Nonprotein Nitrogen

N wastes include _ _ _

1. creatinine

2. urea

3. uric acid

creatinine is synthesized in _ _ _ (organs)

1. kidneys

2. liver

3. pancreas

phosphocreatine is a ___ that is used for ___

and creatinine in bloodstream is influenced by ___.

high-energy compound // muscle contraction (phosphocreatine → creatine → creatinine) // dietary meat intake

GFR (mL/min) is a proxy for # of ___

functioning nephrons

high blood creatinine & low GFR = advanced renal failure

creatinine test methods

chemical

1. Jaffe rxn

enzymatic

1. creatininase

2. creastininase & creatinase

3. creatine deaminase

isotope-dilution mass spec (more accurate for lower creatinine conc)

Jaffe rxn = ___

• problems include:

creatinine + NaOH → orange-red complex

• lack of specifity

• many interferent cmpds & bilirubin=neg interferant

• overestimates by ~20%

• imprecision at lower creatinine conc → greater GFR estimation error

creatininase method

creatinine → creatine

not widely used

creatininase & creatinase method → yields → _ _ _

• where is this method used?

sarcosine + urea // glycine + formaldehyde + H2O2(=detected & measured)

• used in point of care

creatinine deaminase method detects _

• also used in _

NH4+ (ammonia) → quantified by reflectance spec

urea is formed by the ___ in the urea cycle:

proteins → amino acids → ___ → ___ → removed by ___

liver

ammonia // urea // nephrons (>90%) but also GI tract & skin

_ makes up >75% of nonprotein nitrogen excreted

urea

creatinine or urea gives better kidney fxn info?

creatinine since 90-95% of Cr is excreted in urine → better eval for kidney fxn

---

urea - significant amount is reabsorbed in kidneys

PRE-renal non-renal factors that inc [urea] plasma

1. high protein diet

2. inc protein catabolism

3. reabsorption of blood proteins (GI hemorrhage)

4. cortisol

5. dehyrdation

6. dec perfusion of kidneys (eg CHF)

POST-renal obstructive eg _ _ _

malignancy, nephrolithiasis, prostatism

plasma Cr & urea conc inc

blood urea nitrogen (BUN) / Cr ratio is calculated as

BUN:Cr = serum BUN / serum creatinine (mg/dL)

normal BUN:Cr ratio

10-20

in prerenal azotemia

BUN

Creatinine

Ratio

inc

normal

inc

---

via CHF, renal arterial stenosis, high protein diet

in renal azotemia

BUN

Cre

ratio

inc

inc

N

in postrenal azotemia

BUN

Cr

ratio

inc

inc

inc

dec BUN:Cr <10:1 indicates

intrarenal damage

via acute tubular necrosis, inc protein intake, starvation, severe liver dz (dec urea synth)

urea clearance is an ___ indicator of GFR bc ___

production rate dependent on nonrenal factors ie

• high protein diet → inc urea in urine

  • back diffusion ie its reabsorbed in the kidneys

plasma urea ref range

adults 6-20 mg/dL

adults >60 y/o 8-23 mg/dL

urea test methods

1. Fearon rxn

   1. no longer used

2. urea hydrolysis (urease)

3. spec: Berthelot rxn // Glutamate DH

4. potentiometry: ammonium ISE (POC)

uric acid is the major product of _ _ catabolism

adenosine & guanosine (= purine nucleosides)

where do we get our uric acid?

1. diet G/A → uric acid

   a. dietary sources ~300 mg

2. endogenous nucleic acid → uric acid

   a. daily synthesis ~400 mg

total urate body pool (purine free diet) normal vs Gouty arthritis

men ~1200 mg

women 600 mg

---

18,000-30,000 mg

only _ % of uric acid is excreted in the urine

6-12%, most is reabsorbed in the PCT

inherited purine disorder metabolism is ___

symptoms include:

rare

• kidney failure or stones in young

• gravel in infant’s diaper

• unexplained neuro problems in young

• gout in <30 y/o

hyperuricemia ref range

plasma uric acid

men > 7 mg/dL

women > 6 mg/dL

___ crystals in joint fluid cause Gout & in kidneys can cause ___ → intense inflammatory response including _ _ _

• classic site is ___

• these crystals are ___

monosodium urate // kidney stones

PMN, macrophages

• classic site = big toe joint

• negatively bifringent & needle shaped

primary/essential gout is mostly due to a combination of _

• high purine foods include:

1. metabolic overproduction of purines

2. dec renal excretion

3. inc dietary intake

• ie seafood, alcohol (beer), organs, red meat, carbonated drinks

rare hyperuricemia condition ___ syndrome is due to ___

symptoms include

Lesch-Nyhan // GHPRT defic for purine salvage pathway

1. mental retardation (inc purine to developing brain)

2. self-mutilation

3. acute kidney failure

4. gout

2ry gout is due to

1. uric acid renal retention

2. organic acidemia

3. inc nucleic acid turnover (tumor cells)

Gout management

1. NSAIDs

2. avoid high purine foods

3. avoid drugs that affect urate excretion ie thiazide diuretics

   1. uricosuric drugs to enhance uric acid excretion

pre-eclamptic toxemia is caused by _ _

• plasma urate in xs of _ at 32 weeks gestation assoc’d w inc perinatal mortality rate

1. uteroplacental tissue breakdown

2. dec kidney perfusion

• 6.0 mg/dL

uric acid test methods

1. phosphotungistic acid (many interferances)

2. uricase (interferance ascorbic acid, bili)

   1. HPLC

uric acid ref ranges

male 3.5-7.2 mg/dL

>9.0 mg/dL → 150x more likely to have gouty arthritis

---

female 2.6-6.0 mg/dL

inc after menopause, dec 1st trimester, after 24 weeks gestation inc again