Circulatory pathology Flashcards
What are the layers of an blood vessel wall? from lumen out
Intima
Internal elastic lamina
Media
Adventitia
What are the functions of endothelial cells?
Permeability barrier
Release anti-coagulant, anti-thrombotic and fibrinolytic regulators
Regulate prothrombotic molecules
Regulate ECM
Regulate blood flow and vascular reactivity
Inflammation and immunity
Regulate cell growth
Regulate oxidation of LDL
What are endothelial cells like in the basal state?
Non-adhesive, non-thrombogenic surface
What are endothelial cells like in the activated state?
Increased expression of procoagulants, adhesion molecules, and proinflammatory factors
Altered expression of chemokines, cytokines and growth factors
What stimuli cause endothelial cells to take on an activated state?
Turbulent flow, hypertension, cytokines, complement, bacterial products, lipid products, hypoxia/acidosis, viruses, cigarette smoke
What is the role of vascular smooth muscle?
Mediate vasoconstriction/vasodilation
Role in normal vascular repair and pathologic processes e.g. atherosclerosis
When stimulated, can proliferate, upregulate ECM collagen, elastin and proteoglycan production, and secrete growth factors and cytokines
How can blood pressure be calculated?
Cardiac output x peripheral resistance
What factors infleunce cardiac output?
Blood volume:
- Sodium
- Mineralcorticoids
- Atrial natriuretic peptide
Cardiac factors:
- Heart rate
- Contractility
What factors influence peripheral resistance?
Humoral factors: constrictors/dilators
Local factors: autoregulation, pH, hypoxia
Neural factors: contrictors/dilators
What is hypertension?
Persistent elevation of BP in systemic arterial circulation
Accelerates atherosclerosis and causes degenerative changes in walls of large and medium sized arteries > lead to aortic dissection and cerebrovascular haemorrhage
What is the aetiology of hypertension?
95% idiopathic/’essential’ due to reduced renal Na+ secretion, increased vascular resistance, genetic factors, environmental factors
Rest is secondary hypertension due to primary renal/endocrine/CVS/neurologic disease
What examples of renal, endocrine, CVS and neurologic disease can cause hypertension?
Renal: chronic renal disease, polycystic disease, acute glomerulonephritis
Endocrine: hypo/hyperthyroidism, pre-eclampsia
CVS: increased intravascular volume, increased cardiac output
Neurologic: psychogenic, increased intracranial pressure, acute stress
What pathological changes may be seen with hypertension?
Hyperplastic atherosclerosis:
- onion skinning
- concentric proliferation of smooth muscle cells
- causes luminal obliteration
Hyaline atherosclerosis:
- Arteriolar wall thickened by deposited amorphous, proteinaceous material
What is the vascular wall response to injury?
Neointimal response
Injury > endothelial cell loss/dysfunction > smooth muscle cell migration and mitosis into intima, ECM synthesis in the intima > thickened intima
Forms a neointima covered by an intact EC layer
What are the three factors that promote thrombosis?
Virchow’s triad:
- Endothelial injury
- Abnormal blood flow
- Hypercoagulability
This are interacting factors:
EI > ABF > H
EI >H
ABF > EI > H
How can endothelial injury lead to thrombosis?
Promotes platelets adhesion and aggregation
> production of pro-coagulant factors
In heart and arterial circulation due to:
- over ulcerated plaques in atherosclerosis
- endocardial injury in MI - mural thrombus (attached to a wall)
- traumatic or inflam vascular injury - vasculitis
How can abnormal blood flow lead to thrombosis?
Prevents blood diluting activated clotting factors. Causes:
Stasis > venous thrombosis
- allows platelets to encounter endothelium and slows washout of activated clotting factors
Turbulence > arterial, near valves/cardiac thrombosis
- physical trauma to endothelial cells/dysfunction
- counter-currents and local pockets of stasis
What causes a hypercoagulable state?
Primary (born with):
- Leiden factor V mutation, congenital deficiency of antithrombin III, protein C&S
Secondary (increased concentration of fibrinogen and prothrombin):
- Immobilisation, MI, neoplasia, tissue damage, cancer, prosthetic cardiac valves
- Various syndromes
How do arterial and venous thrombi differ?
Arterial:
Secondary to atheroma
Consists of platelets
Common in brain, middle cerebral artery, coronary arteries
Cause - Endothelial injury
Venous thrombosis:
Slow BF, low pressure
Consists of red cells, platelets and fibrin
Common in Deep calf veins, deep hepatic portal vein
Cause - Stasis
What are pathological features of arterial thrombus?
Lines of Zahn: laminations of fibrin and platelets
What can happen to thrombi?
Lysis: due to thrombolytic activity of blood
Propagation: increase size as acts as focus for further thrombosis
Organisation: invasion of connective tissue elements, causes thrombus to become firm and grey/white
Canalisation: new lumens lined by endothelial cells form in an organised thrombus
Embolisation: thrombus becomes dislodged, travels through circulation, lodges in blood vessel some distance from site of thrombus formation
What is embolism?
Detached fragments from
- solid (thrombus), liquid (amniotic fluid) or gas (nitrogen)
- carried by blood to distant site
Most common is thromboembolism
What is a pulmonary embolism?
Most pulmonary emboli are small, then undergo organisation
Or pass through right heart to pulmonary circulation
Smaller emboli - pulmonary hypertension ventilated areas no perfused by blood
Massive embolus - sudden death
Differenr effect of emboli in different areas of the lungs
Lungs have dual blood supply
PE less likely to lead to infarction - red infarct, but can occur in peripheral areas or with poor bronchial circulation
Embolus
