360 - Non-Protein Nitrogenous Compounds Flashcards
a mechanism for regulating body water and sodium content
reni-angiotensin-aldosterone system
The ______________ cells of the kidney release renin into the plasma in response to stimuli such as _________ or a ___________ in the sodium concentration in the fluid in the distal tubule
juxtaglomerular; hypotension; decreases
what does renin do?
catalyzes the conversion of circulating angiotensinogen to angiotensin I
what happens to angiotensin I after renin comes in?
it’s converted to angiotensin II by angiotensin-converting enzyme as it passes through the lungs
role of angiotensin II
acts on the adrenal cortex to stimulate the release of aldosterone, which acts on the kidney to promote sodium reabsorption, potassium excretion, and water retention
aldosterone stimulates this
thirst center
ADH
- synthesized and stored in the hypothalamus
- release stimulated by osmotic and barometric receptors in response to increased plasma osmolality and decreased blood volume
- ADH controls water homeostasis
- presence of ADH = the water permeability of the distal convoluted tubule and the collecting duct is increased
where is ammonia produced?
in the liver by the deamination of proteins
produced in the intestine by bacterial and endogenous enzymes
Renal tubular cells can produce ammonia from glutamine and other amino acids
what happens to ammonia produced in the renal tubular cells?
it diffuses into the tubule lumen and combines with free hydrogen ions to form ammonium
at which pH is it favourable to form ammonium??
favoured by an acidic urine pH
when is plasma [ammonia] increased?
instances of liver and kidney disease and the central nervous system disorder Reyes syndrome
most common method of measuring ammonia
glutamate dehydrogenase method
(GLDH)
specimen for measuring ammonia
heparin or EDTA
should be placed immediately at 4C
ammonia measurement interference
- hemolyzed samples should not be used (RBCs have ammonia)
- cigarette smoke significantly INCREASES ammonia concentrations
- Ethanol ingestion INCREASES ammonia
- prolonged venous occlusion and fist clenching INCREASE ammonia
- ammonium heparin anticoagulant and delayed handling INCREASES ammonia
how is creatinine formed?
formed spontaneously in skeletal muscle from creatine and by the enzymatic action of creatine kinase
Serum creatinine levels are a function of …
muscle mass, so levels are higher in males than in female
what is increased creatinine caused by ?
muscle crush injuries and by any disorder that decreases GFR
when do decreased creatinine occur?
when there is an inadequate conversion from creatine, i.e. muscular dystrophy
how is creatinine measured?
Jaffe kinetic rxn
describe the Jaffe kinetic method
- alkaline medium
- creatinine + picrate to form a creatinine-picrate complex
- absorbance at 490-500 nm
NOTE: other wavelengths have been used to reduce spectral interference
interferences with the Jaffe kinetic rxn
- ketone, ascorbate, cephalosporin, glucose and protein produce Jaffe-like chromogen and cause spectral interference
- bilirubin and hemoglobin are NEGATIVE interferents
- lipemia may introduce error
where is urea produced?
in the liver from ammonia
increased urea is associated with this
increased protein deamination due to increased dietary intake, and increased protein catabolism from tissue breakdown
what is urea an indicator of?
renal function
90% of urea is excreted by the kidneys
in severe liver disease and individuals with low protein intake, urea production DECREASES
interference of urea measurement
- sodium fluoride containing anticoagulant INHIBIT urease
- ammonium heparin can be a POSITIVE interferent in the 2nd reaction
- endogenous ammonia can also interfere with the 2nd rxn
- RBCs have ammonia; hemolysis is a POSITIVE interferent
how is uric acid formed?
from the oxidation of purine bases
T or F. Levels of uric acid are higher in females than males
F! higher in males than females
Hyperuricemia may be observed in…
acute and chronic renal failure due to decreased excretion
increased production of uric acid –> increased plasma concentrations; associated with leukemia and diets rich in nucleoproteins
increased = kidney stones and gout
how does liver disease affect uric acid levels?
decrease in the enzymes required for depurination, causing hypouricemia
method for measuring uric acid
using the enzyme uricase in a two-step colourimetric rxn
specimen for uric acid
Separated serum or heparin plasma are acceptable specimens
interferences in measuring uric acid
- anticoagulants containing sodium fluoride
- bilirubin and ascorbate can interfere with the uricase reaction
- bilirubin may falsely DECREASE results in peroxidases catalyzed reactions
- hemolysis may cause DECREASED results
creatinine clearance (CC)
- test of glomerular function
- blood specimen must be drawn within 72 hours of either the start or finish time of the urine collection
- height and weight required
- urine must be ref throughout collection period
urine collection for CC
- Void into toilet emptying the bladder. Record this as the TIME STARTED.
- Collect ALL urine after this point into the container provided until 24 hours has elapsed.
- To finish the collection, exactly 24 hours after the DATE/TIME STARTED, urinate and empty bladder completely. Add this urine to the collection container
formula for CC
C= [UV/P] x [1.73/SA]
U= urine concentration of creatinine that was cleared in μmol/L
P= plasma concentration of creatinine in μmol/L
V= volume of urine in a unit of time (e.g. mL/s or mL/min)
SA= surface area of the patient (calculated using height and weight)
24 hours= 86,400 seconds
T or F. The creatinine clearance test overestimates the GFR
T! approximately 10% of creatinine in urine is the result of tubular secretion
main sources of error for measuring CC
pre-analytical errors due to patient compliance with timing, collection, and storage of urine
what happens to CC in renal disease and heart disease
DECREASES due to decreased GFR
estimated GFR
Equations can be used to estimate GFR without the need for a urine collection. Certain factors must be considered, such as gender, age, weight, and serum creatinine.
CKI-EPI equation
used by AHS
- eGFR
- different for males vs females
estimates of GFR may not be reliable in the following cases:
- acute kidney injury
- unusually high or low muscle mass
- the patient is on medication that interferes with the tubular secretion of creatinine, i.e. salicylates, and loop diuretics
Persistent proteinuria is a marker of this
kidney disease
- can be the result of the excretion of albumin or low molecular weight globulin
T or F. Albumin is not normally found in the urine
T!
- presence of albumin in the urine can indicate damage to the glomeruli and basement membranes
- albuminuria = chronic kidney disease such; diabetic nephropathy
- proteinuria due to the excretion of low molecular weight globulins is a marker for some forms of tubular damage
Microalbuminuria
albumin excretion above the normal range but below the level of detection for total protein
the ratio of albumin to creatinine (ACR) is used to…
overcome urinary variations that are due to albumin concentration or hydration
a spot urine sample is preferred over a 24 h sample because of patient compliance issues
how are adults screened for kidney disease?
using a urine reagent strip
then if two screens, three months apart are positive = follow up with ACR
two or more positive ACR results are required for a diagnosis of chronic kidney disease (CKD)
how is chronic kidney disease (CKD) monitored?
ACR or with a total protein: creatinine ratio if the ACR becomes too high
what is b2-microglobulin
- a small peptide that is part of the major histocompatibility complex
- surface of cells; low but usually constant concentrations in the plasma
- freely and completely filtered by the glomerulus and then is reabsorbed and catabolized by the PCT cells
b2-microglobulin is a good indicator of …
GFR in normal patients; unaffected by muscle mass and diet
when is b2 mic increased?
certain inflammatory diseases, renal failure, and malignancies
this small peptide is used for assessing the integrity of the renal tubules, particularly in renal transplant patients and those who have been exposed to heavy metals (e.g. Hg, Cd)
blood and urine b2-microglobulin
a rapid reduction in kidney function
AKI
acute kidney injury
how does AKI present?
AKI may present as oliguria or increased plasma creatinine
risk factors for AKI
increased age, diabetes, chronic kidney disease, heart disease and administration of nephrotoxic drugs
T or F. Acute renal failure can progress to chronic renal disease or recovery of renal function can occur
T!
PRE-RENAL AKI
factors affecting the blood supply going to the kidney
commonly caused by cardiac failure, and hypovolemia due to burns, hemorrhage, vomiting, diarrhea, and sepsis
renal AKI
result of vascular, glomerular, or interstitial damage
damage to the renal tubules is common; it can be the result of aminoglycosides, nonsteroidal anti-inflammatory drugs, myoglobinuria, or heavy metal poisoning
POSTRENAL AKI
the result of an obstruction in the flow of urine after it leaves the kidney
obstruction can be caused by prostatic enlargement, renal stones, fibrosis, or neoplasms of the urinary tract
the result of a progressive loss of renal function
chronic kidney disease (CKD)
T or F. The loss of renal function in CKD is REVERSIBLE
F! it is IRREVERSIBLE
- number of functioning nephrons is decreased
- urine tends to have a fixed specific gravity, isosthenuria, indicating a lack of concentrating ability
how is CKD defined and staged?
by estimated glomerular filtration rate, eGFR, and urinary albumin/creatinine ratio
primary cause of CKD
DM followed by hypertension
other causes: glomerular nephritis, inherited disorders, infection, and systemic diseases
