Renal Diseases PPT

1 Renal Diseases  2 Outline Glomerular Disorders Tubular Disorders Interstitial Disorders Renal Failure and Renal Calculi Metabolic Disorders  3 Introduction  U...

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  Streptococci form immune complexes with their corresponding antibodies and become deposited on glomerular membranes  Affects all ages  Commonly in children 4-12 years old  Acute Poststreptococcal 8 Glomerulonephritis  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 9 (RPGN)  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 10 Glomerulonephritis  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)  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  Treatment the urinary sediment of a  patient with chronic Focuses on identifying the underlying cause if known gromerulonephritis complicated  NS may go away once the underlying cause has been treated with nephrotic syndrome  Reducing high cholesterol, blood pressure, and protein in urine through diet, medications, or both  16 Tubular Disorders 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 Disorders There are over 65,000 families affected by Metabolic Diseases in the USA There are several hundred metabolic  Adreno- diseases… - McArdle’s Disease leukodystrophy - Mitochodrial Disorders  Galactosuria - Niemann-Pick Disease  Gaucher Disease - Prader-Willi Syndrome  Glycogen Storage Disease  53 Who has a question???