus effect modified by genetic factors, DNA repair
o Agents render the cell susceptible to neoplasm but genetic change.
Promotion hormones, local tissue responses, immune responses.
o Transient exposure to a promoting agent will not cause neoplasm
o They cause increase cell turnover. With continued exposure to the agent cells which
have an initial genetic abnormality develop secondary genetic abnormalities.
Progression Number and type of genes modified
o New genetic mutations occur, with development of sub-clones of neoplastic cells.
Development of Neoplastic cell
To Note: It is not just an alteration to one gene it is an accumulation of alterations and many
factors are involved.
Incidence, Prognosis and treatment
4 most common cancers, breast, lung, large bowel and prostate
<10 – childhood neoplasms (nephroblastoma, neuroblastoma, retinoblastoma), leukaemia, CNS
10-19 – Leukaemia (generally acute myeloid type), osteosarcomes (in long bones)
20-29 – Leukaemia, teratomas, lymphoma
30-39 – Carcinoma, seminoma, lymphoma sarcoma
40-49- carcinoma, lymphoma, glioma, sarcoma
50> - carcinoma, sarcoma, lymphoma, (chronic) leukaemia.
How the tumour has spread, the size of the tumour and the node status.
It is a mixture of biochemical tests, pathology and scans.
Dukes staging for neoplasm of rectum:
A – Not extending through muscularis propria >90% 5 year survival
B – Extending through muscularis propria 70% 5 year survival
C – Lymph nodes involved 30% 5 year survival
TNM (tumour, node, metastasis)
e.g. breast, lung
T1 = <2cm size T2 = 2-5cm T3=Skin and/or chest wall involved
N0- no axillary nodes involved
N1 = mobile nodes involved
M0 – no metastases
M1 – demonstrable metastases
i. one group of nodes involved
ii. two separate groups, same side of diaphragm
iii. nodes involved both sides of diaphragm plus spleen
iv. Bone marrow, lung, other sites
A. no symptoms
B. Fever itching
T1 too small to be seen on scans or felt during examination.
T2 is completely inside the prostate gland
T3 has broken through the capsule of the prostate gland
T4 has spread into other body organs nearby, such as the rectum or bladder.
N0 No cancer cells found in any lymph nodes
N1 One positive lymph node smaller than 2cm across
N2 More than one positive lymph node. Or one that is between 2 and 5cm across
N3 Any positive lymph node that is bigger than 5 cm across
M0 No cancer spread outside the pelvis
M1 Cancer has spread outside the pelvis
Predicts prognosis, how differentiated it is. It is a measure of aggressiveness and how it is likely to
behave. It determines treatment and prognosis.
Prognosis = Grade and stage. They are independent variables
Breast degree of differentiation which means degree of tubule formation, extent of nuclear
variation and number of mitoses.
Prostate scale 1 to 5 of degree of gland formation and architectural pattern. Gleason system.
Grade 1 – well formed glands ... Grade 5 – sheets of cells, poorly formed glands
Squamous cell carcinomas well differentiated (grade 1) to anaplastic (>75% undifferentiated)
Colon G1 looks like normal tissue to grade 4 very abnormal tissue.
(surgery?) Primary depends on nature of tumour and the stage
Cells and tissue of the body and their tumours vary in their capacity to sustain injury. Depends on
phase of cell cycle, repair mechanisms and their oxygenation.
High lymphoma, leukaemia and seminoma
Fairly high squamous carcinomas
Moderate GI, breasta
Drugs used have effects at particular stages of the cell cycle. Effects depend on tumour cells being in
cell cycle. But also have an effect on rapidly diving cells e.g. bone marrow.
Cyclophosphamide – can act on cells in G1, S phase and mitosis
Vincristine – can block cells entering cell cycle and act on mitosis
Methotrexate – acts on cells in S phase.
In breast cancer if HER-2 present as detected by hercep Test, then can use Herceptin for treatment.
Tumour markers are products liberated from tumour into blood stream. May aid diagnosis and can
be used to gauge response to therapy and for follow up.
Alpha fetoprotein – Hepatocellular carcinoma or germ cell tumours
Human chorionic gonadotrophin – trophoblastic tumours
Acid phosphatase or prostate specific antigen – prostatic carcinoma
Carcinoembryonic antigen – GI tract antigen
Hormone products – endocrine tumours
Parathyroid hormone – parathyroid adenoma.
Aims to detect pre-malignant, non invasive and early invasive cancers to improve prognosis
Cervical – relies on cytological examination of smears to detect ‘early’ changes – dysplasia
Factors include – age range screened, population at risk, adequate smear, cytological examination
Breast – Aims to identify invasive cancers before they can be felt (10 -15 mm) and DCIS (ductal
carcinoma in situ)
Relies on mammography between 5-69 years. Factors frequency of screening, age range and
whether all lesions would progress.
Improving prognosis – Identify ‘at risk’ groups familial occupational. Detect at an earlier stage. Lastly