copyright © 2006 by elsevier, inc. figure 26-3; guyton and hall nephron: functional unit of the...

Copyright © 2006 by Elsevier, Inc.

Figure 26-3;Guyton and Hall

Nephron:functional unit of

the kidney

Nephron:functional unit of

the kidney



Nephron Tubular Segments


Structure ofthe juxtaglomerular apparatus: macula

densa

Structure ofthe juxtaglomerular apparatus: macula

densa



Cortical and JuxtamedullaryNephron Segments



• http://www.youtube.com/watch?v=glu0dzK4dbU


Summary of Kidney Functions

• Excretion of metabolic waste products: urea, creatinine, bilirubin, hydrogen

• Excretion of foreign chemicals: drugs, toxins, pesticides, food additives

• Secretion, metabolism, and excretion of hormones- renal erythropoetic factor- 1,25 dihydroxycholecalciferol (Vitamin D)- Renin

• Regulation of acid-base balance• Gluconeogenesis: glucose synthesis from amino acids• Control of arterial pressure• Regulation of water & electrolyte excretion


Basic Mechanisms of Urine Formation



Renal Handling ofDifferent Substances



Renal Handling of Water and Solutes

Filtration Reabsorption Excretion

Water (liters/day) 180 179

Sodium (mmol/day) 25,560 25,410 Glucose (gm/day) 180 0Creatinine (gm/day) 1.8 1.8

1

1800

150


Glomerular Capillary Filtration

Barrier

Glomerular Capillary Filtration

Barrier



The Ability of a Solute to Penetrate the Glomerular Membrane Depends on:

• Molecular size ( small molecules > filterability)• Ionic charge (cations > filterability)


Effects of Size and Electrical Charge of Effects of Size and Electrical Charge of Dextran on Filterability by Glomerular Dextran on Filterability by Glomerular CapillariesCapillaries

Effects of Size and Electrical Charge of Effects of Size and Electrical Charge of Dextran on Filterability by Glomerular Dextran on Filterability by Glomerular CapillariesCapillaries



Clinical Significance of Proteinuria

• Early detection of renal disease in at-risk patients- hypertension: hypertensive renal disease- diabetes: diabetic nephropathy- pregnancy: gestational proteinuric hypertension (pre-eclampsia)- annual “check-up”: renal disease can be silent

• Assessment and monitoring of known renal disease

• “Is the dipstick OK?”: dipstick protein tests are not very sensitive and not accurate: “trace” results can be normal & positives must be confirmed by quantitative laboratory test.


Glomerular Hydrostatic Pressure (PG)

• Is the determinant of GFR most subjectto physiological control

• Factors that influence PG- arterial pressure (effect is buffered by autoregulation)- afferent arteriolar resistance- efferent arteriolar resistance


Re

Effect of Afferent and Efferent Arteriolar Constriction on Glomerular Pressure

PG

GFR

Ra

Ra GFR + Renal Blood Flow

Blood Flow

GFR

PG

Re GFR + Renal Blood Flow

Blood Flow



Effect of changes in afferent

arteriolar or efferent arteriolar

resistance

Effect of changes in afferent

arteriolar or efferent arteriolar

resistance


RE

RBF G

GFR

PG

+

_

determined by : FF = GFR / RPF


Kf GFR

PB GFR

G GFR

A G

FF G

PG GFR

RA PG

RE PG

Summary of Determinants of GFR

GFR

GFR

GFR(as long as RE < 3-4 x normal)


Assessing Kidney Function

• Albumin excretion (microalbuminuria)• Plasma concentration of waste products

(e.g. BUN, creatinine)• Urine specific gravity, urine concentrating ability• Imaging methods (e.g. MRI, PET, arteriograms,

iv pyelography, ultrasound etc)• Isotope renal scans• Biopsy• Clearance methods (e.g. 24-hr creatinine clearance)• etc


Clearance

• Clearance is a general concept that describes the rate at which substances are removed (cleared) from the plasma.


Clearance Technique

Renal clearance of a substance is the volume of plasma completely cleared of a substance per min.

Cs = Us x V Ps

Cs x Ps = Us x V

Where: Cs = clearance of substance SPs = plasma conc. of substance SUs = urine conc. of substance SV = urine flow rate


For a substance that is freely filtered, but not reabsorbed or secreted (inulin, 125 I-iothalamate, ~creatinine), renal clearanceis equal to GFR

Use of Clearance to Measure GFR

amount filtered = amount excreted

GFR x Pin = Uin x V

GFR = Pin

Uin x V



Calculate the GFR from the following data:

Pinulin = 1.0 mg / 100mlUinulin = 125 mg/100 mlUrine flow rate = 1.0 ml/min

GFR =125 x 1.0

1.0= 125 ml/min

GFR = Cinulin =Pin

Uin x V


Steady-state relationship

betweenGFR and serum

creatinine concentration



Clearances of Different Substances

Clearance of inulin (Cin) = GFRif Cx < Cin: indicates reabsorption of x

Substance Clearance (ml/min) inulin 125 glucose 0 sodium 0.9 urea 70

Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)if Cx > Cin: indicates secretion of x


1. Sympathetic Nervous System RA + RE GFR + RBF

Control of Glomerular Filtration

3. Angiotensin II RE GFR + RBF

(prevents a decrease in GFR)

2. Catecholamines ( norepinephrine) RA + RE GFR + RBF



5. Endothelial-Derived Nitric Oxide (EDRF)RA + RE GFR + RBF

4. ProstaglandinsRA + RE GFR + RBF

6. EndothelinRA + RE GFR + RBF



7. Autoregulation of GFR and Renal Blood Flow• Myogenic Mechanism• Macula Densa Feedback

(tubuloglomerular feedback) • Angiotensin II ( contributes to GFR but

not RBF autoregulation)


Renal ArteryPressure (mmHg)

100

80

Renal Blood Flow

Glomerular Filtration Rate

Renal Autoregulation

Time (min)0 1 2 3 4 5

120



Renal Blood Flow and GFRAutoregulation



Macula Densa Feedback

GFR

Distal NaCl Delivery

Macula Densa NaCl Reabsorption

Afferent Arteriolar Resistance

GFR (return toward normal)

(macula densa feedback)


Myogenic Mechanism

Stretch ofBlood Vessel

Cell Ca++

PermeabilityArterial Pressure

Intracell. Ca++Blood Flow VascularResistance


Regulation of GFR by Ang II

GFR Renin

AngII

Efferent ArteriolarResistance

Macula Densa NaCl

BloodPressure


Macula densa feedback

mechanismfor GFR

autoregulation


copyright © 2006 by elsevier, inc. figure 26-3; guyton and hall nephron: functional unit of the...

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