HEMODYNAMIC DETERMINANTS Blood Pressure - P generated when the heart contracts against the resistance of the BV MAP = CO * SVR

MAP = DBP + (SBP DBP)/3 CO Cardiac Output MAP Mean Arterial Pressure SVR Systemic Vascular Resistance CO = SV * HR SV Stroke Volume HR Heart Rate Causes of HTN - SVR rather than CO MODULATORS OF CARDIAC OUTPUT Extracellular Fluid - Total body sodium content not plasma sodium concentration - Regulated by sodium handling by the kidney Contractility/Heart Rate - Sympathetic tone - Inotropic effectors (cathecholamines: NorE, E) * Natriuresis P, Sodium Content MODULATORS OF SVR Humoral Factors - Sensors baroreceptors, JG apparatus (Kidney), Atrium - Mediators BP, distal tubule chloride delivery, atrial stretch - Effectors o Vasoconstrictors Angiotensin II, NorE, Thromboxane, Endothelin By AKC 15 JULY 2013

o o

Vasodilators Prostaglandins, Bradykinin, Atrial Natriuretic Peptide Other Effects altered sodium excretion by the kidney & manipulation of ECF

*Hypotension less supply to other organs Local Factors - Mediators endothelial cells, vascular smooth muscle cell - Signals BP, shear stress(blood flow/viscosity, vessel diameter), humoral factors - Effectors (produced in BV) o Vasoconstrictors Myogenic Response (depends on muscle contraction), Prostaglandins, Leukotrienes, Endothelin, Endothelium-derived Constricting Factor (EDCF), Angiotensin o Vasodilators Endothelium-derived Relaxing Factor (EDRF), Prostaglandins - Local Mechanisms o Allow for autoregulation of blood flow and capillary pressure to various organs (brain, kidney - most prominently) o Allow for modulation of hemodynamics in an individual vascular bed with lesser changes in systemic hemodynamics * BP activates sensors chain of rxn will happen * volume of heart trigger baroreceptors PRIMARY HTN - AKA Essential HTN - Etiology unknown - Accounts for 90% of hypertensive pts - Onset: 5th-6th decade of life - Strong Family Hx 70%-80% o HTN in both parents risk is 250% Page 1

BP correlations are stronger among parent and child than between spouses, suggesting that environmental factors < genetic factors Certain races (African-Americans) - risk

*cholesterol will not really lead to HTN SECONDARY HTN pag natreat, wala ng HTN - Kidney Dse - Renal Artery Stenosis - Hyperaldosteronism - Pheochromocytoma - Represents 10% of all HTN - Has specific therapy - Potentially curable * sodium water retention (ECF) * sodium stimulates aldosterone (vasoconstrictor) * aldosterone stimulates renin production stimulates angiotensin I production stimulates angiotensin II production vasoconstriction BP ROLE OF KIDNEY - With progressive loss of kidney fxn, virtually 10% of pts become hypertensive - Chronic kidney dse MC form of 2 HTN - BP frequently improved with hemodialysis - Theories: o Kidney failure impaired sodium excretion expansion of ECF, volume overload & subsequent systemic HTN o Impaired kidney sodium excretion necessary to sustain all forms of HTN o Persistent HTN necessitates abnormal pressure natriuresis phenomena * Natriuretic P, iihi ng iihin to correct BP By AKC 15 JULY 2013

ROLE OF RENIN-ANGIOTENSION SYSTEM - All infusion/overproduction causes HTN - Mechanism of Hypertensive Effects: o Angiotensin II directly induces vascular smooth muscle contraction o Angiotensin enhances sodium reabsorption ROLE OF ALDOSTERONE - Infusion of mineralocorticoids produces HTN - Aldosterone stimulates sodium retention & hypervolemia *Chronic Steroid Use HTN RENAL ARTERY STENOSIS AND HTN - Usually severe HTN - Clinical Clues: o Old, white male, smokers in wheelchair after amputation o High BP with low potassium o Presence of bruit (palpate jugular vein, mabilis yung flow) *Flow to kidney is impaired perfusion low volume activates renin-angiotensin system ROLE OF SYMPATHETIC NERVOUS SYSTEM (SNS) - Persistent increased SNS tone HTN - NorE modulates sympathetic tone - Increased levels HTN (Pheochromocytoma, Emotional Stress) - Mechanisms: o NorE directly stimulates vascular smooth muscle contraction and SVR through receptor mediated binding o NorE induces kidney sodium retention o NorE stimulates renin release *Predominant tone in the body: Parasympathetic *Pheochromocytoma NorE-secreting tumor Page 2

*Type A personality agitated, closed to changes; may have 1 HTN PHEOCHROMOCYTOMA - Tumor that secretes NorE or NorE/Epinephrine - Rare condition - Usually produces severe HTN - Assoc. c other signs of increased cathecholamines (sweating and palpitation) JNC VII BP Classification Normal PreHTN Stage 1 HTN Stage 2 HTN Examples: 120/70 Normal 130/90 PreHTN 130/100 Stage 2 160/90 Stage 2 FOLLOW-UP RECOMMENDATION Initial BP Normal PreHTN Stage 1 HTN Stage 2 HTN SBP <120 120-130 140-159 160 DBP & <80 Or 80-90 Or 90-99 Or 100

If c DM, kidney dse, lifestyle modification trial to reduce BP to 130/80 or less; if not, may give medication

ISOLATED SYSTOLIC HTN - SBP more important cardiovascular risk factor p age of 50 - DBP more important before age of 50 HYPERTENSIVE URGENCIES - Severely elevated BP - Without progressive end-organ dysfunction - Example: highly elevated BP s severe headache, SOB or chest pain - Usually d/t uncontrolled HTN - Lower BP within days HYPERTENSIVE EMERGENCIES - Severely elevated BP - With progressive target organ dysfunction - Require emergent lowering of BP *slurry speech, vomiting, seizures, blurry vision, etc HYPERTENSION IN WOMEN - Oral contraceptives may increase BP - Risk of HTN increases c duration of use - Women c HTN who become pregnant should be followed up regularly o Increased risk to mother & fetus o Recommended drugs: methyldopa, Betablockers, Vasodilators o ACEI & ARB Contraindicated d/t potential fetal defects - Preeclampsia o HTN + Pregnancy o Occurs p the 20th wk of pregnancy o New-onset or worsening HTN, albuminuria & hyperuricemia *High risk; followed up every wk or 2wks Page 3

Follow-up Recheck in 2 yrs Recheck in 1 yr Confirm within 2 mos Evaluate or refer within 1 mo If c very high BP (>180/110mmHg) evaluate & treat within 1 wk

PREHYPERTENSION - Not a dse category - Designation for individuals at high risk for developing HTN - Not candidate for drug therapy - Advised lifestyle modification, targeting risk factors By AKC 15 JULY 2013

HYPERTENSION IN CHILDREN & ADOLESCENT - BP (on repeated measurement) at the 95 percentile or greater adjusted for age, height & gender (may map); common in obese pts - Lifestyle modifications strongly recommended - Identify possible causes of HTN - Uncomplicated HTN not reason to restrict children from participating in physical activities o Long term exercise may lower BP RESISTANT HYPERTENSION - Failure to reach goal BP in pts who are adhering to full doses of an appropriate 3-drug regimen that includes diuretic COMPLICATION OF PROLONGED UNCONTROLLED HYPERTENSION - Changes in vessel wall vessel trauma & arteriosclerosis throughout the vasculature - Complications arise d/t the target organ dysfunction & ultimately failure - Damage to the BV can be seen on fundoscopy *Hemorrhagic Stroke HTN EFFECTS ON CARDIOVASCULAR SYSTEM - Ventricular Hypertrophy, Dysfunction & Failure - Arrhythmias - Coronary Artery Disease, Acute MI - Arterial Aneurysm, Dissection & Rupture EFFECTS ON KIDNEYS - Glomerular sclerosis impaired kidney fxn & end stage kidney dse - Ischemic kidney dse especially when renal artery stenosis cause of HTN EFFECTS ON CENTRAL NERVOUS SYSTEM By AKC 15 JULY 2013

Stroke Cerebral Atrophy ((-) substance ng brain) and Dementia (early onset)

EFFECTS ON EYES - Retinopathy - Vitreous Hemorrhage, Retinal Detachment - Neuropathy extraocular muscle paralysis & dysfunction BP Lifestyle Initial Drug Initial Drug Classification Modification Therapy Therapy Without With Compelling Compelling Indication Indication Normal Encourage No Anti-HTN drug Drugs for indicated compelling indications PreHTN Yes Stage 1 HTN Yes Thiazide type Drugs for diuretics for most; compelling may consider ACEI, indications ARB, BB, CCB or combination Stage 2 Yes 2-drug combination for most (thiazidetype diuretics + ACEI or BB or CCB) LIFESTYLE MODIFICATION Modification Recommendation WEIGHT REDUCTION Maintain normal body wt (BMI: 18.5 -24.9kg/m2)

Approx. SBP Reduction 5-20mmHg /10kg wt loss 8-14mmHg Page 4

ADOPT DASH Consume a diet rich in fruits, EATING PLAN vegetables & low fat dairy

products c a content of saturated & total fat DIETARY dietary sodium intake to no SODIUM more than 100mmol/day (2.4g RESTRICTION sodium or 6g NaCl) PHYSICAL Engage in regular aerobic ACTIVITY physical activity (at least 30min/day, most days of the wk) MODERATE Limit intake to no more than 2 ALCOHOL INTAKE drinks (1oz or 30ml ethanol, 24oz beer, 10oz wine, 3oz/80proof whiskey)/day in men and to no more than 1 drink per day in women

2-8mmHg

4-9mmHg

2-4mmHg

GENERAL STRATEGIES IN MX OF HTN - Increase Sodium Excretion (Diuretics) - Inhibits Aldosterone Production (Spironolactone) - BV smooth muscle relaxation/vasodilation (Vasodilators, CCB, BB) - Inhibits angiotensin II production and action (ACEI, ARB)
COMPELLING INDICATIONS HEART FAILURE POST-MI HIGH CORONARY DISEASE RISK DIABETES CHRONIC KIDNEY DISEASE RECURRENT STROKE PREVENTION RECOMMENDED DRUGS BB ACEI ARB CCB (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+) (+)

DIU (+) (+) (+) (+)

AA (+) (+)

By AKC 15 JULY 2013

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