L-44 Blood Flow And Glomerular Filtration

Front 1

Organization of lobule

Back 1

Cortex

Outer medulla

Inner medulla

Front 2

Blood flow in kidney

Back 2

Aorta -> renal artery -> arteries between lobules -> arcuate arteries (at corticomedullary junction) -> interlobular/cortical penetrating arteries -> afferent aa. -> glomerulus capillaries -> efferent aa -> vasa recta (countercurrent exchange)

Front 3

Renal Plasma Flow

Back 3

Renal blood flow * (1- Hematocrit)

Front 4

Filtration fraction

Back 4

GFR/Renal Plasma Flow

Around 22% of plasma volume is filtered

Front 5

Filtered load

Back 5

Mass flow rate of substance presented to nephron

GFR * [P(Na)] = 28,000 mEq/day

Dietary sodium is 100 mEq and ECF has 2,000 mEq

Front 6

Glomerular filtration rate of kidney

Back 6

180 L/day

Front 7

Determinants of glomerular filtration

Back 7

Afferent aa -> network of glomerular capillaries -> efferent

Some water is filtered - forces across capillary basement membrane into Bowman's capsule.

GFR = Kf{(Pgc - Pbc) - PIgc}

Pgc = hydrostatic pressure of glomerular capillary, dynamic

Pbc = hydrostatic pressure of Bowman's capsule, constant

PIgc = osmotic pressure of glomerular capillary

PIbc = hydrostatic pressure of bowman's capsule, around 0 because proteins are not filtered

Front 8

Renal resistance vessels and intrarenal pressure profile - normal

Back 8

Aortic pressure is around 110 mmHg. Very little pressure drop until afferent arteriole - major site of resistance.

Pgc does not change much from afferent to efferent end because many parallel capillaries.

Pressure drops over efferent arteriole again - significant site of resistance.

Front 9

Constrict afferent aa.

Back 9

Increase in resistance, larger pressure drop, lower Pgc and all downstream pressures.

Usually constricted as myogenic response to increase in blood pressure. Pathological constriction may lead to renal failure.

Front 10

Constrict efferent aa.

Back 10

Bigger pressure drop in efferent arteriole and less pressure drop upstream. Pgc rises.

One of the mechanisms of angiotensin II during volume depletion.

Front 11

Dilate afferent aa.

Back 11

Decrease resistance, smaller pressure drop, Increase in Pgc and increase in renal blood flow.

Used when blood pressure falls to increase GFR to a stable, autoregulatory range.

Front 12

Dilate efferent aa.

Back 12

Decrease in resistance, decrease in Pgc

Front 13

Changes in glomerular capillary oncotic pressure

Back 13

GFR equation is only accurate on average.

Glomerular osmotic pressure increases over course of capillary.

Thus driving force at efferent end of capillary is 0.

Small net pressures can determine flitrate formation.

Front 14

Static capillary pressures

Back 14

Pgc and Pbc are static.

Front 15

How do you overcome filtration equilibrium?

Back 15

Increase flow through system - less filtration can occur so PIgc does not rise so quickly. Allows filtration all along capillary.

Front 16

Homeostatic regulation requires:

Back 16

1) Matching Na+ and water urinary excretion to dietary intake

2) Tight regulation of delivery of salt and water to distal nephron (must urinate 2-3 L/day of 180 L)

3) Distal nephron is site of fine regulation of reabsorption

Front 17

Autoregulation

Back 17

Maintain constant flow (GFR or RPF) independent of blood pressure.

Prevents large swings in delivery to distal nephron.

Driven by myogenic response - arteriole sense stretch-induced pressure and intrinsically constricts to maintain flow. Occurs in afferent aa.

Front 18

Tubuloglomerular feedback

Back 18

Macula densa (at junction of distal tubule and pole of parent glomerulus) senses NaCl concentration.

Low salt concentration indicates low flow rate - most of salt is reabsorbed in thick ascending limb

High salt concentration indicates high flow rate - little salt reabsorption in thick ascending limb

Front 19

Tubuloglomerular feedback mechanism

Back 19

Transport of NaCl into macula densa forms ATP which exits cell via maxi-anion channel and heads to afferent arteriole.

Metabolized to adenosine on the way and binds to A1 receptors causing constriction of afferent arteriole.

Constriction of afferent arteriole reduces Pgc and reduces GFR and distal flow.

Effect modulated by neural activity, NO, prostaglandings, angiotensin II

Front 20

Renin secretion

Back 20

Granular (juxtaglomerular) cells at end of afferent aa. near pole of glomerulus releases proteolytic enzyme renin in response to conditions in which salt should be retained - low perfusion presure, low ECF volume, sympathetic activity, low macula densa Na+ delivery.

Front 21

Renin-Angiotensin-Aldosterone Axis

Back 21

Angiotensinogen released by liver and kidney is processed by renin into angiotensin 1.

Angiotensin 1 is converted to angiotensin 2 by angiotensin-converting enzyme.

Angiotensin II is a vasoconstrictor, increases thirst, and stimulates adrenal aldosterone secretion.

All of these substances are also produced and modified intrinsically in kidney.

Net effect is to decrease U(Na) * V. Defends losses of salt and water from ECF.

Front 22

Glomerulotubular balance

Back 22

Increase of proximal tubule reabsorption with increases in GFR to reduce impact on distal delivery of Na+ and H2O.

Luminal cilia on proximal tubule acts as flow mechanosensor.

Deformation enhances activity of basolateral and apical salt transporters in proximal tubule. Also enhances water absorption.

High GFR also raises oncotic pressure of peritubular capillaries, helping reabsorb salts from proximal tubule to blood.

Front 23

Glomerular permselectivity

Back 23

Solvent drag allows some solute through filtration barrier. Permselectivity depends on size, shape, and charge of molecules.

Molecules less than 1kDa mass (water, urea, glucose) freely filter ([Filtrate]/[Plasma] = 1)

Molecules of 5kD or higher (inulin) are only partially filtered.

Albumin (69 kDa) is not filtered at all ([Filtrate]/[Plasma] = 0) - unless unhealthy filtration barrier.

Front 24

Why is hemoglobin partially reabsorbed and albumin is not at all?

Back 24

Both are similar mass but hemoglobin is elliptical and uncharged whereas albumin is spherical and negative.

Front 25

Assessing glomerular permselectivity

Back 25

Use dextrans - polymer of polysaccharide that can be polydispersed (contains different MW ranges)

Large dextrans have lower [Filtrate]/[Plasma].

Cationic dextrans filter better at given molecular weight.
Polyanionic (sulfated dextrans) filter poorly - recall negative albumin does not filter.

Front 26

Filtration barrier composition

Back 26

Podocytes

Trilaminar basement membrane - lamina rara externa, lamina rara interna, and lamina densa

Fenestrated endothelium

Front 27

What is filtration barrier?

Back 27

Slit diaphragm between podocyte foot processes

Mutations in slit diaphragm proteins (i.e. mice KO, human disease) results in nephrotic mice or familial nephrotic syndrome.