GFR Regulation Flashcards
Renal blood flow (RBF)
About 20% of CO (renal fraction)
Proportionally greater than for most organs
Since need to filter the blood etc
Also high demand for oxygen with all the Na/K ATPases
Normal: 1200mL/min
Oxygen shunting by the vasa recta
Shunt from the descending vasa recta —> ascending
Thus, the O2 supply to the deep medullary is limited (relies more on anaerobic metabolism)
Dual microvascular beds of the kidney
Glomerular and post-glomerular vascular beds
Separate the filtering and reabsorptive processes
What creates a ‘nesting’ of glomerular capillaries between the afferent and efferent arterioles
Preglomerular resistance (afferent)
Post-glomerular resistance (efferent)
…allows the maintenance of a high glomerular pressure that can be regulated precisely
What pressure is primarily responsible for the formation of filtrate?
Glomerular pressure
What does a low peritubular capillary pressure allow?
Elevated plasma colloid osmotic pressure to predominate
Thus be responsible for the return of the tubular reabsorbate to the circulation
Afferent arteriole resistance =
(Renal a. Pressure - Glomerular pressure) / RBF
Efferent arteriole resistance (renal)
(Glomerular pressure - Capillary pressure) / (RBF - GFR)
Normally, filtration continues throughout the entire length of the glomerular capillaries
Where there remains a finite + ?
Effective filtration pressure (EFP)
At the efferent end of the capillaries
Glomerular Filtration Rate (GFR) =
Kf(Pg - Pb - pi-g)
Kf = filtration coefficient
Pg = glomerular hydrostatic pressure
Pb = counteracting pressure in bowman’s space
Pi-g = average colloid osmotic pressure in the glomerular capillaries
Decreases in filtration coefficient can occur in what pathological states?
HTN
Diabetes
Glomerulosclerosis.
—> all lead to decreased GFR
Selective increase in afferent resistance
Reduces —>
Both plasma flow and glomerular hydrostatic pressure
GFR decreases MORE than plasma flow…therefore the FF decreases
Increase in renal efferent resistance
Reduces —>
Plasma flow
BUT INCREASES glomerular pressure
GFR will increase slightly at first…but eventually will decrease due to the counteracting effects of the glomerular colloid osmotic pressure
RPF falls more than GFR —> FF increases
Can changes in FF alone determine localization of resistance changes?
NO
Effective filtration pressure (EFP) =
= net force driving filtration at the glomerulus
Glomerular p. (Minus) Bowman’s p. (Minus) colloid osmotic pressure
Glomerular filtration coefficient (K-f)
Characteristic of the glomerular membrane that defines how much fluid will filter across the glomerulus per unit driving force
Autoregulation of RBF and GFR
Stabilize the glomerular pressure and filtered volume to the tubules under conditions of moderate variations of cardio function
Such as sleeping
= a constant negative feedback control system that maintains an optimum filtered load in the face of varying external influences
Autoregulatory responses are mediated by active adjustments of ?
SmM tone
Primarily in the afferent arterioles leading to highly efficient autoregulation of both RBF and GFR in response to …
Changes in perfusion pressure
Afferent vs efferent resistance
Response to increasing renal artery pressure
Afferent increases linearly
Efferent stays constant (due to afferent increasing resistance)
RBF vs increasing renal artery pressure
Increases then maxes at 4mL/min*g
When renal arterial pressure ~ 100mmHg
Glomerular, proximal tubule, and capillary pressure
In response to increasing renal arterial pressure
All increase slightly then remain constant
Total relative pressure:
Glomerular > PT > capillary
GFR in response to increasing renal arterial pressure
Increases until max at 0.4mL/min*g
Myogenic auto-regulatory feedback system
Renal
Allows preglomerular arterioles to sense changes in vessel wall tension and respond with appropriate adjustments in vascular tone
Increase wall tension —> initiates SmM contraction (interlobular and afferent arterioles)
To keep blood flow constant
Macula densa TGF mechanism
Responds to disturbances in distal tubular fluid flow past the macula densa
Increases in flow elicit afferent constriction
Decreases = vice versa
Factors that would reduce sensitivity of the macula densa TGF mechanism
Distal volume expansion
(-)ANG II
(-) Cytochrome P450
(+) NO
(+) PGI2
Factors that would increase sensitivity of the macula densa TGF mechanism
Thus decreasing amount of fluid and electrolytes delivered to the distal tubule for any given GFP
Distal volume contraction
(+) ANG II
(-) NO
(+) Thromboxane
(+) HETE
Angiotensin II mechanism
Increases cyotsolic Ca2+
By enhancing Ca2+ entry through voltage dependent Ca2+ channels as well as by mobilization of Ca2+ from intracellular storage sites
—> vasocontriction of afferent arterioles
Calcium channel blockeres
Stops ANGII effect on afferent arteriole
But efferents still constrict
Nitric Oxide
Vasodilation (paracrine factor / endothelial)
Formed IC by NO synthase, cleave NO from L-Arg
NO diffuses out of endothelial cells
Stimulation of guanylate cyclase —> increase cGMP —> vasodilation
Analogues of Arg = block NO formation
—> 25-40% increase in renal resistance with the decreases in RBF being greater than GFR decreases
= ‘NO blockade’
Can be mediated by enhanced renin-angiotensin system activity
Both efferent and afferent responsive to NO…which is why NO blockade decreases GFR less than RBF
Prostaglandins (eicosanoids)
Influence renal vascular resistance, arterial pressure, Na and water exceretion, and renin release
Made from ARA
Cycloxygenase pathway
PGE2, PGF2, PGI2, and TXA2
From ARA
Lipoxygenases
Make leukotrienes and lipoxins from ARA
Administration of PGE2 or PGI2 into renal artery
Causes vasodilation
TXA2 and leukotrienes into renal artery =
Vasoconstriction
Cytochrom P450 monooxygenase enzyme system
Production of eicosanoids
Exert actions on both renal vasculature and tubules
When do prostaglandins act on the kidney
Not normal conditions
Exert protective effects in response to vasoconstrictor stimuli, hypovolemic states, or hypotensive episodes
Sustain constriction (like elevated catecholamine levels) —> prostaglandin production increases to counteract these effects
NSAIDs
Block cycloxygenase
Leave unopposed the vasoconstriction influence of elevated levels of ANGII and catecholamine and decrease RBF, GFR, and sodium excretion
Sympathetic nervous activity
Increase with stress, trauma, etc
Increases renal resistance directly
—> decreases in RBF and GFR, increases in renin release and increases in PT Na and water retention
