Non-Protein Nitrogens and Glomerular Function Tests Flashcards
List the non-protein nitrogen compounds
- Amino acids: 20%
- Ammonia (deamination): 0.2%
- Creatine (muscle contraction): 2%
- Creatinine (muscle creatine): 5%
- Urea (detoxification of ammonia): 45%
- Uric acid (purine metabolism): 20%
2 specific sources of urea
- Detoxification product of ammonia from the urea cycle
- Product of dietary protien intake
3 sites in the nephron where urea is filtered, reabsorbed, or secreted
- Filtered: freely filtered in glomerulus
- Reabsorbed: 40-50% in PCT
- Secreted: Loops of Henle
Urea
- Relative usefulness for glomerular function assessment compared to creatinine
The BEST clinical use of BUN measurements lies w/ concomitant creatinine measurements
Urea
- 2 principal diagnostic uses of its measurement
Pre-renal and post-renal azotemia problems
Reference range of urea
8-26 mg/dL
5 factors that affect BUN levels
- State of hydration (affects renal blood flow rate)
- Renal function (but not until GFR falls to 50% of normal)
- Liver funciona
- Amount of protein in diet
- Amount of protein breakdown body
5 conditions that increase the nitrogen load
- Febrile illness
- Corticosteroid or tetracycline therapy
- Large protein ingestion
- GI bleed w/ blood absorption in gut
- Elevated thyroid hormone concentration
4 conditions that decrease the nitrogen load
- Low protein diet
- ↑ androgens
- Growth hormone
- Pregnancy
What test should be analyzed along w/ BUN in order to obtain the best assessment of renal function?
Creatinine
5 pre-renal causes of azotemia due to decreased blood flow to the kidney and decrease urea filtration
- Congestive heart failure
- Shock
- Hemorrhage
- Dehydration
- Marked decrease in blood volume
What is one cause of renal azotemia?
Renal failure
What are the 3 causes of post-renal azotemia that cause decreased excretion of urea?
- Reanl lithiasis (stones)
- Tumors of the bladder or prostate
- Severe infections
3 specific sources of creatine
- Kidneys
- Liver
- Pancreas
Enzyme necessary for conversion of creatine to phosphocreatine
Creatine Kinase (CK)
1 specific source of creatinine
Anhydride byproduct of creatine
3 sites in the nephron where creatinine is filtered, reabsorbed, or secreted
- Filtered: freely
- Reabsorbed: not reabsorbed by tubules
- Excreted: at constant rate w/ insignificant secretion
Creatinine
- 3 reasons why creatinine’s measurement may be used to estimate the GFR
- Freely filtered by glomeruli
- Not reabsorbed by tubules
- Excreted at constant rate w/ insignificant secretion
Creatinine
- Usefulness for detecting early glomeruluar dysfunction
- Detect kidney disease (decreases as disease worsens)
- Monitor patients w/ known renal disease
- Plan life sustaining therapy for those w/ end-stage renal disease
- Adjust drug dosage for agents excreted by kidney
Creatinine
- Reference range for men and women
- Men: 0.9-1.5 mg/dL
- Women: 0.8-1.2 mg/dL
4 clinical uses of GFR calculations
- Detect kidney disease (decreases as disease worsens)
- Monitor patients w/ known renal disease
- Plan life sustaining therapy for those w/ end-stage renal disease
- Adjust drug dosage for agents excreted by kidney
What chemical creatinine method has creatinine reacting directly w/ picrate ions under alkaline conditions to form a red-orange complex?
Principle of Jaffe creatinine method
Special reagents used in Jaffe creatinine method
Alkaline picrate ions
3 enzymes used for enzymatic determination of creatinine
- Creatininase
- Creatininase and creatinase
- Creatinine iminohydrolase
Normal ratio of BUN: creatinine
12:1-20:1
Specific cause for a constant ratio of 10:1-15:1 in the BUN:creatinine ratio
Patient probably has intrinsic renal disease
Uric acid
- One specific pathologic source
Catabolism of the purine base nucleosides, adenoside, and guanosine (= purine base metabolism)
Uric acid
- Two specific normal sources
- Food
- Conditions of increased nucleic acid turnover (cancer patients)
Uric acid
- Four sequential steps in its renal handling
- Free glomerular filtration
- Reabsorption of >90% in PCT
- Tubular secretion in the distal portion of the PCT
- Reabsorption in the DCT
Uric acid
- Two primary causes of hyperuricemia associated w/ increased formation
- Idiopathic
- Inherited metabolic disorders
Uric acid
- Five secondary causes of hyperuricemia associated w/ increased formation
- Excess dietary purine intake
- Increased nucleic acid turnover (chemotherapy, radiotherapy, myeloma, leukemia, trauma)
- Altered ATP metabolism (alcohol toxicity, tissue hypoxia)
- Preeclampsia
- Down Syndrome
Uric acid
- One primary cause associated w/ decreased excretion
Idiopathic
Uric acid
- Causes of primary gout
- Overproduction of purines
- Decreased renal secretion of uric acid
- Increased dietary intake of purines (problem handling uric acid)
Uric acid
- Causes of secondary gout
- Consumption of alcohol
- Fructose drinks
- Meat and seafood (dietary gout, acute/chronic renal disease)
Uric acid
- Reference range for men and women
- Men: 4.0-8.5 mg/dL
- Women: 2.7-7.3 mg/dL
Reagents used and scientist’s name associated w/ the chemical method for uric acid
Caraway method
- Oxidation of uric acid w/ reduction of phosphotungstic acid to tungsten blue
Reagents used in the enzymatic method for uric acid
Uricase method → uricase oxidizes urate to allantoin
Ammonia
- Three specific sources
- Deamination of proteins in the liver
- Bacerial proteases, creases, and amine oxidases act on contents of colon in GI tract
- Hydrolysis of the glutamine in both the small and large intestines
Ammonia
- One primary cause of increased ammonia
Inherited urea cycle deficiencies
Ammonia
-Three secondary causes of increased ammonia
- Advanced liver disease and renal failure
- Reye’s syndrome
- Hepatic encephalopathy in individuals w/ cirrhosis
Ammonia
- Four special collection and handling procedures
- Good venipuncture technique must be used
- Must be put on ice immediately and analyzed w/in 20 minutes of venipuncture
- Patient must not smoke after midnight for a fasting specimen draw; no smoking in phlebotomy area
- Lab area and glassware should be free from ammonia contamination
Ammonia
- Reference range
14-45 umol/L
Uric acid
- Two general causes of hyperuricemia
- Increased formation
- Decreased excretion
Uric acid
- Five secondary causes of hyperuricemia associated w/ decreased excretion
- Acute or chronic kidney disease
- Increased renal reabsorption or reduced secretion
- Lead poisoning (↑ PCT reabsorption, ↓ secretion of uric acid)
- Preeclampsia (↑ PCT reabsorption)
- Presence of organic acids (lactate or acetoacetate) (inhibits urate excretion)
Ammonia
- Reagents used in the enzymatic method
?
3 sites in the nephron where ammonia is filtered, reabsorbed, or secreted
- Filtered: freely
- Reabsorbed: PCT
- Secretion: DCT
The major nitrogen-containing byproduct of protien catabolism; ~75% of all NPNs excreted
BUN
Higher-than-normal blood level of urea or other nitrogen-containing compounds; caused by inability of the kidneys to excrete NPNs
Azotemia
What causes ↓ blood flow to the kidney, ↓ urea filtration, and subsequently ↑ urea levels in teh blood
Prerenal causes of azotemia
What causes obstruction of urine flow in the urinary tract; ↓ excretion causes ↑ urea in the blood
Postrenal causes of azotemia
Analytical methods for urea
- Enzymatic
- Chemical
Reagents used in the enzymatic methods for urea
- (Berthelot rxn): phenol and hypochlorite
- Coupled enzymatic rxn of ammonium ion w/ glutamate dehydrogenase
Reagent used in the chemical method for urea
Diazine
Describe the metabolism of creatine and its importance in muscle contraction
- Interconversion of phosphocreatine and creatine takes plce in muscle contraction
- Amount of creatinine produced daily depends on muscle mass and animal muscle in the diet
- Therefore, plasma levels do not vary greatly day-to-day
A condition caused by hyperuricemia and deposition of uric acid crystals in joint and body fluids
Gout
Describe primary gout
- Monosodium urate precipitates from supersaturated body fluids
- Uric acid crystals deposit in joint fluids, as well in surrounding tissue, causing a characteristic inflammatory response and pain
- Arises from enzyme deficiencies in catabolizing uric acid
Consumption of coffee, vitamin C, and dairy products, as well as physical fitness appears to ____ risk of ____, probably due to decreasing insulin resistance
Decrease; gout
Rate at which the kidneys are able to remove a filterable substance from the blood per unit of time
Clearance
Clearance depends on what 2 things?
- Plasma concentration of that substance
- Ability of kidneys to remove it
3 reasons why creatinine is used, rather than urea, for glomerular function assessment
- Majority of creatinine is handled in the glomerulus; BUN is reabsorbed adn secreted at other renal sites
- Production of creatinine is fairly stable day-to-day (muscle mass doesn’t change much on a daily basis); BUN is affected by state of hydration and dietary intake of protein
- There aren’t many diseases that affect muscular function (urea production is affected by liver function)
2 reasons why creatinine clearance calculation is used to assess glomerular function
- Its production is faily constant day-to-day
- It’s freely filtered at the glomerulus and not secreted by teh renal tubules
List the 3 instructions which should be given to a patient who is collecting a timed urine specimen
- Void into toilet and note the time
- Collect every urine thereafter until the collection period is over, refrigerating specimen in b/w voids
- At the end of the collection period, void and include this specimen in collection
- Do NOT include first AND last voids
GFR equation
?
Calculate a corrected creatinine clearance in mL/min
[(U/V)/P] x (1/t) x (1.73/SA)
Calculate a creatinine excretion (“check”) in g/volume
[(UCR x TV x (1/1000) x (1/100)]
State the usefulness of calculating creatinine excretion (“check”) in g/volume
- Calculated to assess the “completeness” of a 24-hr urine collection, since creatinine production is fairly constant
- If < 0.5, it’s probably an incomplete collection
List 2 compounds that may be used instead of creatinine when a more precise assessment of glomerular function is required
- Inulin clearance
- Cystatin C
