Pathology of Hypertension Lecture Notes PDF

Pathology of Hypertension Dr Adam Botha Division of Anatomical Pathology University of the Witwatersrand / National Health Laboratory Service Learning objectives By the end of the session, the student will be able to define hypertension By the e...

Pathology of Hypertension Dr Adam Botha Division of Anatomical Pathology University of the Witwatersrand / National Health Laboratory Service Learning objectives By the end of the session, the student will be able to define hypertension By the end of the session, the student will be able to list the different types and causes of hypertension By the end of the session, the student will be able to describe the pathogenesis of different types of hypertension By the end of the session, the student will be able to recognise and describe the pathological features, complications and target organ damage associated with hypertension Hypertension Defined as having a systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg Importance of hypertension Common disease – approximately 29% of general population hypertensive based on the above criteria Largely clinically silent (until late stages of the disease) Causes complications in multiple end organs If left untreated- half of patients will die of heart complications (ischaemic heart disease or congestive heart failure), and another third of stroke Treatment with blood pressure-lowering drugs dramatically reduces incidence and death rates attributable to hypertension- related pathology Types of hypertension Essential hypertension Secondary hypertension Essential hypertension 90-95% of cases of hypertension “Idiopathic” Essential hypertension – “Idiopathic” Does not mean that there is no cause / underlying risk factors Cumulative effect of: Multiple non-genetic factors (e.g. stress, salt intake, obesity, smoking) Multiple (individually minor) genetic polymorphisms controlling: Vasomotor tone and blood volume regulation Sodium homeostasis e.g. enzymes that influence aldosterone synthesis, renal epithelial sodium channel proteins Secondary hypertension Attributable to a single or well-defined group of identifiable underlying causes / diseases May divide into categories depending on system involved: Renal Endocrine Cardiovascular Neurologic Secondary hypertension- Renal causes Renovascular hypertension As a result of renal artery stenosis or fibromuscular dysplasia Decreased glomerular flow and decreased pressure in afferent arteriole of glomerulus → renin secretion → ↑ vascular tone and blood volume Younger than other causes of hypertension (3rd to 4th decade), > Renal artery stenosis: Responsible for 2-5% of hypertension cases Curable by surgery 70% caused by narrowing at origin by atheromatous plaque (older, diabetes) Fibromuscular dysplasia: Heterogenous entity characterised by thickening of intima, media or adventitia Robbins and Cotran Pathologic Basis of Disease, 9th Ed. Mitchell RN, Kumar, V et al. Eds. Elsevier Saunders, Philadelphia, 2017 Secondary hypertension - Renal causes Acute glomerulonephritis Chronic renal disease Polycystic disease Renal vasculitis Renin-producing tumours (e.g. reninomas - benign tumors originating from the cells of the juxtaglomerular apparatus) Secondary hypertension – Endocrine causes Adrenocortical hyperfunction Exogenous hormones Pheochromocytoma Acromegaly Hypothyroidism Hyperthyroidism Pregnancy-induced Secondary hypertension – Endocrine causes Adrenocortical hyperfunction Cushing syndrome Primary aldosteronism Congenital adrenal hyperplasia Licorice ingestion Secondary hypertension – Endocrine causes Exogenous (iatrogenic) hormones: Glucocorticoids Oestrogen Sympathomimetics Tyramine-containing foods Monoamine oxidase inhibitors  Secondary hypertension – Endocrine causes Phaeochromocytoma Neoplasm of the adrenal medulla 90% present with hypertension (particularly paroxysmal episodes with palpitations) Important treatable secondary causes of hypertension in younger individuals Robbins and Cotran Pathologic Basis of Disease, 9th Ed. Mitchell RN, Kumar, V et al. Eds. Elsevier Saunders, Philadelphia, 2017 Secondary hypertension – Cardiovascular causes Aortic disease Coarctation Rigidity Vasculitis Increased intravascular volume or increased cardiac output Secondary hypertension – Neurologic causes Psychogenic Increased intracranial pressure Sleep apnea Pathological features Target organ damage predominantly as a result of vascular pathology: Large vessels (as well as medium and small vessels) Accelerates atherosclerosis Degenerative changes in walls (↑risk aortic dissection, cerebrovascular haemorrhage) Small arterioles – arteriolosclerosis = general term denoting arterial wall thickening and loss of elasticity  Pathological features Arteriolosclerosis in hypertension – two forms: 1. Hyaline arteriolosclerosis: Endothelial cell injury → plasma leakage into arteriole wall → ↑smooth muscle cell matrix Microscopically: diffuse pink hyaline arteriolar wall thickening with luminal stenosis Robbins and Cotran Pathologic Basis of Disease, 9th Ed. Mitchell RN, Kumar, V et al. Eds. Elsevier Saunders, Philadelphia, 2017  Pathological features Arteriolosclerosis in hypertension – two forms: 2. Hyperplastic arteriolosclerosis Occurs in severe hypertension Reduplication of basement membrane and smooth muscle cell proliferation Microscopically: concentric laminated (“onion-skin”) thickening of walls with luminal narrowing Robbins and Cotran Pathologic Basis of Disease, 9th Ed. Mitchell RN, Kumar, V et al. Eds. Elsevier Saunders, Philadelphia, 2017 “Malignant” hypertension Small percentage of hypertensive persons (up to 5%) Show rapidly rising blood pressure – if untreated leads to death within 1-2 years Characterised by severe hypertension – often systolic blood pressure > 120mmHg and diastolic blood pressure >120mmHg Other features: encephalopathy, renal failure, retinal haemorrhage and exudates (with or without papilledema) Microscopically: hyperplastic arteriolosclerosis + fibrinoid deposits and vessel wall necrosis = necrotising arteriolitis  Complications / target organ damage Kidney: Long-standing blood pressure: Nephrosclerosis: A term used for the renal pathology associated with sclerosis of small renal arteries and arterioles Macroscopy: Fine, granular cortical surface Microscopy Tubular atrophy, interstitial fibrosis and glomerular sclerosis due to ischaemia Hyaline arteriosclerosis Robbins and Cotran Pathologic Basis of Disease, 9th Ed. Mitchell RN, Kumar, V et al. Eds. Elsevier Saunders, Philadelphia, 2017  Complications / target organ damage Kidney: Malignant hypertension results in: Malignant nephrosclerosis: Macroscopy: Small, pinpoint petechial haemorrhages on the cortical surface of the kidney – imparting a ‘flea bitten’ appearance Microscopy: Fibrinoid necrosis of arterioles, necrotic glomeruli infiltrated by neutrophils, thrombosed glomerular capillaries, necrotising arteriolitis Robbins and Cotran Pathologic Basis of Disease, 9th Ed. Mitchell RN, Kumar, V et al. Eds. Elsevier Saunders, Philadelphia, 2017 Complications / target organ damage Heart: Hypertensive heart disease (HHD) is a consequence of increased demand placed on the heart by hypertension, causing pressure overload and ventricular hypertrophy Pathologic criteria for diagnosis: Concentric left ventricular hypertrophy in the absence of other cardiovascular pathology Clinical history or pathologic evidence of hypertension in other organs Macroscopy: Hypertrophy often >2cm in thickness, total heart weight >500g, hypertrophy leads to stiffness that impairs diastolic filling, inducing left atrial enlargement Microscopy: Increased diameter of cardiac myocytes with variable degrees of cellular and nuclear enlargement Interstitial fibrosis Complications / target organ damage Central nervous system (CNS): Lacunar infarcts Slit haemorrhages Hypertensive intraparenchymal haemorrhage Hypertensive encephalopathy Complications / target organ damage - CNS Lacunar infarcts Pathogenesis: Deep penetrating arteries and arterioles that supply the basal ganglia and hemispheric white matter as well as the brainstem develop arteriolar sclerosis and may become occluded Macroscopy: Single or multiple, small cavitary infarcts - lake-like spaces,