GFR Regulation Flashcards by Nick Mankowski

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

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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)

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Dual microvascular beds of the kidney

Glomerular and post-glomerular vascular beds

Separate the filtering and reabsorptive processes

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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

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What pressure is primarily responsible for the formation of filtrate?

Glomerular pressure

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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

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Afferent arteriole resistance =

(Renal a. Pressure - Glomerular pressure) / RBF

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Efferent arteriole resistance (renal)

(Glomerular pressure - Capillary pressure) / (RBF - GFR)

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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

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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

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Decreases in filtration coefficient can occur in what pathological states?

HTN

Diabetes

Glomerulosclerosis.

—> all lead to decreased GFR

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Selective increase in afferent resistance

Reduces —>

Both plasma flow and glomerular hydrostatic pressure

GFR decreases MORE than plasma flow…therefore the FF decreases

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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

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Can changes in FF alone determine localization of resistance changes?

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Effective filtration pressure (EFP) =

= net force driving filtration at the glomerulus

Glomerular p. (Minus) Bowman’s p. (Minus) colloid osmotic pressure

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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