Non-Protein Biomarkers Flashcards
What is the renin-angiotensin-aldosterone system
a mechanism for regulating body water and sodium content
the juxtaglomerular cells of the kidney release renin into the plasma in response to hypotension or decrease in sodium concentration
renin catalyzes the conversion of circulating angiotensinogen to angiotensin I which is converted to angiotensin II as it passes through the lungs. 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
What is antidiuretic hormone
synthesized and stored in the hypothalamus
release of ADH is stimulated by osmotic and barometric receptors in response to increased plasma osmolality and decreased blood volume
What is ammonia
produced in the liver by the deamination of proteins. Ammonia is produced in the intestine by bacterial and endogenous enzymes. Renal tubular cells can produce ammonia from glutamine and other amino acids
What is the clinical significance of ammonia
plasma levels of ammonia are increased in instances of liver and kidney disease and the central nervous system disorder Reyes syndrome
What are interferences with ammonia
RBC contain ammonia, hemolyzed samples should not be used
cigarette smoke and ethanol significantly increases ammonia concentrations
prolonged venous occlusion and fist clenching increase ammonia
ammonium heparin anticoagulant and delayed handling increase ammonia
What is urea
produced in the liver from ammonia, freely filtered but 40-50% is reabsorbed in the proximal tubules
What is the clinical significance of urea
increased urea is associated with increased protein deamination due to increased dietary intake and increased protein catabolism from tissue breakdown and GI bleeds
in severe liver disease and individuals with low protein intake urea protein decreases
not a good indicator of renal function
What are interferences with urea
sodium fluoride containing anticoagulant inhibits urease
ammonium heparin tubes and endogenous ammonia can be a positive interferent with the second step in the reaction
RBC contain ammonia, therefore hemolysis is a positive interferent
What is uric acid
formed from the oxidation of purine bases, is freely filtered and some is reabsorbed in the proximal tubule and the distal tubule excretes uric acid into the urine
What is the clinical significance of uric acid
hyperuricemia may be observed in chronic renal failure due to decreased excretion but can also be associated with thiazide diuretics, hypertension and metabolic syndrome
increased production of uric acid is associated with chemotherapy treatment of leukemia, tumor lysis syndrome and diets rich in nucleoproteins
allopurinol is a drug administered to patients undergoing chemotherapy to decrease their circulating uric acid levels to prevent gout and kidney stones which are associated with high concentrations of uric acid
hypouricemia is associated with a decrease in the liver enzymes required for depurination
fanconi syndrome affects the proximal tubules which causes the loss if uric acid in urine causing hypouricemia
What are the interferences for uric acid
anticoagulants using sodium fluoride should not be used
bilirubin and ascorbate can interfere with the uricase reaction
bilirubin may falsely decrease results in peroxidase catalyzed reactions
hemolysis may cause decreased results
What is creatinine
formed spontaneously in skeletal muscle from creatine and by the enzymatic action of creatine kinase
freely filtered and a small amount is secreted by the renal tubules into urine
What is the clinical significance of creatinine
used to estimate glomerular filtration rate, a test of glomerular function
increased concentrations can be caused by any disorder that decreases GFR it can also be transiently increased by diet
decreased concentrations can occur when there is an inadequate conversion from creatine
measured by the Jaffe kinetic reaction
What are interferences for creatinine
ketones, ascorbate, cephalosporin, glucose and proteins produce Jaffe like chromogen and cause spectral interference
bilirubin and hemoglobin are negative interferents
lipemia may introduce error
What are the test conditions for creatinine clearance testing
a blood specimen must be drawn within 72 hours of either the start or finish time of the urine collection
patients height and weight must be recorded
a 24 hour urine must be collected and refrigerated through out the collection period
What is the formula for creatinine clearance
(UV/P)x(1.73/SA)
U = urine concentration of creatinine
P = plasma concentration of creatinine
V = volume of urine in a unit of time (mL/s)
SA = surface area of the patient
there are 86400 seconds in 24 hours
What is the reference interval for creatinine clearance
1.30-2.30 mL/sec/1.73m^2
Why does the creatinine clearance test overestimate the GFR
because approximately 10% of creatinine in urine is the result of tubular secretion
What are the sources of error in the creatinine clearance test
pre-analytical errors due to patient compliance with timing, collection, and storage of urine
What causes a decrease of creatinine clearance
renal disease and heart disease
What is the estimated GFR
equations can be used to estimate GFR without needing a urine collection
When will estimates of GFR not be reliable
acute kidney injury, unusually high or low muscle mass, if the patient is on medication that interferes with the tubular secretion of creatinine
What does the presence of albumin in the urine indicate
damage to the glomeruli and basement membranes such as chronic kidney disease as seen in diabetic nephropathy
What does proteinuria due to low molecular weight globulins indicate
tubular damage
What is microalbuminuria
albumin excretion above the normal range but below the level of detection for total protien
What is the albumin creatinine ratio used for
used to overcome urinary variations that are due to albumin concentration of hydration
the spot urine is preferred over the 24 hour collection due to patient compliance
How is screening done for kidney disease
urine reagent strips are used, if two screen three months apart are positive then the ACR is used as follow up
What is B-microglobulin
a small peptide that is part of the major histocompatibility complex
it is present on the surface of cells and is found in low but usually constant concentrations in plasma
it is freely and completely filtered by the glomerulus and then is reabsorbed and catabolized by the PCT cells
food indicator of GFR in normal patients
When is B-microglobulin increased
certain inflammatory diseases, renal failure and malignancies
When is blood and urine B-microglobulin used
to assess the integrity of the renal tubules particularly in renal transplant patients and those exposed to heavy metals
What is the characterization of acute kidney injury
a rapid reduction in kidney function that may present as oliguria or increased plasma creatinine
risk factors include increased age, diabetes, chronic kidney disease, heart disease and administration of nephrotoxic drugs
What is prerenal AKI
caused by factors affecting the blood supply to the kidney
commonly caused by cardiac failure and hypoglycemia due to burns, hemorrhage, vomiting, diarrhea and sepsis
What is renal AKI
the result of vascular, glomerular or interstitial damage
can be the result of aminoglycosides, nonsteroidal anti-inflammatory drugs, myoglobinuria or heavy metal poisoning
What is post renal AKI
the result of an obstruction in the flow of urine after it leaves the kidney
can be caused by prostatic enlargement, renal stones, fibrosis, or neoplasms of the urinary tract
What is CKD
the result of a progressive loss of renal function
the loss of renal function is irreversible
the number of functioning nephrons is decreased, urine tends to have a fixed specific gravity, isosthenuria indicates a lack of concentrating ability
How is CKD defined and staged
using estimated glomerular filtration rate, eGFR and urinary albumin/creatinine ratio
What is the primary cause of CKD
diabetes mellitus
What are other causes of CKD
glomerular nephritis, inherited disorders, infection and systemic diseases
What is the reference range for eGFR
<60 mL/min/1.73m^2
What is the reference range for plasma ammonia
<35 umol/L
critical - >199 umol/L
What is the reference range for creatinine
females - 40-100 umol/L
males - 50-120 umol/L
What is the reference range for urea
2.5-8.0 mmol/L
What is the reference range for uric acid
females - 150-400 umol/L
males - 200-500 umol/L
