Long-Term Regulation of Blood Pressure PDF

LONG - TERM REGULATION OF ARTERIAL PRESSURE NRAN 80413 SPRING 2024 RON ANDERSON, M.D. 1 PRESSURE DIURESIS Renal Function Curve (renal urinary output curve) Urinary volume increases with increasing arterial pressure, as does urine sodium output. GUYTON 2 PRESSURE DIURESIS All baroreflex (nervous) mec...

LONG - TERM REGULATION OF ARTERIAL PRESSURE NRAN 80413 SPRING 2024 RON ANDERSON, M.D. 1 PRESSURE DIURESIS Renal Function Curve (renal urinary output curve) Urinary volume increases with increasing arterial pressure, as does urine sodium output. GUYTON 2 PRESSURE DIURESIS All baroreflex (nervous) mechanisms blocked. Rapid infusion of 400ml of blood. Immediate increase in: – CO to >2x normal – BP from 95-205mm Hg – Urine output 12x Over ~ 1 hour BP and CO return to normal GUYTON 3 LONG-TERM BLOOD PRESSURE REGULATION Primarily a function of the kidneys in regulating salt and water balance with nervous and hormonal input. Pressure Diuresis – Increased arterial pressure produces increased renal water loss Pressure Natriuresis – Increased arterial pressure produces increased renal salt loss 4 INFINITE FEEDBACK GAIN MECHANISM Based on two intersecting curves – Renal function curve – Salt and H2O intake curve Equilibrium point is where the two lines intersect. 5 GUYTON DETERMINANTS OF LONG-TERM ARTERIAL PRESSURE Two mechanisms available to move the equilibrium point – Shift the renal function curve along the pressure axis – Alter the salt and water intake 6 GUYTON EFFECT OF TOTAL PERIPHERAL RESISTANCE ON LONG-TERM BLOOD PRESSURE An abrupt increase in total peripheral resistance may produce a short-term increase in arterial pressure, but: In the presence of normal renovascular resistance and renal function, the arterial pressure will rapidly return to normal. GUYTON 7 EFFECT OF INCREASED CARDIAC OUTPUT ON ARTERIAL PRESSURE Two mechanisms by which increased cardiac output increases arterial pressure – Direct effect – Increased total peripheral resistance via autoregulation Makes it possible for a small increase in cardiac output to result in a much larger increase in arterial pressure GUYTON 8 IMPORTANCE OF SALT INTAKE Salt accumulation is the main determinant of ECF volume Mechanisms – Increased fluid osmolality stimulates the thirst center – Increased osmolality stimulates the H-P-A axis to secrete ADH 9 CHRONIC HYPERTENSION Almost always a result of impaired renal fluid excretion Main complications of hypertension – Excess work load on the heart – Injury to vascular endothelium – Neurovascular disease – Renal injury or failure 10 VOLUME-LOADING HYPERTENSION Hypertension resulting from excess accumulation of extracellular fluid Three examples: – Decreased renal mass and increased salt – Dialysis in renal failure – 10 Aldosteronism 11 VOLUME-LOADING HYPERTENSION GUYTON 12 CIRCULATORY CHANGES IN VOLUMELOADING HYPERTENSION Two sequential stages – Increased fluid volume produces increased cardiac output, which increases arterial pressure – Increased arterial pressure and total peripheral resistance with essentially normal fluid volume and cardiac output Increased TPR is a result of the hypertension rather than the cause. GUYTON 13 VOLUME-LOADING HYPERTENSION Two other sources of volume-loading hypertension: – Inadequate dialysis – Primary aldosteronism Mechanism is exactly the same: 1. Excess fluid load leads to increased cardiac output initially 2. Secondary increase in total peripheral resistance follows with return of cardiac output to more normal levels 3. End result is a high peripheral resistance hypertension 14 RENAL PERFUSION SYMPATHETIC STIMULATION (β) ANGIOTENSINOGEN RENIN ANGIOTENSIN I RENIN RELEASE ( from JG cells of renal afferent arterioles) CONVERTING ENZYME ANGIOTENSIN II AMINOPEPTIDASE ALDOSTERONE ANGIOTENSIN III RENIN – ANGIOTENSIN - ALDOSTERONE 15 RENIN-ANGIOTENSIN SYSTEM Actions of Angiotensin II – Vasoconstriction Significant arteriolar constriction Mild venous constriction – Decreased excretion of salt and water by kidneys Direct effect on tubular cells Renal arteriolar constriction Stimulates aldosterone release GUYTON 16 ONSET OF ACTION Slower in onset than nervous control, but: Begins to work in minutes, reaches full acute effect in ~ 20 minutes GUYTON 17 VARIATION IN SALT INTAKE Negative feedback in the Renin-Angiotensin system compensates for a wide variation in salt intake GUYTON 18 HYPERTENSION INVOLVING ANGIOTENSIN One-Kidney Goldblatt – Acute renal artery constriction produces a rapid rise in renin and blood pressure due to: Early: – Angiotensin-induced vasoconstriction Later: – Salt and water reabsorption – As the arterial pressure reaches a level where there is adequate perfusion of the constricted renal artery Renal artery pressure returns to normal Renin secretion returns to normal 19 HYPERTENSION INVOLVING ANGIOTENSIN Two-Kidney Goldblatt – Partial occlusion of one renal artery produces decreased perfusion pressure and release of renin – This results in increased angiotensin and aldosterone which also cause the normally perfused kidney to retain salt and water “Patchy” Kidney Disease – Small, localized areas of inadequate perfusion secret renin leading to a “global” response from the remaining healthy renal tissue 20 OTHER TYPES OF HYPERTENSION Coarction of the Aorta Preeclampsia Neurogenic Hypertension Autonomic Hyperreflexia 21 COARCTATION OF THE AORTA Constriction of the aorta distal to the branches feeding the head and neck, but proximal to the renal arteries Results in hypertension proximal to constriction and normotension distal 22 PREECLAMPSIA aka PIH, Toxemia of pregnancy, Hypertensive Disorder of Pregnancy Believed to result when ischemic areas of the placenta release substances toxic to vascular endothelium into the bloodstream Decreased release of nitric oxide and other vasodilators leads to vasoconstriction Also appears to directly produce glomerular membrane thickening which requires higher pressure to adequately function. 23 NEUROGENIC HYPERTENSION Following sympathetic discharge due to excitation or anxiety. May occur following disruption of the baroreceptor nerves – Loss of inhibitory impulses leads to an over-active vasomotor center and increased sympathetic outflow – Diminshes over ~ 2 days due to central resetting, and blood pressure returns to normal 24 AUTONOMIC HYPERREFLEXIA Stimulus below level of injury Activation of spinal reflex Vasoconstriction Vasodilation Bradycardia Baroreflexes Hypertension Following return of spinal reflexes Incidence ~85% above T6, but rare below T10 Hallmarks are hypertension and reflex bradycardia Initiated by stimulus such as surgery or distention of a hollow viscus Managed with a short-acting vasodilator 25 PRIMARY HYPERTENSION Characteristics – Increased cardiac output – Increased sympathetic nervous system activity – Increased angiotensin II and aldosterone levels – Impaired pressure natriuresis Salt sensitivity – A continuum of effect – Often increases with age GUYTON 26 TREATMENT OF PRIMARY HYPERTENSION Weight loss Increased physical activity Drugs which produce renal vasodilation – Inhibition of sympathetic output or blockade of effect – Direct relaxation of vascular smooth muscle – Block of renin-angiotensin system Drugs which decrease reabsorption of salt and water – Diuretics/ natriuretics 27 INTEGRATION OF MULTIPLE SYSTEMS Rapid (seconds – minutes) – Baroreceptor reflexes – Chemoreceptor reflexes – CNS ischemic response Intermediate (minutes – hours) – Renin-angiotensin system – Vascular stress-relaxation – Capillary fluid shift Long-term – Renal body fluid mechanisms GUYTON 28 SOURCES Textbook of Medical Physiology- Guyton, Hall. 2021. 14th Edition. 29