Renal failure Investigations • Dr. WASIF ALI KHAN • MD-PATHOLOGY (UNIVERSITY OF BOMBAY) • Assistant Prof. in Pathology • Al Maarefa College
Serum sodium 136-145 mEq/L, SI-136-145 mmol/L Critical level--<120 or >160 mEq/L • Serum potassium Adult: 3.5–5.0 mEq/L: SI units: 3.5–5.0 mmol/L • Critical Levels: <2.5 or >6.5 mEq/L
Serum calcium- Adult: 8.2 to 10.5 mg/dL; SI units: 2.05–2.54 mmol/L • Critical levels: >12 mg/dL; SI units: 2.99 mmol/L (coma, death). • <7mg/dL; SI units: 1.75 mmol/L (tetany, death)
SerumMagnesium- 1.6–2.2 mg/dL; SI units: 0.66–0.91 mmol/L • Critical Levels: <1 or >5 mg/dL Serum Phosphorus- • Adult: 2.5–4.5 mEq/dL; SI units: 0.78–1.52 mmol/L • Critical Levels: <1 mg/dL
Serum Chloride- • Adult: 96–106 mEq/L; SI units: 96–106 mmol/L • Critical levels: < 80 mEq/L or >115 mEq/L • Serum BUN • Adult: 10–20 mg/dL; SI units: 3.6–7.1 mmol/L • Critical Levels: • >40 mg/dL (not dehydrated/no history of renal disease) • >100 mg/dL (patient with history of renal disease) • >20 mg/dL increase in 24 hr (indicates acute renal failure)
Serum Creatinine Adult: Male: 0.6–1.2 mg/dL; SI units: 53–106 mol/L. Female: 0.5–1.1 mg/dL; SI units: 44–97 mol/L Serum Uric Acid • Adult: Male: 4.0–8.5 mg/dL; SI units: 0.24–0.51 mmol/L. • Female: 2.8–7.3 mg/dL; SI units: 0.16–0.43 mmol/L • Critical Levels: > 12 mg/dL
RENAL FUNCTION TESTS • Routine tests • Tests for renal function proper • Tests for structural integrity of kidney
1.ROUTINE TESTS • Urine analysis – 2. Bloodbiochemistry • Serum creatinine • Blood urea nitrogen (BUN) Serum uric acid Electrolytes-Na, K, Ca, Ph, Cl Acid –base analysis-H, HCO3
Urine Analysis consists of : • Collection of Urine sample • Physical Examination • Chemical Examination • Microscopic Examination
Collection of urine • Sample should be fresh and examined immediately ( within 1 hr). • Keeping at room temp • Reaction changes • Precipitation of crystalline substance • Disintegration of casts • Sample may be contaminated by bacterial growth.
Urine sample For routine examination: random sample Early morning sample (most concentrated) - preferred for cellular elements and casts. Specimen collected 2-3 hrs after a meal for albumin and sugar Quantitative studies - 24 hr collection 150 to 200 cc of urine subjected for examination
Urine sample • Bacteriological examinations- -midstream sample in sterile test tube -for females, clean perineum and vulva with soap, water and clean gauze in sequence. -In males retract the foreskin • For mycobacterial studies - 24 hr specimen is recommended. • For pregnancy tests- early morning specimen.
Preservatives added (for 24hr collection) • Thymol (0.1gm/100ml.) • Toluol (enough to form a surface film) • Formaldehyde – for preserving cells and casts • NaF to inhibit glycolysis
Volume • Normal adult excretes about 750-2000 ml of urine per day Factors affecting volume of urine • Fluid intake • Diet • Environmental temp. • Humidity • Exercise • Age • Excretion of fluid by respiratory, intestinal tracts and skin
Causes of altered urine volume Polyuria- diabetes mellitus, diabetes insipidus,during disappearance of oedema, chronic nephritis and certain nervous diseases Oliguria- (decrease urination) acute and chronic glomerulonephritis, CCF, shock, febrile states, dehydration from any cause Anuria- severe hypotension, acute GN, crush injuries, mercurial poisoning, after mismatched transfusion.
Specific gravity Directly proportional to concentration and inversely proportional to volume Normal range 1.003 to 1.030 In diabetes volume as well as specific gravity is increased In end stage chronic glomerulonephritis the specific gravity is fixed at 1.010 despite the low volume of urine. Proteinuria also raises the specific gravity
Colour • Normal- pale yellow- urochromes Alterations • Yellow green- bile or acriflavin • Red or brown - hemoglobin, beet, aniline dyes • Smoky red or brown - blood, rhubarb, senna • Milky - pus, bacteria, fat or chyle • Black - melanin, homogentisic acid, phenol • Redish purple - porphyrins
Appearance • Freshly voided is clear • Cloudiness on standing is due to -Precipitation of phosphates in neutral/ alkaline urine and urates in acidic urine • Turbidity is due to presence of pus and epithelial cells, chyle or bacteria
Reaction Normal urine is slightly acidic, pH is 6 Reaction depends on the diet, metabolic state of the body and micro-organisms in urine. Reaction is tested by pH papers, litmus paper and pH meters.
Odour Normal is aromatic Ammoniacal odour is due to decomposition from stasis in the bladder (cystitis) Fruity odour is due to presence of ketone bodies seen in diabetes.
PROTEINS • Normal urine - 50mg in 24 hrs sample which is not detected by routine methods • Protienuria - increased glomerular permeability. • Most commonly filtered is albumin-albuminuria • Abnormal globulins like Bence-Jones proteins in multiple myeloma
Glucose • Diabetes mellitus • Benedicts test
Ketones Ketonuria Diabetic ketoacidosis, anorexia, fasting, Starvation fever prolonged vomiting,
Blood • Blood- intact RBC (hematuria) or hemoglobin (hemoglobinuria) Benzidine test • urine→ centrifuge →sediment →mix equal volume of reagent (saturated benzidine in glacial acetic acid+ equal quantity of hydrogen peroxide) • Appearance of blue colour- positive test
Causes of hematuria Renal diseases • Acute infections, chronic glomerulonephritis, tuberculosis of the kidney, nephrotic syndrome, toxic damage to glomerulus, malignant hypertension, infarction, renal calculi, trauma to kidneys, acute cystitis, calculi and tumors in the ureter or bladder. Other clinical conditions • Bleeding disorders such as leukemia, thrombocytopenia, coagulation factor deficiency, sickle disease or trait, scurvy. • Use of anticoagulant drugs.
Hemoglobinuria • Hemoglobinuria-the presence of free hemoglobin in the urine as a result of intravascular hemolysis. • Hemoglobinuria without hematuria occurs as a result of hemoglobinemia (i e presence of free hemoglobin in the blood). The conditions— • Hemolytic anemias autoimmune like G6PD deficiency • Poisoning from snake venom, • spider bites • bacterial toxins like clostridium botulinum • Severe burns • Hemolytic transfusion reactions 8. Sulfonamide and phenacetin administration
Microscopic examination • Following are examined under the microscope after centrifuging urine at 2000 rpm for 10 min • Cells • Red cells • Epithelial cells • Pus cells • Casts • Hyaline casts • Epithelial casts • Granular casts • Waxy casts • Broad casts • Pus cells • Cylindroids and pseudo casts
Crystals and amorphous materials Crystals in acidic urine: • Uric acid • Urates and • calcium oxalates Crystals in alkaline urine: • Triple phosphates • Amorphous phosphates of calcium and magnesium • Calcium carbonate • Ammonium biurate
Abnormal crystals • Cystine • Cholesterol • Leucine • Tyrosine • Sulfonamide
Cytological Examination • Look for malignant cells – early diagnosis of urinary tract malignancies • Fresh urine sample sediment smears stained by H &E and Papanicolaou stain
ESTIMATION OF GFR-Creatinine clearance • Normal values- male-105+/- 20 ml/min female-95+/-20 ml/min • Decrease creatinine clearance- significant reduction of renal function, glomerular filtration.
Creatinine clearance test • Creatinine clearance : max vol of ml plasma cleared/minute/standard surface area = Ucrx V x 1.73/ Pcrx A Ucr- concentration of creatinine in urine( mg/dl). Pcr- Concentration of creatinine in plasma or serum. V- Volume of urine flow in ml/minute A-Body surface area
Formulas for creatinine clearance • Cockcroft-Gault formula • Estimated GFR- • Modification of Diet in renal diseases-MDRD formula—ser. Creat, age, ethnicity and gender. • eGFR= 186 x Ser.Creat-1.154 x Age-0.203x (1.212 if black)x (0.742 if female) • eGFR in mg/dl.
Evaluation of renal sodium excretion Most diagnostically distinguishing is the fraction of filtered sodium excreted (FENa). FENa = Nau x Crs x 100 Nas x Cru < 1% with adequate tubular function > 2% with acute tubular necrosis
3.TESTS FOR STRUCTURAL INTEGRITY OF KIDNEY Plain X-ray or KUB IVP Retrograde pyelography Antegradepyelography Micturatingcystourethrogram Renal angiography 7. USG 8. Radio isotope renal scan 9. Renal biopsy.
RENAL BIOPSY: 1. Done when • Near normal kidney size • Clear cut diagnosis can not be made by less invasive measures. • Reversible disease process can be clarified.
2. The lesions diagnosed are – • Glomerulonephritis • Vasculitis • H U syndrome • Allergic nephritis 3. The biopsy specimen is subjected to light microscopy, immunofluorescence, electron microscopy
4. Contraindications- 1. Bilateral small kidney 2. Polycystic kidney 3. Uncontrolled HTN 4. Urinary tract or perinephric infection 5. Bleeding disorder