Nitrogenous BAses and IRon Compunds – Flashcards
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| NPN |
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| Non Protein Nitrogen |
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| Pre-Renal |
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| Process that occurs before reaching the kidneys |
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| Renal |
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| PRocesses that occur in the kidney |
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| Post-Renal |
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| Processes that occur after the kidneys |
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| Renal Clearance |
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| Volume of plasma from which kidneys can remove all of a given substance in a give time. Usuallya minute. |
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| Urea |
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| Primary nitrogenous compound in blood. Waste product of protein metabolism. Liver is the sole site of formation. |
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| What determines the amount of urea in the blood? |
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| the amount of dietary protein and the kidney's ability to excrete urea. |
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| Creatinine |
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| nitrogenous compound, production is fairly stable and this is more indicitive of kidney failure. formation and release is constant and has a direct correlation to muscle mass |
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| How is creatinine Formed? |
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| Creatinine phosphate loses phosphoric acid and creatine loses water. |
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| Creatine |
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| provides athletes with quick bursts of energy, and helps them recover. |
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| Uric Acid |
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| primary waste product of purine metabolism. |
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| Elevated levels of uric acid causes: |
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| Gout, increased catabolism of nucleic acids, Renal diseases |
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| Ammonia |
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| treated as a NPN, but is excreted by the liver and not by the kidneys. Arises from the break down of amino acids. High concentrations are neurotoxic. |
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| Nitrogenous Compounds (4) |
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| URea, Creatinine, Uric Acid, Ammonia |
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| Purpose of Urea testing |
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| provides an indication of renal performance. |
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| Blood Urea Nitrogen (BUN) |
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| measures the amount of nitrogen found in blood urea. Oldest method, time consuming. |
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| Principle of testing Urea |
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| Urea is hydrolyzed to NH4+ . measures the rate of disappearance of NADH at 340nm. Reported in mg/dL |
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| Urea Specimen requirements |
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| Serum, Plasma, heparin tubes, should be analyzed quickly or preserved. Urine is a 24 hour collection. |
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| Interpreting Results |
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| compared with creatinine to determine if elevation is due to renal or non renal causes. |
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| Purpose of Creatinine Testing |
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| measure of renal function especially glomerular function, not affected by diet, dehydration, or protein metabolism. More reliable than urea. |
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| Methodology of Testing for Creatinine |
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| Jaffe Method. |
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| Principle of testing creatinine |
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| in the presence of an alkaline PH, creatinine reacts with picric acid. Acid eliminates interference. Sample is measure colometrically. |
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| Specimen for Creatinine |
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| Serum, plasma, heparinized. URine: 24 hour, diluted. May refrigite up to 1 week, seperate immediately. affected by hemolysis |
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| Intrepeting Results of Creatinine |
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| 4mg/dL or higher indicate severe renal damage. |
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| Purpose of Testing URic Acid |
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| provides an indication of renal performace |
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| How is Uric acid tested? |
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| Caraway MEthod |
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| Principle of URic Acid testing |
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| Uric acid is oxidized to allantoin which acts as a reducing agent in a colormetric reaction. |
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| Specimen requirements for uric acid |
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| serum, diet affects levels. heparinized plasma. 24 hour urine. |
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| Purpose of Ammonia testing |
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| indicator of sever liver disease |
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| Methodology of ammonia testing |
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| Couple ezymatic analysis |
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| Principle of ammonia testing |
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| causes the oxidation of NADPH to NADP+ which is measured colorimetrically. |
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| Specimen Requirements for Ammonia |
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| plasma: heparine, or EDTA, non hemolyzed, filled completely, placed on ice and analyzed as soon as possible, smoking can cause a false increase. |
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| Criteria for selecting a clearance metabolite |
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| natural product of metabolism analyzed inexpensively by colometric methods produced at a constant rate eliminate solely by renal action |
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| Principle of Creatine Clearance Testing |
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| provides a basis for determining renal performance. ration of serum creatinine to urine creatinine is determined. |
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| Specimen Requirements for Creatinine Clearance |
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| 24 hour urine, and a serum collected within the same 24 hours. |
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| Creatinine Clearance Equation |
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UC x TV SCxMIN
UC: Urine Clearance SC: Serum Clearance TV: Total Volume MIN: Minutes of Collection |
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| Functions of Iron |
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| binds reversibly with oxygen aids in electron transport. |
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| Hemoglobin in reference to Iron |
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| Largest concentration of iron in the body. |
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| Myoglobin |
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| Contains iron, it is the o2 binding protein of striated and cardiac muscle. |
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| Metabolic Role of Iron |
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| catalase, peroxidase, cytochromes and other metabolic enzymes require Fe as a cofactor. Many of the enzymes are necessary for ATP. |
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| What are the Iron containing compartments? |
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| Hb, Tissue IRon, Myoglobin, Labile Pool, Transport. |
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| Hemoglobin as a storage for iron |
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| contains 65-70% of body's iron. approximately 2.5g |
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| Tissue IRon |
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| approximately 8mg. Found in all nucleated cells in the body. |
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| How much iron does Myoglobin store? |
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| approximately 130mg |
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| Labile Pool |
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| approximately 80mg, contains iron in transition. no clear anatomical location. |
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| Transport |
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| approximately 2.5mg, accomplished by the protein apotransferrin. |
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| Storage of IRon |
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| males - approximately 800mg females - 0-200mg |
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| Distribution of Iron |
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| average male has about 4g of iron average female has about 3g of iron. |
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| Daily requirements for Iron |
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| daily diet contains 10-15mg/day mostly from meat in the form of hb and mb. |
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| Iron storage compartments |
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| Liver - 1/3 Bone Marrow - 1/3 Spleen and other tissues - 1/3 |
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| transferrin |
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| apotransferrin binded with iron |
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| What two forms is iron stored in? |
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| Feritin and Hemosiderin |
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| Ferritin |
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| major iron storage compound, ferritina ccepts ferrous iron, and oxidizes it to ferric. deposits iron within its core. |
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| Hemosiderin |
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| found predominately in liver, spleen, and bone marrow. iron is released slowly, it occurs in large aggreates and has a much smaller surface/volume ratio. |
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| When body iron is high, what happens? |
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| apoferritin is also high, transferrin is low. Iron that enters the cell is trapped in ferritin. Iron is lost when cell is sloughed, this reduces iron absorption. |
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| When body iron is low, what happens? |
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| apoferritin is low, transferrin and apotransferrin are high. Less iron is trapped in ferritin, iron that enters the cell is more readily absorbed. |
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| What form must iron be in to be absorbed? |
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| Ferrous. Fe2, ferric iron (Fe3) will not be abosorbed until it is reduced. |
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| How is ferric iron converted to ferrous iron? |
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| highly acid gastric secretions perform it. However most dietariy iron is in the form of heme. HEem is directly absorbed because of it's ferrous state. |
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| Mechanism of iron transport? |
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| Transferrin. Iron needs a carrier protein because free iron is toxic and insoluble. |
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| Transferrin |
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| principle transport protein for iron, apotransferrin bonded with iron, can bind two atoms of ferric iron. delivers iron to thos cells with appropriate receptors. |
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| Transferrin saturation |
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| Iron binding sites are normally 15-50% saturated depending on gender. |
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| PAthway of iron metabolism |
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| closed cycle. only small amounts of iron are lost. 1) iron passes from transferrin to the bone marrow where it is included in Hb 2) Mature RBCS are released into the blood, after 4 months iron is released after death of RBCS 3) Iron returns to transferrin. Small quantities of iron are diverted to other compartments. |
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| Excretion of iron |
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| Iron is not excreted conventionally Normal loss is 1-2 mg/day through: 1)Normal shedding of epithelial cells 2)Small number of RBCs lost through urine and feces 20-40mg of iron are lost with each menstrual cycle. |
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| Procedure for Serum Iron Determination |
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| 1)PH of serum is lowered to release iron 2) Fe3 is reduced to Fe2 3) complexes with chromagen 4)absorbance is proportional to Fe concentration. MEasured at 530-560nm |
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| What are two widely used chromogens for measuring serum iron? |
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| ferrozine, and bathophenanthroline. |
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| Procedure for measuring total iron binding capacity |
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| 1)Sufficent Fe3 is added to serum to completely saturate transferrin. 2) remaining iron is removed by chelation using a chelator like magnesium carbonate. 3) specimen is then analyzed for total iron. |
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| Unsaturated Iron Binding Capacity (UIBC) calculation |
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| UIBC = TIBC - Serum Iron |
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| Transferrin Saturation calcuation |
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| Tranferrin sat% = total iron concentration x 100% |
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| Ferritin Testing Principle |
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| May be performed by one of several methods including Enzyme linked immunosorbent Assay (ELISA) and Immunoradiometric (IRMA) assay. |
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| Clinical Significance of eleveated BUN values |
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| Pre-Renal Azotemia caused by:dehydration, increased protein, congestive heart failure. REnal azotemia caused by: glumerulonephritis, tubular necrosis. Post reneal azotemia : tumors, renal calculi. |
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| Decreased levels of BUN |
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| little significance. |
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| Elevated Serum Creatinie |
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| Moderate to sEvere kidney damage, urinary obstruction, muscle damage, congestive heart failure, hypothyroidism. |
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| Decreased serum creatinine |
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| chronic inactivity, hyperthyroidism |
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| Increased URine creatinine |
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| muscle injury, glomerulonephritis, pyelonephritis, reduced blood flow. |
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| Decresed urin creatinine |
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| Uncommon, decreaased muscle mass |
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| Elevated Uric Acid |
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| Gout, consuption of purine rich foods, and lesch-nyan syndrome spasticity. |
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| Iron Deficiency |
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| one of the most prevalent human disorders, primarily affects children, young women, and elderly. |
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| CAuses of iron deficiency |
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| IRon deficient anemia, blood loss, impaired or malabsorbiton of iron, dietary deficiencies. |
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| Laboratory findings during iron deficiency |
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| hypochromic and microcytic RBCs, decrease in Hb, serum iron, RBC indices, % saturation and serum ferritin, increase in transferrin and TIBC. |
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| Causes of Iron overload |
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| Hemochromatosis, sideroblastic anemia, hemosiderosis, change in analyte in disease. |
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| Hemochromatosis |
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| error of iron absortion, mechanism is unknown, progressive increase in iron absorption, deposited directly in the parenchymal cells of the liver, hear, pancreas, and other organs, leads to tissue destruction and ultimately organ failure. |
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| Laboratory Findings in Hemochromatosis |
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| Decreased TIBC, increased serum iron, ferritin, % saturation, trasferrin saturation. Liver biopsy is the definitive test for Hemochromatosis |
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| Sideroblastic Anemia |
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| iron-loading disorder causing over accumulation of iron. Excessive chronic iron digestion. |
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| Laboratory findings in Sideroblastic Anemia |
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| Increased serum iron, ferritin and % saturation. Normal or decreased transferrin. |
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| Hemosiderosis |
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| condition of iron overload as demonstrated by increased serum iron and transferrin or TIBC, but no tissue damage. |
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| Change in Analyte in disease |
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| combination of both hematological and biochemical studies are required to determine disorders in iron metabolism. |
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| Hematology findings in change in analyte. |
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| Hb concentrations, RBC indices, Peripheral blood smear. |
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| Serum Iron |
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| measurment does not include Hb iron, TIBC and transferrin sat. should also be evaluated. IRon pool turns over 10-20 times per day. |
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| FActors influencing serum iron concentration |
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| day to day variation, even in healthy people. and dirunal variation. Must be interpreted with regards to the time of day. |
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| Diurnal variation |
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| concentrions are lower in the afternoon than in the morning. |
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| Specimen of choice for serum iron and TIBC |
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| fasting morning specimen. |
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| Increased variation of analyte concentration |
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| red cell disorders, bone marrow hypoplasia, acute hepatitis, acute iron poisoning, hemachromatosis. |
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| decreased variation of analyte concentration |
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| iron deficiency, malignancies, inflammation, blood loss. |
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| Total Iron Binding Capacity (TIBC) |
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| amount of iron that could be bound by saturatiing transferrin and other minor iron binding proteins in the serum or plasma sample. About 1/3 of sites are saturate, accompanies serum iron, 20-50%. |
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| Increased TIBC |
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| iron deficiency, oral contraceptives. |
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| Decreased TIBC |
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| Malignancies, chronic inflammatory disorders, hemachromatosis. |
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| Serum Ferritin |
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| very low concentrations, in equilibrium with body stores. declines very early in iron deficiency. large diurnal variation. |
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| decrease in serum ferritin |
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| very sensitive indicator of iron deficiency |
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| Increased ferritin |
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| chronic infections, chronin inflammatory, heart disease, hemosiderosis and hemachromatosis |
