39513136-Guyton-Hall-Physio-Chapter-26-Urine-Formation-by-the-Kidneys.ppt

guyton hall

1. 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 D
3 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 glucose
from 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

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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

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Figure 26-4;
Guyton and Hall
Nephron Tubular Segments

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Cortical and Juxtamedullary
Nephron 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 of
Different 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) 180 180
Creatinine (gm/day) 1.8 1.8
1
0
0
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
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
Dextran on Filterability by Glomerular
Capillaries
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 with
microalbuminuria are 10-20 fold more
likely to develop persistent proteinuria

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Determinants of Glomerular
Filtration 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
K
f = 12.5 ml/min per mmHg, or
4.2 ml/min per mmHg/ 100gm
(400 x greater than in
tissues such a muscle)

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Glomerular Capillary Filtration
Coefficient (K
f)
•K
f= hydraulic conductivity x surface area
•Disease that can reduce K
fand 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 (P
B)
•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
P
B = 18
P
G= 60

G= 28
P
G= 60

G= 36
Net Filtration Pressure Decreases Along
the Glomerulus because of Increasing
Glomerular Colloid Osmotic Pressure
14 6

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Figure 26-13; Guyton and Hall
Increase in Colloid Osmotic Pressure
in Plasma Flowing through Glomerular
Capillary

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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 (P
G)
•Is the determinant of GFR most subject
to physiological control
•Factors that influence P
G
-arterial pressure (effect is buffered by autoregulation)
-afferent arteriolar resistance
-efferent arteriolar resistance

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50 100 150 200
0
Arterial Pressure (mmHg)
Glomerular
Hydrostatic
Pressure
(mmHg)
60
40
20
80
Autoregulation of Glomerular
Hydrostatic Pressure
Normal kidney
Kidney disease

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Renal Blood Flow and GFR
Autoregulation
Figure 26-16;
Guyton and Hall

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Glomerular Hydrostatic
Pressure (P
G)
•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
P
G
GFR
Ra
Ra GFR + Renal
Blood Flow
Blood Flow
GFR
P
G
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

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R
e
RBF 
G
GFR
P
G
+
_
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 R
e< 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
R
e GFR + RBF
(prevents a decrease in GFR)
2. Catecholamines ( norepinephrine)
R
a + R
e GFR + RBF

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Control of Glomerular Filtration
5. Endothelial-Derived Nitric Oxide (EDRF)
Ra+ Re GFR + RBF
4. Prostaglandins
Ra+ Re GFR + RBF
6. Endothelin
R
a+ R
e 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)

53. Renal Artery
Pressure (mmHg)
100
80
Renal Blood
Flow
Glomerular
Filtration Rate
Renal Autoregulation
Time (min)
012345
120
Copyright © 2006 by Elsevier, Inc.

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Renal Blood Flow and GFR
Autoregulation
Figure 26-16;
Guyton and Hall

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Myogenic Mechanism
Stretch of
Blood Vessel
Cell Ca
++
Permeability
Arterial
Pressure
Intracell. Ca
++
Blood Flow
Vascular
Resistance

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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 of
the 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 Arteriolar
Resistance
Macula
Densa NaCl
Blood
Pressure

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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
Normal
Ang II Blockade

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Macula densa
feedback
mechanism
for GFR
autoregulation
Figure 26-18;
Guyton and Hall

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Other Factors That
Influence GFR
•Prostaglandins: increase GFR; non-steroidal
anti-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 of
diabetes
Optimal Control
Poor control of blood pressure
and /or blood glucose
Antihypertensive Therapy
Days –Weeks –Years 515 25 35 45
120
80
40
160

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