Large pressure drops across afferent and efferent arterioles
Pcap high in glomerulus (about 50 mm Hg)
Control Mechanisms for renal blood flow
- autoregulation
- protects fragile capillaries
- stabilizes GFR and RBF
- myogenic reflex - increases in renal artery pressure not transmitted to glomerulus because afferent arterioles constrict. (stretch stimulates VSM to constrict). Little myogenic reflex in efferent arterioles (would cause increased capillary pressure)
- tubuloglomerular feedback - modified epithelial cells = macula densa cells, monitor Na and Cl delivery to distal portion of nephron. If GFR is increased a Paracrine factor released (maybe adenosine, thromboxane, ATP) causes vasoconstriction of afferent arterioles = decreased GFR. If GFR is decreased, reduced Na and Cl delivery causes release of different paracrine factor (NO?) to cause vasodilation of afferent arteriole.
- Extrinsic regulation
- No predictable relationship among plasma Na and ECF volume = need for two control systems:
- Osmoregulation pathway
- senses plasma osmolarity
- sensors - hypothalamus osmoreceptors
- effectors - ADH
- affected - urine osmolarity, thirst
- Volume regulation pathways
- senses tissue perfusion (effective blood volume) (MACULA DENSA, ATRIAL RECEPTORS, CAROTID SINUS)
- Effectors = Renin-angiotensin system; ANP; SNS; ADH
- Affected = urinary Na reabsorption; thirst
- Renin-Angiotensin System (RAS)
- local RAS systems in kidney, brain, heart
- starts with renin release
- SNS beta 1 = increased renin release
- inc. NaCl stimulates macula densa = decreased renin
- afferent arteriole stretch = decreased renin
- ends with increased AT2
- constricts afferent and EFFERENT arterioles
- this maintains GFR in face of low perfusion pressure
- ACE inhibitors would block this autoregulation and could lead to renal failure. ACE inhibitors would be contraindicated in patients with hypertension due to renal artery stenosis.
- increases Na reabsorption in proximal tubule
- constricts systemic arteries to increase pressure
- increases NE release (central and peripheral)
- AT2 receptors in hypothalamus (stimulate thirst)
- stimulates ADH release
- stimulates adrenal cortex (zona glomerulosa) to secrete aldosterone
- SNS effects
- increases Na reabsorption (alpha receptors)
- vascular smooth muscle
- afferent and efferent vasoconstriction (alpha receptors) = decreased renal blood flow buffered by autoregulation.
- stimulates renin secretion (beta-1 receptors)
- Atrial Natriuretic Peptide (ANP)
- dilates afferent and contricts efferent arterioles = inc. GFR
- decreases Na reabsorption in collecting duct = increases Na excretion and water excretion (diuresis)
- inhibits secretion of aldosterone, renin, and ADH
- BNP (stretch of ventricles)
- same mechanism of action (lower affinity for receptor but longer half life = useful marker for CHF)
- Endothelin-1 (ET-1) - decreases GFR = decreased Na excretion = increased volume. ET-1 also inhibits Na reabsorption.
- Prostaglandins
- do not regulate GFR under normal conditions
- SNS stimulation (e.g., fight or flight) stimulates production of PGI2 and PGE2 vasodilators that counter the SNS vasoconstriction and potential renal failure due to decreased GFR.
- dangerous to have COX inhibitors (remove above protective mechanism)
- NO
- inhibits Na reabsorption in distal tubule
- NO inhibitors cause Na retention (can cause hypertension)
intake of NaCl activates osmolarity and volume regulation pathways = incr. ADH, ANP, & RAS
intake of water also activates both pathways but inhibits ADH and RAS and stimulates ANP.
intake of isotonic NaCl does not activate osmolarity pathway, stimulates ANP and this increase in ANP inhibits RAS.
nice RAS figure:
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