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List the main methods of cell injury

- Hypoxia
- Toxins
- Heat
- Cold
- Trauma
- Radiation
- Micro-organisms
- Immune mecha`nisms


What is Hypoxia

Hypoxia is reduced O2. It is often due to Ischaemia, the interruption of blood supply. Ischaemia is used as a model for understanding the pathogenesis of cell injury:

Reversible Changes:
o Oxidative phosphorylation decreases
o Amount of ATP decreases
o Increased amount of anaerobic glycolysis, decreasing pH (Lactate)
o Low ATP means Na+ accumulates in the cell
o This means the cell swells via osmosis
o Detachment of ribosomes also leads to a decrease in protein synthesis

Irreversible Changes:
o Massive accumulation of cytosolic Ca2+
o Several enzymes activated resulting in cell death

Different cells react differently, e.g. a neurone can only withstand Ischaemic conditions for a few minutes, whereas fibroblasts can last for hours.


What are the structural changes seen in hypoxia

Structural Changes
Structural changes can be seen under the electron microscope

o Swelling
o Chromatin clumping
o Autophagy
o Rinosome dispersal
o Blebs (Little bumps on membrane surface where cytoskeleton has detached)

o Nuclear changes
o Lysosome rupture
o Membrane defects
o Endoplasmic reticulum lysis


LO 1.2 Define Necrosis and Apoptosis

Necrosis – Changes that occur after cell death in living tissue

Apoptosis – Programmed cell death


LO 1.3 Discuss Coagulative Necrosis

o More protein denaturation than enzyme release

o Cellular architecture is somewhat preserved, creating a ‘ghost outline’.

o Tends to be due to Infarcts (Infarct in the brain = Liquefactive)


LO 1.3 Discuss Liquefactive Necrosis

o More enzyme release than protein denaturation

o Tissue is lysed and disappears

o Tends to be due to infection


LO 1.3 Discuss Caseous Necrosis

o Tissue appears amorphous

o “Half way” between Coagulative and Liquefactive

o Caseous necrosis in the lung is very likely to be TB.


LO 1.3 Discuss Fat Necrosis

Occurs when cell death occurs in adipose tissue


LO 1.3 Discuss Gangrene

o Clinical term for grossly visible necrosis

‘Dry’ gangrene
o Coagulative
o E.g. umbilical cord after birth

‘Wet’ gangrene
o Liquefactive
o Infection -> Neutrophils -
> Proteolytic enzymes


What is an Infarct

Necrosis due to ischaemia

Can be white or red, depending on how much haemorrhage there is

White Infarct
o E.g. kidney
o Occlusion of end artery, no peripheral blood vessels, leaving the area entirely without blood

Red Infarct
o E.g. Bowel
o Occlusion of blood vessel leads to build up of blood, which all haemorrhages at once. Increased pressure decreases blood flow, leading to ischaemia and infarct.


LO 2.1 Discuss the major causes and biological purposes of acute inflammation

Acute inflammation is the response of living tissue to injury, initiated to limit the tissue damage.

Causes of Acute Inflammation:
o Microbial infections - E.g. Pyogenic Organisms
o Hypersensitivity reactions (acute phase)
o Physical agents
o Chemicals
o Tissue necrosis


LO 2.2 List the macroscopic features of acute inflammation

Calor – Heat
Rubor – Erytherma (Redness)
Tumor – Oedema (Swelling)
Dolor – Pain

And Loss of function


LO 2.3 Characterise the microscopic features of acute inflammation, including how they are brought about and relate to the macroscopic ones

1. Vasodilation
Small adjacent blood vessels dilate with increased blood flow.

2. Gaps form in endothelium
Endothelial cells swell and retract; there is no longer a completed intact internal lining.

3. Exudation
Vessels become leaky. Water, salts and small plasma proteins leak through. (Exudate)

4. Margination and Emigration
Circulating neutrophils adhere to swollen endothelial cells. (Margination.)
Neutrophils then migrate through the vessel basement membrane. (Emigration).

5. Macrophages and Lymphocytes
Migrate in a similar way to Neutrophils.


LO 2.4 Briefly mention some of the chemical mediators of acute inflammation

Vasodilation -Histamine, Prostaglandins, C3a, C5a

Inc. Vascular Permability -Histamine, Prostaglandins, Kinins

Emigration of Leukocytes - Leukotrienes, IL-8, C5a


LO 2.5 Discuss the action of neutrophils

Neutrophils phagocytose microorganisms, by making contact, recognising and internalising them. Phagosomes are then fused with lysosomes to destroy the contents.

Neutrophils move to the site of injury by chemotaxis. An activated neutrophil may also release toxic metabolites and enzymes, causing damage to the host tissue.


LO 2.6 Discuss the systemic consequences of acute inflammation

Decreased appetite, raised heart rate, altered sleep patterns and changes in plasma concentration of Acute Phase Proteins, such as C-Reactive Protein (CRP), Fibrinogen and 1-antitrypsin.

The spread of micro-organisms and toxins can lead to Shock, a clinical syndrome of circulatory failure (See CVS Session 12)

Endogenous pyrogens (substances that produce fever) IL-1, TNFA and prostaglandin are produced.

IL-1 and TNFA produce an accelerated release from marrow. Macrophages, T-Lymphocytes produce colony-stimulating factors.


LO 2.7 What may happen after the development of acute inflammation?

1. Complete resolution
2. Continued acute inflammation with chronic inflammation (Abscess)
3. Chronic inflammation and fibrous repair, probably with tissue regeneration
4. Death

All mediators of acute inflammation have short half-lives and may be inactivated by degradation, dilution in exudate or inhibition.

Gradually all of the changes of acute inflammation reverse, and the vascular changes stop. Neutrophils no longer marginate, and the vessel permeability and calibre returns tot normal.
Therefore, the exudate drains via the lymphatics, fibrin is degraded by plasmin/other proteases and the neutrophils die.

Damaged tissue may then be able to regenerate, but if tissue architecture has been destroyed, complete resolution is not possible.


LO 2.8 Describe some possible complications of acute inflammation

Blockage of tubes, e.g. bile duct, intestine

Compression, e.g. cardiac tamponade

Loss of fluid
E.g. burns

Pain and loss of function
Especially if prolonged


LO 2.9 Give a few clinical examples of acute inflammation - Skin Blister

Caused by heat, sunlight, chemicals

Pain and profuse exudate

Collection of fluid strips off overlying epithelium

Inflammatory cells relatively few, therefore exudate is clear

Resolution or scarring


LO 2.9 Give a few clinical examples of acute inflammation - Abscess

Solid Tissues

Inflammatory exudate forces tissue apart

Liquefactive necrosis in centre

May cause high pressure, therefore pain

May cause tissue damage and squash adjacent structures


LO 2.9 Give a few clinical examples of acute inflammation - Pericarditis

Inflammation of serous cavity

Pericardium becomes inflamed and increases pressure on the heart


LO 2.10 Discuss inherited disorders of the acute inflammatory process - general

Disorders of Acute Inflammation are rare diseases, but illustrate the importance of apparently small parts of this complex web of mechanisms.

Examples include:
o A1 anti-trypsin deficiency
o Inherited complement deficiencies
o Defects in neutrophil function
o Defects in neutrophil numbers


LO 2.10 Discuss inherited disorders of the acute inflammatory process - Hereditary Angio-Oedema

o Hereditary Angio-Oedema is caused by a deficiency of C1 inhibtor.
o C1 is a complement protein that cleaves C2 and C4 to form C3.
o C1 inhibitor does not only inhibit C1, but Bradykinin too. Uninhibited Bradykinin vastly increases the permeability of endothelia, causing Oedema.
o Hereditary Angio-Oedema is treated with C1 inhibitor infusion or fresh frozen plasma.


LO 2.10 Discuss inherited disorders of the acute inflammatory process - α1-antitrpysin Deficiency

o α1-antitrpysin inhibits Elastase.
o Without this inhibition elastase breaks down lung/liver tissue
o Causes emphysema and Liver Sclerosis.


LO 2.10 Discuss inherited disorders of the acute inflammatory process - Chronic Granulomatous Disease

o Recessive sex linked
o Immune phagocytes can’t form ROS
o Can’t kill some bacteria without ROS
o Granulomas formed in an attempt to contain the bacteria


What is chronic inflamation

Chronic response to injury with associated FIBROSIS


LO 3.1 Discuss how Chronic Inflammation Arises

1. May ‘take over’ from acute inflammation
o If damage is too severe to be resolved within a few days…

2. May arise de novo
o Some autoimmune conditions (E.g. RA)
o Some Chronic Infections (E.g. viral hepatitis)
o “Chronic low-level irritation”

3. May develop alongside acute inflammation
o In severe, persistent or repeated irritation


LO 3.2 List the effects of Chronic Inflammation

o Fibrosis
Gall bladder (chronic cholecystitis), chronic peptic ulcers, cirrhosis

o Impaired function
Chronic Inflammatory Bowel Disease
Rarely, increased function, e.g. mucus secretion, thyrotoxicosis

o Atrophy
Gastric mucosa, adrenal glands

o Stimulation of immune response
Macrophage-Lymphocyte interactions


LO 3.3 List the cells principally involved in chronic inflammation and the role of each - Macrophages

Important in acute and chronic inflammation

Various levels of activation

o Phagocytosis and destruction of debris and bacteria
o Processing and presentation of antigen to the immune system
o Synthesis of cytokines, complement components, clotting factors and proteases
o Control of other cells via cytokine release


LO 3.3 List the cells principally involved in chronic inflammation and the role of each - Lymphocytes

Sometimes called ‘chronic inflammatory cells’

o Complex, mainly immunological
o B Lymphocytes (Plasma Cells) differentiate to produce antibodies
o T Lymphocytes involved in control (CD4+) and some cytotoxic (CD8+) functions


LO 3.3 List the cells principally involved in chronic inflammation and the role of each - Eosinophils

Allergic reactions
Parasite infections
Some tumours


LO 3.3 List the cells principally involved in chronic inflammation and the role of each - Fibroblasts/Myofibroblasts

Recruited by macrophages, make collagen


LO 3.3 List the cells principally involved in chronic inflammation and the role of each - Giant’ Cells

Giant cells are multinucleate cells made by the fusion of macrophages, through the process of frustrated phagocytosis. There are several types recognised:

Langhans -> Tuberculosis
Foreign Body Type
Touton -> Fat Necrosis


LO 3.4 Give some major clinical examples of chronic inflammation, how they arise, the complications which ensue and the treatment which is available -
Chronic Cholecystitis (Fibrosis)

Repeated obstruction of the gall bladder with gallstones. Repeated acute inflammation leads to chronic inflammation and fibrosis of the gall bladder wall.

Treated with the surgical removal of the gall bladder.


LO 3.4 Give some major clinical examples of chronic inflammation, how they arise, the complications which ensue and the treatment which is available - Gastric Ulceration (Fibrosis)

Acute gastritis (alcohol, drugs)
Chronic gastritis (Helicobacter pylori)

Ulceration occurs because of an imbalance between acid production and mucosal defence.

H. pylori triple treatment:
o PPI Inhibitor – E.g. Omeprazole
o 2 Antibiotics – E.g. Clarithromycin / Amoxicillin


LO 3.4 Give some major clinical examples of chronic inflammation, how they arise, the complications which ensue and the treatment which is available - Inflammatory Bowel Disease (Impaired Function)

Inflammatory disease affecting the large and small bowl. Patients present with diarrhoea, rectal bleeding and other symptoms.

Ulcerative colitis
o Superficial
o Diarrhoea
o Bleeding
o Treat with immunosuppression, surgical removal of the large bowel (colectomy)

Crohn’s disease
o Transmural
o Strictures
o Fistulae (Abnormal connection between two epithelia)
o Treat with lifestyle modifications, diet/hydration, immunosuppression


LO 3.4 Give some major clinical examples of chronic inflammation, how they arise, the complications which ensue and the treatment which is available - Liver Cirrhosis (Fibrosis + Impaired Function)

Chronic inflammation with fibrosis leading to disorganisation of architecture and attempted regeneration -> Cirrhosis.

Common causes of cirrhosis:
Infection with HBV/HCV
Fatty liver disease
Drugs and toxins

Liver cirrhosis cannot be reversed, so treatment involves lifestyle changes to prevent further damage, and transplantation of a new liver if necessary.


LO 3.4 Give some major clinical examples of chronic inflammation, how they arise, the complications which ensue and the treatment which is available - Thyrotoxicosis (Increased Function)

Graves disease


LO 3.4 Give some major clinical examples of chronic inflammation, how they arise, the complications which ensue and the treatment which is available - Rheumatoid arthritis

Autoimmune disease

Localised and systemic immune response

Localised chronic inflammation leads to joint destruction

Systemic immune response (Can affect other organs and cause amyloidosis)


LO 3.5 Describe and give examples of Granulomatous Inflammation

Chronic inflammation and immune responses overlap.

Immune diseases cause pathology by chronic inflammation

Chronic inflammatory processes can stimulate immune responses

Granulomas form when the immune system walls off something that it is unable to eliminate, for example bacteria, fungi and other foreign material. Granulomas arise with persistent, low-grade antigenic stimulation and hypersensitivity.


Main Causes of Granulomatous Inflammation

Mildly irritant foreign material

o Mycobacteria: Tuberculosis, leprosy
o Syphilis
o Some fungi

Unknown causes
o Sarcoid
o Wegener’s Granulomatosis
o Crohn’s disease

Caused by mycobacteria
Produces no toxins/lytic enzymes
Causes disease by persistence and induction of cell-mediated immunity


Outcomes of Granulomatous Inflammation

1. Arrest, fibrosis, scarring
2. Erosion into bronchus
3. Tuberculous empyema (collection of pus)
4. Erosion into blood stream


LO 4.1 Understand and describe Fibrous repair - the first step

Initiate fibrous repair by combining to form granulation tissue.

1. Cell Migration

Inflammatory Cells
o Phagocytosis of debris: Neutrophils, macrophages
o Chemical Mediators: Lymphocytes, macrophages

Endothelial Cells
o Angiogenesis

o ECM proteins e.g. collagen
o Wound contraction


What is Fibrous repair

The replacement of functional tissue by scar tissue


LO 4.1 Understand and describe Fibrous repair - the second step

2. Angiogenesis

The development of a blood supply is vital to wound healing, to provide access to the wound for the above cells, and to deliver oxygen and other nutrient.
o Endothelial proliferation induced by proangiogenic growth factors such as VEGF

o Preexisting blood vessels sprout new vessels

o These mechanisms are exploited by malignant cells

o Endothelial proteolysis of basement membrane

o Migration of endothelial cell via chemotaxis

o Endothelial proliferation

o Endothelial maturation and
tubular remodelling

o Recruitment of periendothelial cells


LO 4.1 Understand and describe Fibrous repair - the third step

3. ECM production/remodelling

o Supports and anchors cells
o Separates tissue compartments (e.g. basement membrane)
o Sequesters growth factors
o Allows communication between cells
o Facilitates cell migration


What are the 3 main stages of fibrous repair

Key Components:
1. Cell migration
2. Blood vessels – angiogenesis
3. ECM production/remodelling


Describe the actual steps of fibrous repair as a whole

1. Inflammatory cell infiltrate
Blood clot forms
Acute inflammation around the edges
Chronic inflammation – Macrophages and lymphocytes migrate into the clot

2. Clot replaced by granulation tissue (A combination of capillary loops and myofibroblasts).
Angiogenesis – Capillaries and lymphatics sprout and infiltrate
Myo/fibroblasts migrate and differentiate.
ECM is produced by myo/fibroblasts

3. Maturation
Comparatively long lasting
Cell population falls
Collagen increases, matures and remodels
Myofibroblasts contract – Reduces volume of defect
Vessels differentiate and are reduced
Left with fibrous scar


Describe the control of fibrous repair

Inflammatory cells are recruited by chemotaxis

Angiogenesis is due to angiogenic cytokines

Fibrosis is due to macrophages releasing pro-fibrotic cytokines causing fibroblast proliferation.


LO 4.2 What is Regeneration

Regeneration – The replacement of dead or damaged cells by functional, differentiated cells. Differentiated cells are derived from stem cells.


What are Stem Cells

Stem cells have potentially limitless proliferation, daughter cells either remain as a stem cell to maintain the stem cell pool or differentiate to a specialised cell type. In early life stem cells develop into many different cell types.

Unipotent – Can only produce one type of differentiated cell – E.g. epithelia

Multipotent – Can produce several types of differentiated cell – E.g. Haematopoietic

Totipotent – Can produce any type of cell – I.e. embryonic stem cells


Describe the propensity of different cell types to regenerate

1. Labile Cells
E.g. Epithelial or haematopoietic cells
Normal state is active cell division: G1 – M - G1
Usually rapid proliferation

2. Stable cells
E.g. Hepatocytes, osteoblasts, fibroblasts
Resting state: G0
Speed of regeneration variable

3. Permanent cells
E.g. Neurones, cardiac myocytes
Unable to divide – G0
Unable to regenerate


Describe the factors controlling regeneration

Growth factors
o Promote proliferation in the stem cell population
o Promote expression of genes controlling cell cycle
o Hormones, oestrogen, testosterone, growth hormone
o Autocrine, paracrine and endocrine cells from many cell types, inflammatory, mesenchyme etc.
o Proteins, PDGF, EGF etc

Contact between basement membranes and adjacent cells
o Signalling through adhesion molecules
o Inhibits proliferation in intact tissue
o Contact inhibition
o Loss of contact promotes proliferation
o Exploited in cancer


LO 4.3 Describe and discuss the healing of a clean incised skin wound

Healing by Primary Intention

Incised wound
Apposed edges
Minimal clot/granulation tissue
Epidermis regenerates
Dermis undergoes fibrous repair
Sutures out at 5-10 days. Approx 10% normal strength.
Maturation of scar continues up to two years
Minimal contraction and scarring, good strength
Risk of trapping infection -> Abscess


LO 4.4 Describe and discuss the healing of a large skin defect

Healing by Secondary Intention

Infarct, ulcer, abscess or any large wound

Quantitative differences
o Unapposed wound edges
o Large clot dries to form ‘scab’
o Epidermis regenerates from the base up
o Repair process produces much more granulation tissue

Comparison with primary intention:
o Produces more contraction to reduce volume of defect
o Produces a larger scar; not necessarily weaker
o Takes longer


LO 4.5 Discuss factors influencing the efficacy of healing and repair - local factors

Local Factors
1. Type, size, location of wound
2. Apposition, lack of movement
o Skin wounds, bone fractures, severed nerves
3. Blood supply: Arterial, venous
4. Infection: Suppuration, gangrene, systemic
5. Foreign material: dirt, glass, sutures, necrotic tissue
6. Radiation damage


LO 4.5 Discuss factors influencing the efficacy of healing and repair - General Patient Factors

General Factors
1. Age
2. Drugs (steroids) and hormones
3. General dietary deficiencies e.g. protein
4. Specific dietary deficiencies
o Vitamin C – Alpha chain hydroxylation
o Essential amino acids
5. General State of Health
o Chronic diseases, e.g. diabetes, RA etc
6. General Cardiovascular status


LO 4.6 Describe and discuss special aspects of haling and repair in various tissues

Cardiac Muscle
o Fibrosis

o Callus formation

o Acute damage -> Regeneration
o Chronic damage -> Cirrhosis
Live hepatocytes have some regenerative capacity, but hepatocyte architecture does not regenerate. The imbalance between hepatocyte regeneration and the ability to regenerate architecture leads to cirrhosis and nodules.

Peripheral Nerve
o Wallerian degeneration
o Proximal degeneration, distal proliferation (~1mm/day)

o No regenerative capacity
o Glial cells can proliferate -> Gliosis

o Cardiac / Smooth -> Permanent tissues. Will be replaced by a scar
Vascular smooth muscle has some, limited, regeneration
o Skeletal
Limited regenerative capacity due to satellite cells


LO 5.1 Define and discuss Haemostasis

Haemostasis is the body’s response to stop bleeding and loss of blood.

Successful Haemostasis depends on:
o Vessel wall - Constricts to limit blood loss
o Platelets
- Adhere to the damages vessel wall and to each other
-Form platelet plug
o Coagulation System
- Cascade, series of inactive components -> active components
- 1ml of blood can generate enough Thrombin to convert all of the fibrinogen in the body to fibrin, so tight regulation is required
- Balance of procoagulant and anticoagulant forces
o Fibrinolytic System


LO 5.2 Discuss the regulation of the coagulation system

Thrombin positively feeds back on factors V, VIII and XI
- Thrombin inhibitors
o Anti-thrombin III*
o Alpha 1 anti-trypsin
o Alpha 2 macroglobulin
o Protein C/S*

*Inherited deficiencies in antithrombin III or Protein C/S -> Thrombophilia and thrombosis

The breakdown of fibrin, by Plasmin.

Fibrinolytic therapy is widely used, e.g. Streptokinase, which activates Plasminogen. They are known as clot/thrombus busters. This is a very drastic treatment, used only in a serious situation, e.g. coronary artery occlusion or thrombus cutting off circulation to a limb.


LO 5.3 Define Thrombosis

Thrombosis – The formation of a solid mass of blood within the circulatory system during life


What are the factors affecting thrombus formation

Virchow’s Triad

Changes in blood flow
o Stagnation, turbulence

Changes in vessel wall
o Atheroma, injury, inflammation

Changes in blood components
o Smokers, pregnancy


Compare arterial and venous thrombi

Arterial Thrombi
Lines of Zahn
Lower Cell Content

Venous Thrombi
Deep Red
Higher Cell content


LO 5.4 Discuss the effects of thrombosis

- Ischaemia
- Infarction
- Depends on site and collateral circulation

- Congestion
- Oedema
- Ischaemia (If Tissue Pressure due to Oedema > Arterial Pressure)
- Infarction


LO 5.5 Discuss the outcomes of thrombosis

Lysis – Complete dissolution of the thrombus, Fibrinolytic system active, blood flow re-established. This is most likely when thrombi are small

Propagation – The progressive spread of thrombosis, distally in arteries, proximally in veins

Organisation – A reparative process with ingrowth of fibroblasts and capillaries. Lumen remains obstructed

Recanalisation – Blood flow re-established but usually incompletely. One of more channels formed through organising thrombus.

Embolism – Part of the thrombus breaks off, travels through the bloodstream and lodges as a distant site, e.g. coronary artery -> MI


LO 5.6 Define Embolism

Embolism – The blockage of a blood vessel by a solid, liquid or gas at a site distant from its origin.


What are the types of embolism

- Thrombo-emboli - 90%
- Air
- Amniotic fluid
- Nitrogen (divers get ‘the bends’)
- Medical equipment
- Tumour cells


Where do thromboembolisms travel to?

From Systemic Veins
Pass to the lungs (Pulmonary Emboli), as they will not get stuck in the large veins near the heart. The next time the emboli meets a vessel smaller than itself where it can get stuck is the lung.

From the Heart
Pass via the aorta to renal, mesenteric and other arteries

From Atheromatous Carotid Arteries
To the brain (Stroke)

From Atheromatous Abdominal Aorta
To the arteries of the legs


What is a Pulmonary Embolism

Massive PE > 60% reduction in blood flow - Rapidly fatal

Major PE – Medium sized vessels blocked
o Shortness of breath, cough, blood stained sputum

Minor PE – Small peripheral pulmonary arteries blocked
o Asymptomatic or minor shortness of breath

Recurrent PE’s -> Pulmonary hypertension


What are the causes Deep Vein Thrombosis

o Immobility/bed rest
o Post-operative
o Pregnancy and post-partum
o Oral contraceptives
o Severe burns
o Cardiac failure
o Disseminated cancer


What are the treatments of Deep Vein thrombosis

Intravenous Heparin
o Anticoagulant
o Co-factor for anti-thrombin III

Oral Warfarin
o Interferes with synthesis of vitamin K dependent clotting factors
o Slow effect


Descrbie Fat Embolism - causes and symptoms

o Fractures of long bones or Lacerations of adipose tissue

Rash, shortness of breath, confusion


Describe Cerebral Embolism

Atrial fibrillation -> Stasis -> Thrombus

If in left heart, can go to the brain and cause a stoke or transient ischaemic attack


Describe an Iatrogenic Embolism

Embolism due to medical treatment, e.g. air embolism from an injection


Nitrogen Embolism

Nitrogen bubbles form in the blood with rapid decompression e.g. The bends


Describe Disseminated Intravascular Coagulation (DIC)

DIC is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases.
Small clots form throughout the body, disrupting normal coagulation as they use up all the clotting factors.
Abnormal bleeding occurs from the skin.

Triggers: Infection, trauma, liver disease, obstetric complications


Describe Haemophilia

Type A and Type B

X-linked recessive, so more common in boys
Deficiencies in different clotting factors
o A = Factor VIII
o B = Factor IX

o Can be mild, moderate or severe due to various mutations
o Due to a nonsense point mutation
o Haemorrhage into major o joints, synovial hypertrophy, pain
p Muscle bleeding causes pressure and necrosis of nerves (painful)
p Can haemorrhage into retroperitoneum / urinary tract
o Treat with self-administered factor replacement therapy


Describe Thrombocytopenia

Platelet count is way below the reference range

Due to either:
o Failure of platelet production
o Increase in platelet destruction
o Sequestering of platelets

Usually accompanied by a bone marrow dysfunction, E.g. leukaemia, anaemia

If it is due to sequestering, cause may be DIC


LO 6.1 Define Atheroma, Atherosclerosis, Arteriosclerosis

Atheroma – The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

Atherosclerosis – The thickening and hardening of arterial walls as a consequence of atheroma

Arteriosclerosis – The thickening of the walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus


LO 6.2 Describe the morphological appearance of Atheroma - macroscopic


Fatty Streak
o Lipid deposits in the intima
o Yellow, slightly raised

Simple Plaque
o Raised yellow/white
o Irregular outline
o Widely distributed
o Enlarge and coalesce

Complicated Plaque
o Thrombosis
o Haemorrhage into plaque
o Calcification
o Aneurysm formation


LO 6.2 Describe the morphological appearance of Atheroma - Microscopic

Early changes
o Proliferation of smooth muscle cells
o Accumulation of foam cells
o Extracellular lipid

Later changes
o Fibrosis
o Necrosis
o Cholesterol clefts - Cholesterol deposition in the tissue, not the plaque
o +/- Inflammatory cells


Describe the cellular events in atheroma formaiton

Endothelial damage -
> Platelets -> PDGF -> Smooth muscle proliferation

Proliferation and migration of smooth muscle takes the lipid with it.

Macrophages arrive and phagocytose the fat, becoming foam cells


LO 6.3 Explain some of the effects of severe atherosclerosis at specific anatomical sites - Coronary Artery

Ischaemic Heart Disease
o Sudden Death
o MI
o Angina pectoris
o Arrhythmias
o Cardiac Failure


LO 6.3 Explain some of the effects of severe atherosclerosis at specific anatomical sites - Cerebral Ischaemia

Transient ischaemic attack
o Infarction of part of the brain. Symptoms for 24hrs (transient)

Cerebral infarction (stroke)

Multi-infarct dementia


LO 6.3 Explain some of the effects of severe atherosclerosis at specific anatomical sites - Mesenteric Ischaemia

Ischaemic colitis
Intestinal infarction
Anneurism due to the high pressure, hardening and weakening


LO 6.3 Explain some of the effects of severe atherosclerosis at specific anatomical sites - Peripheral Vascular Disease

Intermittent claudication
Leriche syndrome
Ischaemic rest pain (Intermittent claudication in the iliac artery -> Gluteal pain)


LO 6.4 Discuss the risk factors for Atheroma

o Slowly progressive throughout adult years
o Risk factors operate over years

o Women protected relatively before menopause
o Presumed hormonal basis

o High plasma cholesterol associated with atheroma
o LDL most significant
o HDL protective
o Familial Hyperlipidaemia
o Corneal Arcus
o Xanthalasma

Cigarette Smoking
o Risk factor for IHD

o Strong link between IHD and high BP
o Endothelial damage caused by raised BP?

Diabetes mellitus
o Doubles IHD risk
o Also associated with high risk of cerebrovascular and peripheral vascular disease

o >5 units/day  Inc risk of IHD

o Chlamydia
o Helicobacter pylori

Lack of exercise
Oral contraceptives


LO 6.5 Discuss the Unifying Hypothesis of Atherogenesis

Endothelial injury due to
o Raised LDL
o ‘Toxins’ e.g. cigarette smoke
o Hypertension
o Haemodynamic stress

Endothelial injury causes
o Platelet adhesion, PDGF release, SMC proliferation and migration
o Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages
o Migration of monocytes into intima

Stimulated SMC produce matrix material - Foam cells secrete cytokines causing

o Further SMC stimulation
o Recruitment of other inflammatory cells


LO 6.6 Discuss the prevention of Atheroma

- Stop smoking
- Modify diet
- Treat hypertension
- Treat diabetes
- Lipid lowering drugs


Coronary Heart Disease

Genetic – Disorders can increase risk, e.g. Familial Hypercholesterolemia

Geographical – Less common in the Mediterranean (diet)

Ethnicity – CHD common in Asians

Risk Factors
- Smoking
- Gender – More common in men
- Hypertension – Increased epithelial damage (see cellular events above)
- Diabetis – Increased IHD risk
- Alcohol - > 5 units per day is harmful
- Infection – H. pylori (recent evidence, unsure how but there is an association)


LO 7.1 Describe the different phases of the cell cycle and their control

The restriction (R) point, towards the end of G1, is the most critical checkpoint.

Passage beyond the R point is governed by the phosphorylation of the Retinoblastoma Protein (pRb)


LO 7.2 Describe Labile, stable and permanent cells

1. Labile Cells
o E.g. Epithelial or haematopoietic cells
o Normal state is active cell division: G1 – M - G1
o Usually rapid proliferation

2. Stable cells
o E.g. Hepatocytes, osteoblasts, fibroblasts
o Resting state: G0
o Speed of regeneration variable

3. Permanent cells
o E.g. Neurones, cardiac myocytes
o Unable to divide – G0
o Unable to regenerate

Tissue stem cells power proliferative capacity, replenishing loss of differentiated cells.

Labile Cell populations
o Stem cells divide persistently to replenish losses

Stable Cell populations
o Stem cells normally quiescent or proliferate very slowly
o Proliferate persistently when required

Permanent Cell Populations
o Stem cells present, but cannot mount an effective proliferative response to significant cell loss


Define Regeneration

Replacement of cell losses by identical cells to maintain tissue or organ size.


Define Hyperplasia

Increase in tissue or organ size due to increased cell numbers.

Can only occur in labile or stable cell populations

Physiological Causes
o Proliferative endometrium
o Bone marrow at altitude

Pathological Causes
o Thyroid goitre


Define Hypertrophy

Increase in tissue or organ size due to increased cell size.

Permanent cells cannot divide, so increase organ size by hypertrophy

In cells where division is possible, hypertrophy may occur with hyperplasia

Physiological Causes
o Skeletal Muscle
o Pregnant uterus (hypertrophy AND hyperplasia)

Pathological Causes
o Ventricular cardiac muscle hypertrophy
o Bladder smooth muscle hypertrophy


Define Atrophy

Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells.

Organ/Tissue atrophy is typically due to a combination of atrophy and apoptosis

Physiological Causes
o Ovarian atrophy in post menopausal women

Pathological Causes
o Muscle Atrophy (denervation)
o Cerebral atrophy (Alzheimer’s disease)


Define Metaplasia

Reversible change of one DIFFERENTIATED cell type to another.

Most clearly adaptive in epithelial tissues

Change in epithelium to be more suited to new environment
o E.g. Smoker. Pseudostratified Ciliated -> Squamous cells (more robust)

Sometimes a prelude to dysplasia and cancer


Define Aplasia

Complete failure of a specific tissue or organ to develop


Define Hypoplasia

Incomplete development of a tissue or organ


Define Dysplasia

Abnormal maturation of cells within a tissue


LO 9.1 Define Neoplasia

Benign Neoplasia – The abnormal growth of cells, which persists after initiating stimulus has been removed.
o Rounded mass due to the pushing growth. Remains at site of origin.

Malignant Neoplasm – Abnormal growth of cells, which persists after initiating stimulus has been removed AND invades and spreads to distant sites
o Irregular mass due to infiltrative growth edges. May spread to distant site forming secondary growth (Metastasis).


LO 9.2 Describe the alterations to DNA which cause neoplasia

For neoplasms to develop there has to be a change in DNA. The change must cause an alteration in cell growth and behaviour, and the change must be not lethal and passed onto daughter cells.

Neoplasms arise from a series of genetic alterations (~7).

These alterations occur in Proto-oncogenes OR Tumour Suppressor Genes. If a mutation permanently activates a proto-oncogene so it becomes an Oncogene or if a Tumour Suppression gene is permanently inactivated neoplasia will occur.

Neoplastic cells have key differences from normal cells:
Self sufficient growth signals
o HER2 gene amplification
Resistance to anti-growth signals
o CDKN2A gene deletion
Grow indefinitely
o Telomerase gene activation
Induce new blood vessels
o Activation of VEGF expression
Resistance to apoptosis
o BCL2 gene translocation
Invade and produce metastases
o Altered E-cadherin expression


LO 9.3 Describe the clonality of neoplasms

Neoplasms are monoclonal. They are a cell population that are descended from a common ancestral cell (the cell which originally acquired the mutation to escape normal growth control).


LO 9.4 Describe and compare benign and malignant tumours

Variation in size and shape (Pleomorphism) minimal
Low mitotic count. Mitoses have normal form.
Retention of tissue specialisation
(Well differentiated)

Variation in size and shape (Pleomorphism) minimal to marked
Low to high mitotic count. Mitoses may have abnormal forms.
Variable loss of tissue specialisation
(Well to poorly differentiated)


LO 9.6 Distinguish between in-situ and malignancy

Carcinoma In-Situ has all of the features of a malignant neoplasm in an epithelium, but no invasion through the basement membrane.


LO 9.7 Discuss how Neoplasms are classified/named

Neoplasms are classified by:
1. Benign or malignant

2. By tissue type
o Epithelial
o Connective tissue
o Lymphoid/haematopoietic
o Germ cell


LO 9.8 Describe the basic histological types of benign and malignant neoplasm - Benign Epithelial Neoplasms


Stratified Squamous
o Squamous papilloma
o Any tumour with finger-like projections
o E.g. Skin, buccal mucosa

o Transitional cell papilloma
o E.g. Bladder mucosa

o Adenoma
o E.g. Adenomatous polyp of the colon


LO 9.8 Describe the basic histological types of benign and malignant neoplasm - Malignant Epithelial Neoplasms

Malignant – CARCINOMA

Squamous Cell Carcinoma
o Skin, larynx, oesophagus

Transitional Cell Carcinoma
o Bladder, ureters

o Stomach, colon, lung, prostate, breast, pancreas

Basal Cell Carcinoma
o Skin


What is the name for as benign and a malignant neoplasm of Smooth Muscle

Leiomyoma - Leiomyosarcoma


What is the name for as benign and a malignant neoplasm of Fibrous Tissue

Fibroma - Fibrosarcoma


What is the name for as benign and a malignant neoplasm of Bone

Osteoma - Osteosarcoma


What is the name for as benign and a malignant neoplasm of Cartilage

Chondroma - Chondrosarcoma


What is the name for as benign and a malignant neoplasm of Fat

Lipoma - Liposarcoma


What is the name for as benign and a malignant neoplasm of Nerve

Neurofibroma - Neurofibrosarcoma


What is the name for as benign and a malignant neoplasm of Nerve Sheath

Neurilemmoma - Neurilemmosarcoma


What is the name for as benign and a malignant neoplasm of Glial cells

Glioma - Malignant Glioma


Lymphoid and Haematopoietic Neoplasms

All regarded as malignant (Cells in blood already)

Lymphoid = Lymphoma (B and T)
- Occurs in lymphoid tissue
- Usually lymph nodes
- Hodgkins Disease and Non Hodgkins lymphoma

Haematopoietc = Acute and Chronic Leukaemia
- Occurs in bone marrow
- Abnormal cells then enter the blood



- Sounds like a benign muscle neoplasm

But its not! Malignant plasma cell neoplasm in bone marrow, destroying adjacent bone


Germ Cell Neoplasms

Malignant Teratoma

Benign Teratoma (Dermoid cyst)


LO 10.1 Define invasion and metastasis

Invasion – The ability of cells to break through the basement membrane and spread
o Direct invasion – Into surrounding tissue
Into Lymphatic/vascular channels

Metastasis – The spread of a malignant tumour to a distant (i.e. non adjacent) site
o A metastasis is often referred to as a secondary tumour, with the site of origin being the primary tumour.


LO 10.2 Describe the mechanisms facilitating invasion and metastasis

Altered Cell Adhesion
Altered Enzyme Synthesis and Interaction


Descirbe Altered Cell Adhesion in cancer

Cell – Cell Interactions
Reduced expression of Cadherins, which normally bind cells together, allows cells to move apart.

Cell – Stroma Interactions
Reduced expression of Integrins in malignant cells allows for movement.


Describe Altered Enzyme Synthesis and Interaction in cancer

Metastatic cells synthesise and release Matrix Metalloproteinases. These enzymes digest collagen, allowing the metastatic cells to digest the ECM and move to and break through the basement membrane.
MMP1 – Type I Collagen
MMP2/9 – Type IV Collagen


Describe Angiogenesis in cancer

Once a tumour has reached 1-2mm3 it’s growth is halted due to lack of nutrients/oxygen. This alters the tumour’s microenvironment, making it hypoxic. This causes the upregulation of pro-angiogenesis factors, e.g. angiopoietin, VEGF.

This causes the growth of new, thin wall blood vessels that not only allows for the continued growth of the tumour but provides another opportunity to enter the bloodstream as well.


LO 10.3 Describe the routes and common sites of metastasis- Lymphatics

Spread to local and distant lymph nodes
Frequent route of spread of carcinomas (malignant epithelial tumour)
Can involve lymphatics of the lung



Spread through capillaries and veins to various organs. Common sites are lung, liver, bone and brain.

To Lung
o Can occur with a wide range of malignant neoplasms
o Sarcomas, e.g. osteocarcoma
o Carcinomas, e.g. breast, stomach, large intestine
o Kidney, e.g. “cannonball”
o Testis, e.g. malignant teratoma

To Liver
o Common site for carcinomas of the large intestine (portal vein)
o Carcinomas, e.g. Bronchial, Breast

To Bone
o Can cause destruction of bone, leading to pathological fracture
Carcinomas, e.g. Bronchial, Breast, Thyroid, Renal
o Can cause produce of dense bone (Osteosclerosis) - Prostate

To Brain
o Cause a wide range of neurological symptoms and act as a space occupying lesion (SOL)


In what cancers are metastases common?

Bronchial carcinoma
Breast carcinoma
Testicular carcinoma
Malignant melanoma


LO 10.4 Describe the local effects of benign and malignant neoplasms - Benign

Cause compression
o Pressure atrophy
o Altered function e.g. pituitary

In a hollow viscus cause partial or complete obstruction

Ulceration of surface mucosa

Space occupying lesion (brain)


LO 10.4 Describe the local effects of benign and malignant neoplasms - Malignant

Tend to destroy surrounding tissue

In a hollow viscus cause partial or complete obstruction, constriction


Infiltration around and into nerves, blood vessels, lymphatics

Space occupying lesion (brain)


LO 10.5 Describe the systemic effects of benign and malignant neoplasms -

- Anaemia
o Due to malignant infiltration of bone marrow (Leukaemia, metastasis)

Low white cell and platelets
o Infiltration of bone marrow
o Consequence of treatments

o Carcinoma of pancreas


LO 10.5 Describe the systemic effects of benign and malignant neoplasms -

Excessive secretion of hormones
o Benign and malignant neoplasms of endocrine glands e.g. parathyroid hormone, corticosteroids

Ectopic hormone secretion
o ACTH by small cell carcinoma of bronchus


LO 10.5 Describe the systemic effects of benign and malignant neoplasms - Skin

Increased pigmentation
o Many carcinomas

Pruritis (Itching)
o Jaudice, Hodgkin’s disease

Herpes zoster
o Lymphoma

o Bronchial carcinoma


LO 10.5 Describe the systemic effects of benign and malignant neoplasms -

- Problems with balance
- Sensory/sensorimotor neuropathies
- Myopathy and myasthenia
- Progressive multifocal leucoencepalopathy
- Not due to metastasis to the brain


LO 10.5 Describe the systemic effects of benign and malignant neoplasms - General

Cachexia – Loss of weight, muscle atrophy, loss of appetite in someone who is not actively trying to lose weight

Malaise – A feeling of general discomfort or uneasiness

Pyrexia - Fever


LO 10.6 Explain why Neoplasms kill people

Local Effects – Raised ICP, perforation, haemorrhage (Benign or malignant)

Systemic Effects – Replacement of essential body organs, bone marrow, lung tissue, liver parenchyma (Malignant neoplasms).


LO 11.1 Give examples of inherited susceptibility to the development of tumours

Retinitis (Xeroderma) Pigmentosum
Increased risk of skin cancers when exposed to UV rays in sunlight

Ataxia Telangiectasia
Defective response to radiation damage, profound susceptibility to lymphoid malignancies, usually die before age 20

Fanconi’s Anaemia
Sensitivity to DNA cross-linking agents, marrow hypo function and multiple congenital anomalies, predisposition to cancer


LO 11.2 Give examples of the inheritance of certain tumours

Familial Adenomatous Polyposis - APC gene

Breast Cancer - BRCA1/2 gene

Li Fraumeni Syndrome -
p53 gene


LO 11.3 Discuss the functions of oncogenes and the changes which occur in neoplasia

Proto-Oncogenes – A normal gene that can become an oncogene due to mutations or increased expression

Proto-oncogenes are present in all normal cells, and are involved in normal growth and differentiation. They have a DNA sequence identical to viral oncogenes.

Proto-Oncogenes can be modified to become oncogenes (Mutation, amplification, translocation), making their products oncoproteins.
This allows the cell to escape normal growth control, becoming self sufficient without external signals required to grow.

Only one allele of a proto-oncogene needs to be mutated to cause neoplasia.


LO 11.3 Discuss the functions of tumour suppressor genes and the changes which occur in neoplasia

Tumour Suppressor Genes – A gene that encodes proteins that suppress growth and therefore cancer

In normal cells, Tumour Suppressor Genes encode proteins that suppress growth. Loss or alteration of the gene results in the loss of growth suppression.

Both alleles of a Tumour Suppressor gene need to be mutated to produce neoplasia (Knudson’s 2-hit hypothesis).

Inheritance of the ‘First Hit’ can lead to susceptibility to cancers (see above).

E.g. Retinoblastoma:


LO 11.4 Discuss the role of certain oncogenes

- Normally transmits growth-promoting signals to the nucleus
- Mutant Ras is permanently activated resulting in continuous stimulation of cells
- 15-20% of all Cancers
- Colon and lung cancer

- Binds to DNA, stimulates synthesis
- Amplified (over-expressed)
o Neuroblastoma, breast cancer
- Translocation 8  14
o Burkitt’s lymphoma

- Encodes for a growth factor receptor
- Amplified (over-expressed)
- ~25% of breast cancers
- Herceptin is a competitive antagonist at the HER-2 Receptor


LO 11.5 Discuss the role of certain tumour suppressor genes

- Passage beyond the R checkpoint at G1S boundary is governed by the phosphorylation of pRb.
- A defect in both alleles of pRb leads to the cell escaping cell cycle control.
- Retinoblastoma

- ‘Guardian of the genome’
- Approximately 50% of tumour contain p53 mutations
- Gene encodes a nuclear protein, which binds to and modulates expression of genes important for cell-cycle arrest, DNA repair and Apoptosis


LO 11.6 Discuss the initiator stage in carcinogenesis

Carcinogenic agent, e.g. polycyclic hydrocarbon, radiation
- Exposure of cells to a sufficient dose of initiator
- Cell is altered, potentially capable of producing tumour
- Permanent DNA damage (mutations)
- Irreversible and has ‘memory’
- Effect modified by genetic factors, DNA repair
- Initiation alone is not sufficient for tumour formation


LO 11.6 Discuss the promoter stage in carcinogenesis

E.g. Hormones, local tissue responses, immune responses
- Can induce tumours in initiated cells
- Non-tumourigenic on their own
- Need exposure after initiation
- Cellular changes are reversible
o Remove promoter and`cell should be okay and return to normal
- Enhance proliferations, especially in mutated cells and increase incidence of further mutations – can result in cancer
o Think of all the mutations necessary for metastasis… this makes it more likely


LO 11.7 List the Agents that can result in the development of tumours

Other Agents


LO 11.7 Discuss Agents that can result in the development of tumours and their mechanisms of action - Radiation

Causes a wide range of different types of damage to DNA, including single/double strand breaks and base damage. The effect depend on the quality of radiation and the dose. If DNA repair mechanisms are overwhelmed, leaving DNA damage unrepaired, mutations in oncogenes/Tumour suppressor genes can lead to cancer.

Ionising radiation
o E.g. Hiroshima (Early leukaemia/lymphoma -> Late Thyroid/breast)

Ultraviolet radiation
o E.g. Squamous cell carcinoma, Basal cell carcinoma, Malignant melanoma


LO 11.7 Discuss Agents that can result in the development of tumours and their mechanisms of action - Chemicals

Carcinogens interact with DNA in one of a number of ways. Some act directly, others require metabolic conversion to an active form.

- Polycyclic aromatic hydrocarbons
o Produced in combustion of tobacco and fossil fueld
o Hydroxylated to active form
o Lung Cancer, bladder cancer, skin cancer (scrotal skin in chimney sweeps)

- Aromatic Amines
o Hydroxylated in liver and conjugated with glucuronic acid (Phase 2 drug metabolism, non toxic)
o Deconjugated to active form in urinary tract by urinary glucuronidase
o Active form sits in bladder -> Bladder cancer
o Rubber and dye workers

- Alkylating Agents
o Bind directly to DNA – Nitrogen mustard


LO 11.7 Discuss Agents that can result in the development of tumours and their mechanisms of action - Other Agents

o Malignant mesothelioma, lung cancer

o Hepatocellular carcinoma (collaborates with HBV)

o Bladder cancer

o Gastric cancer and lymphoma

o Androgens and hepatocellular carcinoma


LO 11.8 Describe some conditions that predispose tumours

Ulcerative Colitis
- Colorectal carcinoma
- DNA damage and microsatellite instability
- May mask symptom of cancer

- In west present in 85-90% of hepatocellular carcinoma
- Some of association due to chronic viral hepatitis

Adenoma of colon/rectum
- Adenocarcinoma


LO 12.1 Describe the Staging of Malignant Tumours - use breast cancer as an example

TMN Staging System
- T = Primary Tumour
- N = Regional Lymph Node involvement
- M = Metastasis

TMN varies for each specific form of cancer, but the general principles are:

- With increasing size in primary lesion, T1 -> T4
- N0 = No nodal involvement, N1 -> N3 = involvement of an increasing no./range of nodes
- M0 = No distant metastases, M1 = Presence of blood borne metastases

TNM Staging for Breast Cancer
TIS – Carcinoma in situ
T1 - < 2cm
T2 – 2-5cm
T3 - > 5 cm
T4 – Through the chest wall/skin

N0 – No nodal
N1 – Axillary
N2 – Mammary
N3 - Supraclavicular

M0 – No metastasis
M1 – Presence of metastasis


What is the staging system for colorectal cancers

Dukes’ Staging for Colorectal Carcinomas

- A
o Confined to bowel wall
o Not extending through muscularis propria
o >90% 5 year survival

- B
o Through bowel wall (Muscularis propria)
o 70% 5 year survival

- C1/2
o Lymph nodes involved
o 30% 5 year survival
o C1 = Regional Lymph nodes involved
o C2 = Apical node (furthest away node) involved


LO 12.3 Know which systems are used to classify Hodgkin’s disease and Prostate Carcinoma

Hodgkin’s Disease – Ann Arbor Classification

I – One lymph node involved
II – Two lymph nodes on one side of the diaphragm
III - > Two lymph nodes on both sides of the diaphragm
IV – Multiple foci (Bloody everywhere)


LO 12.5 Define and discuss Grading

Grading – Based on the degree of differentiation of tumour cells. Attempts to judge the extent to which tumour cells resemble or fail to resemble their normal counterparts.

Graded 1-3 or 1-4 with increasing anaplasia.
Gx = Grade of differentiation cannot be assessed
G1 = Well differentiated
G2 = Moderately differentiated
G3 = Poorly differentiated
G4 = Undifferentiated


What is the grading system used for Grading of Breast Carcinoma

Scarff-Bloom-Richardson Grading system
- Degree of tubule formation
- Extent of nuclear variation
- Number of mitoses

Grade 1 – 85% 10-year survival
Grade 2 – 60% 10-year survival
Grade 3 – 15% 10-year survival


What grading system is used for Prostate Carcinoma

Gleason Grading System


LO 12.4 Discuss the biological basis for the use of different cancer treatments - Radiotherapy

- External radiation to rumour at fractionated doses with shielding of adjacent normal tissues
- Causes damage to DNA of rapidly dividing cells
- If DNA damage is extensive -> Apoptosis

- High
o Lymphoma
o Leukaemia
o Seminoma (Testicular)

- Fairly High
o Squamous carcinomas

- Moderate
o GI, Breast

- Low
o Sarcoma


LO 12.4 Discuss the biological basis for the use of different cancer treatments - Chemotherapy

Drugs used have effects at particular stages of the cell cycle. Also have effects on rapidly dividing cells, e.g. bone marrow.
- Cyclophosphamide
o Act on cells in G1/S and mitosis

- Vincristine
o Block cells entering cell cycle/act on mitosis

- Methotrexate
o Acts on cells in S phase


LO 12.4 Discuss the biological basis for the use of different cancer treatments - Hormone Therapy

- Tamoxifen
o Competes for binding to Oestrogen Receptor
o 50-80% of Breast Cancers express oestrogen receptors
o Surgical (Orchidectomy)/clinical castration

- Herceptin
o HER-2 Growth factor receptor
o Overexpressed in 20-30% of breast carcinomas
o Herceptin = Humanised monoclonal antibody
o Side effects – Cardiac/pulmonary toxicity, can be fatal

- Prostate Cancer
o Depends on androgens
o To treat, deprive tumour of testosterone


LO 12.5 Discuss the use of tumour markers in diagnosis and monitoring of disease

Carcinoembryonic Antigen
Normally only in embryonic tissue, but cancer basically does what it wants and expresses it again. It is clinically useful to see if there is any residual disease left after the removal of tumours.

Human Chorionic Gonadotrophin
Used in:
- The evaluation of testicular masses
- To indicate residual disease after Orchidectomy
- In monitoring response to therapy and prediction of recurrence
- Raised in nonseminomatous testicular tumours, especially when choriocarcinomatous elements present (high levels)
- Seminomas with syncytiotrophoblastic giant cells

Alpha-Fetoprotein (AFP)
- Normally synthesised early in foetal life by yolk sac, foetal liver and foetal GIT.
- Raised plasma levels associated with cancer of liver and yolk sac tumour of testis (nonseminomatous testicular tumours)


LO 12.6 Discuss the value of screening

Screening aims to detect pre-malignant, non invasive and early invasive cancers to improve prognosis


What cancers are screening tools used for



Describe Breast screening

- Identify invasive cancers before they can be felt
o 10-15mm in size

- Relies on mammography (x-ray of breast)
o Identifies densities and calcifications

- Of every 500 women screened, one life will be saved

- 50-69 years
o Every 3 years


Describe cervical screening

- Cytological smears to detect “early” pre-cancerous changes
o Cervical Intraepithelial Neoplasia (CIN)

- Treatment can then be given before invasion occurs and is curative

25 Years First invitation
25-49 -3 Yearly
50-64 - 5 Yearly
65+ - Those who have no been screened since age 50 or who have had recent abnormalities