Flashcards in CVS Deck (84):
three layers of the arteries
intima, media, adventitia
endothelial cells, maintain permability barrier, elaborate anti/prothrombotic molecules, modulate blood flow and vascular reactivity, egulate inflammation and immunity (IL-1, IL-6, V-CAM 1/ ICAM, regulation of cell growth with PDGF and TGF beta, do oxidation of low density lipoprotein.
smooth muscle cells- vasoconstriction and dlation, elaboration of growth factors and cytokines, when intima is damaged it migrates to intima and proliferates. it moves across the elastic lamina to do so. when they migrate they change their phenotype to undergo division and expansion.
rapid and reversible, independent of new protein synthesis, has an anticoagulant surface, low leukocyte adhesivity, produces nitric oxide
alteration in gene expression and protein synthesis- has prothrombotic surface, doesn't produce NO, increased leukocyte activity
Endothelial activators/induced genes
cytokines/adhesion molecules, bacterial products/cytokines & chemokines, hemodynamic forces/growth factors, virus/MHC molecules.
Two principle mechanism for diseases of the blood vessels.
narrowing or complete obstruction of lumen either progressively (atherosclerosis), suddenly (thrombosis) or both (MI)
Weakening of the wall of the vessel leading to dilatation or rupture.
chronic inflammatory disorder of the intima of the large arteries characterized by formation of fibro fatty plaques called atheroma
uncertain, unquantifiable or lesser risk factors for atherosclerosis
hyper homocysteinemia (homocystinuria) this is due to a b12 or folate deficiency and uria due to genetic defect.
Lipoprotein (a) altered LDL
-- inhibitors of fibrinolysis,- high PA-1 inhibitor
-- C-reactive protein
C reactive protein does this
acute phase reactant, endothelial cell activator, decreased by statins/ healthy life.
only organism that increases risk of atherosclerosis.
Non modifiable risk factors for atherosclerosis
Age- beings in childhood, 40-60 five fold increase in incidence of MI
Sex- Males greater than females if premenopausal. Favorable response to HRT.
=Genetics- familial clustering, familial hypercholesterolemia.
increase in cholesterol is most important due to increase risk of LDL, and decrease in HDL.
defect in LDL receptor means decrease in uptake of LDL which increases LDL levels in blood , increase in lDL could also be becasue of abnormal apeE which means it fails to bind to LDL receptor.
DM and hypothyrodism
premature and sever A.S.
insulin resistance dyslipidemia and pro-inflammatory state.
Evidences linking increased cholesterol with athersclerosis.
atheromas contain cholesterol and cholesterol esters, increase in LDL=increase in severit of A.S. high cholesteral diets produce experimental A.S. levels of cholesterol decrease in diet/drugs = progression of A.s.
Hypertension as risk for A.S.
after age 45 if you ahve above 170/95 you increase risk of Ischemic heart disease, antihypertensive therapy reduces incidence of A.S. associated diseases.
creates more reactive oxygen species which causes more endothelial dysfunction, proliferation of vascular smooth muscle cells, lipid peroxidation, and oxidation of LDL
altered form of LDL, causes lipid accumulation, endothelial cell modulation, smooth muscle cell proliferation, control of neo vascularization.
--ApoB-100 portion of LDL + apolipoprotein A
Pathogenesis of atherosclerosis
chornic inflammatory and healing repsonse of the arterialwall initiated by some form of the injuy to the endothelium. this incorporates both dominant theories of intimal cellular proliferation and repetitive thrombus formation/organization. CRP is used to measure artherslcerosis.
Role of endothelial cell sin endothelial injury
endothelial activation causes increased permeability, adhesion of leukocytes, expression of adhesion molecules (VCAM-1) and growth factors.
determinants of endothelial alterations.
hemodynamic factors - hypertension, and increased turbulence at branch points and ostia of vesselsl.
Hypercholesterolemia- increased fats.
role of lipids in response to injury
cytotoxic to endothelium, oxidized lipids; readily ingested by macrophages form foam cells, chemotactic for circulating monocytes, inhibits the motility of macrophages already in lesion, stimulates release of growth factors and cytokines.
role of macrophages
cytockines like IL-1, TNF, growth factors.
role of smooth muscle proliferation
conversion of fatty streat to fibrofatty atheroma by secreting ECM which expands and occludes the lumen. uses collagen and smooth muscle cells.
fatty dots coalesce to form fatty streaks and are composed of lipid laden macrophages, sen in children older than 10 years.
three principle components of plaque
Cells- smooth muscle, macrohpages, leukocytes,
ECM- collagen, elastic fibers, proteoglygans
complicated lesion of A.S.
calcification(patchy or massive), focal rupture or gross ulceration leading to thrombus or emboli, hemorrhage, superimposed thrombus, aneurysmal dilatation( atrophy due to decreased oxygenation)
most common sites for athersclerosis
1. distal aorta and common iliac 2. proximal coronary arteies 3. thoracic aorta, femoral and popliteal arteries, 4. internal carotid. 5. middle cerebral arteries.
A.S. clinical manifestations
CHD- acute MI, angina (stable or unstable) chronic ischemic heart disease leading to congestive heart failure, sudden cardiac death
AAA- abdominal aortic aneurysm
Cerebral vascular disease- stroke, transient ischemic attack, chronic ischemic encephalopathy
- Peripheral vascular disease- cluadication ischemic bowel disease mesenteric occlusion gangrene.
sustained increase in blood pressure, 140/90, systiolic mild +20, moderate +40, Severe+80, malignant hypertension 210/120
shows acute end organ damage, which is a medical emergency, this is due to CNS problems, heart failure, and renal failure, papilledma is an example of a sign.
necrotizing arteriolitis, organ failure, renal failure, left ventricular faiulre, hypertensive encephalopathy.
hypertension is a leading risk factor for
MI and stroke
endocrine factors for BP
renin, angiotensin, ANP, ADH, aldosterone
Nural Factors for BP
Blood volume factors for BP
sodium, mineralocorticoids, ANP
Cardiac factors for BP
heart rate and contractility
Hypertension is a leading risk factor for
MI and Stroke and chronic, end organ and vascular damage.
Regulation of BP
Renin Angitotensin, ANP, ADH, Aldosterone, Sodium, Mineralcorticoids, ANP, if kidney experiences low perfusion, it decides to raise perfusion everywhere else.
etiology of secondary hypertnesion
Renal- GN, RAS, Renin Tumors
--Endocrine- Cushing, OCP, Thyrotoxicosis Myxcdema, Pheochromocytoma, acromegaly
--Vascular- coarctation of Aorta, PAN, Aortic insufficiency
--Neurogenic- Pesychogeic, Intracranial pressure, polyneuritis.
Pathgenesis of Essential/Primary HTN
increasesed sympathetic tone, stress, hormonal, neural, genetic, family , life style
Pathogenesis of Secondary HTN
a known abnormal control.
clincal evidence of acute end organ damage, it s an emergency, due to CNS problems, heart failure and renal faiulre, papelleedema is an example of a sign of this. 210/120 - necrotiziang areteriolitis
Complications of Hypertension
Athersclerosis, arteriolosclerosis- hyaline and hyperplastic, left ventricular hypertrophy, hypertensive cardiomyopathy ---Ischemic heard disease and MI,
hypertensive retinopaty, brain hemorrhage and infarct.
pink hyaline thickening of walls of the arterioles with loss of underlying structural details and with narrowing of the lumen,
leakage of plasma across vascular endothelium and increasing extracelular matrix production by smooth muscle cells.
chronic hymodynamic stress in hypertension or metabolic stress in dabetes causes more endothelial injury
relaed to more acute or sever elevation sof blood pressure, onion skin, concentric laminated thickening of the walls of arterioles with progressive narrowing of the lumens, necrotizing arteriolitis- deposits of fibrinoid and acute necrosis of the vessel wall.
Giant cell arteritis,
Most common, arteries of head (temporal vertebral, ophtalmic)
DIAGNOSE- temporal artery biposy, muple, elastic trichorme, elevated ESR
TREATMENT- steorids analgesics
ASSOCATION- polymyalgia rheumatica
MORPHOLOGY- focal nodular thickening of lumen, granulomatous inflammation of INIMA and INNERMEDIA, gaint cells, mononuclear cells, FRAGMENTATION of the elastic lamina
CLINICAL- 50+ m/f, fever, weight loss, fatigue, facial pain, headache, diplopia, progressive hazy vision, loss of vision.
Granulomatosu vacsculitis of medium and large arteries. obliteration of lumen, most common in arch of aorta, narrowing or obliteration of origins of great vessels arising in arch. can also involve the pulmonary, coronary and renal arteries. AKA aortitis, mostly proximal branches of the aorta
CLINICAL females <40, visual disturbances, retinal hemorrhage, blindness. diminution of upper limb pulses cold numb fingers (pulseless disease) Low BP in upper limb, dizziness, focal weakness or complete hemiparesis.
MORPHOLOGY- Irregular thickening of aorta or branch vessel wall with intimal wrinkling and narrow lumen, mononuclear inflammation of MEDIA, granulomatous change leading to patchy necrosis in MEDIA, Collagenous fibrosis involving ALL LAYERS of the vessell wall.
Polyarteritis Nodosa PAN
systemic, TRANSMURAL necrotizing inflammation of small or medium sized muscular arteris, typically renal and viscerl, SPARES pulmonary, arterolescapillaries and venules are not affected.
CLINICAL- no glomerulonephritis, Young Adults, assocaited with HBV antigen in serum , no hematuria.
MOrPHOLOGY- GROSSLesions in 1. Kidney, 2. Heart, 3 Liver, 4 GIT, all usually at branching or bifurcations HISTO- transmural inflammation, fibrinoid necrosis of inner half, replaced by fibrous thickening of vessel wall. ALL STAGES MY COEXIST IN DIFFERENT OR SAME VESSEL
COMPLICATIONS- weakeing of arterial wall, may cause anerysm dilatation or rupture, impairment of perfusion causing ulcerations, infarcts ischemic atrophy or hemorrhages.
Chu syndromerg Straus
allergic granulomatosis and angitis, eosinophilic vasculitis with granuolmas, asthm allergies MPO ANCA
necrotizing vasculitis, Like PAN but small vessels involves the lung NOT Hep B MPO ANCA
Autoantibodies against the endothelium, smooth muscle cells leading to acute vasculitis,
CLINICAL- fever conjunctial and oral erythema, edema of hands and feet skin rash with desquamation, enlargement of cervical lymph nodes.
TREATMENT- IVIG and aspirin
MORPHOLOGY- Lesions destruction of wall by segmental necrotizing process, moderate fibrinoid change and dense infiltrate of inflammtory cells, can be mild with INTIMA ONLY, acute may lead to aneuryms formation
ASSOCATION- Acute leads to thrombosis and myocardial infarction.
characterized by segmental thrombosing acute and chronic inflammation of medium sized and small arteries, mainly tibial and radial arteries caused by CIGARETTE SMOKING, hypersensitivity to tobacco and is DIRECT cell injury has som genetic influence.
CLINICAL- superficial phlebitis, cold sensitivity, claudication pain, severe progressive pain on exercise at rest. Chronic ulceration of toes feet and fingers, with gangrene
MORPHOLOGY- Thrombus w/microabscesses marked by central focus of neutrophils surrounded by granulomatous inflammation.
MORPHOLOGY-Classic triad- Acute necrotizing granulomas of upper and lower RT, Focal necrotizing or granulomatosu vasculitis(ulcerative lesion fo nose, pharynx and palate), prominent in lungs and upper airways(dispersed focal necrotizing granulomas produce nodules/cavitations. , REnal disease form of focal or necrotizing ,often crescentric glomerulitis.
HISTO- necorsis rimmed by lymphocytes, plasma cells, macrohpages, and giant cells, lesions undergo progressive fibrosis and organization.
CLINICAL- MALES more, average 40yo PR3- ANCA, Persistent pneumonitis with bilateral nodular and cavitary infiltrates, chronic sinusitis, mucosal ulceration of the nasopharynx, renal disease.
ASSOCIATION- necrotizing vasculitis
congenital or aquired weakness in the media.
complete but attenuated vessel wall. the blood remains within the confines of the ciruclatory system. there are atherosclerotic, syphilitic and congential vascular
false or pseudoaneurysm
an extravascular hematoma that communicates with the intravascular space. a contained homorrhage.
Etiology of aneurysm
Athersclerosis, syphilis, Mycotic-infective, vasculitis(PAN, KAWASAKI's disease)
congenital disease, berry aneurysm, Iatrogenic (dialysis)
development defect in the circle of willis in the brain causes this.
MORPHOLOGY- GROSS-most are distal to renal arteries and proximal to the bifurcation, usually fusiform, may be saccular, majority are lined by raised ulcerated and calcified complicated athersclerotic lesions HISTO-athersclerotic lesions with destructino of normal arterial wall, replaced by fibrous tissue, thikened and focally inflamed adventitia
CLINICAL- asymptomatic, abdoinal mass, occulsion of branch cessl of renal, mesenteric, vertebral vessels. embolism, impingemnt of uereter or erosion of vertebrae. may rupture (2% for ,4cm, 25-40 for >5cm
TREATMENT- Large aneurysm- prostehtic, graft, need timely surgery.
tertiary syphilis, obliterative endarteritis of the VASA VASORUM of aorta- destroys tunica media. narrows lumen causing ishcmia of aortic media with inflammation and scaring.
MORPHOLOGY- tree bark wrinkling of oartic intima, aortica valve ring dilation(valvular insufficiency, massive hypertropy of left ventrical (cor bovinum)
ASSOCIATION- COR Bovinum and aortic valvular insufficiency with aortic regurgitation.
CLINICAL- encroachment of mediastinal structures, Dyspnea, difficulty swallowing, recurrent laryngeal nerve pressure(cough), pain due to erosion of ribs or vertebrae, valvular incompetence(aortic regurgitation , cardiac ischemai due to obstruction of coronary ostia. rupture of aneurysm. most common cause of death- heart failure due to aortic regurge.
Aortic dissection. (dissecting hematoma
entry of blood in between and along the laminar planes of media and its extension along the length of the vessel, often ruptures, not usually associated with marked dilation of the aorta.
2 types Type A- proximal, can be either ascending only or both ascending and descending. Type B, distal lesion does not involve ascending usually beginning distal to subclavian artery. descending only
ETIOPATHOGENESIS- men 40-60 yo, Hypertension almost always present. , also seen in younger patients with marfan's or eherlins danlos syndrome. can come as a complication of arterial cannulation, or during pregnancy (unknown reason) (coronary artery dissection)
MORPHOLOGY- intimal tear (starting point, occurs most often in ascending aorta, 1-2 cm above aortic ring) separates teh inner two thirds of media from outer third, can extend proximally toward heart as well as distally along the aorta to variable distances, if you re-rupture the lumen it creates a double barreled aorta.
CLINICAL tearing pain in anterior chest radiating to the back, and moving downward. loss of arterial pulse is common.
COMPLICATIONS-Most common COD is uruptre into bodie cavities. retrograde dissection into aortic root leading to disruption of aortic valvular apparatus. compression of spinal arteries, transverse myelitis, Cardiac tamponade, aortic insufficiency and MI
Cystic Medial Degeneration
lesion consist of focal loss of elastic and muscle fibers in the media which leads to cystic spaces filled with myxoid material, inflammation is absent, CMD is frequently found in Marfan's
Mycotic (infectious) aneurysm
result from the weakening of the vessel wall by a microbial infection- common sites are aorta, cerebral vessels and mesenteric, renal and splenic arteries.
May originate at the site of sticking of a dislodged septic embolus within a vessell usually as a complication of infective endocarditis, or may originate as an extension of suppurative process like TB or bacterial abscess, can also originate from circulating organisms directly infecting the arterial wall like salmonella gastroenteritis.
Etiology of heart faiulre
SYSTOLIC- inability to contract properly, MI, volume overload, valvular regurgitation, cardiomyopathy(dilated)
DIASTOLIC- inability of heart to relax expand and fill sufficiently due to massive ventricular hypertrophy, amyloidosis, contrstictive pericarditis. , hypertension, acute tamponade
Left sided heart failure can be caused by
systemic hypertension, mitral or aortic valve disease, ischemic heart diseae, cardiomyopathy
right sided heart failure can be caused by
left heart failure, or intrinsic disease of lung parenychyma/vasculature like COPD and Pulmonary hypertension(COR pulmonale
compensated heart failure
dilated ventricle is able to maintain cardiac output to meet the needs of the body.
decompensated heart faiulre
failing myocardium is no longer able to propel sufficient blood to meet the needs of the body even at rest.
decreased cardiac output leads to renal hypoperfusion which leads to activation of renin angiotensin system which leads to sodium and water retention, which causes edema
passive congestion of pulmonary circulation leads to pulmonary edema, pulmonary arterial hypertension is severe and sustained which causes right heart failure and systemic venous congestion which leads to edema.
Morphological changes of Left Heart failure
heart is sually hypertrotphied and often dialted, chronic ischemia and or HTN are the number one cuases, cardiomyopathy and valvular disease Aortic and mitral.
in the Lungs- heavy and wet lungs exudes frothey mixutre of surfactant. rich fluid and blood - congestion of pulmonary capillaries, edema fluid in alveolar speace, brown induration of lungs.
Morphological chagnes of right heart failure
Liver- chornic passive congestion, nutmet liver, centrolobular congestions expansion of the central vein results in injury of cell and fibrosis aka cardiac cirrhosis Spleen- elargement and congestionof spleen, Soft tissue edema, pleural and peritoneal effusions. (ascites)
Clinical features left and right failure
LEFT- dyspnea, Orthopnea, Paroxysmal nocturanl dyspnea when they lie down they don't breath well.
RIGHT- systemic venosu congestion, distended neck veins, enlarged tender liver. softe tissue edema.
Ischemic heart disease
imbalance between mycardial need for and supply of oxygenated blood.
leading cause of death for men and women most common in older individuals, greater in males than females unitl 80's
ETIOLOGY- Athersclerosis (90%) aneima/hypoxemia, shock, vasculitis (kawasaki, pan,) increased cardiac demand, aoritc or coronary dissection.
PATHOGENESIS- Fixed cornoary obstruction+ acute plaque changes+ coronary intraluminal thrombosis+ vasoconstriction.
angina pectoris, acute MI, Sudden cardiac death( arryhtmia) chronic ischemic heart disease with congestive heart failure.
Acute coronary syndromes
MI, unstable angina, sudden cardiac death.
atherosclerotic lesions causing at least 70% reduction in cross sectional area of one or more major coronary arteries. augmented coronary flow through compensation is no longer sufficient.
disruption of plauque
mechanical stress causes it, is what most often initiates IHD. can include hemorrhage, rupture or fissuring erosion or ulceration. UNSTABLE -moderately stenosed 50-75% core rich in lipid, macros and T cells, less smooth muscle proliferation, not uniform aroundthe vessell circumference.
Coronary artery thrombosis
Plauque rupture, erosion or ulceration causes exposure of thrombogenic lipid and subendothelial collagen, platelet aggregation, thrmobin fgeneration and thrombus formation, if the vessel is completely occluded- Sudden cardiac death. incomplete obstruction causes unstable angina or arrhythmias(sudden cardiac death. emoblization to distal branches and micro infarcts.