MLS Review - AUBF - Renal and Metabolic Diseases

MEDICAL LABORATORY SCIENCE REVIEW ANALYSIS OF URINE AND OTHER BODY FLUIDS: RENAL AND METABOLIC DISEASES OUTLINE • Renal Diseases • Metabolic Diseases o Glomerular Disease o Qualitative Test: Screening of o Tubular Disease Metabolic Disorders o Tubulointerstitial Disease & o Metabolic Disorders Urinary Tract Infections o Carbohydrate Disorders o Vascular Disease TUBULAR DISEASE ACUTE TUBULAR NECROSIS (ATN) • • Destruction of Renal Tubular Epithelial Cells 2 Distinct Types: o Ischemic o Toxic • Ischemic ATN o Follows hypotensive event that result in decrease perfusion of the kidneys followed by renal tissue ischemia o Principal Cause: ▪ Sepsis ▪ Shock ▪ Trauma Toxic ATN o Results from exposure to nephrotoxc agents o Caused by variety of agents separated into categories: ▪ Endogenous ▪ Exogenous o Endogenous Nephrotoxin - Normal solutes or substances that become toxic when their concentration in the bloodstream is excessive: ▪ hemoglobin - hemoglobinuria - severe hemolytic events ▪ myoglobin - myoglobinuria -rhabdomyolyis ▪ uric acid ▪ immunoglobulin light chain o Exogenous Nephrotoxin - Substances ingested or absorbed ▪ therapeutic agents ▪ anesthetics ▪ radiographic contrast media d. chemotherapeutic drugs ▪ recreational drugs ▪ industrial chemicals RENAL DISEASES • • • • • Classified into 4 Types: Based on morphologic component initially affected Glomerular - Most often are immune-mediated Tubular - Result from infectious or toxic substances Interstitial - Result from infectious or toxic substances Vascular - Causes renal perfusion that subsequently induces both morphologic & functional changes in the kidney • GLOMERULAR DISEASE • Nephrotic Syndrome o Increased permeability of the glomeruli to the passage of plasma proteins (albumin) o Heavy Proteinuria (3.5g/day) o Hypoproteinemia (Plasma albumin usually <3g/dL → liver synthesis unable to compensate for the large amount of protein EXCRETED in the urine. o Hyperlipidemia (increased plasma levels of triglycerides, cholesterol, phospholipids, & VLDL) TYPES OF GLOMERULONEPHRITIS • • • • • Acute Glomerulonephritis o One cause: Post-Streptococcal Infection → known as: Acute Poststreptococcal Glomerulonephritis ▪ Group A β-hemolytic Streptococci - those with M protein in their cell wall induces this type of nephritis) o Blood: Elevated ASO Titer o Non-AGN: non-streptococcal agent (bacteria: pneumococci; viruses: mumps, Hepa B; parasitic infection: malaria) Focal Segmental Glomerulonephritis o Sclerosis of the glomeruli o Focal - Occurring in some glomeruli o Segmental - Affecting specific area of the glomerulus o Predominant Feature: PROTEINURIA Membranoproliferative Glomerulonephritis o Cellular Proliferation of the mesangium along with leukocyte infiltration thickening of the glomerular basement membrane IgA Nephropathy o Most prevalent type of glomerulonephritis world wide o Deposition of IgA in the glomerular mesangium Chronic Glomerulonephritis o Development: Slow and Silent o 80%: have previously some form of glomerulonephritis o 20%: form of glomerulonephritis that has been unrecognized TUBULAR DYSFUNCTION • Single Defect in Proximal Tubular Dysfunction o Renal Glucosuria - Impaired ability to reabsorbed glucose o Cystinuria (Cystine and Dibasic AA) - Impaired ability to reabsorbed specific amino acids o Hartnup Disease (Monoamino - Monocarboxylic AA) - Impaired ability to reabsorbed specific amino acids o Bartter's Syndrome - Impaired ability to reabsorb sodium o Renal Tubular Acidosis Type Il - Impaired ability to reabsorb bicarbonate o Idiopathic Hypercalciuria - Impaired ability to reabsorb calcium o Hypocalciuric Familial Hypercalcemia - Excessive reabsorption of calcium o Gordon's Syndrome - Excessive reabsorption of sodium o Pseudohypoparathyroidism - excessive reabsorption of phosphate 1 o • Fanconi Syndrome - Generalized loss of proximal tubular function ▪ Not reabsorbed form the ultrafiltrate excreted in the urine: (AA, Glucose, Water, Phosphorous, Potassium, Calcium) Distal Tubular Dysfunction o Familial Impaired Hypophosphatemia (Vitamin D Resistant Rickets) - ability to reabsorb phosphate o Idiopathic Hypercalciuria - Impaired ability to reabsorb calcium o Renal Tubular Acidosis, Types I and IV - Impaired ability to acidify urine o Renal Salt-Losing Disorder - Impaired ability to retain sodium o Nephrogenic Diabetes - Impaired ability to concentrate urine o Liddle's Syndrome - Excessive reabsorption of sodium o Renal Phosphaturia - Inability to reabsorb inorganic phosphates o • • TUBULOINTERSTITIAL DISEASE & URINARY TRACT INFECTIONS URINARY TRACT INFECTIONS • • • • • • Lower UTI o Urethra (Urethritis) o Bladder (Cystitis) ▪ Painful Urination (Dysuria) ▪ Burning Sensation ▪ Frequent urge to urinate Upper UTI o Renal Pelvis Alone (Pyelitis) o Renal Pelvis including Interstitium (Pyelonephritis) Acute Pyelonephritis o Bacterial infection that involves the renal tubules, interstitium, renal pelvis o Mechanism: ▪ Movement of bacteria from the lower urinary tract to the kidney ▪ Localization of the bacteria from the bloodstream in the kidneys hematogenous infection Chronic Pyelonephritis - Develops when permanent inflammation of renal tissue causes permanent scarring that involves the renal calyces and pelvis Acute Interstitial Nephritis - allergic response to the interstitium of the kidney o Most common cause: Acute Allograft Rejection of transplanted kidney Yeast Infections - Candida species (e.g. Candida albicans) normal flora of GIT vagina o Proliferation of yeasts due to: changes in pH, adversely disrupted by antibiotics Mechanism: ▪ Pre-Renal - result from decrease renal blood flow (25% of cases) • Urine sodium concentration is low increased amount of sodium being reabsorbed ▪ Renal - renal damage, can result from glomerular, tubular or vascular disease process • Increased Urinary Excretion Of Sodium • Approx. 65% of cases ▪ Post-Renal - obstruction in the urine flow • Approx. 10% of cases Chronic Renal Failure o Progressive loss of renal function caused by: ▪ Irreversible & intrinsic renal disease ▪ Decreasing GFR slowly but continuously decreases o "End-stage renal disease end-stage kidneys" - CRF that progresses to advanced renal disease Calculi o “Stones" - renal calyces, pelvis, bladder, ureter o Calcium 75% ▪ With Oxalate 35% ▪ With Phosphate 15% ▪ With others 25% o Magnesium Ammonium Phosphate 15% o Uric Acid 6% o Cystine 2% METABOLIC DISEASES QUALITATIVE TEST: SCREENING OF METABOLIC DISORDERS • • • • • • Ferric Chloride Test o Alkaptonuria (Homogentisic Acid) o MSUD o Melanoma (Melanin) o PKU Ammoniacal Silver Nitrite - Alkaptonurla (Homogentesic Acid) Benedict's Test - Alkaptonuria (Homogentesic Acid) Nitrosonaphthol Test - Tyrosinuria Hoesch Test - Porphyria (Porphobilinogen) Watson-Schartz Test - Porphyria (Porphobilinogen) QUALITATIVE TEST: SCREENING OF METABOLIC DISORDERS LIVER & KIDNEY • • • • Actively involved in the metabolism of Amino Acids Transamination: Interconvertion of AA Deamination: Degradation of AA mS AA → results in formation of ammonium ions → this Al is used to form → Urea (subsequently eliminated from the body by the kidneys) VASCULAR DISEASE • AMINOACIDURIA Acute Renal Failure o Clinically sudden: ▪ Decrease of GFR ▪ Azotemia ▪ Oliguria (Urine Output <400mL) • • Overflow Aminoaciduria o Cause: Increase in the plasma levels of AA o Renal Threshold for AA reabsorption: exceeded → additional AA are excreted in the urine No-Threshold Aminoaciduria o AA not reabsorbed by the tubules o Increase in blood increase in urine 2 • • • Renal Aminoaciduria o Plasma levels of AA: normal o Cause: Defect in tubules (congenital/acquired) → Not reabsorbed by the tubules = increase amount in urine Primary Aminoaciduria o a.k.a. "inbom errors of metabolism o Result from: inherited defect o 2 Types of Defects: ▪ Enzyme is defective (deficient) in the specific AA metabolic pathway ▪ Tubular Reabsorptive Dysfunction Secondary Aminoaciduria o Induced by: Severe liver disease or Generalized tubular dysfunction (e.g. Fanconi Syndrome) CYSTINOSIS • • • • • MOI: Autosomal Recessive Lysosomal Storage Disease → results in → deposition of cystine in the lysosomes of cells throughout the body (Kidneys, Eyes, Bone Marrow Spleen) Nephropathic Cystinosis o Most common severe form o Accumulated cystine crystallizes within the proximal tubular cells of the nephrons → causing → generalized tubular dysfunction → development of fanconi syndrome o Evident: FIRST YEAR OF LIFE Intermediate Cystinosis o Rare form o Clinical Features: Same with Nephropathic Cystinosis o Evident: Adolescence Ocular Cystinosis o Rare form o Cystine deposition in the cornea → Ocular Impairment CYSTINURIA • • MOL Autosomal Recessive Due to: Nephrones (PTC) = unable to reabsorbed AA (cysteine, dibasic AA e.g. arginine, lysine, ornithine) ALKAPTONURIA • • • • MOI: Autosomal Recessive Excretion of large amount of Homogentisic Acid (HGA) in the urine Unusual darkening of the urine when alkali is added Deficient Enzyme: homogentisic acid oxidase TYROSINURIA • Increased amount of tyrosine in the urine occurs when tyrosine levels in plasma is abnormally high MELANURIA • • • Melanin: Color of hair, eyes, & skin Hypomelanosis/Albinism: Defective melanin production Melanuria (Increased excretion of urinary melanin) = increased production of melanin its colorless precursors (e.g. 5,6- dihydroxyindole) CARBOHYDRATE DISORDERS • • • Diabetes Mellitus o "Diabetes" → copious amount of urine (polyuria) that this disorder produces o "mellitus" → means "sweet" o Polyuria with presence of glucose in the urine o High: SG Diabetes insipidus o "Diabetes" → copious amount of urine (polyuria) that this disorder produces o "insipidus" → refers to "bland taste" of urine produced o LOW: SG Galactosemia o Enzymes Responsible for Galactosemia: ▪ Galactose 1-phosphate uridylyltransferase (GALT) ▪ Galactokinase (GALK) ▪ Uridine diphosphate galactose-4epimerase (GALE) o MAPLE SYRUP URINE DISEASE • • • MOI: Autosomal Recessive Accumulation of branched-chain AA (leucine, isoleucine, valine) and their corresponding a-keto acids in blood, urine, CSF Deficient Enzyme: Branched-Chain a-Keto Acid Dehydrogenase (BCKD) PHENYLKETONURIA • • • • MOI: Autosomal Recessive Increased urinary excretion of phenylpyruvic acid (a ketone) and its metabolites Deficient Enzyme: Phenylalanine Hydroxylase Urine, Sweat Breath: Characteristic Mousy/Musty Odor o caused by Phenylacetic Acid o MOI: Autosomal Recessive 3