Fishbein2.txt

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emm64
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134871
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Fishbein2.txt
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2012-02-13 00:54:11
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Fishbein Systems
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Fiscbein 2 systems
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  1. Normal Hemostasis
    • Intact blood vessel wall
    • Normal platelet function
    • Normal coagulation system
  2. Endothelium Antithrombotic properties
    • Antiplatelet effects-PGI2(prostacyclin), NO, adenosine phospotase
    • Anticoagulant-heparin-like, thrombomodulin
    • Fibrinolytic-tissue plaminogen
  3. Endothelium Prothrombotic properties
    • Production of von Willebrand factor
    • Production of factor VIII
    • Production of tissue factor
    • Binds activated coagulation factors IXa and Xa
    • Secrete inhibitors of plasminogen activators
  4. Coagulation Control
    • Natural anticoagulants - (antithrombin III, proteins C and S, thrombomodulin)
    • Activation of fibrinolytic system
    • Clot retraction
  5. FIBRINOLYTIC CASCADE
    • breakdown clots
    • tPA converts plasminogen to plasmin, which breaks down fibrin to fibrin split products
    • Free plasmin binds to circulating α2-antiplasmin and becomes inactivated
    • Endothelial cells secrete PAIs to abrogate tPA effect
  6. Hematoma
    • accumulation of blood within TISSUE
    • Petechiae (1 to 2 mm)
    • Purpura (3 to 5 mm)
    • Ecchymoses (1 to 2 cm)
  7. Hemorrhage Causes
    • Trauma
    • Vascular disorders (vasculitis)
    • Platelet disorders (thrombocytopenia)
    • Clotting factor deficiencies
  8. Hypercoagulable states
    • Part of Virchow's Triad other than alterations in flow and endothelial injury
    • Primary (genetic)
    • Factor V mutation, prothrombin mutation
    • Secondary (acquired)
    • Oral contraceptive use, pregnancy
    • Certain cancers
    • Smoking
    • Antiphospholipid antibody syndrome
    • Nephrotic syndrome
    • Severe trauma
  9. PULMONARY EMBOLISM
    • 95% deep leg veins
    • 60-80% clinically silent
    • cor pumonale
    • Chronic pulmonary thromboembolism may result in pulmonary hypertension and cor pulmonale
  10. SYSTEMIC EMBOLISM
    • most from mural intracardiac thrombi
    • Ulcerated atherosclerotic plaques, aortic aneurysms, or valvular vegetation comprise remainder
    • Paradoxical embolism rare (venous -> arterial)
    • 75% go to lower extremities
    • 10% brain
    • other intestine, kidney, spleen
  11. cholesterol thromboembolus.
    Cholesterol crystals are the white, needle-shaped structures
    • Red V White Infarcts
    • Red (hemorrhagic)
    • Venous occlusions, spongy tissues, dual circulations, congested tissues, reperfused tissues
    • White (anemic) infarcts
    • Arterial occlusions, solid tissues
    • DISSEMINATED INTRAVASCULAR COAGULATION
    • Thrombohemorrhagic disorder occurring as secondary complication of other diseases
    • Widespread activation of coagulation cascade with formation of microthrombi within capillaries and arterioles
    • Consumption of platelets and coagulation factors and secondary activation of fibrinolysis (AKA consumptive coagulopathy)
    • Consequences:
    • Micro-infarctions of multiple organs
    • Bleeding at multiple sites
  12. PATHOGENESIS OF DISSEMINATED INTRAVASCULAR COAGULATION
    • sepsis, endothelial issue, massive tissue destruction (SHOCK) causes widespread thrombosis
    • -there is combination of bleeding & clotting
  13. Thrombotic Consequences (DIC)
    • The left most panel shows the cut surface of the liver which has a nutmeg appearance. This is due to centrilobular necrosis in this particular case. The arrow is pointing to the area of necrosis which is yellow.
    • The central panel shows a glomerulus with multiple thrombi (one is indicated by the arrow) within the glomerular capillaries. Since the blood supply of the renal tubules comes from the efferent arteriole, thrombi within the glomerular capillaries block the blood flow to the tubules resulting in acute tubular necrosis.
    • The right most panel is a photomicrograph of lung tissue with an intracapillary thrombus (arrow).
    • -center: clots in glomeruli of the kidney
    • -clots cannot be seen with the naked eye; microscopic clots
  14. Tunica intima
    • Innermost layer consisting of endothelial, subendothelial, and elastic/fenestrated layer
    • Endothelial layer
    • Direct contact with blood
    • Basement membrane separates endothelium from subendothelium
    • Subendothelial layer
    • Delicate connective tissue and scattered stellate cells
    • Elastic/fenestrated layer
    • Membrane consisting of elastic fiber network
    • Forms bulk of tunica intima
    • Thickness depends on type and size of vessel
  15. Tunica media
    • concentric layer of smooth muscle cells and extracellular matrix
    • Smooth muscle cells
    • Thickness depends on type and size of blood vessel
    • Produce extracellular matrix
    • Extracellular matrix
    • Elastic fibers, reticulin fibers, proteoglycans
    • Main functions
    • Conduction of blood along vascular system
    • Control of peripheral vascular resistance
    • Maintenance of blood hydrostatic pressure
  16. Tunica adventitia
    • Connective tissue
    • collagen, elastic fibers, vasa vasorum, and nerves
    • Vasa vasorum supplies nutrients to media of larger blood vessels (e.g. aorta)
    • Nerves regulate vascular muscle tone
  17. Aterial v Venous Systems
    • Arteries high velocity, high pressure, least cross sectional area.
    • Elastic arteries
    • aorta & main branhes, pulmonary trunk
    • tunica media is bulk (1/3 muscle 2/3 elastic)
    • Elastic->conducting blood-> prevent overexpansion and collapse
    • maintains pressure during diastole

    • MUSCULAR ARTERIES
    • Large muscular arteries->Distributing arteries
    • Smaller musclular arteries-> resistance arteries
  18. Which arteries is blood pressure determined?
    • Blood pressure is determined by peripheral vascular resistance
    • This is determined by degree of muscle tone (i.e., muscle contraction) in SMALL MUSCULAR ARTERIES AND ARTERIOLES
    • Autonomic nervous system
    • Circulating hormones
    • Local, endothelial-derived vasoactive mediators
    • These mechanisms also act on arteriolar smooth muscle
  19. Arterioles
    • 30-400 microns in diameter with 1-2 smooth muscle layers
    • Main site of BP regulation
    • Finely regulated process
    • Small changes in muscle tone induce large changes in resistance
    • Other functions
    • Redistribution
    • Shunting of blood
    • Metarterioles
    • Connects arterioles & capillaries
    • Individual smooth muscle cells form precapillary sphincter which constricts to reduce or shut off blood flow to their respective capillaries, shunting blood elsewhere
    • Pericytes
    • contractile cells of capillaries that reside outside of the basement membrane
    • CONTINUOUS CAPILLARIES
    • Most common type of capillary found in skeletal muscle, cardiac muscle, brain, skin, lung, exocrine glands
    • Endothelial cells have no fenestrae and are anchored together by tight junctions, which prevent diffusion between cells
    • Basal lamina is continuous
    • Fenestrated Capillaries
    • Have fenestrae (60-80 nm in diameter) with or without diaphragms that allow relatively free passage of substances (e.g. endocrine glands, intestinal villi, renal glomerulus)
    • Basal lamina is continuous
    • SINUSOIDS
    • AKA discontinuous capillaries
    • Large diameter, discontinuous endothelial layer, and discontinuous basal lamina
    • Macrophages are usually within the vicinity (e.g. spleen, liver)
    • VEINS & VENULES
    • Function mostly as reservoir vessels
    • Post-capillary venules receive blood from capillaries
    • Appear similar to capillaries except wider lumens and more pericytes
    • Preferential site for WBC migration
    • As venules become larger, they have fewer pericytes and more smooth muscle to form muscular veins (not as thick as arteries)
    • Discontinuous elastic lamina with relatively thick adventitia
    • Large veins have valves to maintain unidirectional flow
    • LYMPHATIC VESSELS
    • Drainage system that removes excess interstitial fluid and immune cells to lymph nodes
    • Have blind ends and valves
    • Larger vessels have thin muscle layer and adventitia
    • Similar histologically to veins except have no red blood cells
  20. Aneurysm
    • Localized dilatation of vessel or heart
    • True aneurysm
    • All components of arterial wall or heart (within walls)
    • Atherosclerotic, syphilitic, congenital, left ventricular aneurysm post-MI
    • False aneurysm (pseudoaneurysm) (contained hematoma w propensity to rupture)
    • Injury of vessel wall leading to extravascular hematoma that communicates with intravascular space
    • Post-MI rupture contained by pericardial adhesion, leakage at anastomotic site of vascular graft
  21. Abdominal aortic aneurysms
    • Most common atherosclerotic aneurysm
    • Rare before age 50 years and more frequently seen in men
    • Majority occur below renal arteries and above aortic bifurcation
    • Complicated atherosclerotic plaques result in destruction and thinning of aortic media
    • Often partially or completely filled by thrombus
  22. AORTIC DISSECTION
    blood in media, which often ruptures-> hemmorage
    • Cystic medial degeneration
    • Most common pre-existing histologic finding in aortic dissection if present
    • Characterized by elastic tissue fragmentation, “cyst”-like areas of amorphous ECM (+Alcian blue), and absence of inflammation
    • Frequently seen in Marfan syndrome
  23. vasculitides
    inflammation of vessel wall causes damage to endothelium causes thrombosis, which may then damage organs of the body
    • GIANT CELL AORTITIS/ARTERITIS
    • Most common systemic vasculitis in older adults (rare before 50 years of age) affecting small to large mainly in the head, esp. temporal arteries
    • Granulomatous and mononuclear inflammation of inner half of media with fragmentation of internal elastic lamina
    • Negative biopsy does not exclude diagnosis
    • Patchy and segmental distribution
    • Small biopsy samples
    • Treatment before biopsy
    • Upper panel shows a muscular artery with giant cell arteritis. There is a lymphoplasmacytic inflammatory infiltrate within the intima with giant cells at the degenerated internal elastic lamina (arrow).
    • Lower panel is an elastic tissue stain showing destruction of the internal elastic lamina.
    • -pts present w headaches, bc there is vasculitides of the temporal arteries; often affects arteries of the eye as well
    • -virtually curable 100% of the time w steroids; this is an important diagnosis to make, bc it is treatable
  24. Takayasu Arteritis
    • Granulomatous vasculitis of medium and large arteries of Asian females <40 years="" characterized="" by="" upper="" extremity="" pulselessness="" and="" ocular="" disturbances="" br="">Classically involves aortic arch +/- great vessels and pulmonary arteries leading to marked fibrointimal thickening of vessel wall
    • Similar histologically to giant cell arteritis
    • Eventual fibrosis of all vascular layers, esp. intima
    • POLYARTERITIS NODOSA (PAN)
    • Systemic vasculitis of young adults involving small to medium-sized arteries, typically renal and visceral but not pulmonary vessels
    • Acute phase
    • Segmental transmural necrotizing acute inflammation with fibrinoid necrosis and luminal thrombosis
    • Chronic phase
    • Fibrous thickening of vessel wall and aneurysm formation at branch points
    • All stages of activity may coexist in same or different vessels
    • Clinical manifestations due to distal organ ischemia/infarction
    • No association with ANCA
    • High mortality unless treated
    • Photomicrograph demonstrates muscular artery with intense neutrophilic inflammatory infiltrate with associated fibrinoid necrosis. The vessel lumen is essentially occluded resulting in distal organ ischemia/infarction.
    • -collagen vascular disease, which can affect many organs- vessel obstructed by inflammation, with the problem being eventually infarcs and damage to organs
  25. WEGENER GRANULOMATOSIS
    • Affects males >> females
    • Peak incidence in 5th decade
    • Classic form is characterized by triad of:
    • Acute necrotizing granulomas of upper and lower respiratory tracts
    • Necrotizing granulomatous vasculitis affecting small- to medium-sized vessels
    • Focal necrotizing or crescentic GN
    • C-ANCA present in 95% patients with active disease
    • High mortality if untreated
  26. BP hemodynamic factors
    • Cardiac output
    • *Heart rate
    • *Stroke volume
    • *Total peripheral resistance
    • Mainly determined at level of arterioles
    • Dependent on neural & hormonal influences as well as blood viscosity (hematocrit)
  27. Renin-angiotensin system
    • Affects both peripheral resistance & Na+ homeostasis
    • Juxtaglomerular cells secretes renin in response to decreased distal tubular Na+
    • Renin converts angiotensinogen to angiotensin I, which is converted to angiotensin II by angiotensin-converting enzyme (ACE)
    • Angiotensin II
    • Vasoconstriction of vascular smooth muscle cells
    • Stimulates aldosterone secretion, which increases distal tubular reabsorption of Na+
  28. Atrial natriuretic peptide (ANF)
    • Secreted by atria in response to atrial distension (increased blood volume)
    • Inhibit Na+ reabsorption in distal tubules
    • Vasodilation of blood vessels
  29. RENAL REGULATION OF BLOOD PRESSURE
    • Local regulators (prostaglandins & NO) produced by kidney have vasodepressor effects
    • Decreased GFR results in increased proximal tubular reabsorption of Na+
    • Atrial natriuretic peptide (ANF)
    • Secreted by atria in response to atrial distension (increased blood volume)
    • Inhibit Na+ reabsorption in distal tubules
    • Vasodilation of blood vessels
  30. ESSENTIAL HYPERTENSION Diagram
  31. HTN Effects
    • Small arteries/arterioles
    • Arteriolosclerosis (especially kidneys)
    • Medium & large arteries (including aorta)
    • Accelerated atherogenesis
    • Dissection & aneurysm due to medial degeneration
    • Heart
    • Concentric hypertrophy of left ventricle
    • Coronary artery atherosclerosis & consequences
    • Brain
    • Hemorrhagic & ischemic cerebrovascular accidents
    • Acute encephalopathy
    • Retina
    • Only site where effects of hypertension directly observable
    • HYALINE ARTERIOLOSCLEROSIS
    • Seen in both hypertension & diabetes mellitus
    • Homogeneous, pink hyaline thickening of arteriolar wall with narrowing of lumen
    • Leakage of plasma components across vascular endothelium
    • Excessive extracellular matrix production by smooth muscle cells
    • Photomicrograph of glomerulus with afferent arteriole (arrow) exhibiting homogeneous, pink hyaline thickening of its wall with resultant narrowing of the lumen.
    • -thickening of vessels in glomerulus, so that eventually they occlude, causing renal failure
    • HYPERPLASTIC ARTERIOLOSCLEROSISCharacteristic of, but n
    • ot limited to, malignant hypertension
    • Onion-skin, concentric, laminated thickening of arteriolar walls with progressive narrowing of lumen
    • Ultrastructurally, laminations consist of SMCs and thickened and reduplicated basement membrane
    • Photomicrograph of an arteriole in a patient with malignant hypertension showing concentric, laminated thickening of the arteriolar walls with severe narrowing of its lumen.
    • -proliferation of smooth muscle cells
  32. HTN Consequences
    • Heart Failure
    • MI
    • Stroke
    • Renal Failure
    • Retinopathy

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