Renal Diseases: Glomerular, Tubular, and Metabolic Disorders
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This document outlines different renal diseases. It covers glomerular disorders, tubular disorders, interstitial disorders, renal failure, renal calculi, and metabolic disorders affecting the kidneys. Conditions mentioned include glomerulonephritis, nephrotic syndrome, and Fanconi's syndrome.
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1 Renal Diseases 2 Outline Glomerular Disorders Tubular Disorders Interstitial Disorders Renal Failure and Renal Calculi Metabolic Disorders 3 Introd...
1 Renal Diseases 2 Outline Glomerular Disorders Tubular Disorders Interstitial Disorders Renal Failure and Renal Calculi Metabolic Disorders 3 Introduction Urinalysis not only provides information about renal disease but may shed light on metabolic diseases as well Urinalysis may detect abnormalities before symptoms appear Tool for monitoring progression of diseases and evaluating the effectiveness of therapy Disorders throughout the body can affect renal function and produce abnormalities in the urinalysis The kidneys are consistently exposed to potentially damaging substances Renal disease is classified as being glomerular, tubular, or interstitial 4 Glomerular Disorders Introduction to Glomerular 5 Disorders Renal disease of glomerular origin Majority of disorders associated with the glomerulus are of immune origin Immune complexes from immunologic reactions throughout the body Increased serum immunoglobulins are deposited on the glomerular membranes Immune system mediators: complement migrate and produce change and damage to membranes Non-immunologic causes include exposure to chemicals and toxins Nephrotic syndrome Glomerulonephritis (GN) 6 In general: Inflammatory process that affects the glomerulus and is associated with the finding of blood, protein and urinary casts Proteinuria Hematuria Types of glomerulonephritis progress through various disorders Acute glomerulonephritis-> chronic glomerulonephritis -> nephrotic syndrome -> renal failure Acute Poststreptococcal Glomerulonephritis (AGN) Sudden onset of symptoms consistent with damage to the glomerular membrane Immune complexes deposit on glomerular membranes Symptoms due to damage to glomerular membrane Edema, Fever, Fatigue, Nausea, Hypertension, Oliguria, Hematuria Follows respiratory infections Usually certain strains of group A streptococcus Usually 1-4 weeks after infection of the pharynx or skin Etiology Streptococciform immune complexes with their corresponding antibodies and become deposited on glomerular membranes Affects all ages Commonly in children 4-12 years old Acute Poststreptococcal Glomerulonephritis 8 Urinalysis findings Hematuria, proteinuria, oliguria Red blood cell (RBC) casts, dysmorphic RBCs Hyaline and granular casts White blood cells Other Significant Tests Serum antistreptolysin O titer (ASO) if elevated indicates the disease is of the streptococcal origin Treatment Manage symptoms (hypertension) Maintain water and electrolyte balance Immune complexes will eventually clear the blood Permanent renal damage seldom occurs Rapidly Progressive Glomerulonephritis (RPGN)9 Syndrome in which damage to glomeruli is accompanied by rapid and progressive decline in renal function (within weeks to months) Can rapidly result in renal failure Increased risk is associated with systemic diseases (systemic lupus erythematosus) Etiology Deposition of immune complexes from systemic immune disorders on the glomerular membrane Most common in people aged 40-60 Slightly more common in men Rapidly Progressive Glomerulonephritis 10 Urinalysis findings Initially similar to acute GN but become more abnormal as disease progresses Markedly increased protein levels Macroscopic hematuria Red blood cell casts Other Significant Tests Low glomerular filtration rates (GFR) GFR is the rate at which an ultrafiltrate of plasma is produced by glomeruli per unit of time GFR is an estimate of the number of functioning nephrons Creatinine clearance is a test of glomerular filtration rate Treatment Immunosuppression Glucocorticoids & Cyclophosphamide Plasmapheresis to remove antibodies and immune complexes if necessary 11 Chronic Glomerulonephritis Acute and other glomerular diseases can turn into chronic depending on amount and duration of damage occurring to glomerulus Chronic can lead to renal failure (end stage renal disease) Etiology Marked decrease in renal function resulting from glomerular damage precipitated by other renal disorders Is subtle and progresses slowly until death, unless patient undergo dialysis or have renal transplant 12 Chronic Glomerulonephritis Urinalysis findings Hematuria Proteinuria Glucosuria Cellular and granular casts Waxy and broad casts Other Significant Tests Markedly decreased GFR Electrolytes Imbalance Treatment Management of precipitating condition Dialysis and Transplant may be necessary Nephrotic Syndrome Condition often caused by any of a group of diseases that damage the glomeruli The nephrotic syndrome is not itself a disease Marked by very high levels of protein in the urine & low levels of protein in the blood; swelling, especially around the eyes, feet, and hands Protein passes through membrane; albumin depleted, causing increased lipid production Usually a result of an underlying disease Can occur as a complication of acute and chronic glomerulonephritis Secondary to systemic diseases (diabetes mellitus, SLE, infections, malignancy) 14 Nephrotic Syndrome 2 Types Adult NS Childhood NS Can occur at any age but is most common between the ages of 1½ and 5 years It affects boys more often than girls Can progress into renal failure Hallmark is Massive proteinuria Low levels of serum albumin High levels of serum lipids Pronounced edema Increased permeability of the glomerular membrane results in: Passage of proteins into urine – albumin = proteinuria Depletion of plasma albumin increases loss of fluid into the tissues = edema & hypoalbuminemia Liver producing more lipids – increased lipids in circulation = high cholesterol (=lipidemia and lipiduria) 15 Nephrotic Syndrome Urinalysis findings Heavy proteinuria Microscopic hematuria Renal tubular cells Oval fat bodies Fat droplets Fatty and waxy casts Other Significant Tests Elevated Cholesterol, triglycerides Low serum albumin Clump of oval fat bodies from the Treatment urinary sediment of a patient with Focuses on identifying the underlying cause if known chronic gromerulonephritis NS may go away once the underlying cause has been treated complicated with nephrotic syndrome Reducing high cholesterol, blood pressure, and protein in urine through diet, medications, or both 16 Tubular Disorders 17 Introduction to Tubular Disorders Disorders affecting the renal tubules include those in which tubular function is disrupted as a result of actual damage to the tubules and those in which a metabolic or hereditary disorder affects the functions of the tubules 18 Acute Tubular Necrosis What is it? Acute tubular necrosis (ATN) is the death of tubular cells Acute onset of renal dysfunction usually resolved when underlying cause is corrected 2 Causes of ATN: Ischemic causes Damage to RTE cells produced by decreased blood flow = lack of oxygen presentation to the tubules (ischemia) Toxic causes Or presence of toxic substances in the urine filtrate 19 Acute Tubular Necrosis Causes of ischemic ATN: Shock Any severe condition decreasing the flow of blood throughout the body such as cardiac failures, sepsis, massive hemorrhage, burns Trauma Crushing injuries, surgical procedures Causes of toxic ATN: Exposure to nephrotoxic agents Aminoglycoside antibiotics Antifungal agents Radiographic dye Ethylene glycol (antifreeze) Heavy metals Other poisons Regardless, mechanism is oxidative damage from ROS 20 Acute Tubular Necrosis Urinalysis Microscopic hematuria Proteinuria Renal tubular epithelial cells Renal tubular epithelial cell casts Hallmark finding Hyaline, granular, waxy, broad casts Other Laboratory Findings Elevated serum creatinine, BUN Hyponatremia, hyperkalemia, hypocalcemia 21 Fanconi’s syndrome What is it? An impairment in the proximal tubular function of the kidney This damage causes certain compounds -- which should be absorbed into the bloodstream by the kidneys -- to be excreted in the urine instead Compounds that may be lost in the urine include glucose, amino acids, phosphorus, sodium, potassium, bicarbonate, water 2 Types Inherited Acquired (children and adults) Toxic agents Heavy metals, prescribed drugs Complication of multiple myeloma and renal transplant 22 Fanconi’s syndrome Symptoms Excess amounts of glucose, amino acids, phosphorus, sodium, potassium and bicarbonate in urine Urinalysis Glucosuria Other Lab Findings Treatment Treat underlying disease or the symptoms Diabetic Nephropathy Most common cause of end-stage renal disease Damage to the glomerular membrane occurs due to: Glomerular basement membrane thickening Increased proliferation of mesangial cells Increased deposition of cellular and acellular material within glomerular matrix Deposition associated with glycosylated proteins from poorly controlled diet Results in sclerosis of vascular structure Reason for early microalbumin testing 24 Non-Nephronic Disorders 25 Renal Interstitium The renal interstitium is the space between the nephron units Within the interstitium are interstitial cells that are in close proximity to the medullary blood vessels and tubule cells Considering close proximity between renal tubules and interstitium, disorders affecting the interstitium also affect the tubules Introduction to 26 Extranephric Disorders Most common of all renal diseases is the UTI (urinary tract infection) Can be upper urinary tract (renal tubules and interstitium) Or lower urinary tract (urethra and bladder) Interstitial Inflammatory Disorders Interstitial Nephritis Interstitial Cystitis Lower Urinary Tract Infaction 27 Cystitis- Infection of Bladder Urethritis- Infection of Urethra Symptoms Increased urine frequency Burning upon urination Urinalysis Pyuria Bacteriuria Microscopic hematuria Mild proteinuria Increased pH Other Lab Findings Positive Urine Culture Mild Leukocytosis Causative Organisms E. Coli- 85% of Community-Acquired Cases S. saphrophyticus- 10% of cases Wider variation in nosocomial cases Klebsiella, Pseudomonas, Enterococcus, Etc 28 Pyelonephritis (Upper UTI) Etiology Infection of the renal tubules and interstitium (can be referred to as kidney infection) Symptoms High fever, Vomiting, Radiating Abdominal Pain, Painful urination Occurs in acute and chronic forms Chronic is recurrent infections of the renal tubules and interstitium caused by structural abnormalities affecting the flow of urine Acute form have high rate of fatality (>40%) in elderly patients Acute Pyelonephritis Ascending movement of bacteria Conditions affecting emptying of bladder increase risk Calculi, pregnancy, reflux of urine from bladder to ureters Urinalysis Findings: similar to cystitis with one exception: presence of WBC casts Other Laboratory Findings Marked Leukocytosis (Neutrophilia) Positive Urine Cultures Causative Organisms Similar to Lower UTI Chronic Pyelonephritis Damage to tubules, possible renal failure Congenital structural defects causing reflux are most common cause Can affect emptying of collecting ducts Recurrent cycles of infection and inflammation cause scarring Most often diagnosed in children Early urinalysis similar to acute pyelonephritis Later: granular, waxy, and broad casts; increased protein, hematuria, ↓ renal concentration Acute Interstitial Nephritis (AIN) 31 What is it? Rapidly developing inflammation that occurs within the interstitium Causes Allergic reaction to medications that occur in the renal interstitium Antibiotics and nonsteroidal anti-inflammatory drugs Symptoms Renal dysfunction symptoms Oliguria, edema, possible decreased in GFR Fever Presence of skin rash Develop weeks after start of new medication Penicillin, methicillin, ampicillin, cephalosporins, sulfonamides Acute Interstitial Nephritis 32 Urinalysis Hematuria Proteinuria Pyuria WBC casts No bacteria (Sterile Pyuria) Staining for the presence of increased eosinophils may be useful to confirm diagnosis Other Laboratory Findings Eosinophilia in CBC Hyperkalemia Metabolic Acidosis Treatment Discontinuation of medication Administration of steroids to control inflammation 33 Renal Failure and Renal Calculi 34 Renal Failure Acute and chronic forms Chronic Renal Failure Often result of other renal disease that has progressed AKA End stage renal disease End stage renal disease characterized by: Decrease in the glomerular filtration rate Steadily rising serum BUN Blood urea nitrogen Waste product removed by the kidneys Tested in chemistry Urinalysis Proteinuria Glycosuria Granular, waxy, broad casts 35 Acute Renal Failure Sudden loss of renal function Frequently reversible Causes Prerenal Decreased cardiac output, burns, surgery, hemorrhage, septicemia Renal Renal diseases : Acute glomerulonephritis, acute tubular necrosis, acute pyelonephritis, acute interstitial nephritis Post renal Renal calculi, tumors Urinalysis Similar to chronic results Findings relate to the primary cause 36 Renal Calculi (Nephrolithiasis) AKA kidney stones Hardened mineral deposits that form in the kidney Originate as microscopic particles that develop into stones over time Form in the calyces and pelvis of the kidney, ureters and bladder Vary in size from barely visible to large stones Symptoms Waves of Excruciating Flank Pain (Renal Colic) Urinary Urgency Nausea/Vomiting Urinalysis No true indication on urinalysis Possible clumps of crystals in urine suggest condition right for forming calculi Hematuria is commonly seen when passing a stone Renal Calculi 37 Conditions favoring formation of renal calculi pH Chemical concentration High level of calcium, oxalate or uric acid Urinary stasis In dehydration, high levels of substances do not dissolve completely = may form crystals that slowly build into stones Common types of stones Calcium Calcium Phosphate or Oxalate 75-80% of stones High in take of calcium and/or oxalates Magnesium ammonium phosphate AKA Struvite Stones 10% of stones Assoicated with repeated UTIs Uric acid 9% of stones Primarily in Gout Cystine 1% of stones Only see in Cystinuria Renal Calculi Treatment/Management Increase fluid intake, urine output (diuretics) Stone may dissolve Small calculi (24 h Metabolites appear first in the blood Analyze by tandem mass spectrophotometry, MS/MS Amino Acid Disorders Disorders with urinary screening Phenylketonuria Tryosyluria Melanuria Alkaptonuria Maple syrup urine disease Organic acidemias Indicanuria Cystinuria Cystinosis Phenylalanine-Tyrosine Disorders Major inherited disorders Phenylketouria (PKU) Tyrosyluria Alkaptonuria Phenylketonuria (PKU) 47 Build-up of phenylalanine in the serum producing urinary overflow Caused by missing or non-functional phenylalanine hydroxylase Used in the breakdown of phenylalanine – if not present breakdown cannot occur Excess or build-up of phenylalanine leads to irreversible intellectual disability 1 in 10,000 to 20,000 births Results in severe intellectual disability Seizures, hyperactivity, development delay and psychiatric disturbances may be present Autosomal recessive Management: Eliminate phenylalanine from diet Meat, Eggs, Dairy, Soy, Nuts, Legumes, Artificial Sweeteners 48 Phenylketonuria Mousy odor to urine Required test on all newborns PKU Test Blood test Initial screening is not part of urinalysis, because increased blood levels of phenylalanine must occur prior to urinary excretion (which may take 2 – 6 weeks) Bacterial inhibition test by Guthrie Blood from a heelstick is absorbed into filter paper circles Blood impregnated disks are then placed on culture media streaked with the organism Bacillus subtilis Growth observed around disk indicates positive 49 Other Amino Acid Disorders Tyrosyluria (Tyrosinemia) Defect in Fumarylacetoacetase, tyrosine aminotransferase, or hydroxyphenylpyruvate dioxygenase Excess of tyrosine in the plasma producing urinary overflow Alkaptonuria Defect in Homogetiate 1,2-dioxygenase Involved in breakdown of tyrosine and phenylalanine Results in accumulation of homogentisic acid = black alkaline urine Liver & cardiac issues later in life Maple syrup urine disease Defect in Branched-Chain Alpha-Ketoacid Dehydrogenase Inability to metabolize branched amino acids Leucine, Isoleucine, Valine Infants exhibit failure to thrive within 1 week Results in increased keto acids in the urine Urine produces odor resembling maple syrup 50 Cystine Disorders Cystinuria Genetic defect in amino acid transporter proteins Cystine cannot be reabsorbed by renal tubules Increased cystine secretion through urine Urine will smell of sulfur Often asymptomatic unless stones form Cystinosis Lysosomal Storage Disease Defects in Cystinosin Membrane transport protein for lysosomes Causes increased intracellular cystine accumulation Toxic in many tissues Will also secrete cystine in urine Crystals and sulfur odor 51 Purine Disorders Lesch-Nyhan disease Inherited sex-linked recessive Massive excretion of uric acid crystals Motor defects, intellectual disability, self-destruction, gout, renal calculi Normal development 6 to 8 months Orange sand in diaper Be alert for increased uric acid crystals in pediatric patients Other Metabolic 52 Disorders Thereare over 65,000 families affected by Metabolic Diseases in the USA There are several hundred metabolic diseases… Adreno-leukodystrophy - McArdle’s Disease Galactosuria - Mitochodrial Disorders Gaucher Disease - Niemann-Pick Disease Glycogen Storage Disease - Prader-Willi Syndrome 53 Who has a question???
