Pathology: Hypertensive and Atherosclerotic Cardiovascular Disease Flashcards
List the finctions of the vasular endothelium in basal state
Maintain a permeability barrier, provide a nonthrombogenic surface to maintain blood In liquid state, elaboration of mediators for hemostasis, produce ECM, modulate blood flow and vasomotor tone by producing relaxing factors (NO) and contracting factors (endothelin) Regulate inflammation, regulate growth by elaboration of growth factors, metabolize some hormones (angiotensin)
Endothelial cell activation
in response to certain stimuli (turbulant flow, increased BP, etc) the endothlial cells activat and respond by aquiring new (indicible) properties
endothelial cell inducing stimuli
cytokines (bacterial products), hemodynamic stresses and lipid products, advanced glycation end products of DM, viruses, complement components, hypixia
Activated endothelia cell response examples
expression of adhesion molecules, production of cytokines, chemokines, growth factors, and vasoactive molecules. Prodcution of MHC molecules, procoagulant and/or anticoagulant molecules and other biologically active molecules
Endothelial Dysfunction
endothelium becomes proinflammatory or prothromboyoc. Some forms are slow onset (hours to days) - require alterations in gene expression and protein synthesis othe rforms are rapid onset (minutes) - do not require change in gene extression and protein synthesis
what cell type is responsible for vasoconstriction and vasodilation in repons eto pysiologic or phramacologic stimuli (ex: blood pressure
Vascular smooth muslce cells
Vascular smooth muscle cells
responsible for vasoconstriction/dilation in response to stimuli, play role in norma vascular repair and pathological proceses, capacity to prolifereate when appropriately stimiled (ex: prolonged HTN) Can synthesize collagen, elastin, and proteoglycans (ground sunstance) and can elaboratte growth factors and cytokines (inflammatory mediators)
sterotypical response of vessel wall to injury
intimal thickening
Descrive the vascular response to injury
endothelial cell involved in repair migrate to injured areas, smooth muscle or preucursor cells migrate to the intima and proliferate secrete ECM. Neointimal smooth muscle cells are motile and can divide but not contract. Healing process results in permanent intimal thickening. With persistent or recurrent insults excessive thickening can cause narrowing or stenosis of small and medium blood vessels (eg: atherosclerosis) impeding downstream tissue perfusion
Main regulation of blood volume
renal sodium excretion or resorption (renin angiotensin aldosterone axis)
Normal BP
less than 120/80
Elevated BP
systolic between 120-129 and diastolic less than 80
Stage 1 BP
Systolic between 130-139 or diastolic between 80-89
Stage 2 BP
Systolic at least 140 or diastolic at least 90
Hypertensive crisis
Systolic over 180 and/or diastolic over 120 - patinets need prompt changes in medications if there are no other indications of problems or immediate hospitalization if there are signs of organ damage
Essential Hypertension
90-95% of cases - cause is unknown: multifactorial (tends to run in families)
Secondary hypertension causes
1.) Renal 2.) Endocrine 3.) Cariovascular 4.) Neurologic
Renal causes of secondary hypertension
acute glomeronephritis, polycystic disease, renal artery stenosis, renal vasculitis, renin producing tumors
Endocrine causes of secondary hyertension
adrenocortical hyperfucntion, exogenous hormones, pheochromocytoma, acromegaly, hyperthyroidism/hypothyroidism, pregnancy induced
Cardiovascular causes of secondary hypertension
coarctation of aorta, polyarteritis nodosa, increased intravascular volume (volume overload) aortic rigidity
Neurologic causes of secondary hypertension
Psychogenic, increased intracranial pressure, sleep apnea,a cute stress (including surgery)
Clinical features of HTN
Most cases are clinically silent for yearts. Headaches, shortness of breath, nosebleeds (nonspecific symptoms that do not show up intil hypertension is severe)
Clinical features of malignant hypertension
rapidly rising blood pressure leading to severe hypertension (often leads to death within 1-2 years if untreated) Most commonly is superimposed on chronic hypertension. Renal failure, retinal hemorrhages and exudates, +/- papilledema
Complictaions of HTN
Acceleration of atherosclerosis, cardiac hypertrophy and heart failure (hypertensive heart disease), multi-infarct dementia, aortic dissection, renal failure, stroke (hemorrhagic or ischemic)
Pathogenesis of renovascular HTN
renal artery stenosis leads to decreased blood pressure and flow in the glomerular afferent arteriole which stimulates renin secretion leading to increased vascular tone and blood volume via the angiotensin aldoserone pathway
Monckeberg’s Medical Calcific Sclerosis
Calcific depositis in the muscular arteries in people over the age of 50 (especially women) that does NOT involve the limen. This is the most significant form of arterioscleosis
Arteriolosclerosis
diseaseof small vessels and arterioles associated with hypertension and diabetes
Hyaline arteriolosclerosis
due to endothelial injury with leakage of plasma into arteriolar walls and increased smooth muscle cell matrix synthesis. Arteriolar wall is thicked with increased plasma protein deposition and markedly narrow lumen (stenosis)
Hyperplastic arteriolosclerosis
“onion skinning” causing obliteration of the lumen. Occurs in severe (malignant) HTN
which form of arteriolosclerosis occurs in malignant HTN
Hyperplastic arteriolosclerosis
what is the most frequent and clinically important pattern of ateriosclerosis
Atherosclerosis
foam cells
macrophages stuffed with mdified ingested lipids (seen in atherosclerosis)
Early gross changes of atherosclerosis
aorta with fatty streaks mainly associated wit the ostia where blood flow is more tubulent and non-denuding ednothelial damage is most frequent
where does athrosclerosis distribule
more in the abdominal aorta than the thoracic aorta. Predilection for the ostia of major branches (points of increased turbulence)
modifiable risk factors for atherosclerosis
Hyperlipdemia (even in the absence of other risk factors) Hypertension, cigarette smoking, diabetes mellitus
Progression and sequelae of atherosclerosis
1.) calcification, 2.) rupture, ulceration, erosion of plaques, inducing thombosis 3.) Hemorrhage into plaques 4.) Atheroembolism 5.) Aneurysmal dilatation (especially in the abdominal aorta)
Hypertensive Heart Disease
Hypertension leads to pressure overlad and ventricular hypertrophy in order to meet the increased demands placed on the heart
Minimal criteria for diagnosing Systemic (left sided) hypertensive heart disease
1.) Left ventricular Hypertrophy (usually concentric) in the absence of other cardiovascular pathology (aortic stenosis,etc) 2.) Histroy or Pathologic evidence of hypertension
Discribe the gross mophology of systemic (left sided) hypertension
thickened left ventricle (>1.5cm) , ventricle becomes stiff and noncompliant due to interstitial fibrosis leading to ventricular filling defect and often subsequent left atrial enlargement
earliest microscopic change seen in systemic hypertensive heart disease
myocyte hypertrophy(increase in the diameter)
Potential sequelae of systemic hypertensive heart disease
1.) Ischemic heart disease 2.) Renal damage 3.) Cerebrovascular damage 4.) Progressive heart failure or sudden cardiac death from arrythmia 5.) Development of aneurysms (especially aortic - also can be thoracic)
Pulmonary (right sided) HTN disease
stems from pressure overload in the right ventricle. Pulmonary vasculature is typically low pressure and the normal right ventricle is thinner compared to the left ventricle
cor pulmonale
isolated pulmonary hypertensive heart disease. Characterized by 1.) Right ventricular hypertrophy (concentric) 2.) Right ventricular dilation (results in venous back up which can cause symptoms such as JVD and ansacara) 3.) Potential right heart failure secondary to pulmonary hypertension
MCC of cor pulmonale (isolated pulmonary hypertension)
Lung disease
Acute cor pulmonale
marked dilation of the right ventricle (ovoid shape) WITHOUT hypertrophy
Chronic cor pulmonale
1.) Right sided ventricular wall thickening 2.) Fat in the walls disappear and fat align themselves circumfrentially 3.) Hypertrophied right ventricle may compress left ventricle or lead to recurgitation and thickening of the tricuspid valve
Potential sequelae of Pulmonary Hypertensive Heart Disease
1.) Tricuspid valve Incompetence 2.) right sided heart failure (JVD, ansacara, dyspnea, fatigue, weakness, fainting, palpations and arrythmias)
