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BLOCK: URIN 313PHYSIOLOGY OF THE URINARY SYSTEM LECTURE 2

Dr. Amel Eassawi

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GLOMERULAR FILTRATION

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OBJECTIVESThe student should be able to: Understand the forces involved in forming the glomerular ultrafiltrate and the

interaction between them.Define RBF, RPF, GFR, and filtration fraction, and give the normal values for each.Describe the effects of changes in afferent and efferent arteriolar resistances on renal

blood flow.Understand the mechanisms involved in the autoregulation of RBF and GFR.Compare and contrast the myogenic and tubuloglomerular feedback (TGF)

components in the autoregulatory response. Predict the change in RBF and GFR that would occur with an increase in renal

sympathetic nerve activity.Understand the contributions of circulating and locally generated substances on the

regulation of RBF and GFR. Identify the component of the filtration barrier whose damage would result in

hematuria and proteinuria.Define the filtration coefficient at the glomerular capillary and explain its role in

determining GFR.

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GLOMERULAR FILTRATION

• Is the first step in urine formation.• Glomerular filtration is the transfer of fluid and solutes

from the glomerular capillaries into Bowman's capsule due to pressure gradient.

• When blood passes through glomeruli, blood cells (RBC, WBC, Platelet) and plasma protein are not filtered.

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GLOMERULAR FILTRATION• Glomerular Filtration occurs through glomerular

membrane.• Glomerular membrane has 3 layers:

1. Glomerular capillary endothelial cells

2. Basement membrane

3. Inner layer of Bowman’s capsule – epithelial cells

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GLOMERULAR FILTRATION1.Glomerular membrane is more permeable than capillaries because

the glomerular capillary wall has single layer of endothelial cells. It is perforated by many large pores called Fenestrations, that makes it 100 time more permeable to water and solutes than other capillaries in the body.

2. Basement membrane – it does not have cells, but is composed of collagen and glycoprotein. Glycoprotein are negatively charged.

3. Inner layer of Bowman’s capsule – epithelial cells. Epithelial cells are called Podocytes. Each podocyte has foot processes. Narrow silts between adjacent foot processes are known as Filtration silts, they allow the fluid to enter the lumen of Bowman’s capsule.

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GLOMERULAR FILTRATIONThe glomerular filtrate is nearly protein free and contains most inorganic ionsand low-molecular-weight organic solutes in virtually the same concentrationsas in the plasma.

The major barriers of filtration of macromolecules are: molecular size and electrical charge. Negatively charged macromolecules are filtered to a lessextent, and positively charged macromolecules to a greater extent, than neutralmolecules.

Molecular weights less than 7000 daltons are freely filtered. (eg. glucose, urea amino acids and many hormones).

The filtration barrier almost totally excludes plasma albumin (molecular weights of approximately 66,000 daltons). Molecular weight is a reference for size, in reality, it is the molecular radius that is critical. Albumin is not filtered due to its

negative charge, it is repel by basement membrane negative charges.

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GLOMERULAR FILTRATIONProteinuria (protein in urine) occur in kidney disease because negative charge on basement membrane are lost, therefore, albumin is filtered and lost in urine.

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Table 26-1

Filterability of Substances by Glomerular Capillaries Based on Molecular Weight

Substance

Molecular Weight

Filterability

Water

18

1.00

Sodium

23

1.0

Glucose

180

1.0

Inulin

5,500

1.0

Myoglobin

17,000

0.75

Albumin

69,000

0.005

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GLOMERULAR FILTRATION Four Forces are involved in glomerular filtration;

1. Glomerular capillary blood pressure - 55mmHg (Favors filtration)

(PGC)

2. Plasma Colloid Osmotic Pressure – 30mmHg (Opposes filtration)

(πGC)

3. Bowman’s Capsule Hydrostatic – 15mmHg (Opposes filtration)

Pressure (PBS)

4. Bowman’s capsular colloidal osmotic pressure (πBC) is Zero (Favors filtration)

Net filtration pressure = PGC - (πGC + PBS)

Net filtration pressure = 55 – (30+15) = 10 mmHg

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Figure 26-12 Summary of forces causing filtration by the glomerular capillaries. The values shown are estimates for healthy humans.

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GLOMERULAR FILTRATION RATEGLOMERULAR FILTRATION RATE (GFR)

It is the filtrate produced by all the nephrons of both kidneys per minute.

• Normal young adult male GFR = 125ml/min OR 180 liters/day

• In female GFR = 115ml/min OR 160 liters/day

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GLOMERULAR FILTRATION RATE• Glomerular Filtration Rate (GFR) depends on:

1. Filtration Pressure

2. Glomerular Surface Area

3. Permeability of Glomerular Membrane

• The surface area and permeability are referred to as filtration coefficient (Kf).

GFR = Kf × net filtration pressure

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GLOMERULAR FILTRATION RATEFactors affecting Glomerular Filtration Rate (GFR)1-Increased Glomerular Capillary Hydrostatic Pressure

(PGC) -> increase GFR

2-Increase colloid osmotic Pressure (πGC)-> decrease GFR e.g. Dehydration, Diarrhea

3-Increase Bowman’s capsule Pressure (PBS)->decrease GFR e.g. urinary tract obstruction, enlarged prostrate

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GLOMERULAR FILTRATION RATE - If afferent arteriole is constricted by epinephrine, norepinephrine,

endothelin (increased resistance), blood flow will decrease, therefore, GFR will decrease

- If afferent arteriole dilate by Nitric oxide, Prostaglandin(decreased resistance), blood flow will increase, therefore, increase GFR

- If efferent arteriole constrict by Angiotensin- II, pressure in glomeruli will increase, therefore, increase GFR

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Increased bloodflow to other organs

Increased resistancein afferent arteriole

Decreased resistancein afferent arteriole

Decreased capillary blood pressure( PH)

Decreased RBF

DecreasedGFR

(b)

? PH

? GFR

? RBF

Afferent arteriole

Arterial resistance

Efferent arteriole

Bowman’s capsule

Renal blood flow (RBF)

Glomerularfiltration rate(GFR)

(a)

IncreasedGFR

Increased resistancein efferent arteriole

Decreased RBF

(c)

Increased PH

Glomerulus

Flow to other organs

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GLOMERULAR FILTRATION RATE

GFR IS AFFECTED BY CHANGES IN FILTRATION COEFFICIENT• Filtration coefficient (Kf) depends on glomerulus surface area and

permeability of glomerular membrane.• Kf can be modified by contractile activity in the glomerular

membrane by mesangial cells and Podocytes, foot processes in Bowman capsule (physiological) .

• Kf can be reduced by pathological process e.g. Diabetes mellitus, Hypertension, Glomerulonephritis

• If Kf decreased – decreased GFR – in hypertension, diabetes mellitus, GMN, reduced Kf occurs due to increased thickness of glomerular basement membrane and damage to glomeruli.

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Determinants of Renal Blood Flow

Renal blood flow is determined by the pressure gradient across the renal vasculature (the difference between renal artery and renal vein hydrostatic pressures), divided by the total renal vascular resistance:

(Renal artery pressure – Renal vein pressure)Total renal vascular resistance

Note: Renal artery pressure is about equal to systemic arterial pressure and renal vein pressure averages about 3-4 mmHg under most conditions.

A typical Renal blood flow is 1.1 L/min.

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RENAL PLASMA FLOW AND FILTRATION FRACTION

Renal blood flow (RBF) is closely related to Renal plasma flow (RPF)which is the volume of blood plasma delivered to the kidneys per unit time. The normal range for RPF is 585 – 605 ml/min.

Thus of the 585 – 605 mL of plasma that enters the glomeruli viathe afferent arterioles, 125/605, or 20%, filters into Bowman’s space.The remaining 480 mL passes via the efferent arterioles into theperitubular capillaries.

This ratio – GFR/RPF – is known as the filtration fraction.Because freely filtered substances are passing into Bowman’s spacealong with the water, about 20% of all freely filtered substances (eg,sodium) that enter the kidney also move into Bowman’s space.

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Figure 19-4 The filtration fraction

>19% of fluidis reabsorbed.

Plasma volumeentering afferentarteriole = 100%

<1% ofvolume isexcreted toexternalenvironment.

Remainderof nephron

Bowman’scapsule

Glomerulus

>99% of plasmaentering kidneyreturns to systemiccirculation.

Efferent arteriole Peritubularcapillaries

Afferentarteriole

20% ofvolumefilters.

80%

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2 3

4

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GLOMERULAR FILTRATION RATE

Controlled adjustments in GFRGlomerular capillary blood pressure can be controlled to adjust GFR to suit the body’s needsTwo major control mechanisms

1. Autoregulation (aimed at preventing spontaneous changes in GFR)i. Myogenic mechanismii. Tubuloglomerular feedback (TGF)

2. Extrinsic sympathetic control (aimed at long-term regulation of arterial blood pressure)

iii. Mediated by sympathetic nervous system input to afferent arterioles

iv. Baroreceptor reflex

Copyright © 2010 Pearson Education, Inc.

The major function of auto-regulation in the kidneys is to maintain a relatively constant GFR and to allow precise control of renal excretion of water and solutes.

The GFR normally remains auto-regulated, despite considerable arterialpressure fluctuations that occur during usual activities.

In general, renal blood flow is auto-regulated in parallel with GFR, but GFR is more efficiently auto-regulated under certain conditions.

AUTO REGULATION OF GFR AND RENAL BLOOD FLOW

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MYOGENIC AUTOREGULATION OF RENAL BLOOD FLOW AND GFR

The ability of individual blood vessels to resist stretching during increasedarterial pressure.

Stretch of the vascular wall allows increased movement of calcium ions fromthe extracellular fluid into the cells causing them to contract.

The contraction prevents over distension of the vessel and at the same time,by raising vascular resistance, helps prevent excessive increases in renalblood flow and GFR when arterial pressure increases.

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Adjustments of AfferentArteriole Caliber to AlterThe GFR

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Figure 26-16 Autoregulation of renal blood flow and glomerular filtration rate but lack of autoregulation of urine flow during changes in renal arterial pressure.

Downloaded from: StudentConsult (on 14 January 2010 08:45 PM)

© 2005 Elsevier

29Figure 26-18 Macula densa feedback mechanism for autoregulation of glomerular hydrostatic pressure and

glomerular filtration rate (GFR) during decreased renal arterial pressure.

Tubuloglomerular Feedback Mechanism

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Figure 26-17 Structure of the juxtaglomerular apparatus, demonstrating its possible feedback role in the control of nephron function.

Downloaded from: StudentConsult (on 14 January 2010 08:45 PM)

© 2005 Elsevier

Autoregulation

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Baroreceptor Reflex: Influence on the GFR in Long-term Regulation of Arterial Blood Pressure

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Other Factors That Increase Renal Blood Flow and GFR: High ProteinIntake and Increased Blood Glucose

A high protein meal increases the release of amino acids into the blood, whichare reabsorbed in the proximal tubule.

Increased amino acid reabsorption also stimulates sodium reabsorption in theproximal tubule.

The decrease in sodium delivery to the macula densa.

Glucose, like some of the amino acids, is also reabsorbed along with sodium in theproximal tubule, increased glucose delivery to the tubules causes them to reabsorbexcess sodium along with glucose.

The decrease in sodium delivery to the macula densa.

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MEASUREMENT OF GLOMERULAR FILTRATION RATE• Renal clearance means that the substance is removed from the

blood and excreted in the urine.

Substances used to measure GFR

1. Inulin – polymer of fructose, it is filtered, but not reabsorbed, not secreted by renal tubule.

2. Creatinine – it is little secreted, therefore, not so accurate as inulin.

Inspite of this clearance of endogenous creatinine is frequently used to measure GFR.

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REFERENCES

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Human physiology by Lauralee Sherwood, seventh edition

Text book physiology by Guyton &Hall,11th edition

Text book of physiology by Linda .s contanzo, third edition