Hypertension

HYPERYTENSION

BY

Dr Amira Hammad

HYPERTENSION

A sustained diastolic pressure greater than 90 mm Hg or a sustained systolic pressure in excess of 140 mm Hg is considered to constitute hypertension.

•Hypertension is a major risk factor for atherosclerosis at all ages, but after 45 yrs HTN is stronger risk factor than hypercholesterolemia.

Men at age 45 - 62 whose BP exceeds 169/95 mm Hg have greater risk of IHD than those with BP of 140/90 mm Hg or lower.

Both systolic and diastolic levels are important in increasing risk, epidemiological studies reveal systolic pressure to be more important

• HTN is a risk factor for coronary HTN is a risk factor for coronary artery disease, hypertrophy of the artery disease, hypertrophy of the heart, heart failureheart, heart failure

• CVACVA

• Aortic dissectionAortic dissection

• Renal failureRenal failure

According to etiology hypertension may be

Essential (95%)(idiopathic and apparently primary)

OR

Secondary(secondary to an identifiable cause)

1.1. Essential HypertensionEssential Hypertension

2.2. Secondary Secondary HypertensionHypertension

RenalRenal• Acute glomerulonephritisAcute glomerulonephritis• Chronic renal diseaseChronic renal disease• Polycystic diseasePolycystic disease• Renal artery stenosisRenal artery stenosis• Renal artery fibromuscular Renal artery fibromuscular

dysplasiadysplasia• Renal vasculitisRenal vasculitis• Renin producing tumoursRenin producing tumours

EndocrineEndocrine

• Adrenocortical hyperfunctioningAdrenocortical hyperfunctioning• Exogenous hormonesExogenous hormones• PheochromocytomaPheochromocytoma• AcromegallyAcromegally• HypothyroidismHypothyroidism• HyperthyroidismHyperthyroidism• Pegnancy inducedPegnancy induced

Secondary hypertension continuedSecondary hypertension continued

CardiovascularCardiovascular• Coarctation of aortaCoarctation of aorta

• PANPAN

• Increased intravascular Increased intravascular volumevolume

• Increased cardiac out putIncreased cardiac out put

• Rigidity of aortaRigidity of aorta

NeurologicNeurologic• PsychogenicPsychogenic

• Increased intracranial Increased intracranial pressurepressure

• Sleep apneaSleep apnea

• Acute stress, including Acute stress, including surgerysurgery

Clinical subgroups of hypertentionClinical subgroups of hypertention1.1. Benign HypertensionBenign Hypertension – generally does not cause short – generally does not cause short

term problems specially when controlled. It is term problems specially when controlled. It is asymptomatic and compatible with long life unless an asymptomatic and compatible with long life unless an MI or CVA supervene.MI or CVA supervene.

2.2. Accelerated or Malignant HypertensionAccelerated or Malignant Hypertension The syndrome is characterized by severe hypertension The syndrome is characterized by severe hypertension

(systolic over 200 and diastolic over 120mmhg), renal (systolic over 200 and diastolic over 120mmhg), renal failure and retinal hemorrhages and exudates with or failure and retinal hemorrhages and exudates with or without papilloedema. Usually develops on preexisting without papilloedema. Usually develops on preexisting benign hypertension whether essential or secondary but benign hypertension whether essential or secondary but may arise in normotensives.may arise in normotensives.

PATHOGENESIS OF ESSENTIAL HYPERTRNSION

Arterial hypertension occurs when the relationship between cardiac output and total peripheral resistance is altered.

REGULATION OF NORMAL BLOOD PRESSURE

Blood pressure level is a complexed trait that is determined by interaction of

• Genetic factors

• Environmental factors

• Dermographic factors

Factors 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 contdRegulation of normal blood pressure contd

The magnitude of the arterial pressure depends on two fundamental hemodynamic variables:

Cardiac outputTotal peripheral resistance

Regulation of normal blood pressure contdRegulation of normal blood pressure contd

• Cardiac out putCardiac out put is is highly dependent on highly dependent on blood volume, which blood volume, which in turn is greatly in turn is greatly influenced by body influenced by body

Na homeostasisNa homeostasis

• Peripheral Peripheral resistanceresistance is is determined mainly at determined mainly at the arteriolar level -- the arteriolar level -- neural and hormonal neural and hormonal factors. Resistance factors. Resistance vessels exhibit vessels exhibit auto auto regulationregulation

Figure 12.14

Regulation of normal blood pressure contdRegulation of normal blood pressure contd

Role of kidneyRole of kidney• Renin angiotensin system-Renin angiotensin system- Regulates both Regulates both

peripheral resistance and sodium peripheral resistance and sodium homeostasis( direct action on vessels, homeostasis( direct action on vessels, increase blood volume by producing increase blood volume by producing aldosterone secretion).aldosterone secretion).

• Kidney Kidney produces vascular relaxing factorsproduces vascular relaxing factors or antihypertensive substances(PG, NO)or antihypertensive substances(PG, NO)

• When BV reduces—GFR fallsWhen BV reduces—GFR falls leading to leading to increased absorption of sodium by the increased absorption of sodium by the proximal tubules.proximal tubules.

Regulation of normal blood pressure contdRegulation of normal blood pressure contd Role Role of kidneyof kidneycontdcontd

• Role of Naturetic factors (including the atrial Role of Naturetic factors (including the atrial and ventricular factors)-- inhibit Na and ventricular factors)-- inhibit Na reabsorption in the distal tubules. Induce reabsorption in the distal tubules. Induce vasodilatation— vasodilatation— endogenous inhibitors of endogenous inhibitors of renin angiotensin system.renin angiotensin system.

• In In renal excretory failure, increased arterial renal excretory failure, increased arterial pressure is a compensatory mechanismpressure is a compensatory mechanism that that helps restore fluid and electrolyte balance.helps restore fluid and electrolyte balance.

Mechanism of essential hypertension contdMechanism of essential hypertension contd

• Genetic or environmental factors that affect Genetic or environmental factors that affect cardiac output or peripheral resistance or bothcardiac output or peripheral resistance or both

• Single gene disorders cause rare severe forms Single gene disorders cause rare severe forms of HTN. E.g. of HTN. E.g.

Genetic defects in aldosterone metabolismGenetic defects in aldosterone metabolism mutations in proteins that affect sodium mutations in proteins that affect sodium

reabsorption-Liddles syndrome in which there reabsorption-Liddles syndrome in which there is a mutation in ENaC protein leading to is a mutation in ENaC protein leading to increased reabsorption of Na.increased reabsorption of Na.

Mechanism of essential hypertension-contdMechanism of essential hypertension-contd

• Inherited variations in blood pressure may also Inherited variations in blood pressure may also depend on cumulative effects of allelic forms of depend on cumulative effects of allelic forms of several genes e.g.. Predisposition to essential several genes e.g.. Predisposition to essential hypertension is associated with variations in hypertension is associated with variations in

o gene encoding components of renin gene encoding components of renin angiotensin systemangiotensin system

o Polymorphism in both angiotensinogen locus Polymorphism in both angiotensinogen locus and the angiotensinogen II type I receptor and the angiotensinogen II type I receptor locuslocus

o These variations may contribute to the known These variations may contribute to the known racial differencesracial differences

Environmental factorsEnvironmental factors

• StressStress

• ObesityObesity

• SmokingSmoking

• Physical activityPhysical activity

• Heavy salt consumptionHeavy salt consumption

WHAT ARE THE PRIMARY DEFECTS IN ESSENTIAL

HYPERTENSION?

1.Renal Retention of Excess Sodium2. Vasoconstriction and Hypertrophy

FIGURE 12-16

Mutations causingMutations causing

• HypotensionHypotension

o Gitelman syndromeGitelman syndrome

o Barter syndromeBarter syndrome

o 21 hydroxylase 21 hydroxylase defficiencydefficiency

o Aldosterone synthetase Aldosterone synthetase defficiencydefficiency

• HypertensionHypertension

o Liddles syndromeLiddles syndrome

o 17 alpha hydroxylase 17 alpha hydroxylase defficiencydefficiency

o 11 beta hydroxylase 11 beta hydroxylase defficiencydefficiency

Disorders affecting blood pressureDisorders affecting blood pressure

• GeneticGenetic

o Fibromuscular Fibromuscular hyperplasiahyperplasia

o Angiotensinogen variantsAngiotensinogen variantso Liddles syndromeLiddles syndromeo 17 alpha hydroxylase 17 alpha hydroxylase

defficiencydefficiencyo 11 beta hydroxylase 11 beta hydroxylase

defficiencydefficiency

• AcquiredAcquired

o Oral contraceptivesOral contraceptives

o Renal Artery stenosisRenal Artery stenosis

o Renin secreting tumoursRenin secreting tumours

o Licorice ingestionLicorice ingestion

o Cushing syndromeCushing syndrome

VASCULAR PATHOLOGY

accelerates atherogenesis causes degenerative changes in the structure of the walls of large and medium sized blood vessels that potentiate both aortic dissection and cerebrovascular hemorrhage.

It is associated with two forms of small blood vessel disease: hyaline arteriosclerosis hyperplastic arteriosclerosis

MORPHOLOGYMORPHOLOGY

HYALINE ARTERIOSCLEROSISHYALINE ARTERIOSCLEROSIS• More generalized and severe in patients with diabetes and More generalized and severe in patients with diabetes and

hypertension but also seen in elderlyhypertension but also seen in elderly

• It is a major morphologic characteristic of benign nephrosclerosisIt is a major morphologic characteristic of benign nephrosclerosis

• Vascular lesion consists of a homogenous. Pink, hyaline Vascular lesion consists of a homogenous. Pink, hyaline thickening of the wall of the arterioles with loss of underlying thickening of the wall of the arterioles with loss of underlying structural details and narrowing of lumenstructural details and narrowing of lumen

• The lesion reflects leakage of plasma components across The lesion reflects leakage of plasma components across endothelium and excessive extracellular matrix production by endothelium and excessive extracellular matrix production by SMC secondary to chronic homodynamic stress of HTN or SMC secondary to chronic homodynamic stress of HTN or metabolic stress in diabetes that accentuates endothelial cell injurymetabolic stress in diabetes that accentuates endothelial cell injury

Hyaline arteriosclerosis. The arteriolar wall is hyalinized and lumen is markedly narrowed.

MORPHOLOGY (contd..)MORPHOLOGY (contd..)HYPERPLASTIC ARTESCLEROSISHYPERPLASTIC ARTESCLEROSIS

• Is generally related to more acute or severe elevations of Is generally related to more acute or severe elevations of blood pressureblood pressure

• It is characteristic of malignant hypertension (diastolic It is characteristic of malignant hypertension (diastolic pressure usually > 120 mm hg)pressure usually > 120 mm hg)

• Can be identified as onion skin, concentric, laminated Can be identified as onion skin, concentric, laminated thickening of the walls of arterioles with progressive thickening of the walls of arterioles with progressive narrowing of lumensnarrowing of lumens

• The laminates are composed of SMC and thickened BM The laminates are composed of SMC and thickened BM materialmaterial

• In malignant hypertension there can be is fibrinoid and In malignant hypertension there can be is fibrinoid and acute necrosis of the vessel wall – necrotizing arteriolitis. acute necrosis of the vessel wall – necrotizing arteriolitis. Favored site of involvement is arterioles of kidney.Favored site of involvement is arterioles of kidney.

Hyperplastic arteriosclerosis (onion skinning causes luminal obliteration.

ConclusionConclusion• Essential HTN is a complexed multifactorial Essential HTN is a complexed multifactorial

disorderdisorder

• It results from combined affects of mutations It results from combined affects of mutations or polymorphism at several gene loci that or polymorphism at several gene loci that influence the blood pressure interacting with influence the blood pressure interacting with environmental factorsenvironmental factors

• Single gene mutation—is rareSingle gene mutation—is rare

• Sustained HTN requires participation of the Sustained HTN requires participation of the kidneykidney

• In established HTN both increased blood In established HTN both increased blood volume and increased peripheral resistance volume and increased peripheral resistance contributecontribute