Guyton & Hall Physio : Chapter 26 Urine Formation by the Kidneys

U N I T V

Textbook of Medical Physiology, 11th Edition

GUYTON & HALL

Copyright © 2006 by Elsevier, Inc.

Chapter 26:Urine Formation by the Kidneys:

I. Glomerular Filtration, Renal Blood Flow, and Their Control

Slides by John E. Hall, Ph.D.


Kidney Functions


Excretion of Metabolic Waste Products

• Urea (from protein metabolism)• Uric acid (from nucleic acid metabolism)• Creatinine (from muscle metabolism)• Bilirubin (from hemoglobin metabolism)


Excretion of Foreign Chemicals

• Pesticides• Food additives• Toxins• Drugs


Secretion, Metabolism,and Excretion of Hormones

• Erythropoetin • 1,25 dihydroxycholecalciferol (Vitamin D)• Renin• Urokinase

Hormones produced in the kidney

Hormones metabolized and excreted by the kidney

• Most peptide hormones (e.g., insulin, angiotensin II, etc.)


Regulation of Erythrocyte Production

O2 Delivery Kidney

Erythropoetin

Erythrocyte Production in Bone Marrow


Regulation of Vitamin D Activity

• Kidney produces active form of vitamin D(1,25 dihydroxy vitamin D3 )

• Vitamin D3 is important in calcium and phosphate metabolism


Regulation of Acid-Base Balance

• Excrete acids (kidneys are the only means of excreting non-volatile acids)

• Regulate body fluid buffers ( e.g. Bicarbonate)


Glucose Synthesis

Gluconeogenesis: kidneys synthesize glucosefrom precursors (e.g., amino acids) during prolonged fasting


Regulation of Arterial Pressure

Endocrine Organ• renin-angiotensin system• prostaglandins• kallikrein-kinin system

Control of Extracellular Fluid Volume


Regulation of Water and Electrolyte Balances

• Sodium and Water• Potassium• Hydrogen Ions• Calcium, Phosphate, Magnesium


Figure 26-1; Guyton and Hall

Effect of Increasing Sodium Intake 10-fold on Urinary Sodium Excretion and Extracellular Fluid Volume

Effect of Increasing Sodium Intake 10-fold on Urinary Sodium Excretion and Extracellular Fluid Volume


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


Kidneys and Urinary Tract System



Figure 26-3;Guyton and Hall

Nephron:functional unit of

the kidney

Nephron:functional unit of

the kidney



Nephron Tubular Segments


Cortical and JuxtamedullaryNephron Segments



Urinary Bladder and Its Innervation



Normal Cystogram



Basic Mechanisms of Urine Formation



Excretion = Filtration – Reabsorption + Secretion****AQUI GRUPO No. 3*****• Filtration: somewhat variable, not selective (except for proteins), averages 20% of renal plasma flow

• Reabsorption: highly variable and selective, most electrolytes (e.g. Na+, K+, Cl-) and nutritional substances (e.g. glucose) are almost completely reabsorbed; most waste products (e.g. urea) poorly reabsorbed

• Secretion: variable; important for rapidly excreting some waste products (e.g. H+), foreign substances (including drugs), and toxins


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 180Creatinine (gm/day) 1.8 1.8

1

00

150


Glomerular Filtration

• GFR = 125 ml/min = 180 liters/day

• Plasma volume is filtered 60 times per day

• Glomerular filtrate composition is about the same as plasma, except for large proteins

• Filtration fraction (GFR/Renal Plasma Flow) = 0.2 (i.e., 20% of plasma is filtered)


Glomerular Capillary Filtration

Barrier

Glomerular Capillary Filtration

Barrier



Glomerular Capillary Membrane Filtration Barrier

• Endothelium (fenestrated, 160-180 A pores)

• Basement Membrane (70-80 A pores), negative charged proteoglycans, restriction site for proteins

• Epithelial Cells (podocytes, 80-80 A pores) restriction site for proteins


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.


Microalbuminuria

• Definition: urine excretion of > 25-30 but < 150mg albumin per day

• Causes: early diabetes, hypertension, glomerular hyperfiltration

• Prognostic Value: diabetic patients withmicroalbuminuria are 10-20 fold morelikely to develop persistent proteinuria


Determinants of GlomerularFiltration Rate

GFR = Filtration Coefficient x Net Filtration Pressure

GFR = Kf x NFP


Determinants of Glomerular Filtration Rate

Normal Values:GFR = 125 ml/min

Net Filtration Pressure = 10 mmHg

Kf = 12.5 ml/min per mmHg, or4.2 ml/min per mmHg/ 100gm(400 x greater than intissues such a muscle)


Glomerular Capillary Filtration Coefficient (Kf)

• Kf = hydraulic conductivity x surface area

• Disease that can reduce Kf and GFR- chronic hypertension- obesity / diabetes mellitus- glomerulonephritis

• Normally not highly variable


Lean Obese

Obesity Causes Glomerular Basement Membrane Thickening


Bowman’s Capsule Hydrostatic Pressure (PB)

• Normally changes as a function of GFR, not a physiological regulator of GFR

• Tubular Obstruction- kidney stones- tubular necrosis

• Urinary tract obstruction- Prostate hypertrophy/cancer


• Filtration Fraction (FF) FF G

Factors Influencing Glomerular Capillary Oncotic Pressure ( G)

• Arterial Plasma Oncotic Pressure (A) A G

FF= GFR / Renal plasma flow


Net Filtration Pressure

PB = 18

PG = 60G = 28

PG = 60G = 36

Net Filtration Pressure Decreases Along the Glomerulus because of IncreasingGlomerular Colloid Osmotic Pressure

14 6

Copyright © 2006 by Elsevier, Inc.Figure 26-13; Guyton and Hall

Increase in Colloid Osmotic Pressure Increase in Colloid Osmotic Pressure in Plasma Flowing through Glomerular in Plasma Flowing through Glomerular CapillaryCapillary

Increase in Colloid Osmotic Pressure Increase in Colloid Osmotic Pressure in Plasma Flowing through Glomerular in Plasma Flowing through Glomerular CapillaryCapillary


Factors Influencing Glomerular Capillary Oncotic Pressure ( G)

• Plasma Protein Concentration Arterial Plasma Oncotic Pressure (A)

A G

• Filtration Fraction (FF) FF G

FF= GFR / Renal plasma flow


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


50 100 150 2000

Arterial Pressure (mmHg)

GlomerularHydrostatic Pressure(mmHg)

60

40

20

80

Autoregulation of GlomerularHydrostatic Pressure

Normal kidney

Kidney disease


Renal Blood Flow and GFRAutoregulation



Glomerular Hydrostatic Pressure (PG)

• Is the determinant of GFR most subject to 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)


Control of Glomerular Filtration

• Neurohumoral

• Local (Intrinsic)


1. Sympathetic Nervous System Ra + Re GFR + RBF


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



Myogenic Mechanism

Stretch ofBlood Vessel

Cell Ca++

PermeabilityArterial Pressure

Intracell. Ca++Blood Flow VascularResistance




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

not RBF autoregulation)


Structure ofthe juxtaglomerular apparatus: macula

densa

Structure ofthe juxtaglomerular apparatus: macula

densa



Macula Densa Feedback

GFR

Distal NaCl Delivery

Macula Densa NaCl Reabsorption

Afferent Arteriolar Resistance

GFR (return toward normal)

(macula densa feedback)




(tubuloglomerular feedback) • Angiotensin II (contributes to autoregulation

of GFR but not RBF)


Regulation of GFR by Ang II

GFR Renin

AngII

Efferent ArteriolarResistance

Macula Densa NaCl

BloodPressure


50 100 150 2000

Renal Blood Flow ( ml/min)

1600

1200

800

0

400

120

80

0

40

Glomerular Filtration Rate (ml/min)

Arterial Pressure (mmHg)

Ang II Blockade Impairs GFR Autoregulation

NormalAng II Blockade


Macula densa feedback

mechanismfor GFR

autoregulation



Other Factors That Influence GFR

• Prostaglandins: increase GFR; non-steroidalanti-inflammatory agents can decrease GFR,especially in volume depleted states

• Fever, pyrogens: increase GFR• Glucorticoids: increase GFR• Aging: decreases GFR ~10%/decade after 40 yrs• Dietary protein: high protein increases GFR

low protein decreases GFR• Hyperglycemia: increases GFR (diabetes mellitus)


The Stages of Diabetes Induced Nephropathy

GFR(ml/min)

Onset ofdiabetes Optimal Control

Poor control of blood pressure and /or blood glucose

Antihypertensive Therapy

Days – Weeks – Years 5 15 25 35 45

120

80

40

160


Determinants of Renal BloodFlow (RBF)

RBF = P / R

P = difference between renal artery pressure and renal vein pressure

R = total renal vascular resistance = Ra + Re + Rv = sum of all resistances in kidney vasculature


Functions of Renal Blood Flow

• To deliver enough plasma to kidneys forglomerular filtration

• To deliver nutrients to kidney so that therenal cells can perform their functions (only about 20% of renal blood flow needed for this function)

Guyton & Hall Physio : Chapter 26 Urine Formation by the Kidneys

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Transcript of Guyton & Hall Physio : Chapter 26 Urine Formation by the Kidneys