Transcript Slide 1

Urine Formation by the Kidneys:
I. Glomerular Filtration, Renal
Blood Flow and Their Control
L1- L2
1
University of Jordan
Faculty of Medicine
Department of Physiology and Biochemistry
Renal Physiology (Dental) spring 2014
Textbook:
Textbook of Medical Physiology
By : Arthur C. Guyton and John E. Hall, 12th ed. 2011
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Lect. No. Topic
12th Ed.
1-2
Glomerular Filtration, Renal
303-307
Blood Flow and their Control
310-321
3-5
6-7
8
9.
Tubular Reabsorption and
Secretion
323-343
Urine concentration and Dilution
345-360
Acid-Base Regulation
Micturition
379-392
307-310
Faisal I. Mohammed. MD, PhD
Email: [email protected]
Optional Reading:
1.Physiology, by: Robert Berne & Matthew Levy, 6th. ed. 2010
2. Human physiology, by: Lauralee Sherwood, last edition.
2
Objectives
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List the functions of the renal system
Describe the processes of urine formation
Describe glomerular filtration
Explain the control of glomerular filtration
Describe renal blood flow and its control
Explain the glomerulotubular feedback
mechanism as a way for control of GFR.
Body fluid
regulation.
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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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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
7
Secretion, Metabolism, and Excretion of
Hormones
Hormones produced in the kidney
• Renal erythropoetic factor
• 1,25 dihydroxycholecalciferol (Vitamin D)
• Renin
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
9
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
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
14
Organs of the urinary system
University of Jordan
15
Internal anatomy of the kidneys
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16
Blood
supply of
the kidneys
University of Jordan
17
Nephron Tubular Segments
18
Cortical and juxtamedullary nephrons
19
Basic
Mechanisms of
Urine Formation
20
Structures and functions of a nephron
Renal tubule and collecting duct
Renal corpuscle
Afferent
arteriole
Glomerular
capsule
Urine
(contains
excreted
substances)
Fluid in
renal tubule
1 Filtration from blood
plasma into nephron
2 Tubular reabsorption
from fluid into blood
Efferent
arteriole
Peritubular capillaries
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3 Tubular secretion
from blood into fluid
Blood
(contains
reabsorbed
substances)
21
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 : highly 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
23
Renal Handling of Water and Solutes
Filtration
Reabsorption
Excretion
Water
180
(liters/day)
179
Sodium
25,560
(mmol/day)
25,410
Glucose
(gm/day)
180
0
0
1.8
180
Creatinine 1.8
(gm/day)
1
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
26
Effects of size and electrical charge of dextran on
filterability by glomerular capillaries.
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Clinical Significance of Proteinuria
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Early detection of renal disease in at-risk
patients
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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
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Microalbuminuria
• Definition: urine excretion of > 30 but < 150
mg 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
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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
many tissues)
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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
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Glomerular Injury in Chronic Diabetes
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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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Factors Influencing Glomerular Capillary
Oncotic Pressure ( G)
• Arterial Plasma Oncotic Pressure (A)
A
G
• Filtration Fraction (FF)
FF
G
FF = GFR / Renal plasma flow
= 125 / 650 ~ 0.2 (or 20%)
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Increase in colloid osmotic pressure in plasma
flowing through glomerular capillary
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Net Filtration Pressure Decreases Along the
Glomerulus Because of Increasing Glomerular
Colloid Osmotic Pressure
PG = 60
G = 28
Net Filtration Pressure
PG = 60
14
6
G = 36
PB = 18
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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 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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Autoregulation of Glomerular
Hydrostatic Pressure
80
Glomerular
Hydrostatic
Pressure
(mmHg)
Normal kidney
60
Kidney disease
40
20
0
50
100
150
200
Arterial Pressure (mmHg)
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Autoregulation of
renal blood flow
and GFR but not
urine flow
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Effect of afferent and efferent arteriolar
constriction on glomerular pressure
Ra
Re
PG
Blood
Flow
Ra
GFR
GFR + Renal
Blood
PG
Blood
Flow
GFR
Re
GFR +
Renal
Blood
Flow
Flow
42
Effect of changes in
afferent arteriolar
or efferent arteriolar
resistance
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G determined by : FF = GFR / RPF
G
RBF
_
GFR
RE
+
PG
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Summary of Determinants of GFR
Kf
PB
G
A
FF
PG
RA
RE
(as long as
GFR
GFR
GFR
G
G
GFR
PG
PG
GFR
GFR
GFR
RE < 3-4 x normal)
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Determinants of Renal Blood Flow (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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Renal blood flow
• High blood flow (~22 % of cardiac output)
• High blood flow needed for high GFR
• Oxygen and nutrients delivered to kidneys
normally greatly exceeds their metabolic
needs
• A large fraction of renal oxygen consumption is
related to renal tubular sodium reabsorption
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Renal oxygen
consumption
and
sodium
reabsorption
48
Control of GFR and renal blood flow
• Neurohumoral
• Local (Intrinsic)
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Control of GFR and renal blood flow
1. Sympathetic Nervous System /catecholamines
RA + RE
GFR +
RBF
e.g. severe hemorrhage
2. Angiotensin II
RE
GFR + RBF
(prevents a decrease in GFR)
e.g. low sodium diet, volume depletion
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Control of GFR and renal blood flow
3. Prostaglandins
RA + RE
GFR +
RBF
Blockade of prostaglandin synthesis → ↓ GFR
This is usually important only when there are
other disturbances that are already tending to
lower GFR
e.g. nonsteroidal antiinflammatory drugs in a
volume depleted patient, or a patient with heart failure,
cirrhosis, etc
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Control of GFR and renal blood flow
4. Endothelial-Derived Nitric Oxide (EDRF)
RA + RE
GFR +
RBF
• Protects against excessive vasoconstriction
• Patients with endothelial dysfunction (e.g.
atherosclerosis)
may have greater risk for excessive decrease in GFR in
response to stimuli such as volume depletion
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Control of GFR and renal blood flow
5. Endothelin
RA + RE
GFR +
RBF
• Hepatorenal syndrome – decreased renal function
in cirrhosis or liver disease?
• Acute renal failure (e.g. contrast media nephropathy)?
• Hypertensive patients with chronic renal failure?
Endothelin antagonists may be useful in these conditions
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Summary of neurohumoral control of
GFR and renal blood flow
Effect on GFR
Effect on RBF
Sympathetic activity
Catecholamines
Angiotensin II
EDRF (NO)
Endothelin
Prostaglandins
increase
decrease
no change
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Local Control of GFR and renal
blood flow
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 Autoregulation
120
Renal Artery
Pressure
(mmHg)
100
80
Glomerular
Filtration Rate
Renal Blood
Flow
0
1
2
3
Time (min)
4
5
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Importance of Autoregulation
Arterial
Pressure
GFR
Reabsorption
Urine Volume
Poor Autoregulation + no change in tubular reabsorption
100
125
124
120
150
124
1.0
26.0 = 37.4 L/day!
Good Autoregulation + no change in tubular reabsorption
120
130
124
5.0
Good Autoregulation+adaptive increase in tubular reabsorption
120
130
128.8
1.2
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Arterial
Pressure
Stretch of
Blood Vessel
Blood Flow
and
GFR
Vascular
Resistance
Cell Ca++
Entry
Intracell. Ca++
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Structure of
the
juxtaglomerular
apparatus:
macula densa
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Macula Densa Feedback
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
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Macula Densa Feedback
Proximal NaCl
Reabsorption
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
GFR
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Regulation of GFR by Ang II
GFR
Macula
Densa NaCl
Renin
Blood
Pressure
AngII
Efferent Arteriolar
Resistance
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Ang II Blockade Impairs GFR
Autoregulation
1600
Renal
Blood Flow
( ml/min)
1200
800
Normal
Ang II Blockade
400
0
Glomerular
Filtration
Rate (ml/min)
120
80
40
0
0
50
100
150
Arterial Pressure (mmHg)
200
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Macula densa
feedback
mechanism for
regulating GFR
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Other Factors That Influence GFR
• Fever, pyrogens: increase GFR
• Glucorticoids: increase GFR
• Aging: decreases GFR 10% / decade after 40 yrs
• Hyperglycemia: increases GFR (diabetes mellitus)
• Dietary protein: high protein increases GFR
low protein decreases GFR
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Protein Ingestion
Amino Acids
Tubular Amino Acid Reabs.
Proximal Nacl Reabs.
Macula Densa NaCl
(macula densa feedback)
Afferent Arteriolar Resist.
GFR
66
Thank You