D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 10 - CLOTTING & VASCULAR DISORDERS
Chapters 8 & 9
1.
Thrombosis:
• intravascular clotting (fig. 8 - 3 & ppt. 1): endothelial damage triggers
platelet adherence (mediated by vWF); platelet aggregation & degranulation that
follows activates intrinsic pathway for coagulation (platelet factor 3)
- Hageman factor (activated when exposed to collagen, mediated by vWF)
also instigates the intrinsic pathway
- thrombosis - thrombi are much more organized (layered platelets and red
cells) than external clots, which are homogeneous masses of formed elements and
fibrin (fig. 8 - 2)
- causes: endothelial damage, abnormal flow, hypercoagulation
- endothelial damage may result from normal wear & tear, hypertension,
or from surgical or therapeutic interventions (iatrogenic)
- abnormal flow may involve slow flow or stasis; compromised cardiac
pumping, increased blood viscosity, physical inactivity or defective valves (veins)
(fig. 8 - 4 & ppt. 2); abnormal flow may involve turbulence (due to heart valve damage
or to a deformed vessel, e.g. tumor, plaque or aneurysm), which results in increased
contact with endothelium by platelets (fig. 8 - 5 & ppt 3)
- hypercoagulability may be a genetic condition, involving imbalance
between procoagulants and anticoagulants, or by other conditions that are not well
understood
Bio 307/607 lec 10
- p. 2 -
- sequelae: resolution involves normal arrest of clotting (by anticoagulants)
breakdown of clot (by fibrinolysins)
- organization (healing & recanalization - fig. 8 - 6 & ppt. 4)
- propagation (growth in direction of flow - fig. 8 - 7 & ppt. 5)
- infarction (necrosis due to ischemia) -- heart and brain are the most
vulnerable organs; collateral circulation (anastomosis) is preventive (fig. 8 - 8, 8 - 9 &
ppt. 6)
- embolism (obstruction of vessel by thromboembolus) (figs. 8 - 10
through 8 - 13 & ppts. 7 to 10)
- treatment: anticoagulants (heparin, warfarin), fibrinolysins, e.g.
streptokinase, aspirin (table 8 - 1, fig. 8 - 14 & ppt. 11)
Bio 307/607 lec 10
- p. 3 -
2.
Blood Pressure Dynamics:
• vessel wall structure: tunica intima (endothelium, basement membrane &
connective tissue) = innermost layer (thinner in veins than arteries; possesses oneway valves in dependent veins); tunica media (smooth muscle + elastic connective
tissue) = middle layer (thinner and less elastic tissue in veins); tunica adventitia
(connective tissue that merges with surroundings) (figs. 9 - 1 through 9 - 3 & ppts. 12
& 13)
• normal blood pressure regulation (fig. 9 - 4 & ppt. 14): product of cardiac
output x vascular resistance (mostly controlled in arterioles through vasoconstriction or
vasodilation); also affected by change in blood volume; normally 120/80 (systolic
over diastolic); sympathetic ns & renin-angiotensin system play major regulatory roles
3.
Vascular Disorders:
• hypertension (140/90 or greater):
- essential hypertension (aka primary hypertension): involves conditions,
usually genetic, which increase blood volume, increase arteriolar tension, or increase
sympathetic nervous system signals (90 - 95% of cases of hypertension)
- secondary hypertension (5 - 10% of cases): largely due to conditions that
stimulate renin-angiotensin system --- kidney releases renin; renin converts
angiotensinogen to angiotensin I; angiotensin I is converted in lung (by angiotensin
converting enzyme - ACE) to angiotensin II; angiotensin II stimulates systemic
vasoconstriction & aldosterone secretion (fig. 9 - 5 & ppt. 15)
- excessive levels of other hormones may also be causes
- benign = slowly progressive (either essential or secondary); malignant =
rapidly progressive (1 - 5% of hypertensives)
Bio 307/607 lec 10
- p. 4 -
• hypertensive vascular disease:
- arteriolosclerosis due to benign hypertension features thickening of intima &
media with deposit of plasma proteins + proliferation of extracellular matrix (ECM);
this is hyaline arteriolosclerosis
malignant hypertension stimulates thickened arteriolar walls due to
proliferation of endothelial cells and smooth muscle cells; this hyperplastic
arteriolosclerosis
- treatments: improved lifestyle, diuretics, ACE inhibitors, vasodilators,
calcium channel blockers, & b-blockers (fig. 9 - 7 & ppt. 16)
• atherosclerosis: sequel of hypertension -- mostly in large arteries (fig. 9 - 8 &
ppt. 17)
- plaque (atheroma) formation: numerous fatty streaks (due to macrophages
entering intima & accumulating fat) occur in vessels as a normal development in
youth (fig. 9 - 9); societies with higher living standards progress to plaque formation
(merging of streaks, continued macrophage entry, endothelial damage that attracts
platelets)
- smooth muscle cells accumulate fat along with macrophages --> forming
'foam cells'
- fibrosis follows, producing fibrous cap
- further complications include dystrophic calcification, hemorrhage,
breakdown of tunica media (weakening of vessel wall), & ulceration of intima (figs. 9 10 through 9- 13 & ppt. 18)
Bio 307/607 lec 10
- p. 5 -
- causes of plaque are summarized as 'response to injury' hypothesis that is
widely accepted (fig. 9 - 14 & ppt. 19): initial endothelial injury facilitates admittance
of lipid, monocytes, & platelets to the intima
Bio 307/607 lec 10
- p. 6 -
- main risk factor -- hyperlipidemia (especially LDL cholesterol - fig. 9 - 15 &
ppt. 20); this involves liver interaction with other tissues in lipid metabolism (figs. 9 16, 9 - 17 & ppts. 21 & 22); genetic predispositions involve abnormal metabolism of LDLs
- treatments of hyperlipidemias include various drugs aimed at lowering
LDLs & cholesterol (table 9 - 4)
- other risk factors include hemodynamic stress (normal wear & tear of
pulsatile flow through large vessels), smoking (hypoxia & hypoxemia involvement),
age & gender (more prevalent with older arteries & male arteries), diabetes mellitus
(hyperglycemia involved with LDLs), & other factors such as obesity and excessive
alcohol consumption (fig. 9 - 19 & ppt. 23)
- sequelae: coronary artery disease (fig. 9 - 20 & ppt. 24), plaque embolisms
(fig. 9 - 21 & ppt. 25) & aneurysms (figs. 9 -22 through 9 - 25 & ppts. 26 & 27)
• thrombophlebitis: inflammation of veins followed by thrombus formation;
mainly due to elevated venous pressure in lower limbs, which causes varices due to
weakening of the walls & compromise of the valves (figs. 9 - 27, 9 -28 & ppt. 28)