EXTRINSIC CONTROLS (NEURAL AND HORMONAL MECHANISM)
The purpose of the extrinsic controls regulating the glomerular filtration rate is to maintain systemic blood pressure – sometimes to the detriment of the kidneys.
- Symphatetic nervous system controls
Neural renal controls serve the needs of the body as a whole. When the volume of the extracellular fluid is normal and the sympathetic nervous system is at rest , the renal blood vessels are dilated and renal autoregulation mechanisms prevail. However, during extreme stress or emergency when it is necessary to shunt blood to vital organs, neural controls may overcome renal autoregulatory mechanisms.
Norepinephrine released by symphatetic nerve fibers (and epinephrine released by the adrenal medulla) acts on alpha-adrenergic receptors on vascular smooth muscle, strongly constricting afferent arterioles, thereby inhibiting filtrate formation. This, in turn, indirectly trips the renin-angiotensin mechanism by stimulating the macula densa cells. The sympathetic nervous system also directly stimulates the granular cells to release renin.
- RENIN-ANGIOTENSIN MECHANISM
The renin-angiotensin mechanism is triggered when various stimuli cause the granular cells to release the hormone renin. Renin acts enzymatically on angiotensinogen, a plasma globulin made by the liver, converting it to angiotensin I. This, in turn, is converted to angiotensin II by angiotensin converting enzyme (ACE) associated with the capillary endothelium in various body tissues, particularly the lungs.
Angiotensin II acts in five ways to stabilize systemic blood pressure and extracellular fluid volume. (1) As a potent vasoconstrictor , angiotensin II activates smooth muscle of arterioles throughout the body, raising mean arterial blood pressure. (2) Angiotensin II stimulates reabsorption of sodium, both directly by acting on renal tubules and indirectly by triggering the release of aldosterone from the adrenal cortex. Because water follows sodium osmotically, blood volume and blood pressure rise. (3) Angiotensin II stimulates the hypothalamus to release anti diuretic hormone and activates the hypothalamic thirst center, both of which increase blood volume. (4) Angiotensin II also increases fluid reabsorption by decreasing peritubular capillary hydrostatic pressure. This pressure drop occurs because the efferent arterioles constrict, and the downstream drop in hydrostatic pressure allows more fluid to move back into the peritubullar capillary bed. (5) Angiotensin II targets the glomerular mesangial cells, causing them to contract and reduce the glomerulus filtration rate by decreasing the total surface area of glomerular capillaries available for filtration.
While this seems daunting list at first, it will help that all of the effects of angiotensin II are aimed at restoring blood volume and blood pressure. Of angiotensin II’s many effects, the first two are the most important.
Several factors acting independently or collectively can trigger renin release:
- Reduced stretch of the granular cells. A drop in mean systemic blood pressure below 80 mmHg (as might be due to hemorrhage, dehydration, etc) reduces the stretch of the granular cells and stimulates them to release more renin
- Stimulation of the granular cells by input from activated macula densa cells. When macula densa cells sense low NaCl concentration (slowly moving filtrate), they signal the granular cells to release renin. This signal may decrease release of ATP (also thought to be the tubuloglomerular feedback messenger), increased release of the prostaglandin PGE2, or both
- Direct stimulation of granular cells via β1-adrenergic receptors by renal symphatetic nerves.