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

UNIT V
Textbook of Medical Physiology, 11th Edition
Chapter 26:
Urine Formation by the Kidneys:
I. Glomerular Filtration, Renal Blood Flow, and Their Control
Slides by John E. Hall, Ph.D.
GUYTON & HALL

Copyright © 2006 by Elsevier, Inc.
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
Hormones produced in the kidney
• Erythropoetin
• 1,25 dihydroxycholecalciferol (Vitamin D)
• Renin
• Urokinase
Hormones metabolized and excreted by the kidney
• Most peptide hormones (e.g., insulin,
angiotensin II, etc.)

Regulation of
Erythrocyte Production
O2 Delivery Erythropoetin
Kidney
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 glucose

from 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

Effect of Increasing Sodium Intake 10-fold on
Urinary Sodium Excretion and Extracellular
Fluid Volume
Figure 26-1;
Guyton and Hall
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 26-2; Guyton and Hall

Nephron:
functional unit of
the kidney
Figure 26-3;
Guyton and Hall
Nephron Tubular Segments
Figure 26-4;
Guyton and Hall
Cortical and Juxtamedullary
Nephron Segments
Figure 26-5;
Guyton and Hall
Urinary Bladder and Its
Innervation

Normal Cystogram
Figure 26-7;
Guyton and Hall
Basic Mechanisms
of Urine Formation
Figure 26-8;
Guyton and Hall
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 of
Different Substances
Figure 26-9;
Guyton and Hall
Renal Handling of Water
and Solutes
Filtration Reabsorption Excretion
Water (liters/day) 180 179 1

Sodium (mmol/day) 25,560 25,410 150
Glucose (gm/day) 180 180 0
Creatinine (gm/day) 1.8 0 1.8

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
Figure 26-10;
Guyton and Hall
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
Dextran on Filterability by Glomerular
Capillaries
Figure 26-11;
Guyton and Hall
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 with

microalbuminuria are 10-20 fold more
likely to develop persistent proteinuria

Determinants of Glomerular
Filtration Rate
GFR = Filtration Coefficient x Net Filtration

Pressure
GFR = Kf x NFP

Figure 26-12;
Guyton and Hall
Determinants of Glomerular
Filtration Rate
Normal Values:
GFR = 125 ml/min
Net Filtration Pressure = 10 mmHg

Kf = 12.5 ml/min per mmHg, or
4.2 ml/min per mmHg/ 100gm
(400 x greater than in
tissues such a muscle)

Glomerular Capillary Filtration
Coefficient (Kf)
• Kf = hydraulic conductivity x surface area

• Normally not highly variable
• Disease that can reduce Kf and GFR
- chronic hypertension
- obesity / diabetes mellitus
- glomerulonephritis

Obesity Causes Glomerular
Basement Membrane Thickening
Lean Obese
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

Factors Influencing Glomerular
Capillary Oncotic Pressure ( G)
• Arterial Plasma Oncotic Pressure (A)

A G
• Filtration Fraction (FF)

FF G
FF= GFR / Renal plasma flow

Net Filtration Pressure Decreases Along
the Glomerulus because of Increasing
Glomerular Colloid Osmotic Pressure
Net Filtration Pressure

PG = 60 14 6 PG = 60
G = 28 G = 36
PB = 18

Increase in Colloid Osmotic Pressure
in Plasma Flowing through Glomerular
Capillary

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 subject

to physiological control
• Factors that influence PG

- arterial pressure (effect is buffered by autoregulation)
- afferent arteriolar resistance
- efferent arteriolar resistance

Autoregulation of Glomerular
Hydrostatic Pressure
80
Normal kidney
Glomerular 60
Hydrostatic
Pressure Kidney disease
(mmHg) 40
20
0 50 100 150 200
Arterial Pressure (mmHg)
Renal Blood Flow and GFR
Autoregulation
Figure 26-16;
Guyton and Hall
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

Effect of Afferent and Efferent Arteriolar
Constriction on Glomerular Pressure
Ra Re
PG PG
Blood Flow Blood Flow
GFR GFR
Ra GFR + Renal Re GFR + Renal

Blood Flow Blood Flow

Effect of changes
in afferent
arteriolar or
efferent arteriolar
resistance
Figure 26-14;
Guyton and Hall
determined by : FF = GFR / RPF
RBF G
_
Re GFR
+
PG

Summary of
Determinants of GFR
Kf GFR
PB GFR
G GFR
GFR
A G
FF G
PG GFR GFR
Ra PG GFR
(as long as Re < 3-4 x normal)
Re PG
Control of Glomerular Filtration
• Neurohumoral
• Local (Intrinsic)

1. Sympathetic Nervous System

Ra + Re GFR + RBF
2. Catecholamines ( norepinephrine)
Ra + R e GFR + RBF
3. Angiotensin II
Re GFR + RBF
(prevents a decrease in GFR)

4. Prostaglandins
Ra + R e GFR + RBF
5. Endothelial-Derived Nitric Oxide (EDRF)
Ra + R e GFR + RBF
6. Endothelin
Ra + R e 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 Autoregulation
120
Renal Artery 100
Pressure (mmHg) 80
Glomerular
Filtration Rate
Renal Blood
Flow
0 1 2 3 4 5
Copyright © 2006 by Elsevier, Inc. Time (min)
Renal Blood Flow and GFR
Autoregulation
Figure 26-16;
Guyton and Hall
Myogenic Mechanism
Arterial Stretch of Cell Ca++

Pressure Blood Vessel Permeability
Blood Flow Vascular Intracell. Ca++

Resistance


• Angiotensin II ( contributes to GFR but
not RBF autoregulation)

Structure of
the juxtaglomerular
apparatus: macula
densa
Figure 26-17;
Guyton and Hall
Macula Densa Feedback
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption

(macula densa feedback)
Afferent Arteriolar Resistance
GFR (return toward normal)


• Angiotensin II (contributes to autoregulation
of GFR but not RBF)

Regulation of GFR by Ang II
Macula Renin
GFR
Densa NaCl
Blood AngII
Pressure
Efferent Arteriolar
Resistance

Ang II Blockade Impairs GFR
Autoregulation
1600
Renal 1200
Blood Flow 800
Normal
( ml/min)
400 Ang II Blockade
0
120
Glomerular
Filtration 80
Rate (ml/min) 40
0
0 50 100 150 200
Arterial Pressure (mmHg)
Macula densa
feedback
mechanism
for GFR
autoregulation
Figure 26-18;
Guyton and Hall
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)

The Stages of Diabetes Induced
Nephropathy
160
Poor control of blood pressure
and /or blood glucose
120
Onset of
diabetes Optimal Control
Antihypertensive Therapy
GFR 80
(ml/min)
40
Days – Weeks – Years 5 15 25 35 45

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 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)

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

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UNIT V

Textbook of Medical Physiology, 11th Edition

GUYTON & HALL

Copyright © 2006 by Elsevier, Inc.

• Urea (from protein metabolism)

Copyright © 2006 by Elsevier, Inc.

Copyright © 2006 by Elsevier, Inc.

Copyright © 2006 by Elsevier, Inc.

Copyright © 2006 by Elsevier, Inc.

• Kidney produces active form of vitamin D

• Vitamin D3 is important in calcium and

Copyright © 2006 by Elsevier, Inc.

• Excrete acids (kidneys are the only means

• Regulate body fluid buffers

Copyright © 2006 by Elsevier, Inc.

Gluconeogenesis: kidneys synthesize glucose

Copyright © 2006 by Elsevier, Inc.

Control of Extracellular Fluid Volume

Copyright © 2006 by Elsevier, Inc.

• Sodium and Water

Copyright © 2006 by Elsevier, Inc.

Figure 26-2; Guyton and Hall

Copyright © 2006 by Elsevier, Inc.

Figure 26-6; Guyton and Hall

Copyright © 2006 by Elsevier, Inc.

• Reabsorption: highly variable and selective, most

Filtration Reabsorption Excretion

Water (liters/day) 180 179 1

Copyright © 2006 by Elsevier, Inc.

• GFR = 125 ml/min = 180 liters/day

Copyright © 2006 by Elsevier, Inc.

• Endothelium (fenestrated, 160-180 A pores)

Copyright © 2006 by Elsevier, Inc.

• Molecular size ( small molecules > filterability)

Copyright © 2006 by Elsevier, Inc.

• Assessment and monitoring of known renal disease

Copyright © 2006 by Elsevier, Inc.

• Causes: early diabetes, hypertension,

• Prognostic Value: diabetic patients with

Copyright © 2006 by Elsevier, Inc.

GFR = Filtration Coefficient x Net Filtration

Copyright © 2006 by Elsevier, Inc.

Net Filtration Pressure = 10 mmHg

Copyright © 2006 by Elsevier, Inc.

• Kf = hydraulic conductivity x surface area

Copyright © 2006 by Elsevier, Inc.

• Normally changes as a function of GFR, not

Copyright © 2006 by Elsevier, Inc.

• Arterial Plasma Oncotic Pressure (A)

• Filtration Fraction (FF)

FF= GFR / Renal plasma flow

Copyright © 2006 by Elsevier, Inc.

Net Filtration Pressure

Copyright © 2006 by Elsevier, Inc.

Figure 26-13; Guyton and Hall

• Plasma Protein Concentration

FF= GFR / Renal plasma flow

Copyright © 2006 by Elsevier, Inc.

• Is the determinant of GFR most subject

• Factors that influence PG

Copyright © 2006 by Elsevier, Inc.

• Is the determinant of GFR most subject to

• Factors that influence PG: