HYPERTENSION

Roll No. : 46, 47, 48, 49, 50Teacher In charge : Dr. G.S. Ranga

Determinants of arterial pressure

12:09 AM

What is HYPERTENSION ?

Transitory or sustained elevation of systemic arterial blood pressure to a level likely to induce cardiovascular damage or other adverse consequences

12:09 AM

Classification of hypertension

Systolic Diastolic

Normal <120 And <80

Prehypertension 120-139 Or 80-89

Stage 1 hypertension 140-159 Or 90-99

Stage 2 hypertension >=160 Or >=100

Isolated systolic hypertension

>=140 <90

12:09 AM

Etiology of Hypertension

There are two types on the basis of etiology:

•Primary hypertension– 90-95% of cases – also termed “essential” of “idiopathic”

•Secondary hypertension– about 5% of cases

12:09 AM

Primary (Essential) hypertension

•Cause unknown•Tends to be familial•Is a polygenic disorder; different patients

carry different subsets of genes associated with obesity, dyslipidemia, insulin resistance, etc,

•Consequence of interaction between environment and genetic factors

12:09 AM

Risk factors for essential hypertension

•Old age•Smoking•Obesity•Excessive intake of salt•Alcohol consumption•Stress•Family history •Low dietary intake of vitamin D, calcium and

potassium

12:09 AM

Secondary hypertension

•A specific underlying disorder is the cause of hypertension

•Accounts for only 5 – 10% cases

12:09 AM

Causes of secondary hypertension

▫ Metabolic syndromes Dyslipidemia Insulin resistance

▫ Renal parenchymal or renovascular disease

▫ Obstructive sleep apnea▫ Preeclampsia and

eclampsia▫ Neurogenic causes

Acute increased intracranial pressure

Acute spinal cord section

Endocrine disease Phaeochomocytoma Cusings syndrome Conn’s syndrome Acromegaly , hypothyroidism and hyperthyroidism

Coarctation of the aorta Mendelian forms of hypertension Iatrogenic

Hormonal / oral contraceptive NSAIDs

12:09 AM

12:09 AM

PATHOGENESIS OFHYPERTENSION

Roll no. 47 – Mohit Chhabra

• Local Regulation – Autoregulation, Vasodilator metabolites, Localized vasoconstriction

• Endothelial factors – NO, Endothelins, Prostacyclins and Thromboxane A2

• Systemic regulation by hormones – Kinins, Natriuretic hormones (ABC), circulating vasoconstrictors (vasopressin, norepinephrine, angiotensin II).

• Vasoconstrictive influences: Ion transport/ Endothelial factors

12:09 AM

Vascular Regulatory Mechanisms

12:09 AM

Increased Na+-H+ activity in the vessel wall

Increased intracellular Na+

Increased intracellular pH

Increased smooth muscle contractility and vasoconstriction

Vascular Regulatory Mechanisms

• Baroreceptors monitoring the arterial circulation are present in the carotid sinus and the aortic arch.

• Stimulated by distention/raised BP• Increased baroreceptor discharge inhibits

tonic discharge of the sympathetic nervous system

12:09 AM

Regulatory Mechanisms of the Autonomic Nervous System: Baroreceptors

12:09 AM

Action of Baroreceptors

Regulatory Mechanisms of the Autonomic Nervous System

Inhibition of RVLM/ Vasomotor Center

Inhibited α receptors on blood vessels

Inhibited β receptors in heart

Decreased HR & CO

Decreased PVR

Lowered Blood Pressure

12:09 AM

• Kidney regulates BP by two main mechanisms:1. Regulation of sodium and water homeostasis2. Renin-Angiotensin-Aldosterone-System

• Significant renal impairment is associated with hypertension in large part due to disturbance in sodium handling.

• Reduced renal perfusion leading to raised BP, relates to the activity of the Renin-Angiotensin-Aldosterone System.

12:09 AM

Regulatory Mechanisms of the Kidney

12:09 AM

Sodium Homeostasis

• There are 3 major stimuli for renin secretion:1. Decreased NaCl transport to the macula densa2. Decreased stretch within the renal afferent

arteriole (Baroreceptor mechanism)3. Stimulation of β1 adrenoreceptors in JG cells

• Other stimulatory factors – Prostaglandins• Other inhibitory factors – Angiotensin II,

Vasopressin

12:09 AM

Renin-Angiotensin-Aldosterone System

12:09 AM

Renin-Angiotensin-Aldosterone Axis

Increased activity of the renin-angiotensin-aldosterone axis is not

invariably associated with hypertension

• The main effector molecules of RAAS are Angiotensin II and Aldosterone.

• Angiotensin II acts on AT1 receptors:– In the adrenal cortex to release Aldosterone which

increases Na+ reabsorption by epithelial sodium channel (ENaC) on the collecting duct with resultant hypokalemia and alkalosis to maintain electric neutrality.

– In the arterioles to cause vasoconstriction

• AT2 receptor antagonizes AT1 by causing vasodilation and sodium excretion.

12:09 AM

Renin-Angiotensin-Aldosterone System

Main factors involved in the pathogenesis of hypertension are:•Genetic factors•Environmental and lifestyle influences•Impact of fetal and infant growth•Prehypertension•Renal mechanisms•Vascular mechanisms•Neurohumoral control systems

12:09 AM

Pathogenesis of Essential Hypertension

Genetic Factors

Gene Role

Angiotensinogen Substrate for Renin

ACE Converts AI to AII

Angiotensin II receptor Type I Vascular receptor for Angiotensin II

Aldosterone synthase Promotes aldosterone synthesis

ENaC in collecting duct (Liddle Syndrome) Site of action of aldosterone

12:09 AM

It is more likely that essential hypertension results from interactions of mutations or polymorphisms at several

loci that influence blood pressure

Lancet, 349, 1353-7

Environmental & Lifestyle Influences

• Dietary salt intake influences not only blood pressure but also cardiovascular disease outcomes. Sodium balance has an impact on blood pressure.

• Visceral adiposity seems important in defining the relationship between blood pressure and obesity.

• Alcohol intake – Intervention trials confirm that blood pressure falls when alcohol is withdrawn from heavy drinkers.

• Clear cut association between obstructive sleep apnea and hypertension.

• Psychosocial stress and blood pressure.

12:09 AM

Impact of fetal and infant growth

• Association between low birth weight and risk of developing hypertension.

• Inverse relationship between birth weight & gestational age with systolic BP.

12:09 AM

Prehypertension

• Annual rate of progression to hypertension is higher amongst pre-hypertensives.

• Prehypertension is also more common in people with diabetes

12:09 AM

• For most forms underlying pathways are well understood:

Pathogenesis of Secondary Hypertension

Secondary Hypertension

Renal diseases – Reno vascular diseases, Renin-producing tumors, AGN*

Endocrine – Cushing’s, Conn’s, Phaeochromocytoma, Hypo/hyperthyroidism

Cardiovascular – Coarctation of aorta

Neurologic – Raised ICP

* http://books.google.co.in/books?id=QfsjuUncJE0C&pg=PA147&lpg=PA147&dq=AGN+and+hypertension&source=bl&ots=MEsoSD5bTf&sig=lN_zKxoD1j5hXR7nKiGSZFlgCPs&hl=en&ei=VzOCTtYHo6mIB9avpf0O&sa=X&oi=book_result&ct=result&resnum=4&ved=0CDcQ6AEwAw#v=onepage&q=AGN%20and%20hypertension&f=false12:09 AM

SOURCES

Harrison’s Principles of Internal Medicine, 18/eRobbins and Cotran Pathologic Basis of Disease,

8/eOxford Textbook of Medicine, 5/eGanong’s Review of Medical Physiology, 23/ePrinciples of Pharmacology by KK Sharma, 2/e

12:09 AM

12:09 AM

DIAGNOSIS OF HYPERTENSION

Roll no. 48 – Mohit Garg12:09 AM

• A complete history should be taken which assess the following points:

Duration Previous therapies Family history of hypertension and cardiovascular

diseasesDietary and psychosocial historyOther risk factors : weight change, dyslipidemia,

smoking, diabetes and physical activity Evidence of secondary hypertension: spells of

sweating, palpitations, tremors, erratic sleep and snoring etc.

History

12:09 AM

• Body habitus, including weight and height.

• At the initial examination, blood pressure should be measured in both arms

• Heart rate

• The neck should be palpated for an enlarged thyroid gland, and patients should be assessed for signs of hypo- and hyperthyroidism

• Examination of blood vessels

• Kidneys of patients with polycystic kidney disease may be palpable in the abdomen.

• The physical examination also should include evaluation for signs of CHF and a neurologic examination.

Physical Examination

12:09 AM

Measured using a sphygmomanometer

Seated quietly for 5 minutes

Centre of the cuff at the level of the heart.

Width of the bladder cuff should equal at least 40% of the arm circumference

the length of the cuff bladder should be enough to encircle at least 80% of the arm circumference

Inflate 20-30 mmHg above loss of radial pulse

Deflate at 2mmHg per second

Physical Examination

12:09 AM

Systolic Diastolic

Normal <120 And <80

Prehypertension 120-139 Or 80-89

Stage 1 hypertension 140-159 Or 90-99

Stage 2 hypertension >=160 Or >=100

Isolated systolic hypertension

>=140 <90

Classification of hypertension

12:09 AM

Laboratory Tests

12:09 AM

12:09 AM

12:09 AM

COMPLICATIONS OF HYPERTENSION

Roll no. 49 – Mohit Sharma

Complications of Hypertension

• Damage Heart - CHF, MI, Sudden death, angina

Kidneys - renal failure, proteinuria

Peripheral Vascular disease

CNS - Stroke, retina damage

12:09 AM

Cardiovascular complications

Heart

- Increased workload on left ventricle

Left ventricular hypertrophy

left ventricular failure.

- Greater thickness of left ventricle

decreased perfusion and ischaemia of

subendocardial region of myocardium.

12:09 AM

Consequences of Hypertension

• Cardiac - LVH

12:09 AM

Arteries

- Accelerated atherogenesis.

- risk of developing aortic dissecting aneurism.

Arterioles: Arteriolosclerosis

- Benign HT:

Deposition of eosinophilic (‘hyaline’) material in vessel

walls due to influx of plasma proteins.

- Malignant HT:

Thickening of intima.

Necrosis of vessel walls ('fibrinoid' necrosis) and

formation of micro-aneurisms in brain.12:09 AM

CNS Complications:- Rupture of micro-aneurisms of small penetrating

arteries Intracerebral haemorrhage.

- Risk of cerebral infarction due to atherosclerosis

of circle of Willis.

- Acute malignant HT: ‘Hypertensive encephalopathy’

due to cerebral oedema (headache, nausea and vomiting,

visual disturbances, seizures and disturbances of

consciousness).

12:09 AM

Consequences of Hypertension - CNS

12:09 AM

Peripheral vascular disease

Classical presentation : Intermittent claudication (aching pain in calves or

buttocks while walking that is relived by rest)

Ankle-brachial index:-Ratio of SBP ankle to arm- <0.90 : diagnostic

12:09 AM

Peripheral Vascular Disease

12:09 AM

Renal complications

Arteriolosclerosis

Ischaemic sclerosis of glomeruli and

tubular atrophy.

Proteinuria and microscopic haematuria,

especially in malignant HT .

12:09 AM

Consequences of Hypertension -Kidney

12:09 AM

Factors responsible:

-Vasoconstriction

-Vascular leakage: lead to flame shaped retinal hmg & retinal edema

-Arterioloscelerotic changes

Consequences of Hypertension - Retina

12:09 AM

Grading- Hypertensive retinopathy

Grade 1: subtle broadening of the arteriolar light reflex, mild generalized arteriolar

attenuation, particularly of small branches, and vein concealment Grade 2: obvious broadening of the arteriolar light reflex and deflection of veins at

arteriovenous crossings (Salus sign) Grade 3:-‘Copper-wiring’ of arterioles -Banking of veins distal to arteriovenous crossings (Bonnet sign)-Tapering of veins on both sides of the crossings (Gunn sign) and right-angled

deflection of veins.Grade 4: ‘Silver-wiring’ of arterioles & papilloedema associated with grade 3 changes

12:09 AM

Consequences of Hypertension - Retina

12:09 AM

12:09 AM

MANAGEMENT OF HYPERTENSION

Roll no. 50 – Naman Bansal

Learning Objectives

• Who to treat?• When to treat?• How to treat?

Treatment options• Till when to treat?

12:09 AM

Goals of Treatment

1. Reduce cardiovascular and renal morbidity and mortality.

2. Obtain target BP goals of <140/90 mmHg or <130/80 mmHg with diabetes or renal disease.

 

12:09 AM

Classification of hypertension

Systolic Diastolic

Normal <120 And <80

Prehypertension 120-139 Or 80-89

Stage 1 hypertension 140-159 Or 90-99

Stage 2 hypertension >=160 Or >=100

Isolated systolic hypertension

>=140 <90

12:09 AM

High Risk for Adverse Prognosis

• Black Race• Male Sex• Persistent diastolic pressure >115 mmHg• Smoking• Diabetes Mellitus• Hypercholestrolemia• Obesity• Excess alcohol intake• Evidence of end organ damage

1.Cardiac2.Eyes3.Renal4.Nervous System

12:09 AM

JNC 7 Management Algorithm

12:09 AM

 

 

12:09 AM

Pharmacologic Therapy

• Only agents shown to decrease morbidity and mortality related to CHD in major trials

• Decrease plasma volume and CO• Reduce peripheral vascular resistance• Most of anti-hypertensive effect at low

doses; biochemical effects are dose related

• Thiazides; loop; potassium sparing

Diuretics

12:09 AM

Diuretics

Adverse effects:• Electrolyte imbalance:

potassium, magnesium, sodium, calcium, uric acid, glucose

• Hypercholesterolemia

Diuretics

Useful in:• All populations• Isolated systolic hypertension• CHF• Renal insufficiency (loop diuretics if

CrCl < 30-50)• Combination with second drug

Beta Adrenergic Blockers

• Decrease HR, CO, renal blood flow• Inhibit vasoconstriction/decrease

peripheral resistance

Beta Adrenergic Blockers

Useful in:• Patients with LVH, angina,

tachycardia, anxiety, migraine, glaucoma

• Patients with CHD; provide significant protection against MI recurrence

Beta Adrenergic Blockers

Adverse effects:• CHF exacerbation acutely; AV block• Bronchospasm (in reversible disease)• CNS (lipid solubility)

o Propranolol, metoprolol >> atenolol

• ? Carbohydrate metabolism• ? Lipid metabolism

Angiotensin Converting Enzyme Inhibitors

• Block formation of angiotensin II• Promote vasodilation &

decrease aldosterone• Increase bradykinin &

vasodilatory PG’s

Angiotensin Converting Enzyme Inhibitors

Preferred in:• Congestive heart failure• Diabetes type I and II• Known coronary heart disease• At high risk for CHD• Nephropathy

Angiotensin Converting Enzyme InhibitorsAdverse effects:• Cough (5-15% of patients)• Skin rash, taste alterations (esp. Captopril)• Hyperkalemia• Hypotension, dizziness• Renal dysfunction (up to 35% inc in SCr)• Rare: angioedema (most frequent in African

Americans), neutropenia, proteinuria• Teratogenic

Angiotensin Receptor Blockers

• Losartan, valsartan, candesartan, et.al.

• No cough, rare angioedema• Less potent antihypertensive

effect--improves if combined with diuretic

• Teratogenic

Calcium Channel Blockers

• Peripheral vasodilators• Non-dihydropiridines: diltiazem,

verapamil• Dihydropiridines: amlodipine,

felodipine, isradipine, nicardipine, nifedipine, nisoldipine

• Short-acting dihydropiridines

Calcium Channel Blockers

Adverse effects:• Dizziness, headache, peripheral

edema• DHP’s: worse edema, flushing,

tachycardia, rash• Non-DHP’s: CHF exacerbation, AV

block, bradycardia, constipation

Calcium Channel Blockers

• Useful in: angina• Most effective in African Americans

as single drug therapy• In patients with DM, its use assoc.

with greater risk of MI compared with ACEI

Alpha Adrenergic Blockers

• Prazosin, terazosin, doxazosin• Can cause postural hypotension and

syncope• Use with caution in elderly• Useful in men with BPH

Central Sympatholytics

• Adverse effects: sedation, drowsiness, dry mouth, bradycardia, heart block

• Clonidine withdrawal: hypertension, headache, palpitations, perspiration

• Methyldopa: hepatitis, lupus-like syndrome, thrombocytopenia, hemolytic anemia

Direct Vasodilators

• Tachycardia can aggravate angina• Headache, dizziness, fluid retention• Hydralazine: lupus-like syndrome,

hepatitis• Minoxidil: hirsutism, pericardial

effusion

12:09 AM