clinical investigation of urine. changes in the urine in pathological processes of internal organs

CLINICAL CLINICAL INVESTIGATION OF INVESTIGATION OF

URINEURINE. CHANGES IN THE . CHANGES IN THE URINE IN PATHOLOGICAL URINE IN PATHOLOGICAL PROCESSES OF INTERNAL PROCESSES OF INTERNAL

ORGANSORGANS

DefinitionDefinition

Examination of urine by chemical, physical, Examination of urine by chemical, physical, or microscopic means. Routine urinalysis or microscopic means. Routine urinalysis usually includes performing chemical screening usually includes performing chemical screening tests, determining specific gravity, observing tests, determining specific gravity, observing any unusual color or odor, screening for any unusual color or odor, screening for bacteriuria, and examining the sediment bacteriuria, and examining the sediment microscopically.microscopically.

Method Method Multiple reagent test strip Multiple reagent test strip Urine Microscopic ExamUrine Microscopic Exam

Collection Collection First morning sample First morning sample Midstream, clean catch Midstream, clean catch

collection collection Minimum volume of 3 ml (1 Minimum volume of 3 ml (1

ml for children) ml for children) Analyze within 1-2 hours or Analyze within 1-2 hours or

refrigerate refrigerate

General Tests General Tests

Urine Appearance ( (Urine Color) ) Urine Odor Urine Specific Gravity Urine pH Urine Microscopic Exam

Urine cells (RBCs, WBCs, epithelial cells) Urine cells (RBCs, WBCs, epithelial cells) Urine bacteria Urine bacteria Urine Casts s Urine Crystals s

Urine Appearance ( (Urine Color))

Cloudy urine causes Cloudy urine causes Urine with high phosphate, oxalate, lipids, Urine WBCs Urine with high phosphate, oxalate, lipids, Urine WBCs High purine food intake (increased High purine food intake (increased Uric Acid) )

Brown urine causes Brown urine causes Bile pigment Bile pigment Myoglobinuria Fava beans Fava beans Medications (Levodopa, Medications (Levodopa, Flagyl, , Nitrofurantoin) )

Black urine causes Black urine causes Melanin Methemoglobinuria Methemoglobinuria Cascara or senna or senna Methydopa Methydopa

Blue or green urine Blue or green urine Urinary Tract Infection due to Pseudomonas due to Pseudomonas Bilverdin Bilverdin Medications Medications

Amitriptyline, , Triamterene Intravenous mendications (Intravenous mendications (Cimetidine, , Phenergan) )

Dyes Dyes Methylene blue Methylene blue Indigo carmine or indigo blue Indigo carmine or indigo blue

Orange to yellow urine Orange to yellow urine Increased urine concentration Increased urine concentration Bile pigments Bile pigments Phenothiazines Phenothiazines Pyridium Pyridium Carrots Carrots Tetracycline Rhubarb (red in alkaline urine) Rhubarb (red in alkaline urine) Senna (red in alkaline urine) (red in alkaline urine)

RED URINE CAUSES RED URINE CAUSES Red Urine Red Urine

Microscopic Hematuria Urinary tract source Urinary tract source

Urethra or bladder Urethra or bladder Prostate Prostate Ureter or kidney Ureter or kidney

Non-Urinary tract source Non-Urinary tract source Vagina Vagina Anus or rectum Anus or rectum

Pseudohematuria (non-Pseudohematuria (non-Hematuria related red urine) related red urine) Myoglobinuria Hemoglobinuria Phenolphthalein Laxatives s Phenothiazines Phenothiazines Porphyria Porphyria Rifampin Pyridium Pyridium Bilirubinuria uria Phenytoin Pyridium Pyridium Red diaper syndrome Red diaper syndrome Foods (Beets, Blackberries, Rhubarb) Foods (Beets, Blackberries, Rhubarb)

Causes of Asymptomatic Gross Causes of Asymptomatic Gross Hematuria by Incidence Hematuria by Incidence

Acute Cystitis (23%) (23%) Bladder Cancer (17%) (17%) Benign Prostatic Hyperplasia (12%) (12%) Nephrolithiasis (10%) (10%) Benign essential Benign essential Hematuria (10%) (10%) Prostatitis (9%) (9%) Renal cancer (6%) Renal cancer (6%) Pyelonephritis (4%) (4%) Prostate Cancer (3%) (3%) Urethral stricture (2%) Urethral stricture (2%)

Medical Causes of abnormal urine Medical Causes of abnormal urine odor odor

Sweet or fruity odor Sweet or fruity odor Diabetic Ketoacidosis Maple syrup urine disease (infants, rare) Maple syrup urine disease (infants, rare)

Ammonia odor Ammonia odor Bladder retention Bladder retention Urine at room temperature for prolonged period Urine at room temperature for prolonged period

Fecal odor Fecal odor Bladder-Intestinal fistula Bladder-Intestinal fistula

Pungent odor Pungent odor Urinary Tract Infection

Strong odor Strong odor Concentrated urine Concentrated urine

Musty odor Musty odor Phenylketonuria

Sulfur odor Sulfur odor Cystine decomposition ine decomposition

Food and medication causes of abnormal urine Food and medication causes of abnormal urine odor odor

Asparagus Asparagus Vitamin B6 Supplementation Supplementation

Inborn Errors of Metabolism causing urine odorInborn Errors of Metabolism causing urine odor Phenylketonuria Maple syrup urine disease (infants, rare) Maple syrup urine disease (infants, rare) Glutaric acidemia Glutaric acidemia Isovaleric acidemia Isovaleric acidemia Hawkinsinuria Hawkinsinuria Hypermethioninemia Hypermethioninemia Multiple carboxylase deficiency Multiple carboxylase deficiency Oasthouse urine disease Oasthouse urine disease Trimethylaminuria Trimethylaminuria Tyrosinemia Tyrosinemia

Specific Gravity: 1.005-1.030Specific Gravity: 1.005-1.030

Increased Increased Dehydration Dehydration Fever Vomiting Diarrhea Diabetes Mellitus and other causes of and other causes of Glycosuria Congestive Heart Failure Syndrome Inappropriate ADH Secretion ( (SIADH) ) Adrenal Insufficiency X-Ray contrastX-Ray contrast

Decreased Decreased Diabetes Insipidus Excessive hydration Excessive hydration Glomerulonephritis Pyelonephritis Diuretics s Adrenal Insufficiency Aldosteronism Renal insufficiency Renal insufficiency

Urine pH Urine pH

Normal Normal 4.5-8.0 (usually 5.5 to 6.5) 4.5-8.0 (usually 5.5 to 6.5)

Background Background Urine pH reflects serum pH except with RTA Urine pH reflects serum pH except with RTA In In Renal Tubular Acidosis (RTA), urine pH >5.5 (RTA), urine pH >5.5

Urine cannot be acidified despite acid load Urine cannot be acidified despite acid load

Decreased (Acidic urine) Decreased (Acidic urine)

Acidosis Acidosis Diabetes Mellitus Starvation Starvation Diarrhea Uric Acid Calculi Acidic fruits (Cranberry) Acidic fruits (Cranberry) Drugs Drugs

Ammonium chloride Ammonium chloride

Urine Microscopic Exam

Sample preparation Sample preparation Obtain fresh urine sample Obtain fresh urine sample Centrifuge 10-15 ml at 1500 to 3000 rpm for 5 minutes Centrifuge 10-15 ml at 1500 to 3000 rpm for 5 minutes Decant supernatant and resuspend remainder of urine Decant supernatant and resuspend remainder of urine Place 1 drop of urine on slide and apply cover slip Place 1 drop of urine on slide and apply cover slip

Examination Examination Urine Cells Urine Cells

Urine Urine White Blood Cells s Normal <2/hpf in men and <5/hpf in women Normal <2/hpf in men and <5/hpf in women

Urine Urine Red Blood Cells s Normal <3/hpf Normal <3/hpf Dysmorphic RBCs suggest glomerular disease Dysmorphic RBCs suggest glomerular disease

Epithelial cells Epithelial cells Transitional epithelial cells are normally present Transitional epithelial cells are normally present Squamous epithelial cells suggest contamination Squamous epithelial cells suggest contamination Renal tubule epithelial cells suggest renal disease Renal tubule epithelial cells suggest renal disease

Bacteria Bacteria Five bacteria per hpf represents 100,000 CFU/ml Five bacteria per hpf represents 100,000 CFU/ml Diagnostic for Diagnostic for Urinary Tract Infection

Men: Any bacteria Men: Any bacteria Women: 5 or more bacteria per hpf Women: 5 or more bacteria per hpf

Urine Crystals s Types Types

Calcium oxalate crystals (square envelope shape) Calcium oxalate crystals (square envelope shape) Triple phosphate crystals (coffin lid shape) Triple phosphate crystals (coffin lid shape)

Associated with increased Associated with increased Urine pH (alkaline) (alkaline) Associated with Associated with Proteus Urinary Tract Infection

Uric Acid crystals (diamond shape) crystals (diamond shape) Cystine crystals (hexagonal shape) ine crystals (hexagonal shape)

Urine Casts s Cast Types Cast Types

Epithelial cell casts of renal tubule Epithelial cell casts of renal tubule Acute Tubular Necrosis Interstitial Nephritis Eclampsia Heavy metal poisoning Heavy metal poisoning Rejected transplant Rejected transplant

Red Blood Cell casts casts Glomerulonephritis May be normal in collision sport athletes May be normal in collision sport athletes

White Blood Cell casts casts Pyelonephritis Glomerulonephritis Interstitial Nephritis

Hyaline or mucoprotein casts Hyaline or mucoprotein casts Normal finding Normal finding Pyelonephritis Chronic renal disease Chronic renal disease

Granular casts Granular casts Severe renal disease Severe renal disease

Waxy casts Waxy casts Severe renal disease Severe renal disease

Fatty casts Fatty casts Nephrotic Syndrome

Hypothyroidism

Kidney and Urinary Tract Kidney and Urinary Tract Disease Tests Disease Tests

Urine Protein Urine Blood Urine Blood

Gross Hematuria Microscopic Hematuria

Urine ProteinUrine Protein

Normal Normal Dipstick with trace protein or less Dipstick with trace protein or less

Technique Technique First morning void collected First morning void collected Detection Method Detection Method

Initial: Dipstick urine protein Initial: Dipstick urine protein Confirmation: Confirmation: Sulfosalicylic acid

Dipstick turns from yellow to green for protein present Dipstick turns from yellow to green for protein present Negative: <10 mg/dl Negative: <10 mg/dl Trace: 10-20 mg/dl Trace: 10-20 mg/dl Protein 1+: 30 mg/dl Protein 1+: 30 mg/dl Protein 2+: 100 mg/dl Protein 2+: 100 mg/dl Protein 3+: 300 mg/dl Protein 3+: 300 mg/dl Protein 4+: 1000 mg/dl Protein 4+: 1000 mg/dl

False Positive False Positive Alkaline urine (Alkaline urine (Urine pH >7.5) >7.5) Increased Increased Urine Specific Gravity (concentrated) (concentrated) Specimen contaminated by chlorhexidine detergent Specimen contaminated by chlorhexidine detergent Dipstick immersed too long in urine Dipstick immersed too long in urine Medications Medications

Penicillin Sulfonamide Tolbutamide Phenazopyridine Phenazopyridine

Body fluid contamination Body fluid contamination Gross Hematuria present present Pus Pus Semen Semen Vaginal secretions Vaginal secretions

Urine Protein to Creatinine RatioUrine Protein to Creatinine Ratio Indication Indication

Monitor persistant Monitor persistant Proteinuria Efficacy Efficacy

More accurate than More accurate than 24 Hour Urine Protein collection collection

Most accurate if first morning void is used Most accurate if first morning void is used Technique: Random urine collection Technique: Random urine collection

Urine Creatinine in mg in mg Urine Protein in mg in mg Calculate Calculate Urine Protein mg to mg to Urine Creatinine mg mg

Ratio Ratio

Interpretation of Urine Protein to Interpretation of Urine Protein to Urine Creatinine Ratio Urine Creatinine Ratio

Child under age 2 years Child under age 2 years Normal Ratio <0.5 Normal Ratio <0.5

Adults and children over age 2 years Adults and children over age 2 years Normal ratio <0.2 grams protein per gram Normal ratio <0.2 grams protein per gram

Creatinine Correlates with 0.2 g protein/day Correlates with 0.2 g protein/day

Nephrotic Ratio >3.5 (correlates with 3.5 g Nephrotic Ratio >3.5 (correlates with 3.5 g protein) protein)

Interpretation of Urine Albumin to Interpretation of Urine Albumin to Creatinine Ratio Creatinine Ratio

Normal Ratio (in general <30 mg/g is normal) Normal Ratio (in general <30 mg/g is normal) Men: < 0.017 (or 17 mg albumin to 1 gram Men: < 0.017 (or 17 mg albumin to 1 gram Creatinine) ) Women: <0.025 (or 25 mg albumin to 1 gram Women: <0.025 (or 25 mg albumin to 1 gram

Creatinine) ) Microalbuminuria: 30-300 mg albumin/g Microalbuminuria: 30-300 mg albumin/g

Creatinine Macroalbuminuria: >300 mg albumin/g Macroalbuminuria: >300 mg albumin/g

Creatinine

Proteinuria in AdultsProteinuria in Adults

Causes Causes

Glomerular Causes (Increased glomerulus Glomerular Causes (Increased glomerulus permeability) permeability)

Primary Glomerulonephropathy Primary Glomerulonephropathy Minimal Change Disease Minimal Change Disease IgA Nephropathy IgA Nephropathy Idiopathic membranous Idiopathic membranous Glomerulonephritis Focal segmental Focal segmental Glomerulonephritis Membranoproliferative Membranoproliferative Glomerulonephritis

Secondary Glomerulonephropathy Secondary Glomerulonephropathy Diabetes Mellitus ( (Diabetic Nephropathy) ) Systemic Lupus Erythematosus ( (Lupus Nephritis) Nephritis) Amyloidosis Preeclampsia ( (Pregnancy Induced Hypertension) ) Infection Infection

HIV Infection Hepatitis B Hepatitis C Poststreptococcal Glomerulonephritis Syphilis Malaria Endocarditis Endocarditis

Lung Cancer Gastrointestinal Cancer Gastrointestinal Cancer Lymphoma Renal transplant rejection Renal transplant rejection

Microscopic Urinalysis findings of findings of renal disease renal disease

Urine fats (Urine fats (Nephrotic Syndrome) ) Urine WBCs without bacteruria (Renal Urine WBCs without bacteruria (Renal

Interstitial) Interstitial) Dysmorphic erythrocytes (Glomerular Dysmorphic erythrocytes (Glomerular

disease) disease) Cellular or granular casts (chronic renal Cellular or granular casts (chronic renal

disease) disease) Urine Urine Eosinophils s

Urine Leukocyte EsteraseUrine Leukocyte Esterase

Mechanism Mechanism Neutrophil Granulocytes contain esterases s contain esterases Positive test suggests pyuria Positive test suggests pyuria

Dipstick requires 5 minutes to change color Dipstick requires 5 minutes to change color

Normal Normal Negative Negative

Abnormal: Positive Abnormal: Positive Urinary Tract Infection Vaginal contaminant Vaginal contaminant

Causes of false negative Leukocyte Causes of false negative Leukocyte esterase on Urinalysis esterase on Urinalysis

Inadequate time allowed for dipstick reading Inadequate time allowed for dipstick reading Increased Increased Urine Specific Gravity Urine Glucose present ( present (Glycosuria) ) Urine Ketones present (Ketonuria) s present (Ketonuria) Proteinuria Keflex Nitrofurantoin Tetracycline Gentamicin Vitamin C

Causes positive Leukocyte esterase Causes positive Leukocyte esterase and negative culture and negative culture

Chlamydia Ureaplasma urealyticum urealyticum Balanitis Bladder Cancer Nephrolithiasis Tuberculosis Urinary tract foreign body Urinary tract foreign body Glomerulonephritis Medications (Medications (Corticosteroid, Cytoxan) , Cytoxan)

Acute GlomerulonephritisAcute Glomerulonephritis

Labs: Initial (characterize condition) Labs: Initial (characterize condition) Urine sediment examination Urine sediment examination

Proteinuria Glomerular Glomerular Hematuria

Pigmented or Pigmented or Red Blood Cell casts casts Dysmorphic Dysmorphic Red Blood Cellss

Twenty-four hour urine collection Twenty-four hour urine collection 24 Hour Urine Protein Creatine Clearance Clearance

Renal insufficiencyRenal insufficiency

Acute GlomerulonephritisAcute Glomerulonephritis

Routine blood testing Routine blood testing Serum chemistries Serum chemistries Albumin and Albumin and Liver Function Tests s Total Cholesterol

If over age 40 with If over age 40 with Proteinuria >1 gram/24 hours >1 gram/24 hours Serum Protein Electrophoresis ( (SPEP) ) Urine Protein electrophoresis electrophoresis

Acute GlomerulonephritisAcute Glomerulonephritis Labs: Next (Screen for etiology) Labs: Next (Screen for etiology)

Serum Complement (C3, C4, CH50) Serum Complement (C3, C4, CH50) Antinuclear Antibody (ANA) (ANA) Rheumatoid Factor (RF) (RF) Erythrocyte Sedimentation Rate (ESR) (ESR) Anti-Anti-Glomerular Basement Membrane Antibody titer titer Hepatitis serology (Hepatitis serology (HBsAg, , xHBc IgM, HCV) , HCV) Anti-Anti-Neutrophilic cytoplasmic ic cytoplasmic Antibody ( (ANCA) ) Anti-streptolysin O titer ( (ASO Titer) ) Human Immunodeficiency Virus (HIV) (HIV)

ACUTE PYELONEPHRITISACUTE PYELONEPHRITIS Labs Labs

Urinalysis Leukocyte esterase or nitrite positive esterase or nitrite positive Hematuria may be present may be present Microscopic examination may show WBC casts Microscopic examination may show WBC casts

Urine Culture (positive in 90% of pyelonephritis) (positive in 90% of pyelonephritis) Diagnosis requires at least 10,000 CFU/mm3 Diagnosis requires at least 10,000 CFU/mm3 Consider lower threshold in men and in pregnancy Consider lower threshold in men and in pregnancy

Blood Culture indications (not indicated in most cases) indications (not indicated in most cases) Immunocompromised patient Immunocompromised patient Unclear diagnosis Unclear diagnosis

Hematogenous source suspectedHematogenous source suspected

Acute Renal FailureAcute Renal Failure

Urinalysis with Urine sediment examination with Urine sediment examination Urine Specific Gravity

Prerenal Failure: Specific Gravity >1.020 : Specific Gravity >1.020 Intrarenal Failure: Specific Gravity 1.010 - 1.020 Intrarenal Failure: Specific Gravity 1.010 - 1.020

Vascular disease Vascular disease Urine RBCs often present Urine RBCs often present

Glomerulonephritis Urine RBCs Urine RBCs Granular casts Granular casts Proteinuria

Acute Renal FailureAcute Renal Failure Interstitial Nephritis

Pyuria Pyuria Eosinophils s White Blood Cell and and Eosinophil casts casts

Drug hypersensitivity nephritis Drug hypersensitivity nephritis Eosinophils s

Tubular Necrosis Tubular Necrosis Pigmented granular casts Pigmented granular casts Tubular epithelial cells Tubular epithelial cells Granular casts Granular casts

Prerenal Failure Hyaline Casts Hyaline Casts

Autoimmune Testing for Glomerular Autoimmune Testing for Glomerular Disease Disease

Antinuclear Antibody (ANA) (ANA) Antineutrophil Cytoplasmic Antibody Antiglomerular basement membrane Antiglomerular basement membrane

Antibody

NKF Classification System NKF Classification System

Stage 1: GFR >90 ml/min despite kidney damage Stage 1: GFR >90 ml/min despite kidney damage Microalbuminuria present Microalbuminuria present

Stage 2: Mild reduction (GFR 60-89 min/min) Stage 2: Mild reduction (GFR 60-89 min/min) GFR of 60 may represent 50% loss in function GFR of 60 may represent 50% loss in function Parathyroid Hormone starts to increase starts to increase

Chronic Renal FailureChronic Renal Failure

Stage 3: Moderate reduction (GFR 30-59 Stage 3: Moderate reduction (GFR 30-59 ml/min) ml/min)

Calcium absorption decreases Calcium absorption decreases Malnutrition onset Malnutrition onset Anemia secondary to secondary to Erythropoietin deficiency deficiency Left Ventricular Hypertrophy

Stage 4: Severe reduction (GFR 15-29 ml/min) Stage 4: Severe reduction (GFR 15-29 ml/min) Serum Triglycerides increase Serum Triglycerides increase Hyperphosphatemia Hyperphosphatemia Metabolic Acidosis Metabolic Acidosis Hyperkalemia Hyperkalemia

Stage 5: Kidney Failure (GFR <15 ml/min) Stage 5: Kidney Failure (GFR <15 ml/min) Azotemia Azotemia

Acute Interstitial NephritisAcute Interstitial Nephritis Urinalysis Urinalysis

Eosinophiluria Eosinophiluria Proteinuria Proteinuria Fractional Excretion of Sodium >1% Fractional Excretion of Sodium >1%

Renal Function tests with renal insufficiency Renal Function tests with renal insufficiency Serum Creatinine increased Serum Creatinine increased Blood Urea Nitrogen increased Blood Urea Nitrogen increased

Miscellaneous Miscellaneous Hyperchloremic Metabolic Acidosis Hyperchloremic Metabolic Acidosis