HYPERTENSION Sufia Husain Pathology Department KSU, Riyadh March 2014

LECTURE OUTLINE Introduction Definition Classification Primary vs secondary HTN Benign vs malignant HTN Causes of secondary HTN Pathogenesis Regulation of blood pressure Vascular morphology in HTN Heart in HTN Complications of HTN LR

H YPERTENSION - I NTRODUCTION Common problem (25% of population) Asymptomatic until late- Silent Killer – painless – Leading risk factor – MI & Stroke Complications alert to diagnosis but late…

H YPERTENSION AND H YPERTENSIVE V ASCULAR D ISEASE  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

R ISK FACTORS FOR H YPERTENSION Hereditary, Genetics- family history Race. African-Americans Gender. Men & postmenopausal women Age Obesity Diet, particularly sodium intake Lifestyle-stressfu l Heavy alcohol consumption Diabetes Use of oral contraceptives Sedentary or inactive lifestyle

C LASSIFICATION : BASED ON ETIOLOGY / CAUSE I. Primary/Essential Hypertension (95%) : Mechanisms largely unknown. It is idiopathic. II. Secondary Hypertension (5-10%): it can be due to pathology in the renal, endocrine, vascular or neurogenic systems

C AUSES OF S ECONDARY H YPERTENSION Renal Glomerulonephritis, Renal artery stenosis, Renal vasculitis Adult polycystic disease Chronic renal disease, Renin producing tumors Endocrine Adrenocortical hyperfunction (Cushing 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

P OLYCYSTIC KIDNEY

H YPERTENSION CLASSIFICATION BASED ON CLINICAL Benign hypertension : it can be essential/idiopathic HTN or secondary HTN Malignant hypertension: it can be essential/idiopathic HTN or secondary HTN

C LASSIFICATION BASED ON CLINICAL FEATURES. Benign: Modest level. Fairly stable over years to decades. Compatible with long life. Malignant(5%): there is rapidly rising BP which often leads to end organ damage It can complicate any type of HTN (i.e. essential or secondary) It is seen in 5% of HTNive patients. The diastolic pressure is usually over 120mmHg It is associated with:  Widespread arterial necrosis and thrombosis  Rapid development of renal failure  Retinal hemorrhage and exudate, with/without papilledema  Hypertensive encephalopathy  Left ventricular failure  Leads to death in 1 or 2 years if untreated.

P OSTULATED MECHANISMS /PATHOGENESIS OF E SSENTIAL H YPERTENSION 1.Defect in sodium excretion 2.Defect in cell membrane function: -Na/Ca transport 3.Increased sympathetic/ vasoconstrictive response

R EGULATION OF B LOOD P RESSURE (BP) BP = Cardiac Output x Peripheral Resistance Endocrine Factors Renin, Angiotensin, ADH, Aldosterone Neural Factors Sympathetic & Parasympathetic Humoral factors vasoconstrictors and vasodilators Blood Volume Sodium, Mineralocorticoids Cardiac Factors Heart rate & Contractility NOTE: Peripheral resistance is regulated predominantly at the level of the arterioles. Reduced renal sodium excretion in the presence of normal arterial pressure is probably a key initiating event; it is a final common pathway for the pathogenesis of most forms of hypertension

R EGULATION OF B LOOD P RESSURE (BP)

 GFR Renin by JGA Angiotensin IIAldosterone Sodium Retention  Blood Volume Vasoconstriction  P. Resistance Hypertension C OMBINATION OF ENDOCRINE AND OTHER FACTORS

B LOOD PRESSURE REGULATION Blood pressure is a function of cardiac output and peripheral vascular resistance  two hemodynamic variables that are influenced by multiple genetic, environmental, and demographic factors

A TRIAL NATRIURETIC PEPTIDE / FACTOR /H ORMONE (C ARDIONATRINE /C ARDIODILATINE / ATRIOPEPTIN ) It is a powerful vasodilator, and a protein (polypeptide) hormone secreted the heart muscle cells in the atria (atrial myocytes). It is involved in the homeostatic control 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 glomerulos.

R ENIN - ANGIOTENSIN - ALDOSTERONE AND ATRIAL NATRIURETIC PEPTIDE RULE

M ORPHOLOGY : Large Blood Vessels (Macroangiopathy) Atherosclerosis. HT is a major risk factor in AS. Small Blood Vessels (Microangiopathy) Arteriolosclerosis Hyaline arteriolosclerosis Hyperplastic arteriolosclerosis:

S MALL B LOOD V ESSELS (M ICROANGIOPATHY ) A RTERIOLOSCLEROSIS Hyaline arteriolosclerosis: Characteristic of benign hypertension Can also be seen in elderly without hypertension and in diabetic patients. Leads to benign nephrosclerosis due to diffuse renal ischemia. Hyperplastic arteriolosclerosis: Characteristic of malignant hypertension. May be associated with necrotizing arteriolitis (fibrinoid necrosis)

A. Hyaline arteriolosclerosis: hyalinosis of arteriolar wall with narrowing of lumen. B. Hyperplastic arteriolosclerosis (onionskinning) causing luminal obliteration of vascular lumen (periodic acid–Schiff [PAS] stain). V ASCULAR PATHOLOGY IN HYPERTENSION.

V ASCULAR P ATHOLOGY IN H YPERTENSION Hyaline/ Benign hypertension Hyperplastic/ Malignant hypertension

Left ventricular cardiac hypertrophy (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 induces left ventricular pressure overload which leads to hypertrophy of the left ventricle with increase in the weight of the heart. The free LV wall is > 2cm and the weight of the heart is > 500 grams In time, the increased thickness of the left ventricular wall impairs diastolic filling. This often induces left atrial enlargement.

L EFT V ENTRICULAR H YPERTROPHY

COMPLICATIONS /O RGAN DAMAGE IN HTN: 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 especially seen in malignant hypertension. Brain Haemorrhage, infarction leading to Cerebrovascular accidents A B

S UBARACHNOID H AEMORRHAGE C EREBRAL H EMORRHAGE

L ACUNAR I NFARCT C EREBRAL I NFARCTION