14 Cardiovascular Flashcards
Front (Term)
Back (Definition)
What are some anticoagulant and antithrombotic molecules produced by endothelial cells?
Prostacyclin
Thrombomodulin
Plasminogen activator
Heparin-like molecules
What are some prothrombotic molecules produced by endothelial cells?
Von willebrand factor Plasminogen activator inhibitor
What immunomodulatory molecules are produced by endothelial cells?
IL1, 6, 8, adhesion molecules, histocompatibilty antigens.
1.Maintenance of permeability barrier controlling transfer of molecules into and out of the vascular system.
- Regulation of thrombotic and antithrombotic prcesses
Formation of anticoagulant and antithrombotic molecules Prostacyclin
Thrombomodulin Plasminogen activator Heparin-like molecules
Formation of prothrombotic molecules Von willebrand factor Plasminogen activator inhibitor
- Modulation of blood flow and vascular reactivity
Formation of endothelin, ACE
Formation of prostacyclin, NO - Regulation of inflammation by controlling white cell interaction with vessel wall.
IL1, 6, 8, adhesion molecules, histocompatibilty antigens.
5. Formation of extracellular matrix Collagen Proteoglycans Regulation of growth of other cell types Production of growth stimulators and inhibitors PDGF, CSF, FGF Heparin, TNF beta Modification of lipoproteins LDL oxidation Metabolisation of hormones Angiotensin 1
What activates endothelial sells to produce mediators?
Cytokines
Complement products
Advanced glycosylation end products
Lipid products
Bacterial products, Viruses
Haemodynamic forces
Hypoxia
Activated endothelial cells respond by producing mediators listed above
What are the promoters and inhibitors of endothelial cell proliferation/synthesis of growth factors/matrix proteins?
Promotors
PDGF FGF IL1
Inhibitors
Heparin NO Gamma interferon
What is the response of endothelial cells to vascular injury?
Vascular injury stimulates intimal thickening due to
Smooth muscle cell migration from media to intima Smooth muscle cell mitosis
Production of extracellular matrix
Smooth muscle cells characteristically change from contractile phenotype to proliferative-synthetic phenotype
Define Atherosclerosis
Slowly progressive disease of large and medium arteries characterized by focal intimal fibrofatty plaques and predisposing to narrowing of the vessel lumen, thrombosis and aneurysm.
Global distribution, virtually ubiquitous in developed nations with significant consequences for health systems.
Risk inversely related to HDL.
Multiple risk factors are additive.
What is the pathogenesis of atherosclerosis?
Chronic endothelial injury:
Likely mostly due to haemodynamic disturbances and hypercholesterolaemia
Endothelial dysfunction
Increased vascular permeability including to LDL (with high cholesterol content)
Adhesion of platelets, monocytes, leukocytes
Monocyte migration
Macrophage activation, smooth muscle migration from media to intima.
Macrophages and smooth muscle cells engulf lipid.
Smooth muscle proliferation, extracellular matrix deposition, deposition of extracellular lipids.
What do atherosclerotic plaques look like morphologically?
Characteristic atheroma
Macroscopically
White/yellow intimal lesion up to 1.5cm diameter protruding into the vessel lumen.
Distribution (in order): Affect abdominal aorta, coronary arteries, popliteal arteries, descending thoracic aorta, internal carotids, circle of willis
What do atheromas look like under the microscope?
Superficial fibrous cap
containing smooth muscle cells, scattered white cells, and dense connective tissue.
Cellular zone
containing smooth muscle cells, macrophages, T lymphocytes.
Necrotic core
containing dead cells, lipid, cholesterol, foam cells and plasma proteins.
Atheroma may be preceeded by fatty streaks that are intimal collections of foam cells and smooth muscle cells.
Complicated plaques are calcified and fissured or ulcerated and predispose to cholesterol microemboli, local thrombosis, haemorrhage, medial thinning and aneurysm.
What % of hypertension is essential hypertension?
Essential hypertension (90-95%)
What are the renal causes of hypertension?
Acute glomerulonephritis Chronic renal disease Polycystic disease Renal artery stenosis Renal vasculitis Renin producing tumours
What is the pathogenesis of essential hypertension?
Essential hypertension occurs when there are changes that alter the relationship between blood volume (renal sodium homeostasis) and total peripheral resistance (vascular reactivity and vascular wall thickness).
Genetic factors:
Normal distribution in blood pressure.
Genetic differences control of blood volume
- Genes defects in the control of aldosterone metabolism
- Gene defects in proteins affecting sodium reabsorption
- Genetic variation in the renin angiotensin system. –Genetic variation in vascular smooth muscle growth.
Genetic differences in the control of TPR:
-Genetic variation in the renin angiotensin system. –Genetic variation in smooth muscle sensitivity to vasoconstrictor agents.
Environmental factors:
Stress, obesity, smoking, physical inactivity, salt consumption.
What are the small vessel diseases caused by essential hypertension?
Hyaline arteriolosclerosis
Hyperplastic arteriolosclerosis
What is a true aneurism?
Bounded by complete but generally attenuated arterial wall components. Blood always remains within the vascular space.
What is a false aneurism?
Extravascular haematoma that communicates with the intravascular space.
What is a mycotic aneurism?
Infection of an artery resulting in weakening of the arterial wall
May be due to:
Complication of infective endocarditis
Extension of an adjacent suppurative process Haematogenous spread of infection elsewhere in the body
What are the 3 morphological classifications of aneurisms?
Berry – spherical dilation due to congenital wall weakness, most common in the circle of willis.
Saccular aneurysm – large spherical dilatation up to 20cm diameter often partially filled with thrombus. Generally occur secondary to atherosclerosis.
Fusiform – cylindrical dilatation, most commonly seen in aorta. Generally occurs secondary to atherosclerosis.
Define a dissection?
Blood enters the wall of an artery and forms a false lumen.
What is the epidemiology of AAA
Severe atherosclerotic damage of the aortic wall; however, new evidence suggests this is not the only factor, and aneurysmal disease is probably a distinct arterial pathology.
Family history - there are probably strong genetic factors. About 15% of first-degree relatives of a patient with an abdominal aortic aneurysm (AAA), mainly men, will develop an aneurysm.[5]
Tobacco smoking is an important factor.
Male sex.
Increasing age.
Hypertension.
Chronic obstructive pulmonary disease.
Hyperlipidaemia.
In population-based studies, people with diabetes have a lower incidence of aneurysms than non-diabetics have.
Atherosclerosis is the most common cause Additional familial component (in addition to that associated with atherosclerosis itself)
Any factor which causes weakness of the arterial wall can be causative: Congenital defects Infection Trauma Systemic disease including vasculitis
Pathogenesis of AAA?
Atherosclerosis results in destruction of underlying tunica media and weakening of the arterial wall.
Hypertension is a risk factor both for atherosclerosis itself and subsequent aneurysm formation.
(note – syphilitic aneurysms affect ascending aorta and arc
Most likely location for AAA?
Classical location is the abdominal aorta between the renal arteries and common iliacs.
Other sites include renal artery, superior and inferior mesenteric artery, common iliac arteries.
Complications of AAA including % risk of rupture of 5 cm?
Rupture into peritoneal cavity or retroperitoneal tissues. (2% risk if 5cm
Occlusion of a branch by direct pressure or thrombus – particularly iliac, renal, mesenteric, vertebral.
Thromboembolism.
Compression of an adjacent structure – ureter, vertebrae
What causes Ascending thoracic or arch aneurysms?
uncommon, syphillis
Characteristic of tertiary syphilis. Obliterative endarteritis involves the vasa vasorum and causes ischaemia of the aortic media and loss of elastic support. Dissection is unusual due to scarring. Such syphilitic lesions tend to be complicated by atherosclerotic lesions.
Aneurysms less common that aortic valve defects that may result in severe insufficiency and ‘cor bovinum’
Epideiology of aortic dissection?
Most common in 40-60 year age group or in younger patients with Marfans
Csuse of aortic dissection?
Hypertension (causative factor in 90%)
Connective tissue abnormalities – Marfans Rare complication of pregnancy
What is the pathology of aortic dissection?
Intimal tear into the media usually occurs within 10cm of aortic valve. Dissection can extend proximally or distally.
Connective tissue disorders result in cystic medial degeneration characterized by elastic tissue fragmentation and separation of the elastic and fibromuscular components of the media by cystic spaces filled with extracellular matrix. (CMD may also occur in patients with hypertension but there is poor correlation between the presence of CMD and dissection)
Haematoma or false lumen forms between laminar planes between middle and outer third.
What are the types of aortic dissections?
What are the complications of aortic dissections?
Type A involve ascending aorta – more common and more dangerous
Type B involve descending aorta distal to the left subclavian artery
Dissection characterized by severe tearing chest and back pain.
Outcomes: Rupture into peritoneum, pericardium or pleural space. (most common cause of death)
Extension into arterial branches resulting in occlusion.
Retrograde extension resulting in disruption of aortic valve.
What is Virchow’s triad?
Endothelial injury Stasis or turbulence of blood flow Blood hypercoagulability
What are the genetic causes of hyper-coagulability?
Factor V mutations Antithrombin III deficiency Protein C or S deficiency Fibrinolysis defects Homocystinuria Allelic variations in prothrombin levels
Acquired: DIC Heparin induced thrombocytopenia Antiphospholipid antibody syndrome AF Cardiomyopathy Nephrotic syndrome COC Sickle cell anaemia Smoking
What is the prognosis of CCF?
Common Poor prognosis
50% 5-year mortality
The most frequent specific causes are hypertension and IHD
What is the pathogenesis of myocardial hypertrophy?
Hyperlasia cannot occur as myocytes cannot divide Hypertrophied heart has less capillary/myocyte ratio, increased fibrous tissue and dysfunctional proteins and itself contributes to pump failure
Pressure hypertrophy causes increased wall thickness with normal or reduced cavity diameter
Volume hypertrophy causes increased wall thickness accompanied by dilation and increased ventricular diameter.
What are the neurohumeral processes activated by heart failure?
Immediate sympathetic response mediated by baroreceptors
Inotropic and chronotropic response Peripheral vasoconstriction
Release of catecholamines Renin-angiotensin system Atrial natriuretic peptide
Morphology of left heart failure?
Left ventricular hypertrophy Left ventricular dilation. Secondary enlargement of left atrium. Pulmonary congestion and oedema Reduced renal perfusion Reduced brain perfusion.
Morphology of right heart failure?
Congestive hepatomegaly
Congestive splenomegaly Ascites
Renal congestion
Pleural and pericardial effusions Peripheral oedema
