Urea Synthesis and Renal Function Tests

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Questions and Answers

What is the primary site of urea synthesis in the body?

Pancreas

Spleen

Kidneys

Liver (correct)

What is the primary function of the kidneys in relation to urea?

Breakdown of urea

Excretion of urea (correct)

Storage of urea

Synthesis of urea

What is the significance of measuring urea levels in clinical chemistry?

To assess liver function

To assess renal function (correct)

To assess spleen function

To assess pancreatic function

What is the term for the compounds used to assess renal function in clinical chemistry?

Non-Protein Nitrogenous Compounds Signup and view all the answers

What process occurs in the liver to produce urea?

Deamination of amino acids Signup and view all the answers

What is the highest concentration of urea found in?

Blood Signup and view all the answers

What is the term for the waste product of protein metabolism?

Urea Nitrogen Signup and view all the answers

What is the conversion factor to convert BUN to urea?

2.14 Signup and view all the answers

What is the older term still in use to measure nitrogen?

Blood Urea Nitrogen Signup and view all the answers

What is formed in the liver from amino groups and free ammonia?

Urea Signup and view all the answers

What is the primary reason why urea needs to be removed from the circulation?

Because it is a waste product Signup and view all the answers

What is the relationship between BUN and urea?

BUN can be converted to urea by multiplying by 2.14 Signup and view all the answers

What is the significance of the term 'Urea Nitrogen'?

It is a more accurate term for urea Signup and view all the answers

Where is urea primarily formed in the body?

Liver Signup and view all the answers

What is the importance of measuring urea levels in the blood?

To monitor protein metabolism Signup and view all the answers

What does an increase in serum urea level indicate?

Renal failure or dehydration Signup and view all the answers

What can a decrease in serum urea level indicate?

Severe liver disease or malnutrition Signup and view all the answers

What is the significance of measuring urea levels in addition to evaluating renal function?

To evaluate the patient's hydration state and nitrogen balance Signup and view all the answers

Why is measuring urea levels important for patients undergoing dialysis?

To evaluate the adequacy of dialysis Signup and view all the answers

What can measuring urea levels help clinicians assess in addition to renal function?

Hydration state and nitrogen balance Signup and view all the answers

What is the main objective of measuring urea levels in patients undergoing dialysis?

To assess the effectiveness of dialysis treatment Signup and view all the answers

What is the expected outcome of effective dialysis treatment on urea levels?

Urea levels decrease but remain high Signup and view all the answers

What is the relationship between creatinine and urea levels in dialysis patients?

Creatinine levels decrease when urea levels decrease Signup and view all the answers

Why is it essential to monitor urea levels in patients undergoing dialysis?

To adjust the dialysis treatment accordingly Signup and view all the answers

What is the primary reason for measuring urea levels in patients undergoing dialysis?

To assess the effectiveness of dialysis treatment Signup and view all the answers

What is the product of the reaction between urea and glutamine dehydrogenase?

Glutamate + NAD + hydrogen Signup and view all the answers

What is the purpose of diacetyl monoxime in the chemical method of urea analysis?

To react with water to produce hydroxylamine and diacetyl Signup and view all the answers

What is the role of urease in modern analytical methods of urea analysis?

To catalyze the hydrolysis of urea Signup and view all the answers

What is the common method of urea analysis that involves the measurement of the rate of disappearance of NADH at 340 nanometers?

GDH method Signup and view all the answers

What is the reference range for urea levels in the blood?

6-20 milligrams per dL Signup and view all the answers

What specimens can be used for urea testing?

Urine, serum, or plasma Signup and view all the answers

Why is refrigeration of urine specimens necessary?

To prevent bacterial decomposition of urea Signup and view all the answers

What is the term for a high plasma urea concentration accompanied by renal problems?

Uremic syndrome Signup and view all the answers

Is fasting required for urea testing?

No, a single protein-containing meal has a negligible effect Signup and view all the answers

What is the consequence of untreated uremic syndrome?

All of the above Signup and view all the answers

What is creatinine formed from?

Phosphocreatine Signup and view all the answers

What regulates creatinine levels in the body?

Kidney excretion Signup and view all the answers

What is not affected by creatinine levels?

Diet Signup and view all the answers

What is the result of the loss of phosphoric acid from creatine phosphate?

Creatinine Signup and view all the answers

Why do males and females have different normal creatinine values?

Due to differences in muscle mass Signup and view all the answers

What is the primary cause of reduced renal blood flow in the prerenal stage?

Congestive heart failure Signup and view all the answers

What is the result of decreased renal function in the renal stage?

Increased plasma urea concentration Signup and view all the answers

What is the characteristic of the postrenal stage?

Obstruction of the urinary tract Signup and view all the answers

What is the effect of congestive heart failure on the kidney?

Decreased blood flow Signup and view all the answers

What is the result of decreased blood delivery to the kidney?

Decreased urea filtration Signup and view all the answers

What is the consequence of increased protein catabolism?

Increased urea levels Signup and view all the answers

What is the characteristic of prerenal disorders?

Reduced renal blood flow Signup and view all the answers

What is the result of chronic renal disease?

Decreased urea excretion Signup and view all the answers

What is the main difference between prerenal and renal stages?

Prerenal stage has reduced renal blood flow, renal stage has decreased renal function Signup and view all the answers

What is the common characteristic of prerenal disorders?

Reduced renal blood flow Signup and view all the answers

What is the purpose of measuring creatinine clearance?

To measure the amount of creatinine eliminated from the blood by the kidneys Signup and view all the answers

What is required to compute creatinine clearance?

A 24-hour urine collection and a plasma sample Signup and view all the answers

What is the typical reference range for creatinine clearance in males?

0.9-1.3 mg/dL Signup and view all the answers

What is the duration of urine collection for creatinine measurement?

24 hours Signup and view all the answers

What is the purpose of measuring creatinine in urine?

To evaluate the glomerular filtration rate Signup and view all the answers

What is the formula to calculate creatinine clearance?

U * V / P * 1.73 Signup and view all the answers

What is the average body surface area used in creatinine clearance calculations?

1.73 m² Signup and view all the answers

What is the estimated glomerular filtration rate (eGFR) based on?

Blood creatinine and MDRD formula Signup and view all the answers

What is the correction required for estimated glomerular filtration rate (eGFR)?

For gender and race Signup and view all the answers

What is the range of creatinine clearance for males?

105 ± 20 mL/min/1.73 m² Signup and view all the answers

What is uric acid synthesized from?

Purine nucleic acids Signup and view all the answers

Where is uric acid primarily synthesized in the body?

Liver Signup and view all the answers

How is uric acid primarily regulated in the blood?

Through glomerular filtration and reabsorption Signup and view all the answers

What is the term for an abnormal increase in plasma uric acid concentration?

Hyperuricemia Signup and view all the answers

What is a common symptom of excessive uric acid deposition in the joints?

Painful inflammation Signup and view all the answers

What is characterized by neurological and behavioral abnormalities and the overproduction of uric acid?

Lesch-Nyhan syndrome Signup and view all the answers

What is associated with decreased serum uric acid?

Severe liver disease Signup and view all the answers

What is a condition that can lead to increased serum uric acid?

Lactic acidosis Signup and view all the answers

What is an example of a condition that can cause increased metabolism in cell nuclei?

Hemolytic anemia Signup and view all the answers

What is a condition that can lead to increased serum uric acid levels during pregnancy?

Toxemia of pregnancy Signup and view all the answers

What is the product of the reaction between uric acid and phosphotungstic acid?

Allantoin, CO2, and tungsten blue Signup and view all the answers

What is the typical reference range for uric acid levels in males?

3.5 - 7.2 mg/dL Signup and view all the answers

What enzyme is used to react with uric acid to produce allantoin and CO2?

Uricase Signup and view all the answers

What is measured to determine the concentration of uric acid in a sample?

The decrease in absorbance at 293 nm Signup and view all the answers

What is the significance of the color change in the chemical method of uric acid detection?

It indicates the concentration of uric acid Signup and view all the answers

What happens to ammonia in the body when hepatocytes fail to convert it to urea?

It accumulates in the blood. Signup and view all the answers

What is the term associated with a deficiency of urea cycle enzymes?

Hyperammonemia Signup and view all the answers

What is the consequence of high levels of ammonia in the blood?

It becomes more toxic. Signup and view all the answers

Why is measuring ammonia levels significant?

To diagnose inherited metabolic disorders. Signup and view all the answers

What is the role of hepatocytes in the body?

To convert ammonia to urea. Signup and view all the answers

What is the purpose of collecting venous blood in EDTA?

To prevent hemolysis Signup and view all the answers

What is the primary use of blood ammonia levels in clinical diagnosis?

Detecting hepatic failure and Reye's syndrome Signup and view all the answers

What is the most common cause of increased plasma ammonia levels?

Severe liver disease Signup and view all the answers

How long is plasma stable when stored in an ice bath?

3 ½ hours Signup and view all the answers

What is the effect of freezing on plasma ammonia levels?

Levels remain stable Signup and view all the answers

What is the role of glutamate dehydrogenase in the reaction?

To catalyze the reaction of alpha-ketoglutarate and ammonia Signup and view all the answers

What is the decrease in absorbance at 340 nm wavelength proportional to?

The concentration of ammonia Signup and view all the answers

What is a potential source of interference in the reaction?

Incorrect handling of the blood sample Signup and view all the answers

What is the product of the reaction catalyzed by glutamate dehydrogenase?

Glutamate, NADP, and water Signup and view all the answers

What is the potential source of contamination in the reaction?

Ammonia contamination Signup and view all the answers

Study Notes

Synthesis of Urea

Urea is synthesized in the liver through two processes: deamination of amino acids and protein catabolism.
Amino acids undergo deamination, resulting in the synthesis of urea.

Excretion and Measurement of Urea

Urea is excreted by the kidneys.
The level of urea is measured in clinical chemistry as a renal function test, assessing kidney function.
Non-Protein Nitrogenous Compounds (NPNs) are used to assess renal function through tests in clinical chemistry.

Clinical Significance of Urea Measurement

Urea measurement is an important indicator of renal function in clinical chemistry.

Urea as a Waste Product

Urea is a waste product of protein metabolism that needs to be removed from the circulation.
Urea has the highest concentration in the blood due to being the major excretory product of protein metabolism.
Urea is formed in the liver from amino groups and free ammonia generated during protein metabolism.

Blood Urea Nitrogen (BUN)

Blood urea nitrogen (BUN) is an older term still in use, based on previous methodology where nitrogen was measured.
In the lab, BUN is converted to urea by multiplying the value of BUN by 2.14.
To convert BUN to urea, the formula is: BUN x 2.14 = Urea.

Urea as a Waste Product

Urea is a waste product of protein metabolism that needs to be removed from the circulation.
Urea has the highest concentration in the blood due to being the major excretory product of protein metabolism.
Urea is formed in the liver from amino groups and free ammonia generated during protein metabolism.

Blood Urea Nitrogen (BUN)

Blood urea nitrogen (BUN) is an older term still in use, based on previous methodology where nitrogen was measured.
In the lab, BUN is converted to urea by multiplying the value of BUN by 2.14.
To convert BUN to urea, the formula is: BUN x 2.14 = Urea.

Urea Levels and Disease Indications

Increased serum urea levels indicate diseases such as:
Renal failure
Glomerulonephritis
Urinary tract obstruction
Congestive heart failure
Dehydration
Increased protein catabolism

Decreased Urea Levels and Associated Conditions

Decreased serum urea levels suggest:
Severe liver disease
Vomiting
Diarrhea
Malnutrition

Measurement of Urea and Its Significance

The measurement of urea is used to:
Define renal function
Assess the hydration state of the patient
Evaluate nitrogen balance
Monitor the adequacy of dialysis in patients undergoing treatment

Urea Measurement

Urea measurements are originally performed on protein-free filtrate of whole blood.
The measurement is based on the amount of nitrogen in the blood sample.

Analytic Methods

At least 2 analytic methods can be employed in the lab to determine the level of urea in the blood.

Dialysis and Urea

Dialysis patients' creatinine and BUN levels will never go down to normal, but rather remain slightly higher than normal.
During dialysis, the urea level is typically high.
To evaluate the effectiveness of dialysis, the urea level should decrease to at least slightly higher than normal.
For example, if a patient's creatinine level is 1000, it should decrease to 200, which is still high but indicates some improvement.

Kinetic Method

Urea reacts with glutamine dehydrogenase to produce ammonium carbonate, which is then coupled with oxoglutarate and NADH to form glutamate, NAD+, and hydrogen.
This method is used to measure blood urea nitrogen (BUN).

Chemical Method

Diacetyl monoxime reacts with water to produce hydroxylamine and diacetyl.
In the presence of acidified urea, diacetyl reacts to form a yellow diazine derivative, which represents the concentration of urea in the blood.

Modern Analytical Methods

Enzymatic methods, such as the urease method, are used to measure BUN.
Urease catalyzes the hydrolysis of urea, producing an ammonium ion that represents the quantity of urea in the blood sample.
The most common method is the GDH (Glutamate Dehydrogenase) method, which measures the rate of NADH disappearance at 340 nanometers to represent the concentration of urea in the sample.

Reference Range

Normal BUN levels range from 6 to 20 milligrams per deciliter (mg/dL).

Urea Testing

Specimens suitable for urea testing include plasma, serum, or urine.
Urine specimens require refrigeration if not tested immediately to prevent bacterial decomposition of urea.

Preparation for Urea Testing

Fasting is not typically required for urea testing due to the minimal effect of a single protein-containing meal.

Azotemia and Uremic Syndrome

Azotemia is characterized by elevated concentrations of urea in the blood.
High plasma urea concentration is associated with renal problems and renal failure, leading to uremic syndrome (or urea syndrome).
Uremic syndrome is a life-threatening condition that may require dialysis and/or kidney transplant, and can be fatal if left untreated.

Creatinine Formation

Creatinine is a waste product of muscle contraction.
It is formed from phosphocreatine, a high-energy compound.
Phosphoric acid is lost into creatine phosphate and water, yielding creatinine.

Factors Affecting Creatinine Levels

Sex differences in muscle mass result in differences in normal creatinine values.

Regulation of Creatinine Levels

Creatinine levels are regulated by kidney excretion.

Characteristics of Creatinine

Creatinine levels are not affected by diet.
Creatinine levels are not affected by rate of urine flow.
Creatinine is not reabsorbed by renal tubules.

Prerenal Disorders

Prerenal stage is characterized by slightly increasing levels of urea
Prerenal disorders contributing to increased urea levels include:
- Congestive heart failure
- Hemorrhage
- Dehydration
- Increased protein catabolism
- High protein nutrition
These disorders result in reduced renal blood flow, leading to decreased blood delivery to the kidney and consequently, less urea filtration
As a result, more urea accumulates in the circulation

Renal Stage

Acute and chronic renal problems, such as glomerulonephritis and tubular necrosis, contribute to increased urea levels
Decreased renal function causes increased plasma urea concentration due to compromised urea excretion
In chronic renal disease, the kidney is dysfunctional, leading to urea accumulation in the circulation

Postrenal Stage

Obstruction of the urinary tract, caused by:
- Renal calculi
- Tumor of the bladder or prostate
- Severe infection
Decreased urea levels can occur in patients with:
- Protein intake deficiency
- Severe vomiting, diarrhea, and liver disease
- Pregnancy

Diagnosing and Managing Urea Imbalance

Differentiating the cause of abnormal urea concentration can aid in calculating urea nitrogen to creatinine ratio
Accurate diagnosis enables doctors to manage patients effectively

Urine Creatinine

Urine creatinine is an endogenous substance present in urinary samples.
Measurement of urine creatinine is typically done over a 24-hour period.
Alternatively, a 22-hour urine creatinine collection can also be used.

Creatinine Clearance

Creatinine clearance measures the amount of creatinine eliminated from the blood by the kidneys.
It is used to assess the glomerular filtration rate (GFR).
The test requires a plasma sample and a 24-hour urine collection at the same time.
Body surface area and average body surface area are needed to compute creatinine clearance.
Typical reference ranges for creatinine clearance are:
- Male: 0.9-1.3 mg/dL
- Female: 0.6-1.1 mg/dL

Urine Creatinine and Renal Function

Urine creatinine (U) in mg/dL times volume (V) is equal to the urine flow divided by the plasma creatinine (P) times 1.73, which is the average body surface area.
Reference ranges for urine creatinine differ according to age and sex, with values decreasing with age.

Creatinine Clearance

Creatinine clearance can be used to assess renal function, with values of 105 ± 20 mL/min/1.73m² for males and 95 ± 20 mL/min/1.73m² for females.
The values are based on a body surface area of 1.73 square meters.

Estimated Glomerular Filtration Rate (eGFR)

eGFR uses only a blood creatinine and the MDRD (Modification of Diet in Renal Disease) formula.
Correction for gender and race is required for eGFR calculation.
eGFR results are only reported as a numerical value if specific conditions are met.

Uric Acid Production and Regulation

Uric acid is synthesized in the liver as a major waste product of purine (adenosine and guanine) catabolism nucleic acids.
It is also a waste product of normal chemical processes and can be found in blood, urine, serum, and plasma.

Regulation of Uric Acid

Regulation of uric acid in the blood is through glomerular filtration (kidneys) or excretion in the GI tract.
Excretion occurs through secretion by the distal tubules into the urine.
Most uric acid is reabsorbed in the proximal convoluted tubule and reused in high concentration.

Uric Acid in the Body

Uric acid can be deposited in the joints and tissues, causing painful inflammation, commonly seen in older people.
Measured in serum, urine, and plasma, where it is relatively insoluble.

Abnormal Conditions

Gout is an abnormal increase in plasma uric acid concentration, accompanied by pain and inflammation of the joints.
Hyperuricemia is the term for overproduction of uric acid.

Clinical Significance of Uric Acid

Increased metabolism in cell nuclei is associated with elevated uric acid levels
Hemolytic or megaloblastic anemia can lead to increased uric acid levels
Glycogen storage disease and fructose intolerance are also associated with elevated uric acid levels

Increased Serum Uric Acid

Gout is a condition characterized by increased serum uric acid
Renal disorders can lead to increased serum uric acid
Treatment of myeloproliferative disorder can result in increased serum uric acid
Lead poisoning and lactic acidosis are associated with increased serum uric acid
Toxemia of pregnancy can lead to increased serum uric acid
Lesch-Nyhan syndrome is a condition characterized by neurological and behavioral abnormalities and overproduction of uric acid, primarily affecting males

Decreased Serum Uric Acid

Severe liver disease can lead to decreased serum uric acid as a secondary disorder
Tubular reabsorption disorders are associated with decreased serum uric acid
Certain medications can induce decreased serum uric acid

Uric Acid Detection

Chemical methods are used to detect uric acid in samples
Uric acid reacts with phosphotungstic acid to form allantoin, CO2, and tungsten blue
The rate of concentration or density of the color indicates the concentration of uric acid in the sample

Reference Ranges

Male: 3.5 - 7.2 mg/dL
Female: 2.6 - 6.0 mg/dL

Uric Acid Reaction

Uric acid reacts with uricase, an enzyme, to produce allantoin, hydrogen peroxide, and CO2
The decrease in absorbance at 293 nm indicates the presence of uric acid

Ammonia Production and Urea Cycle

Ammonia is produced from the deamination of amino acids
Hepatocytes (liver cells) convert ammonia to urea for excretion

Liver Cell Malfunction and Hyperammonemia

Severe liver cell malfunction leads to increased blood levels of ammonia
Failure of hepatocytes to convert ammonia to urea causes ammonia accumulation in the blood
Hyperammonemia is associated with the deficiency of urea cycle enzymes

Neurotoxic Effects of Ammonia

High levels of ammonia in the blood become neurotoxic
Neurotoxic ammonia is associated with encephalopathy

Measuring Ammonia Levels

Ammonia levels are measured to detect inherited metabolic disorders
Elevated ammonia levels are indicative of severe liver diseases

Blood Sample Collection and Preparation

Venous blood samples should be free of hemolysis and placed on ice immediately to prevent degradation.
When plasma is needed, collect blood in tubes containing ethylenediaminetetra-acetic acid (EDTA) to prevent clotting.

Sample Centrifugation and Storage

Centrifuge the sample within 20 minutes of collection to separate the plasma from the blood cells.
Remove the plasma from the sample and store it in an ice bath to maintain stability for up to 3 ½ hours.
Frozen plasma can be stored for several days.

Blood Ammonia Testing

Blood ammonia testing is useful in detecting hepatic failure, Reye's syndrome, and urea cycle enzyme deficiencies.
Severe liver disease is the most common cause of increased blood ammonia levels.
Elevated plasma ammonia levels are seen in hepatic failure and Reye syndrome.

Glutamate Dehydrogenase (GDH) Reaction

Catalyzes the reaction of alpha-ketoglutarate and ammonia plus NADPH to form glutamate, NADP, and water

Measurement of Ammonia Concentration

Decrease in absorbance at 340 nm wavelength is proportional to the ammonia concentration in the specimen
NADPH consumption in the reaction is measured by the decrease in absorbance

Interferences in Ammonia Measurement

Incorrect handling of blood sample
Ammonia contamination of the sample can affect measurement accuracy

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Description

This quiz covers the synthesis of urea in the liver, its excretion by the kidneys, and its role in measuring renal function through clinical chemistry tests. Non-Protein Nitrogenous Compounds (NPNs) are also covered as they relate to assessing renal function.