King Saud University
College of Science
Department of Biochemistry
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• The texts, tables, figures and images contained in this course presentation
(BCH 376) are not my own, they can be found on:
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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. Regulate blood pressure
2. Participate in acid-base balance
3. Produce erythropoietin for RBC synthesis
4. Hormonal function
5. 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 H
2
O 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

Pumps
Renal Transepithelial
Transport
Carriers Channels
Symporters Antiporters
3Na
+
-2K
+
-ATPase Na
+
-Glucose Na
+
-H
+
3H
+
-ATPase
H
+
-K
+
-ATPase
Ca
2+
-ATPase
Na
+
-Amino acid Na
+
-NH
4
+
2Na
+
-HPO
4
2-
Na
+
-Ca
2+
Na
+
-3HCO
3
-
Cl
-
-HCO
3
-
Na
+
-2Cl
-
-K
+
K
+
-Cl
-
Na
+
K
+
Cl
-
Ca
2+
21

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

Unit = mOsm
Urine Countercurrent
Mechanism, Cont’d
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 B
6
)
32

Renal Threshold Substances
1.
Renal Threshold
• 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
2.
High Threshold Substances
• They are essential for the body and are completely reabsorbed by renal tubules, examples: glucose, amino acids
3.
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.
Allows kidneys to concentrate urine
2.
Secreted by posterior pituitary gland
3.
Works on the collecting ducts by making the ducts permeable to H
2
O
4.
H
2
O is reabsorbed into body
5.
Deficiency in ADH: diminishes blood volume
6.
Excess in ADH: increases blood volume
36

Other Functions
•
Erythropoietin Production
1.
Released in response to decreased oxygen tension
2.
Stimulates RBC production in the bone marrow
•
Vitamin D Activation
1.
Activated vitamin D necessary to absorb calcium and phosphate in the GI tract
2.
Regulation of calcium/phosphorous balance
37

Hormonal Functions, Cont’d
38

Renal Function Tests
1.
To identify renal dysfunction
2.
To diagnose renal diseases
3.
To monitor disease progress
4.
To monitor response to treatment
5.
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.
Urea clearance test
2.
Endogenous creatinine clearance test
3.
Inulin clearance test
4.
Cr
51
-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.
Concentration and dilution test
2.
15 minute-pheonl-sulphthalein (PSP) excretion test
3.
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, Bence-
Jones 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 Urea
Not Protein
Bound
Freely
Filtered
No secretion or absorbtion
Constant endogenous production rate
Easily
Assayed
Yes
Yes
Flow related reabsorption
No
Yes
Creatinine
Yes
Yes
Some secretion
Yes
Yes
Inulin
Yes
Yes
Yes
No
No
99m
TcDTPA
Yes
Yes
Yes
No
No
56

THE END
Any questions?
57