UA Exam 3

Differentiate among renal diseases of various origins, including glomerular, tubular, interstitial, and vascular.

• Glomerular: Damage to filtration unit of kidney

• Tubular: Damage to reabsorption and secreting substances after filtration occurs

• Interstitial: Damage to interstitial → Connective tissue surrounding tubules, blood vessels, and supporting structures

Know the main cause to Glomerular Disorders

Immunologic (majority) and non-immunologic

Know the main cause to Immunologic Glomerular Disorders

• Immune complexes from immunologic reactions throughout the body

  • Chronic infection, autoimmune disorders, plasma cell disorders (multiple myeloma)

• Increased serum immunoglobulins are deposited on the glomerular membranes

  • Increased acute phase reactants: Tissue injury or trauma, infections

• Immune system mediators (complement) migrate and produce change and damage to membranes

Know the main cause to Non-Immunologic Glomerular Disorders

• Exposure to chemicals and toxins

• Disruption of electrical membrane

• Disruption of amyloid materials from chronic inflammation or acute-phase reactants

List the microscopic findings and diagnostic criteria associated with CGN

• Casts: Cellular, granular, waxy, broad

• No RTE

• Criteria:

  • Fatigue, anemia, hypertension, edema, worsening oliguria

    • Markedly decreased GFR

    • Hematuria, proteinuria, glycosuria

List the microscopic findings and diagnostic criteria associated with ATN

• RTE casts containing tubular fragments with three or more cells

• Notable RTE cells

• Casts: Hyaline, granular, waxy, broad

List the microscopic findings and diagnostic criteria associated with AIN

• Casts: WBC casts

• Criteria:

  • Hematuria, proteinuria

  • ↑ WBCs but no bacteria

  • ↓ GFR

List the microscopic findings and diagnostic criteria associated with Nephrotic syndrome

• Casts: Fatty and waxy casts

• RTE cells present

  • Fat droplets, oval fat bodies

Name three renal disorders that also involve acute respiratory symptoms

• Acute post-streptococcal glomerulonephritis (AGN): Follows a respiratory infection from certain strains of GBS  Immune complexes deposit on glomerular membranes

• Immunoglobulin A Nephropathy (Berger’s Disease): Most common cause of glomerulonephritis

  • Follows respiratory or GI viral infection → Stimulates IgA production → IgA complexes on glomerular membrane due to increased serum levels of IgA

• Goodpasture’s syndrome

Know the causes of Acute Renal Failure

• Acute: Sudden onset, often reversible

  • Prerenal: Decreased blood/pressure/cardiac output, Hemorrhage, burns, surgery, septicemia

  • Renal: Acute disease

    • AGN, ATN, acute pyelonephritis, AIN

  • Postrenal: Renal calculi and tumors

• Chronic: Progression from original disorders to end-stage renal disease

Discuss the clinical course and significant laboratory results associated with immunoglobulin A nephropathy

• Mucosal infection (UR or GI) → Excess IgA produced → IgA complexes deposit → Impairs filtration

• Hematuria, RBCs, RBC casts, mild to moderate proteinuria

Compare and contrast the nephrotic syndrome and minimal change disease.

• Nephrotic syndrome: Previous disease that damaged glomerular filtration barrier (especially podocytes and glomerular basement membrane)  Large amounts of protein leak into urine

  • Causes: Primary kidney diseases

    • Minimal chain disease, focal segmental glomerulosclerosis, membrane nephropathy

  • Damage causes protein (albumin) to pass through membrane → Blood albumin depleted → Low albumin causes increased lipid production in liver

  • Lab Results

    • UA: Proteinuria, fat droplets, oval fat bodies, RTEs, fatty and waxy casts, microscopic hematuria

      • Microscopic hematuria rather than gross because the primary injury affects filtration barrier for proteins not capillary wall integrity that allows for large amounts of RBCs to escape

    • ↓ Serum albumin ↑ Serum cholesterol and triglycerides

• Minimal Change Disease (Lipid nephrosis or nil disease): Cellular changes to glomerulus allowing increased protein filtration

  • Seen in children

    • Associated with allergic reactions, immunization, HLA-B12 antigen

    • Lab Results:

      • UA: Heavy proteinuria, transient hematuria

      • ↓ Serum albumin ↑ Serum cholesterol and cholesterol

State two causes of acute tubular necrosis.

Ischemia, toxic substances

Differentiate between diabetic nephropathy and nephrogenic diabetes insipidus.

• Diabetic Nephropathy: Most common cause of end-stage renal disease, increased permeability of glomerular filter

  • 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

  • Microalbuminuria: Small amounts of albumin in urine

• Nephrogenic Diabetes Insipidus: Kidneys do not respond properly to ADH → Cannot concentrate urine → Large quantities of dilute urine

  • Nephrogenic: Action of ADH is disrupted by the inability of the renal tubules to respond to ADH

  • Neurogenic: Failure of hypothalamus to produce ADH

  • UA: ↑↑ Volume of urine, ↓ SG, no glucose, no protein, minimal cells or casts

Know causes of:
Glycosuria with normal serum glucose (renal glycosuria, Fanconi)

Glycosuria with elevated serum glucose (overflow/diabetes)

• Renal Glycosuria: Autosomal recessive, benign

  • Decreased number of glucose transporters in tubules or decreased affinity of transporters for glucose

• Fanconi: Generalized PCT reabsorption failure (Glucose, AA, phosphorus, sodium, potassium, bicarbonate, H2O most affected)

  • Inherited: Cystinosis and Hartnup disease

  • Acquired: Heavy metals, complication of multiple myeloma, renal transplant

Compare and contrast the urinalysis results in patients with cystitis, pyelonephritis, and acute interstitial nephritis

• Cystitis: Bladder infection

  • Many WBCs, bacteria, increased pH, mild proteinuria, hematuria

• Pyelonephritis: Ascending movement of bacteria to upper urinary tract

  • Many WBCs, bacteria, increased pH, mild proteinuria, hematuria (same as cystitis), but also has WBC casts

• AIN: Allergic reaction causing inflammation of interstitial

  • Staining for eosinophils (Hansel stain)

  • Hematuria, proteinuria ↑ WBCs, WBC casts, ↓ GFR, No bacteria

Know the composition of renal calculi and what causes renal calculi to form.

• Renal Lithiasis = Renal calculi

• Composition

  • 75% calcium oxalate or phosphate

  • Magnesium ammonium phosphate (struvite)

  • Uric acid: Increased purine diet, uromodulin-associated kidney disease

  • Cystine: Hereditary cystinosis

• No exact cause, but certain conditions allow formation

  • pH

  • Chemical concentration

  • Urines stasis

  • Dehydration

Know the components in the formation of porphyrins.

• Intermediate compounds in the production of heme synthesis

• Primary Porphyrins: Uroporphyrin, coproporphyrin, protoporphyrin

• Precursors: α-aminolevulinic acid (ALA) and porphobilinogen

What urine color suggests porphobilinogen in the urine?

Port wine color after air exposure

Differentiate overflow metabolic disorders vs renal tubular defects

• Overflow: Large amount of substance in blood, kidneys cannot reabsorb all so it spills into urine

  • Disruption of normal metabolic pathway

  • Increased plasma concentrations of non-metabolized substances

  • Overrides reabsorption ability of renal tubules

  • Inborn Error of Metabolism: Inherited lack of specific enzyme for protein, fat, or carbohydrate

• Renal: Malfunction in tubular reabsorption mechanism

  • Not metabolites in blood, something wrong with kidney function

Name the metabolic defect in phenylketonuria, and describe the clinical manifestations it produces.

• Body cannot remove phenylalanine from body  Builds up  Cross blood-brain barrier  Mental delay

• Symptoms:

  • Severe intellectual disability, damage to child’s mental capacity

  • Seizures

  • Hyperactivity, developmental delay

  • Psychiatric disturbances

State three causes of tyrosyluria.

• Type 1: Tyrosine broken down to byproducts after metabolism → FAH missing → Byproducts cannot be broken down → Toxic to body → Renal tubular disease and liver failure in infants

• Type 2: Tyrosine aminotransferase deficiency → Tyrosine not broken down at all → Tyrosine crystalizes and causes lesions

• Type 3: Deficiency in HPD → Middle of tyrosine metabolism, byproducts are unable to be broken down

  • Most severe, causes intellectual disability, seizures, and loss of coordination

Name the abnormal urinary substance present in alkaptonuria, and explain how its presence may be suspected.

Homogentisic acid, turns black when exposed to air

What is maple syrup urine disease?

Inborn error of metabolism involving leucine, isoleucine, and valine

Discuss the significance of ketonuria in a newborn.

• Branched chain amino acid disorders: Enzyme deficiencies that prevent breakdown of leucine, isoleucine, and valine → Toxic accumulation and neurologic damage → Overflowing of amino acids in urine

• Two groups: MSUD, organic acidemias (accumulation of organic acids)

Differentiate between the presence of urinary indican due to intestinal disorders and Hartnup disease.

• Tryptophan not being reabsorbed → Sits in intestines → Gut bacteria break down into indole → Indole in bloodstream → Indole to liver → Liver turns it into indole → Excreted into urine

• Hartnup disease: Blue diaper syndrome

  • Inherited disorder affects intestinal reabsorption of indole and renal tubular reabsorption = Fanconi syndrome

What are tryptophan disorders?

Increased urinary excretion of the metabolites indican and 5-HIAA caused by a defect in metabolism that increases tryptophan conversion to indole

Differentiate between cystinuria and cystinosis, including the differences found during analysis of the urine and the disease processes.

• Cystinuria: Inherited disorder affecting renal reabsorption

  • Two modes of inheritance:

    • Only cystine and lysine are not reabsorbed

    • Cystine, lysine, arginine, and ornithine are not reabsorbed

  • Increased calculi formulation early in life

  • Cystine not soluble, will not dissolve → Cystine crystals

• Cystinosis: Inherited lysosomal storage disorder

  • Renal tubules affected by deposits → Fanconi syndrome

    • Deposits: Cornea, BM, lymph nodes, organs

  • Infantile: Rapid progression to renal failure

  • Late-onset: Gradual progression to renal failure

  • Non-nephrotic: Benign, some ocular problems

  • Laboratory findings:

    • Polyuria, aminoaciduria

    • Reducing substances