Health

Ruth Anderson & Robert Stone

Ruth Anderson: Case of secondary hypertension and hypokalemia in a young woman. Be able to recognize clinical characteristics of secondary hypertension and understand underlying physiology to enable diagnostic and treatment strategies

Robert Stone: Understand blood pressure, renin-angiotensin system, and atherosclerosis

1. Renin-Angiotensin-Aldosterone System

* ACEI and pregnancy

* Mechanism of action

* Monitoring of ACEI

* Hypokalemia/hyperkalemia as result of RAAS

2. Hypertension

* Classification of primary and secondary & etiology

* DEEPICT secondary HTN

* Symptoms, labs, when to admit?

* Treatments - Beta-blockers, Ca2+ channel blockers, diuretics

* Refractory HTN

* Atherosclerosis and HTN

3. Review of Case

* Silver wiring

* Creatinine clearance

* Calculation & what it means

* Explain CHF - relation to OTC medications (NSAIDs)

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Renin-Angiotensin System

* Renin is serine acid protease protein enzyme released by kidneys when arterial pressure falls too low

* Renin synthesized and stored in inactive form (prorenin) in juxtaglomerular cells (JG cells) of kidneys

* JG cells are modified smooth muscle cells in walls of afferent arterioles immediately proximal to glomeruli

* Decreased arterial pressure  intrinsic reactions in kidneys cause many prorenin molecules in JG cells to split and release renin

* Most renin enters renal blood and passes out of kidneys into circulation

* Small amts of renin remain in local fluids of kidney and initiate intrareneal functions

* Renin acts enzymatically on another plasma protein called angiotensinogen to release 10-aa peptide, angiotensin I

* Angiotensin I has mild vasoconstrictor properties but not enough to cause significant changes in circulatory function

* w/in few seconds to minutes after formation of angiotensin I, 2 more aa's are split off from angiotensin I to form 8-aa peptide, angiotensin II

* conversion to AII occurs in lungs while blood flows through small vessels of lungs, catalyzed by angiotensin converting enzyme that is present in endothelium of lung vessels

* AII is powerful vasoconstrictor, but only persists in blood for 1-2 mins b/c it's rapidly inactivated by multiple blood and tissue enzymes collectively called angiotensinases

* Angiotensin II has 2 main effects that can elevated arterial pressure

1) vasoconstriction in many areas of body occurs rapidly - acute effect

* arterial vasoconstriction > venous vasoconstriction

* arteriole constriction increases total peripheral resistance  raises arterial pressure

* mild venous constriction promotes increased venous return of blood to heart  helps heart pump against increasing pressure

2) decreased excretion of both salt and water by kidneys - long-term effect

* causes increase in extracellular fluid volume  increased arterial pressure during subsequent hours and days

* renin-angiotensin vasoconstrictor system requires 20 min to become fully active

* thus: slower to act for pressure control than nervous reflexes and sympathetic norepinephrine-epinephrine system

* angiotensin II causes kidneys to retain both salt and water in 2 major ways:

1) AII acts directly on kidneys to cause salt and water retention

* Mechanisms of AII on kidneys:

* Constrict renal arterioles  diminishes blood flow through kidneys  less fluid filters through glomeruli into tubules

* Slows flow of blood through kidney  reduces pressure in peritubular capillaries  causes rapid reabsorption of fluid from tubules

* Direct effect on tubular cells  increase tubular reabsorption of sodium and water

2) AII causes adrenal glands to secrete aldosterone  aldosterone increases salt and water reabsorption by kidney tubules

* Activation of renin-angiotensin system causes rate of aldosterone secretion to also increase

* Function of aldosterone  increase sodium reabsorption by kidney tubules  increases total body extracellular fluid sodium  increased Na causes water retention  increases extracellular fluid volume  long-term elevation of arterial pressure

* Direct effect of angiotensin on kidneys is perhaps 3 or more times as potent as indirect effect acting through aldosterone

Role of Renin-Angiotensin system in maintaining normal arterial pressure despite salt intake

* Increased salt intake  elevated extracellular fluid volume  elevated arterial pressure  increased blood flow through kidneys  reduced rate of secretion of renin  decreased renal retention of salt and water  return of extracellular fluid volume almost to normal  return of arterial pressure almost to normal

* Thus: renin-angiotensin system is automatic feedback mech. that helps maintain arterial pressure at or near normal level even when salt intake is increased

* When system functions normally, arterial pressure rises no more