U4 LEC: NPNs: UREA (PT. 1) Flashcards by maki 🐈‍⬛

Q

These are nitrogen containing substances found in blood that are not proteins

A

Nonprotein Nitrogen Compounds

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Q

NPNs are used for the?

A

assessment and monitoring of renal function

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Q

NPNs are considered as?

A

waste products

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Q

Historically, nitrogen content was measured with?

A

removal of proteins

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Q

Specimen used in historical methods for NPN

A

Protein Free Filtrate

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Q

Clinically significant NPNs

A

Urea / BUN
Amino acids
Uric Acid
Creatinine
Creatine
Ammonia

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Q

Concentration in Plasma and Urine

Urea

A

P: 45-50%
U: 86%

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Q

Concentration in Plasma and Urine

Amino acids

A

P: 25%

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Q

Concentration in Plasma and Urine

Uric Acid

A

P: 10%
U: 1.7%

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Q

Concentration in Plasma and Urine

Creatinine

A

P: 5%
U: 4.5%

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Q

Concentration in Plasma and Urine

Creatinine

A

P: 1-2%

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Q

Concentration in Plasma and Urine

Ammonia

A

P: 0.2%
U: 2.8%

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Q

This NPN should not be present in the bloodstream as it can go up to the brain and become neurotoxic.

A

Ammonia

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Q

NPNs not present in Urine

A

Amino acids (repurposed)
Creatine

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Q

This is the major excretory product from protein metabolism, and is the major NPN found in the blood.

A

Urea

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Q

The amino acid from protein metabolism will enter 3 pathways which are?

A

for energy
entering the urea cycle
for another amino acid

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Q

Synthesis of Urea happens where?

A

liver

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Q

When does urea synthesis start?

A

after digestion of protein > ammonium is made > enters liver for conversion to urea

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Q

The Urea Cycle is also known as the?

A

Krebs Henseleit Cycle

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Q

The Urea Cycle takes place in?

A

hepatocytes

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Q

Urea Cycle

Primary Function

A

conversion of ammonium ions to urea in liver/hepatocyte for excretion by kidney

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Q

The Urea Cycle is a _________ process between the?

A

compartmentalized, mitochondria and cytosol

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Q

Urea Cycle

This starts when amino acid from ____________ generated in protein metabolism binds with?

A

ammonia, CO2

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Q

Urea Cycle

Ammonia first enters the?

A

mitochondria of hepatocyte

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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?

1. renal function / perfusion 2. protein content of diet 3. 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)