Renal Physiology 2:Renal Physiology 2:

Renal Haemodynamic & Renal Haemodynamic & Glomerular Filtration RateGlomerular Filtration Rate

Dr Ahmad Ahmeda

aahmeda@ksu.edu.saMobile No: 0536313454

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Learning Objectives

• Describe that the mechanism of urine formation include three basic processes; glomerular filtration, tubular reabsorption and tubular secretion.

• Define GFR and quote normal value.

• Identify and describe the factors controlling GFR in terms of starling forces, permeability with respect to size, shape and electrical charges and ultra-filtration coefficient.

• Describe Intrinsic and extrinsic mechanism that regulate GFR.

• Describe autoregulation of GFR & tubuloglomerular feedback mechanism.

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Blood supply to the kidney

• Approximately one-fourth (1200 ml) of systemic cardiac output flows through the kidneys each minute

• Arterial flow into and venous flow out of the kidneys follow similar paths

• The cortex receives more than 90% of the blood that perfused into the kidney, which is perfused at a rate of about 500 ml/min per 100 gm tissue.

(100 times greater than resting muscle blood flow)

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Blood supply to the kidney

• The remainder of the renal blood supply goes to the capsule and the renal adipose tissue.

• Some of the cortical blood then passes to the medulla, the outer medulla has a blood flow of 100ml/min per 100 g tissue, and the inner medulla a flow of 20 ml/min per 100 g tissue.

• Due to high blood flows to the cortex so, more oxygen than required and that lead to the arterio-venous oxygen difference is only 1-2 %

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Blood supply to the kidney

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1= interlobar arteries 1a= interlobar vein

2= arcuate arteries

2a= arcuate vein

3= interlobular arteries

3a= interlobular vein

4= stellate vein

5= afferent arterioles

6= efferent arterioles

7a,7b= glomerular capillary network

8,8a = descending vasa recta

9= ascending vasa recta

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Capillary Beds of the Nephron• Every nephron has two capillary beds

– Glomerulus – Peritubular capillaries

• Each glomerulus is: – Fed by an afferent arteriole – Drained by an efferent arteriole

• Blood pressure in the glomerulus is high because:– Arterioles are high-resistance vessels– Afferent arterioles have larger diameters than efferent

arterioles

• Fluids and solutes are forced out of the blood throughout the entire length of the glomerulus

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Capillary Beds

• Peritubular bedsPeritubular beds are low-pressure, porous capillaries adapted for absorption that: – Arise from efferent arterioles– adhere to adjacent renal tubules– Empty into the renal venous system

• Vasa rectaVasa recta – long, straight efferent arterioles of juxtamedullary nephrons

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Vascular Resistance in Microcirculation

• Afferent and efferent arterioles offer high resistance to blood flow

• Blood pressure declines from 95mm Hg in renal arteries to 8 mm Hg in renal veins

• Resistance in afferent arterioles:– Protects glomeruli from fluctuations in systemic blood

pressure

• Resistance in efferent arterioles:– Reinforces high glomerular pressure– Reduces hydrostatic pressure in peritubular capillaries

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Measurement of renal blood flow

1)1) Clearance methodsClearance methods:

Use of a substance which is filtered, secreted but not reabsorbed by the nephrons and apply the clearance formula.

An example is para-amino-hippuric acid (PAH) which is freely filtered, secreted by the organic pumps of the proximal tubule and is 100% removed on passage through the kidney.

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Measurement of renal blood flow

• Direct dynamic measurementsDirect dynamic measurements: Electromagnetic flowmeter

• Ultrasound flowmeterUltrasound flowmeter

• Laser-Doppler flowmetryLaser-Doppler flowmetry : Intrarenal haemodynamics

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Glomerular capillary bedHigh pressure vascular bed,increasing oncotic pressure

Good for filtration

Peritubular capillary bed,Low pressure vascular bed,

high oncotic pressure.

Good for re-absorption

Afferent arteriole

Efferent arteriolePeritubular capillaries

Bowman’s capsule

Proximal convoluted tubule

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Mechanisms of Urine Formation

• The kidneys filter the body’s entire plasma volume 40 times each day.

• The filtrate:– Contains all plasma components except protein– Loses water, nutrients, and essential ions to

become urine

• The urine contains metabolic wastes and unneeded substances

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Mechanisms of Urine Formation

• Urine formation and adjustment of blood composition involves three major processes – Glomerular

filtration– Tubular

reabsorption– Secretion

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Glomerular Filtration

• The first step in urine formation

• Blood flows through the glomerulus, allowing protein-free plasma to be filtered through the glomerular capillaries into the Bowman’s capsule.

• ~20% of plasma entering the glomerulus is filtered

• 125 ml/min filtered fluid

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Tubular Reabsorption

• Movement of substances from tubular lumen back into the blood

• Reabsorbed substances not lost in the urine, but are carried by the peritubular capillaries to the venous system

• Most of the filtered plasma is reabsorbed

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Tubular Secretion

• The selective transfer of substances from the peritubular capillary into the tubular lumen

• Allows for rapid elimination of substances from the plasma via extraction of the 80% of unfiltered plasma in peritubular capillaries and adding it to the substances already in tubule as result of filtration

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Urine Excretion “The end product”

• The elimination of substances from the body in the urine

• All plasma constituents filtered or secreted, but not reabsorbed remain in the tubules and pass into the renal pelvis to be excreted as urine and eliminated from the body

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Types of Tubular Reabsorption

• Reabsorption can be transcellular (across the cell) or paracellular (between the cells)

• Once the substance has moved pass the tubular epithelium cell into the interstitial space bulk flow then accounts for its movement back into the peritubular capillaries

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Passive Reabsorption

• Bulk flow results from the imbalance of osmotic or hydrostatic forces at the peritubular capillary. Exactly the same as at the peripheral capillary or the glomerulus

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Active Reabsorption

• Major substances are reabsorbed via active transport. These are substances that are needed by the body (e.g. Na+, glucose, aas, other electrolytes)

• Sodium reabsorption-99.5% of filtered sodium is absorbed– Proximal tubules (67%)– Loop of Henle (25%)– Distal/Collecting tubules (8%)

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Active Reabsorption

• Active reabsorption is via primary active transportprimary active transport based on ATP hydrolysis (e.g. Na+) or secondarysecondary active transportactive transport based on an ion gradient (e.g. glucose)

• Known transporters:– Na+/K+ ATPase– H+ ATPase– H+/K+ ATPase– Ca++ ATPase

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Net Filtration Pressure (NFP)

• The pressure responsible for filtrate formation

• NFP equals the glomerular hydrostatic pressure (HPg) minus the oncotic pressure of glomerular blood (OPg) combined with the capsular hydrostatic pressure (HPc)

NFP = HPg – (OPg + HPc)Or

NFP = PGC – PBS - OGC

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Glomerular Filtration Rate

• Glomerular filtration rate (GFR) is the rate of production of filtrate at the glomeruli from plasma

– Typically 80 – 140 ml/min depending on age, sex etc

– Sum of the filtration rates of all functioning nephrons

– Index of kidney function

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GFR• Factors governing filtration rate at the

capillary bed are:– Total surface area available for filtration– Filtration membrane permeability– Net filtration pressure

• GFR is directly proportional to the NFP• Changes in GFR normally result from

changes in glomerular blood pressure

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GFR

• If the GFR is too hightoo high:– Needed substances cannot be reabsorbed

quickly enough and are lost in the urine

• If the GFR is too lowtoo low:– Everything is reabsorbed, including wastes that

are normally disposed of

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glomerular hydrostatic pressure (GHP)push fluid out of vessels

capsular hydrostatic pressure (CsHP)push fluid back into vessels

net hydrostatic pressure (NHP)

NHP = GHP - CsHP

50 - 1535 = mm Hg

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blood colloid osmotic pressure (BCOP)

proteins in blood (hyperosmotic)

draw water back into blood

~ 25 mm Hg

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FP = NHP - BCOP

35 - 2510 = mm Hg

importance of blood pressure

20% drop in blood pressure50mm Hg to 40mm Hg

filtration would stop

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• Driven by Starling forces

• Pressure inside capillaries > Pressure outside

movement of fluid from blood

• Forces in capillaries: hydrostatic pressure PGC = + 60mmHg

• oncotic pressure GC = - 29 mmHg

net outward pressure = 60 – 29 = 31mmHg

• Forces in capsule: hydrostatic pressure PBS = -15mmHg

• oncotic pressure GBS = 0 mmHg

• Overall: 31 – 15 = 16 mmHg outward

• Male adults GFR: ~ 90 – 140 ml/min

• Female: 80 – 125 ml/min

• 125 ml/min usually good average32

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