renal structure and function - ut southwestern

Renal Structure and FunctionSodium Transport

Orson W. Moe, M.D.Department of Internal Medicine

Division of Nephrology

UTSouthwestern STARS Program

organism world

Maintain constancy

CompositionQuantity

Afferent Sensor

Efferent Effector

Physiologic parameter

Disease

Excretion

Endocrine

Metabolism

Renal FunctionGood stuffBad stuffEndocrine hormoneMetabolic substrate

Gross anatomy

Medulla (Pyramids)

Capsule

Medullary rays

Cortex

Major calyx

Minor calyx

Renal pelvis

Ureter

Column of Bertin

MedullaOuter

Outer stripeInner stripe

Inner

Papilla

Afferent arteriole

Cortical ascending

Arcuate

Interlobar

Renal arterySegmental branches

Main branch

Interlobar

Arcuate

Renal Vasculature

Arcuate

Cortical ascending

Afferent arteriole

Efferent arteriole

Renal CirculationLittle or no anastomosesHighest blood flow per gram tissueMultiple capillaries in tandem Functional arteriovenous shunts

Renal CirculationLittle or no anastomosesHighest flow per gram tissueMultiple capillaries in tandemFunctional AV shunts

Renal CirculationLittle or no anastomosesHighest flow per gram tissueMultiple capillaries in tandemFunctional AV shunts

<2% Body mass

25-30% Cardiac output

Renal venous pO2 Highest (60-70 mm Hg)Renal A-VO2 difference Lowest (10-15%)

Renal CirculationLittle or no anastomosesHighest flow per gram tissueMultiple capillaries in tandemFunctional AV shunts

Glomerular capillary

Peritubular capillary

Renal CirculationLittle or no anastomosesHighest flow per gram tissueMultiple capillaries in tandemFunctional AV shunts

Cortical ascending

Afferent arteriole

Glomerular capillary

Efferent arteriole

Peritubular capillary

Vasa recta

Functional AV shunts

Excretion

Secretion

Ultrafiltration

Reabsorption

Nephron

Secretory

Filtration-Reabsorption

Secretory

Filtration-Reabsorption

Nephron

Dump

Secretory

Filtration-Reabsorption

Nephron

Dump

300 marbles

Remove 294

300 marbles

Remove 294

300 marbles

Remove 294

Put 6 back

170 L/day

169 L/day

1 L/day

1 L/day1 L/day

0.95 L/day 0.95 L/day

160 L/day

10 L/day

Error = 50 ml

Error = 9L

What does that mean?

5% error

5% error

Filtration-Secretion

Filtration-Reabsorption

Filtration

Fractional excretion

Amount excreted

Amount filtered

Amount filtered

Amount filtered

Amount excreted

Amount excreted

Amount excretedAmount filtered

> 1

= 1

< 1

Walk the nephron

Juxtamedullary nephron

Medullary collecting tubule

Cortical collecting tubule

Distal convoluted tubule

Thick ascending limb

Thinascendinglimb

Loop of Henle

Descending thin limb

Proximal straight tubule

Proximal straight tubule

Efferentarteriole

Glomerulus

Afferent arteriole

Proximalconvoluted

tubule

Proximalconvolutedtubule

InnerMedulla

Cortex

OuterMedulla

Cortical nephron

Overview

The Glomerulus

Form an ultrafiltrate

Parietal epithelium

Tubule

GBM

Afferent arteriole

Efferent arteriole

Mesangium

Visceral epithelium

Bowman’s space Urinary lumen

Tubule lumenVisceral

epithelial cells(podocytes)

Bowman's space

Bowman's capsule

Parietal epithelial cells

Nervefibers

Afferentarteriole

Juxtaglomerulargranular

cells

Maculadensacells

Efferent arteriole

Smoothmuscle cells

Mesangialcells

Mesangialextracellular

matrix

Glomerularcapillarylumen

Capillaryendothelial

cells

Capillarybasementmembrane

Visceralepithelial cell

(foot processes)

Distal endof the thick

ascending limb

Extraglomerular mesangium

Podocyte

Capillary

Bowman space

Podocyte

Mesangial cell

Mesangial matrix

Foot process

Endothelial cell

Podocyte

Foot process

Endothelium

Endothelium

Podocyte foot process

Basement membrane

Blood cellsLarge proteinsSmall proteinsElectrolytesWater

Small proteinsElectrolytesWater

Transition to tubule

Renal Tubules

Modify the ultrafiltrate into final urine

Juxtamedullary nephron

Medullary collecting tubule

Cortical collecting tubule

Distal convoluted tubule

Thick ascending limb

Thinascendinglimb

Loop of Henle

Descending thin limb

Proximal straight tubule

Proximal straight tubule

Efferentarteriole

Glomerulus

Afferent arteriole

Proximalconvoluted

tubule

Proximalconvolutedtubule

InnerMedulla

Cortex

OuterMedulla

Cortical nephron

Overview

Proximalconvoluted

tubule

Proximalstraighttubule

Thickascending

limb

Descendingthin limb

Ascendingthin limb

Innermedullarycollecting

tubule

Corticalcollecting

tubule

Distaltubule

Principalcell

Intercalatedcell

PolarizedApicalBasolateral

Amplification of surface areaBrush borderInfoldingInterdigitation

TransportTranscellularParacellular

Infoldings Interdigitation

ProtrusionsBrush border

Tight junctions

Intercellular space

Features of tubular epithelia

Currency for Solute Transport

High energy metabolic substrates

ATP

Electrochemical gradients

ATP

Urine Interstitium/ Plasma

Glutamine

2K+

Low [Na+]-ve voltage

3Na+

Coupled Transporters Paracellular Transport Proteins

ATP

ATPaseNa+

K+

Cotransporter

Na+ Glucose

Na+

OH-H+

Cl-

Ca2+

Channel

Na+

Countertransporter

Na+

H+

NaCl

Yanomami Indians

Daily ingestion & excretion

Yanomani DallasiteK+ 400-500 mEq/day 40 mEq/dayNa+ <10 mEq/day 200 mEq/day

Cortex

Medulla

50-60% 7-10%

2-5%

30%

100%

NaCl

1-2%

Proximalnephron

Distalnephron

Urinary Lumen

Interstitium/CapillaryTranscellularpathway

Paracellularpathway

High capacity Low capacity

Low gradient High gradient

~

3Na+

~ ~~

Lumen

High capacity Low capacity

Low gradient High gradient

Capillary

Cl-Cl-

Proximal Distal

3Na+

~

2K+

~

3Na+

2K+2K+

~

2K+

~

3Na+

X

XNa+ Na+ Na+Na+ Cl-Na+ 2Cl-K+

Proximal tubule

Thick ascending limb

Distal convoluted tubule

Collecting tubule

Afferent Sensor

Efferent Effector

Physiologic parameter

Disease

Ultrafiltrate

Urine