Glomerular Filtration

Normally, 3 Starling forces are at work in glomerular filtration

• Regulation of the GFR is critical to maintaining

homeostasis and is regulated by an assortment of

local and systemic mechanisms:– Renal autoregulation occurs when the kidneys

themselves regulate GFR.

– Neural regulation occurs when the ANS regulates renal

blood flow and GFR.

– Hormonal regulation involves angiotensin II and atrial

natriuretic peptide (ANP).

Glomerular Filtration

• Renal autoregulation of GFR occurs by two means:– Stretching in the glomerular capillaries triggers

myogenic contraction of smooth muscle cells in afferent arterioles (reduces GFR).

– Pressure and flow monitored in the macula densa provides tubuloglomerular

feedback to the glomerulus, causing the

afferent arterioles to constrict (decreasing

blood flow and GFR) or dilate (increasing

blood flow and GFR) appropriately.

Glomerular Filtration

• Neural regulation of GFR is possible because the

renal blood vessels are supplied by sympathetic

ANS fibers that release norepinephrine causing

vasoconstriction.– Sympathetic input to the kidneys is most

important with extreme

drops of B.P. (as occurs

with hemorrhage).

Glomerular Filtration

Two hormones contribute to regulation of GFRAngiotensin II is a potent vasoconstrictor of both

afferent and efferent arterioles (reduces GFR).A sudden large increase in BP stretches the cardiac

atria and releases atrial natriuretic peptide (ANP).•ANP causes the

glomerulus to relax, increasing the surface area for filtration.

Glomerular Filtration

Filtration slitPedicel of podocyte

Fenestration (pore) ofglomerular endothelial cell

Basal lamina

Lumen of glomerulus

(b) Filtration membrane

TEM 78,000x

(a) Details of filtration membrane

Filtration slitPedicel

Fenestration (pore) of glomerularendothelial cell: prevents filtration ofblood cells but allows all componentsof blood plasma to pass through

Podocyte of viscerallayer of glomerular(Bowman’s) capsule

1

Filtration slitPedicel of podocyte

Fenestration (pore) ofglomerular endothelial cell

Basal lamina

Lumen of glomerulus

(b) Filtration membrane

TEM 78,000x

(a) Details of filtration membrane

Filtration slitPedicel

Fenestration (pore) of glomerularendothelial cell: prevents filtration ofblood cells but allows all componentsof blood plasma to pass through

Basal lamina of glomerulus:prevents filtration of larger proteins

Podocyte of viscerallayer of glomerular(Bowman’s) capsule

1

2

Filtration slitPedicel of podocyte

Fenestration (pore) ofglomerular endothelial cell

Basal lamina

Lumen of glomerulus

(b) Filtration membrane

TEM 78,000x

(a) Details of filtration membrane

Filtration slitPedicel

Fenestration (pore) of glomerularendothelial cell: prevents filtration ofblood cells but allows all componentsof blood plasma to pass through

Basal lamina of glomerulus:prevents filtration of larger proteins

Slit membrane between pedicels:prevents filtration of medium-sizedproteins

Podocyte of viscerallayer of glomerular(Bowman’s) capsule

1

2

3

The Filtration Membrane

Glomerular Filtration(Interactions Animation)

Renal Filtration

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NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1

Proximal convoluted tubule

NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1 2

Proximal convoluted tubule

NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

BLOOD COLLOIDOSMOTIC PRESSURE(BCOP) = 30 mmHg

CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1 2

3

Proximal convoluted tubule

Pressures That Drive Glomerular Filtration

Tubular Reabsorption• Tubular reabsorption is the process of returning

important substances (“good stuff”) from the filtrate back

into the renal interstitium, then into the renal blood

vessels... and ultimately back into the body.

Tubular ReabsorptionThe “good stuff” is glucose, electrolytes, vitamins, water,

amino acids, and any small proteins that might have

inadvertently escaped from the blood into the filtrate.

Ninety nine percent of the glomerular filtrate is

reabsorbed (most of it before the end of the PCT)!To appreciate the magnitude of tubular reabsorption, look

once again at the table in the next slide and compare the

amounts of substances that are filtered, reabsorbed, and

excreted in urine.

Tubular ReabsorptionTotal

Amount in

Plasma

Amount in 180 L of

filtrate (/day)

Amount returned to

blood/d (Reabsorbe

d)

Amount in Urine (/day)

Water (passive)

3 L 180 L 178-179 L 1-2 L

Protein (active)

200 g 2 g 1.9 g 0.1 g

Glucose (active)

3 g 162 g 162 g 0 g

Urea (passive)

1 g 54 g 24 g (about 1/2)

30 g (about 1/2)

Creatinine 0.03 g 1.6 g 0 g(all filtered)

1.6 g(none

reabsorbed)

• Reabsorption into the interstitium has two routes:– Paracellular reabsorption is a passive process that

occurs between adjacent tubule cells (tight junctions do not completely seal off interstitial fluid from tubule fluid.)

– Transcellular reabsorption is movement through an individual cell.

Tubular Reabsorption

• It is a tremendous feat to reabsorb all of the nutrients and fluid we must to survive, while still filtering out, concentrating and excreting toxic substance.– To accomplish this, the kidney establishes a

countercurrent flow between the filtrate in the limbs of the Loops of Henle and the blood in the peritubular capillaries and Vasa Recta.• Two types of countercurrent mechanisms exist in the kidneys:

countercurrent multiplication and countercurrent exchange.

Tubular Reabsorption

• Countercurrent multiplication is the process by which a progressively increasing osmotic gradient is formed in the interstitial fluid of the renal medulla as a result of countercurrent flow.

• Countercurrent exchange is the process by which solutes and water are passively exchanged between the blood of the vasa recta and interstitial fluid of the renal medulla as a result of countercurrent flow.– This provides oxygen and nutrients to the renal medulla

without washing out or diminishing the gradient.

Tubular Reabsorption

Both mechanisms contribute to reabsorption of fluid and electrolytes and the formation of concentrated urine.

Tubular Reabsorption

Tubular Reabsorption Reabsorption of fluids, ions, and other substances occurs

by active and passive means.

A variety of symporters and antiporters actively transport Na+ ,

Cl– , Ca2+, H+, HCO3– , glucose, HPO4

2– , SO42– , NH4

+, urea, all amino

acids, and lactic acid.

Reabsorption of water can be obligatory or facultative, but it always moves by osmosis down its concentration gradient depending on the permeability of the tubule cells (which varies between the PCT, the different portions of the loop of Henle, DCT, and collecting ducts).

Tubular Reabsorption• Obligatory reabsorption of water occurs when

it is obliged to follow the solutes as they are reabsorbed (to maintain the osmotic gradient).

• Facultative reabsorption describes variable water reabsorption, adapted to specific needs.– It is regulated by the effects of ADH and aldosterone on the principal cells of the renal tubules and collecting ducts.

• This graphic depicts the formation of a dilute urine, mostly through obligatory reabsorption of water.

• Compare this process to the one depicted on the next slide where urine is concentrated by the action of ADH on the DCT and collecting ducts of juxtamedullary nephrons.

Tubular Reabsorption