week 2 - NPN, renal function
Branched chain AAs, leucine crystals
A clinical symptom of aminoacidopathies includes the presence of ____ in the blood, urine, and CSF, and ___ in urine; can result in severe mental retardation &/or death
Ketogenic
AA deamination intermediate can generate ketone bodies
Glucogenic
AA deamination intermediate serves as glucose precursors
Essential amino acids
AAs needed to make proteins that cannot be synthesized fast enough to meet needs
Inborn errors of metabolism, renal tubular disease
Amino acids are a diagnostic aid for ___ (2)
Renal disease, liver disease, inborn errors of metabolism
Ammonia can be used as a diagnostic aid for ____ (2)
Jaffe reactions
An endpoint method based on reaction of creatinine + picrate ion to form → red-orange complex; interference from proteins, alpha-keto acids, cephalosporins, bilirubin & hemoglobin;
Pre-renal
An increase in the urea/creatinine ratio with normal creatinine levels indicates the issue is
Tyrosine crystals in urine
An indication of tyrosinemia in the clinical lab is the presence of ____
Urease
An indirect method to measure BUN includes utilizing the enzyme ___ to convert urea to ammonia by hydrolysis
Ion-sensitive electrode
Analytical method for testing ammonia conc: Ammonia diffuses across selective membrane into NH4Cl, causing pH change & pH change is measured potentiometrically
Enzymatic
Analytical method for testing ammonia conc: a colorimetric assay, using glutamate dehydrogenase & conc measured by spectrophotometer
urea/creatinine
BUN ratio used to assess GFR
Amino acids
Building blocks of proteins; able to enter urinary filtrate but are transported back into plasma; originate from proteins & are used to produce proteins
Non-protein nitrogenous (NPN) compounds
By-products of protein & nucleic acid metabolism
Type I
Citrullinemia type that is the most common; buildup of citrulline & toxic ammonia
Type II
Citrullinemia type where individual cannot make the protein citrin, which is involved in the transportation of molecules that aid in production/catabolism of sugars, proteins & nucleotides
Renal disease
Creatinine can be used as a diagnostic aid for __ (1)
Secreted
Creatinine is __ by the proximal tubule; can be inhibited by drugs
Urea
Decreased filtration rates & decreased urine flow both result in increases in plasma ___ concentrations
Uric acid
Degradation product of purine metabolism; used to diagnose purine synthesis & catabolism disorders, also used to monitor drug therapies & gouth
Ammonia
During Citrullinemia, there is a buildup of _____ (NPN)
Dry
Enzymatic hydrolysis is most frequently used in ___ chem analyzers
Amino group, carboxylic acid, R group
Groups in amino acids (3)
Urea
Major NPN compound in both plasma & urine; how body rids itself of toxic ammonia by making a nontoxic product, used to assess renal function & indication of liver disease
Urea
NPN compound in highest concentration in blood; major excretory product of protein metabolism; often referred to BUN
Plasma, urine
NPN compounds are detected in ______ within the clinical lab (2)
Ammonia
NPN produced by intestinal flora & tissues; important intermediate in AA synthesis & is normally removed by portal circulation & is converted to urea via the liver
Fasting heparinized blood, random urine
Specimens for AA testing (2)
Excreted through the Kidneys
The majority (90%) of urea is _____
Renal
The normal urea/creatinine ratio indicates the issue is
Type I
Tyrosinemia type that is the most severe; Low levels of fumarylacetoacetate hydrolase → leads to liver / kidney / NS problems
Type II
Tyrosinemia type with a deficiency of tyrosine aminotransferase → leads to mental retardation / photophobia / skin lesions
Liver, CO2, ammonia
Urea is produced in the ____, from ___ and _____
Disorders of urine synthesis & catabolism
Uric acid can be used as a diagnostic aid for ____ (1)
Gout
Uric acid crystals in the joints of toes & inflammation due to supersaturated body fluids
Glucogenic, TCA intermediate, ketogenic
When AAs are deaminated, their intermediates are either _____ (3)
Increases
When the liver is damaged, ammonia concentration ____
Protein
Where amino acids come from
Amino acids
Where ammonia comes from
Phosphocreatine
Where creatinine comes from
Liver
Where toxic ammonia is converted to nontoxic urea
Ammonia
Where urea comes from
Purine nucleosides
Where uric acid comes from
Homogentisic acid (HGA)
a clinical symptom of Alkaptonuria may be the presence of ___ in urine, making it a dark color; can also deposit into cartilage / tendons, leading to ochronosis
Hypouricemia
a decrease in uric acid plasma levels; rare, usually secondary to liver disease
Chromophore
a direct method to measure BUN is measuring the ____ formed using a mass spec
Post-renal
an increase in the urea/creatinine ratio with increased creatinine indicates the issue is
Prerenal azotemia
caused by reduced renal blood flow; less blood = less urea to kidney = less urea being filtered
Azotemia
condition of increased blood urea
Freely filtered
creatinine is _____ by the glomeruli of kidneys
Renal function, GFR
creatinine is used to assess ___, a measure of ___ in mL
Decreases, increases
creatinine production ____ as plasma concentration of creatinine _____
Tubular necrosis
damage to the tubules of the nephron is called =
Increase, decrease
during liver disease, ammonia concentrations __ and BUN levels ____
Urea
excretion of ___ is related to renal blood flow, glomerular filtration rate & urine flow
Congestive heart failure
failure of heart to pump sufficiently
Ammonium (NH4+)
form of ammonia most predominant in plasma
Nephrons
functional units of the kidneys that filter plasma, remove waste, exchange electrolytes, and reabsorb nutrients
Aminoacidopathies
genetic disorders in which there is a defect in one of the enzymes to metabolize or transport a particular amino acid
Renal damage
gout can lead to
Secondary gout
gout due to drug therapy or renal disease
Primary gout
gout due to overproduction or under-secretion without an underlying cause
Hyperammonemia
high concentration of ammonia in plasma; due to liver diseases, renal failure, of inherited deficiency of urea cycle enzymes
Pulmonary edema
if the left side of the heart cannot sufficiently pump blood to the body, pressure builds up toward the lungs, called
Abdominal, leg, ankle edema
if the right side of the heart cannot sufficiently pump blood to the lungs, pressure builds up toward the body, called ___
Urea
if there is a decrease in cardiac output, during congestive heart failure, a decrease in renal blood flow increases plasma ___
Aminoacidopathies (maple syrup urine disease)
inborn error of metabolism; Deficiency of branched-chain alpha-keto acid decarboxylase needed for metabolism of leucine, isoleucine, & valine; patient may have maple syrup smelling urine & breath
Alkaptonuria
inborn error of metabolism; Lack of homogentisate oxidase, the enzyme involved in metabolism of tyrosine & phenylalanine
Phenylketonuria
inborn error of metabolism; absence of phenylalanine hydroxylase, which converts phenylalanine → tyrosine; results in increased plasma levels of phenylalanine & metabolites
Tyrosinemia
inborn error of metabolism; body cannot break down AA tyrosine
Hyperuricemia
increase in uric acid plasma levels; overproduction or reduced excretion
Uremia
increased BUN with renal failure =
Acromegaly, giantism, muscle necrosis
increased creatinine conditions (3)
Glomerulonephritis
inflammation of the glomerulus
Renal medulla
inner region of kidneys that contains the loop of Henle & receives urine from collecting ducts
Renal azotemia
intrinsic renal disease (direct result of kidney issues) is called =
Body
left side of the heart pumps blood to the ___
Higher
men have a ___ uric acid concentration than women & this increases with age
Enzymatic hydrolysis
method to detect creatinine that is less specific than the Jaffe reaction; uses ion-specific electrode & spectrophotometry to measure Creatinine → ammonia, or creatinine → creatine
Phosphotungstic acid (PTA)
method to detect uric acid; reagent gets reduced by urate in alkaline conditions, forming a blue product that is read spectrophotometrically; many interferences
Uricase
method to measure uric acid that detects the bacterial enzyme ____, which converts uric acid to allantoin; reaction is coupled with peroxidase step to detect amount of peroxide formed; few interferences
Post-renal azotemia
obstruction of renal flow due to kidney stone / prostate tumor; problem is result of something after urine has left kidney
Renal cortex
outer region of kidneys that contains glomeruli
Homogentisate
oxidase enzyme involved in the metabolism of tyrosine & phenylalanine
Uric acid crystals
patients with gout have ___ in the joints of their toes
Decrease
plasma urea (BUN) levels ___ during pregnancy
Creatinine
product formed from creatine + phosphocreatine, which are found in muscles/brain; maintain ATP levels & is elevated in muscle disorders / injuries
Lungs
right side of the heart pumps blood to the ___
EDTA or heparinized plasma
specimen type for Ammonia tests
Plasma, serum (not heparinized)
specimens for creatinine tests (2)
Wet
the Jaffe reaction is most frequently used in ___ chem analyzers
Uric acid
the major product of metabolism of purine nucleosides (adenosine/guanosine); approx 75% is excreted into urine & remainder is secreted through GI tract
Ammonia
toxic NPN found in small amounts in the plasma; excreted into urine & is water soluble; comes from breakdown of AAs
High dose vitamin C
treatment for alkaptonuria
Increases, increases
tubular creatinine production ___ as the plasma conc ____
Type III
tyrosinemia type that is very rare; deficiency of 4-hydroxylphenyl-pyruvate dioxygenase → leads to mild mental retardation / seizures
Renal disease, liver disease
urea can be used as a diagnostic aid for ___ (2)
Citrullinemia
urea cycle disorder
Urate
when plasma pH is above 5.7, the H+ is removed from uric acid and the product formed is __
