Pathology Flashcards
Acute rheumatic fever cause
Group A streptococcus bacteria infects upper respiratory tract causing sore throat and later auto-immune response
Latency period between GAS infection and ARF symtoms
3 weeks
Rheumatic heart disease
Damage to mitral or aortic valves that remains after ARF has resolved
Populations most likely to get ARF
Children between 5 and 15
North island
Maori (20 x higher) and Pacific (40 x higher)
Link between ARF and socio-economic status
Crowded housing conditions
Barriers to primary healthcare
Untreated strep throat infections
Symptoms of ARF
Sore knee, elbow, ankle, wrist joints due to moving inflammation Skin rash Fever Fatigue Breathlessness Fidgety, jerky movements
Primary prevention of ARF
Appropriate treatment of sore throats in high risk populations
Intramuscular penicillin or 10 day course oral penicillin
Secondary prevention of ARF
Continuous administration of antibiotics in those with recurrent ARF or RHD to prevent infection with GAS again
Primordial prevention of ARF
Social and environmental risk factors
Overcrowding, poor living conditions and other effects of poverty
RHD
Most often the mitral valve with mitral regurgitation
Fibrosis of leaflets and subvalvular structures
Valve leaflets become immobile
Eventually dilation of left ventricle leading to myocardial fibrosis and eventually ventricular dysfunction and cardiac failure
Mitral stenosis leads to atrial dilatation which can cause atrial fibrillation and thromboembolism
Main causes of CHD and stroke
High LDL High saturated fat diet High blood pressure High BMI HIgh salt and alcohol intake High blood sugar Smoking
Atherosclerosis
Disease affecting the inenrmost layer of large and medium sized arteries
Plaques
Deposits of fibrous tissue and lipids
Arteriosclerosis
General term for hardening or arteries of which atherosclerosis is a type
Four major positive risk factors for atherosclerosis
Hyperlipidaemia
Smoking
Hypertension
Diabetes mellitus
Four additional positive risk factors for atherosclerosis
Age
Family history
Obesity
Alcohol intake
Three major negative risk factors for atherosclerosis
High HDL
Moderate alcohol consumption
Cardiovascular fitness
4 stages of atherosclerosis
Endothelial cell injury
Leukocyte migration
Smooth muscle cell activation and migration
Lipoprotein infiltration
Endothelial cell injury in atherosclerosis
Initiator of atherosclerosis
Caused by a comibination of hypertension, chemical insult and cytokines
3 things endothelial cell injury leads to
Altered permeability
Adhesion of leukocytes
Activation of thrombosis
Leukocyte migration in atherosclerosis
Acute inflammation - neutrophil invasion
Monocytes enter atherosclerotic lesion and mature into macrophages
Macrophages eat oxidised lipoproteins and turn into foam cells
Dead foam cells in the centre form a necrotic core, cholesterol crystals and calcifications
Role of mast cells in atherosclerosis
Degrade protective HDL and promote smooth muscle cell and leukocyte migration into the plaque
Smooth muscle cell activation and migration in atherosclerosis
Growth factors activate vascular smooth muscle cells
SMCs proliferate and migrate into the TI from the TM
Cytokines produced, leukocytes activated
Leukocytes take up lipids and produce specialised ECM proteins
Lipoprotein infiltration in atherosclerosis
Become oxidised in plaques
Attract monocytes
Stimulate cells to release growth factors and cytokines
Cause dysfunction and apoptosis in SMCs, macrophages and endothelial cells
3 consequences of atherosclerosis
MI
Peripheral vascular disease
Cerebrovascular disease
Haemostasis
Physiological response of blood vessels to injury
Plugs leaks in injured vessels and sets them up for repair
Endothelial cells in haemostasis
ECs normally inhibit haemostasis in healthy vessels and activate haemostais in injured vessels
3 key substances endothelial cells secrete in healthy vessels
NO and prostacyclin to inhibit platelet activation
Antithrombin to bind and inactivate thrombin
3 key substances endothelial cells secrete in damaged vessels
Endothelin for vasoconstriction
von Willebrand factor to promote platelet adhesion
Tissue factor which activates the coagulation cascade
Activation of platelets
Extracellular matrix proteins, mostly collagen but also other connective tissue proteins
Cooperation of haemostasis
Endothelial cells
Platelets
Clotting cascade
3 chemical signals platelets secrete
Thromoxane A, vasoactive amines and ADP
All promote vasoconstriction and platelet aggregation
Purpura
Bleeding from skin capillaries
Coagulation
Cascade of proteolytic reactions through which inert circulation zymogens are sequentially activated
Thrombin
Penultimate step in clotting cascade
Catalyses conversion of fibrinogen to fibrin
Activates platelets and catalyses several earlier steps in coagulation cascade (positive feedback loop)
Fibrin
Strands form meshwork with fused platelets to form stable haemostatic plug
Fibrinolytic system
Disassembles haemostatic plug when no longer needed
