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 __