CVS 1 Pathology PDF

1 Cardiovascular diseases 1 Cardiovascular diseases 1 04 January 2025 20:35 Cvs 1 patho 03 January 2025 13:39 Vascular diseases are cla...

1 Cardiovascular diseases 1 Cardiovascular diseases 1 04 January 2025 20:35 Cvs 1 patho 03 January 2025 13:39 Vascular diseases are classified into: Hypertensive Vascular Vascular tumors Disease: Arteriolosclerosis Vasculitis (Affects arterioles) Atherosclerosis Aneurysms (due to deposition of & Dissections cholesterol, cholesterol esters → narrowing the vessels) 1-HYPERTENSIVE VASCULAR DISEASE is a disease affecting the blood vessels in hypertension - Essential hypertension: gradual age-associated rise in blood pressure. (which increases as we age ) Increase the risk for: Stroke Heart failure (hypertensive heart disease) Atherosclerotic coronary heart disease Aortic dissection Cardiac hypertrophy Multi-infarct dementia Renal failure Mechanisms leading to hypertension in vast majority of cases remain unknown - Interplay between: Genetic factors + Environmental factors Leading to increase blood volume and/or peripheral resistance. As you know the blood pressure is a function of the cardiac output which increases with the increase in the blood volume multiplied by the peripheral resistance, so any increase in the peripheral resistance or in the blood volume will result in increased blood pressure year 3 Page 1 2 04 January 2025 20:35 Cutoffs in diagnosing hypertension in clinical practice requires: Sustained diastolic pressures greater than 90 mm Hg or sustained systolic pressures more than 140 mm Hg However, patients with other cardiovascular risk factors (e.g., diabetes), lower thresholds may be applicable (meaning that we diagnose hypertension at 130 over 80 for example instead of 140 over 90). Associated with increased risk for atherosclerosis. Reduction of Bp reduces the incidence and clinical sequelae (including death) of all forms of hypertension- related disease. (so we have to treat hypertension in order to decrease the risk of these consequences) Even we treat the asymptomatic HTN to decrease these consequences (preventive medicine) 5% of patients develop malignant hypertension (should be treated promptly) defined as: - Rapidly rising blood pressure, if untreated, leads to death within 1-2 years. - Severe elevation over along period (not an acute one) (systolic pressures over 200 mm Hg or diastolic pressures over 120 mm Hg) - Frequently with renal failure and retinal hemorrhages, with or without papilledema Hypertension is divided into two forms according to Pathogenesis: Primary idiopathic (95%) Secondary to an identifiable underlying condition (5%) - the underlying cause is not known - mostly in younger age groups and there is an - most of the time it's a factor of - With associated health condition like: aging, genetics & others. Primary renal disease Renal artery narrowing (stenosis) renovascular hypertension (in which there's a problem in the kidney, the vasculature and the renin angiotensin production) Adrenal disorders year 3 Page 1  Mechanisms of Essential Hypertension The Essential Hypertension is a primary hypertension in which no identifiable specific cause is founded. Reduced renal sodium excretion. (which occurs as a result of aging the kidney will retain the sodium which will reabsorb water which will increase the blood volume thus increasing the blood pressure) Increased vascular resistance (chronic vasoconstriction). Genetic factors - important but there is no single gene responsible for hypertension - (genetic polymorphisms in genes involved in regulation of renin angiotensin and angiotensinogen and in the regulation of the lipid metabolism so they are multiple genes, farnilial clustering of hypertension) Environmental factors (stress, obesity, smoking, physical inactivity, and high levels of salt consumption (highly linked to hypertension)) Effects on blood vessels Accelerates atherogenesis & Degenerative changes in the walls of Small blood vessel (arterioles) disease: development of atherosclerosis. large- and medium-sized arteries: - Hyaline arteriolosclerosis - aortic dissection - Hyperplastic arteriolosclerosis - cerebrovascular hemorrhage Hyaline arteriolosclerosis Hyperplastic arteriolosclerosis - With benign hypertension. - Typical of severe/malignant hypertension. - In kidneys lead to nephrosclerosis (glomerular scarring) - In malignant hypertension + fibrinoid deposits + which will lead with time to the renal failure associated vessel wall necrosis (necrotizing arteriolitis), with hypertension. particularly prominent in the kidney. - Can be seen in elderly normotensives (not specific to - Under microscope: hypertension). Vessels exhibit "onion skin", concentric, laminated thickening of arteriolar walls and luminal narrowing - Common in diabetic microangiopathy. and decrease the blood supply. - It is characterised microscopically by: - the appearance of Homogeneous, - pink hyaline thickening of the arteriolar walls, - with loss of underlying structural detail, - and luminal narrowing thus decreasing the blood supply to the effected organs. - Due to leakage of plasma components across injured ECM into vessel walls year 3 Page 1  4 04 January 2025 20:35 - So, it is characterized as you can see here by a pink hyaline - There is a concentric narrowing which we call it "onion material in the wall of the small arteriole this will lead to skin" leading to a very small lumen in the blood vessel narrowing of the lumen and decrease blood supply 2-ATHEROSCLEROSIS Is Intimal lesions (atheromas or atherosclerotic plaques) that can: - Impinge on the vascular lumen (stenosis), - can rupture and cause superimposed sudden occlusion (thrombosis) - or weaken the underlying media (aneurysms) because of the compression of the underlying media by these atherosclerotic plaques and decrease supply of the media of the blood vessel this will lead to aneurismal dilatation of the blood vessel. - So, atherosclerosis is associated first by stenosis, second by superimposed thrombosis and acute block of the blood supply and third by the development of the aneurysms - Underlies the pathogenesis of coronary, cerebral, and peripheral vascular disease effecting the lower extremities. →Atheromatous plaques: raised lesions (usually are yellow in color) composed of soft friable lipid cores (mainly cholesterol and cholesterol esters, with necrotic debris) covered by fibrous caps. This area represents the extracellular lipid which is Also, you can see the lipid composed of cholesterol and cholesterol esters core contains migrating smooth muscle cells Covered by a Some of the lipid is present in the macrophages within the With time will undergo atrophy and weakening macrophages as yellow droplets (considered intracellular) which lead to aneurysmal dilatation year 3 Page 1 5 04 January 2025 20:35 Constitutional (nonmodifiable) Risk Factors for atherosclerosis Modifiable Genetics Hyperlipidemia - familial hypercholesterolemia specifically hypercholesterolemia. - multifactorial traits like HTN and diabetes Hypertension Are associated with an injury Age (important risk factor): to vessel wall accelerating the - incidence of MI or stroke increases 5-fold between 40-60 Cigarette smoking process of atherosclerosis years of age. - Death rates as well. Diabetes mellitus (increased risk of all atherosclerosis associated Gender: complications IHD (ischemic heart disease), stroke and gangrene of the lower limbs) - premenopausal women are protected against atherosclerosis, - after menopause incidence increases and can exceed that in men. (Sometimes this is attributed to the effect of estrogen as protective factor in premenopausal women, but this idea have some problems because the administration of hormone replacement therapy in postmenopausal ladies is not associated with a decreased risk of vascular accidents where it is actually increasing the risk) Hyperlipidemia: More specifically hypercholesterolemia. (LDL: low density lipoprotein) cholesterol (bad cholesterol) →increased risk. (HDL: high density lipoprotein ) cholesterol (good cholesterol) → reduced risk. So the aim is always to decrease level of LDL and increase level of HDL : High dietary intake of cholesterol and saturated fats (egg yolks, animal fats, and butter) raises plasma cholesterol levels. Omega3 (abundant in fish oils) is beneficial (can raise the HDL levels). Exercise raise HDL levels, whereas obesity and smoking lower them. year 3 Page 1 MORPHOLOGY (either macroscopic or microscopic). Series of morphologic changes Fatty Streaks lipid-filled foamy macrophages in the wall blood vessel near the intima near the endothelial, minimally raised lesion, do not cause any significant flow disturbance, Occur in childhood as early as infancy period. However not all fatty steaks will develop into Atherosclerotic Plaque, some of these fatty steaks Will fuse together and enlarge to from the Atherosclerotic Plaque. Atherosclerotic Plaque intimal thickening and lipid accumulation, yellow raised lesions covered by fibrous caps, patchy (they do not involve the whole circumference of blood vessel, usually they come at eccentric location with time they enlarge and impede the blood flow and cause the narrowing of the lumen of the blood vessel. In descending order of severity (frequency): 1- infrarenal abdominal aorta, 2- the coronary arteries 3- the popliteal arteries (lower limbs) 4- the internal carotid arteries which increases the risk of stroke and cerebral accidents 5- the vessels of the circle of Willis at the base of the brain For unknown reasons vessels of the upper extremities usually are spared, as are mesenteric and renal arteries,   except at their ostia (openings where they emerge from the aorta). year 3 Page 1 7 04 January 2025 22:45 Atherosclerotic lesions Fatty streaks As the patient ages, atherosclerotic plages appear more commonly and they are larger & elevated yellowish lesion. As you can see in picture A and picture B, these atherosclerotic lesions are associated with complications like ulceration or superimposed thrombosis giving them this brown color Opening of the blood vessels from the aorta and this aorta is opened longitudinally and you can see small yellow lines are called fatty streaks which are not associated with an elevated lesion under the microscope, they are only macrophages filled will lipid and they can occur in the childhood Atherosclerotic plaques are susceptible to acute clinically important changes: Rupture, ulceration, or erosion exposes highly thrombogenic substances like lipid core for example thrombus formation which can totally occlude the blood vessel resulting in an acute syndrome like myocardial infraction if we are talking about coronary arteries. Hemorrhage into a plaque leading to formation of hematoma within the plaque this will increase the size of it and can occlude the blood vessel Athero-embolism where some part of these atherosclerotic plaques will detach and is carried in the circulation and act like embolus Aneurysm formation (aneurysmal dilation and rupture). This is due the weakness in the underlying media due to atrophy by the enlarging plaques and due to decreased blood supply year 3 Page 1  8 04 January 2025 22:45 Starts early as in childhood in the from of fatty steaks Now the clinical phase is accompanied by the and these are yellow in color but usually, complication which we talked about they are not associated with any health complications like repute or erosion of the plaque where the because they will occlude or narrow the blood vessel as superimposed thrombus formation, they enlarge, hemorrhage into the plaque leading to hematoma, they will develop into fibrofatty plaques which are aneurismal dilatation and rupture of the blood usually eccentric with a lipid core on the blood vessel vessel and sometimes progressive growth of the lumen plaque leading to luminal narrowing with advancing size it will lead to critical narrowing. will lead to critical stenosis leading to a severe narrowing of the blood vessel deceasing the blood supply to the affected organ. Plaque rupture with and w/o superimposed thrombus Rapture of the hematoma And this rapture can be accompanied by the superimposed thrombus which can totally occlude the blood vessel year 3 Page 1  9 04 January 2025 22:45 Clinicopathologic Consequences of Atherosclerosis Large elastic arteries (aorta, carotid, and iliac arteries) and large- and medium-sized muscular arteries (coronary, renal, and popliteal arteries) are the vessels most commonly involved by atherosclerosis so the consequences will be: Myocardial infarction Cerebral infarction (stroke) Aortic aneurysm Peripheral vascular disease (heart attack) if it' s in the cerebral blood if it's in the aorta (gangrene of extremities) if if it' s in the coronaries vessels or the carotid it's in the iliac blood vessels or in the popliteal arteries Atherosclerotic Stenosis whenever we have atherosclerotic plaque, and it enlarges. - Impinge or decrease on blood flow either by: 1. Acute plaque change like superimposed thrombus for example or aeroembolism. OR 2. Gradually increasing size of the atherosclerotic plaque → critical stenosis → chronic occlusion → limits blood flow to the organs Critical stenosis (70% occluded) causes: → angina (heart) which will precede the development of the myocardial infraction (a chronic problem), → bowel ischemia, → ischemic encephalopathy which may precede the development of a stroke, → intermittent claudication which is pain in the limbs upon walking due to the decreased blood supply of the lower limbs due to this stenosis. year 3 Page 1