Urinalysis test 2

Diabetes insipidus

decrease in ADH, or inability of tubules to respond Nephrogenic: sex-linked recessive or acquired-Li, PCKD (polycystic kidney disease) Urinalysis: low SG (from very dilute urine), pale yellow, false negative chemical tests normal blood glucose

Porphyrias

disorder of porphyrin metabolism Can be inherited or acquired-inherited is rarer Inherited-failure to inherit the gene that produces the enzyme needed in the metabolic pathway Classified by symptoms: neurologic/psychiatric, cutaneous photosensitivity or both

Inborn error of metabolism

disruption of enzyme function-caused by: Failure to inherit the gene to produce an enzyme Organ malfunction

Minimal Change Disease (lipid nephrosis)

increased filtration of protein - most frequent cause of nephrotic syndrome in children - edema, heavy proteinuria, transient hematuria, normal BUN and creatinine - cause is thought to be allergic reactions, recent immunization, and HLA-B12 antigen - treat with corticosteroids, good prognosis

Glomerulonephritis

sterile, inflammatory process - urine findings: blood, protein, and casts - variety of types - may also progress from one form to another (ie acute → chronic → nephrotic syndrome → renal failure) Variety of types: Acute Poststeptococcal Rapidly Progressive (Crescentic) Goodpasture Syndrome Wegener's Granulomatosis Henoch-Schonlein Purpura

Alkaptonuria

"alkali lover", urine turns black upon exposure to air—if alkaline Caused by: failure to inherit the gene to produce the enzyme homogentisic acid oxidase w/o this enzyme the phenylalanine tyrosine pathway cannot proceed to completion and homogentisic acid accumulates in the blood, tissue, and urine Usually not diagnosed in childhood Later in life, brown pigment becomes depositied in the tissues, esp. ears, deposits in cartilage leads to arthritis Liver and cardiac disorders too Urinary screening tests often rely on the reducing ability of the HGA Ferric chloride test, copper reduction High levels of vit C interfere w/ darkening urine Confirm with thin layer or high performance chromatography

Maple syrup urine disease

(a Branched chain AA disorder) inborn error of metabolism; (autosomal recessive trait) Absence or greatly reduced activity of the alpha-keto acid decarboxylase Required to metabolize leucine, valine and isoleucine Increased levels in blood and urine Symptoms: infants show failure to thrive after abt 1 week Urine has strong odor of maple syrup Screening test for detecting keto acids: 2,4 dinitophenylhydrazine reaction (DNPH)-not specific Pos reaction—yellow turbidity or precipitate Confirmation: amino acid chromatography

Normal RBC values in urine and hematuria

- Normal is less than 5 cells per high power field Increased red cells in urine = hematuria, which can be due to: inflammation, necrosis, trauma, tumor, neoplasia need to interpret hematuria in order to determine where bleeding is coming from -Method of collection must be considered: void and clean catch are not traumatic, caths can be more traumatic so more RBCs will be present

RBCs in urine

- appear as smooth, non-nucleated, biconcave disks - identified on high power (40X) - in concentrated urine: cells shrink - in dilute urine: liquid moves into the cell and can lyse it - confused with: budding yeast, oil droplets, bubbles, calcium oxalate crystals Clinical significance - associated with damage to glomerular membrane or vascular damage within the genitourinary tract - renal in origin when accompanied by RBC casts - dysmorphic RBCs specific for glomerular bleeding

Acute pyelonephritis

- ascending movement of bacteria from a lower UTI into the renal tubules and interstitium - downward flow of urine from the ureters to the bladder or the incomplete emptying of the bladder during urination - symptoms include rapid onset of urinary frequency and lower back pain - urinalysis: increased WBC & bacteria, mild proteinuria & hematuria, WBC casts (signifies infection in tubules), bacterial casts

Chronic Renal failure

- decreased glomerular filtration rate, rising BUN and creatinine azotemia), electrolyte imbalance, lack of renal concentrating ability - produces an isosthenuric urine, proteinuria, renal glycosuria, abundance of granular, waxy, and broad casts

Chronic glomerulonephritis

- end-stage of glomerular diseases -symptoms: fatigue, anemia, hypertension, edema, oliguria - urinalysis: hematuria, proteinuria, glycosuria (from disease damaging the tubules; cannot reabsorb the glucose), many casts - lab findings: decreased glomerular filtration rate, increased BUN and cret, electrolyte imbalance

Fanconi's syndrome

- failure of tubular reabsorption in the proximal convoluted tubule -glucose, amino acids,phosphorous, sodium, potassium, bicarbonate, water -may be inherited association with cystinosis and Hartnup disease or acquired-toxic agents (heavy metals, outdated tetracycline) or as a complication of multiple myeloma and renal transplant

Wegener's granulomatosis

- granuloma-producing inflammation of the small blood vessels of the kidney and respiratory system - produces ANCA (anti-neutrophilic cytoplasmic antibody) - bind to neutrophils located in vascular wall, and form granulomas - have hematuria, proteinuria, RBC casts, increased BUN & Creatinine

Sediment stains for urine

- increases overall visibility of sediment elements - increases visibility by changing refractive index - imparts identifying characteristics to cellular structures - ie: flagella, nucleus, cytoplasm edges, mucous Sternheimer-Malbin- most common stain (KOVA Stain) - consists of crystal violet and safranin O - absorbed well by WBCs, epithelial cells, and casts - nuclei and cytoplasm are stained contrasting colors -2 drops per sediment Toluidine blue- enhancement of nuclear detail - good for: distinguishing white cells Acetic Acid- also enhances nuclear detail, lyses red cells. confirms if you see red cells or not Sudan III or Oil Red O- lipids (triglycerides, neutral fats, cholesterol) - - Triglycgerides and neutral fats stain orange, whereas cholesterol doesn't stain but is capable of polarization. Hansel stain- stains eosinophils—allergic reaction or parasitic infection Prussian Blue- following hemoglobinuria, yellow-brown granules in RTEs and casts or free-floating in sediment; confirms: presence of hemosiderin

Clue Cells

- indicative of vaginal infection by: G vaginalis and coccobacillus - squamous epithelial cell covered in bacteria - routine testing by vaginal wet prep but may be present in urinary sediment

Pyelonephritis

- infection of upper UT including both the tubules and interstitium - can be acute or chronic

Rapidly progressive glomerulonephritis

- initial lab results similar to acute glomerulonephritis - become more abnormal as disease progresses: markedly ↑ protein, very low GFR - some forms also show ↑ FDPs, cryoglobulins, deposition of IgA immune complexes - damage by macrophages to the capillary walls releases cells and plasma into Bowman's space - production of crescentic formations containing macrophages, fibroblasts, and polymerized fibrin

Nephrotic Syndrome

- massive proteinuria (> 3.5 g/d), decreased serum albumin, increased serum lipids, marked edema - increased permeability of the glomerular membrane is attributed to damage to the membrane and changes in the electrical charges in the basal lamina and podocytes** - albumin is primary protein depleted from circulation - hypoalbuminemia stimulates increased production of lipids by the liver - lower oncotic pressure in the capillaries results from the depletion of plasma albumin and the increased loss of fluid into the interstitial spaces which along with sodium retention produces the edema - urinalysis: ↑proteinuria, fat droplets, oval fat bodies, renal tubular epithelial cells, epithelial, fatty, and waxy casts, microscopic hematuria

Immunoglobulin A Nephropathy (Berger's disease)

- most common cause of glomerulonephritis - serum IgA due to mucosal infection--deposited on the glomerular membrane - seen most commonly in children and young adults - macroscopic hematuria after an infection or strenuous exercise - after recovery may still have microhematuria and serum IgA - asymptomatic for 20 years or more (?!) - progression to chronic glomerulonephritis and ESRD

Urinary Tract Infection

- most common renal disease - may involve lower lower urinary tract (urethra and bladder) or the upper urinary tract (renal pelvis, tubules, interstitium)

Chronic pyelonephritis

- permanent damage to the renal tubules and chronic renal failure - congenital urinary structural defects that produce a reflux nephropathy -urinalysis: similar to acute pyelonephritis (increased WBC & bacteria, mild proteinuria & hematuria, WBC casts, bacterial casts) - until disease advances: then may see variety of granular, waxy, and broad casts, increased proteinuria, hematuria, decreased renal concentration

Acute Tubular Necrosis (ATN)

- produced by decreased blood flow causing lack of oxygen to the tubules (ischemia) shock, trauma such as crush injuries, surgical procedures OR: -toxic substances in the urinary filtrate--aminoglycoside antibiotics, amphotericin (antifungal), cyclosporine, radiographic dye, organic solvents (ie ethylene glycol, heavy metals, mushroom poisoning -affects function of RTE (renal tubular epithelial) cells: - filtration of lg amounts of Hgb and Myohgb (also nephrotoxic) - urine findings: mild proteinuria, microscopic hematuria, RTE cells and RTE casts containing tubular fragments

Membranous glomerulonephritis

- pronounced thickening of the glomerular basement membrane - deposits of IgG immune complexes - Why? lupus, Sjögren's syndrome, secondary syphilis, hepatitis B, gold and mercury treatments, malignancy -slow progression with possible remission -urinalysis shows microscopic hematuria, urine protein - frequent development of nephrotic syndrome occurs

Transitional (Urothelial) epithelial cells

- smaller than squamous epis, but larger than white cells - several forms: polyhedral, caudate - differences due to: ability to absorb water -increased numbers: indicates bigger issues like necrosis - distinct, centrally located nucleii - originate from lining of the renal pelvis, calyces, ureters and bladder, and from proximal urethra (upper) of males - normal desquamation They may develop refractile, fatty inclusions as they degenerate in older specimens

SPG and affect on RBCs in urine

-In fresh samples with S.G. of 1.010-1.020, RBC's: retain normal disk shape -In more concentrated urines (>1.025), RBC's: shrink, crenation -In more dilute samples: At urine S.G. <1.008 and/or highly alkaline pH, red cell lysis is likely. Lysed red cells appear as very faint "ghosts", or may be virtually invisible.

Focal segmental glomerulosclerosis (FSGS)

-only certain numbers and areas of glomeruli-others remain normal - symptoms-similar to nephrotic syndrome and minimal change disease --damaged podocytes - immune deposits IgM and C3 frequently seen in undamaged glomeruli -abuse of heroin, analgesics, and with AIDS - mod to heavy proteinuria and microscopic hematuria

Acute Interstitial Nephritis (AIN)

-rapid onset of symptoms: oliguria, edema, decreased renal concentrating ability, decreased GFR - fever, skin rash--usually associated with allergic reaction within the renal interstitium to medications - may be caused by binding of meds to interstitial protein - meds could include penicillin, methicillin, ampicillin, cephalosporins, sulfonamides, nonsteroidal anti-inflammatory agents, thiazide diuretics -treatment then: - urinalysis: hematuria, mild to moderate proteinuria, numerous WBC, WBC casts, no bacteria, -check for presence of eosinophils

Membranoproliferative glomerulonephritis (MPGN)

2 alterations in the cellularity of the glomerulus and peripheral capillaries - type I : cellularity in the subendothelial cells of the mesangium (interstitial area of bowman's capsule) -thickening of the capillary walls - type II : extremely dense deposits in the glomerular basement membrane - most pts are children - poor prognosis: type1 nephrotic syndrome type2 chronic glomerulonephritis - labs-hematuria, proteinuria, serum complement levels (from complement being used up) - possible association with autoimmune disorders, infections, malignancies

Porphyrin disorders

3 primary porphyrins -Uroporphyrin -Coproporphyrin -Protoporphyrin Porphyrin precursors: Α-aminolevulinic acid (ALA) Porphobilinogen synthesis of heme can be blocked at any of the stages Porphyrin solubility—varies w/ structure ALA, porphobilinogen, uroporphyrin-most soluble, found in urine Coproporphyrin-less soluble, found in urine Protoporphyrin-not found in urine Lead poisoning—whole blood tested for free erythrocyte protoporphyrin (FEP)

Acute renal failure

: sudden loss of renal function - primary causes: 1. decrease of blood flow to kidney (prerenal) - causes: decreased B/P, decreased cardiac output, hemorrhage, burns, surgery, septicemia 2. acute glomerular and tubular disease (renal) - causes: acute glomerulonephritis, acute tubular necrosis, acute pyelonephritis, acute interstitial nephritis 3. renal calculi or tumor obstruction (postrenal) - general characteristics are decreased GFR, oliguria, edema, azotemia - causes: renal calculi, tumors, crystallization of ingested substances

Tyrosinemia/Tyrosyluria

Accumulation of excess tyrosine in plasmaurinary overflow Caused by inherited or metabolic defects tyrosine and leucine crystals Transitory tyrosinemia Premature infants Underdeveloped liver function-inablility to synthesize adequate enzymes Seldom results in permanent damage, may be confused with PKU (ferric chloride test will produce a green color) Severe liver disease can produce tyrosinemia—more severe Urinary screen for tyrosine: nitrosonaphthol test Orange-red color=positive reaction-further testing necessary Non specific-will react w/ other substances

MPS screening disorders

Acid-albumin and cetyltrimethylammonium biurate (CTAB)—turbidity tests—thick white turbidity Metachromatic staining spot test—uses basic dyes (azure) to react with acidic mps to produce blue color

Mucopolysaccharides (MPS)

Aka: glycosaminoglycans-located primarily in the connective tissue Inherited disorders prevent complete breakdown of the polysaccharide portion Results in accumulation of these in lysosomes of connective tissue and incr. excretion in urine 3 most freq. found in urine: dermatan sulfate, keratin sulfate, heparin sulfate

Types of microscopy

Bright-field microscopy -must reduce light-casts with nothing in it will not be visible -make sure to look in the right plane - make sure that it's had time to settle Phase contrast microscopy - enhances visualization of elements with low refractive indices (through mucous and such) -ie: hyeline cast, trichomonas Polarizing microscopy - aids in identification of: oval fat bodies, fatty casts Interference contrast microscopy - produces a three dimensional image and layer by layer imaging of specimen

Bacterial cast

Casts containing bacilli both within and bound to the protein matrix are seen in pyelonephritis May be pure bacterial casts or mixed with white cells Bacteria-packed casts can resemble granular casts - confirm with a gram stain Consider bacterial cast when you have 1) many free WBCs 2) WBC casts and 3) bacteria in the sediment

Formed elements found in microscopic exam

Cells: Red blood cells, White blood cells, epithelial cells Casts Bacteria Yeast Parasites Crystals Artifacts: - fibers, talcum powder, starch crystals, air bubbles Mucous threads - present in normal urines in small numbers - abundant with inflammation/irritation of urinary tract

3 Classifications of Renal disorders

Classified based on components primarily affected a. Glomerular b. tubular c. interstitial glomerular - immune origin or toxins tubular - damage to the tubules interstitial - infections and inflammatory conditions

IDing WBCs

Primary concern to ID WBCs: - RTEs larger than white cells with eccentric nucleus School bus tire. WBCs with - supravital stains or acetic acid may help Normal: <5 leukocytes/hpf (may be higher in females) WBCs may enter urine through: glomerulus, capillary trauma, infection, inlammation in tissue - pyuria: indicates infection or inflammation in genitourinary tract - frequent causes of pyuria: bacterial infections, non-bacterial glomerulonephritism prostatitis, urethritis, etc

Cystinuria vs. Cystinosis

Cystinuria—defect in renal tubular transport of aa Cystinosis—inborn error of metabolism --has the odor of sulfur

Epithelial Cells

Epithelial Cells - common- - represent normal sloughing of old cells (unless in large numbers or abnormal forms) - 3 types: 1) squamous 2) transitional (urothelial) 3) renal tubular (RTE) - classified according to site of origin Squamous epithelial cell- - most common and the largest -found: lower portion of male urethra and entire female urethra - reported as rare, occ, few/slight, moderate or many/large/lpf - may resemble a cast (folded) - non-pathologic: just means the patient probably didn't perform a proper clean catch EXCEPT for the: Clue cells covered with bacteria, Gardnerella vaginalis, coccobacillus sticks to outside of squamous epithelial cells

Microscopic examination of urine sediment

Fresh or adequately preserved-refrigerated - formed elements disintegrate over time - refrigeration may cause - amorphous stuff to precipitate or change pH -thoroughly mix specimen prior to putting into a centrifuge tube Specimen volume Centrifugation Sediment preparation - centrifuge - pour off supernatant and re-suspend Volume of sediment examined- 20 microleters Examination of sediment- minimum of: 10 fields on both low (10x) and high (40x) - Low power: casts, crystals, mucous, squamous epithelial cells, casts: identify on high - High power- WBC, RBC, renal epithelial cells, bacteria, yeast

Branched amino acid chains

Have a methyl group that branches from the main aliphatic carbon chain

Hyaline cast

Have a smooth texture and a refractive index very much like urine, - difficult to see in cloudy sample of urine Must be distinguished from: mucus Have parallel sides with clear margins and blunted ends Reduced lighting is essential to see hyaline casts Can be present in low numbers (0-1 or 2/LPF) in concentrated urine of otherwise normal patients and not always associated with renal disease Increased: proteinuria of renal or extra-renal origin. e.g., glomerular disease e.g., overflow proteinuria as in myeloma Clinically significant in a congestive heart failure b acute glomerulonephritis C. pyelonephritis D. chronic renal disease

MPS disorders

Hurler's syndrome: abnormal skeletal structure, severe mental retardation, mps accumulate in the cornea, usually fatal in childhood Hunter's syndrome: abnormal skeletal structure, severe mental retardation, usually fatal in childhood Sanfilippo's syndrome—mental retardation

artifacts

Important to collect "clean catch" May be air bubble, hair, cloth fibers, fecal contamination, pollen, starch,oils May resemble true pathological elements: RBC's, casts, ova

Factors affecting crystal formation

In vivo factors include: 1) the concentration and solubility of crystallogenic substances 2) the urine pH 3) presence of crystals in freshly voided specimens associated with concentrated specimens (high specific gravity) In vitro factors include: 1) temperature 2) urine pH

Cystinosis

Inborn error of metabolism Results in crystalline deposits of cystine in many areas of the body— Fanconi's syndrome—major defect in renal tubular reabsorption Lab findings: polyuria, generalized aminoaciduria, pos tests for reducing substances, lack of urine concentration, severe cases=renal failure

Amino Acid disorders

Inborn errors of amino acid metabolism may result in what? Can be overflow or renal AA disorders: PKU, tyrosinuria, alkaptonuria, melanuria, MSUD, organic acidemias, indicanuria, cystinuria, cystinosis

Carbohydrate disorders

Increased urinary sugar (melituria) Most meliturias cause no disturbance in body metabolism, BUT pediatric urines should be screened for reducing substances—why? screening for galactosuria Galactosuria: inability to metabolize galactoseglucose—failure to thrive, liver disorders, cataracts, jaundice, mental retardation Pentosuria—pentose sugars in urine, almost exclusively in Jewish population Lactosuria—seen during pregnancy, lactation, Fructosuria—parenteral feeding, pentosuria w/lg amts of fruit, presence of fructose in urine after ingesting sucrose or fructose

Indicanuria

Indicanuria: caused by obstruction, abnl bacteria, malabsorption syndrome, Hartnup disease --Hartnup's disease: rare, inherited, incr amts of tryptophan are coverted to indol -Excess reabsorbed to blood streamliverconverted to indican then excreted in urine. -Indican reacts w/ acidified ferric chloridedeep blue or violet color then extracted into chloroform -Treat with dietary supplements (niacin)—good prognosis -Hartnup's affects intestinal reabsorption of tryptophan AND renal tubular reabsorption of other amino acids=generalized aminoaciduria=Fanconi's Syndrome

Red blood cell cast

Indicates bleeding within the: nephron Associated with damage to the: glomerulus; most often because of physical injury - usually see red cells in urine not attached to cast and proteinurea. - have also been seen in strenuous contact sports Color: orange-rust-red AND: fragile!! Shape: fragments or irregular shape Must see: red cells in urine also If you have massive hemoglobinuria or myoglobinuria: hemosiderin, red cell cast, granules - associated with acute tubular necrosis often caused by the toxic effects of massive hemoglobinuria: can lead to renal failure - must be present with other pathologic findings (RTE cells and a positive test for blood) Associated with acute glomerulonephritis, IgA nephropathy, lupus nephritis, subacute bacterial endocarditis, renal infarction Will usually see free-standing RBCs and positive reagent strip for blood

Inherited vs. metabolic vs. renal disease examples

Inherited: PKU, tyrosinemia, alkaptonuria, MSUD, organic acidemias, cystinosis, phrphyria, mucopolysaccharidoses, melituria (galactosuria), Lesch-Nyhan disease Metabolic: tyrosinemia, melanuria, indicanuria, 5-HIAA, porphyria Renal: Hartnup disease, cystinuria

Microscopic commercial systems for urine

KOVA- UriSystem Count-10 Quick-Prep Urinalysis System Censlide 2000 Systems provide: provide variety of options - capped, calibrated tubes - decanting pipettes - slides-

White cell cast

Signifies infection or inflammation within the nephron Most frequently associated with: pyelonephritis - primary marker for distinguishing : upper UTI from lower UTI Can also be present in nonbacterial inflammations: AIN, and with RBC casts in glomerulonephritis (if origin is glomerular) Most WBCs are: neutrophils Must also see WBCs in urine Partially disintegrated may be difficult to distinguish from RTE - may need to stain to identify Bacteria also present with pyelonephritis, but not acute interstitial nephritis WBC casts may have irregular borders - make sure matrix is there (WBCs frequently clump)

Homocystinuria

Lab findings: polyuria,generalized aminoaciduria, pos tests for reducing substances, lack of urinary concentration, pos w/cyanide-nitroprusside, renal failure Confirmatory test if cyan-nitroprus is pos: SILVER-nitroprusside test—ONLY HOMOCYSTEINE WILL REACT-spectrophotometrically-better detection at low levels Signs/symptoms: failure to thrive, cataracts, mental retardation, thromboembolic problems, death

Modifications to the Guthrie test can detect:

MSUD homocystinuria, Tyrosinemia, Histidinemia Valinemia Galactosemia

Tryptophan disorders

Major concern w/metabolism of tryptophan—increased urinary excretion of metabolites indican and 5-HIAA A second metabolic pathway of tryptophan is used for the production of serotonin Produced by argentaffin cells in intestine Normally, body uses most of the serotonin Cancer/tumors of argentaffin cells Normal daily exretion of 5-HIAA=2-8 mg Argentaffin cell CA= 160-628 mg/24hrs stringent guidelines for diet: bananas, pineapples, tomatoes, phenothiazines, acetanilids may interfere-incr

Tamm-Horsfall Protein (Uromodulin)

Major constituent of mucus and casts Excreted: at relatively constant rate - increased: with stress/exercise Protein gels more easily under certain conditions: urinary stasis, acid pH Not detected by reagent strip!!! Steps in formation of Tamm-Horsfall protein matrix: pg 122 in text As cast forms, urinary flow within tubule decreases (lumen becomes blocked) Width depends on size of tubule where it's formed

Glomerular disease

Majority have underlying immunologic processes - immune complexes (antigen-antibody combinations) circulate in bloodstream and deposited on the glomerular membranes Glomeruli can be damaged by a variety of diseases other than immunologic - metabolic - hereditary

Urinary tract parasites

Most commonly found parasite in the urine: trichomonas Others include: pinworms, other GI parasites Trich is pear-shaped flagellate with an undulating membrane. Must be moving to be quantitated!!. If not moving, it may be confused with a WBC, transitional or renal tubular epithelial cell

Mucus in urine

Mucus Protein material produced by: glands, squamous epithelial cells major constituent: Tamm-Horsfall (uromodulin) Thread-like structures with a low refractive index Must reduce light intensity to visualize clinical significance? Not usually Unless there is a huge amount Be careful not to confuse clumps of mucus with hyaline casts

Cystinuria

Not due to metabolism-due to inability of tubules to reabsorb cystine (and lysine, arginine, and ornithine) 2 modes of inheritance: 1. Reabsorption of all 4 amino acids is affected 2. Only cystine and lysine are not reabsorbed Clincal significance: tendency to form renal calculi Lab screening tests: cystine crystals, cyanide-nitroprussidered/purple if excess cystine

Cast formation in urine

Only elements found in sediment that are: unique to kidney Shape: parallel sides and rounded ends Any component in the urine can be incorporated into a cast - bacteria, cells, granules, crystals, etc. Detection and enumeration of casts on: low power - Identify on high power Must use: reduced light. why? -Low refractive index The place to look for casts: around edges of the well

Overflow Disorders vs. Renal Disorders

Overflow disorders: increased plasma concentrations of nonmetabolized substances These either override the reabsorption ability of the renal tubules or are not normally reabsorbed from the filtrate b/c usually are in small acts Renal Disorders: Renal disorders: caused by malfunctions in the tubular reabsorption mechanism

PKU

PKU—if left untreated, can cause mental retardation Incr. amts of keto acids, including phenylpvyruvate Occurs when normal conversion of phenylalaninetyrosine disrupted Also decr production of tyrosine and pigmentation metabolite melanin (fair complexion-even in dark skinned family) Cause: failure to inherit the gene to produce the enzyme phenylalanine hydroxylase Treatment—diet, must limit phenylalanine carefully, occurs in almost all natural proteins Low protein foods, fruits, veggies, some cereals Blood test for PKU—Guthrie bacterial inhibition test Heelstick, blood absorbed onto filter paper circles Filter discs placed on culture media streaked w/ Bacillus subtillis Incr PKU levels will counteract beta-2-theinylalanine (inhibitor of B.subtillis) and will have growth around the discs—no halo

Lesch-Nyhan disease

Purine disorder failure to inherit gene to produce the enzyme hypoxanthine guanine phosphoribosyltransferase Results in massive excretion of uric acid crystals in urine and deposits throughout body Severe motor defects, mental retardation, tendency toward self destruction, gout, renal calculi

Urinary crystals

Rarely of clinical significance Important to know pH of the urine Only a few types are clinically significant --usually caused by iatrogenic reasons from treatment - these are indicative of a pathologic process and must be correctly identified - may indicate liver disease, inborn errors of metabolism, or renal damage caused by crystallization of iatrogenic compounds within the tubules . Know which pH crystals beling in which pH of urine Formed by precipitation of urine solutes- inorganic salts, organic compounds, and medications (iatrogenic)

Renal tubular epithelial cells

Renal Tubular Epithelial Cells (RTE) - vary in size and shape - originate from tubules - nucleus small, round (eccentric) - blunted cell membrane. - can sometimes be mistaken for: cast but cast won't have a nucleus, or white cell - - Increase numbers of both:

Waxy Cast

Represent: extreme urine stasis, indicating chronic renal failure Appearance: cast matrix is waxy, more rigid, ends appear jagged or broken, more fragmented usually seen with other types of casts: Highly refractile!! Do not confuse with hyalin cast-rounded edges associated with tubular inflammation and degeneration, chronic renal failure, renal allograft rejection

Vasculitis

Several immune-mediated disorders affecting the systemic vascular system can result in glomerular involvement 2 vasculitis syndromes associated with glomerular involvement: 1. Wegener's granulomatosis 2. Henoch- Schönlein purpura

Epithelial cell cast

Signify: urinary stasis (no urine flow) - produces urinary stasis along with disruption of the tubular linings Causes: heavy metal and drug induced toxicity, viral infections (ie CMV), allograft rejection, pyelonephritis (along with WBC casts), ethylene glycol poisoning - also associated with proteinurea Granular casts often occur with them Fibrils of Tamm-Horsfall protein that make up cast matrix remain attached to the RTE cells - so could see occ tubular cell attached to hyaline cast When tubular damage present some cells may be incorporated into cast matrix, but majority will be attached to the cast surface Cells on the cast are smaller, round, and oval shaped cells (cuboidal, columnar) Fragments of epithelial tissue may also be attached to cast matrix

Preparation of urine sediment for microscopy

Standardization essential for accuracy and precision - volume: 12mL - centrifugation time and speed is 3-5 minutes at about 2500-3000 rpms -recommended RCF (relative centrifugal force)= 400 - volume of sediment: commercial systems- 20 microleter - reporting format depends on facility

Acute Poststreptococcal Glomerulonephritis

Symptoms of glomerular damage: - fever, periorbital edema (swelling around the eyes0, fatigue, HTN, oliguria, hematuria - most often in kids (but can affect any age) - certain strains of group A beta-hemolytic strep have "M protein" in cell walls -nephrogenic - urinalysis findings: marked hematuria, proteinuria, oliguria BLOOD, PROTEIN, CASTS - microscopic: RBC casts, dysmorphic RBCs, hyaline and granular casts, WBCs - ASO (anti-streptolysin O) titer ↑

Organic acidemas

Symptoms—early severe illness, vomiting w/ metabolic acidosis, hypoglycemia, ketonuria, increased serum ammonia 3 most common organic acidemias Isovaleric: urine/pt may have odor of sweaty feet Accumulation of isvalerylglycine due to a deficiency of isovaleryl coenzyme A in the leucine pathway Propionic Methylmalonic: used to rule out things -Both are acidemias that result from errors in the metabolic pathway converting isoleucine, valine, threonine, and methioninesuccinyl coenzyme Screening test for methylmalonic aciduria: Uses p-nitroanalineemerald green color

Branched chain amino acid disorders

Two major groups: Accumulation of one or more of the early aa degradation products (MSUD) Accumulation of organic acids produced further down in the aa metabolic pathway—organic acidemias Significant finding: ketonuria in newborn

Mixed Cellular

Two or more distinct cell types are present Any combination of cells is possible, most often red cells or white cells can be RBC and WBC in glomerulonephritis, WBC and RTE or WBC and bacterial in pyelonephritis in glomerulonephritis, the predominant cast is RBC, in pyelonephritis, it is WBC

WBC in urine

White Blood Cells - larger than RBCs - predominant WBC: neutrophils - contain: granules - lyse quickly in dilute alkaline urine - confused with: trich, epithelial cells - "glitter cells" - Clinical significance - pyuria (leukocyturia): associated with almost all renal diseases and inflammatory conditions of genitourinary tract - bacterial infections:cystitis, pyelonephritis, urethritis - non-bacterial:, glomerulonephritis will cause white cells in urine without infection White Blood Cells - Eosinophils: acute interstitial nephritis (AIN) - may also be seen with UTIs and renal transplant rejection - Hansel's stain (preferred) or Wright Stain: - determine % of eosinophils in 100-500 cells - >1% considered significant - Untreated AIN: cause permanent renal damage and want to detect early to stop drug causing it, usually penicillin - Mononuclear Cells: - lymphs- may look like red cell if small enough - seen in: early transplant rejection - monocytes and macrophages: both actively phagocytic - renal tubulointerstitial diseases resulting from infections or immune rxns - if can't be identified refer to cytology for testing

Alkaline pH crystals in urine

amorphous phosphates triple phosphates calcium phosphates ammonium biurates calcium carbonates

Acid pH crystals in urine

amorphous urates uric acid calcium oxalates cystine

Goodpasture's syndrome

autoimmune disorder -autoantibody (antiglomerular basement membrane antibody) against glomerular and alveolar basement membranes complement activation = capillary destruction morphologically, changes to glomeruli resembles RPGN - can follow viral respiratory infections - urinalysis results: proteinuria, hematuria, RBC casts -blood, protein, casts again. usually can differentiate this from other disorders if patient history has immune disorder - progression → chronic glomerulonephritis & ESRD - complaints are hemoptysis, dyspnea

Collecting duct RTE cells

cuboidal and never round - renal fragments: cells from collecting ducts: - indicate: damage, necrosis Clinical significance: RTE cells are the most clinically significant of all the epithelial cells Conditions that can produce tubular necrosis: exposure to heavy metals, drug induced toxicity, hgb/myoglobin toxicity, Viral infections (hepatitis B, pyelonephritis, allergic rxns, malignant infiltration, acute allogenic transplant rejection

Yeast in urine

in unstained urine sediments are round to oval in shape, colorless, and may have obvious budding Example: pictures below are of fresh urine collected by catheterization. The lower photo shows pseudohyphae formation by the yeasts, which were identified on culture as Candida albicans. Differentiation from RBCs sometimes difficult: - budding -use acetic acid to lyse red cells Seen in diabetics, immunocompromised patients, women with vaginal moniliasis (Monilia- genus of fungus) - As with bacteria, contaminants multiply rapidly

Cystitis

infection of the bladder - seen more often in women and children who present with urinary frequency and burning - urinalysis: numerous WBC and bacteria, mild proteinuria, hematuria, increased pH - if untreated can progress to a more serious upper UTI

Tubulointerstitial disease

infectious and inflammatory conditions - includes UTI, cystitis

Renal Lithiasis

kidney stones - barely visible to large staghorn calculi resembling the shape of the renal pelvis to smooth, round bladder stones with diameters of 2 or more inches - smaller calculi may be passed in the urine - severe pain radiating from lower back to legs - larger stones cannot be passed- need to be surgically removed or by lithotripsy - conditions for producing stones similar to those for crystals - pH, chemical concentration, urinary stasis - need to analyze stones to help with patient treatment - 75% of stones are composed of calcium oxalate or phosphate - primary urinalysis finding:microscopic hematuria irritation to tissues by moving calculus

Spermatozoa in urine

may be seen in urine from males: clinically significant if protein screen is positive may be observed in voided urine from a female: rare clinical significance, usually contaminant clinical significance??? except in cases of infertility Not reported in females at all but if in young girl, pathologist becomes involved positive reagent strip test for protein may be seen Reporting: The presence of sperm is reported only on male specimens if the protein is positive. If found in the urine of a child, immediately notify a pathologist. Do not report until confirmed by a pathologist; follow hospital-specific protocol

Melanuria

melanin, pigment responsible for dark color of hair, skin, eyes; produced by malanocytes 2ary pathway for tyrosine—excess urinary melanin produces darkening of urine after exposure to air Indicates: overproduction of melanocytes malignant melanoma

Hence-Shonlein purpura

mostly in children after upper respiratory infections - purpura--raised, red patches on the skin -blood in the sputum and stools - renal involvement mild to serious - mild to heavy proteinuria and hematuria and RBC casts - 50% of pts show complete recovery

Granular Cast

non-pathologic: origin of granules from the lysosomes excreted by RTE cells during normal metabolism Seen with strenuous exercise or stress (increased cellular metabolism) disease states: origin of granules disintegration of cellular casts and tubule cells or protein aggregates filtered by the glomerulus - pyelonephritis, viral infections, chronic lead poisoning, glomerulointerstitial disease, renal allograft rejection When granular casts stay in the tubules for extended amount of time, granules further disintegrate at appearance becomes waxy

Broad Cast

often referred to as renal failure cast Represent: extreme urine stasis indicates: tubular destruction All types of casts can be broad - most common are granular and waxy

Renal glycosuria

only affects reabsorption of glucose Number of glucose transporters decreased, or affinity of transporters for glucose is decreased Urinalysis: positve glucose Labs: normal blood glucose

Porphyrinuria

red or port wine color to urine 2 screening tests Ehrlcih reaction: only for detection of ALA and porphobilinogen Fluorescence under UV light---used for other porphyrins Porphyrins extracted into mixture of glacial acetic acid and ethyl acetate; solvent layer examined for violet, pink or red fluorescence

Fatty cast

seen with oval fat bodies and free fat droplets associated with nephrotic syndrome, toxic tubular necrosis, diabetes mellitus, crush injuries Commonly seen when there is heavy proteinuria highly refractile under light - confirm with polarized microscopy (Maltese Cross), Sudan III, Oral Red O - cholesterol will demonstrate Maltese cross - triglycerides and neutral fats: rust stained color

Oval Fat Bodies

tubular epithelial cell (RTE) with fat droplets in it Maltese cross pattern with polarized light: maltese cross pattern - can be stained with: Sudan III or Red O - droplets composed of: triglycerides, cholesterol, neutral fats - found in the urine of individuals: tubular damage, nephropathy. Doesn't always mean patient has high lipid levels probably indicate: nephropathy, nephrotic syndrome - are almost always present in patients with: high protein in urine (severe proteinurea)

Bacteria in urine

usually (but not always) accompanied by: nitrite positive dipstick, leukocytes, always considered pathologic -should always be: interpreted in conjunction with WBC result from urinalysis as well as method of collection number and type of bacteria observed is also important: - Example: few bacteria in voided urine with no pyuria and no WBCs=not pathologic. If increased numbers of single type of bacteria from a proper clean catch=pathologic ** bacteria most frequently associated with UTI: E.coli Hint: even if only a few seen on unspun urine means UTI; if only a few seen on spun urine means nothing but probable contamination

Free floating fat globules

vary in size and appear yellow or brown.. Can be differentiated with: Sudan III Oral Red O Lipiduria: is always clinically significant: associated with glomerular damage Caused by: nephrotic syndrome, tubular necrosis, poisoning, kidney damage from diabetes, trauma