HYPERTENSION A sustained diastolic pressuregreater than 90 mm Hg or a sustainedsystolic pressure in excess of 140 mm Hgis considered to constitute hypertension.
•Hypertension is a major risk factor foratherosclerosisat all ages, but after 45 yrs HTN is stronger risk factorthan hypercholesterolemia.Men at age 45 - 62 whose BP exceeds 169/95 mm Hg havegreater risk of IHD than those with BP of 140/90 mm Hgor lower.Both systolic and diastolic levels are important inincreasing risk, epidemiological studies reveal systolicpressure to be more important
• HTN is a risk factor for coronary artery disease, hypertrophy of the heart, heart failure• CVA• Aortic dissection• Renal failure
According to etiology hypertension maybeEssential (95%)(idiopathic and apparently primary) ORSecondary(secondary to an identifiable cause)
Secondary hypertension continuedCardiovascular Neurologic• Coarctation of aorta • Psychogenic• PAN • Increased intracranial• Increased intravascular pressure volume • Sleep apnea• Increased cardiac out put • Acute stress, including• Rigidity of aorta surgery
Clinical subgroups of hypertention1. Benign Hypertension – generally does not cause short term problems specially when controlled. It is asymptomatic and compatible with long life unless an MI or CVA supervene.2. Accelerated or Malignant Hypertension The syndrome is characterized by severe hypertension (systolic over 200 and diastolic over 120mmhg), renal failure and retinal hemorrhages and exudates with or without papilloedema. Usually develops on preexisting benign hypertension whether essential or secondary but may arise in normotensives.
PATHOGENESIS OFESSENTIAL HYPERTRNSIONArterial hypertension occurs whenthe relationship between cardiacoutput and total peripheralresistance is altered.
REGULATION OF NORMAL BLOOD PRESSUREBlood pressure level is a complexed trait that is determined by interaction of• Genetic factors• Environmental factors• Dermographic factorsFactors determining variation in blood pressure within and between populations include age, gender, body mass index, diet, and principally sodium intake.
Regulation of normal blood pressure contdThe magnitude of the arterial pressuredepends on two fundamentalhemodynamic variables:Cardiac outputTotal peripheral resistance
Regulation of normal blood pressure contd• Cardiac out put is • Peripheral highly dependent on resistance is blood volume, which determined mainly at in turn is greatly the arteriolar level -- influenced by body neural and hormonal Na homeostasis factors. Resistance vessels exhibit auto regulation
Regulation of normal blood pressure contdRole of kidney• Renin angiotensin system- Regulates both peripheral resistance and sodium homeostasis( direct action on vessels, increase blood volume by producing aldosterone secretion).• Kidney produces vascular relaxing factors or antihypertensive substances(PG, NO)• When BV reduces—GFR falls leading to increased absorption of sodium by the proximal tubules.
Regulation of normal blood pressure contd Roleof kidneycontd• Role of Naturetic factors (including the atrial and ventricular factors)-- inhibit Na reabsorption in the distal tubules. Induce vasodilatation— endogenous inhibitors of renin angiotensin system.• In renal excretory failure, increased arterial pressure is a compensatory mechanism that helps restore fluid and electrolyte balance.
Mechanism of essential hypertension contd• Genetic or environmental factors that affect cardiac output or peripheral resistance or both• Single gene disorders cause rare severe forms of HTN. E.g.Genetic defects in aldosterone metabolism mutations in proteins that affect sodium reabsorption-Liddles syndrome in which there is a mutation in ENaC protein leading to increased reabsorption of Na.
Mechanism of essential hypertension-contd• Inherited variations in blood pressure may also depend on cumulative effects of allelic forms of several genes e.g.. Predisposition to essential hypertension is associated with variations ino gene encoding components of renin angiotensin systemo Polymorphism in both angiotensinogen locus and the angiotensinogen II type I receptor locuso These variations may contribute to the known racial differences
Environmental factors• Stress• Obesity• Smoking• Physical activity• Heavy salt consumption
WHAT ARE THE PRIMARY DEFECTS IN ESSENTIAL HYPERTENSION?1.Renal Retention of Excess Sodium2. Vasoconstriction and Hypertrophy
Mutations causing• Hypotension • Hypertensiono Gitelman syndrome o Liddles syndromeo Barter syndrome o 17 alpha hydroxylaseo 21 hydroxylase defficiency defficiency o 11 beta hydroxylaseo Aldosterone synthetase defficiency defficiency
Disorders affecting blood pressure• Genetic • Acquiredo Fibromuscular o Oral contraceptives hyperplasia o Renal Artery stenosiso Angiotensinogen variants o Renin secreting tumourso Liddles syndrome o Licorice ingestiono 17 alpha hydroxylase defficiency o Cushing syndromeo 11 beta hydroxylase defficiency
VASCULAR PATHOLOGY accelerates atherogenesis causes degenerative changes in the structure ofthe walls of large and medium sized blood vesselsthat potentiate both aortic dissection andcerebrovascular hemorrhage. It is associated with two forms of small bloodvessel disease: hyaline arteriosclerosis hyperplastic arteriosclerosis
MORPHOLOGYHYALINE ARTERIOSCLEROSIS• More generalized and severe in patients with diabetes and hypertension but also seen in elderly• It is a major morphologic characteristic of benign nephrosclerosis• Vascular lesion consists of a homogenous. Pink, hyaline thickening of the wall of the arterioles with loss of underlying structural details and narrowing of lumen• The lesion reflects leakage of plasma components across endothelium and excessive extracellular matrix production by SMC secondary to chronic homodynamic stress of HTN or metabolic stress in diabetes that accentuates endothelial cell injury
Hyaline arteriosclerosis. The arteriolar wall ishyalinized and lumen is markedly narrowed.
MORPHOLOGY (contd..)HYPERPLASTIC ARTESCLEROSIS• Is generally related to more acute or severe elevations of blood pressure• It is characteristic of malignant hypertension (diastolic pressure usually > 120 mm hg)• Can be identified as onion skin, concentric, laminated thickening of the walls of arterioles with progressive narrowing of lumens• The laminates are composed of SMC and thickened BM material• In malignant hypertension there can be is fibrinoid and acute necrosis of the vessel wall – necrotizing arteriolitis. Favored site of involvement is arterioles of kidney.
Conclusion• Essential HTN is a complexed multifactorial disorder• It results from combined affects of mutations or polymorphism at several gene loci that influence the blood pressure interacting with environmental factors• Single gene mutation—is rare• Sustained HTN requires participation of the kidney• In established HTN both increased blood volume and increased peripheral resistance contribute