Epidemiology Physiology of the heart The basic unit

Epidemiology

Physiology of the heart • The basic unit of contraction is the sarcomere, which is aligned to those of adjacent myofibrils. • Actin filaments are attached and interdigitate with thicker parallel myosin filaments. • During contraction, shortening of the sarcomere results from the interdigitation of the actin and myosin molecules. • The force of cardiac muscle contraction, or inotropic state, is regulated by the influx of calcium ions through ‘ slow calcium channels’.

Pathophysiology • Cardiac output depends upon : 1. Preload 2. Afterload 3. Myocardial contractility

Physiology of BP Two important determinants of B. P. A. Cardiac output (determined by stroke volume + Heart rate) B. Peripheral resistance (determined by vascular function + v. structure)

Heart Physiology

Physiologic Principles • More than 90% of cases of hypertension do not have a clear cause. • Hypertension clusters in families and results from a complex interaction of genetic and environmental factors. • The hypertension‐related genes identified to date regulate renal salt and water handling. • Major pathophysiologic mechanisms of hypertension include activation of the sympathetic nervous system and renin– angiotensin–aldosterone system. • Endothelial dysfunction, increased vascular reactivity, and vascular remodeling may be causes, rather than consequences, of blood pressure elevation; increased vascular stiffness contributes to isolated systolic hypertension in the elderly.

Physiologic Principles • Essential hypertension, or hypertension of unknown cause, accounts for more than 90% of cases of hypertension. • It tends to cluster in families and represents a collection of genetically based diseases or syndromes with several resultant inherited biochemical abnormalities. • The resulting phenotypes can be modulated by various environmental factors, thereby altering the severity of blood pressure elevation and the timing of hypertension onset.

Physiologic Principles • Many pathophysiologic factors have been implicated in the genesis of essential hypertension: increased sympathetic nervous system activity, perhaps related to heightened exposure or response to psychosocial stress; overproduction of sodium‐retaining hormones and vasoconstrictors; long‐term high sodium intake; inadequate dietary intake of potassium and calcium

Physiologic Principles • Increased or inappropriate renin secretion with resultant increased production of angiotensin II and aldosterone; deficiencies of vasodilators, such as prostacyclin, nitric oxide (NO), and the natriuretic peptides; alterations in expression of the kallikrein–kinin system that affect vascular tone and renal salt handling; abnormalities of resistance vessels, including selective lesions in the renal microvasculature; diabetes mellitus; insulin resistance; obesity; increased activity of vascular growth factors; alterations in adrenergic receptors that influence heart rate, inotropic properties of the heart, and vascular tone; and altered cellular ion transport

Role of the sympathetic nervous system in the pathogenesis of cardiovascular diseases.

Physiologic Principles • The novel concept that structural and functional abnormalities in the vasculature, including endothelial dysfunction, increased oxidative stress, vascular remodeling, and decreased compliance, may antedate hypertension and contribute to its pathogenesis has gained support in recent years.

Pathophysiologic mechanisms of hypertension.

Physiologic Principles • Although several factors clearly contribute to the pathogenesis and maintenance of blood pressure elevation, renal mechanisms probably play a primary role, as hypothesized by Guyton and reinforced by extensive experimental and clinical data. Other mechanisms amplify (for example, sympathetic nervous system activity and vascular remodeling) or buffer (for example, increased natriuretic peptide or kallikrein– kinin expression) the pressor effects of renal salt and water retention. • These interacting pathways play major roles in both increasing blood pressure and mediating related target organ damage. Understanding these complex mechanisms has important implications for the targeting of antihyper‐tensive therapy to achieve benefits beyond lowering blood pressure.

Control of Blood Pressure • Changes in blood pressure are routinely made in order to direct appropriate amounts of oxygen and nutrients to specific parts of the body. For example, when exercise demands additional supplies of oxygen to skeletal muscles, blood delivery to these muscles increases, while blood delivery to the digestive organs decreases. • Adjustments in blood pressure also required when forces are applied to your body, such as when starting or stopping in an elevator.

Control of Blood Pressure • Blood pressure can be adjusted by producing changes in the following variables: • Cardiac output can be altered by changing stroke volume or heart rate. • Resistance to blood flow in the blood vessels is most often altered by changing the diameter of the vessels (vasodilation or vasoconstriction). • Changes in blood viscosity (its ability to flow) or in the length of the blood vessels (which increases with weight gain) can also alter resistance to blood flow

The following mechanisms help regulate blood pressure • The cardiovascular center provides a rapid, neural mechanism for the regulation of blood pressure by managing cardiac output or by adjusting blood vessel diameter. Located in the medulla oblongata of the brain stem, it consists of three distinct regions: • The cardiac center stimulates cardiac output by increasing heart rate and contractility. These nerve impulses are transmitted over sympathetic cardiac nerves.

The following mechanisms help regulate blood pressure • The cardiac center inhibits cardiac output by decreasing heart rate. • These nerve impulses are transmitted over parasympathetic vagus nerves. • The vasomotor center regulates blood vessel diameter. Nerve impulses transmitted over sympathetic motor neurons called vasomotor nerves innervate smooth muscles in arterioles throughout the body to maintain vasomotor tone, a steady state of vasoconstriction appropriate to the region.

The cardiovascular center receives information about the state of the body through the following sources: • Baroreceptors are sensory neurons that monitor arterial blood pressure. Major baroreceptors are located in the carotid sinus (an enlarged area of the carotid artery just above its separation from the aorta), the aortic arch, and the right atrium.

Chemoreceptors • Chemoreceptors are sensory neurons that monitor levels of CO 2 and O 2. These neurons alert the cardiovascular center when levels of O 2 drop or levels of CO 2 rise (which result in a drop in p. H). • Chemoreceptors are found in carotid bodies and aortic bodies located near the carotid sinus and aortic arch.

Chemoreceptors • Higher brain regions, such as the cerebral cortex, hypothalamus, and limbic system, signal the cardiovascular center when conditions (stress, fight‐or‐flight response, hot or cold temperature) require adjustments to the blood pressure.

The kidneys provide a hormonal mechanism for the regulation of blood pressure by managing blood volume. • The renin‐angiotensin‐aldosterone system of the kidneys regulates blood volume. In response to rising blood pressure, the juxtaglomerular cells in the kidneys secrete renin into the blood. Renin converts the plasma protein angiotensinogen to angiotensin I, which in turn is converted to angiotensin II by enzymes from the lungs. Angiotensin II activates two mechanisms that raise blood pressure:

The kidneys provide a hormonal mechanism for the regulation of blood pressure by managing blood volume. • Angiotensin II constricts blood vessels throughout the body (raising blood pressure by increasing resistance to blood flow). • Constricted blood vessels reduce the amount of blood delivered to the kidneys, which decreases the kidneys' potential to excrete water (raising blood pressure by increasing blood volume).

The kidneys provide a hormonal mechanism for the regulation of blood pressure by managing blood volume. • Angiotensin II stimulates the adrenal cortex to secrete aldosterone, a hormone that reduces urine output by increasing retention of H 2 O and Na + by the kidneys (raising blood pressure by increasing blood volume).

Various substances influence blood pressure. Some important examples follow: • Epinephrine and norepinephrine, hormones secreted by the adrenal medulla, raise blood pressure by increasing heart rate and the contractility of the heart muscles and by causing vasoconstriction of arteries and veins. These hormones are secreted as part of the fight‐or flight response.

Various substances influence blood pressure. Some important examples follow: • Antidiuretic hormone (ADH), a hormone produced by the hypothalamus and released by the posterior pituitary, raises blood pressure by stimulating the kidneys to retain H 2 O (raising blood pressure by increasing blood volume).

A pathway for the development of salt-sensitive hypertension.

Various substances influence blood pressure. Some important examples follow: • Atrial natriuretic peptide (ANP), a hormone secreted by the atria of the heart, lowers blood pressure by causing vasodilation and by stimulating the kidneys to excrete more water and Na +(lowering blood pressure by reducing blood volume). • Nitric oxide (NO), secreted by endothelial cells, causes vasodilation.

Various substances influence blood pressure. Some important examples follow: • Nicotine in tobacco raises blood pressure by stimulating sympathetic neurons to increase vasoconstriction and by stimulating the adrenal medulla to increase secretion of epinephrine and norepinephrine. • Alcohol lowers blood pressure by inhibiting the vasomotor center (causing vasodilation) and by inhibiting the release of ADH (increasing H 2 O output, which decreases blood volume).

Endothelial function in the normal vasculature and in the hypertensive vasculature.

Cardiovascular Risk Factors

BMI In Worldwide

Normal pressure values (Left Side)- mm • • • Arterial Peak Systolic 90 -140 Arterial end-diastolic 60 -90 Arterial mean 70 -105 LV Peak Systolic 90 -140 LV End diastolic 4 -12 LA - mean 4 -12

Normal pressure values (Right side) - mm • • • Pulm. Art. Peak Systolic Pulm. Art. End Diastolic Pulm. Art. Mean RV Peak Systolic RV End Diastolic RA Mean 15 -30 5 -15 10 -20 15 -30 0 -5

Risk Factors for Atherosclerosis • Age & Sex * Family History • Smoking • Hypertension • Hypercholesterolemia

Hypertension and Obesity

Undiagnosed Hypertension, DM and Hypercholesterolemia

Risk Factors ( Cont. ) • • • DM Physical inactivity Obesity Diet & alcohol Personality & Social factors

Hypertension and Location

Endothelial Function • Vasodilators Nitric Oxide Prostacyclin Endothelium derived Hyperpolar Factor • Vasoconstrictors Endothelin – l Angiotensin – ll * Formation & Disolution of Thrombus

BLOOD PRESSURE • → Rest the patient for five minutes • → In ambulant patients, measurements are normally made with the patient seated. Either arm can be used. • → Support the patient's arm comfortably at about heart level. • → Apply the cuff to the upper arm with the centre of the bladder over the brachial artery. • → Palpate the brachial pulse. • → Inflate the cuff until the pulse is impalpable. Note the pressure on the manometer. This is a rough estimate of systolic pressure. • → Now inflate the cuff another 10 mm. Hg and listen through the stethoscope over the brachial artery. • → Deflate the cuff slowly until regular sounds are first heard. Note the reading to the nearest 2 mm. Hg. This is the systolic pressure. • → Continue to deflate the cuff slowly until the sounds disappear. • → Record the pressure at which the sounds completely disappear as diastolic pressure. Occasionally muffled sounds persist and do not disappear, in which case the point of muffling is the best guide to the diastolic pressure

Notes on BP measurement • Take BP after 5 minutes rest & ask patient not to take coffee or to smoke 30 minutes before measuring BP. One reading of high BP does not mean HT except when very high. • Always start with BP measurement by palpation.

Notes on BP measurement • Pay attention to placement of cuff & stethoscope • Inflation & deflation should not be very slow or fast • For the 1 st time measure in both arm & in arm and leg ( Coaractation )

Notes on BP measurement • BP is variable. It is lower at night. Absence of this dip (non dipper) is associated with high risk of CV complication especially thrombotic stroke. • Blood Pressure tends to be higher in early morning hours…People with accentuation of this rise have higher incidence of cerebral haemorrhage.

MEASUREMENT OF BLOOD PRESSURE • Use a machine that has been validated, well maintained and properly calibrated • Measure sitting BP routinely, with additional standing BP in elderly and diabetic patients and those with possible postural hypotension • Remove tight clothing from the arm • Support the arm at the level of the heart • Use a cuff of appropriate size (the bladder must encompass > two‐thirds of the arm) • Lower the mercury slowly (2 mm per second) • Read the BP to the nearest 2 mm. Hg • Use phase V (disappearance of sounds) to measure diastolic BP • Take two measurements at each visit

Ventricular Enlargement - LVH 1. Voltage Criteria (SV 1+RV 5 or RV 6) = 35 mm or more 2. ST depression + T inversion (Strain pattern) ** Voltage criteria is seen in volume load conditions while strain pattern is seen in pressure load

LVH with Strain pattern

Bundle Branch Block - LBBB

4. Echocardiography • 2 D Echo (chamber, valve, pericardium & great vessels) • Doppler Echo (flow across valve & vessels) & coloured doppler (shunt) • TEE (posterior structure of the heart (left atrium, mitral valve & aorta. . Useful in dissecting aneurysm). * Stress Echo

European Society of Ht classification Optimal Normal High Normal HT ( grade 1) HT ( grade 2 ) HT ( grade 3) Systolic Diastolic 120 80 129 85 130 -139 85 -89 140 -159 90 -99 160 -179 100 -109 180 + 110+

Epidemiology of HT • 10 -30% of adult population are Hypertensive. The figure is more than that in certain ethnic groups. * 50% of people above 60 are hypertensive * 95% of hypertensive have primary HT.

Pathogenesis of HT 1. 2. 3. 4. 5. 5. Genetic Factors Sympathetic System Blood vessel elasticity Renin-Angiotensin Defect in natriuresis Intracellular Na & Ca

Exacerbating factors 1. 2. 3. 4. 5. 6. 7. 8. Obesity Excessive Na intake Excessive alcohol Smoking Lack of exercise Polycythemia Low K intake Drugs (NSAID)

The objectives of the initial evaluation of a patient with high blood pressure reading are 1. To obtain accurate and representative measurements of blood pressure. 2. To identify contributory factors and any underlying cause. 3. To assess other risk factors and quantify cardiovascular risk. 4. To detect any complications( target organ damage) that are already present. 5. To identify comorbidity that may influence the choice of antihypertensive therapy.

Secondary HT • Secondary hypertension should be suspected when HT is diagnosed before the age of 20 * Secondary cause should be suspected when a well controlled Ht becomes uncontrollable.

Examine patient with high blood pressure 1. Check the pulse rate‐irregularly irregular suggests atrial Fibrillation. 2. Measure the blood pressure in both arms. 3. Check for radiofemoral delay (coarctation of the aorta). 4. Examine the optic fundi for hypertensive retinopathy. 5. Look for features of Cushing’s syndrome or virillization. 6. Examine the heart for the heave of LVH and for fourth Heart sound. 7. Look for evidence of heart failure. 8. Palpate the abdomen for renal enlargement and abnormal pulsation of an abdominal aortic aneurysm. 9. Listen for bruits over the renal arteries(R. artery stenosis)

Causes of secondary HT 1. Chronic Renal Disease 2. Obstructive uropathy 3. Reno-vascular 4. Coaractation of the aorta 5. 6. 7. 8. Cushing disease & acromegaly Pheochromocytoma Primary aldosteronism Thyroid and Parathyroid disease 9. Sleep apnea 10. Hypercalcemia (all causes) 11. Drug induced hypertension (estrogen, NSAID, cyclosporine)

Investigations Routine Investigations 1. General urine examination 2. Biochemical (BU, Creatinine, electrolytes FBS, Lipid profile ) 3. ECG , Chest x-ray , Echo Specific Tests Cortisol , Aldosterone/ Renin, Renal ultra-sound, CT scan, MRI, Renal angiography, Aortogram, Catecholamines….

HYPERTENSION: INVESTIGATION OF SELECTED PATIENTS • Chest X‐ray: to detect cardiomegaly, heart failure, coarctation of the aorta • Ambulatory BP recording: to assess borderline or 'white coat' hypertension • Echocardiogram: to detect or quantify left ventricular hypertrophy • Renal ultrasound: to detect possible renal disease • Renal angiography: to detect or confirm presence of renal artery stenosis • Urinary catecholamines: to detect possible phaeochromocytoma • Urinary cortisol and dexamethasone suppression test: to detect possible Cushing's syndrome • Plasma renin activity and aldosterone: to detect possible primary aldosteronism

Drugs that may cause resistant HT 1. 2. 3. 4. 5. 6. 7. 8. NSAID Decongestant Diet pills Cocaine Amphetamine Oral contraceptive pills Cyclosporine Steroids

Special types of HT 1. White coat HT 2. Systolic HT (elderly) 3. Paroxysmal HT (Pheochromocytoma) 4. Malignant HT ( encephalopathy or nephropathy + papilloedema)

Common Mistakes (patients) 1. Non-compliance to drug therapy 2. Wrong concept that drug can be discontinued once BP is normal 3. Patient thinks that his BP is normal as long as there is no headache 4. Poor follow-up 5. Fear of diuretics

Common mistakes (physician) 1. Not enough time for patient’s education. 2. Withdraw drugs once BP is normal. 3. Prescribes drugs with small dose or wrong frequency of use. 4. Prescribes two drugs of the same mode of action.

Drug Therapy