gh_kapitel_026 physiology Chapter 26 Kidneys.pdf

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

Regulation of Water and
Electrolyte Balances
• Sodium and Water
• Potassium
• Hydrogen Ions
• Calcium, Phosphate, Magnesium

Effect of
increasing sodium
intake 10fold
(from 30 to 300
mEq/day) on
urinary sodium
excretion and
extracellular fluid
volume.
The shaded areas
represent the net
sodium retention
orthenetsodiumlos
s, determined from
the difference
between sodium
intake and sodium
excretion.

Regulation of AcidBase Balance
• Excrete acids (kidneys are the only means
of excreting non-volatile acids)
• Regulate body fluid buffers
( e.g. Bicarbonate)

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
• Renal erythropoetic factor
• 1,25 dihydroxycholecalciferol (Vitamin D)
• Renin
Hormones produced in the kidney
Hormones metabolized and excreted by the kidney
• Most peptide hormones (e.g., insulin,
angiotensin II, etc.)

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
Erythrocyte Production
O2 Delivery
Kidney
Erythropoetin
Erythrocyte Production
in Bone Marrow

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
• short term
Control of Extracellular Fluid Volume
,long term

• kidneys play a dominant role
in longterm regulation of
arterial pressure by excreting
variable amounts of sodium
and water.

• The kidneys also contribute to short
term arterial pressure regulation by
secreting vasoactive factors or
substances, such as renin, that lead
to the formation of vasoactive
products (e.g., angiotensin II).

Summary of Kidney Functions
• Regulation of water & electrolyte excretion
• 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

Basic Kidney Anatomy
• Kidneys paired, about 150 gm each
• Urine forming units:
– Cortex
– Medulla (lobed: renal pyramids)
– Cortex and medulla composed chiefly of nephrons and
blood vessels
– Supplied by renal arteries (branches of descending aorta)
and renal veins (branches of inferior vena cava)
• Urine collecting and expelling units:
– Calyces
– Renal pelvises
– Ureters
– Bladder
– Urethra

Anterior Surface of Kidney

Hilum of Kidney

Renal Calices

Internal Anatomy

Kidneys and Urinary Tract System
Figure 26-2; Guyton and Hall

The Nephron is the Fundamental UrineProducing Unit of
the Kidney
• total 2 million nephrons in the 2 kidneys of young
person
• Components of the nephron
– Glomerulus- tuft of capillaries where
filtration occurs
– Bowman's capsule- surrounds
glomerulus, collects filtrate
– Proximal convoluted tubule
– Loop of Henle
– Distal convoluted tubule
– Collecting duct- adjusts volume &
concentration of urine

Figure 26-4;
Guyton and Hall
Nephron Tubular Segments

Cortical and Juxtamedullary
Nephron Segments
Figure 26-5;
Guyton and Hall

Distinctive feature: the tubule makes a sharp
bend at the loop of Henle
Because of the bend, tubule fluid moves
downward into regions of increasing
osmotic pressure
After the bend the tubule fluid moves
upward through regions of decreasing
osmotic pressure
Glomerulus has large pores, allowing filtration
of large volumes of fluid
Number of nephrons declines with age, to about
50% at age 60; this causes the GFR to drop to
50% of value in a young person
Loss of nephrons can cause drug overdose

Although the Kidneys are Tiny Organs They
Receive 25% of the Cardiac Output
• The 2 kidneys are only 0.4% of the body weight but
receive about 25% of the blood flow
– Blood flow rate per kilogram of tissue is almost
8 times higher in the kidneys than through
muscles doing heavy exercise!
• Kidney: 4 liters/kg-min
• Exercising muscle: 0.55 liters/kg-min
• Extremely important function: to regulate the
composition and volume of body fluids
• Blood flows in and out of kidney leaving behind the
1% which becomes urine
• Urine flows through ureters to bladder and then
through urethra to outside world
• The bladder is under both voluntary and autonomic
control

Kidneys Filter About 180 Liters of Plasma Every Day, But
Make Only 2 Liters of Urine
• The kidneys filter approximately 180 liters of plasma/day
(each of the 3 liters of plasma gets filtered about 60
times)
• To replace this much water you would have to drink a 12
ounce soft drink every 3 minutes of the day
• Fortunately 99% of the filtrate gets reabsorbed, leaving
1.52 liters of urine per day
• It is remarkable that the kidney filter can be used
continuously for 70 years or more without becoming
clogged

Figure 26-3;
Guyton and Hall
Neph
ron:
funct
ional
unit
of
the
kidn
ey
Neph
ron:
funct
ional
unit
of
the
kidn
ey

Blood Supply to the Kidneys
Figure 26.5c, d

Basic
Mechan
isms
of
Urine
Formati
on
Figure 26-8;
Guyton and Hall

Excretion = Filtration –
Reabsorption + Secretion
• 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
Substanc
es
Figure 26-9;
Guyton and Hall

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

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)

The Basic Processes of the Kidney are Filtration, Reabsorption and
Secretion
• Filtration:
– About 20% of the plasma that passes through the kidney gets filtered into the nephron
– Filtration is takes place in the glomerulus
– Driven by the hydrostatic pressure of the blood (osmosis opposes filtration, but the
hydrostatic pressure is larger)
• Water and small molecules are filtered; blood cells and large molecules (most proteins) do not pass through the filter
Filtration


Glome
rular
Capill
ary
Filtrati
on
Barrie
r
Glome
rular
Capill
ary
Filtrati
on
Barrie
r
Figure 26-10;
Guyton and Hall

Glomerular Capillary
Membrane Filtration Barrier
• Endothelium (fenestrated, 160180 A pores)
• Basement Membrane (7080 A pores),
negative charged proteoglycans, restriction
site for proteins
• Epithelial Cells (podocytes, 8080 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
Capillaries
Capillaries
Capillaries
Figure 26-11;
Guyton and Hall

Clinical Significance of
Proteinuria
• Early detection of renal disease in atrisk patients
hypertension: hypertensive renal disease
diabetes: diabetic nephropathy
pregnancy: gestational proteinuric hypertension (preeclampsia)
annual “checkup”: 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 1020 fold more
likely to develop persistent proteinuria

Determinants of Glomerular
Filtration Rate
GFR = Filt. Coefficient x Net Filt. Press
GFR = Kf x NFP

Figure 26-12;
Guyton and Hall

Forces Favoring Filtration (mm Hg)
Glomerular hydrostatic pressure 60
Bowman's capsule colloid osmotic pressure 0
Forces Opposing Filtration (mm Hg)
Bowman's capsule hydrostatic pressure 18
Glomerular capillary colloid osmotic pressure 32

Determinants of Glomerular
Filtration Rate
Normal Values:
GFR = 125 ml/min
Net Filt. Press = 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
• 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 = 60
G = 28
PG = 60
G = 36
Net Filtration Pressure Decreases Along the Glomerulus
because of Increasing Glomerular Colloid Osmotic
Pressure
14 6

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

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

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

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

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

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

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. Prostaglandins
RA + RE GFR + RBF
6. Endothelin
RA + 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 Artery
Pressure (mmHg)
100
80
Renal Blood
Flow
Glomerular
Filtration Rate
Renal Autoregulation
Time (min)
0 1 2 3 4 5
120

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

Regulation of GFR via Tubuloglomerular
Feedback
As GFR , flow through DCT 
Macula densa cells:
release paracrines
juxtaglomerular cells
(smooth muscle fibers from
afferent arteriole): contract
Thus GFR 
Fig 1910

Structure
of
the
juxtaglo
merular
apparatus
: macula
densa
Structure
of
the
juxtaglo
merular
apparatus
: macula
densa
Figure 26-17;
Guyton and Hall

Macula Densa Feedback
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
Afferent Arteriolar Resistance
GFR (return toward normal)
(macula densa feedback)

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)

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

50 100 150 200
0
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

Macula
densa
feedbac
k
mechani
sm
for GFR
autoregu
lation
Figure 26-18;
Guyton and Hall

Other Factors That
Influence GFR
• Prostaglandins: increase GFR; nonsteroidalanti
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 of
diabetes 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 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)

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