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Chapter 4 Renal Function

Professor A. S. Alhomida

Chapter 4 Renal Function

Professor A. S. Alhomida

Disclaimer• The texts, tables, figures and images contained in this course presentation (BCH 376) are

not my own, they can be found on: • References supplied• Atlases or• The web

King Saud University

College of Science

Department of Biochemistry

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Role of Kidney

• Primary Role1. Maintain body fluid volume and

composition

2. Filter waste products for elimination

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• Secondary Role1. 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

Role of Kidney, Cont’d

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Renal Anatomy

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Renal Anatomy, Cont’d

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Renal Nephron

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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

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Urine Formation

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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

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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

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Glomerular Filtration, Cont’d

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Glomerular Filtration, Cont’d

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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

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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

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Factors Affecting Glomerular Filtration

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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

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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)

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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

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Tubular Reabsorption, Cont’d

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Tubular Secretion1. 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

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Renal Transepithelial Transport

Symporters Antiporters3Na+-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+-Cl-

Pumps Carriers Channels

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Renal Transepithetial Transport, Cont’d

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Renal Transepithetial Transport, Cont’d

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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

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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

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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

Mechanism of Urine Countercurrent, Cont’d

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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

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Urine Countercurrent Mechanism, Cont’d

Unit = mOsm

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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

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Renal Clearance, Cont’d

• Renal Clearance1. 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

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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

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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)

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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

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Hormonal Functions

• Renin Production1. When there is a decrease in:

• Blood flow• Volume, or • Blood pressure

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Hormonal Functions, Cont’d

2. Physiological effects:• Na reabsorption

• Systemic vasoconstriction

• Sympathetic nerve stimulation

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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 H2O

4. H2O is reabsorbed into body

5. Deficiency in ADH: diminishes blood volume

6. Excess in ADH: increases blood volume

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Other Functions• Erythropoietin Production

1. Released in response to decreased oxygen tension

2. Stimulates RBC production in the bone marrow

• Vitamin D Activation1. Activated vitamin D necessary to absorb calcium and

phosphate in the GI tract

2. Regulation of calcium/phosphorous balance

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Hormonal Functions, Cont’d

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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)

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Renal Function Tests, Cont’d

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Classification of Renal Function Tests

• Tests Based on Glomerular Filtration1. Urea clearance test2. Endogenous creatinine clearance test3. Inulin clearance test

4. Cr51-EDTA clearance test

• Tests to Measure Renal Plasma Flow1. Para-Amino hippurate test2. Filtration fraction

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• Tests Based on Tubular Function1. Concentration and dilution test

2. 15 minute-pheonl-sulphthalein (PSP) excretion test

3. Measurement of tubular secretory capacity

• Certain Miscellaneous Tests1. Determine size, shape, asymmetry, obstruction, tumor,

infarct, etc

Classification of Renal Function Tests, Cont’d

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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

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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

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Biochemical Tests of Renal Function

1. Urinalysis• Appearance

• Volume• Odor• Color

• Specific gravity• Osmolality• pH• Glucose• Protein• Urinary sediments

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Biochemical Tests of Renal Function, Cont’d

2. Measurement of GFR• Clearance tests• Plasma creatinine

3. Tubular function Tests

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Role of Biochemical Testing

1. Presentation of Patients• Routine urinalysis

• Symptom or physical sign

• Systemic disease with known renal component

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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)

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Role of Biochemical Testing, Cont’d

3. Role of Biochemistry• Rarely establishes the cause

• Screening for damage

• Monitoring progression

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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)

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Urinalysis, Cont’d

3. pH• Normal = acidic, except after meal

4. Glucose• Increased blood glucose • Low renal threshold or other tubular disorders

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Urinalysis, Cont’d5. 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

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Urinalysis, Cont’d6. 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

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Urinalysis, Cont’d6. Urine Sediments

• Lower urinary tract infection (UTI) polymorphs no casts

• Acute glomerulnephritis = hematuria, cells, casts

• Chronic glomerulonephritis = less sediment

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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

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Properties of Agents Used to Determine GFR

Property Urea Creatinine Inulin 99mTcDTPA

Not ProteinBound

Yes Yes Yes Yes

FreelyFiltered

Yes Yes Yes Yes

No secretionor absorbtion

Flow relatedreabsorption

Somesecretion

Yes Yes

Constantendogenousproductionrate

No Yes No No

EasilyAssayed

Yes Yes No No

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THE END

Any questions?