p.3
Physiological Significance of Amino Acids and NPN Compounds
What are essential amino acids?
Amino acids that must be obtained from the diet.
p.17
Analytical Methods for NPN Compound Measurement
What is the purpose of the filtering layer in the dry slide technique?
To remove cellular components or interfering substances.
p.9
Urea Cycle and Ammonia Detoxification
What percentage of urea is passively reabsorbed by the renal tubules?
Between forty and seventy percent.
p.9
Clinical Relevance of Plasma and Urine NPN Concentrations
What is azotemia?
An increased concentration of urea in the blood.
p.10
Clinical Relevance of Plasma and Urine NPN Concentrations
What is post-renal azotemia?
A condition resulting from issues occurring after urine has left the kidneys, primarily due to urine flow blockage.
p.15
Creatinine as a Marker for Renal Function
What factors influence creatinine production?
Muscle mass, gender, age, and physical activity.
p.1
Sources and Classification of NPN Compounds
What are five examples of non-protein nitrogenous substances?
Amino acids, ammonia, creatinine, urea, and uric acid.
p.16
Analytical Methods for NPN Compound Measurement
What is the Jaffe reaction used for?
Determining creatinine concentration.
p.15
Clinical Relevance of Plasma and Urine NPN Concentrations
Why is creatinine a useful marker for glomerular function?
Because it is freely filtered by the glomerulus and not resorbed in the tubules.
p.4
Amino Acid Metabolism and Disorders
What are the symptoms of untreated phenylketonuria?
Increased phenylalanine levels, musty odor in urine, and potential mental retardation.
p.13
Uric Acid Metabolism and Gout
What are the two classifications of gout?
Primary gout and secondary gout.
p.13
Uric Acid Metabolism and Gout
How do uric acid concentrations vary?
They vary with gender and age, with men generally having higher concentrations.
p.14
Analytical Methods for NPN Compound Measurement
What advantage do enzymatic methods have over other methods for uric acid measurement?
They are more specific and have fewer interferences, and protein precipitation can be omitted.
p.14
Amino Acid Metabolism and Disorders
Why is creatine elevated in muscle disorders?
Because it is associated with muscle contraction and energy supply.
p.3
Clinical Relevance of Plasma and Urine NPN Concentrations
What is the role of uric acid in diagnosing disorders?
It is used to diagnose disorders of purine synthesis and catabolism.
p.17
Analytical Methods for NPN Compound Measurement
What is one enzymatic method involving creatinine?
Creatinine is converted to creatine, then to sarcosine and urea.
p.3
Amino Acid Metabolism and Disorders
What is the significance of the R group in amino acids?
It provides another functional group that contributes to the amino acid's properties.
p.6
Urea Cycle and Ammonia Detoxification
What is the most common form of Citrullinemia?
Type I, occurring in one out of every fifty-seven thousand live births.
p.2
Urea Cycle and Ammonia Detoxification
What is urea made from?
Two ammonia molecules and one molecule of carbon dioxide.
p.1
Physiological Significance of Amino Acids and NPN Compounds
Why are non-protein nitrogenous compounds significant in laboratory analysis?
They are small and soluble in aqueous solutions, allowing them to pass through the glomerular filtration barrier and appear in urine.
p.6
Urea Cycle and Ammonia Detoxification
What is the role of the protein citrin in Type II Citrullinemia?
Involved in the transport of molecules for the production and catabolism of sugars, proteins, and nucleotides.
p.4
Amino Acid Metabolism and Disorders
What is deamination in the context of amino acids?
The process that forms intermediates which can be glucogenic or ketogenic.
p.13
Uric Acid Metabolism and Gout
What forms in the joints and tissues of gout patients?
Needle-like crystals formed from urate and sodium.
p.4
Amino Acid Metabolism and Disorders
What causes Type I tyrosinemia?
A defect in the enzyme fumarylacetoacetate hydrolase.
p.7
Clinical Relevance of Plasma and Urine NPN Concentrations
What is Reye’s syndrome primarily associated with?
Central nervous system disorder and some liver dysfunction.
p.8
Analytical Methods for NPN Compound Measurement
What reaction occurs in the enzymatic method for measuring ammonia?
Plasma ammonium ions react with 2-oxoglutarate and NADPH to form glutamate, NADP, and water.
p.7
Interferences and Errors in NPN Analysis
What effect does hemolysis have on ammonia concentration measurements?
It should be avoided because ammonia concentration in red blood cells is higher than in plasma.
p.2
Physiological Significance of Amino Acids and NPN Compounds
What role does phosphocreatine play in muscle cells?
It helps maintain high ATP levels needed for muscle contraction.
p.16
Creatinine as a Marker for Renal Function
What factors affect the excretion of creatinine in urine?
Glomerular filtration and renal blood flow.
p.9
Physiological Significance of Amino Acids and NPN Compounds
What happens in congestive heart failure?
The heart can't pump blood sufficiently, causing a backup of blood.
p.4
Physiological Significance of Amino Acids and NPN Compounds
What are amino acids primarily known as?
The building blocks of proteins.
p.9
Clinical Relevance of Plasma and Urine NPN Concentrations
How does congestive heart failure affect renal blood flow?
It results in decreased renal blood flow and increased plasma urea.
p.1
Analytical Methods for NPN Compound Measurement
What is the importance of specimen handling for NPN determinations?
Appropriate specimen and handling are crucial for accurate measurements of amino acids, creatinine, urea, uric acid, and ammonia.
p.15
Clinical Relevance of Plasma and Urine NPN Concentrations
What are the normal creatinine reference ranges for adult males and females?
Males: 0.6 to 1.2 mg/dL; Females: 0.1 mg/dL less than males.
p.6
Urea Cycle and Ammonia Detoxification
How is ammonia detoxified in the liver?
By combining two ammonia molecules with a carbon dioxide molecule to form urea.
p.4
Amino Acid Metabolism and Disorders
What is the treatment for phenylketonuria?
A low protein diet and the drug Kuvan for some patients.
p.4
Amino Acid Metabolism and Disorders
What is the treatment for tyrosinemia?
A low protein diet and a drug to prevent toxic metabolite formation.
p.13
Analytical Methods for NPN Compound Measurement
What does the phosphotungstic acid method measure?
The reduction of phosphotungstic acid by urate to form tungsten blue.
p.7
Analytical Methods for NPN Compound Measurement
What analytical method can be used to analyze ammonia?
Ion selective electrodes.
p.2
Non-Protein Nitrogenous Compounds
What is creatinine a by-product of?
Phosphocreatine, a high energy compound found in muscle cells.
p.17
Analytical Methods for NPN Compound Measurement
What can be used to determine the amount of urea formed?
Converting urea to ammonia and using ion selective electrodes or enzymatic methods.
p.10
Clinical Relevance of Plasma and Urine NPN Concentrations
What causes renal azotemia?
Direct problems with the kidneys, such as acute and chronic renal failure, glomerular nephritis, and tubular necrosis.
p.5
Amino Acid Metabolism and Disorders
What symptom is associated with Alkaptonuria?
Change in color of urine upon standing.
p.10
Analytical Methods for NPN Compound Measurement
What are the different ways plasma urea values can be expressed?
As milligrams of urea nitrogen per deciliter, milligrams of urea per deciliter, or millimoles of urea per liter.
p.11
Analytical Methods for NPN Compound Measurement
What is the principle of direct methods for urea analysis?
Urea reacts directly with a reagent to form a colored compound that can be quantified spectrophotometrically.
p.10
Interferences and Errors in NPN Analysis
What should be avoided when collecting specimens for urea testing?
Using ammonium heparin as an anticoagulant and fluoride for enzymatic assays.
What happens to creatinine secretion as plasma concentration increases?
The amount secreted by the proximal tubule increases.
p.13
Uric Acid Metabolism and Gout
Who were some historical figures that suffered from gout?
Benjamin Franklin, Henry the Eighth, Thomas Jefferson, and Sir Isaac Newton.
p.5
Amino Acid Metabolism and Disorders
What is Isovaleric acidemia characterized by?
Distinctive odor of sweaty feet.
p.11
Clinical Relevance of Plasma and Urine NPN Concentrations
What does an increased urea/creatinine ratio with increased creatinine suggest?
A likely post-renal issue.
p.4
Amino Acid Metabolism and Disorders
What are the symptoms of Type I tyrosinemia?
Failure to thrive, vomiting, diarrhea, distended abdomen, and a cabbage-like odor.
p.13
Analytical Methods for NPN Compound Measurement
What method tends to give higher results for uric acid concentration?
The phosphotungstic acid method.
p.10
Clinical Relevance of Plasma and Urine NPN Concentrations
What is pre-renal azotemia?
A condition where the problem is not with the kidneys themselves, but with issues occurring before urine formation.
p.5
Amino Acid Metabolism and Disorders
What enzyme deficiency causes Alkaptonuria?
Lack of homogentisate oxidase.
p.12
Uric Acid Metabolism and Gout
Why do uric acid crystals form in acidic urine?
Because the urate form is ten times more soluble than the uric acid form.
p.15
Creatinine as a Marker for Renal Function
How does diet affect plasma creatinine concentration?
Plasma concentration does not change significantly, but large meat intakes can increase it by up to ten percent.
p.15
Creatinine as a Marker for Renal Function
How does creatinine production relate to plasma concentration?
Creatinine production decreases as plasma concentration increases.
p.4
Physiological Significance of Amino Acids and NPN Compounds
What role do amino acids play in metabolic pathways?
They are involved in the synthesis of enzymes and structural proteins.
p.6
Urea Cycle and Ammonia Detoxification
What can trigger Type II Citrullinemia in adults?
Certain medications, infections, surgery, and alcohol intake.
p.16
Analytical Methods for NPN Compound Measurement
What does the Jaffe reaction involve?
Creatinine reacting with picrate in an alkaline solution to form a red-orange complex.
p.4
Amino Acid Metabolism and Disorders
What are aminoacidopathies?
Genetic disorders caused by defects in enzymes that metabolize or transport amino acids.
p.11
Clinical Relevance of Plasma and Urine NPN Concentrations
What does a normal urea/creatinine ratio indicate in renal problems?
Both urea and creatinine concentrations are affected by kidney function.
p.8
Analytical Methods for NPN Compound Measurement
What does a change in electrical potential indicate in ammonia measurement?
It is proportional to the ammonia present in the plasma.
p.7
Amino Acid Metabolism and Disorders
What can cause increases in plasma ammonia concentrations due to genetic disorders?
Defects in the enzymes of the urea cycle.
p.7
Analytical Methods for NPN Compound Measurement
What should be done to blood samples after collection for ammonia analysis?
Place them on ice immediately to slow down amino acid deamination.
p.8
Urea Cycle and Ammonia Detoxification
How is urea produced in the liver?
From two ammonia molecules and one molecule of carbon dioxide in the urea cycle.
p.9
Clinical Relevance of Plasma and Urine NPN Concentrations
What condition results from increased plasma urea concentration due to renal failure?
Uremia or uremic syndrome.
p.2
Clinical Relevance of Plasma and Urine NPN Concentrations
What can cause increased ammonia concentrations in the plasma?
Liver damage or renal disease.
p.16
Clinical Relevance of Plasma and Urine NPN Concentrations
Which conditions can lead to increased plasma creatinine concentrations?
Acromegaly, giantism, and muscle necrosis (rhabdomyolysis).
p.5
Amino Acid Metabolism and Disorders
What condition can result from the accumulation of homogentisic acid?
Ochronosis and arthritis-like condition.
p.11
Analytical Methods for NPN Compound Measurement
What colored compound is formed when urea reacts with diacetyl?
A colored diazine compound that absorbs light at 540 nanometers.
p.1
Clinical Relevance of Plasma and Urine NPN Concentrations
What is the relationship between NPN test results and clinical conditions?
Test results for amino acids, urea, uric acid, creatinine, and ammonia can be correlated with various clinical conditions.
p.11
Clinical Relevance of Plasma and Urine NPN Concentrations
What does an increased urea/creatinine ratio indicate in pre-renal conditions?
Increased urea with normal creatinine concentration.
p.13
Uric Acid Metabolism and Gout
What renal damage can gout cause?
Urate deposits in the parenchyma and tubular cells of the kidneys.
p.13
Uric Acid Metabolism and Gout
What causes primary gout?
Overproduction or undersecretion of uric acid without an underlying cause.
p.14
Analytical Methods for NPN Compound Measurement
What is the role of uricase in the enzymatic method for uric acid measurement?
Uricase converts uric acid to allantoin and peroxide.
p.14
Analytical Methods for NPN Compound Measurement
What is HPLC and its relevance to uric acid detection?
High performance liquid chromatography can detect uric acid but is not commonly used for routine testing.
p.14
Clinical Relevance of Plasma and Urine NPN Concentrations
What is a limitation of creatine analysis in clinical laboratories?
Analytical methods for creatine are not readily available.
p.2
Clinical Relevance of Plasma and Urine NPN Concentrations
What factors can change the concentration of nonprotein nitrogenous compounds in plasma?
Diet, exercise, and environmental stress.
p.2
Amino Acid Metabolism and Disorders
Why do amino acids make up less than five percent of nonprotein nitrogenous compounds in urine?
They are actively transported back into the plasma.
p.15
Creatinine as a Marker for Renal Function
What percentage of creatine in muscle converts to creatinine?
About one to two percent.
p.1
Introduction to Non-Protein Nitrogenous Compounds
What are non-protein nitrogenous compounds (NPN)?
They are building blocks and breakdown products of proteins and nucleic acids in the body.
p.16
Analytical Methods for NPN Compound Measurement
What types of samples are acceptable for creatinine assays?
Plasma or serum, but not grossly hemolyzed samples.
p.10
Analytical Methods for NPN Compound Measurement
How stable is urea in plasma?
Stable for up to 24 hours at room temperature, several days if refrigerated, and for several months when frozen.
p.5
Amino Acid Metabolism and Disorders
What distinct odor is associated with Maple Syrup Urine Disease?
Smell like maple syrup or burnt sugar.
p.16
Analytical Methods for NPN Compound Measurement
Why were protein-free filtrates originally used in the Jaffe assay?
To eliminate interference from proteins in serum or plasma.
p.6
Analytical Methods for NPN Compound Measurement
What analytical methods can be used for amino acid identification?
Thin-layer chromatography, high performance liquid chromatography, ion exchange chromatography, capillary electrophoresis, and tandem mass spectrometry.
p.7
Clinical Relevance of Plasma and Urine NPN Concentrations
Why do newborns have higher ammonia concentrations?
Their liver has not matured sufficiently to effectively clear ammonia.
p.8
Analytical Methods for NPN Compound Measurement
What is the role of the electrode membrane in ammonia measurement?
It must be well maintained for accurate and precise results.
p.7
Analytical Methods for NPN Compound Measurement
What is essential for accurate ammonia blood sample results?
Proper collection and rapid processing of the blood.
p.8
Urea Cycle and Ammonia Detoxification
What is urea in relation to ammonia?
Urea is the non-toxic product formed from toxic ammonia in the liver.
p.17
Analytical Methods for NPN Compound Measurement
How do enzymatic methods compare to the Jaffe reaction?
They are more specific and have fewer interferences.
p.5
Amino Acid Metabolism and Disorders
How common is Alkaptonuria?
Occurs in one out of every 250,000 live births.
p.10
Clinical Relevance of Plasma and Urine NPN Concentrations
How does plasma urea concentration vary with age?
It tends to be lower in children and increases with age.
p.12
Uric Acid Metabolism and Gout
What is hypouricemia?
A decrease in plasma uric acid concentration.
p.10
Analytical Methods for NPN Compound Measurement
Why is it important to know the units of urea concentration being reported?
Because reference ranges change with the units used.
Is creatinine resorbed in the kidneys?
No, it is not normally resorbed like urea.
p.6
Amino Acid Metabolism and Disorders
What dietary approach helps minimize the effects of amino acid disorders?
A low protein or protein-restrictive diet.
p.16
Interferences and Errors in NPN Analysis
What substances can interfere with the Jaffe assay?
Proteins, alpha keto acids, cephalosporins, hemoglobin, and bilirubin.
p.13
Uric Acid Metabolism and Gout
What is the result of needle-like crystals in gout?
Irritation of the synovial lining and acute inflammatory response.
p.8
Analytical Methods for NPN Compound Measurement
How do some ammonia electrodes measure ammonia gas?
By using a high pH solution where ammonium ions become ammonia gas.
p.14
Amino Acid Metabolism and Disorders
What is creatinine and its relationship to muscle function?
Creatinine is a nonprotein nitrogenous compound that results from the interconversion of creatine and phosphocreatine during muscle contraction.
p.9
Clinical Relevance of Plasma and Urine NPN Concentrations
What factors can affect plasma urea concentration?
The amount of protein in the diet, the rate of protein catabolism, and the patient's liver function.
p.3
Amino Acid Metabolism and Disorders
What functional groups do amino acids contain?
An amino group and a carboxylic acid group.
p.2
Urea Cycle and Ammonia Detoxification
What happens to ammonia in the liver?
It is converted to nontoxic urea.
p.10
Clinical Relevance of Plasma and Urine NPN Concentrations
What can cause decreased plasma urea concentrations?
Liver disease, starvation, severe vomiting and diarrhea, repeated hemodialysis, and inborn errors of metabolism.
p.9
Physiological Significance of Amino Acids and NPN Compounds
What occurs when the left side of the heart cannot pump effectively?
Increased blood pressure in the lungs, leading to pulmonary edema.
p.9
Physiological Significance of Amino Acids and NPN Compounds
What is the result of damage to the right side of the heart?
Fluid is pushed out of the veins into the tissues, causing edema in the extremities and abdomen.
How does creatinine pass through the kidneys?
Creatinine freely passes through the glomerulus and enters the urinary filtrate.
p.4
Physiological Significance of Amino Acids and NPN Compounds
What are some nonprotein nitrogenous compounds synthesized from amino acids?
Purines, pyrimidines, porphyrins, creatine, histamine, thyroxine, epinephrine, and NAD.
p.4
Amino Acid Metabolism and Disorders
How do amino acids contribute to the body's energy?
They provide 12-20% of the body's energy as proteins are metabolized.
p.11
Clinical Relevance of Plasma and Urine NPN Concentrations
What is the normal ratio of urea nitrogen to creatinine?
Between twelve to twenty.
p.16
Analytical Methods for NPN Compound Measurement
What advancement has reduced the need for protein-free filtrates in the Jaffe assay?
The use of a kinetic method instead of an endpoint method.
p.5
Amino Acid Metabolism and Disorders
What are potential complications of homocystinuria?
Osteoporosis, connective tissue problems, and thrombosis.
p.13
Uric Acid Metabolism and Gout
What can cause secondary gout?
An underlying cause such as chemotherapy or renal disease.
p.3
Physiological Significance of Amino Acids and NPN Compounds
List three essential amino acids.
Arginine, histidine, isoleucine.
p.17
Analytical Methods for NPN Compound Measurement
What is a limitation of high performance liquid chromatography for creatinine testing?
It is expensive and time-consuming.
p.9
Clinical Relevance of Plasma and Urine NPN Concentrations
What can cause pre-renal azotemia?
Conditions like shock, hemorrhage, dehydration, and congestive heart failure.
p.11
Analytical Methods for NPN Compound Measurement
What do indirect methods measure in urea analysis?
The amount of ammonia formed after hydrolyzing the urea present.
p.16
Clinical Relevance of Plasma and Urine NPN Concentrations
What is the clinical significance of decreased creatinine concentrations?
They do not provide any relevant clinical information.
p.1
Clinical Relevance of Plasma and Urine NPN Concentrations
What factors can affect the concentration of non-protein nitrogenous compounds in plasma and urine?
Physiologic reasons for increased or decreased concentrations.
p.5
Amino Acid Metabolism and Disorders
What can happen if Maple Syrup Urine Disease is not treated?
Severe mental retardation, seizures, and death.
p.7
Clinical Relevance of Plasma and Urine NPN Concentrations
What is the normal ammonia concentration in adult plasma?
10 to 35 micromoles per liter (or 19 to 60 micrograms per deciliter).
p.14
Interferences and Errors in NPN Analysis
What compounds can interfere with the uric acid assay?
Glucose, ascorbic acid, caffeine, cysteine, and some drugs like Tylenol and theophylline.
p.8
Analytical Methods for NPN Compound Measurement
What method do most automated chemistry analyzers use to determine plasma ammonia concentration?
An enzymatic method involving glutamate dehydrogenase.
p.8
Interferences and Errors in NPN Analysis
What is a potential source of error in ammonia assays?
Smoking by the patient can contaminate results.
p.9
Urea Cycle and Ammonia Detoxification
How is urea primarily excreted from the body?
About ninety percent is excreted by the kidneys.
p.12
Uric Acid Metabolism and Gout
What can cause increased plasma uric acid concentrations?
Increased production or decreased excretion of uric acid.
p.11
Analytical Methods for NPN Compound Measurement
Why must endogenous ammonia be determined in urine samples?
To subtract it from the amount of ammonia formed by the breakdown of urea.
p.5
Amino Acid Metabolism and Disorders
What is the cause of Maple Syrup Urine Disease?
Deficiency of branched chain alpha ketoacid decarboxylase.
p.5
Amino Acid Metabolism and Disorders
How common is Maple Syrup Urine Disease?
Occurs in one out of every 150,000 live births.
p.6
Analytical Methods for NPN Compound Measurement
Why must patients fast before amino acid analysis?
Consuming proteins will increase plasma amino acids.
p.4
Amino Acid Metabolism and Disorders
What is phenylketonuria (PKU)?
A disorder caused by the absence of phenylalanine hydroxylase, leading to toxic levels of phenylalanine.
p.14
Analytical Methods for NPN Compound Measurement
What is required before performing the assay for uric acid?
Protein in the sample must be removed by protein precipitation.
p.7
Clinical Relevance of Plasma and Urine NPN Concentrations
How does renal failure affect ammonia levels?
It results in hyperammonemia.
p.7
Interferences and Errors in NPN Analysis
Why should ammonium heparin tubes not be used for ammonia analysis?
They contain ammonium heparin, which interferes with ammonia measurement.
p.7
Interferences and Errors in NPN Analysis
How can cigarette smoking affect plasma ammonia concentrations?
It can increase concentrations by 10 to 20 micrograms per deciliter if smoked an hour before collection.
