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GLOMERULAR FILTRATIONLecture – 2Dr. Zahoor

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Basic Renal ProcessesGlomerular filtrationTubular

reabsorptionTubular secretion

Urine results from these three processes.

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Glomerular filtrationIs the first step in urine

formation.

Definition: Glomerular filtration is the transfer of fluid and solutes from the glomerular capillaries into Bowman's capsule due to pressure gradient.

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GLOMERULAR FILTRATIONGlomerular 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

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

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Layers of Glomerular Membrane

Filtration silt

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GLOMERULAR FILTRATION Glomerular membrane is more permeable

than capillaries elsewhere. WHY ? Because i). 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.

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GLOMERULAR FILTRATION (cont) ii). Basement membrane – it does not have cells,

but is composed of collagen and glycoprotein. Glycoprotein are negatively charged.

iii). 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 FILTRATION (cont)Three 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)

Net filtration pressure = PGC - (πGC + PBS) Net filtration pressure = 55 – (30+15) = 10 mmHg

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Forces involved In Glomerular Filtration

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FILTRATIONIMPORTANTFiltration through glomerular membrane also

depends on size, molecular weight and electrical charge.

E.g. Albumin – 6 nanometerPores in capillary – 8 nanometerBut Albumin is not filtered due to its negative

charge, it is repulsed by basement membrane negative charges.

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FILTRATION - APPLIEDIn kidney disease, we get proteinuria (protein

inurine). WHY?Because negative charge on basement

membrane are lost, therefore, albumin is filtered and lost in urine.

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GLOMERULAR FILTRATION RATEWhat is GLOMERULAR FILTRATION RATE

[GFR]? It is filtrate produced by all the nephrons of

both kidneys per minute.

Normal GFR = 125ml/min OR 180 liters/dayIn female, GFR = 115ml/min OR 160 liters/day

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GLOMERULAR FILTRATION RATEGFR depends on 1. Filtration Pressure 2. Glomerular Surface Area 3. Permeability of Glomerular Membrane

These properties of Glomerular membrane (surface area and permeability) are referred as filtration coefficient (Kf).

GFR = Kf × net filtration pressure

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GLOMERULAR FILTRATION RATEFactors affecting GFR1-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 RATEOther factors 1. If afferent arteriole is constricted by epinephrine,

norepinephrine, Endothelin (increased resistance), blood flow will decrease, therefore, GFR will decrease

2. If afferent arteriole dilate by Nitric oxide,

Prostaglandin(decreased resistance), blood flow will increase, therefore, increase GFR

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

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Adjustments of AfferentArteriole Caliber to AlterThe GFR

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GFR IS AFFECTED BY CHANGES IN FILTRATION COEFFICIENTFiltration 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) .

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GLOMERULAR FILTRATION RATEAPPLIED

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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AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR

There is AUTOREGULATION mechanism in kidney by which it maintains constant blood flow by maintaining constant blood pressure.

Autoregulation is done when systemic mean BP is in the range of 80- 180 mmHg.

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AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR

If GFR increase due to increased BP, it will be reduced to normal by constricting the afferent arteriole.

If GFR decrease due to decreased BP, afferent arteriole will be dilated to increase blood flow and bring GFR back to normal.

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AUTO-REGULATION MECHANISM IN KIDNEY FOR GFRHow kidneys maintain the constant BP ? By altering the diameter of Afferent

arteriole , there by adjusting the flow to glomeruli .

Auto regulation is done by TWO mechanism 1) Myogenic mechanism 2) Tubulo glomerular feed back mechanism.

We will study each one

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AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR1) Myogenic mechanism Myogenic means muscle response. Arterial vascular smooth muscle contracts in

response to stretch accompanying increased pressure with in vessel, therefore, afferent arteriole constricts and decreases blood flow.

But when BP decreases, there is relaxation of afferent arteriole, therefore, increase blood flow occurs in the glomerulus.

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Myogenic Mechanism

Stretch ofBlood Vessel

Cell Ca++

PermeabilityArterial Pressure

Intracell. Ca++Blood Flow VascularResistance

Vascular smooth muscle contraction in response to increased stretch

(afferent arteriole)

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AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR2) Tubulo glomerular feed back mechanism It involves Juxta glomerular apparatus (formed by

Afferent and Efferent arteriole and DCT, Macula Densa Cells).

So, if GFR increases due to increased BP, more fluid will pass to DCT, therefore, increase Na+ delivery to DCT.

In response to that Macula Densa cells release ATP and Adenosine, both act locally by paracrine way and increase calcium entry to afferent arteriole and cause constriction, therefore, reducing glomerular blood flow and returning GFR to normal.

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IMPORTANCE OF AUTO REGULATION As Myogenic and Tubulo glomerular feedback

mechanism work for auto regulation, therefore, they prevent changes in GFR.

If no auto regulation, changes in GFR will occur and will lead to imbalance of fluid and electrolytes and waste product excretion.

NOTE – If mean arterial BP is less than 80mmHg or more than 180mmHg, auto regulation will NOT take place and there will be changes in GFR.

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BLOOD SUPPLY TO THE KIDNEYKidney normally receives 20-25% of cardiac

output i.e. 1.1 liter of blood flow per minute.About 625ml/min of plasma flows to the

kidney.20% of plasma is filtered and converted to

glomerular filtrate and passes to Bowman’s Capsule, therefore, average GFR is 125ml/min.

The remaining [80%] of plasma passes to efferent arterioles then into the peritubular capillaries

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BLOOD SUPPLY TO THE KIDNEYIMPORTANT POINTSRenal blood flow 1.1L (1100ml/min)Renal plasma flow 625ml/minGFR 125ml/minKidney composes less than 1% of total body

weight but gets 20-25% cardiac output. WHY? Because of its function i.e. regulating

water , electrolyte balance and getting rid of waste products.

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MEASUREMENT OF GFRSubstances 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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What is a Glomerular Filtration Fraction?

The Filtration Fraction (FF) is the ratio of the GFR to the renal plasma flow (GFR/RPF).

Filtration fraction = GFR/Renal Plasma flow

= 125/625

= 0.2 = 20%

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