U4 LEC: NPNs: UREA (PT. 1) Flashcards
These are nitrogen containing substances found in blood that are not proteins
Nonprotein Nitrogen Compounds
NPNs are used for the?
assessment and monitoring of renal function
NPNs are considered as?
waste products
Historically, nitrogen content was measured with?
removal of proteins
Specimen used in historical methods for NPN
Protein Free Filtrate
Clinically significant NPNs
- Urea / BUN
- Amino acids
- Uric Acid
- Creatinine
- Creatine
- Ammonia
Concentration in Plasma and Urine
Urea
P: 45-50%
U: 86%
Concentration in Plasma and Urine
Amino acids
P: 25%
Concentration in Plasma and Urine
Uric Acid
P: 10%
U: 1.7%
Concentration in Plasma and Urine
Creatinine
P: 5%
U: 4.5%
Concentration in Plasma and Urine
Creatinine
P: 1-2%
Concentration in Plasma and Urine
Ammonia
P: 0.2%
U: 2.8%
This NPN should not be present in the bloodstream as it can go up to the brain and become neurotoxic.
Ammonia
NPNs not present in Urine
- Amino acids (repurposed)
- Creatine
This is the major excretory product from protein metabolism, and is the major NPN found in the blood.
Urea
The amino acid from protein metabolism will enter 3 pathways which are?
- for energy
- entering the urea cycle
- for another amino acid
Synthesis of Urea happens where?
liver
When does urea synthesis start?
after digestion of protein > ammonium is made > enters liver for conversion to urea
The Urea Cycle is also known as the?
Krebs Henseleit Cycle
The Urea Cycle takes place in?
hepatocytes
Urea Cycle
Primary Function
conversion of ammonium ions to urea in liver/hepatocyte for excretion by kidney
The Urea Cycle is a _________ process between the?
compartmentalized, mitochondria and cytosol
Urea Cycle
This starts when amino acid from ____________ generated in protein metabolism binds with?
ammonia, CO2
Urea Cycle
Ammonia first enters the?
mitochondria of hepatocyte
This enzyme converts ammonia to carbamoyl phosphate.
CPS1
CPS1 stands for?
Carbamoyl Phosphate Synthetase 1
Urea Cycle
This is considered the first step. This enters the cycle and eventually becomes Urea.
Carbamoyl Phosphate
Urea Cycle
Carbamoyl phosphate is converted into citrulline by the enzyme?
Ornithine Transcarbomylase (OTC)
Urea Cycle
OTC stands for?
Ornithine Transcarbomylase
Urea Cycle
Products of OTC
Citrulline, Inorganic phosphate
Urea Cycle
Citrulline will enter?
cytoplasm/cytosol
Urea Cycle
This enzyme converts Citrulline to Arginosuccinate.
Arginosuccinate Synthetase
Urea Cycle
Citrulline is converted to?
Arginosuccinate
Urea Cycle
Arginosuccinate meets what enzyme to release Arginine and Fumarate?
Arginosuccinate lyase
Urea Cycle
Arginosuccinate lyase produces?
Arginine and Fumarate
Urea Cycle
Arginine will meet what enzyme for conversion to Ornithine?
Arginase
Urea Cycle
What will be formed during conversion of Arginine to Ornithine by Arginase?
Urea
What is increased (↑) if there is non production of urea?
(↑) Ammonia
(kasi di siya nacconvert to urea)
T/F: Any enzyme deficiency concerning the urea cycle will result to non production of urea.
True
Urea is filtered by?
glomerulus
Parts of the Nephron that contains Urea
- Proximal convoluted tubules
- Loop of Henle
- Collecting tubules
Exit from nephron (palabas) will be brought back to?
capillary (bloodstream)
Entry to nephron will be brought to?
urine
Urea is reabsorbed in the?
proximal convoluted tubules
Percent of Urea that is reabsorbed
40%
Percent of Urea excreted in urine
50%
Percent of Urea excreted in GI tract (stool) or skin perspiration (Sweat)
< 10%
Concentration of urea is dependent on?
- renal function / perfusion
- protein content of diet
- amount of protein metabolism (madami kang kinakain but can it convert to urea)
Why do we need to reabsorb Urea back in blood?
maintain balance in content or osmolality of blood if dehydrated (konting fluid, need may ibalik na salt or compound)
T/F: Urea is different from Urea nitrogen (Urea N) and BUN in terms.
True
1 mmol N is equal to?
14mg N
1 mmol Urea is equal to how many mmol of N?
2 mmol N
1 mmol Urea is equal to how many mg of Urea?
60 mg Urea
1 mg/dL BUN is equal to how many mg/dL of Urea?
2.14 mg/dL Urea
Conversion Factor of BUN to Urea
2.14
Clinical application
Excretion and reabsorption
Evaluate renal function
Clinical application
Increased urea in blood might pose a problem in the?
glomerulus
Clinical application
Decreased urea levels can indicate?
no reabsorption in the nephron
Clinical application
This refers to how levels of Urea will depend on blood volume
Hydration status
Clinical application
Diluted masyado, decreased (↓) urea levels
Overhydrated
Clinical application
(↑) Increased urea levels
Dehydrated
Clinical application
Representation of Nitrogen compound
Assess Nitrogen Balance
Clinical application
This machine works as your new kidneys
Verify adequacy of dialysis
Elevated concentration in the blood but asymptomatic or no problems in kidney (early pa)
Azotemia
Symptomatic, very high levels of plasma urea accompanied by renal failure
Uremia / Uremic Syndrome
Treatment for Uremia
dialysis or kidney transplant
In Azotemia, levels of _____ are also being measured along with BUN
Creatinine
Under pre-renal
Impaired perfusion:
- Cardiac failure
- Sepsis
- Blood loss
- Dehydration
- Vascular occlusion
Under renal
- Glomerulonephritis
- Small-vessel vasculitis
- Acute tubular necrosis (Drugs, Toxins, Prolonged hypotension)
- Interstitial nephritis (Drugs, Toxins, Inflammatory disease, Infection)
Under Post-Renal
- Urinary calculi
- Retroperitoneal fibrosis
- Benign prostatic enlargement
- Prostate cancer
- Cervical cancer
- Urethral structure/valves
- Meatal stenosis/phimosis
Pathophysiology of Pre-renal Azotemia
reduction in blood flow to kidney / decreased blood flow to kidney
Examples of decreased blood flow to kidneys (Pre-renal)
- Congestive heart failure
- Shock
- Hemorrhage
- Dehydration (no fluid, wala ring ippump)
Other causes of Pre-renal Azotemia
level of protein metabolism
Conditions of other causes of Pre-renal Azotemia
- High protein diet
Increased protein catabolism
Fever
- Major illness
- Stress
- Burns
- Corticosteroid therapy
- GI bleeding
Pathophysiology of Renal Azotemia
- Acute/chronic Renal failure
- Glomerulonephritis
- Tubular necrosis
- Other intrinsic renal disease
Renal Azotemia
Problem in the filter
Glomerulus
Renal Azotemia
Problem in the tubules, not capable of reabsorption
Tubular necrosis
Conversion from azotemia to uremia is focused on?
Renal azotemia
Post-renal Azotemia refers to?
Urinary tract obstruction
Causes of Post-renal Azotemia / Obstruction
1.) renal calculi or kidney stones
2.) tumors (prostate / bladder)
The types of Azotemia can be distinguished by computing for the?
Urea Nitrogen : Creatinine Ratio
Normal N:C ratio
10:1 - 20:1
Normal BUN in Conventional Unit
6-20 mg/dL
Increase in urea
> 20
Normal Creatinine
1.5 mg/dL
T/F: Creatinine has to be excreted, no reabsorption occurs.
True
Urea Nitrogen and Creatinine
Pre-renal Azotemia
High urea (decreased blood flow)
Normal creatinine
ELEVATED RATIO
Urea Nitrogen and Creatinine
Renal Azotemia
High urea
High creatinine
ELEVATED/NORMAL RATIO
Urea Nitrogen and Creatinine
Post-Renal Azotemia
Normal (?, dapat high) urea
High creatinine
ELEVATED RATIO
T/F: In renal azotemia, there is a proportional increase for both urea and creatinine.
True
T/F: Urea in Post-Renal Azotemia can also be high.
True
This is a marker of kidney filtration.
Creatinine
Conditions with decreased levels of plasma urea and decreased N:C ratio
- decreased protein intake
- poor nutrition
- overhydration
- severe liver disease (cannot synthesize ammonia)
- severe vomiting and diarrhea (GI tract)
- increased protein synthesis (recycled to make another protein)
Measures urea as a whole
Direct method
Measures only nitrogen content of Urea
Indirect method
Conversion Factor of Urea to BUN
0.467
BUN Conventional to BUN SI Unit
0.357
6-20mg/dL is equal to what SI unit of BUN?
2.1 - 7.1 mmol/L
Urea Determination
Condensation with Diacetyl Monoxime Method
Fearon’s Reaction
Urea Determination
Fearon’s Reaction is also known as?
Friedman’s Method or Xanthydrol Method
Fearon’s Reaction
Reagents
strong acid, oxidizing agent, ferric ions, thiosemicarbazide
Fearon’s Reaction
Product
Yellow diazine derivative (Ferric)
Fearon’s Reaction
Advantages
- Ammonia does not interfere
- Used in autoanalyzers
Fearon’s Reaction
Disadvantages
- non specific
- uses toxic substances
Fearon’s Reaction
DAM with water produces?
diacetyl and H+
Urea Determination
Reaction with o-phtalaldehyde and napthylethylene will produce?
chromogen or colored product
Reaction with o-phtalaldehyde and napthylethylene
Reagents
Isoindoline and napthylethylene diamine
Reaction with o-phtalaldehyde and napthylethylene
Advantages
- No ammonia interference
- Used in automation (spectrophotometry)
Reaction with o-phtalaldehyde and napthylethylene
Disadvantage
sulfa containing drugs interfere
This method also produces yellow product, converting ammonium to ammonia.
Micro-Kjeldahl Nessler Method
Enzymatic methods utilizes?
Urease
Enzymatic Methods
This method utilizes the Nessler’s Reagent to form yellow product.
Urease-Nessler’s Method
Enzymatic Methods
This uses phenol hypochlorite to release product that is indophenol blue.
Urease-Berthelot’s Method
Urease-Berthelot’s Method
Disadvantages
- non specific (since it is a measure of ammonia)
- very sensitive to interference from endogenous NH3
Enzymatic Methods
Most common
Urease-L-Glutamate Dehydrogenase (GLDH) Method
GLDH Method
Coupling reaction with what enzyme, and releases what products?
GLDH, 2-oxoglutarate to glutamate
GLDH Method
Measures the?
reduction of NADH to NAD
T/F: Disappearance of NADH is proportional to Urea levels.
True
Enzymatic Methods
Conductivity of ammonium is measured
Urease-Conductimetric Method
Proposed Reference Method
Isotope Dilution Mass Spectrophotometry (IDMS)
Specimen Requirements for BUN
Refrain tubes that have?
- Sodium citrate
- Sodium fluoride
Action of Na Citrate and NaF
inhibits urease
Urea is susceptible to _______, which results in urea converted back to ammonia
bacterial decomposition
Bacteria in urine can cause?
ammoniacal odor / mapanghi (increased ammonia)
Urine sample should be?
refrigerated
T/F: Diet influence or no fasting requirement will not affect BUN.
True
pwede daw sya maginfluence pero hindi agad agad
Urine should be collected for?
24 hours
Urea Nitrogen in Urine
12-20 g/dL (0.43-0.71 mol urea/d)