King Saud University College of Science Department of Biochemistry 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 Chapter 4 Renal Function Professor A. S. Alhomida 1 Primary Role Role of Kidney 1. Maintain body fluid volume and composition 2. Filter waste products for elimination 2 1
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 2
Renal Anatomy, Cont d 5 Renal Nephron 6 3
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 4
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 5
Glomerular Filtration, Cont d 11 Glomerular Filtration, Cont d 12 6
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 7
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 8
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 9
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 10
Pumps Renal Transepithelial Transport Carriers Channels 3Na + -2K + -ATPase Symporters Na + -Glucose Antiporters Na + -H + Na + 3H + -ATPase H + -K + -ATPase Ca 2+ -ATPase Na + -Amino acid 2Na + 2- -HPO 4 Na + - -3HCO 3 Na + -2Cl - -K + Na + + -NH 4 Na + -Ca 2+ Cl - - -HCO 3 K + Cl - Ca 2+ K + -Cl - 21 Renal Transepithetial Transport, Cont d 22 11
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 12
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 13
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 14
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 15
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 16
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 17
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 18
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 19
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 20
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 21
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 22
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 23
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 24
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 25
3. ph Urinalysis, Cont d 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 26
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 27
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 U rea C reatinine Inulin 99m TcD TPA N ot Protein B ound Freely Filtered N o secretion or absorbtion C onstant endogenous production rate Easily Assa yed Yes Yes Yes Yes Yes Yes Yes Yes Flow related reabsorption Som e secretion Yes Yes N o Yes N o N o Yes Yes N o N o 56 28
THE END Any questions? 57 29