My Pathology

• Inflammatory exudate into damaged area
• Aids in destruction of an agent
• Breakdown and removal of damaged tissue

• Endo and exotoxins from infection
• Viruses replicating intracellularly = cell lysis
• Physical agents, e.g. heat, cold, UV
• Tissue necrosis e.g. starvation, ischaemia
• Irritants or corrosives

Toxin dilution; Ig entry; drug transport; fibrin formation; nutrient delivery

Digests normal tissue; swelling can be damaging; damaging if an inappropriate response

• Small blood vessel dilation
• Increased blood flow and fluid accumulation in ECM

• Purulent (suppurative/pus): plasma with active and dead neutrophils, fibrinogen and necrotic parenchymal cells.
• Fibrinous: fibrinogen and fibrin. Found in rheumatic carditis, strep throat, pneumonia. Difficult to resolve.
• Catarrhal: High mucous content. Found in nose and throat
• Serous (transudate): Serum-like with little protein content. Seen in mild inflammation, found in TB
• Malignant: Exudate containing cancerous cells. Usually in pleural effusion.

• Histamine: Vasodilation and immediate transient permeability.
• Lysosomal compounds: Increase vascular permeability and activate complement
• Prostaglandins: Potentiate increase in vascular permeability. Used in COX-2 inhibitors.
• Leukotrienes: Vasoactive
• Serotonin: Vasoconstrictor

• Resolution: Complete restoration of tissues. Occurs when minimal necrosis, tissue can regenerate and causal agent destroyed.
• Suppuration: Pus formation, due to pyogenic bacteria. Membrane forms = abscess, reducing Ig, lymphocyte + antibiotic access
• Organisation: Granulation tissue replaces necrotic tissue when too large or too difficult to digest. Insufficient fibrinolysis occurs.

When cells are stressed too severely to adapt to damage, or when the cells are exposed to damaging agents

• When functional or morpholigical changes occur, which reverse when the damaging stimulus is removed.
• Characteristics include: reduced oxidative phosphorylation, ATP depletion, cellular swelling from water and ion influx/efflux.

• When the cell cannot recover after continued damage and invariably undergoes cell death after morphological changes.
• Structural changes, such as amorphous densities in damaged mitochondria, and functional changes e.g. loss of membrane permeability

• When damage to the membrane caused by an external factor = severe membrane damage = lysosomal enzymes entering cytoplasm = content leakage + premature cell death. No cytokine signals sent to macrophages.
• Coagulative: Seen in hypoxia; injury denatures destructive proteins and 'preserves' cells
• Liquefactive: Cell destruction with pus formation, usually via bacteria or ischaemic injury to the brain
• Caseous: Granulomas surround necrotic tissue and give it a cheesy appearance

• A normal function (e.g. in foetal growth) or due to damage, particularly DNA
• Exogenous: Fas/TNF pathway or T cells. Endogenous: stress/virus = mitochondrial membrane depolarisation and caspase release.
• Caspases activate = structural or nuclear protein cleavage. Also activate DNAses.
• Cells degraded to apoptotic bodies; easily digested by phagocytes

DNA mutation = hydrophobic proteins = aggregation = extracellular beta sheets = amyloid plaques = mitochondrial dysfunction + oxidative stress = cell toxicity = organ dysfunction

Examples include alzheimer's, parkinsons, DM2 and huntingtons.

Skin darkening caused by increased melanin production and deposition in epidermis. Can be focal or diffuse. Age reduced melanin production control.

Ischaemia = activated phosphatases = calcium salt deposits in mitochondria = Necrosis = build up of calcium in soft tissues = hardening. Either dystrophic or metastatic (increased serum calcium).

• Fixation: Sample transferred to cassette and reagents added: ethanol, toluene + hot paraffin. Set in mould. Tissue sliced using microtome.
• Staining: Stain highlight cellular components, sometimes specific cells. Counterstains can be used to provide contrast.
• Interpretation: The sliders examined by a pathologist, a report formed and tissues are diagnosed.

• H+E: Haematoxylin (blue) and eosin (pink). H stains nuclei blue, eosin stains cytoplasm and ECM pink.
• Wright's: Stains several blood cells different colours.
• Immunohistochemistry: used to stain proteins, lipids and carbohydrates via antigens. Mainly used in cancerous tissues.

• Determined by its genetic, biochemical or structural properties which enable it to produce disease.
• The competency of the host's immune system, and the avoidance mechanisms of the pathogen.

• Invasiveness: Ability to invade tissues, including colonization and defense avoidance
• Toxigenesis: Ability to produce exo or endotoxins which damage the body

• Virulence: A measure of the severity of disease produced by a pathogen
• Pathogenicity: A measure of an organisms ability to produce disease, but not its severity
• Commensal: A symbiote, which benefits from an unaffected organism
• Pathogen: An organism, or substance, capable of causing disease
• Sterilising immunity: An immune response completely effective at preventing infection

The alteration of antigens, especially found in extracellular pathogens, allowing avoidance of defences based on specific detection and neutralisation.

• Diversity: Large number of pathogen sub-species decreases likelihood of antigen similarity
• Antigenic drift/shift: Where progressive mutations in a recognised protein allow avoidance. Shift is when viral strains combine to share properties
• DNA rearrangement: Where a major antigen repeatedly changes in a programmed manner

• - Antigenic variation
• - Replication cessation
• - Defence resistance
• - Immunosuppression

• As viruses are detected when they direct viral protein synthesis (being displayed on MHC), entering growth latency prevents this
• The virus does not cause disease in this state, but no non-self MHC proteins mean no detection or destruction by T lymphocytes
• A stimulus causes the virus to exit latency, where it invades, is destroyed and reenters latency after spreading to new hosts.

• Some pathogens induce a normal immune response, but have evolved specialised mechanisms for resisting effects
• An example is in TB: mycobacteria are engulfed but use macrophages as their primary host by preventing phagosome/lysosome fusion.

• Hypercoagulability: Caused by oestrogen therapy, sepsis, thrombophilia
• Vascular wall injury: Trauma/surgery, venepuncture, atherosclerosis
• Circulatory stasis: Atrial fibrillation, immobility, varicose veins

• - White thrombus: many platelets, small amounts of fibrin. Due to high flow.
• - Red thrombus: Large amount of fibrin with trapped red cells, due to low flow.

• - The formation of plasmin from plasminogen
• - The smoothness of the endothelial wall and a high flow
• - Endogenous anticoagulants released by local cells, e.g. heparin, antithrombin. Low flow allows collection and anti-coagulant effect.

• Normally presents with painful swollen leg. 50% with asymptomatic PE.
• Factors affecting Virchow's triad: surgery, varicosity, obesity, thrombophilias
• Blood tests (fibrin D-dimer). Compression US. Venography
• Anticoagulation for 3-6 months; LMWH, warfarin. Target INR 2.5. Risk factor removal. Pain relief.

• Dyspnoea, chest pain and haemoptysis. If massive = collapse.
• Risk factors reflect those of DVT; virchow's triad

Crushing pain and sweating

Atheroma = stenosis. Rupture = thrombus = occlusion = infarction

History: Dysfunction evidence (ECG, fainting). Biochemistry: Elevated troponin. Imaging.

Antiplatelets/anticoagulants. Thrombolysis (PCI), balloon angioplasty. Long term: statin and antiplatelet

• Unilateral limb weakness and facial muscle paralysis
• Emboli can occur in the left atrium, ventricular wall or in an atheromatous carotid
• CT and ECG for atrial fibrillation (stroke risk factor)
• Removal/correction via anticoagulation, cardioversion or heart valve replacement

• 3: Clinical features of DVT
• 3: PE is most likely diagnosis
• 1.5: Tachycardia (100bpm)
• 1.5: Immobilised >3 days
• 1.5: Previous PE or DVT
• 1: Haemoptysis
• 1: Malignancy or treatment within 6/12

<4 unlikely

• Inflammation of prolonged duration, where tissue destruction, inflammatory processes and repair proceed simultaneously
• Characterised by lymphocyte and plasma cell infiltration, necrosis and fibrosis

• Acute inflammation progresses to chronic
• Repeated bouts of acute inflammation
• New; infection, forgeign insoluble material, autoimmunity

• Mixture of cells: plasma cells, macrophages, t lymphocytes and eosinophils
• No neutrophils

• Macrophages
• T lymphocytes

• Macrophages present antigens to the lymphocytes
• Lymphocytes produce IL-2 to cause macrophage infiltration and epitheloid appearance

• Citrate is added to a blood sample to chelate calcium
• This is centrifuged to remove platelets
• Constiuents are added to the plasma
• Assays occur at body temperature
• The time to clot is measured and compared to normal plasma

• Tissue factor and phospholipids added to treated plasma, then calcium added
• Assesses extrinsic pathway: each step requires phospholipid and calcium
• 10-12 seconds (1.0-1.2 ratio)

• Contact factor and phospholipids added, then calcium
• The intrinsic pathway, but more importantly factor presence for deficiency
• 30-40 seconds

Tissue factor on certain stromal cells, e.g. fibroblasts, binding with factor VII

Complex involving factor XII and collagen forms, activating XI

• Bovine thrombin added to plasma: factor activation doesn't occur
• The conversion of fibrinogen to fibrin
• 17 seconds usual time taken

Factor deficiency (including warfarin therapy)

• Factor deficiency
• Von Willebrand's disease (needed for contact factor bond)
• Lupus anticoagulant (antiphospholipid)

• Heparin
• Hyperfibrinolysis

• Measuring APTT, then a 'mixing test' performed
• Patient's plasma mixed with normal plasma - if still prolonged APTT then deficiency ruled out
• Russel's viper venom test performed

• Thrombin deficiency (Factor II)
• Factor V or X deficiency (needed for prothrombin conversion)

• Shaft
• Can you dig it?

• Factor VIII deficiency
• X linked recessive inheritance
• Prolonged APTT, others normal

• Increased destruction: AI affecting vWF or VIII
• Decreased production: vitamin K deficiency, warfarin, liver failure
• Anticoagulation: heparin
• Platelet dysfunction: thrombocytopenia, NSAIDS

• Disseminated intravascular coagulation; widespread fibrin generation in blood vessels
• Cascade activates = microthrombi + cascade exhaustion
• Sepsis, malignancy, trauma, pregnancy