2016-03-07 Pathology of Hypertension Honghe Zhang honghezhang@zju.edu.cn Tel:88208199 Department of Pathology
❶ Genetic predisposition ❷ Dietary factors ❸ Environmental factors ❹ Others
Definition and classification of hypertension (WHO/ISH) Category Systolic Blood Pressure Diastolic Blood Pressure Normal < 130 <85 Pre-hypertension 130-139 85-89 Hypertension Stage 1 140-159 90-99 Hypertension Stage 2 160-179 100-109 Hypertension Stage 3 180 110
Regulation of BP
Etiological Classification
Etiology
Hypotheses 1. Neural disorder Stress, disorder of the central regulation of BP Constrictors, dilators, peripheral resistance increasing 2. Endocrine disorder
3. Renal hypotheses Renin---angiotensin---aldosterone system Juxtaglomerular cells Renin--- ACE angiotensinogen-----angiotensin1---- angiotensin2 Direct action on vessel smooth muscle vasoconstriction Aldosterone increases distal tubular reabsorption of sodium and water
Science 272:676, 1996
4. Inheritable hypotheses Familial aggregation of hypertension Depend on the cumulative effects of allelic forms of several genes that affect BP 5. Other environmental factors obesity, smoking, heavy consumption of salt
Alpine ibex cling to a near-vertical rock face of a northern Italian dam in summer 2010
Summary Complex disorder More than one cause Disturbances in any of the factors Genetically predisposed individual
Type and pathology 1. Benign hypertension 2. Malignant hypertension
Benign hypertension Remaining at a modest level; Fairly stable over years to decades; With long life.
1. Functional change of vessels (first stage) Arterial discontinuous spasm; BP change; No obvious clinical feature.
2. Structure changes of vessels (second stage) 1) Hyaline arteriole Arterial continuous spasm--increased permeability of the small vessels-- endothelial injury--plasma proteins deposition Microscopically Vessel wall replaced by homogenous eosinophilic material ; Reduction of luminal diameter.
2) Progressive thickening of muscular artery walls Hypertrophy of the muscular media and later fibrosis; fibroelastic hyperplasia Highly increased BP; obvious clinical features.
3. Organ changes (third stage)
Pathogenesis of vascular changes
1) Heart: hypertensive heart disease Compensation: concentric left ventricular hypertrophy Grossly: larger size, heavy weight, thickened wall and papillary muscles Microscopically: hypertrophy of myocardium, enlarged nuclei Decompensation : ventricular dilatation cardiac failure (left right)
Left ventricular hypertrophy The left ventricle is markedly thickened in this patient with severe hypertension that was untreated for many years. The myocardial fibers have undergone hypertrophy.
This left ventricle is very thickened, but the rest of the heart is not greatly enlarged.
2) Kidney: hypertensive nephrosclerosis (Primary granulo-contraced kidney) Grossly: small and hard with a surface of diffuse, fine granularity; atrophic thinning of the cortex; poor demarcation of cortex from medulla on cut surface.
Primary granular atrophy of the kidney
Microscopically: Hyaline arteriolosclerosis: hyaline thickening of the walls of the small arteries and arterioles--narrowed lumen--decreased blood flow---ischemic atrophy Nephron: Coexisting of atrophy and hypertrophy Interstitial fibrosis and lymphocytic infiltrate Clinical feature: proteinuria
Hyaline arteriolosclerosis is seen in the elderly, but more advanced lesions are seen in persons with diabetes mellitus and/or with hypertension.
3) Brain Cerebral edema: increase in intracranial pressure herniation, hypertensive encephalopathy, hypertensive crisis Softening of the brain Cerebral hemorrhages: most severe and lethal complication, most located at basal nucleus and internal capsule
The large hemorrhage in this adult brain arose in the basal ganglia region of a patient with hypertension. This is one cause for a "stroke".
Lacunar Infarct
4) Retinal changes Small white foci of retinal ischemia (cotton-wool spots). Yellow hard exudates, due to lipid deposition deep in the retina.
1. Far less common, young people, kidney is the most often affected organ. 2. Charactristic change: Fibrinoid necrosis of arterioles and arteries (necrotizing arteriolitis) Hyperplastic arterioles; an onion-skin appearance 3. Rapidly rising BP, especially DBP 130mmHg
4. Necrotizing glomerulitis with micro- thrombi, proteinuria, hematuria, azotemia, uremia; 5. Obvious retinal changes: retinal hemorrhages and exudates, papilloedema, visual impairments, blindness 6. Most patients die of uremia, cerebral hemorrhage and cardiac failure within1-2 years without treatment.
One complication of hyperplastic arteriolosclerosis with malignant hypertension is fibrinoid necrosis, as seen here in a renal arteriole.
Malignant hypertension. The arteriole here has an "onion skin" appearance typical of hyperplastic arteriolosclerosis.