Investigations

Renal failure

Dr. WASIF ALI KHANMD-PATHOLOGY (UNIVERSITY OF BOMBAY)

Assistant Prof. in PathologyAl 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)

Serum Magnesium- 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 CreatinineAdult: 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

Normal values for electrolytes in urineConventional unit (mg/day)

SI unit(mmol/day))

Sodium 30-280 30-280

Potassium 40-80 40-80

Chloride 110-250 110-250

Calcium <275—male<250--female

<6.8-male<6.2-female

Magnesium <150 3-4.3

Phosphorus 0.9-1.3 29-42

RENAL FUNCTION TESTS

1.Routine tests

2.Tests for renal function proper

3.Tests for structural integrity of kidney

1.ROUTINE TESTS1.Urine analysis –

2. Blood biochemistry

•Serum creatinine

•Blood urea nitrogen (BUN) • Serum uric acid

Electrolytes-Na, K, Ca, Ph, Cl

Acid –base analysis-H, HCO3

Collection of Urine samplePhysical ExaminationChemical ExaminationMicroscopic Examination

Urine Analysis consists of :

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

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.

Urine sample

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

Physical examination

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

Urinometer to measure specific gravity

Colour Normal- pale yellow- urochromesAlterations 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

Measure Turbidity

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.

Chemical examination

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

Diabetes mellitus Benedicts test

Glucose

Ketones

Ketonuria Diabetic ketoacidosis, anorexia, fasting,Starvation fever prolonged vomiting,

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

Blood

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.

Causes of hematuria

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—

1. Hemolytic anemias autoimmune like G6PD deficiency

2. Poisoning from snake venom,

3. spider bites4. 5. bacterial toxins like clostridium botulinum

6. Severe burns

7. Hemolytic transfusion reactions

8. Sulfonamide and phenacetin administration

Hemoglobinuria

Microscopic examination

Following are examined under the microscope after centrifuging urine at 2000 rpm for 10 min

Cells 1. Red cells 2. Epithelial cells3. Pus cells Casts 1. Hyaline casts2. Epithelial casts3. Granular casts4. Waxy casts5. Broad casts6. Pus cells7. Cylindroids and pseudo casts

Crystals and amorphous materialsCrystals in acidic

urine: Uric acid Urates and calcium oxalatesCrystals in alkaline

urine: Triple phosphates Amorphous

phosphates of calcium and magnesium

Calcium carbonate Ammonium biurate

Abnormal crystals

Cystine Cholesterol Leucine Tyrosine Sulfonamide

Look for malignant cells – early diagnosis of urinary tract malignancies

Fresh urine sample sediment smears stained by H &E and Papanicolaou stain

Cytological Examination

Normal values- male-105+/- 20 ml/min female-95+/-20 ml/min Decrease creatinine clearance- significant

reduction of renal function, glomerular filtration.

ESTIMATION OF GFR-Creatinine clearance

Creatinine clearance : max vol of ml plasma cleared/minute/standard surface area = Ucr x V x 1.73/ Pcr x AUcr- concentration of creatinine in

urine( mg/dl).Pcr- Concentration of creatinine in plasma

or serum.V- Volume of urine flow in ml/minuteA-Body surface area

Creatinine clearance test

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.

Formulas for creatinine clearance

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

Evaluation of renal sodium excretion

3.TESTS FOR STRUCTURAL INTEGRITY OF KIDNEY

1. Plain X-ray or KUB2. IVP 3. Retrograde pyelography4. Antegrade pyelography5. Micturating cystourethrogram6. Renal angiography7. USG8. Radio isotope renal scan9. 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 kidney3. Uncontrolled HTN4. Urinary tract or perinephric infection5. Bleeding disorder