1030 Unit 4 Flashcards
Most glomerular disorders are caused by what?
Immunologic disorders
Dysmorphic RBC casts would be significant findings in what?
—good pasture syndrome
—AGN
—Henoch-Schonlein purpura
Occasional episodes of macroscopic hematuria over periods of 20 or more years are seen in patients with what?
IgA nephropathy
What is Antiglomerular basement membrane antibody is sent with?
—Goodpasture syndrome
What is ANCA a diagnostic for?
GPA
Respiratory and renal symptoms are associated with what?
—GPA
—Henoch-Schonlein purpura
—good pasture syndrome
the presence of fatty casts is associated with what?
–nephrotic syndrome
–FSGS
–MCD
where are the highest levels of proteinuria seen?
–NS
what does ischemia frequently produce?
–acute renal tubular necrosis
what disorder is associated with polyuria and low specific gravity?
Nephrogenic DI
what inherited disorder produces a generalized defect in tubular reabsorption?
–fanconi syndrome
A teenage boy developed gout in his big toe and has high serum uric acid should be monitored for what?
–uromodulin-associated kidney disease
what is the only protein produced by kidney?
–uromodulin
what does presence of RTE cells and casts indicate?
ATN
The presence of what can differentiate between cystitis and pyelonephritis?
–WBC cast
what does the presence of WBCs and WBC casts with no bacteria indicate?
–AIN
What are some characteristics of ESRD?
–isothenuria
–azotemia
–electrolyte imbalance
what can cause prerenal acute renal failure be caused by?
–massive hemorrhage
what is the most common component of renal calculi?
calcium oxalate
uranalysis on a patient with severe back pain being evaluated for renal calculi would be most beneficial if it showed what?
–microscopic hematuria
abnormal urine screening tests categorized as an overflow disorder include what?
–alkaptonuria
–melanuria
–galactosemia
why do all states require newborn screening for PKU?
–for early modification of diets
what disorders can be detected by newborn screenings?
–tyrosyluria
–MSUD
–galactosemia
what is the best specimen for early newborn screening?
–blood specimen
what disorders are associated with the phenylalanine-tyrosine pathway?
–Alkaptonuria
–albinism
–tyrosinemia
what is the least serious form of tyrosylemia?
–immature liver function
what overflow disorder of phenylalanine-tyrosine pathway that would produce a positive reaction with reagent strip for ketones?
–MSUD
what overflow disorder can produce a false-positive reaction with the clinitest procedure?
–alkaptonuria
A urine that turns black after sitting by the sink for several hours could indicate what?
–alkaptonuria
–melanuria
what is ketonuria in a newborn indicate?
–methylmalonic acidemia
–MSUD
–isovaleric acidemia
what urine characteristic would be expected in newborns with MSUD?
–sweet odor
Hartnup disease is disorder that is associated with the metabolism of what?
–tryptophan
5-HIAA is a degradation product of what?
–serotonin
what are elevated urinary levels of 5-HIAA associated with?
carcinoid tumor
what are false-positive levels of 5-HIAA can be caused by?
–a diet high in bananas`
cystinuria or cystinosis in IEM?
cystinosis
cystinuria or cystinosis in “inherited disorder of tubular reabsorption”
cystinuria
cystinuria or cystinosis in Fanconi syndrome?
cystinosis
cystinuria or cystinosis in cystine deposits in the cornea?
cystinosis
cystinuria or cystinosis in early renal calculi formation
cystinuria
what is blue diaper syndrome associated with?
Hartnup disease
what is homocystinuria caused by?
–failure to metabolize methionine
what will the Ehrlich reaction detect?
porphorbilinogen
what is the classic urine color for porphyria?
–port wine
what specimens can be used for porphyrin testing?
–feces
–blood
–urine
Acetyl acetone is added tp the urine before performing Ehrlich test when checking for what?
–porphobilinogen
what are two stages of heme formation affected by lead poisoning ?
–aminolaevulinic acid and protoporphyrin
Hurler, Hunter, and Sanfilippo syndromes are hereditary disorders affecting what?
the metabolism of mucopolysaccharides
what do many uric acid crystals in pediatric urine specimen indicate?
–Lesch-Nyhan disease
deficiency of the GALT enzyme with produce what?
–positive clinitest
–galactosemia
what odor is associated with PKU?
mousy odor
what color is associated with indacinuria?
blue color
what odor is associated with cystinuria?
–sulfur odor
what color is associated with alkaptonuria?
black color
**also homogentisitic acid
what appearance is associated with Lesch-Nyhan disease
– orange sand in diaper
what odor is associated with isovaleric acidemia?
–sweaty feet odor
what conditions are marked by Nephrotic syndrome?
–massive proteinuria
–low levels of serum albumin
–pronounced edema
–high levels of serum lipids
what is most commonly found in patients with renal calculi
–hematuria
what is seen is all cases of renal disease?
proteinuria
Describe Goodpastures Syndrome
–autoimmune disease seen following a viral infection where attachment of autoantibodies to the glomeruli membrane that results in proteinuria, hematuria, and RBC cases
–often progresses from glomerulonephritis to end stage renal failure
describe cystinuria
a hereditary problem of the kidney tubules that do not reabsorb cystine
describe cystinosis
IEM - mild to fatal elevated amounts of cystine
what is alkaptonuria
–rare inborn error of metabolism where the patient lacks the enzyme homogentistic acid
what is seen in patients who have defects in the metabolism of homocystine?
–cataracts
–thromoembolytic problems
what are screening tests for melanuria?
–Ferric chloride tube test (gray-black precipitate
–sodium nitroprusside test (red color)
–Ehrlich test
what are urine tests for phenylketonuria?
–ferric chloride tube test
–clinitest
–alkalization of fresh urine
what condition shows an increased amount of 5-HIAA in urine?
–Argentaffin cell tumors
what test is for MSUD?
DNPH
what is most significant sign of Lesch-Nyhan
–orange sand in diaper
what are the tests for tyrosyluria?
–ferric chloride tube test (transient green color)
–nitroso-naphthol (red color)
describe minimal change disease
–also known as lipid nephrosis that affects children due to an allergic reaction (after immunization) that responds well to treatment and has good prognosis
describe porphyrinurias
–can be hereditary or acquired
–most common acquired cause is lead poisoning
*Newborn with severe vomiting’s and metabolic acidosis.
*uranalysis positive for ketones, negative for glucose.
*what screening would come back positive?
DNPH
When a ferric chloride test was performed the urine produced a green-gray color. Is this an expected result? Why or why not?
Yes, this is the color produced in ferric chloride when ketones are present
For the most accurate diagnosis of the newborn’s condition, what additional testing should be performed?
MS/MS
describe immunological reaction
–immune complexes from an immunological reaction-increased immunoglobulins
–IgA: deposit on the glomerular membrane
–components of immune system (complement, lymphocytes, neutrophils, monocytes and cytokines) are attracted to the deposit and change or damage the membrane
–results in thickening of glomerular basement membrane
what are non immunological reaction causes?
–exposure to chemicals and toxins
–disruption of the electrical membrane charges (nephrotic syndrome)
–deposits of amyloid material may create chronic inflammation
–thickening of the basement membrane with diabetic nephrography
describe acute poststreptococcal glomerulonephritis
–AGN or PSGN
–sudden onset commonly in children after respiratory infection (strep. Group A)
–no permanent damage to kidneys
–findings : hematuria, oliguria, and proteinuria
–increased BUN
–RBC cast, RBC, granular cast, and WBCs
–anti-streptolysin O (ASO) and anti-Dnase B = positive
–contains M protein in cell wall
what is BUN?
blood urea nitrogen
what are the symptoms of acute poststreptococcal glomerulonephritis?
–fever
–nausea
–edema
–fatigue
–hypertension
–oliguria
–hematuria
–proteinuria
describe classic clinical features of glomerulonephrit
–inflammatory process affecting the glomerulus
–findings: proteins, blood, and casts
–antigen-antibody complex from recent strep infection
–antigen-antibody complex in the glomeruli causing: inflammation and decrease in Glomerular filtration rate
what are symptoms of classic glomerulonephritis?
–proteinuria
–hematuria
–oliguria
–dysuria
–low grade fever
–headache
–high BP
–facial/periorbital edema
–lethargic
–weight gain (edema)
what is the classic order of glomerulonephritis disorders?
Acute–> chronic–> nephrotic syndrome – renal failure
what is the treatment of acute poststreptococcal glomerulonephritis ?
–successful treatments of management of secondary complications
–ASO
–Anti-DNase B
describe rapidly progressive glomerulonephritis
–(Crescentic)
–RPGN
–more serious than AGN w/ poor prognosis resulting in renal failure
–findings: same as AGN. Becomes more abnormal as it progresses
–increase protein
–GFR very low
–may result in fibrin degradation products, cryoglobulin, and deposits of IgA
what are symptoms of rapidly progressive glomerulonephritis?
–immune complexes due to another disorder such as SLE
–Damage to capillary wall causing crescentic formation from macrophages, fibroblast and fibrin causing permanent damage to Bowman capillary walls
what is hallmark characteristic of acute glomerulonephritis?
RBC casts
what does the presence of Broad cast indicate?
–seen in chronic glomerulonephritis that progresses to ESRD
describe goodpastures syndrome
–resembles RPGN in that is it an autoimmune disorder
–cytotoxic autoantibodies appear in the glomerulus after a viral infection
–findings: protein, blood, and RBC casts
–chronic glomerulonephritis and ESRD is common
what are symptoms of goodpastures syndrome?
–onset hemoptysis and dyspnea followed by hematuria
how is goodpastures syndrome detected?
antiglomerular basement membrane antibody
describe granulomatosis with polyangiitis
–GPA
–also known as Wegners granulomatosis
–granuloma is small blood vessels of the kidney and respiratory system
–this is a vascular issue as well
–neutrophil antibodies attach to vascular walls forming granuloma
what are the symptoms of granulomatosis with polyangiitis?
–hematuria
–proteinuria
–RBC cast
–Serum creatinine
–increased BUN
–respiratory issues changing into renal problems
what are testing procedures done for granulomatosis with polyangiitis?
-ANCA
what is p-ANCA?
–formed if neutrophils are fixed in ethanol
– creates perinuclear pattern
what is c-ANCA?
–formed if neutrophils are fixed with formalin/formaldehyde
–pattern is granular throughout cytoplasm
what 3 things are associated with ANCA
–Granulomatosis with polyangiitis
–microscopic polyangiitis
–eosinophilic granulomatosis with polyangiitis
describe Henoch-Schonlein purpura
–see in children after respiratory infection
–purpura = raised red patches
–renal complications are monitored
–50% of patients resume kidney functions, the other develop glomerulonephritis
–See RBC casts
what are the symptoms of Henoch-Schonlein purpura?
– purpura
–hematuria
–proteinuria
–see blood in sputnum and stool
what are 3 renal disorders that are also respiratory disorders?
–Henoch-Schonlein syndrome
–Acute poststreptococcal glomerulonephritis
–Goodpasture syndrome
describe membranous glomerulonephritis
–MGN
–thickening of glomerular basement membrane from the deposits of IgG immune complexes
–prognosis: slow progression and may develop other complications (thrombosis)
–etiology is unknown in 75% of the cases
what are examples of membranous glomerulonephritis?
–SLE
–Sjogren syndrome
–secondary syphilis
–Hepatitis B
–malignancy
–Au + Mg treatment
what are symptoms of membranous glomerulonephritis?
–hematuria
–increased protein (similar to nephrotic syndrome)+
–positive identification for one of the causes is helpful
describe membranoproliferative glomerulonephritis
–MPGN
–there are 3 types (type I, type II, and type III)
–can be seen with autoimmune disorders, infections, and malignancy
describe the 3 types of membranoproliferative glomerulonephritis
–type I: cellular damage in the subendothelial cells of the mesangium (interstial area of Bowmans capsule). Create thickened wall of capillary walls
–type II: dense deposits in glomerular basement membranes; tubules and bowman capsule
–type III: both type I and II. found is children and has poor prognosis
what can type I membranoproliferative glomerulonephritis lead to?
–nephrotic syndrome
what can type II membranoproliferative glomerulonephritis lead to?
–chronic glomerulonephritis
what are symptoms of membranoproliferative glomerulonephritis?
–hematuria
–proteinuria
–serum decrease complement
describe immunoglobulin A nephropathy
–Berger disease
–deposits of IgA complexes are deposited in glomerular membrane
–patient will have a increased serum IgA levels (from mucosal infection
–frequent in children and young adults
–findings: macroscopic hematuria after infection or strenuous exercise
–may be asymptomatic for up to 20 years
–recover spontaneously, reoccurrence with microhematuria
what is the most common cause of glomerulonephritis?
IgA nephropathy
what is the “definition” of nephrotic sydrome?
1) massive proteinuria (>3.5 g/day)
2) low levels of albumin
3) increased lipids (hyperlipidemia)
4) pronounced edmea
Describe the acute onset of Nephrotic syndrome
–circulatory disruption
–systemic shock (lower BP and flow to kidneys)
–progression of glomerulonephritis complications
what happens to the kidneys with nephrotic syndrome?
–permeability increase due to damage of the podocytes = producing a more freely open barrier
—->this allows high molecular weight molecules (protein and lipids) into the urine
—-.albumin is depleted in the blood. Stimulate the liver to male lipids
–oncotic pressure is low
—->depleting albumin increased fluid loss = in Na+ retention causing edema
—->depletion of immunoglobulins = infection
—->depletion of coagulation disorders
describe minimal change disorder
–also known as lipid necrosis
–little cellular change in glomerulus except in the podocytes (shield of negativity result in increased proteins in urine
–seen in children
– etiology is unknows but possibly related to allergic reactions, immunizations and HLA-B12
–related to T-cell release cytokines
–prognosis: good- frequently go into remission
how is minimal change disease treated?
corticosteroids
what are the symptoms of minimal change disease?
–increased proteinuria
–transient hematuria
–edema
–normal BUN and creatinine levels
what is the most common cause of nephrotic syndrome in children?
minimal change disease
what would be the urinalysis results of acute poststreptococcal glomerulonephritis?
–Macroscopic hematuria
–RBC casts
–proteinuria
–granular cast
–OTHER significant test: anti-group A streptococcal enzyme test
what would be the urinalysis of rapidly progressive glomerulonephritis?
–Macroscopic hematuria
–RBC casts
–proteinuria
–OTHER significant test: BUN, creatinine and eGFR
what would be the urinalysis of Goodpasture syndrome?
–Macroscopic hematuria
–RBC casts
–proteinuria
–OTHER significant test: Antiglomerular basement membrane antibody
what would be the urinalysis of Granulomatosis with polyangiitis?
–Macroscopic hematuria
–RBC casts
–proteinuria
–OTHER significant test: antineutrophilic peripheral or cytoplasmic antibody
what would be the urinalysis of Henoch-Schonlein purpura?
–Macroscopic hematuria
–RBC casts
–proteinuria
–OTHER significant test: stool occult blood`
what would be the urinalysis of Membranous glomerulonephritis?
–Microscopic hematuria
–proteinuria
–OTHER significant tests: antinuclear antibody, hepatitis B surface antigen, and fluorescent treponemal antibody-absorption tests (FTA-ABS)
what would be the urinalysis of membranoproliferative glomerulonephritis?
–Hematuria
–proteinuria
–OTHER significant test: serum complement levels
what would be the urinalysis of chronic glomerulonephritis?
–Hematuria
–Proteinuria
–glucosuria
–cellular and granular casts
–waxy and broad cast
–OTHER significant tests: BUN, serum creatinine, eGFR, and electrolytes
what would be the urinalysis of IgA nephropathy in the early stages?
–macroscopic or microscopic hematuria
–OTHER significant test: Serum IgA
what would be the urinalysis of IgA nephropathy is the late stages?
–Hematuria
–Proteinuria
–glucosuria
–cellular and granular casts
–waxy and broad cast
**same as chronic glomerulonephritis
what would be the urinalysis of minimal change disease?
–transient hematuria
–heavy proteinuria
–fat droplets
–OTHER significant tests: serum albumin, cholesterol and triglycerides
what would be the urinalysis of nephrotic syndrome?
–microscopic hematuria
–heavy proteinuria
–RTE cells
–oval fat bodies
–fat droplets
–fatty and waxy casts
–OTHER significant tests: serum albumin, cholesterol and triglycerides
what would be the urinalysis of alport syndrome?
–microscopic hematuria
–heavy proteinuria
–RTE cells
–oval fat bodies
–fat droplets
–fatty and waxy casts
–OTHER significant test: genetic testing
**same as nephrotic syndrome
what would a urinalysis of Diabetic nephropathy in late stage?
–Hematuria
–Proteinuria
–glucosuria
–cellular and granular casts
–waxy and broad cast
–OTHER significant test: blood glucose
what are the 2 causes of acute tubular necrosis?
–hereditary
–metabolic
describe acute tubular necrosis
–damage to RTE due to lack of oxygen- decreased blood flow = ischemia or because of toxic materials (heavy metals, antifreeze, antibody, antifungal, radiographic dye)
what are the symptoms of tubular necrosis?
–shock (decrease flow of blood through body)
—-cardiac failure
—-toxigenic bacteria
—-massive hemorrhage
—-electrical (high voltage)
–trauma –crushing injury
what is the treatment for acute tubular necrosis?
–correct the ischemia or remove toxins
name urinary sediment that is most indicative of renal tubular damage
RTE cells
describe Fanconi syndrome
–most frequent , failure to tubular reabsorption in the PCT
–sees issues with glucose, amino acids, Na+, K+, H20, and HCO3-
–disrupts energy to transport
–can be acquired through toxic agents (heavy metals, outdated medications)
–see with multiple myeloma and renal transplant
–may be inherited in association to cystinosis and Hartnup disease
what would be the urinalysis for Fanconi syndrome?
–glucosuria
–possible cystine crystals
–proteinuria
–low pH
describe Alport syndrome
–disorder of collagen production affecting the membrane (thinning glomerular basement)
–sex-linked (males affected more) to children
– after respiratory infection
–may develop vision or hearing loss
–progress to nephrotic syndrome or ESRD
what are symptoms of Alport syndrome?
–hematuria
–proteinuria
–renal insufficiency
–can progress to nephrotic and ESRD
what are substances that are affected more noticeably in Fanconi syndrome?
–glucose
–amino acids
–phosphorous
–sodium
–potassium
–bicarbonate
–water
describe uromodulin-associated kidney disease
–glycoproteins produced in PCT and DCT’
–inherited autosome mutation in the production of uromodulin-producing decrease in production of normal glycoproteins with abnormal form
–abnormal form accumulates leading to damage
–could result in renal transplant
–increased about of uric acid resulting in gout at a young age
describe renal glycosuria
–opposite of Fanconi’s – only reabsorbs glucose
–autosomal inherited recessive trait
–no glucose transporters
–once it is over its threshold, glucose will spill ober into urine. (Threshold 160-180 mg/dl)
–benign disorder
describe diabetic nephropathy
–caused by
—->thickening of basement membrane
—->proliferation of mesangial cells
—->increased cellular and noncellular deposits
—->deposits of glycosylated proteins from poorly controlled blood glucose levels
—->resulting sclerosis
what is the most common form of ESRD?
–diabetic nephropathy
what are the causes of nephrogenic diabetes insipidus?
–inherited
–acquired from medications
–tubular defect of tubular response of ADH
–pale yellow
what would be the urinalysis of acute tubular necrosis?
–microscopic hematuria
–proteinuria
–RTE cells
–RTE cell casts
–hyaline, granular, waxy and broad cast
–OTHER significant tests: hemoglobin and hematocrit and cardiac enzymes
what would be the urinalysis of uromodulin- associated with kidney disease in early stages?
–RTE cells
–OTHER significant test: serum uric acid
what would be the urinalysis of uromodulin-associated with kidney disease in later stages?
—-Hematuria
–Proteinuria
–glucosuria
–cellular and granular casts
–waxy and broad cast
what would be the urinalysis of nephrogenic diabetes insipidus?
–polyuria
–low specific gravity
–OTHER significant test: ADH testing
what would be the urinalysis of renal glucosuria?
–glucosuria
–OTHER significant test: blood glucose
describe cystitis/UTI
–lower UTI: urethra and bladder in women and children
–upper UTI: renal pelvis, tubules
–interstitium
describe acute pyelonephritis
–acute form is result of bacteria moving from lower UTI tubules
–could be caused by obstruction such as calculi
–can be corrected without renal damage
–symptoms: frequent urination with burning and lower back pain
–from untreated cystitis
describe chronic pyelonephritis
–most severe
– can result tubular damage or renal failure
–can be related to structural defect causing reflux in the bladder to the ureters now allowing the collecting duct to empty
describe acute interstitial nephritis
–inflammation(allergic) of the renal interstitium (renal tubules)
–dialysis may be used in rare cases
what are the symptoms of acute interstitial neprhritis
–oliguria
–edema
–GFR
–fever
–rash
–decreased renal concentration
what are some common medications that can cause acute interstitial nephrtitis?
–penicillin, methicillin, ampicillin
–cephalosporins
–NSAIDS
–diuretics
what would be the urinalysis of cystitis?
–microscopic hematuria
–mild proteinuria
–bacteriuria
–leukocyturia
–increased pH
–NO CASTS!!!
–OTHER significant test: urine culture
what would be the urinalysis of acute pyelonephritis
–microscopic hematuria
–proteinuria
–bacteriuria
–leukocyturia
–WBC casts
–bacterial casts
–OTHER significant test: urine culture
what could be the urinalysis of chronic pyelonephritis
–hematuria
–proteinuria
–bacteriuria
–leukocyturia
–WBC casts
–bacterial casts
–granular, waxy, and broad casts
–OTHER significant test: urine culture, BUN, creatinine, and eGFR
what would be the urinalysis of acute interstial nephritis?
–hematuria
–proteinuria
–leukocyturia
–WBC casts
–OTHER significant tests: urine eosinophil, BUN, creatinine, and eGFR
what is the “definition” of renal failure
–GFR<25 ml/min
–increased BUN
–electrolyte inbalance
–lack of concentration ability
–proteinuria
–renal glycosuria without serum glucose increased
–granular, waxy and broad casts
describe acute renal failure
–sudden onset
–sudden decrease in blood flow to kidney
what are some urinalysis causes of acute renal failure?
–RTE cells
–RBC-glomerular damage
what are some causes WBC/casts causes of acute renal failure?
–infection
–inflammation
–urothelial cells-bladder tumor
what are some prerenal causes of acute renal failure?
–decreased BP/ cardiac output
–hemorrhage
–burns
–surgery
–septicemia
what are some renal causes of acute renal failure?
–acute glomerulonephritis (AGN)
–acute tubular necrosis (ATN)
–acute pyelonephritis
–acute interstitial nephritis (AIN)
what are some post renal causes for acute renal failure?
–renal calculi
–tumors
–crystallization of ingested substances
describe Renal calculi
–formation of stones (renal liethisus)
–calculi (kidney stone)- come from calyces and pelvis of kidneys, ureters, and bladder
–shape and size can vary
–larges ones that can not pass must be shocked with high energy to break them down using lithotripsy
–sometimes has to be surgically removed
what are conditions that favor formation of renal calculi?
–pH
–chemical concentrations
–urinary stasis
what is the composition of a renal calculi
–75% are calcium oxalate and calcium phosphate
–other types
—->magnesium ammonium phosphate (accompanying a UTI)
—->uric acid - linked to food high in purine (pH=acidic)
—->cystine - see with hereditary diseases (most maintain correct pH)
explain abnormal accumulations of metabolites in the urine in terms of overflow and renal disorders
–disruption of a normal metabolic pathway
–increased plasma concentrations of the nonmetabolized substances
–overrides reabsorption ability of renal tubules or present a minute amount
–inherited lack of specific enzyme for proteins, fats or carbohydrates
describe renal disorder
–accumulation of chemicals because of the malfunction of the tubular reabsorption
–organ malfunction due to disease or toxicity
what are some overflow inherited disorders/
–phenlyketonuria
–tyrosinemia
–alkaptonuria
–MSUD
–organic acidemia
–cystinosis
–porphyria
–mucopolysaccaridoses
–galactasemia
–Lesch-Nyhan disease
what are some metabolic disorders?
–infantile tyrosemia
–melanuria
–indicanuria
–5-HIAA
–porphyrins
what are some renal disorders?
–Hartnup disease
–cystinuria
what does the Benedict test screen for?
alkaptonuria
`what does Ferric chloride test screen for?>
–alkaptonuria
–MSUD
–melanuria
–PKU
what does Hoesch test screen for?
porphyrins
what are does nitrosonaphthol test screen for?
tyrosinuria
what does the silver nitrate test screen for?
alkaptonuria
what does watson-shwartz test screen for?
porphyrins
what crystal would you see with homogentistic acid?
cystine
what crystal would you see with melanin?
leucine
what crystal would you see with indican?
tyrosine
what crystal would you see with porphyrins?
Lesch-Nyhan disease
what are 3 causes of tyrosyluria?
–metabolic issues
–frequently seen in premature infants because the liver has not developed fully to produce enzyme
–acquired severe liver damage
describe tyrosine metabolism
1) build up of tyrosine
2)breakdown product = p-hydroxphenylpyruvic acid or p-hydroxy phenylactic acid. inherited diseases –> no enzyme produced to breakdown the metabolic pathway. Fatal conditions to liver and renal tubular disease
what are the 3 types of tyrosyluria
–types I: deficient in enzyme fumarylacetoacetate hydrolase (FAH)
–type II: tyrosinemia-lack tyrosine amino transferase
–type III: tyrosinemia-lack of p-hydroxyphenylpyruvic acids dioxygenase
describe type I of tyrosyluria
–renal tubular disorders and progressive liver failure in infants
–newborn screen = tyrosine and succinylacetone-blood and urine
–genetic testing to confirm the newborn screen
describe type II of tyrosyluria
–corneal erosions
–lesions on palms, fingers and soles of feet
—DX: measure the tyrosine levels and genetic markers
describe type II of tyrosyluria
–intellect disabilities
–seizures
–must watch diet
–DX: tyrosine in plasma and urine has metabolites. Need genetic studies, May see tyrosine or leucine
what is the Nitroso-Naphthol Test procedure?
–for tyrosine
1)place five drops of urine in a tube
2)add 1 mL of 2.63N nitric acid
3)add one drop of 21.5% sodium nitrite
4)add 0.1 mL 1-nitroso-2-napthol
5)mix
6)wait 5 minutes
7)observe for an orange-red color, indicating tyrosine metabolites
what is the Ferric chloride Test procedure?
–for alkaptonuria, MSUD, PKU, melanuria
1)place 1 mL of urine in a tube
2)slowly add five drops of 10% ferric chloride
3)observe color for a permanent blue-green color
describe PKU
–melanin
– most common amino acid disorder
–failure to inherite gene to produce enzyme (phenylalanine hydroylase)
–autosomal recessive w/o characteristics; heterozygous carries will show characteristics
–milk –get phenylalanine from
what are some symptoms of PKU?
–seen in fair children with light colored hair and eyes
–seizures, hyperactivity, delay development, and psychiatric disturbances
–if undetected can lead to mental retardation
–increased keto acids
what are 3 abnormal urinary substance present in alkaptonuria?
–dark urine or urine that turns dark on standing
–ochronosis (bluish-black pigmentation in connective tissue)
–arthritis of the spine and larger joints.
describe alkaptonuria
–failure to inherit the gene to produce enzyme, homogenic acid oxidase
–build up of homogentic acid in blood, tissue and urine
–brown pigment settles in tissue (ears especially) leads to arthritis
–have issues with liver and cardias
what screenings are performed for alkaptonuria?
–ferric chloride
–clinitest
–homegentisic acid
what is the Homogentisic acid test procedure?
1) place 4 mL of 3% silver nitrate in a tube
2)add 0.5 mL of urine
3) mix
4) add 10% NH4OH by drops
5) observe for black color
describe melanuria
–2nd pathway for tyrosine - responsible in producing melanin, tryroxine, epinephrine, protein, and tyrosine sulfate
–melanin = dark color of skin, hair, and eyes
–deficeint = albinism
–increase = melanuria
–urine will darken after exposure to air
–over production of melanin from melanocytes (malignant myeloma)
describe MSUD
–early degradation of amino acids causing an accumulation of one out of two amino acids
–rare- inherited autosomal recessive trait
–amino acids involved = leucine, isoleucine, and valine
–part of newborn screening
–failure to inherit enzyme to produce oxidation decarboxylation of the keto acids results in accumulation in blood and urine
–detected by sweet smelling urine because of rapid accumulation of ketones
–failure to thrive at week 1
what is 2,4-DNPH test procedure?
1) place 1 mL of urine in a tube
2)add 10 drops of 0.2%, 2,4-DNPH in 2N HCl
3) wait 10 minutes
4)observe for yellow turbidity or precipitate
discuss significance of ketonuria in a newborn
–early detection of MSUD or organic acidemia
describe indicanuria
–excess indole gets reabsorbed - liver, where it is converted to indican and excreted in urine/feces
–colorless until oxidized by air = indigo blue
–increased indican produced during lack of protein digestion
Fanconi + Hartnup =
renal tubular damage
describe Hartnup disease
–affects the absorption of tryptophan
–elevated amounts of trytophan are converted into indole
–increased levels of indican levels are seen in urine
describe 5-HIAA
–2nd metabolic pathway or tryptophan (production/stimulate smooth muscle)
–degradation product of serotonin, which is excreted in the urine in small amounts
– serotonin is formed from tryptophan by interstinal argentaffin cells and carried by platelets through the body
–body uses almost all of its serotonin but when carcinoid tumors associated with argentaffin cells develop, serotonin is produced leading to a 5-HIAA urine
what is the significance of increase 5-HIAA in the urine?
–greater than 25 mg indicates argentaffin cells tumor
what foods to avoid will screening for serotonin
–avocado
–kiwi
–walnut
–tomatoes
–bananas
–pineapple
–plums
what is the nitroprusside test procedure
1)place 1 mL of urine in tube
2)add 2 drops of concentrated NH4OH
3)add 0.5 mL 5% silver nitrate
4)wait 10 minutes
5)add five drops sodium nitroprusside
6) observe for purple-black color
What is the cyanide-nitroprusside test procedure for cystine
1) place 3 mL of urine in tube
2) add 2 mL sodium cyanide
3) wait 10 minutes
4) add five drops 5% sodium nitroprusside
5)observe for red-purple color
What is the silver-nitroprusside test procedure for homocysteine?
1) place 1 mL of urine in tube
2) add two drops of concentrated NH4OH
3) add 0.5 mL 5% silver nitrate
4) wait 10 minutes
5) add five drops sodium nitroprusside
6) observe for red-Purple color
Describe homocystinuria
—defects in metabolism of the amino acid methionine produce an increase in homocysteine through body
—included in newborn screening using MS/MS
What must done if the urine test positive using the cyanide-nitroprusside test?
—follow with testing with silver-nitroprusside test for homocysteine
What do cystinosis and cystinuria have in commen?
—both an error in metabolism
Describe cystinuria
—large amount of cystine in urine
—caused by renal tubular not able to reabsorb cystine, along with lysine, arginine, ornithine
—develop stones early in life
—cystine is more soluble
What are 3 modes of inheritance
—reabsorb all 4 amino acids affected
—only cystine and leucine affected
—homogenous or heterogenous inheritance
What test screens for cystinuria?
—cyanide-Nitroprusside test
Describe cystinosis
—3 variations, not showing until adult hood
—2 categories
—defects in lysosomal membrane preventing cystine to release to be metabolized
—deposits in many area of the body (cornea, bone marrow, lymph nodes and internal organs)
—treatment: renal transplant and cystine depleting medication
What are the 2 categories of cystinosis
1) Nephrotic
——infantile-rapid progression to renal failure
—— late-onset - gradual progression
2) non-nephrotic - benign except ocular issues
How does fanconi disease develop?
Due to defect in renal tubular reabsorption (especially in PCT)
What are 3 primary porphyrins
—uroporphyrin
—coproporphyrins
—protoporphyrins
What are the 2 precursors of heme production?
—alpha-aminolevulinic acid (ALA)
—porphobilnogen
What specimens are tested in gene synthesis?
—blood
—urine
—feces
—bike
What is detected in the urine when testing in heme synthesis pathway
—ALA
—porphobilinogen
—urobilinogen
*these are also most soluble
What is least soluble in the heme synthesis pathway?
—coproporphyrin (in urine and feces)
—protoporphryins (feces
Describe porphyria’s
— porphyrins metabolism disorder
—inherited and acquired from erythrocytic and hepatic malfunction
—port wine color when exposed to air
What are common acquired causes of porphyrins?
— lead poisoning
—excessive alcohol
—iron deficiency
—chronic liver disease
—renal disease
What are inherited causes of porphyrins ?
—failure to inherit a gene to produce an enzyme needed in pathway
What are tests for porphyrins
— Ehrlich reaction; only for ALA and porphobilinogen
—fluorescence under ultraviolat light 550 - 600 nm range. (Violet, pink or red)
—Watson Schwartz
Describe Watson Schwartz test differentiation test
1) tube 1 gets: 2 mL urine, 2 mL chloroform and 4 mL sodium acetate
2) tube 2 gets: 2mL urine, 2 mL butanol and 4 sodium acetate
3) observe the color of the layers
What are the interpretations of Watson Schwartz
—urobilinogen = red chloroform with clear urine and red butanol with clear urine
—porphobilinogen = clear chloroform and clear butanol with red urine
—other Ehrlich reactive substances = clear chloroform with red urine and red butanol with clear urine
—both = red chloroform with red urine and red butanol layer with red urine layer
What is the Watson-Schwartz test procedure?
1) tube 1 gets: 2 mL urine, 2 mL chloroform, and 4 mL sodium acetate
2) tube 2 gets: 2 mL urine, 2 mL butanol, 4 mL sodium acetate
3) vigorously shake both
4) place in rack for layers to settle
5) observe both tubes for red color in the layers
Describe mucopolysaccharides
—inherited disorder preventing the metabolism of glycosaminoglycans in connective tissue
—prevents breakdown of polysaccharides portions
—bone marrow transplant and gene therapy
— newborn screening
—CTAB turbidity testing
What would you find in the urine with mucopolysaccharides?
—dermatan sulfate
—keratan
—sulfate
—heparin sulfate
What are the most common mucopolysaccharides disorders
—hurler syndrome: abnormal skeletal structure, corneal damage, severe mental retardation
—hunter syndrome: abnormal skeletal structure, severe mental retardation, inherited sex link recessive trait, rare in female
—sanfilippo : mental retardation
What is the CTAB test procedure?
1) place 5 mL of urine in tube
2) add 1 mL 5% CTAB in citrate buffer
3) read turbidity in 5 minutes
Describe Lesch-Nyhan disease
—purine disorder
—inherited sex-link recessive
—Massive excretion of Uric acid crystals
—motor defects, mental retardation, self-destruction.
