Transcript Chapter 04 (Renal Function).

King Saud University
College of Science
Department of Biochemistry
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Chapter 4
Renal Function
Professor A. S. Alhomida
1
Role of Kidney
•
Primary Role
1. Maintain body fluid volume and
composition
2. Filter waste products for elimination
2
Role of Kidney, Cont’d
•
Secondary Role
1.
2.
3.
4.
5.
Regulate blood pressure
Participate in acid-base balance
Produce erythropoietin for RBC synthesis
Hormonal function
Metabolize vitamin D to active form
3
Renal Anatomy
4
Renal Anatomy, Cont’d
5
Renal Nephron
6
Composition of Urine
•
•
What is urine?
A sterile Fluid Composed of:
1. Water (95%)
2. Nitrogen containing waste
•
•
•
•
Urea
Uric acid
Ammonia
creatinine
3. Electrolytes
7
Urine Formation
8
Glomerular Filtration
1. Water and Dissolved Substances
•
•
They move from the vascular system to the glomerulus
Then into Bowman’s capsule
2. Glomerular Filtrate is Composed of:
•
•
•
•
Water
Electrolytes
Waste products
Metabolic substrate
9
Glomerular Filtration, Cont’d
3. Glomerular Filtrate Measures Plasma
Volume
•
It can be cleared of any given substrate within a certain time
frame
4. Glomerular Filtration Rate (GFR)
•
•
Normal 125 mL/min or 180 L/24 hr filtered
Only 1.5 L (1-3 L) of urine excreted in 24 hr
10
Glomerular Filtration, Cont’d
11
Glomerular Filtration, Cont’d
12
Influence of Filtration Rate
1. Variation in blood pressure in glomerular
capillary
2. Concentration of the plasma proteins
3. Factors altering intratubular pressure:
•
•
Raise with ureteral obstruction
During osmotic diuresis
4. State of blood vessels
13
Volume of Glomerular Filtrate
Formed
1. Depends on:
•
•
•
Number of glomeruli functioning at a time
Volume of blood passing through the glomeruli per minute
Effective of glomerular filtration pressure
2. Under normal conditions
•
About 700 mL of plasma flow through the kidneys per
minute and 120 mL of fluid are filtered into Bowman's
capsule
14
Factors Affecting Glomerular
Filtration
15
Tubular Reabsorption
1. Second stage of urine formation
2. Reabsorption of water and solute occurs
throughout entire length of tubule
3. Most reabsorption occurs in proximal
convoluted tubule (PCT) via peritubular
capillaries
16
Tubular Reabsorption, Cont’d
4. Approximately 99% of all water goes back into
the body
5. It occcurs via two transport systems:
•
•
Active
Passive (diffusion)
17
Tubular Reabsorption, Cont’d
1. What is reabsorbed?
•
•
•
•
Glucose completely
Water and Na: 99%
Urea: 50%
Creatinine: minimal to none
2. Passive and active transport
•
Example: Na actively transported and H2O and Cl follow
passively
18
Tubular Reabsorption, Cont’d
19
Tubular Secretion
1. Third stage of urine formation
2. Substances secreted into the tubules to be
excreted in the final stage of urine formation
•
•
Distal tubules
Collecting ducts
20
Renal Transepithelial
Transport
Pumps
Carriers
Channels
Symporters
Antiporters
3Na+-2K+-ATPase
Na+-Glucose
Na+-H+
Na+
3H+-ATPase
Na+-Amino acid
Na+-NH4+
K+
H+-K+-ATPase
2Na+-HPO42-
Na+-Ca2+
Cl-
Ca2+-ATPase
Na+-3HCO3-
Cl--HCO3-
Ca2+
Na+-2Cl--K+
K+-Cl21
Renal Transepithetial
Transport, Cont’d
22
Renal Transepithetial
Transport, Cont’d
23
Mechanism of Urine
Countercurrent
1. The amount of water that is eliminated with the
urine is regulated a complex mechanism within
the nephron that is influenced by ADH
2. The process is called countercurrent mechanism
(concentration of urine) because it involves
fluid traveling in opposite directions within the
loop of Henle
24
Mechanism of Urine
Countercurrent, Cont’d
3. As the filtrate passes through the loop of Henle,
salts, especially Na, are active pumped out by
the cells of the nephron, with the result that
interstitial fluid of the medulla becomes
increasingly concentrated
4. Because nephron is NOT very permeable to
water, the fluid within the nephron becomes
increasingly dilute
25
Mechanism of Urine
Countercurrent, Cont’d
5. As the fluid passes through the more permeable
DCT and through collecting tubule, water is
drawn out by the concentrated fluid around the
nephron and return to the blood
6. Urine becomes more concentrated and its
volume is reduced depending on:
• Osmotic pressure in the medulla
• ADH Secretion
26
Mechanism of Urine
Countercurrent, Cont’d
7. Role of ADH is to make the walls of DCT and
collecting tubule more permeable to water, more water
will be reabsored and less will be excreted with urine
depends on:
•
Body hydration = ADH = Urine Volume
•
Body Hydration = ADH = Urine Volume
27
Urine Countercurrent
Mechanism, Cont’d
Unit = mOsm
28
Renal Clearance
•
Clearance
1. It is a measure of the volume of plasma
completely freed of a given substance per minute
by the kidney
2. It is the efficiency with which the plasma is
cleared of a given substance
29
Renal Clearance, Cont’d
•
Renal Clearance
1. It is the ratio of the renal excretion of the substance to its
concentration in the blood plasma
2. Clearance = (U xV)/P
Where
U is the urinary concentration of substance x
V is the rate of urine formation (mL/min)
P is the plasma concentration of substance x
30
Renal Tubular Transport
(Reabosorption and Secretion)
1. Renal Tubular Transport Maximum (Tm)
•
It refers to the maximal amount of a give solute that can be
transported (reabsorbed or secreted) per minute by the
renal tubules
2. Maximum Tubular Reabsortion Capacity (Tr)
•
•
It is the highest attainable rate of reabsorption
Substances that are reabsorbed by an active transport
process and that have a Tr include phosphate, sulfate,
glucose, many AA, uric acid and albumin
31
Renal Tubular Transport
(Secretion(
3. Maximum Tubular Secretion Capacity (Ts)
•
•
It is the highest attainable rate of secretion
Substances that are secreted by the kidneys and have a Ts
include penicillin, certain diuretics, salicylate, and
thiamine (vitamin B6)
32
Renal Threshold Substances
1.
Renal Threshold
•
2.
Certain substances which are reabsrobed completely by tubules when
their concentration in the plasma remains within normal range, and
appear in the urine when their normal levels are exceeded
High Threshold Substances
•
3.
They are essential for the body and are completely reabsorbed by renal
tubules, examples: glucose, amino acids
Low Threshold Substances
•
They are reabsorted slowly or not at all, example: creatinine, urea, and
uric acid
33
Hormonal Functions
•
Renin Production
1. When there is a decrease in:
•
•
•
Blood flow
Volume, or
Blood pressure
34
Hormonal Functions, Cont’d
2. Physiological effects:
•
•
•
Na reabsorption
Systemic vasoconstriction
Sympathetic nerve stimulation
35
Hormonal Functions, Cont’d
•
Antidiuretic Hormone (ADH)
1.
2.
3.
4.
5.
6.
Allows kidneys to concentrate urine
Secreted by posterior pituitary gland
Works on the collecting ducts by making the ducts
permeable to H2O
H2O is reabsorbed into body
Deficiency in ADH: diminishes blood volume
Excess in ADH: increases blood volume
36
Other Functions
•
Erythropoietin Production
1.
2.
•
Released in response to decreased oxygen tension
Stimulates RBC production in the bone marrow
Vitamin D Activation
1.
2.
Activated vitamin D necessary to absorb calcium and
phosphate in the GI tract
Regulation of calcium/phosphorous balance
37
Hormonal Functions, Cont’d
38
Renal Function Tests
1.
2.
3.
4.
5.
To identify renal dysfunction
To diagnose renal diseases
To monitor disease progress
To monitor response to treatment
To assess changes in function that may impact on
therapy (e.g. Digoxin, chemotherapy)
39
Renal Function Tests, Cont’d
40
Classification of Renal
Function Tests
•
Tests Based on Glomerular Filtration
1.
2.
3.
4.
•
Urea clearance test
Endogenous creatinine clearance test
Inulin clearance test
Cr51-EDTA clearance test
Tests to Measure Renal Plasma Flow
1. Para-Amino hippurate test
2. Filtration fraction
41
Classification of Renal
Function Tests, Cont’d
•
Tests Based on Tubular Function
1.
2.
3.
•
Concentration and dilution test
15 minute-pheonl-sulphthalein (PSP) excretion test
Measurement of tubular secretory capacity
Certain Miscellaneous Tests
1.
Determine size, shape, asymmetry, obstruction, tumor,
infarct, etc
42
Symptoms of Renal Failure
1. Symptoms of Uremia
•
Nausea, vomiting, lethargy
2. Disorders of Micturation
•
Frequency, nocturia, retention, dysuria
3. Disorders of Urine Volume
•
Polyuria, oliguria, anuria
43
Symptoms of Renal Failure,
Cont’d
4. Alterations in Urine Composition
•
Hematuria, proteinuria, bacteriua, leujocyturia, calculi
5. Pain
6. Edema
•
Hypoalbuminemia, salt and water retention
44
Biochemical Tests of Renal
Function
1. Urinalysis
•
Appearance
•
•
•
•
•
•
•
•
•
Volume
Odor
Color
Specific gravity
Osmolality
pH
Glucose
Protein
Urinary sediments
45
Biochemical Tests of Renal
Function, Cont’d
2. Measurement of GFR
•
•
Clearance tests
Plasma creatinine
3. Tubular function Tests
46
Role of Biochemical Testing
1. Presentation of Patients
•
•
•
Routine urinalysis
Symptom or physical sign
Systemic disease with known renal component
47
Role of Biochemical Testing,
Cont’d
2. Effective Management of Renal Disease
Depends upon Establishing a Definitive
Diagnosis
•
•
Detailed clinical history
Diagnostic imaging and biopsy (immunology)
48
Role of Biochemical Testing,
Cont’d
3. Role of Biochemistry
•
•
•
Rarely establishes the cause
Screening for damage
Monitoring progression
49
Urinalysis
• Fresh Sample = Valid Sample
1. Appearance
•
•
•
Blood
Color (hemoglobin, myoglobin, etc)
Turbidity (infection, nephrotic syndrome, chyle, etc)
2. Specific Gravity
•
Sticks measure ionic species only (not glucose)
50
Urinalysis, Cont’d
3. pH
•
Normal = acidic, except after meal
4. Glucose
•
•
Increased blood glucose
Low renal threshold or other tubular disorders
51
Urinalysis, Cont’d
5. Proteinuria
•
•
Normal < 200 mg/24 h, Urine sticks +ve = > 300
mg/L
Causes
• Overflow (raised plasma low MW Proteins, BenceJones protein, myoglobin)
• Glomerular leak
• Decreased tubular reabsorption of protein (RBC,
albumin)
• Protein renal origin
52
Urinalysis, Cont’d
6. Urine Sediments
•
Microscopic examination of sediment from freshly passed
urine
• Looking for cells, casts (Tamm-Horsfall protein), fat
droplets
• Red cell casts - hematuria - glomerular disease
• White cell cast + polymorphs + bacteruiria =
pylonephrites
53
Urinalysis, Cont’d
6. Urine Sediments
•
•
•
Lower urinary tract infection (UTI) polymorphs no casts
Acute glomerulnephritis = hematuria, cells, casts
Chronic glomerulonephritis = less sediment
54
Determination of Renal
Clearance
1. Clearance = (U x V)/P
•
•
•
Where U is the urinary concentration of substance x
V is the rate of urine formation (mL/min)
P is the plasma concentration of substance x
2. Units = volume/unit time (mL/min)
3. If Clearance = GFR then substance x properties:
•
•
•
Freely filtered by glomerulus
Glomerulus = sole route of excretion from the body (no
tubular secretion or reabsorbtion)
Non-toxic and easily measurable
55
Properties of Agents Used to
Determine GFR
Property
99m
Urea
Creatinine
Inulin
Not Protein
Bound
Yes
Yes
Yes
Yes
Freely
Filtered
Yes
Yes
Yes
Yes
Some
secretion
Yes
Yes
No
Yes
No
No
Yes
Yes
No
No
No secretion Flow related
or absorbtion reabsorption
Constant
endogenous
production
rate
Easily
Assayed
TcDTPA
56
THE END
Any questions?
57