guyton & hall physio : chapter 26 urine formation by the kidneys
TRANSCRIPT
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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.
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Kidney Functions
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Excretion of Metabolic Waste Products
• Urea (from protein metabolism)• Uric acid (from nucleic acid metabolism)• Creatinine (from muscle metabolism)• Bilirubin (from hemoglobin metabolism)
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Excretion of Foreign Chemicals
• Pesticides• Food additives• Toxins• Drugs
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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.)
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Regulation of Erythrocyte Production
O2 Delivery Kidney
Erythropoetin
Erythrocyte Production in Bone Marrow
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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
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Regulation of Acid-Base Balance
• Excrete acids (kidneys are the only means of excreting non-volatile acids)
• Regulate body fluid buffers ( e.g. Bicarbonate)
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Glucose Synthesis
Gluconeogenesis: kidneys synthesize glucosefrom precursors (e.g., amino acids) during prolonged fasting
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Regulation of Arterial Pressure
Endocrine Organ• renin-angiotensin system• prostaglandins• kallikrein-kinin system
Control of Extracellular Fluid Volume
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Regulation of Water and Electrolyte Balances
• Sodium and Water• Potassium• Hydrogen Ions• Calcium, Phosphate, Magnesium
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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
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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
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Kidneys and Urinary Tract System
Figure 26-2; Guyton and Hall
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Figure 26-3;Guyton and Hall
Nephron:functional unit of
the kidney
Nephron:functional unit of
the kidney
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Figure 26-4;Guyton and Hall
Nephron Tubular Segments
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Cortical and JuxtamedullaryNephron Segments
Figure 26-5;Guyton and Hall
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Urinary Bladder and Its Innervation
Figure 26-6; Guyton and Hall
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Normal Cystogram
Figure 26-7; Guyton and Hall
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Basic Mechanisms of Urine Formation
Figure 26-8;Guyton and Hall
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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
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Renal Handling ofDifferent Substances
Figure 26-9;Guyton and Hall
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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
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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)
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Glomerular Capillary Filtration
Barrier
Glomerular Capillary Filtration
Barrier
Figure 26-10;Guyton and Hall
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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
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The Ability of a Solute to Penetrate the Glomerular Membrane Depends on:
• Molecular size ( small molecules > filterability)• Ionic charge (cations > filterability)
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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
Figure 26-11;Guyton and Hall
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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.
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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
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Determinants of GlomerularFiltration Rate
GFR = Filtration Coefficient x Net Filtration Pressure
GFR = Kf x NFP
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Figure 26-12;Guyton and Hall
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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)
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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
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Lean Obese
Obesity Causes Glomerular Basement Membrane Thickening
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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
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• Filtration Fraction (FF) FF G
Factors Influencing Glomerular Capillary Oncotic Pressure ( G)
• Arterial Plasma Oncotic Pressure (A) A G
FF= GFR / Renal plasma flow
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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
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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
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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
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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
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50 100 150 2000
Arterial Pressure (mmHg)
GlomerularHydrostatic Pressure(mmHg)
60
40
20
80
Autoregulation of GlomerularHydrostatic Pressure
Normal kidney
Kidney disease
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Renal Blood Flow and GFRAutoregulation
Figure 26-16;Guyton and Hall
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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
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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
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Figure 26-14;Guyton and Hall
Effect of changes in afferent
arteriolar or efferent arteriolar
resistance
Effect of changes in afferent
arteriolar or efferent arteriolar
resistance
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Re
RBF G
GFR
PG
+
_
determined by : FF = GFR / RPF
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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)
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Control of Glomerular Filtration
• Neurohumoral
• Local (Intrinsic)
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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
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Control of Glomerular Filtration
5. Endothelial-Derived Nitric Oxide (EDRF)Ra + Re GFR + RBF
4. ProstaglandinsRa + Re GFR + RBF
6. EndothelinRa + Re GFR + RBF
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Control of Glomerular Filtration
7. Autoregulation of GFR and Renal Blood Flow• Myogenic Mechanism• Macula Densa Feedback
(tubuloglomerular feedback) • Angiotensin II ( contributes to GFR but
not RBF autoregulation)
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Renal ArteryPressure (mmHg)
100
80
Renal Blood Flow
Glomerular Filtration Rate
Renal Autoregulation
Time (min)0 1 2 3 4 5
120
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Renal Blood Flow and GFRAutoregulation
Figure 26-16;Guyton and Hall
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Myogenic Mechanism
Stretch ofBlood Vessel
Cell Ca++
PermeabilityArterial Pressure
Intracell. Ca++Blood Flow VascularResistance
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Control of Glomerular Filtration
7. Autoregulation of GFR and Renal Blood Flow• Myogenic Mechanism• Macula Densa Feedback
(tubuloglomerular feedback) • Angiotensin II ( contributes to GFR but
not RBF autoregulation)
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Structure ofthe juxtaglomerular apparatus: macula
densa
Structure ofthe juxtaglomerular apparatus: macula
densa
Figure 26-17;Guyton and Hall
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Macula Densa Feedback
GFR
Distal NaCl Delivery
Macula Densa NaCl Reabsorption
Afferent Arteriolar Resistance
GFR (return toward normal)
(macula densa feedback)
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Control of Glomerular Filtration
7. Autoregulation of GFR and Renal Blood Flow• Myogenic Mechanism• Macula Densa Feedback
(tubuloglomerular feedback) • Angiotensin II (contributes to autoregulation
of GFR but not RBF)
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Regulation of GFR by Ang II
GFR Renin
AngII
Efferent ArteriolarResistance
Macula Densa NaCl
BloodPressure
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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
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Macula densa feedback
mechanismfor GFR
autoregulation
Figure 26-18;Guyton and Hall
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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)
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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
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Copyright © 2006 by Elsevier, Inc.
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
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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)