GFR, Renal Clearance and Autoregulation of Renal Blood Flow

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Gomerular Filtration Rate

'product of net filtration pressure across the glomerular filter and the filtration co-efficient (Kf)'

Filtration co-efficient = product of fluid permeability of glomerular filter and the area available for filtration.

GFR is vital for normal kidney function and shows how well the kidneys are producing filtrate, with it being impaired during pathological abnormalities.

Forces governing GFR

Protein-Osmotic/Oncotic Pressures: almost 0 in Bowman's Space

Hydrostatic Pressures: favours filtration, only force promoting it in the glomerular capillaries

GFR = Kf x net filtration pressure

GFR = forces out - forces in

= Pcap - (pi*cap + Pbc)

Opposing Forces to filtration = hydrostatic pressure in Bowman's Space and osmotic pressure in plasma

Changes in pressures along the Glomerular Capillary

Net Hydrostatic Pressure: doesn't change

Oncotic Pressure: increases as the filtrate is forced out into Bowman's Space

Net Filtration Pressure: decreases

NET FILTRATION = NET HYDROSTATIC PRESSURE - ONCOTIC PRESSURE

-filtration is faster at the beginning of the capillary than the end

Effects of Renal Blood Flow on pressure rates - a change in blood flow leads to a change in the increase/decrease of oncotic pressure along the length of the glomerular capillary

LARGE REDUCTION: equilibrium is reached between the forces promoting and opposing filtration before the end of the capillary is reached, so the last part of the glomerular capillary is not involved in filtration

LARGE INCREASE: less plasma filters out, which reduces the oncotic pressure and so the GFR increases

Factors affecting GFR

GFR can also be affected by:

the surface area available for filtration

permeability of the filtration barrier

GFR = KS [(Pcap) - (Pbc + pi*cap)]

K = permeability of the filtration barrier

S = surface area of the filtration barrier

- a breakdown of the filtration barrier increases GFR

- protein deposits block the barrier and so reduce GFR

Other Factors:

Blood Pressure: low = renal failure and no filtration ; high = damage to barrier and increase in GFR

Plasma protein levels: low protein-oncotic pressure increases filtration

Hydrostatic pressure in BC: kidney stones block the ureter, decreasing filtration and increasing HP of BC

Protein levels in BC: an increase in oncotic pressure increases filtration

Hydrostatic Pressure and GFR

Constriction of afferent arteriole: decreased HP and decreased blood flow = reduced filtration

Constriction of efferent arteriole: increased HP and decreased blood flow = little change in filtration

- as afferent and efferent arterioles can be adjusted separately, it allows independent regulation of GFR

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Renal Clearance = volume of plasma that would have to be fully cleared for the substance to account for the amount of substance appearing in the urine per minute

' measure of how efficient/effective the kidney is at removing a substance from the blood'

the substance enters the nephron from the afferent arteriole at a specific concentration

fluid is filtered in the glomerulus along with some of the substance

a different concentration of the substance leaves the glomerulus in the blood

some of the substance is reabsorbed

a different concentration of the substance leaves the kidney in the blood

the volume of the blood is cleared of the substance in accordance with its relative concentration

Clearance = (conc in urine x volume urine produced/minute) / conc in plasma

expressed as ml/min

-the value for GFR is the most important piece of information to diagnose kidney function

- GFR can be determined by measuring the clearance of Creatinine

Creatinine and GFR

creatinine is filtered as easily as water and isn't reabsorbed from tubules

plasma volume filtered per minute is completely cleared of creatinine

clearance value of creatinine = GFR

Inulin and GFR

Inulin clearance can be used as a measure of GFR

it's infused into the blood stream at a constant level

it isn't secreted or reabsorbed, so the amount passed in the urine should be the amount infused

Amount per minute in urine = amount filtered per minute

Comparing Clearance Ratios

The clearance of a substance can be compared with Inulin:

Clearance of X is lower than Inulin = X is not freely filtered or is reabsorbed (more retained in blood and not fully cleared)

Clearance of X is higher than Inulin = X is secreted (more taken from blood beyond filtration into tubular fluid) e.g. PAH

PAH

-the clearance of PAH (an organic acid) can be used to work out how much plasma is perfusing the kidney

-PAH is freely filtered, with the remainder being secreted into the proximal tubule

PAH in urine = PAH filtered + PAH secreted

- amount of PAH is equal to the amount of plasma flowing through the kidney

Filtration Fraction = fraction of the plasma perfusing the kidney that is filtered

= GFR/RPF

- normally 0.15-0.20

Filtered Load = the amount of a solute that is filtered in one minute given that the solute is freely filtered

-calculated from the GFR and plasma concentration of a solute

filtered load = GFR X Plasma concentration

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Autoregulation of Renal Blood Flow

renal blood flow and GFR is very constant, which protects the GFR so that kidney processes aren't changed by a change in initial filtration

renal blood flow is the main determinant of GFR

resistance of afferent arterioles can vary against changes in arterial blood pressure

Pressure Autoregulation = a change in arterial blood pressure is met correspondingly with a change in resistance in renal afferent arterioles (not efferent)

- autoregulation prevents large changes in GFR and urine output, however arterial pressure changes will still affect renal excretion to some extent (mainly to do with the concentrations of ions)

'PRESSURE DIURESIS = increased urinary excretion due to an increase in arterial blood pressure'

-it doesn't depend on nerve supply, with it being an inherent ability of the kidneys due to intrinsic factors

MYOGENIC: smooth muscle in afferent arterioles can contract and relax as needed to stabilize perfusion and filtration ; an increased blood pressure stretches the capillaries and leads to a constriction of afferent arterioles

TUBULO-GLOMERULAR FEEDBACK: an increase in blood flow/GFR leads to signalling paracrine hormones being released that causes constriction of afferent arterioles ; causes blood flow and filtration to return to normal levels

Extrinsic Control

Sympathetic Control: increased sympathetic activity leads to constriction of afferent and efferent arterioles which reduces blood flow to the kidneys, but filtration is only minimally changed ; increased the conservation of water and salts ; neural input is most effective at preventing a fall in arterial blood pressure

Vasoconstriction: local relase of vasodilators reduces the constriction within the arteries e.g. Angiotensin 2

Severe reduction in arterial blood pressure will depress RBF and may lead to acute renal failure: there must be a minimal level of GFR at all times for basic kidney function

Angiotensin 2

- constricts efferent arterioles to help maintain filtration/GFR

- increases tubular reabsorption by increasing hydrostatic pressure in glomerular capillaries and decreasing the hydrostatic pressure in peritubular capillaries