Lecture 8 - Hypertension Disorders PDF

Lipoprotein disorders, arteriolosclerosis, vessel aneurysms, venous system disorder; lymphatic disorders; vascular tumors and tumor-like conditions; vascular disorders; hypertension. Hypertension & Hypertensive Vascular Disease ⮚Common problem ⮚Asymptomatic until late - Silent Killer – painless....

Lipoprotein disorders, arteriolosclerosis, vessel aneurysms, venous system disorder; lymphatic disorders; vascular tumors and tumor-like conditions; vascular disorders; hypertension. Hypertension & Hypertensive Vascular Disease ⮚Common problem ⮚Asymptomatic until late - Silent Killer – painless. ⮚Complications alert to diagnosis but late. ⮚Hypertension: Definition: a sustained diastolic pressure more than 90 mm Hg or a sustained systolic pressure in excess of 140 mm Hg (>140/90) ⮚In the early stages of HTN there are few or no symptoms. ⮚Hypertension is an important factor which contributes in development of: ◦ Coronary heart disease. ◦ Cerebrovascular accidents (stroke) ◦ Cardiac hypertrophy ◦ Congestive heart failure. ◦ Aortic dissection. ◦ Renal failure. ◦ Retinopathy Risk factors for Hypertension 🞆 Hereditary,Genetics- family history 🞆 Race. African-Americans 🞆 Gender. Men & postmenopausal women 🞆 Age 🞆 Obesity 🞆 Diet, particularly sodium intake 🞆 Lifestyle-stressful 🞆 Heavy alcohol consumption 🞆 Diabetes 🞆 Use of oral contraceptives 🞆 Sedentary or inactive lifestyle Classification: based on etiology/cause I. Primary/Essential Hypertension (95%) : Mechanisms largely unknown. It is idiopathic. I. Secondary Hypertension (5-10%): it can be due to pathology in the renal, endocrine, vascular or neurogenic systems  Causes of Secondary Hypertension Glomerulonephritis, Renal Renal artery stenosis, Renal vasculitis Adult polycystic disease Chronic renal disease, Renin producing tumors Adrenocortical hyperfunction (Cushing Endocrine syndrome, primary aldosteronism, congenital adrenal hyperplasia) Hyperthyroidism/Thyrotoxicosis Hypothyroidism/Myxdema, Pheochromocytoma Acromegaly Exogenous hormones (glucocorticoids, estrogen e.g. oral contraceptives) Pregnancy-induced Vascular Coarctation of aorta Vasculitis e.g.Polyarteritis nodosa Increased intravascular volume Increased cardiac output Rigidity of the aorta Neurogenic Psychogenic Increased intracranial pressure Sleep apnea Acute stress, including surgery  PATHOGENESIS of Essential Hypertension Essential HTN occurs when the relationship between cardiac output and peripheral resistance is altered. Multiple genetic and environmental factors ultimately increase the cardiac output and/or peripheral resistance (BP = Cardiac Output x Peripheral Resistance) 1.Genetic factors: There is a strong genetic component (family history) e.g. a genetic effect is involved in making people more susceptible or less susceptible to high salt diet etc. a) Defect in renal sodium homeostasis: reduced renal sodium excretion is a key initiating event in most forms of essential hypertension. This decreased sodium excretion will result in increase in fluid volume and therefore increase in cardiac output, thereby elevating blood pressure. This is usually due to defect in cell membrane function: affecting Na/Ca transport. b) Functional vasoconstriction: abnormality in vascular tone such as increased sympathetic stimulation will cause vasoconstriction leading to increased peripheral resistance. c) Structural abnormality in vascular smooth muscle also leads to increased peripheral resistance. PATHOGENESIS of Essential Hypertension d) Also rare gene disorders can cause HTN by increasing renal sodium reabsorption e.g. Liddle syndrome. Liddle syndrome is an inherited autosomal dominant type of HTN, that begins in childhood. It is caused by mutations of the epithelial sodium channel protein (ENaC) which leads to increased sodium reabsorption in the renal tubules (followed by water), which leads to hypertension. Reabsorption of sodium is also correlates with potassium loss (hypokalemia). 2. Environmental factors: stress, obesity, smoking, physical inactivity and heavy consumption of salt also play a role. NOTE: In hypertension, both increased blood volume and increased peripheral resistance contribute to the increased pressure. However reduced renal sodium excretion in the presence of normal arterial pressure (initially) is probably a key initiating event. PATHOGENESIS of Essential Hypertension ENDOCRINE FACTORS: role of renin- angiotensin- aldosterone in regulating BP  Atrial natriuretic peptide / factor / Hormone (Cardionatrine / Cardiodilatine / atriopeptin) ▪ It is a protein (polypeptide) hormone secreted by the heart muscle cells in the atria of heart (atrial myocytes). ▪ It is a powerful vasodilator and is involved in the homeostatic balance of body water, sodium, potassium and fat. ▪ It is released in response to high blood volume. It acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure. ▪ It has exactly the opposite function of the aldosterone secreted by the zona glomerulosa ▪ In the kidney: ▪ decreases sodium reabsorption and increases water loss. ▪ Inhibits renin secretion, thereby inhibiting the renin–angiotensin– aldosterone system ▪ In adrenal gland: ▪ Reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex. ▪ In arterioles: ▪ Promotes vasodilatation ▪ In adipose tissue ▪ Increases the release of free fatty acids from adipose tissue. complications in HTN: A The organs damaged in HTN are: ▪ Cardiovascular ▪ Left ventricular cardiac hypertrophy(left sided hypertensive cardiomyopathy/ hypertensive heart disease) ▪ Coronary heart disease ▪ Aortic dissection ▪ Kidney ▪ Benign nephrosclerosis (photo A) ▪ Renal failure in untreated or in malignant hypertension ▪ Eyes ▪ Hypertensive retinopathy (photo B) is B especially seen in malignant hypertension. ▪ Brain ▪ Haemorrhage, infarction leading to Cerebrovascular accidents  Left ventricular cardiac hypertrophy (also known as left sided hypertensive cardiomyopathy/ hypertensive heart disease) ▪ Longstanding poorly treated HTN leads to left sided hypertensive heart disease. ▪ Hypertrophy of the heart is an adaptive response to pressure overload due to HTN. HTN induced left ventricular pressure overload which leads to hypertrophy of the left ventricle with increase in the weight of the heart and the thickness of the LV wall. Left Ventricular Hypertrophy Morphology of blood vessels in HTN: ▪ In large Blood Vessels (Macroangiopathy) ▪ Atherosclerosis. HTN is a major risk factor ▪ In small Blood Vessels (Microangiopathy) ▪ Arteriolosclerosis 1. Hyaline arteriolosclerosis: ▪ Seen in benign hypertension ▪ Can also be seen in elderly and diabetic patients even without hypertension. ▪ Can cause diffuse renal ischemia which ultimately leads to benign nephrosclerosis 2. Hyperplastic arteriolosclerosis: ▪ Characteristic of malignant hypertension. ▪ Can show onion-skinning on histology causing luminal obliteration of vascular lumen ▪ May be associated with necrotizing arteriolitis and fibrinoid necrosis of the blood vessel.  Vascular pathology in hypertension A. Hyaline arteriolosclerosis: B. Hyperplastic arteriolosclerosis hyalinosis of arteriolar wall (onionskinning) causing luminal with narrowing of lumen. obliteration of vascular lumen Vessel wall structure  Atherosclerosis Atherosclerosis is a specific type of arteriosclerosis (thickening & hardening of arterial walls) affecting primarily the intima of large and medium-sized muscular arteries. Chronic inflammatory response in the walls of arteries. Slowly progressive. A build-up of fat (cholesterol) within the artery wall. Characterized by intimal lesions called: atheromas, atheromatous or fibrofatty plaques Atherosclerosis Risk factors  LDL Vs. HDL LDL cholesterol : deliver cholesterol to peripheral tissues. HDL, "good cholesterol“: mobilizes cholesterol from developing and existing atheromas and transports it to the liver for excretion in the bile Atherosclerosis Pathogenesis  Atherosclerosis Clinical Complications Myocardial infarction (heart attack) Cerebral infarction (stroke) Aortic aneurysms Mesenteric occlusion Peripheral vascular disease (gangrene of the legs)  Vasculitis 🞆 It is inflammation of vessel walls with many possible symptoms Causes: 1.It is usually immune-mediated ❖ Immune complex deposition ❖ Antineutrophil cytoplasmic antibodies (ANCAs) ❖ Anti-endothelial cell antibodies ❖ Autoreactive T cells 2.It can also be caused by infection, physical or chemical injury  Summary of Vasculitides Vessel Disease comment Giant-cell arteritis >50. Arteries of head. Large Takayasu arteritis F