Urinalysis and other Body Fluids - Renal Diseases

o o o o ANALYSIS OF URINE AND OTHER BODY FLUIDS MODULE 5 - RENAL DISEASE OUTLINE • • • Introduction • Glomerular Diseases o Glomerulonephritis o Nephrotic Syndrome Tubular Disorders • o Acute Tubular Necrosis o Hereditary and Metabolic • Tubular Disorders Tubulointerstitial Diseases o Acute Pyelonephritis o Chronic Pyelonephritis o Acute Interstitial Nephritis Renal Failure o Acute Renal Failure Renal Lithiasis INTRODUCTION • • • Over the years, urinalysis results have been used extensively to evaluate the presence of disease processes in the body. Urinalysis results, at times, may be able to detect the onset of disease even before the onset of symptoms. Furthermore, urinalysis results also give out information as to disease progression and effectiveness of treatment. Classification of Renal Diseases o Glomerular disorders - target the glomerulus o Tubular disorders - target the nephrons o Interstitial disorders - affecting the interstitium and the tubules GLOMERULAR DISORDERS • • Majority are of immunologic disorders o Immune complexes from immunologic reactions throughout the body o Increased serum immunoglobulins are deposited on the glomerular membranes o Immune system mediators: complement migrate and produce change and damage to membranes o Focused on antigen-antibody complex o These immune complexes might pile up to the glomerulus causing damaged. Nonimmunologic o Chemicals and toxins, deposition of amyloid material and acute phase reactants, electrical charge interference, membrane thickening GLOMERULONEPHRITIS • • • General term for sterile, inflammatory process affecting the glomerulus Causes blood, protein, and casts in urine Types of glomerulonephritis progress through various disorders o Acute glomerulonephritis (AGN) to chronic glomerulonephritis (CGN) to nephrotic syndrome to renal failure • RAPIDLY PROGRESSIVE (CRESCENTIC) GLOMERULONEPHRITIS • • • • • • • • • • • Morphological changes resembling crescentric GN Autoimmune disorder against glomerular and alveolar basement membranes o Autoimmune = production of antibodies against glomerulus and alveolar basement membrane Cytotoxic antibody following viral respiratory diseases o Antiglomerular basement membrane antibody Hemoptysis, hematuria, proteinuria, RBC casts Chronic glomerulonephritis to end-stage renal failure is common WEGENER’S GRANULOMATOSIS • • • • • Fever, edema around the eyes, oliguria, and hematuria o Caused by immune complexes deposited in the urine o Oliguria - difficulty in urinating; urine insufficiency o Hematuria – blood in the urine Immune complexes deposit on glomerular membranes Hematuria, proteinuria, oliguria More serious acute form → renal failure Systemic immune disorders o Macrophages damage capillary walls o Fibrin = permanent damage to capillary tufts Urinalysis similar to AGN progresses to more abnormal, elevated protein, low glomerular filtration rate (GFR) May have increased fibrin degradation products (FDP), cryoglobulins and IgA immune complex depositions GOODPASTURE’S SYNDROME ACUTE POSTSTREPTOCOCAL GLOMERULONEPHRITIS (AGN) • Red blood cell (RBC) casts, dysmorphic RBCs Hyaline and granular casts White blood cells Anti–group A streptococcal enzyme tests ▪ ASO test – Anti-streptococcal Test is the key to diagnosis. ▪ S. pyogenes is the causative agent ▪ It will start on having a sore throat in children (strep throat). If not diagnosed immediately, the bacteria will travel to the blooding leading to rheumatoid fever, a heart disease. ▪ Patient will have a tea-colored urine. ▪ Treatment is antibiotics that will be injected for life to prevent reoccurrence of bacteria Group A streptococcal infections from organisms with M protein in the cell wall (S. pyogenes) Rapid anti–group A streptococcal enzyme tests o Ease in diagnosis o Decline in incidence Inflammation and granulomas in small blood vessels of kidney and respiratory system Key to diagnosis o Antineutrophilic cytoplasmic antibody (ANCA) Neutrophils initiate immune response, producing granulomas Pulmonary symptoms first, then hematuria, proteinuria, RBC casts, elevated BUN and creatinine levels o BUN and creatinine levels – blood test indicating kidney function. o Normal CL = 88-150 mg/dL Immunofixation for p-ANCA/c-ANCA HENOCH-SCHÖNLEIN PURPURA • • • • • • Children following upper respiratory infections Raised, red patches on skin Blood in sputum and possibly stools Renal involvement is the most serious complication of the disorder o Proteinuria and hematuria, RBC casts 50% complete recovery Follow patients for more serious renal problems MEMBRANOUS GLOMERULONEPHRITIS • • • • IgG immune complexes cause pronounced thickening on glomerular basement membrane o IgG - most prevalent immunoglobulin in the body Systemic lupus erythematosus, Sjögren’s syndrome, secondary syphilis, hepatitis B, gold and mercury treatments, malignancy o These aid in diagnosis o Often unknown etiology o Syphilis - STD caused by bacteria Treponoma pallidum; patient will have shunk in reproductive organs (primary) or attack neighboring organs (secondary) ▪ These aid in diagnosis ▪ Often unknown etiology Slow progression, remission, nephrotic syndrome Microscopic hematuria, very high protein MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN) • • • • Type 1: increased cellularity in the subendothelial cells of the mesangium o Thickening of capillary walls Type 2: extremely dense deposits in the glomerular basement membrane o Poor prognosis Hematuria, proteinuria, ↓ complement Autoimmune disorders, infections, malignancies NEPHROTIC SYNDROME • • • • • • MINIMAL CHANGE DISEASE (LIPID NEPHROSIS) • • • • • Progression from previous disorders Fatigue, anemia, hypertension, edema, oliguria gradually worsening Hematuria, proteinuria, glycosuria (tubular damage), many types of casts including broad and waxy casts Markedly decreased GFR • • • • ACUTE TUBULAR NECROSIS • • • • • FANCONI SYNDROME • • • • • • • • Ischemia: severe decrease in blood flow o Trauma, surgery, cardiac failure, electricity, toxogenic bacteria, anaphylaxis Nephrotoxic agents: aminoglycosides, amphotericin B, ethylene glycol, heavy metals, mushroom poisoning, hemoglobin, myoglobin Remove cause and manage symptoms Noticeable renal tubular epithelial (RTE) cells and casts and RTE fragments Hyaline, waxy, granular, broad casts HEREDITARY AND METABOLIC TUBULAR DISORDERS • • • Similar to nephrotic syndrome but affects only certain numbers and areas of glomeruli; podocytes are damaged IgM and C3 immune deposits Moderate to heavy proteinuria; microscopic hematuria Heroin and analgesic abuse, HIV TUBULAR DISORDERS IMMUNOGLOBULIN A NEPHROPATHY (BERGER’S DISEASE) Most common cause of glomerulonephritis IgA complexes on glomerular membrane o IgA – weak antibody found in saliva, tears and colostrum of mothers Increase serum IgA Early macroscopic hematuria from exercise or infection with spontaneous recovery 20 years later: gradual progression to chronic glomerulonephritis Granular and disintegrating RBC casts in urine Children, allergic reactions, immunization, HLA-B12 o HLA – Human Leukocyte Antigen Heavy proteinuria, edema, transient hematuria; normal BUN and creatinine levels Good prognosis, steroids, remission FOCAL SEGMENTAL GLOMERULONEPHRITIS CHRONIC GLOMERULONEPHRITIS (CGN) • • Acute onset from systemic shock (low blood pressure) or glomerulonephritis complication Glomerular membrane damage and changes in podocyte electrical charges Protein passes through membrane; serum albumin depleted, causing increased lipid production Edema from loss of oncotic pressure Tubular damage Urinalysis o Marked proteinuria >3.5 g/day o Fat droplets, oval fat bodies, fatty casts, renal tubular epithelial cells & casts, waxy casts, microscopic hematuria Generalized proximal convoluted tubule reabsorption failure Inherited with cystinosis and Hartnup disease Acquired: heavy metals, outdated tetracycline Complication of multiple myeloma, renal transplant Glycosuria and electrolyte imbalance ALPORT’S SYNDROME • • • Inherited sex-linked and autosomal disorder affecting basement membrane Males more severely affected Macroscopic hematuria w/ respiratory infections by age 6 • • Membrane laminated with thinning; no immune complexes Mild to persistent hematuria, later nephrotic syndrome, renal failure for some • • UROMODULIN ASSOCIATED KIDNEY DISEASES (UMKD) • • • Formerly Tamm-Horsfal protein is the only protein produced by the kidney Inherited disorder that results in an abnormal buildup of uromodulin in the tubular cells causing their destruction Patients have elevated serum uric acid and gout at an early age, occurs before renal symptoms DIABETIC NEPHROPATHY • • • • • • • Most common cause of end-stage renal disease o Diabetes- disease of the pancreas but the first organ to be attacked is the kidney Glomerular basement membrane thickening Increased proliferation of mesangial cells Increased deposition of cellular and acellular material within matrix of Bowman’s capsule and around capillary tufts Deposition associated with glycosylated proteins from poorly controlled diet Sclerosis of vascular structure Reason for early microalbumin testing NEPHROGENIC DIABETES INSIPIDUS • • Two types o Nephrogenic: failure of tubules to respond to antidiuretic hormone (ADH), inherited sex-linked recessive or lithium and amphotericin B exposure, polycystic kidneys and sickle cell anemia o Neurogenic: failure to produce ADH Urine: pale yellow, low specific gravity (SG), possible negative results for other tests CHRONIC PYELONEPHRITIS • • • • • • • • • • • • • • Infections and inflammations affecting the interstitium and the tubules Most common renal disease is urinary tract infection (UTI) Cystitis (bladder infection) is very common o Untreated: progresses to upper urinary tract o Many WBCs, bacteria, increased pH, mild proteinuria, hematuria o WBCs in urine called pyuria; In males: gonorrhea ACUTE PYELONEPHRITIS • Ascending movement of bacteria o Conditions affecting emptying of bladder o Calculi, pregnancy, reflux of urine from bladder to ureters Allergic reaction causing inflammation of interstitium and tubules; involves WBCs o We have five allergic reactions in our system Medication allergy to penicillin, methicillin, ampicillin, cephalosporins, NSAIDs, thiazide diuretics Discontinue and use steroids to treat Urinalysis: hematuria, proteinuria, ↑ WBCs, WBC casts, no bacteria Hansel stain for eosinophils o Eosinophils – responsible for allergic reactions (orange granules) o Basophils – black granules RENAL FAILURE • • Affects only the reabsorption of glucose Inherited as autosomal recessive Decreased number of glucose transporters in tubules Decreased affinity of transporters for glucose Glycosuria with normal blood glucose level TUBULOINTERSTITIAL DISEASES Damage to tubules, possible renal failure Congenital structural defects causing reflux are most common cause o Inborn defects Can affect emptying of collecting ducts Often diagnosed in children Early urinalysis similar to acute pyelonephritis Later granular, waxy, and broad casts; increased protein, hematuria, ↓ SG ACUTE INTERSTITIAL NEPHRITIS RENAL GLYCOSURIA • • • • • Rapid onset, urinary frequency, burning, lower back pain Urinalysis: similar to cystitis with one exception: presence of WBC casts Acute and chronic forms Chronic renal failure o Progression from original disorders to end-stage renal disease o GFR <25 mL/min, ↑↑ BUN and creatinine levels, electrolyte imbalance, isosthenuria, proteinuria, renal gycosuria; ↑ granular, waxy, broad casts o Normal BUN = 7-20 mg/dL o Renal failure – increased four times ACUTE RENAL FAILURE • • • • Sudden onset, often reversible Decreased blood flow (prerenal), acute disease (renal), renal calculi and tumors (postrenal) Urinalysis related to cause o RTE cells = decreased blood flow o RBCs = glomerular damage o WBCs and casts = infection/inflammation o Urothelial cells = possible bladder tumor Causes of Acute Renal Failure o Prerenal ▪ Decreased blood pressure/cardiac output ▪ Hemorrhage ▪ Burns ▪ Surgery ▪ Septicemia o Renal ▪ Acute glomerulonephritis ▪ Acute tubular necrosis ▪ Acute pyelonephritis ▪ Acute interstitial nephritis o o Postrenal ▪ Renal calculi ▪ Tumors ▪ Crystallization of ingested substances RENAL LITHIASIS • • • • • • • Renal calculi (kidney stones) in calyces and pelvis of kidney, ureters, bladder o Gallstones – cholelithiasis (80% cholesterol; 10-20% bile acids or bile salts) Staghorn, round and smooth, barely seen o Fresh blood – damage is in the ureter or bladder Severe back pain radiating from lower back to legs when passing Lithotripsy: high-energy shock waves break up stones Also surgical removal Formation conditions similar to crystals o pH, concentration, urine stasis o No exact cause of formation known o Increased in the summer, dehydration Types of stones o 75% calcium oxalate or phosphate o Magnesium ammonium phosphate (struvite) ▪ UTI and ↑ pH, like triple phosphate crystals o Uric acid: increased purine diet o Cystine: hereditary cystinosis CHRONIC KIDNEY DISEASE (VIDEO) CHRONIC KIDNEY DISEASE • • • • • • • Causes: o Diabetes (Type 1 and 2) o High blood pressure (hypertension) o Metabolic syndrome 9excess abdominal fat) o Glomerulonephritis (inflammation of glomeruli) o Interstitial nephritis (inflammation of interstitium) o Polycystic kidney disease (cysts in kidneys) o Vesicoureteral reflux (urine to back up into kidneys) o Recurrent kidney infection (pyelonephritis) o Chronic urinary obstruction (enlarged prostate, kidney stones, cancers) The severity of renal disease can be evaluated by glomerular filtration rate (GFR) GFR = function of serum creatinine (Normal = > 90mL/min; End stage = GFR < 15 mL/min) Symptoms develop slowly over time progressing from renal insufficiency to end-stage renal failure. Renal adaptation – initial loss of renal tissue does not produce any symptoms because the remaining healthy tissue becomes more active and can temporarily compensate to the loss The ability to concentrate the urine is usually the first to be impaired followed by fatigue, loss of appetite and decreased mental ability. When kidney functions fail: o Accumulation of nitrogen wastes = nausea, vomiting, confusion, seizures, o Reduced excretion of hydrogen ion = increased blood acidity or metabolic acidosis o Reduced potassium excretion leads to hyperkalemia which may cause cardiac arrhythmias. • • Reduced phosphate excretion results to hyperphosphatemia o Reduced calcitriol production leading to hypocalcemia which means more parathyroid hormones causing calcium to be released from bones (secondary hyperparathyroidism) o Renal osteodystrophy – bones become thin and weakened. Symptoms include bone and joint pain and increased risk of fractures. o Reduced secretion of erythropoietin can lead to anemia. Renal Function Tests o Serum creatinine and urea (BUN) o Serum electrolytes o Urinary sediment o Urine output o Urinalysis (sodium, urea, protein, creatinine) o Ultrasound is also performed to detect renal obstruction. It may also help distinguish CKD from Acute Kidney Injury-CKD patients who usually have smaller kidneys. Treatments o Control the underlying condition (diabetes, high BP) o Treat complications (acidosis, anemia) o Nutrition supplements (calcium, vitamin D) and restrictions (less potassium, proteins) o End-stage kidney disease: dialysis or kidney transplantaton