Kidney Function Tests (PDF)

Kidney Function Tests References  Nephrons The functional unit of the kidney is the nephron. Nephrons ◼ In nearly all types of renal disease, impaired function of the kidneys is attributed to a diminished number of functioning nephrons. Kidney Function Tests ❑URINE ANALYSIS ❑ To...

Kidney Function Tests References  Nephrons The functional unit of the kidney is the nephron. Nephrons ◼ In nearly all types of renal disease, impaired function of the kidneys is attributed to a diminished number of functioning nephrons. Kidney Function Tests ❑URINE ANALYSIS ❑ Total Protein ❑ Albumin ❑ Hemoglobin ❑ Glucose ▪ Blood ANALYSIS ▪ CREATININE ▪ UREA ▪ URIC ACID  Renal Physiology Three basic renal processes Glomerular filtration. Tubular reabsorption. Tubular secretion. Glomerular filtration Glomerular filtration ◼ From incoming blood, all substances except cells and large molecules pass into further sections of the nephron. ◼ Filtration process requires adequate blood pressure by heart pumping. ◼ Most of the filtrate (99+ %) is reabsorbed. GFR ◼ Because glomerular filtration is the initiating phase of all nephron functions, ◼ Here we have the glomerular filtration rate (GFR), Reabsorption Occurs in virtually all segments of the nephron. Renal threshold for each substance determines whether it is reabsorbed or secreted, Glucose, actively reabsorbed in the proximal tubules according to the renal threshold, Na, actively reabsorbed according to the diet.  Previously, we said that: Glucose, ▪ ▪ Oligopeptides Almost 100 percent reabsorbed; , By the secondary ▪ Proteins, active co-transport with Na+, ▪ Amino acids, (co-transportation),  Nephrotic syndrome vs Nephritic syndrome Nephrotic syndrome: 1. Massive proteinuria? 2. Hypoalbuminemia? 3. Edema 4. Hyperlipidemia/hyperlipiduria Nephritic syndrome: 1. Hematuria? 2. Oliguria? 3. Azotemia 4. Hypertension Example: Changes in chemical and cytological properties of the urine,  Presence in urine Of urine Presence in urine Testing Of urine Presence in urine  Proteinuria ❑ A small/undetectable amount of protein (50 – 150 mg / 24 hrs) appears daily in the normal urine. ❑ More than 150 mg/day is defined as proteinuria. ❑ Proteinuria: The presence of detectable amount of proteins in urine. Causes of proteinuria A 24-hour sample is the definitive means of demonstrating and quantifying the presence of proteinuria.  Causes of proteinuria ❑Prerenal Proteinuria : Over flow / over load, increase of LMW protein such as multiple myeloma & excessive Bence Jones protein. ❑Tubular proteinuria: Presence of LMW protein, reabsorption problems.  Over flow / over load Multiple myeloma & excessive Bence Jones protein, a light molecular weight protein, Blood & hemoglobin Hematuria, Hemoglobinuria, What is difference between them?  Pathogenesis of glomerular haematuria Glomerular filtration barrier structure and red blood cell egression leading to haematuria. CL: Capillary lumen; BC: Bowman’s capsule; E: Endothelial cell; GBM: Glomerular basement membrane; Gly: Glycosaminoglicans; M: Mesangium; P: Podocyte; RBC: Red blood cell; SD: Slit diaphragm; SP: Subpodocyte space; TC: Tubular cell; US: Urinary space.  Blood & hemoglobin Hematuria: (the presence of erythrocytes in urine) due to: ❑ Kidney problem such as: Renal disease Renal tumor. Renal calculi Trauma. Lower Urinary tract problem Infection Tumor Calculi Trauma URINE ANALYSIS ◼ Hemoglobinuria: The presence of hemoglobin in the urine due to intravascular hemolysis in the body (eg thalassemia, sickle cell anemia),  Hemolytic disorders and blood disease ❑ Hemoglobinuria: Leukemia Thrombocytopenia Hemophilia Sickle cell trait ❑ Intravascular hemolysis Hemoglobinuria Glucose, a threshold substance ◼ Under normal conditions, all most all of glucose filtered by glomerulus is reabsorbed actively in the proximal convoluted tubule, ❖ Threshold substance: ❑ The threshold of glucose is 180 mg / dl.  Proximal tubule cells The fructose transporter SLC2A9 (GLUT9, urate transporter 1 (URAT1), organic anion transporters 1,3,4 (OAT1, OAT3, OAT4), multi-drug resistance protein 4 (MRP4), sodium- coupled monocarboxyl transporters SMCT1,2, and human ATP-binding cassette, subfamily G, 2 (ABCG2) ❖ Glycosuria may be due to: ❖ Reabsorption defect (Renal diabetes), ❖ Increase Blood glucose, in the following cases: ▪ Diabetes mellitus, ▪ Alimentary glycosuria (transitory), after meal. ▪ Stress with elevation of cortisol which increases gluconeogenesis. ▪ Decrease reabsorbtion ability (due to drugs)  Causes of myoglobinuria (presence of myoglobin in urine in case of: Muscular trauma Prolonged coma Convulsions.  Nitrite A positive nitrite test indicates that bacteria may be present in significant numbers in urine, Gram negative rods such as E. coli are more likely to give a positive test.  Nitrite Negative test can not exclude the presence of bacteria. Bacteria will transform Nitrate Nitrite All bacteria do not give a positive test, and are negative for the Nitrite test,  Bilirubin ❑ Bilirubin derived from Hb, is conjugated in the liver and excreted in the bile, ❑ Some reabsorbed urobilinogen is excreted in the urine, ❑ Normal urine has a small amount of: ❑ Urobilinogen 0 – 4mg / day ❑ Urobilin 10 – 130 mg / day. Schematic representation of bilirubin metabolism  While bilirubin is present in urine: ❑ Conjugated bilirubin will appear in urine if: The normal degradation cycle is obstructed by the bile duct, Or when the integrity of liver is damaged allowing, leakage of conjugated bilirubin into the circulation such as cholestasis & hepatitis,  Urinary Urobilinogen/Bilirubin A High Urinary Urobilinogen/Serum Total Bilirubin Ratio Reported in Abdominal Pain Patients Can Indicate Acute Hepatic Porphyria  Keton bodies ❑ There are 3 intermediate product of fat metabolism called keton body Acetone (78%) Aceotacetic acid (20%) Beta-hydroxybutyric acid (2%).  Ketonurea occurs in: ❑ Starvation, ❑ Excessive Carbohydrate loss, Ascorbic acid interferes with glucose, hemoglobin, nitrite, and bilirubin at different concentrations causing false‐negative results.  Noormal levels for pH ▪ Normal urine pH is (4.6 – 8.0) as average (6.0) ▪ Urine pH must vary to compensate for diet and products of metabolism, ▪ In the distal convoluted tubule the secretion of both H+ & NH3 + and reabsorption of bicarbonate is occurred. Conditions related to pH of Urine ◼ Alkaline urine is found in: Patient with alkalemia, UTI, diets high in citrus fruits or vegetables. ◼ Acidic urine is found in: Patient with acidemia, starvation, dehydration, diets high in meat products  Clinical significance of pH 1. Determining: 1. the existence of metabolic acid-base disorder. 2. Precipitation of crystals to from stones ◼ Stones require specific pH for each type to form, ◼ pH control may inhibit the formation of stones, Formation of stones at alkaline pH ❑ Crystals found in alkaline urine: Ca carbonate, Ca phosphate, Mg phosphate, Amorphous phosphate. Formation of stones at acidic pH ❑ Crystals found in acidic urine: Ca oxalate, Uric acid, Cystine, Xanthine, Amorphous urate.  Acid-Base Equilibria ◼ The kidneys role in controlling body pH is accomplished by preserving HCO3– and removing metabolic acids. ❖ Regeneration of HCO3 – ◼ HCO3 – are filtered by the glomerulus. ◼ HCO3– combines with H+ in the lumen of renal tubules to form H2CO3. ◼ H2CO3 is degraded to CO2 + H2O. Acid-Base Equilibria Kidneys are controlling body pH, by preserving HCO3– and removing metabolic acids.  Acid-Base Equilibria ◼ CO2 diffuses into proximal tubules and is converted to H2CO3 by the action of carbonic anhydrase, ◼ Then it is degraded back to H+ and HCO3. ◼ This regenerated HCO3 is transported into the blood to replace the depleted one by metabolism, ◼ H+ are secreted into the tubular lumen and enter the urine. Sodium/The kidney ❑ Being freely filtered by the kidney glomeruli, ❑ ~ 80% of the filtered Na+ load is then actively reabsorbed in the proximal tubules, with Cl- and water passively following in an iso-osmotic and electrically neutral manner, Transporters The loop of Henle ❑ 20 to 25% is reabsorbed in the loop of Henle, along with Cl- and more water,  The loop of Henle ❑ The basolateral Na+/K+ pump generates concentrations of Na/K, ❑ NaCl is then reabsorbed passively by the NKCC2 transporter. ❑ K+ then is recycled back to the lumen via the ROMKI channel. ❑ This K+ then drives para-cellular resorption of Mg2+ and Ca2+ The loop of Henle. The loop of Henle ❖Bartter's syndrome: ❖Mutations in NKCC2, ROMKI, or CLC-Kb, ❖Hypomagnesemic- hypercalciuric nephrolithiasis: ❖Mutations in paracellin-I Bartter's syndrome: ◼ Autosomal recessive disorder of salt reabsorption, ◼ Resulting in extracellular fluid volume depletion, ◼ With low/normal blood pressure, Distal tubules/ Aldosterone ❖ In the distal tubules, ❖ Interaction of aldosterone with the coupled Na+- K+ and Na+-H+ exchange systems results directly in ❖ the reabsorption of Na+, and indirectly of Cl- ❖ Which determines the amount of Na+ excreted in the urine, Gitelman syndrome/Distal tubule Disease-causing variants of NCC lead to a loss of NCC function, Similar to that seen with thiazide diuretic therapy (causes inhibition of NCC activity). An autosomal recessive, Renal potassium wasting, hypokalemia, Metabolic alkalosis, hypocalciuria, hypomagnesemia, Hyperreninemic hyperaldosteronism, Primary renal tubular hypokalemic hypomagnesemia with hypocalciuria Control of ALD 1. Mainly by the renin-angiotensin system 2. ACTH ◼ Pseudohypoaldosteronism (PHA) ◼ Familial hyperkalemic hypertension (FHH) ◼ Two rare syndromes in which ion handling in the distal nephron is impaired Extreme hyperkalemia is a medical emergency, due to the risk of potentially fatal abnormal heart rhythms (arrhythmia) PHA ◼ PHA is a rare inherited syndrome characterized by mineralocorticoid resistance, which leads to salt loss, hypotension, hyperkalemia and metabolic acidosis  FHH ◼ FHH is a rare autosomal dominant syndrome, characterized by salt retention, hypertension, hyperkalemia and metabolic acidosis. ◼ An inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (1, 2). The primary defect is a hyperactive sodium chloride cotransporter (NCC), expressed exclusively in renal distal convoluted tubule (DCT) Collecting duct/Aldosterone ◼ Aldosterone & Cortisol both bind to the MR, ◼ But cortisol is inactivated to cortisone by 11β-hydroxysteroid dehydrogenase (11β -HSD), ◼ ◼ Na uptake drives K+/H+ secretion, ENaC: epithelial sodium channel,  Collecting duct/Aldosterone ❖ Liddle's syndrome, ❖ mutations increase ENaC activity, ❖ with increased Na+ reabsorption and consequent K+/H+ loss. ENaC: epithelial sodium channel,  Collecting duct/Aldosterone ❖ Pseudohypoaldosteronism type la: ❖ mutations inactivate ENaC, whereas in type Ib, there are MR abnormalities. ENaC: epithelial sodium channel,  Collecting duct/Aldosterone ❖ Pseudohypoaldosteronism type la/Ib: ❖ Both lead to reduced Na+ entry via ENaC, ❖ Causing salt wasting and decreased secretion of K+/H+. ENaC: epithelial sodium channel,  Collecting duct/Aldosterone ❖Licorice (herbal medicine): ❖ Causes hypertension and a hypokalemic metabolic alkalosis: ❖ By inactivating 11β -HSD, allowing cortisol to act as a mineralocorticoid. ENaC: epithelial sodium channel, Schematic representation of the sodium reabsorption system in epithelial cells. (MR: mineralocorticoid receptor, ENaC: epithelial sodium channel, Na+: sodium, K+: potassium, ATP: adenosine triphosphate). In the nucleus, GR dimerizes and binds glucocorticoid responsive element (GRE) sequences in the promoter of regulated genes. The trans-acting elements of GR contain a zinc finger DNA binding domain, flanked by transcriptional control domains that ensure GR binds to GRE and not to other cis-acting elements that may bind zinc fingers. Tubular reabsorption of Na ◼ TR is regulated by both: 1. Humoral factors, 2. Physical factors, Humoral factors that influence TR of Na ◼ A ngiotensin II, ◼ Aldosterone, ◼ The atrial natriuretic peptide family of hormones, ◼ Catecholamines, Catecholamines ◼ Influence sodium reabsorption mainly through their effects on renal blood flow, Salt content of the body ◼ The role of ADH in the regulation of extracellular volume is modest, ◼ Osmolality is the main regulator of ADH secretion, ◼ For this reason, salt content of the body is the main determinant of the extracellular volume, Control of transcellular flux of K+ Causes of hypokalemia ❑ Occurs by one of three main mechanisms: 1. Intracellular shift, 2. Reduced intake, 3. Increased loss, In chloroquine or hydrochloroquine and barium poisoning, hypokalemia develops because of the inhibition of the K+ channel by barium, resulting in inhibition of K+ efflux from the cell, ❑Generation of NH3 ◼ NH3 is formed in the renal tubules as a result of glutamine deamination by glutaminase, ◼ NH3 then react with H+ to form NH4 which is excreted in urine. ❑ May indicate the presence of urinary tract infection caused by urea splitting organisms. urease Urea NH3 + CO2.  ❑ Specific Gravity ❖ Specific gravity = Weight of specific volume of urine Weight of specific volume of water ▪ SG ~ between 1.002 and 1.035,  Measurement of SG ◼ Urinometer: The weighted float displaces a volume of liquid equal to its weight and has been designed to sink to a level of 1.000 in distilled water. ❑ Specific Gravity ❖ Proportional to urine osmolality, which depends on : ❖ Urine concentration, ❖ Urine density, ❖ The ability of the kidney to concentrate or dilute the urine over that of plasma, ⚫ Low specific gravity Diabetes Insipidus. Excessive water intake. Glamerulonephritis. Sever renal damage. ⚫ High specific gravity: Diabetes mellitus. Nephrosis. Fever since urine is conc. X ray contrast media. Microscopic Examination Of Urine What do we look for? ❑Cellsin Urine, ❑Casts in Urine, Markers of distinct-organ disfunctioning ❑Crystals in Urine, ❑Others in Urine,  Cloudy Urine Increased specific Gravity Microscopic Examination Of Urine  Casts in Urine ❑ Casts are collections of: Proteins, Cells, Debris that are formed in the tubules of the kidneys.  Types of Casts ❑ Hyaline cast, ❑ Red blood cell cast, ❑ Wight blood cell cast, ❑ Granular casts, ❑ Bacterial Casts, ❑ Epithelial cell casts,  Casts in Urine ❑ Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct. ❑ They may also differ in length, thickness, and consistency. ❑ A positive protein is often found when many casts are present They vary in shape and size according to the site of their origin. Unorganized Sediments Crystals  Sediments precipitate in Acidic urine Uric acid – Increase levels are seen in gout. – Amorphous Urate yellow brown granules if present in large amount may give urine pink color.  Crystals in Acidic urine ❑ Calcium oxalate Color less, Octahedral resembles envelopes, Associated with high oxalic acid In genetically susceptible person following large doses of ascorbic acid  Crystals in Alkaline Urine ❖ Phosphates are the most common crystals, ❖ Triple phosphate Color less prism ❖ Amorphous phosphate granules, ❖ Calcium phosphate: is color less thin prisms. ❖ If present in large amounts the produce white turbidity in urine.  Abnormal crystals ◼ Cystine, cholesterol, leucine, tyrosine, bilirubin, sulfonamide, radiographic dye, and medications. Ampicillin. Tyrosine crystal Cystine Crystals