Chemistry Flashcards

Question

What is the algorithm for treating a high INR in a patient on warfarin (above 2.0-3.0 or 2.5-3.5, depending on underlying condition)?

Answer 1

If there is significant bleeding, discontinue warfarin, give vitamin K (most likely IV or sub-Q), and give plasma to replace the missing coagulation factors. If there is no significant bleeding, and there is a desire to regain the anticoagulated state as soon as possible OR the INR is less than 10, discontinue warfarin and allow INR to decline. If there is no significant bleeding, and there is no desire to regain the anticoagulated state as soon as possible OR the INR is greater than 10, discontinue warfarin and administer vitamin K (most likely oral).

Answer 2

Heparin is a very negatively charged compound, and protamine sulfate is a positively charged compound. They bind together and heparin is neutralized.

Answer 3

If it is LMWH used for prophylaxis or LMWH therapy in normal weight, normal renal function, non-pregnant patients, no monitoring is needed. If unfractionated heparin is used, target PTT to >2.0x mean of normal range (varies widely depending on reagents and instruments).

Answer 4

Allergic reactions (drug reactions, asthma), parasitic infections (strongyloidiasis, schistosomiasis, filariasis, toxocariasis), metabolic abnormalities (adrenal insufficiency), humoral immunodeficiency (hyperimmunoglobulin E syndrome (Job syndrome), Wiskott-Aldrich syndrome, hyperimmunoglobulin M syndrome, immunoglobulin A deficiency), pulmonary eosinophilias (eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), allergic bronchopulmonary aspergillosis, chronic and acute idiopathic eosinophilic pneumonias), autoimmune blistering skin diseases (dermatitis herpetiformis, bullous pemphigoid).

Answer 5

Most eosinophilias are reactive, polyclonal processes. In all these reactive processes, the increase in AEC appears to be mediated by cytokines, principally IL-5, which promotes proliferation of eosinophils and their precursors. Reactive eosinophilias may also involve overproduction of additional cytokines, such as IL-3 and IL-4, which can lead to concomitant elevation of IgE in reactive eosinophilias.

Answer 6

This association exists because glucocorticoids inhibit eosinophil proliferation and survival, an effect that is exploited clinically when steroids are used as treatment of reactive eosinophilias. In adrenal insufficiency, the converse occurs; low glucocorticoid levels allow increased eosinophil proliferation and survival. This scenario is especially important in critically ill patients, in whom eosinophilia due to adrenal insufficiency is common. Given the inverse relationship between glucocorticoid levels and eosinophil count, the standard evaluation of eosinophilia should include attention to clinical signs of adrenal insufficiency (orthostatic hypotension, skin discoloration); routine chemistries, which may be abnormal in Addison disease; and, in some cases, morning cortisol levels.

Answer 7

Among the reactive eosinophilias in the developed world, allergic reactions are most common, comprising ~80% of cases, and parasitic infections represent the second most-common cause, comprising ~8% of cases.

Answer 8

Paraneoplastic eosinophilia is frequently observed in association with solid organ malignancies, with reported incidences ranging from 0.5% to 7%. The phenomenon is not specific to any particular tumor type, and a broad spectrum of primary tumors have been implicated. Instead, paraneoplastic eosinophilia appears to be most closely related to tumor stage. It has been noted that blood eosinophilia is a poor prognostic sign and, in almost all cases, is associated with advanced metastatic disease. Various mechanisms have been proposed to explain this association. The eosinophilia may disappear after surgical excision and reappear with recurrence.

Answer 9

Direct bilirubin is measured in a diazo-colorimetric assay. It is measured in the reaction with the diazo compound in the absence of an accelerator. Addition of an accelerator, such as alcohol, results in a measurement of total bilirubin. Indirect is calculated as total minus direct.

Answer 10

Cirrhosis, hemolysis, Gilbert syndrome, and Crigler-Najjar syndrome all cause unconjugated hyperbilirubinemia.

Answer 11

Factor VII, at 4-7 hours. Factor I is 72-120 hours, factor II is 48-120 hours, factor V is 12-36 hours, factor VIII is 8-12 hours, factor IX is 18-24 hours, factor X is 24-48 hours, factor XI is 40-84 hours, factor XII is 48-52 hours, and factor XIII is 9-12 days.

Answer 12

Factor XIII, at 9-12 days. Factor I is 72-120 hours, factor II is 48-120 hours, factor V is 12-36 hours, factor VII is 4-7 hours, factor VIII is 8-12 hours, factor IX is 18-24 hours, factor X is 24-48 hours, factor XI is 40-84 hours, factor XII is 48-52 hours.

Answer 13

Physiological jaundice due to hepatic enzymes not being up to full capacity; the infant's liver is not able fully to conjugate bilirubin for excretion. This can be exacerbated by peripartum hemolysis, which leads to an increased bilirubin load, or breast milk jaundice, since breast milk contains inhibitors of bilirubin conjugation.

Answer 14

Jaundice within 24 hours of birth, rising bilirubin after 1 week, persistence past 10 days, a total bilirubin >12 mg/dL, a single day increase in bilirubin >5 mg/dL, or a direct bilirubin >2 mg/dL.

Answer 15

Ischemia and toxic injuries lead to the most profound elevations in transaminases, sometimes >100x the upper limit of normal.

Answer 16

An AST:ALT ratio greater than 2 implies toxic/ischemic/alcoholic hepatitis, while with viral hepatitis it is often less than 1.

Answer 17

PT. A PT prolongation >4.0 seconds indicates severe injury and an unfavorable prognosis. The PT test is a test of loss of function, while viral titers, bilirubin, AST:ALT, and GGT are tests of injury.

Answer 18

There are 6 isoenzymes of serum amylase as analyzed by serum electrophoresis. The fastest migrating are pancreatic; the slowest are salivary.

Answer 19

The salivary isoenzyme of serum amylase is inhibited and the pancreatic isoenzyme is uninhibited by the effect of wheat germ lectin Triticum vulgaris.

Answer 20

Hypertriglyceridemia.

Answer 21

Ig-amylase is referred to as macroamylase. Macroamylase cannot be cleared by the kidney due to its large size, which leads to increased serum amylase and decreased urine amylase.

Answer 22

Lipase is more pancreas-specific, is less reliant on renal clearance, and while it rises in parallel to amylase it remains elevated for longer.

Answer 23

It is a blood test and patients do not need to return to have their skin test read. The results are more objective than those of a skin test, since with the TST there can be reader variability. Also, the test is not affected by previous vaccination with BCG (the TST is).

Answer 24

QuantiFeron-TB Gold and its newer In-Tube version (Cellestis, a Qiagen company, Valencia, California) and T-Spot.TB (Oxford Immunotec Limited, United Kingdom). T-Spot requires isolated WBCs rather than whole blood, which can be more technically demanding; however, the T-Spot may be more sensitive in those who are immunocompromised.

Answer 25

Analysis of postmortem glucose, enzymes, and drugs shows significant differences between specimens taken from the right side of the heart, the left side of the heart, and the peripheral blood vessels. Peripheral venous or peripheral arterial specimens best approximate the antemortem values.

Answer 26

300 uL of blood may be spotted on specialized filter papers. Several samples can be collected, dried overnight, wrapped in plastic wrap, and stored at -20 C. Such samples are useful for genotype and protein analyses available through commercial and academic laboratories. An example would be using tandem mass spectrometry on postmortem blood spotted on filter paper to detect specific enzyme defects. Filter blots of liver tissue, bile, and vitreous humor may also be used.

Answer 27

Vitreous humor provides one of the best samples for postmortem chemical analysis because it comes from a closed space and postmortem values often approximate the antemortem levels. Vitrous humor may not become contaminated after embalming, so it may still provide material for analysis in these cases. However, a sample of the embalming fluid should also be submitted to the laboratory as a control.

Answer 28

Postmortem serum glucose decreases rapidly because of glycolysis, preventing detection of antemortem hypoglycemia. Even elevated levels of postmortem blood glucose require careful interpretation. Death from asphyxia, cerebral hemorrhage, CHF, electrocution, or terminal CPR may increase postmortem peripheral vascular glucose and falsely indicate hyperglycemia. Glycosuria, ketonuria, or elevated serum acetone can help confirm diabetic ketoacidosis. Blood samples taken from the right atrium or IVC may have a high glucose content because of glycogenolysis in the liver and subsequent diffusion of glucose into adjacent vessels. Thus, a low glucose level in blood from the right atrium and a positive test for ketones may support starvation. Vitreous humor provides more reliable data for determination of antemortem hyperglycemia. Glycolysis reduces the postmortem concentration of vitreous humor glucose; however, values greater than 200 mg/dL usually indicate that the decedent had uncontrolled diabetes.

Answer 29

Dehydration Pattern: Increased sodium and chloride concentrations. No significant increase in potassium. Moderate elevation of BUN/Cr levels. Uremic Pattern: No substantial increase in sodium, chloride, or potassium. BUN/Cr levels increased. Low-salt Pattern: Low sodium, chloride, and potassium concentrations. BUN/Cr stable. Decomposition Pattern: Low sodium and chloride concentrations. Increased potassium. BUN/Cr stable.

Answer 30

Urea nitrogen is perhaps the most stable blood constituent after death as it approximates premortem levels even after moderate decomposition. Urea nitrogen also remains stable in CSF, vitreous humor (even after embalming), and synovial fluid. In addition to their use in assessing renal function, urea nitrogen concentrations aid in the interpretation of hypernatremia. Similarly, creatinine levels in the blood remain stable after death, as they do in CSF and vitreous humor, making creatinine a valid postmortem marker of nitrogen retention and renal function.

Answer 31

Of the cytokines, IL-5 is the most specific for the eosinophil lineage. It is responsible for the selective differentiation of eosinophils and release of eosinophils from bone marrow.

Answer 32

Agranulocytosis. The effect is not dose-dependent. The incidence is 0.05-0.5% of all users. In most patients, the agranulocytosis occurs within the first 3 months of treatment. This often presents with pharyngitis, and patients are instructed to seek attention if they develop sore throat, fever, an oral ulcer, or other symptoms of infection (UTI, PNA). Minor depressions in the neutrophil count are much more common than true neutropenia.

Answer 33

Multiple risk factors can contribute to the development of this neoplastic process, such as viral hepatitis infection with HBV or HCV, cirrhosis (independently of cause), exposure to aflatoxin, use of anabolic steroids and tyrosemia.

Answer 34

Nonmolecular methods: Microscopic observation direct susceptibility assay (MODS assay). Light-emitting diode microscopy. MDR-XDRTB Colour Test. Colorimetric assays. Phage amplification assays. Molecular methods: Line probe assays. Automated nucleic acid amplification tests. Loop-mediated isothermal amplification. Oligonucleotide microarray.

Answer 35

In decreasing order of concentration: cardiac muscle, liver, skeletal muscle, kidney, brain, lung, pancreas. ALT is more specific for the liver than AST.

Answer 36

ALT is more specific for the liver than AST, and is found mainly in the liver and kidney.

Answer 37

AST is found both within cytoplasm (~20%) and mitochondria (~80%). ALT is located entirely within the cytoplasm.

Answer 38

In children, AST activity is slightly higher than the ALT, with this pattern reversing by age 20. In adults, AST activity tends to be a little lower than ALT. This ratio may again reverse in old age. Both AST and ALT activities are higher in adult males than adult females, and both are higher in African Americans.

Answer 39

Intra-individual variation is more significant for ALT than AST, with marked diurnal variation (highest in the afternoon) and day-to-day variation of up to 30%.

Answer 40

Both AST and ALT may be elevated in heparin therapy to around 3x of baseline.

Answer 41

In renal failure, AST and ALT are significantly lower than in healthy individuals.

Answer 42

LD1 and LD2 are found in greatest abundance in heart, RBCs, and kidney, with a significantly greater proportion of LD1 than LD2. LD3 is found in lung, spleen, lymphocytes, and pancreas. LD4 and LD5 are found in liver and skeletal muscle.

Answer 43

LD6 is sometimes seen migrating cathodal to LD5. Its presence is thought to be a dire finding, indicative of hepatic vascular insufficiency (usually in the setting of cardiovascular collapse).

Answer 44

Serum: LD2>LD1>LD3>LD4>LD5. CSF: LD1>LD2>LD3>LD4>LD5.

Answer 45

GGT is found in the biliary epithelial cell, particularly those that line the small interlobular bile ducts and bile ductules. (it is also present in hepatocytes) Thus, it is exquisitely sensitive to biliary injury. 5'-nucleotidase (biliary epithelium is the main source) is another test to confirm that an elevated alk phos is due to hepatobiliary disease, but its relatively low sensitivity has kept its utility below that of GGT.

Answer 46

GGT is found to be ~2-3x the upper limit of normal in heavy drinkers. It returns to normal in ~3 weeks with abstinence, and can then be followed as a marker of alcohol consumption.

Answer 47

Warfarin, barbiturates, dilantin, valproate, methotrexate, and alcohol. GGT is found to be ~2-3x the upper limit of normal in heavy drinkers. It returns to normal in ~3 weeks with abstinence, and can then be followed as a marker of alcohol consumption.

Answer 48

False. Total serum alkaline phosphatase is elevated in over 85% of patients, and may be useful in monitoring the disease. Serum calcium, phosphorus, and aminotransferase are normal in Paget disease of bone.

Answer 49

The genes PRSS-1 (cationic trypsinogen), PSTI (pancreatic secretory trypsin inhibitor), and CFTR (cystic fibrosis transmembrane conductance regulator) have all been implicated as causes of recurrent pancreatitis.

Answer 50

Elastase-1. Fecal fat, chymotrypsin, and elastase-1 are all sensitive and specific, but with elastase being the most so.

Answer 51

Pancreatic pseudocyst: high amylase, low CEA, high CA 19-9. Serous cystadenoma: low amylase, low CEA, low CA 19-9. Mucinous cystadenoma: low amylase, high CEA, normal to high CA 19-9. Intraductal papillary mucinous neoplasm: high amylase, high CEA, normal to high CA 19-9. Solid-pseudopapillary tumor: low amylase, low CEA, low CA 19-9.

Answer 52

CK-BB. It is found in nearly all tissues of the body, though found primarily in the brain.

Answer 53

Mitochondrial CK. If seen on electrophoresis, it appears as a faint band migrating slightly slower than CK-MM. Another abnormal CK is macro-CK, which is composed of a complex of antibody-bound CK.

Answer 54

The gene that encodes troponin C is expressed in both cardiac and skeletal muscle, whereas troponin T and troponin I have separate cardiac and skeletal muscle genes. cTnI is marginally more cardiac-specific than cTnT.

Answer 55

Usually within moments of an AMI, there is a elevation of myoglobin. However, myoglobin is very nonspecific and can be elevated due to a number of causes.

Answer 56

The amino terminus of albumin is modified with exposure to a number of conditions, such as acidosis, hypoxemia, and free radicals. The modification decreases the ability of albumin to bind cobalt. It can be used to measure myocardial ischemia, since ischemia-modified albumin rises within minutes of ischemic damage and returns to baseline within a few hours. The assay measures the amount of unbound cobalt, which reflects the level of ischemia-modified albumin.

Answer 57

Brain (B-type) natriuretic peptide (BNP) is released in response to increased ventricular filling pressure. It is released as an inactive pro-BNP peptide, which when cleaved releases an active BNP as well as the regulatory N-terminal pro-BNP, a very stable molecule which provides the most longitudinal information about CHF.

Answer 58

Increased sensitivity. The specificity of a single elevated troponin is very high; serial measurements don't change that. However, a mildly elevated troponin may not be sensitive enough to detect AMI. Serial measurements of troponin increase the sensitivity, but don't change the ability of the test to change its negative predictive value.

Answer 59

Troponin is not helpful in determining the time course of AMI. Troponin rises more slowly and stays elevated longer than CK-MB. If CK-MB continues to rise, it may indicate an acute event or an extension of an existing infarction, while a downward trend of CK-MB may indicate resolution of an infarction.

Answer 60

Ammonium nitrogen released by acid digestion. The Kjedahl technique is cumbersome and makes assumptions about average nitrogen content. Colorimetric assays are preferred for the measurement of protein, and all involve formation of a colored precipitate under alkaline or acidic conditions and then measuring the absorbance at the appropriate wavelength. Refractometry is used but has many interferences. Dye-binding is limited by uneven dye uptake by proteins.

Answer 61

Most proteins bear a net negative charge at physiologic pH and as such migrate toward the anode or positive pole when subject to an electromotive force. Remember, anions have negative charges and are attracted to the positive pole or anode. Cations bear positive charges and are attracted to the negative pole or cathode.

Answer 62

Anions have negative charges and are attracted to the positive pole or anode. Cations bear positive charges and are attracted to the negative pole or cathode.

Answer 63

Albumin accounts for the majority of normal serum protein and is the fastest migrating major protein followed by the alpha, beta, then gamma region proteins.

Answer 64

False. Albumin, rather than pre-albumin, is responsible for maintenance of serum osmotic presure. Pre-albumin does function in the capacity to bind thyroid hormone and vitamin A. TTR misfolding and aggregation is known to be associated with the amyloid diseases senile systemic amyloidosis (SSA), familial amyloid polyneuropathy (FAP), and familial amyloid cardiomyopathy (FAC).

Answer 65

Transthyretin (TTR) is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine (T4) and retinol binding protein bound to retinol. This is how transthyretin gained its name, TRANSports THYroxine and RETINol. It is synthesized in the liver, choroid plexus and retinal pigment epithelium for secretion into the bloodstream, cerebrospinal fluid and the eye, respectively. TTR was originally called prealbumin (or Thyroxine-binding prealbumin) because it ran faster than albumin on electrophoresis gels.

Answer 66

Thyroxine binding globulin has highest binding affinity and lowest plasma concentrations. Transthryetin has mid-range binding affinity and mid-range plasma concentrations. Albumin has lowest binding affinity and highest plasma concentrations.

Answer 67

TSH levels are higher in elderly people. TSH levels are higher in obese people. TSH levels are lower in pregnant women.

Answer 68

Immunoassays employ monoclonal antibodies, which have limited and varying specificity to detect the epitopes of TSH. Which TSH molecules an assay detects will depend on the monoclonal antibody selected. Circulating TSH is heterogeneous, especially with respect to glycosylation. Because of heterogeneity in glycosylation, not all molecular forms of TSH are bioactive. In particular, although the upper limit of TSH is higher in older individuals, not all TSH in older persons may be bioactive. Commercial immunoassays for thyroid function testing may have up to a two-fold divergence between highest and lowest methods for T4 and T3. Ultrafiltration (or equilibrium dialysis) and tandem mass spectrometry are methods that have a better correlation between free T4 and log TSH. Immunoassays may also overestimate levels of T3 and free T3.

Answer 69

Transferrin is the predominant beta-1 protein. On standard serum electrophoresis, beta does not resolve into beta-1 and beta-2, but can on high-resolution electrophoresis. In the beta-2 region migrates IgA. C-reactive protein can be in beta-2 or gamma-2. The predominant alpha-1 band is alpha-1-antitrypsin; alpha-2 has haptoglobin and ceruloplasmin.

Answer 70

Due to its large size, alpha-2-macroglobulin is typically not lost with nephrotic syndrome. As a result of the loss of other smaller proteins and fluid, the alpha-2-macroglobulin concentration increases.

Answer 71

Both the unmodified and asialated forms can cross the blood-brain barrier through active transport.

Answer 72

Bisaslbuminemia is a normal variant seen in heterozygotes for different albumin allotypes. There is no clinical significance.

Answer 73

Predominantly due to increased IgA, beta-gamma bridging is seen with cirrhosis. Cirrhosis can also show hypoalbuminemia with blunted alpha-1 and alpha-2 peaks.

Answer 74

Prominent pre-albumin band. Double beta-transferrin band. Dim albumin band. Dim alpha-2 band.

Answer 75

Multiple sclerosis.

Answer 76

Type I. Type I cryoglobulins are monoclonal and associated with monoclonal gammopathies, such as multiple myeloma or Waldenstrom macroglobulinemia. Type II is a mixture of polyclonal IgG and monoclonal IgM. Type III is a mixture of two or more polyclonal antibodies.

Answer 77

Hepatitis C.

Answer 78

When correcting hyponatremia too slowly: cerebral edema. When correcting hyponatremia too rapidly: central pontine myelinolysis.

Answer 79

Hypovolemic hyponatremia is often due to water loss either through the kidneys or GI tract. Euvolemic hyponatremia is often due to drugs. Hypervolemic hyponatremia is often due to CHF, nephrotic syndrome, or cirrhosis.

Answer 80

Type I, or distal renal tubular acidosis is due to the inability to produce an acid urine. Associated with hypokalemia. Type II, or proximal renal tubular acidosis is due to bicarbonate wasting. Associated with hypokalemia. Type IV renal tubular acidosis is due to aldosterone deficiency. Associated with hyperkalemia.

Answer 81

Type IV. Type I and type II are associated with hypokalemia.

Answer 82

Parathyroid adenoma > parathyroid hyperplasia > parathyroid carcinoma.

Answer 83

Hyperparathyroidism or malignancy (often with the paraneoplastic expression of PTHrP).

Answer 84

Physiologic factors, including diurnal variation, exercise, fasting, diet, ethanol consumption, tobacco smoking, drug ingestion, and posture. Also, common interferences include tobacco smoking (in vivo) and collection-associated variables (in vitro).

Answer 85

Cortisol: Peaks 4–6 AM; lowest 8 PM–12 AM; 50% lower at 8 PM than at 8 AM; increased with stress. ACTH: lower at night; increased with stress. Plasma renin activity: Lower at night; higher standing than supine. Aldosterone: Lower at night. Insulin: Lower at night. GH: Higher in afternoon and evening. Acid phosphatase: Higher in afternoon and evening. Thyroxine: Increases with exercise. Prolactin: Higher with stress; higher levels at 4 and 8 AM and at 8 and 10 PM. Iron: Peaks early to late morning; decreases up to 30% during the day. Calcium: 4% decrease supine. Hyperventilation such as from stress affects acid-base balance and elevates leukocyte counts, lactate, and free fatty acids. Upright position increases hydrostatic pressure, causing a reduction of plasma volume and increased concentration of proteins such as albumin.

Answer 86

Physical activity has transient and long-term effects on laboratory determinations. Transient changes may include an initial decrease followed by an increase in free fatty acids, and lactate may increase by as much as 300%. Exercise may elevate creatine phosphokinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LD), and may activate coagulation, fibrinolysis, and platelets. These changes are related to increased metabolic activities for energy purposes and usually return to preexercise levels soon after exercise cessation. Long-term effects of exercise may increase CK, aldolase, AST, and LD values. Chronic aerobic exercise is associated with lesser increases in plasma concentration of muscle enzymes such as CK, AST, alanine aminotransferase (ALT), and LD. Decreased levels of serum gonadotropin and sex steroid concentrations are seen in long-distance athletes while prolactin levels are elevated.

Answer 87

An individual's diet can greatly affect laboratory test results. The effect is transient and is easily controlled. Glucose and triglycerides, absorbed from food, increase after eating. After 48 hours of fasting, serum bilirubin concentrations may increase. Eating a meal, depending on fat content, may elevate plasma potassium, triglycerides, alkaline phosphatase, and 5-hydroxyindoleacetic acid (5-HIAA). Stool occult blood tests, which detect heme, are affected by the intake of meat, fish, iron, and horseradish, a source of peroxidase, causing a false-positive occult blood reaction.

Answer 88

Certain foods or diet regimens may affect serum or urine constituents. Long-time vegetarian diets are reported to cause decreased concentrations of LDLs, VLDLs, total lipids, phospholipids, cholesterol, and triglycerides. Vitamin B12 deficiency can also occur, unless supplements are taken. A high meat or other protein-rich diet may increase serum urea, ammonia, and urate levels. High protein, low carbohydrate diets, such as the Atkins diet, greatly increase ketones in the urine and increase the serum BUN. Foods with a high unsaturated-to-saturated fatty acid ratio may show decreased serum cholesterol, while a diet rich in purines will show an increased urate value. Foods such as bananas, pineapples, tomatoes, and avocados are rich in serotonin. When ingested, elevated urine excretion of 5-HIAA may be observed. Beverages rich in caffeine elevate plasma free fatty acids and cause catecholamine release from the adrenal medulla and brain tissue. Ethanol ingestion increases plasma lactate, urate, and triglyceride concentrations. Elevated HDL cholesterol, GGT, urate, and MCV have been associated with chronic alcohol abuse.

Answer 89

Using a tourniquet to collect blood to determine lactate concentration may result in falsely increased values. Prolonged tourniquet application may also increase serum enzymes, proteins, and protein-bound substances, including cholesterol, calcium, and triglycerides, as the result of hemoconcentration when plasma water leaves the vein because of back pressure.

Answer 90

Age of the patient has an effect on serum constituents. In the newborn, much of the Hb is Hb F, not Hb A, as seen in the adult. Bilirubin concentration rises after birth and peaks at about 5 days. In cases of hemolytic disease of the fetus and newborn (HDFN), bilirubin levels continue to rise. This often causes difficulty in distinguishing between physiologic jaundice and HDFN. Infants have a lower glucose level than adults because of their low glycogen reserve. With skeletal growth and muscle development, serum alkaline phosphatase and creatinine levels, respectively, also increase. The high uric acid level seen in a newborn decreases for the first 10 years of life, then increases, especially in boys, until the age of 16.

Answer 91

Most serum constituents remain constant during adult life until the onset of menopause in women and middle age in men. Increases of about 2 mg/dL (0.05 mmol/L) per year in total cholesterol and 2 mg/dL (0.02 mmol/L) per year in triglycerides until midlife have been reported. The increase in cholesterol seen in postmenopausal women has been attributed to a decrease in estrogen levels. Uric acid levels peak in men in their 20s but do not peak in women until middle age. The elderly secrete less triiodothyronine, parathyroid hormone, aldosterone, and cortisol. After age 50, men experience a decrease in secretion rate and concentration of testosterone and women have an increase in pituitary gonadotropins, especially follicle-stimulating hormone.

Answer 92

After puberty, men generally have higher alkaline phosphatase, aminotransferase, creatine kinase, and aldolase levels than women; this is due to the larger muscle mass of men. Women have lower levels of magnesium, calcium, albumin, Hb, serum iron, and ferritin. Menstrual blood loss contributes to the lower iron values.

Answer 93

Tobacco smokers have high blood carboxyhemoglobin levels, plasma catecholamines, and serum cortisol. Changes in these hormones often result in decreased numbers of eosinophils, while neutrophils, monocytes, and plasma fatty free acids increase. Chronic effects of smoking lead to increased Hb concentration, RBC count, MCV, and WBC count. Increased plasma levels of lactate, insulin, epinephrine, and growth hormone and urinary secretion of 5-HIAA are also seen. Vitamin B12 levels may be substantially decreased and have been reported to be inversely proportional to serum thiocyanate levels. Smoking also affects the body's immune response. Immunoglobulin (Ig)A, IgG, and IgM are lower in smokers, and IgE levels are higher. Decreased sperm counts and motility and increased abnormal morphology have been reported in male smokers when compared with nonsmokers.

Answer 94

Hemolysis can falsely increase blood constituents such as potassium, magnesium, iron, LD, phosphorus, ammonium, and total protein.

Answer 95

Pseudohyperkalemia can occur in patients with extremely high blast counts in acute or accelerated phase leukemias. Those blasts can be fragile and may lyse during standard phlebotomy, releasing potassium. In contrast, specimens with very high WBC counts that are collected gently can show pseudohypokalemia when potassium is taken up by highly metabolically active leukemic cells along with glucose; such specimens can be transported on ice to slow this enzymatically mediated uptake.

Answer 96

Normally platelets release potassium during clotting, so serum has a slightly higher value of potassium than plasma from the same individual; this difference is accentuated when the platelet count is extremely elevated.

Answer 97

When serum bilirubin approaches 430 mmol/L (25 mg/L), interference may be observed in assays for albumin (4-hydroxyazobenzene-2-carboxylic acid [HABA] procedure), cholesterol (using ferric chloride reagents), and total protein (Biuret procedure).

Answer 98

Lipemia occurs when serum triglyceride levels exceed 4.6 mmol/L (400 mg/dL). Inhibition of assays for amylase, urate, urea, CK, bilirubin, and total protein may be observed.

Answer 99

Blood collection tubes have color-coded stoppers that distinguish the presence of a specific anticoagulant or additive, how the tube is chemically cleaned (e.g., for lead or iron determinations), or if the tube does not contain any additives. Tubes also come in various sizes for adult and pediatric patient populations. Draw volume is determined by the internal vacuum within the sealed tubes (e.g., 3.5, 4.0, 4.5, or 8.5 mL). The use of anticoagulants allows for analysis of whole blood specimens or plasma constituents obtained by centrifugation and separation of the plasma.

Answer 100

Many laboratories have converted from glass to plastic collection tubes to minimize exposure to biohazardous material and broken glass; to lower biohazard waste disposal costs; and to comply with OSHA guidelines mandating substitution. This change from glass to plastic has required a modification in the order of draw. Whereas glass is a natural clot activator, plastic is not. So in order for blood to clot in plastic tubes, manufacturers coat the inside of the tube with a substance to facilitate clotting. However, if the tube following the clot activator tube remained the coat tube, as was the recommended order prior to 2003, carryover threatens the coag results. Glass or plastic tubes with additives, including gel tubes, are drawn after the citrate tube (blue top) to avoid interference with coagulation measurements. Glass or plastic serum tubes, without a clot activator or gel separator, may be drawn before the coagulation tubes are drawn, consistent with National Committee on Clinical Laboratory Standards (NCCLS) guidelines.

Answer 101

Red (glass); None; Serum/chemistry and serology; N/A. Red (plastic/Hemogard); Clot activator; Serum/chemistry and serology; Silica clot activator. Lavender (glass); K3EDTA in liquid form; Whole blood/hematology; Chelates (binds) calcium. Lavender (plastic); K2EDTA/spray-dried; Whole blood/hematology; Chelates (binds) calcium. Pink; Spray-dried K2EDTA; Whole blood/blood bank and molecular diagnostics; Chelates (binds) calcium. White; EDTA and gel; Plasma/molecular diagnostics; Chelates (binds) calcium. Light blue; Sodium citrate; Plasma/coagulation; Chelates (binds) calcium. Light blue; Thrombin and soybean trypsin inhibitor; Plasma/coagulation; Fibrin degradation products. Black; Sodium citrate ; Plasma/sed rates—hematology; Chelates (binds) calcium. Light green/black; Lithium heparin and gel; Plasma/chemistry; Inhibits thrombin formation. Green; Sodium heparin, lithium heparin; Plasma/chemistry; Inhibits thrombin formation. Royal blue; Sodium heparin, K2EDTA; Plasma/chemistry/toxicology; Heparin inhibits thrombin formation, Na2EDTA binds calcium. Gray; Sodium fluoride/potassium oxalate; Plasma/glucose testing; Inhibits glycolysis. Yellow; Sterile containing sodium polyanetholesulfonate; Serum/microbiology culture; Aids in bacterial recovery by inhibiting complement, phagocytes, and certain antibiotics. Yellow; Acid citrate dextrose; Plasma/blood bank, HLA phenotyping, and paternity testing; WBC preservative. Tan (glass); Sodium heparin; Plasma/lead testing; Inhibits thrombin formation. Tan (plastic); K2EDTA; Plasma/lead testing; Chelates (binds) calcium. Yellow/gray and orange; Thrombin; Serum/chemistry; Clot activator. Red/gray and gold; Clot activator separation gel; Serum/chemistry; Silica clot activator.

Answer 102

Light blue; 3.2% sodium citrate; prevents blood from clotting by binding calcium; coagulation. Red or gold (mottled or "tiger" top used with some tubes); serum tube with or without clot activator or gel; clot activator promotes blood clotting with glass or silica particles, gel separates serum from cells; chemistry, serology, immunology. Green; sodium or lithium heparin with or without gel; prevents clotting by inhibiting thrombin and thromboplastin; stat and routine chemistry. Lavender or pink; potassium ETDA; prevents clotting by binding calcium; hematology and blood bank. Gray; sodium fluoride, and sodium or potassium oxalate; fluoride inhibits glycolysis, and oxalate prevents clotting by precipitating calcium; glucose (especially when testing will be delayed), blood alcohol, lactic acid.

Answer 103

1. Blood-culture tubes (yellow). 2. Coagulation sodium citrate tube (blue stopper). 3. Serum tubes with or without clot activator or gel separator. 4. Heparin tubes with or without gel (green stopper). 5. Ethylenediaminetetraacetic acid tubes (lavender stopper). 6. Glycolytic inhibitor tubes (gray stopper).

Answer 104

Pink tubes are used in immunohematology for ABO grouping, Rh typing, and antibody screening. These tubes have a special cross-match label for information required by the American Association of Blood Banks (AABB) and approved by the U.S. Food and Drug Administration (FDA) for blood bank collections.

Answer 105

Heparin has an advantage over EDTA as an anticoagulant, as it does not affect levels of ions such as calcium. However, heparin can interfere with some immunoassays. Heparin should not be used for coagulation or hematology testing. Heparinized plasma is preferred for potassium measurements to avoid an elevation due to the release of potassium from platelets as the blood clots. Lithium heparin may be used for most chemistry tests except for lithium and folate levels; for lithium, a serum specimen can be used instead. Sodium heparin cannot be used for assays measuring sodium levels, but it is recommended for trace elements, leads, and toxicology. Sodium heparin is the injectable form used for anticoagulant therapy.

Answer 106

Gray-top blood collection tubes are generally used for glucose measurements because they contain a preservative or antiglycolytic agent, such as sodium fluoride, which prevents glycolysis for 3 days. In bacterial septicemia, fluoride inhibition of glycolysis is neither adequate nor effective in preserving glucose concentration.

Answer 107

Red/gray- and gold-top tubes contain a clot activator and a separation gel. These tubes are referred to as serum separator tubes (SSTs) and are used most often for chemistry tests. Therapeutic drug monitoring specimens should not be collected in tubes that contain gel separators, as some gels absorb certain drugs, causing a falsely lowered result. Significant decreases in phenytoin, phenobarbital, lidocaine, quinidine, and carbamazepine have been reported. Also, tubes containing gels are not used in the blood bank or for immunologic testing, as the gel may interfere with the immunologic reactions.

Answer 108

Clotting time for tubes using gel separators is approximately 30 minutes, and tubes that have clot activators, such as thrombin, will clot in 5 minutes. Plain red-stoppered tubes with no additives take about 60 minutes to clot completely.

Answer 109

Oxalate anticoagulants may shrink red cells; thus blood anticoagulated with oxalate cannot be used to measure hematocrit. Combined ammonium/potassium oxalate does not have the same effect of shrinking cells.

Answer 110

During storage, the concentration of a blood constituent in the specimen may change as a result of various processes, including adsorption to glass or plastic tubes, protein denaturation, evaporation of volatile compounds, water movement into cells resulting in hemoconcentration of serum and plasma, and continuing metabolic activities of leukocytes and erythrocytes. These changes occur, although to varying degrees, at ambient temperature and during refrigeration or freezing. Storage requirements vary widely by analyte. Stability studies have shown that clinically significant analyte changes occur if serum or plasma remains in prolonged contact with blood cells. After separation from blood cells, analytes have the same stability in plasma and serum when stored under the same conditions.

Answer 111

To minimize leukocyte consumption of oxygen.

Answer 112

Blood specimens drawn from catheters may be contaminated with whatever was administered or infused via the catheter. The solution (usually heparin) used to maintain patency of the vein must be cleared before blood for analysis is collected. Sufficient blood (minimum of 2–5 mL) must be withdrawn to clear the line (and then discarded), so laboratory data are reliable. In a separate syringe, the amount of blood required for the requested laboratory procedure(s) is then drawn. Strict aseptic technique must be followed to avoid site and/or catheter contamination. Coagulation measurements such as prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) are extremely sensitive to heparin interference, so that even larger volumes of presample blood must be withdrawn before laboratory results are acceptable for these tests. The appropriate volume to be discarded should be established by each laboratory. The laboratory is sometimes asked to perform blood culture studies on blood drawn from indwelling catheters. Because the indwelling catheters are in place for a few days, this procedure is not recommended because organisms that grow on the walls of the catheter can contaminate the blood specimen.

Answer 113

Changes in color (Breakdown or alteration of chromogen or other urine constituent (e.g., hemoglobin, melanin, homogentisic acid, porphyrins)). Changes in odor (bacterial growth, decomposition). Increased turbidity (Increased bacteria, crystal formation, precipitation of amorphous material). Falsely low pH (Glucose converted to acids and alcohols by bacteria producing ammonia. Carbon dioxide (CO2) lost). Falsely elevated pH (Breakdown of urea by bacteria, forming ammonia). False-negative glucose (Utilization by bacteria (glycolysis)). False-negative ketone (Volatilization of acetone; breakdown of acetoacetate by bacteria). False-negative bilirubin (Destroyed by light; oxidation to biliverdin). False-negative urobilinogen (Destroyed by light). False-positive nitrite (Nitrite produced by bacteria after specimen is voided). False-negative nitrite (Nitrite converts to nitrogen and evaporates). Increased bacteriuria (Bacteria multiply in specimen before analysis). Disintegration of cells/casts (Unstable environment, especially in alkaline urine, hypotonic urine, or both).

Answer 114

10 g boric acid: aldosterone, cortisol. 10 mL 6N HCl: catecholamines, cystine, homovanillic acid, hydroxyproline, metanephrines, oxalate, VMA. 0.5 g sodium fluoride: glucose.

Answer 115

Amino acids, amylase, calcium, citrate, chloride, copper, creatinine, delta ALA, glucose, 5-HIAA, heavy metals (arsenic, lead, mercury), histamine, immunoelectrophoresis, lysozyme, magnesium, methylmalonic acid, microalbumin, mucopolysaccharides, phosphorus, porphobilinogen, porphyrins, potassium, protein, protein electrophoresis, sodium, urea, uric acid, xylose tolerance.

Answer 116

Synovial fluid found in the joint cavities is an ultrafiltrate of plasma that is passed through fenestrations of the subsynovial capillary endothelium into the synovial cavity. Once in the cavity, it is combined with hyaluronic acid, a glycosaminoglycan secreted by the synovial lining cells. Synovial fluid differs from the other serous fluids in that it contains hyaluronic acid (mucin) and may contain crystals.

Answer 117

Recentrifugation of gel separator tubes has been associated with pseudohyperkalemia. One study demonstrated that after initial centrifugation, a new serum layer will develop under the gel within the cellular layer. During storage, potassium leaks from the cellular layer into the new serum layer, creating hyperkalemia in this layer. When the tube is recentrifuged, the new serum layer will move above the gel layer and cause a pseudohyperkalemia in the serum for analysis. The same authors also demonstrated that a pseudonormokalemia in patients with true hypokalemia may be erroneously reported after recentrifugation.

Answer 118

Ultracentrifuges are high speed and capable of reaching a centrifugal force of 165,000 times gravity. These centrifuges require refrigeration chambers to compensate for the considerable heat produced. Ultracentrifuges are used to clear serum of chylomicrons, which is necessary to avoid interference with clinical testing.

Answer 119

The appropriate tube should always be used for collection of blood specimens because of interferences from some anticoagulants such as EDTA, which chelates both calcium and magnesium, thereby lowering the measurement of those ions and inhibiting some enzymes that require divalent cations (e.g., alkaline phosphatase by also chelating zinc).

Answer 120

Electrolyte measurements are not valid in blood collection tubes with potassium EDTA or sodium citrate.

Answer 121

Small volumes of blood may be acceptable for some chemistry tests or cell counts; however, coagulation tests require a minimal volume of blood in the collection tube to achieve correct balance with citrate anticoagulant, which also chelates calcium. Excess citrate in plasma from insufficient blood volume leads to falsely elevated clotting times. This interference is also important in polycythemia, when the hematocrit is abnormally high and plasma volume in which the citrate distributes is small. Thus, even in an apparently correctly filled tube, polycythemia can lead to falsely prolonged PT and PTT unless the amount of citrate anticoagulant in the tube is reduced proportionally to the decrease in plasma volume in that patient.

Answer 122

A widely used unit for wavelength in the visible spectrum is the nanometer, nm (10−9 m). Electromagnetic radiation in the x-rays or gamma region may be expressed in terms of angstrom units, Å (10−10 m). Finally, because of its much longer wavelength, EMR in the infrared region may have units corresponding to the micrometer, µm (10−6 m). 1 nm = 10−9 m = 10−7 cm; other units sometimes used include the following: 1 µm = 10−6 m = 10−4 cm, 1 Å = 10−10 m = 10−8 cm.

Answer 123

Measurement of analytes in biologic fluids using reflectometry has been used for decades. Two clinical applications include urine dipstick analysis and dry slide chemical analysis. A reflectometer is a filter photometer that measures the quantity of light reflected by a liquid sample that has been dispensed onto a grainy or fibrous solid support.

Answer 124

Nephelometry and turbidimetry are based on the scattering of radiation by particles in suspension. Nephelometry and turbidimetry are used to measure the concentrations of large particles (such as antigen–antibody complexes, prealbumin, and other serum proteins) that because of their size cannot be measured by absorption spectroscopy. Nephelometry detects light that is scattered at various angles; scattered light yields a small signal that must be amplified. In contrast, turbidimetry measures a reduction in light transmission due to particle formation; thus, it detects a small decrease in a large signal.

Answer 125

Osmometry is the measurement of the osmolality of an aqueous solution such as serum, plasma, or urine. As osmotically active particles (e.g., glucose, urea nitrogen, sodium) are added to a solution, causing its osmolality to increase, four other properties of the solution are also affected: osmotic pressure, boiling point, freezing point, and vapor pressure. They are called colligative properties of the solution because they can be related to each other and to the osmolality. Osmometry is based on measuring changes in the colligative properties of solutions that occur owing to variations in particle concentration. Freezing-point depression osmometry is the most commonly used method for measuring the changes in colligative properties of a solution. It is based on the principle that addition of solute molecules lowers the temperature at which a solution freezes.

Answer 126

Flow cytometry is used to count and sort cells, as well as viral particles, DNA fragments, bacteria, and latex beads. Particles must be in suspension as single cells to be analyzed. If not, they can be made suitable for flow cytometry by the use of mechanical disruption or enzymatic digestion. Size restrictions also apply; cells or particles must be from 1–30 µm in diameter. Specialized flow cytometers are designed to handle smaller particles such as DNA fragments or bacteria.

Answer 127

FACS, an acronym for fluorescence-activated cell sorter, describes the ability of a flow cytometer to physically sort cells in a liquid suspension. To do so, the instrument design has to be modified to electrically charge cells of interest. This is done by first vibrating the sheath stream to break it into drops. The stream of drops flows past two charge (high-voltage) plates where cells of interest are electrically charged with a voltage pulse. Then the flow stream enters an electrical field where charged cells are deflected into suitable collection containers. Unwanted cells are not charged and are not deflected upon passing through the field.

Answer 128

Coulometry is used to measure chloride ion in serum, plasma, CSF, and sweat samples. In measuring chloride with coulometry, a constant current is applied across the two silver electrodes, which liberate silver ions into the specimen at a constant rate. Chloride ions in the sample combine with released silver ions to produce insoluble silver chloride. A pair of indicator and reference electrodes senses the excess silver ions and stops the titration. The number of silver ions released by ionization, which is exactly equal to that of chloride ions in the sample, can be calculated from Faraday's law.

Answer 129

Anodic stripping voltammetry is an electrochemical technique used to measure heavy metals such as lead. The measurement of lead in blood occurs in basically two steps. First, free lead is electroplated (deposited) onto the platinum cathodes at a characteristic voltage. Second, the lead is stripped off of the platinum cathode, and the current is monitored over time. The current value is proportional to the amount of lead in the blood sample. This technique allows the sample to be preconcentrated at the electrode, which enables the method to detect very low analyte levels.

Answer 130

Electrolytic conductivity is a measure of the ability of a solution to carry an electrical current. The principles of conductance have several applications associated with clinical laboratory procedures. Examples include monitoring water purity, measuring analytes in blood such as urea, and serving as components of detectors used in high-performance liquid chromatography (HPLC), gas chromatography (GC), cell counters, and capillary electrophoresis.

Answer 131

Electrical impedance measurement is based on the change in electrical resistance across an aperture when a particle in conductive liquid passes through this aperture. Electrical impedance is used primarily in the hematology laboratory to enumerate leukocytes, erythrocytes, and platelets. In a typical electrical impedance instrument by Coulter, aspirated blood is divided into two separate volumes for measurements. One volume is mixed with diluent and is delivered to the cell bath, where erythrocyte and platelet counts are performed. As a cell passes through the aperture, partially occluding it, the electrical impedance increases, producing a voltage pulse, the size of which is proportional to the cell size. The number of pulses is directly related to the cell count. Particles measuring between 2 and 20 fL are counted as platelets, whereas those measuring greater than 36 fL are counted as erythrocytes. The other blood volume is mixed with diluent and a cytochemical-lytic reagent that lyses only the red blood cells. A leukocyte count is performed as the remaining cells pass through an aperture. Particles greater than 35 fL are recorded as leukocytes.

Answer 132

Electrophoresis is the separation of charged compounds based on their electrical charge. When a voltage is applied to a salt solution (usually sodium chloride), an electrical current is produced by the flow of ions: cations toward the cathode, and anions toward the anode. Conductivity of a solution increases with its total ionic concentration. The greater the net charges of a dissolved compound, the faster it moves through the solution toward the oppositely charged electrode. The net charge of a compound, in turn, depends on the solution pH. Electrophoresis separations often require high voltages (50–200 V DC); therefore, the power supply should supply a constant DC voltage at these levels. The buffer solution must have a carefully controlled ionic strength. A dilute buffer causes heat to be generated in the cell, and a high ionic strength does not allow good separation of the fractions. Common support media for electrophoresis in clinical work include cellulose acetate, agarose, and polyacrylamide gels. Total volume of specimen applied depends on the sensitivity of the detection method. For clinical work, 1 µL of serum may be applied. Once the electrophoresis is completed, the support medium is treated with a dye to identify the separated fractions. The most common dyes used for the visualization step include Amido Black, Ponceau S, Fat Red 7B, and Sudan Black B. To obtain a quantitative profile of the separated fractions, densitometry is performed on the stained support medium.

Answer 133

Electrophoresis is the separation of charged compounds based on their electrical charge. Then, to obtain a quantitative profile of the separated fractions, densitometry is performed on the stained support medium. A densitometer measures the absorbance of the stain on a support medium. The basic components of a densitometer include a light source, a monochromator and a movable carriage to scan the medium over the entire area, an optical system, and a photodetector. Signals detected by the photodetector are related to the absorbance of the sample stain on the support, which is proportional to the specimen concentration. The support medium is moved through the light beam at a fixed rate, so that a graph may be constructed that represents multiple density readings taken at different points. Most densitometers have a built-in integrator to find the area under the curve, so that all sample fractions can be quantified.

Answer 134

Isoelectric focusing (IEF) techniques are performed similarly to other electrophoresis methods, except that the separating molecules migrate through a pH gradient. This pH gradient is created by adding acid to the anodic area of the electrolyte cell and adding base to the cathode area. A solution of ampholytes (mixtures of small amphoteric ions with different pIs) is placed between the two electrodes. These ampholytes have high buffering capacity at their respective isoelectric points. The ampholytes close to the anode carry a net positive charge, and those close to the cathode carry a net negative charge. When an electrical voltage is applied, each ampholyte will rapidly migrate to the area where the pH is equal to its isoelectric point. With their high buffering capacity, the ampholytes create stable pH zones for the more slowly migrating proteins. The advantage of isoelectric focusing techniques lies in their ability to resolve mixtures of proteins. Using narrow-range ampholytes, macromolecules differing in isoelectric point by only 0.02 pH units can be identified. Isoelectric focusing has been useful in measuring serum acid phosphatase isoenzymes. Its application has also been extended to detect oligoclonal immunoglobulin bands in CSF and isoenzymes of creatine kinase and alkaline phosphatase in serum.

Answer 135

Their mobile phase (gas chromatography, liquid chromatography).

Answer 136

Carrier gases (mobile phase), which must be chemically inert, include helium, hydrogen, and nitrogen. Other substances used as mobile phases include steam and supercritical fluids. Examples of these are carbon dioxide, nitrous oxide, and ammonia. The carrier gas should be of high purity, and the flow must be tightly controlled to ensure optimum column efficiency and reproducibility of test results.

Answer 137

Samples are manually introduced into the GC using a syringe pipet or an automated syringe pipet system. A pipet tip pierces a plastic septum located in the injector port. Each injection port is heated to very high temperatures. Samples are vaporized and swept onto the column. If the molecule of interest is not volatile enough for direct injection, it is necessary to derivatize it into a more volatile form. Most derivatization reactions belong to one of three groups: silylation, alkylation, and acylation. Silylation is the most common technique that replaces active hydrogens on the compounds with alkylsilyl groups. This substitution results in a more volatile form that is also less polar and more thermally stable.

Answer 138

Examples of detectors used in GC include a flame ionization detector, a thermal conductivity detector, a nitrogen–phosphorus detector, an electron capture detector, a flame photometric detector, and a mass spectrometric detector. Flame ionization detectors (FIDs) are commonly used and are capable of detecting a wide variety of organic compounds and many inorganic compounds. This type of detector measures the ions produced by the compounds when burned in a hydrogen–air flame. An electrode collects the ions, and the magnitude of the resulting electrical current is proportional to the amount of substance. FIDs can be modified to make them especially sensitive to molecules, including many drugs that contain either nitrogen or phosphorus (the so-called nitrogen–phosphorus detector, or NPD).

Answer 139

GC as a separation technique has some restrictions that make liquid chromatography a suitable alternative. Many organic compounds are too unstable or are insufficiently volatile to be assayed by GC without prior chemical derivatization. Liquid chromatography techniques use lower temperatures for separation, thereby achieving better separation of thermolabile compounds. These two factors allow liquid chromatography to separate compounds that cannot be separated by GC. Finally, it is easier to recover a sample in liquid chromatography than in gas chromatography. The mobile phase can be removed, and the sample can be processed further or reanalyzed under different conditions.

Answer 140

Mass spectrometry typically involves the following major steps: (1) conversion of the parent molecule into a stream of ions (usually singly charged positive ions); (2) separation of the ions by mass/charge ratio (m/z), where m is the mass of the ion in atomic mass units and z is its charge; and (3) counting of the number of ions of each type or measurement of current produced when the ions strike a transducer. Because most of the ions formed in mass spectrometers are singly charged, the m/z is often shortened to the more convenient term mass. Strictly speaking, this abbreviation is incorrect, but it is widely used in mass spectrometry literature. This term also represents the x-axis for MS spectrums of molecules plotted against their relative abundance (y-axis).

Answer 141

All mass spectrometers have three basic components: an ion source, a mass analyzer, and an ion detector. The inlet unit admits samples to the mass spectrometer. When the instrument is part of a GC/MS arrangement, the inlet unit must be heated to maintain the volatile compounds in the vapor state upon coming into the ion source unit. It must also strip away most of the carrier gas to adapt to the high-vacuum condition required for mass spectrometry operation.

Answer 142

The matrix-assisted laser desorption ionization (MALDI) source consists of a solid mixture of analyte and matrix (including organic chromophore) on a sample plate, along with a laser light and ion optics. When the chromophore absorbs the laser light, it vaporizes and lifts the analyte ions from the surface into a gas phase directly above the target plate and into the analyzer. The MALDI technique is considered an offline ionization technique because the sample is purified, deposited, and dried on the sample plate before analysis. Surface-enhanced laser desorption ionization (SELDI) is a technique that measures proteins from complex biologic specimens such as serum, plasma, intestinal fluids, urine, cell lysates, and cellular secretion products. Proteins are captured by adsorption, partition, electrostatic interaction, or affinity chromatography on a solid-phase protein chip surface. A laser ionizes samples that have been co-crystallized with a matrix on a target surface.

Answer 143

Surface-enhanced laser desorption ionization (SELDI) is a technique that measures proteins from complex biologic specimens. Proteins are captured by adsorption, partition, electrostatic interaction, or affinity chromatography on a solid-phase protein chip surface. A laser ionizes samples that have been co-crystallized with a matrix on a target surface. The protein chip chromatographic surfaces in SELDI are uniquely designed to retain proteins from complex mixtures according to their specific properties. After the addition of a matrix solution, proteins can be ionized with a nitrogen laser and their molecular masses measured by time-of-flight (TOF) MS. The protein chip arrays are the heart of the SELDI-TOF MS technology and distinguish it from other MS-based systems. Each array is composed of different chromatographic surfaces that, unlike HPLC or GC, are designed to retain, not elute, proteins of interest. The protein chip arrays have an aluminum base with several spots composed of a chemical (anionic, cationic, hydrophobic, hydrophilic, or metal ion) or biochemical (immobilized antibody, receptor, DNA, enzymes, etc.) active surface. Each surface is designed to retain proteins according to a general or specific physicochemical property of the proteins. Chemically active surfaces retain whole classes of proteins, and surfaces to which a biochemical agent, such as an antibody or other type of affinity reagent, is coupled are designed to interact specifically with a single target protein.

Answer 144

Scintillations are flashes of light that occur when gamma rays or charged particles interact with matter. Chemicals used to convert their energy into light energy are called scintillators. If gamma rays or ionizing particles are absorbed in a scintillator, some energy absorbed by the scintillator is emitted as a pulse of visible light or near-UV radiation. A photomultiplier tube detects light directly or through an internally reflecting optic fiber. A scintillation counter is an instrument that detects scintillations using a photomultiplier tube and counts the electrical impulses produced by the scintillations. An application for scintillation counting is radioimmunoassay (RIA). Two types of scintillation methods exist: crystal scintillation and liquid scintillation. Crystal scintillation generally is used to detect gamma radiation, while liquid scintillation is primarily used to count radionuclides that emit beta particles.

Answer 145

Capillary electrophoresis is a separation technique where a sample introduced into a fused silica capillary is separated by electro-osmotic flow by application of a high voltage across the capillary ends. Applications of capillary electrophoresis include separation of serum proteins and hemoglobin variants.

Answer 146

Laboratory results must undergo a two-step postanalytic review for analytic correctness (using delta checks, linearity ranges, etc.) and for clinical significance for the patient (applying critical values, reference ranges, pretest and posttest probability, etc.).

Answer 147

Reference intervals are most commonly defined as the range of values into which 95% of nondiseased individuals will fall; this definition implies that 5% of nondiseased individuals can have laboratory results outside the reference range. In most settings, reference ranges are determined by the laboratory, with varying degrees of input from the clinical staff.

Answer 148

In spectrophotometric assays, lipids interfere mainly by increasing light scatter (turbidity); in assays using ion-specific electrodes for measurement, lipids will affect results by solvent exclusion.

Answer 149

Delta checks are defined as comparing a current laboratory result with results obtained on a previous specimen from the same patient. Parameters chosen for delta checks should not be subject to large intraindividual variations; for example, many laboratories have delta checks in place for the mean corpuscular volume of red cells.

Answer 150

Because diagnostic tests are not perfect, there is always a tradeoff between sensitivity and specificity, making it difficult to determine an optimal cutoff. The receiver operator characteristic (ROC) curve is a useful tool for identifying the optimal cutoff for a diagnostic test by calculating the sensitivity and specificity combinations across the entire range of cutoff values. In addition, the ROC curves of two or more tests can be compared to identify the one with the greatest discriminating ability.

Answer 151

The receiver operator characteristic (ROC) curve is a useful tool for identifying the optimal cutoff for a diagnostic test by calculating the sensitivity and specificity combinations across the entire range of cutoff values. An ROC curve is constructed by calculating sensitivity and specificity across the entire range of cutoffs for the diagnostic test being evaluated. Sensitivity is plotted on the y-axis and 1− specificity (or the FP rate) on the x-axis; construction of the curve shows the tradeoff between sensitivity and specificity at each cutoff. The ROC curve for a test with no ability to predict disease (i.e., random chance) is a 45-degree line drawn through the origin. As the discriminatory ability of a test increases, the curve progresses outward toward the upper left-hand corner. The area under the ROC curve (AUC) is a single measure of the overall discriminating ability of a test; the minimum AUC is 0.5, which is the area under the 45-degree line, and the maximum AUC is 1.0 for a perfect diagnostic test.

Answer 152

The ROC curve for a test with no ability to predict disease (i.e., random chance) is a 45-degree line drawn through the origin. As the discriminatory ability of a test increases, the curve progresses outward toward the upper left-hand corner. The area under the ROC curve (AUC) is a single measure of the overall discriminating ability of a test; the minimum AUC is 0.5, which is the area under the 45-degree line, and the maximum AUC is 1.0 for a perfect diagnostic test. Because diagnostic tests are not absolutely perfect, the AUC will range from 0.5 to 1.0; the higher the AUC, the greater is the overall discriminating ability of the test. In general, an AUC that is greater than 0.8 suggests that the diagnostic test has good discriminatory power.

Answer 153

The receiver operator characteristic (ROC) curve is a useful tool for identifying the optimal cutoff for a diagnostic test by calculating the sensitivity and specificity combinations across the entire range of cutoff values. The optimal cutoff is identified by the coordinate that maximizes discriminatory power, the location on the ROC curve with the largest distance perpendicular from the 45-degree line. The second useful application for the ROC curve is to compare two or more diagnostic methods by calculating the area under the curve. If the area under the curve is similar, then no difference is observed between the two tests. However, if one ROC curve has a greater AUC than a comparison test, it has better sensitivity and specificity at all cutoffs. However, curves may cross, indicating that performance depends on the desired use of the test (i.e., whether a higher sensitivity or specificity is required for clinical use). If test A has a lower FP rate than test B at high sensitivity, test A is a better screening test while test B would be the better confirmatory test because it has greater sensitivity at high specificities.

Answer 154

The likelihood ratio may be used to select the optimal cutoff for an assay that best separates disease from nondisease. The LR, like sensitivity and specificity, varies with the cutoff. To select the optimal discriminatory cutoff, one might simply pick the cutoff resulting in the greatest LR for a positive test. However, this approach does not take into account the clinical impact of the test result. The clinical consequences of a FP test (e.g., unnecessary surgery) or a FN test (e.g., a missed chance to treat) need to be weighed when the optimal cutoff is determined. The positivity criterion is a method that allows one to assess the optimal cutoff with numeric estimates for clinical impact, or consequences, of test results. In determining which cutoff will serve as the positivity criterion, a finite list of possible cutoffs is generated, and an LR for a positive test is calculated for each cutoff value. Next, the consequences of each of the four possible testing outcomes (TP, TN, FP, and FN) are assigned numeric estimates with respect to some outcome (e.g., morbidity, mortality, cost). Values for the estimated consequences, as well as prevalence estimates of the disease, are then used in the LRthreshold equation, which gives the optimal assay cutoff. From the list of possible analyte concentrations, one can now select the cutoff that most closely approximates the LRthreshold. In this way, one may select a test cutoff that not only optimizes the discriminatory power of the assay, but also fits the clinical need that the test is meant to address.

Answer 155

Especially if the patient is younger than 60 years of age, try to attribute all abnormal laboratory findings to a single cause. Only if there is no possible way to correlate all abnormal findings should the possibility of multiple diagnoses be entertained.

Answer 156

The chromicity of the red cells (i.e., the intensity of the red color of the cells due to intracellular Hb) is measured quantitatively by the mean corpuscular hemoglobin concentration, or MCHC.

Answer 157

Iron binding capacity is a direct measure of the protein transferrin, which transports iron from the gut to iron storage sites in bone marrow.

Answer 158

Considerable overlap has been noted between serum levels of iron and iron-binding capacity in IDA and ACD. A somewhat more reliable discriminating measure of IDA is the ratio of serum iron to IBC, known as the transferrin saturation. This ratio is around 1 : 3 for normal individuals, and in IDA it is significantly reduced to values of around 1 : 5 or lower. Again, considerable overlap is seen even in this ratio for patients with IDA and ACD, so the values should always be interpreted with care.

Answer 159

IDA: low ferritin, increased IBC, decreased serum iron, reduced Fe/IBC ratio, generally increased RDW. ACD: generally high ferritin, normal IBC, decreased serum iron, normal Fe/IBC ratio, generally normal RDW.

Answer 160

Schistocytosis, increased reticulocytes, low haptoglobin, elevated carboxyhemoglobin, elevated LD, elevated indirect bilirubin, generally increased RDW.

Answer 161

Aplastic anemia: leukopenia, thrombocytopenia, hypocellular bone marrow, generally normal RDW. Renal failure: elevated BUN and Cr, low erythropoietin, burr cells may be present, generally normal RDW.

Answer 162

B12 and/or folate deficiency: megaloblastic, low B12 and/or folate, hyperlobulated PMNs, macroovalocytes, increased RDW. Hypothyroidism: nonmegaloblastic, elevated TSH, normal RDW.

Answer 163

After erythrocyte membrane breakdown, Hb is extruded. Extruded Hb becomes bound to the α-2 fraction protein haptoglobin. The Hb–haptoglobin complex becomes catabolized by macrophages that engulf these complexes by receptor-mediated endocytosis. Thus an excellent laboratory test for hemolytic anemia is a low haptoglobin value. Extremely sensitive and rapid ELISA assays for haptoglobin are available for this purpose.

Answer 164

When Hb is extruded, large amounts of it become oxidized to methemoglobin. The heme portion dissociates and then becomes oxidized ultimately to bilirubin. The first step in this process is the oxidative opening of the porphyrin ring of heme with attendant liberation of CO. CO may be measured easily by gas chromatographic techniques or even more conveniently by cooximetry, based on spectrophotometry, as carboxyhemoglobin. Elevated CO levels in normochromic, normocytic anemias are an excellent indicator of hemolytic anemia. Because production of bilirubin, which is unconjugated, is increased, at least a transient elevation of serum indirect bilirubin occurs. This elevation, in the presence of normal liver function, will be modest.

Answer 165

Another normocytic, hypoproliferative anemia is the anemia of chronic renal failure. Loss of the kidneys’ excretory function produces an increase in BUN and creatinine, as discussed later, as well as a buildup of metabolic byproducts. The resulting uremia appears to be responsible for changes in red cell shape, with burr cells (echinocytes) and ellipsoidal cells commonly present on peripheral blood films. Identification of burr cells on peripheral blood films during the course of illness may signal the development of renal dysfunction. In addition to decreased excretory function, the kidneys’ ability to produce erythropoietin is decreased, resulting in impaired erythropoiesis, such that the marrow's response to hypoxia becomes inadequate. In contrast to aplastic anemia, white cell and platelet counts usually remain within normal limits.

Answer 166

Proximal convoluted tubule.

Answer 167

In all forms of hyponatremia, the chloride ion concentration is generally low because it is the chief counter-ion for sodium.

Answer 168

Overhydration: low urine Na, low urine osmolality, normal or low serum K, low 24 hour urine Na. Diuretics: low urine Na, low urine osmolality, low serum K, high 24 hour urine Na. SIADH: high urine Na, high urine osmolality, normal or low serum K, high 24 hour urine Na. Adrenal failure: mildly elevated urine Na, normal urine osmolality, high serum K, high 24 hour urine Na. Bartter's syndrome: low urine Na, low urine osmolality, low serum K, high 24 hour urine Na. Diabetic hyperosmolarity: normal urine Na, normal urine osmolality, high serum K, normal 24 hour urine Na.

Answer 169

Roughly, for every 100 mg/dL increase in serum glucose, a 1.6 mEq/L decrease in serum Na concentration is seen.

Answer 170

This condition is usually caused by the presence of excess lipids in serum. No sodium ions are dissolved in lipids, which can take up a considerable volume of serum. If the absolute amount of sodium in a given volume of serum is determined, as with such methods of sodium determination as flame photometry, this value is divided by the sample volume to get the concentration. But part of this volume is lipid that has no sodium. So a falsely low value of sodium can be obtained. This artifact is eliminated by the use of ion-selective electrodes that directly determine the concentration of sodium and do not depend upon knowledge of the volume of serum. Note that although most modern, high throughput chemistry analyzers measure serum sodium using ion-selective electrodes, they perform a predilution of the specimen (so-called indirect potentiometry), and hence the measurement is relative to volume and is susceptible to pseudohyponatremia.

Answer 171

Dehydration: high urine Na, high urine osmolality, normal serum K, 24 hour urine Na varies. Diabetes insipidus: low urine Na, low urine osmolality, normal serum K, low 24 hour urine Na. Cushing's disease or syndrome: low urine Na, normal urine osmolality, low serum K, low 24 hour urine Na.

Answer 172

1. Infusion of insulin to diabetic individuals. This results in rather large influxes of potassium into cells, which lower it in serum. 2. Alkalosis. RBCs are themselves excellent buffers. They are capable of exchanging potassium for hydrogen ions. Thus, in acidosis, H+ ions enter red cells in exchange for K+ ions. Conversely, in alkalosis, H+ ions leave red cells (to neutralize excess base), and K+ ions enter the red cells. 3. Vomiting. The major loss consists of both H+ and K+ from the stomach. Loss of K+ in gastric fluid may be less important than the overall fluid loss, which causes activation of aldosterone and renal wasting of K+.

Answer 173

Concomitant elevations of potassium and LD in serum should be taken as indications of hemolysis that occurs artifactually after a blood sample has been taken from the patient or, less commonly, as hemolysis that results from an underlying hemolytic condition.

Answer 174

Urea is excreted by the renal tubules at a rate that is roughly proportional to the GFR. Note, therefore, that the retained urea (i.e., plasma or serum urea or BUN) is approximately inversely proportional to the GFR.

Answer 175

Creatinine is secreted but is also reabsorbed to an approximately equal extent, so that the net effect is that the amount filtered is the amount excreted. The total amount of creatinine filtered then is its urinary concentration, Ucr × volume of urine (V), over a given time. The total plasma that delivered this quantity of creatinine to the glomerulus is the total amount of creatinine filtered divided by the plasma concentration, Pcr. This quantity is also the creatinine clearance (Ccr). So GFR = Ccr = Ucr x V/Pcr.

Answer 176

Pre-renal disease is where renal plasma flow is reduced from such lesions as renal artery stenosis, renal vein thrombosis, and the like. This causes a reduction in the GFR and a rise in BUN. However, the serum creatinine levels, with a reference range of about 0.5–1.0 mg/dL, generally will remain within normal limits or may be mildly elevated because low GFR will result in lower urine flow. Pcr and Ucr generally will remain within normal limits. Thus a disproportionate rise in BUN over creatinine will be noted. The normal BUN/creatinine ratio is 10–20 : 1, and in pre-renal disease, it rises to well above 20 : 1.

Answer 177

As in pre-renal disease, there will be a rise in BUN due to low GFR. Now, however, creatinine filtration will be compromised, so that its serum level will rise correspondingly. Thus, in true renal disease, both BUN and creatinine rise together, maintaining the BUN/creatinine ratio at 10–20 : 1. This pattern also occurs in so-called post-renal disease.

Answer 178

If a patient is on a fluid-restricted diet, the osmolality of urine (Uosm) should be significantly higher than the osmolality of plasma (Posm). In fact, Uosm/Posm is >1.2 for normal individuals. If a 24-hour urine specimen collection from the above patient on a fluid-restricted diet is measured for Uosm, we can determine where the lesion has occurred. If Uosm/Posm <1.2, then the urine is not being concentrated, so a tubular lesion must be present. On the other hand, if a normal ratio is found, then, by exclusion, the lesion must be glomerular.

Answer 179

CHARD is for causes of hypocalcemia: Calcitonin, Hypoparathyroidism, Alkalosis, Renal failure, vitamin D deficit. CHIMPS is for causes of hypercalcemia: Cancer, Hyperthyroidism, Iatrogenic causes, Multiple myeloma, Hyperparathyroidism, Sarcoidosis (and also acidosis).

Answer 180

About half of the calcium circulating in blood is bound to serum protein, mainly albumin; the remainder may be chelated in tight complexes with ions such as citrate and oxalate or may be found in ionic complexes with counter-ions such as chloride—so-called free calcium.

Answer 181

Blood gas determinations refer to the quantitative measurement of the pH of arterial blood, the partial pressure of carbon dioxide (pCO2), the bicarbonate, the partial pressure of oxygen (pO2), oxygen saturation, and base excess. Three of these quantities are interdependent on one another, that is, the PCO2, the bicarbonate, and the pH, by the Henderson-Hasselbalch equation.

Answer 182

Metabolic acidosis: low bicarb, low pCO2; typical causes are diabetic ketoacidosis, lactic acidosis (as from gram neg sepsis), renal failure. Metabolic alkalosis: high bicarb, high pCO2; typical causes are vomiting (loss of HCl). Respiratory acidosis: high bicarb, high pCO2; typical causes are COPD, PNA, paralysis of respiratory muscles, CNS diseases affecting the brainstem in areas involved in respiratory control. Respiratory alkalosis: low bicarb, low pCO2; typical causes are anxiety or acute pain (hyperventilation).

Answer 183

Normal serum sodium is about 140 mEq/L, chloride is usually around 100 mEq/L, and bicarbonate around 2 mEq/L.

Answer 184

The anion gap is then defined as Na+ − (Cl− + HCO3−), which for normal individuals is around 16. This 16 mEq/L really accounts for the other counter-ions that neutralize sodium but are not measured in serum.

Answer 185

The presence of a widened anion gap signifies the presence of a metabolic acidosis due to a non–chloride-containing acid. If metabolic acidosis is due to the presence of an acid whose counter-ion is not Cl−, such as acetoacetic acid (in diabetic acidosis) or lactic acid as in sepsis or hypoperfusion, then bicarbonate is reduced, as above, but no corresponding increase in Cl− occurs. Therefore, there is an increase in the anion gap, which can reach values of 25–30 mEq/L.

Answer 186

Consistently low anion gaps, typically in the range of 1–3 mEq/L, signify the presence of high levels of basic protein, often a monoclonal paraprotein as occurs in plasma cell dyscrasias. Basic protein contains ammonium ions, the counter-ions for which are chloride. Now the “invisible” ion is ammonium, and a measurable increase in chloride ion occurs. This tends to decrease the anion gap. Persistently low anion gaps are a serious sign of possible malignancy (e.g., multiple myeloma).

Answer 187

To the right.

Answer 188

In nonketotic, hyperosmolar coma, RBC and WBC water flows from the cells into the vascular volume, tending to dilute analytes such as sodium. Thus, the patient may have a hyperosmolar serum, hyperglycemia, hyperkalemia, and hyponatremia. In ketotic states, the patient will have, additionally, a metabolic acidosis and a large anion gap.

Answer 189

Hepatitis: H, H, H, H, N, N, H, N. Cirrhosis: N, N, N, N to sl-H, L, L, H, H. Biliary obstruction: N, N, N, H, N, N, H, N. Space-occupying lesion: N or H, N or H, H, H, N, N, N-H, N. Passive congestion: sl-H, sl-H, sl-H, N to sl-H, N, N, N to sl-H, N. Fulminant failure: very H, H, H, H, L, L, H, H.

Answer 190

AP, GGT, and 5'-N.

Answer 191

Space-occupying lesions of the liver are characterized, for reasons that are not well understood, by isolated elevations of the enzymes AP and LD. The most common cause of this condition is metastatic carcinoma to the liver.

Answer 192

Different genes encode TnI in skeletal and cardiac muscle, giving rise to isoforms that differ significantly in sequence. Cardiac TnI contains an additional 31 amino acid residues on its N-terminal.

Answer 193

Increase in concentration of acute phase reactants (APR) comprises a major pathophysiologic phenomenon that accompanies inflammation and tissue injury. With the acute phase response, normal homeostatic mechanisms are replaced by new set points that presumably contribute to defensive or adaptive capabilities. Despite its name, APR accompany both acute and chronic inflammatory states. They can occur in association with a wide variety of disorders, including infection, trauma, infarction, inflammatory arthritides, and various neoplasms. Acute phase proteins are defined as those proteins whose serum concentrations increase or decrease by at least 25 percent during inflammatory states. Such proteins are termed either positive or negative APR, respectively. Changes in the levels of APR largely reflect altered production by hepatocytes.

Answer 194

Acute phase proteins are defined as those proteins whose serum concentrations increase or decrease by at least 25 percent during inflammatory states. Such proteins are termed either positive or negative APR, respectively. Increases in APR can vary from approximately 50 percent for ceruloplasmin and several components of the complement cascade to 1000-fold or more for CRP and serum amyloid A. Other positive APR include fibrinogen, alpha-1 antitrypsin, haptoglobin, alpha-1 acid glycoprotein (orosomucoid), IL-1 receptor antagonist, hepcidin, ferritin, procalcitonin, and others. Transferrin is decreased with acute inflammation and increased with chronic inflammation. Negative APR include albumin and transthyretin. The ESR, a nonprotein APR, reflects plasma viscosity and the presence of acute phase proteins.

Answer 195

In cases of hypercortisolism, especially when ACTH levels may remain in the reference range or have “borderline” high or low values, it is often desirable to perform the dexamethasone suppression test. Dexamethasone is a potent glucocorticoid that strongly suppresses normal pituitary ACTH secretion. This can be accomplished with low-dose dexamethasone. If low-dose dexamethasone causes diminished serum cortisol levels and low values for urinary free cortisol, pituitary function is most likely normal while the adrenals are hypersecreting cortisol (i.e., primary hyperadrenalism). This test may be used further to distinguish the possible source of primary hyperadrenalism (i.e., hyperplasia vs. adenoma or carcinoma). High-dose dexamethasone will generally lower serum cortisol levels in adrenal hyperplasia, but it will have no effect in adrenal adenoma or carcinoma.

Answer 196

Vitamin D induces absorption of calcium from the gut by acting on vitamin D receptors in the cells lining the gut. It is produced from 7-dehydrocholesterol in skin by ultraviolet light that induces the synthesis of cholecalciferol. In the liver, cholecalciferol is converted to 25-hydroxycholecalciferol, which has a half-life of several weeks. This form is further hydroxylated in the kidneys to 1,25-dihydroxycholecalciferol, the active form of vitamin D. The half-life of active vitamin D is on the order of hours.

Answer 197

7-dehydrocholesterol in skin is converted by ultraviolet light into cholecalciferol. In the liver, cholecalciferol is converted to 25-hydroxycholecalciferol, which has a half-life of several weeks. This form is further hydroxylated in the kidneys to 1,25-dihydroxycholecalciferol, the active form of vitamin D. The half-life of active vitamin D is on the order of hours. Thus, in serum assays for vitamin D, the analyte whose serum level best reflects vitamin D levels is the precursor, 25-hydroxycholecalciferol. This may give falsely elevated levels of vitamin D in cases of renal failure where conversion of the precursor to active vitamin D is impaired. However, 25-hydroxycholecalciferol itself has some effects on calcium reabsorption, although its affinity for the vitamin D receptor is only about one-one thousandth of that for the fully active form.

Answer 198

13s refers to a control rule that is commonly used with a Levey-Jennings chart when the control limits are set as the mean plus 3s and the mean minus 3s. A run is rejected when a single control measurement exceeds the mean plus 3s or the mean minus 3s control limit. 12srefers to the control rule that is commonly used with a Levey-Jennings chart when the control limits are set as the mean plus/minus 2s. In the original Westgard multirule QC procedure, this rule is used as a warning rule to trigger careful inspection of the control data by the following rejection rules. 22s - reject when 2 consecutive control measurements exceed the same mean plus 2s or the same mean minus 2s control limit. R4s - reject when 1 control measurement in a group exceeds the mean plus 2s and another exceeds the mean minus 2s. 41s - reject when 4 consecutive control measurements exceed the same mean plus 1s or the same mean minus 1s control limit. 10x - reject when 10 consecutive control measurements fall on one side of the mean. In addition, you will sometimes see some modifications of this last rule to make it fit more easily with Ns of 4: the 8x and 12x rules.

Answer 199

The 12S rule has a good probability of detecting errors (e.g. almost 90% probability of detecting a 2.5 SD bias) but has a high false alert rate. Because of this high false alert rate, it is not recommended to use a 12S rule. The 10x (or 10m) rules are also not recommended because of an excessive false alert rate. Many contemporary analyzers are very stable and may produce QC results with a small standard deviation interval (SDI) on one side of the target value for extended periods of time. Consequently, a 10x rule generally is not recommended, as this condition does not infer a problem with clinical interpretation of patient results when the magnitude of the difference is small. In contrast, the 13S rule has a low false alert rate, but a lower probability to detect an error (e.g., a 55% probability to detect a 2.5 SD bias). It is recommended to improve the efficiency of QC interpretive rules by combining two or more rules and applying them simultaneously as multi-rule criteria.

Answer 200

Because the matrix-related interaction between a QC material and a reagent can change with a different reagent lot, QC results may not be a reliable indicator of a method's performance for patient samples following a reagent lot change. For this reason, it is necessary to use clinical patient samples to verify the consistency of results between old and new lots of reagents. When a new lot of calibrator is used, with no change in reagents, there is no change in matrix interaction between the QC material and the reagents. In this situation, QC results provide a reliable indication of calibration status with the new lot of calibrator. If the QC results indicate a bias following use of a new lot of calibrator, the calibration has changed and needs to be corrected to ensure consistent results for patient samples.

Answer 201

Some types of laboratory errors can be identified by comparing a patient's current test result against a previous result for the same analyte. This comparison is called a “delta check.” The previous result is taken from a specified time interval in the past during which the result is not likely to have changed physiologically. This limitation restricts the analytes that can be effectively monitored with a delta check. Delta checks can detect analytic errors; however, their main purpose is to detect mislabeled samples and samples altered by dilution with IV fluid. Consequently, an effective delta check process can be established using a limited number of analytes.

Answer 202

Automated approaches to determine the mean (or median) for groups of sequential patient results used as a continuous process control parameter have been described. These methods are called “average of normals” (AON) or “moving average” techniques and are suitable for use in higher volume assays in chemistry and hematology. In general, these approaches evaluate sequential patient results over time intervals such as several hours to 1 or more days. For some analytes, patients may need to be partitioned to obtain subgroups whose results are expected to be homogeneous. Consideration of influences for partitioning includes age, gender, ethnicity, and disease conditions.

Answer 203

The 10 AMA organ or disease-oriented panels (CPT, 2009) are: basic metabolic panel (calcium, ionized), basic metabolic panel (calcium, total), general health panel, electrolyte panel, comprehensive metabolic panel, obstetric panel, lipid panel, renal function panel, acute hepatitis panel, and hepatic function panel. When these panels are performed, they must be coded with the unique panel code and not by each individual test's CPT code. Reimbursement is much lower for a panel than it is for the sum total reimbursement of each test. Coding for each individual test component as opposed to one panel code is considered “unbundling,” which is a fraudulent billing practice.

Answer 204

Basic metabolic panels can include ionized calcium under one CPT code, or total calcium under another CPT code. Including the calcium, a basic metabolic panel includes carbon dioxide, chloride, creatinine, glucose, potassium, sodium, and BUN. A comprehensive metabolic panel includes albumin, total bilirubin, calcium, carbon dioxide, chloride, creatinine, glucose, alkaline phosphatase, potassium, total protein, sodium, ALT, AST, and BUN.

Answer 205

Nerve agents (sarin, tabun, soman, VX, malathion, carbaryl (Sevin)). Blood agents (hydrogen cyanide, cyanogen chloride). Blister agents (nitrogen and sulfur mustards, lewisite). Heavy metals (arsenic). Pulmonary agents (chlorine gas, phosgene). Dioxins (tetrachlorodibenzodioxine - a component of Agent Orange). Incapacitating or psychotomimetic agents (quinuclidinylbenzylate, phencyclidine). Corrosive acids and bases (sulfuric acid, sodium hydroxide).

Answer 206

First responder teams and HAZMAT teams have portable devices that detect and identify hazardous chemicals. First responder teams, HAZMAT teams, and ERs have portable devices to detect radiation. The role of the Level A laboratory is secondary; mainly triage and supportive care of patients affected by the incident (especially after nuclear terrorism). In the case of chemical terrorism, labs can provide some useful analytic data, such as: detecting some nerve toxins by ELISA, PCR, or MS; measuring increased cholinesterase activity such as would be seen in patients exposed to nerve agents; and detecting metabolites of vesicants such as mustard gas or Lewisite by GC-MS.

Answer 207

IgG: 2. IgM: 5 (valency of 10 can be seen with very small haptens). IgA: 2-4. IgD: 1. IgE: 1.

Answer 208

IgM: 10 days, 0.5-2 mg/mL, 6%, fluids. IgG: 21 days, 8-16 mg/mL, 80%, tissue. IgA: 6 days, 1.4-4 mg/mL, 13%, secretions. IgD: 3 days, 0-0.04 mg/mL, 0-1%, -. IgE: 2 days, trace concentration, -, secretions.

Answer 209

IgG - 21 days, IgM - 10 days, IgA - 6 days, IgD - 3 days, IgE - 2 days.

Answer 210

IgM is ++++ inactivated by sulfhydryl reagents; IgA is +/-; IgG is -. Only IgG crosses the placenta. IgM is ++++ at inducing agglutination; IgA is ++, and IgG is +. IgM fixes complement +++ (classical); IgG ++ (classical); IgA + (alternative). IgG has +++ binding to Fc gamma receptors; IgA and IgE are +; IgM and IgD are -.

Answer 211

In vivo half-life in days: 21, 21, 7, 21. Relative serum concentration in %: 64-70, 23-28, 4-7, 3-4. Ability of placental transfer: ++, +/-, ++, ++. Ability of complement fixation: +++, ++, ++++, +/-. Ability of macrophage binding: +++, +, +++, +/-.

Answer 212

The combining site of an antibody, where it is in physical contact with an antigenic determinant or epitope, is called the paratope. Binding involves formation of multiple noncovalent bonds between the antigen and amino acids of the paratope.

Answer 213

D-dimer is reported in mass units and, as these assays have evolved, 2 different types of units have been used to represent D-dimer: the fibrinogen equivalent unit (FEU) at 340 kDa and the D-dimer unit (DDU) at 195 kDa. Fibrin monomer polymerizes end to end and side to side forming a fiber, fibrin, in a process that is not enzymatically driven. The polymerization of fibrin monomer occurs with the association of the D domains of 2 fibrin monomers (referred to as D-dimer) with the E domain of a third. Soluble fragments of fibrin (fibrin degradation products) that contain variable numbers of the D-D domains (D-dimer) are produced. When assayed, the fragments are quantified in 2 different types of units, the DDU and the FEU. The mass of the FEU, related to the mass of fibrinogen, is about 1.7 times greater than the mass of the DDU. Because the D-dimer is reported in mass units, the type of units involved is very important in setting the threshold for the exclusion of venous thromboembolism and for interpretation of reported results. Adding to the complexity of reporting these values is the variability in the magnitude of units reported, for example, ng/mL, μg/mL, and μg/L. Variability in the type and magnitude of units has led to confusion in some laboratories as they attempt to use the assay, especially as they set a threshold for the exclusion of VTE.

Answer 214

Haptoglobin binds free hemoglobin to prevent iron loss and kidney damage during hemolysis. Any hemolytic process (immune, mechanical, environmental) can result in free hemoglobin entering the vascular system.

Answer 215

Positive acute phase reactant.

Answer 216

Haptoglobin is made in the liver as a single polypeptide chain that is cleaved post-translationally to generate alpha and beta subunits. These polypeptide chains can then be linked via disulfide bonds into four peptide chains in two pairs (alpha-beta)2 confirmation, much like hemoglobin.

Answer 217

The beta zone contains transferrin, LDL, and C3.

Answer 218

Types I and V. But they have no increase in risk for atherosclerosis.

Answer 219

Type IIb is the most common. Types IIa and IIb have the highest risk of CAD. Type I can be treated with diet changes only.

Answer 220

Heparin inhibits DNA polymerase.

Answer 221

For each 1 g/dL the albumin drops below the "normal" level of 4 g/dL, add 0.8 mg/dL to the total calcium.

Answer 222

Secondary hyperparathyroidism is due to increased physiological PTH as a response to increased resistance to PTH activity, most commonly in end-stage renal disease.

Answer 223

Calculated. SaO2 is calculated from the hematocrit and the PaO2 plotted on a standard hemoglobin oxygen dissociation curve.

Answer 224

PaO2, PaCO2, and pH are directly measured. SaO2 is calculated from the hematocrit and the PaO2 plotted on a standard hemoglobin oxygen dissociation curve.

Answer 225

The co-oximeter, which has the ability to directly measure the proportions of several hemoglobin subtypes. The other techniques, if they possess the ability to do so, calculate the proportions rather than measure them. In addition, multiple potential confounding elements are present in some of the techniques, such as poor peripheral perfusion or recent transfusion.

Answer 226

[Na+] - ( [Cl-] + [HCO3-] )

Answer 227

Renal azotemia. A maintained but elevated ratio is suggestive of an intrinsic renal defect, most commonly glomerulonephritis or tubulointerstitial nephritis. Deranged ratios, such as when BUN increases more than Cr, is suggestive of impaired renal perfusion, such as prerenal (insufficient volume to the kidney) and postrenal (insufficient volume out of the kidney).

Answer 228

Spontaneous bacterial peritonitis.

Answer 229

Bile ducts, bone, placenta, intestine.

Answer 230

Anodal mobility 1 = biliary. Anodal mobility 2 = bone. Anodal mobility 3 = placenta. Anodal mobility 4 = intestinal.

Answer 231

Bone alkaline phosphatase is produced by osteoblasts and reflects bone-forming activity.

Answer 232

Paget disease of bone.

Answer 233

AKA carcino-placental alkaline phosphatase. Appears to be mostly identical to placental alk phos (same anodal mobility, same degree of inhibition by L-phenylalanine, slightly less degree of heat/urea inhibition). The Regan isoenzyme is observed in ~5% of individuals with carcinoma.

Answer 234

Biliary: -, +. Bone: -/+++. Placenta: +++/-. Intestinal: +++/+. For sensitivity to heat/urea, think "bone burns, placenta persists."

Answer 235

GGT levels are considerably higher in men and African Americans.

Answer 236

Hyperammonemia is nearly always due to liver failure. However, particularly in children, it should raise suspicion for an inborn error of metabolism (especially urea cycle enzyme deficiencies).

Answer 237

Bilirubinuria indicates conjugated hyperbilirubinemia, because unconjugated bilirubin, even when quite elevated, does not appear in urine.

Answer 238

Both, at the same time. This method is only capable of measuring total bilirubin.

Answer 239

In unconjugated hyperbilirubinemia... If the step affected is heme conversion to unconjugated bilirubin (increased production), the pathologic process is extravascular hemolysis. If the step affected is delivery of unconjugated bilirubin to liver, the potential pathologic processes are blood shunting (cirrhosis) or right heart failure. If the step affected is uptake of unconjugated bilirubin into hepatocyte, the potential pathologic processes are Gilbert syndrome and drugs such as rifampin. If the step affected is conjugation of bilirubin in hepatocyte, the potential pathologic processes are Crigler-Najjar syndrome and hypothyroidism.

Answer 240

In conjugated hyperbilirubinemia... If the step affected is transmembrane secretion of conjugated bilirubin into canaliculus (hepatocellular jaundice), the potential pathologic processes are Dubin-Johnson syndrome, hepatitis, endotoxin (sepsis), pregnancy (estrogen), and drugs such as estrogen and cyclosporine. If the step affected is flow of conjugated bilirubin through canaliculi and bile ducts (cholestatic jaundice), the potential pathologic process is mechanical obstruction such as from PBC, PSC, tumor, stricture, or stone.

Answer 241

If conjugated hyperbilirubinemia is prolonged, conjugated bilirubin can become covalently linked to serum albumin, resulting in a moiety known as delta bilirubin. Both liver and kidney are incapable of excreting delta bilirubin; thus, even after resolution of the underlying cause, conjugated hyperbilirubinemia (in the form of delta bilirubin) may persist for some time.

Answer 242

Hepatocellular jaundice: alk phos 3x upper limit of normal, cholesterol normal, and pruritis absent. Cholestatic jaundice: alk phos >3x upper limit of normal, transaminases <3x upper limit of normal, cholesterol increased, and pruritis present.

Answer 243

In autoimmune hepatitis there is a polyclonal increase in IgG, while in primary biliary cirrhosis there is a polyclonal increase in IgM.

Answer 244

Physiologic jaundice. Breast milk jaundice. Polycythemia. Hemolysis (HDN, hemoglobinopathies, inherited membrane or enzyme defects). Bowel obstruction (Hirschprung disease, cystic fibrosis, ileal atresia). Inherited disorders of bilirubin metabolism (Gilbert syndrome, Crigler-Najjar syndrome).

Answer 245

Biliary obstruction (extrahepatic biliary atresia). Sepsis or TORCH infection. Neonatal hepatitis (idiopathic, Wilson disease, alpha-1 antitrypsin deficiency). Metabolic disorders (galactosemia, hereditary fructose intolerance, glycogen storage disease). Inherited disorders of bilirubin transport (Dubin-Johnson syndrome, Rotor syndrome). Parenteral alimentation.

Answer 246

Bilirubin has a special affinity for the globus pallidus, the hippocampus, and the subthalamic nucleus. Many other structures, including the striatum, thalamus, cranial nerve nuclei, inferior olives and dentate nuclei of the cerebellum are less frequently affected.

Answer 247

Unconjugated hyperbilirubinemia. Phototherapy converts unconjugated bilirubin into a molecule that can be excreted without conjugation; phototherapy is not useful for conjugated hyperbilirubinemia.

Answer 248

Usually noted between days 2-3 of neonatal life and rarely rises at a rate greater than 5 mg/dL/day. Usually peaks by days 4-5 and rarely exceeds 5-6 mg/dL.

Answer 249

In a healthy term infant, phototherapy should be considered when bilirubin exceeds 10 mg/dL before 12 hours of age, 12 mg/dL before 18 hours of age, and 14 mg/dL before 24 hours of age.

Answer 250

The AST:ALT is over 2 in 80% of patients with toxic, ischemic, and alcoholic hepatitis. It is usually <1 in viral hepatitis.

Answer 251

Jaundice occurs in 70% of patients with alcoholic hepatitis and acute hepatitis A, and occurs in 20-30% of patients with acute hepatitis B and acute hepatitis C.

Answer 252

The PT is probably the best indicator of prognosis In acute hepatic injury, with PT prolongation >4 seconds indicating severe liver injury and an unfavorable prognosis. But bilirubin >15 mg/dL is also indicative of severe liver injury and an unfavorable prognosis.

Answer 253

Pancreatic and salivary. But when subjected to electrophoresis, 6 bands result, with the first three being salivary and the slowest three being pancreatic.

Answer 254

When serum amylase is subjected to electrophoresis, 6 bands result, with the first three being salivary and the slowest three being pancreatic.

Answer 255

An inhibition test: Salivary amylase is sensitive to inhibition by the wheat germ lectin, triticum vulgaris.

Answer 256

Serum amylase rises within 2 to 24 hours of the onset of acute pancreatitis and returns to normal in 2 to 3 days.

Answer 257

Amylase is primarily cleared by glomerular filtration.

Answer 258

Triglycerides competitively interfere with the amylase assay.

Answer 259

Diabetic ketoacidosis, peptic ulcer disease, acute cholecystitis, ectopic pregnancy, salpingitis, bowel ischemia, intestinal obstruction, renal insufficiency, salivary gland pathology, and macroamylasemia. Amylase may also be raised somewhat by the administration of opioid analgesics, due presumably to contracture of the sphincter of Oddi.

Answer 260

The degree of elevation tends to be higher in acute pancreatitis, but there is considerable overlap in the ranges. Pancreatitis causes amylase in the range of 250-1000 Somogyi units, while other causes are 200-500.

Answer 261

A benign acquired condition (associated with celiac disease, lymphoma, HIV infection, monoclonal gammopathy, rheumatoid arthritis, and ulcerative colitis) with an incidence of ~1%, in which apparently healthy individuals have markedly elevated serum amylase levels (with low urine amylase levels), due to Ig-amylase complexes.

Answer 262

Yes. But unlike amylase, hypertriglyceridemia does not interfere with lipase measurement.

Answer 263

Serum and urine trypsinogen-2 and elastase-1.

Answer 264

Invasive: Secretin-CCK/secretin-pancreozymin test. Noninvasive: Fecal fat. Fecal elastase-1. Fecal chymotrypsin (bentiromide).

Answer 265

An endoscope is introduced, and the duodenal concentrations of pancreatic exocrine products (bicarbonate, amylase, lipase, trypsin) are measured after IV administration of secretin and CCK.

Answer 266

Severe ileal diseases (such as Crohn disease) or ileal resection.

Answer 267

Small bowel mucosal absorptive capacity.

Answer 268

Pseudocyst: inc, dec, inc. Serous cystadenoma: dec, dec, dec. Mucinous cystadenoma (mucinous cystic neoplasm): dec, inc, nl to inc. Intraductal papillary mucinous tumor: inc, inc, nl to inc. Solid-pseudopapillary tumor: dec, dec, dec.

Answer 269

The fastest is CK-BB (CK1). The slowest is CK-MM (CK3).

Answer 270

Stomach, bladder, and prostate.

Answer 271

CK-MM is found in skeletal and cardiac muscle. Skeletal muscle is ~99% MM, and cardiac muscle is ~70% MM.

Answer 272

In normal subjects serum CK is almost 100% CK-MM isoenzyme, mostly from skeletal muscle.

Answer 273

CK-MB is found in skeletal and cardiac muscle. Skeletal muscle is ~1% MB, and cardiac muscle is ~30% MB.

Answer 274

The relative index adds to the ability of either assay alone to distinguish myocardial infarction. A relative index of about 2% is often the chosen cut-off.

Answer 275

There are 2 types. Macro-CK type 1 is a CK-Ig complex, with CK-BB complexing to IgG or IgA. On electrophoresis it migrates between MM and MB. It is found in healthy elderly women. Macro-CK type 2 is a polymeric form of mitochondrial CK. On electrophoresis it migrates cathodal to CK-MM. It is associated with malignancies.

Answer 276

Metabolic breakdown products of CK. With high-resolution electrophoresis, CK-MB resolves into 2 bands and CK-MM resolves into 3 bands. CK-MB2 and CK-MM3 are the tissue forms that are released from damaged myocardium. CK-MB1 is the plasma form and arises as a result of cleavage of a terminal lysine from the M peptide. CK-MM1and CK-MM2 are also cleavage products. A relative increase of tissue forms indicates a recent enzyme leak.

Answer 277

Troponins are a group of enzymes consisting of TnT, TnI, and TnC that are involved in mediating the actin-myosin interactions that result in muscle contraction.

Answer 278

While the same gene encodes cardiac and skeletal TnC, separate genes encode TnI and TnT in cardiac and skeletal muscle.

Answer 279

A small proportion of cardiac muscle troponin is free in the cytoplasm but the vast majority of it is bound to actin and myosin. Thus, there is both an immediate release of cytoplasmic troponin by infarcted cardiac muscle (within 4-8 hours) and a sustained release of bound troponin (over 10-14 days).

Answer 280

A measured quantity of cobalt is added to patient plasma and the amount of unbound cobalt is measured. The quantity of unbound cobalt is a measure of ischemia-modified albumin (rises within minutes of myocardial ischemia and returns to baseline within 6 hours due to rapid hepatic clearance).

Answer 281

ANP is synthesized mainly by atrial myocytes (but synthesis of ANP also takes place in the ventricles, brain, kidney, and adrenals). ANP is stored in granules and stimulation results in a rapid response. BNP is synthesized by ventricular myocytes (predominantly) and brain, as well as atrial myocytes under some conditions. BNP is secreted by a constitutive mechanism; only small amounts are stored and cells are dependent upon activation of the BNP gene when secretion is needed. CNP is synthesized by brain and endothelium.

Answer 282

The specificity of CK-MB cannot equal that of troponin, because of false-positives from non-ischemic cardiac injury (pericarditis, myocarditis) and skeletal muscle disease (rhabdomyolysis, exercise). However, troponin is not useful to determine temporal stage of the MI (it remains elevated for up to 2 weeks following AMI), so serial CK-MB is still useful to see if the infarct is acute or resolving, or if there is a complication of MI such as extension of the infarct.

Answer 283

An indication of successful reperfusion following thrombolysis is the washout phenomenon. In successful reperfusion, all of the cardiac markers peak earlier than normal; although, their sequence of peaks parallels that of normal MI. In addition, their peak concentrations may be higher than they would have been with unreperfused MI.

Answer 284

Refractive index can be accurate for measuring serum protein concentration as dissolved solute for levels above 2.5 g/dL. However, there are many potential interferences and hemolysis, lipemia, icterus, and azotemia produce erroneously high results. Refractive index cannot be used for urine protein measurements because of excess amounts of solutes in relation to the protein.

Answer 285

Measurement of nitrogen content. The Kjeldahl technique consists of acid digestion to release ammonium ions from nitrogen-containing compounds. The ammonium can then be quantitated by conversion to ammonia gas and titration as a base, or by nesslerization, in which double iodides (potassium and mercuric) form a colored complex with ammonia in alkali. Although determination of nitrogen content can be extremely precise, its use for calculation of protein concentration depends on the exact protein composition of a sample, because each protein has a somewhat different nitrogen content according to amino acid composition. For a sample of a purified protein, nitrogen content is highly accurate for estimating protein concentration when the nitrogen content on a molar basis is already known for that purified protein. Because clinical samples consist of unpredictable mixtures of different proteins, and measurement of nitrogen content is not a simple procedure, it is not commonly used in clinical laboratories.

Answer 286

A colorimetric technique highly specific for proteins and peptides is the Biuret method, by which copper salts in alkaline solution form a purple complex with substances containing two or more peptide bonds. The absorbance of the resulting chelate at 540 nm is proportional to total protein concentration. Interferences are minimal, although ammonium ion may acidify the reaction, while hemoglobin and bilirubin absorb in the same region as the Biuret complex (540–560 nm). The Biuret method is extensively used in clinical laboratories, particularly in automated analyzers in which protein concentration can be measured down to 10 or 15 mg/dL.

Answer 287

Electrochemical cells are contained systems in which a redox reaction occurs. There are two types of electrochemical cells: galvanic cells (AKA voltaic cells) and electrolytic cells. Spontaneous reactions occur in galvanic cells, and nonspontaneous reactions in electrolytic cells. Both types contain electrodes at which oxidation and reduction occur. For all electrochemical cells, the electrode at which oxidation occurs is called the anode, and the electrode where reduction occurs is called the cathode.

Answer 288

Trick question. The anode of an electrolytic cell is considered positive, since it is attached to the positive pole of the battery and so attracts anions from the solution. The anode of a galvanic cell is considered negative because the spontaneous oxidation reaction that takes place at the galvanic cell's anode is the original source of that cell's negative charge (i.e. Is the source of electrons). In spite of this difference in designating charge, oxidation takes place at the anode in both types of cells, and electrons always flow through the wire from the anode to the cathode.

Answer 289

Electromotive and endosmotic. When a charge is applied (from a power source), this creates an electromotive force. The solid support has a slight negative charge and is drawn toward the positive pole (anode), but, being a solid support, it cannot move. There is instead a compensatory flow of the fluid buffer towards the negative pole (cathode). This buffer flow is called endosmosis and has the capacity to carry with it substances suspended within the medium. Since most proteins bear a net negative charge, electromotive force tends to pull them to the anode (positive pole), whereas endosmosis pulls them toward the cathode (negative pole). In most proteins, the electromotive force exceeds the endosmotic force, and they move to variable extents towards the anode. However, gamma globulins have a weak net negative charge and the endosmotic force displaces them toward the cathode.

Answer 290

Immunoelectrophoresis, immunofixation electrophoresis, and immunotyping (immunosubtraction) are methods used for characterizing a suspected monoclonal band observed on SPEP or UPEP.

Answer 291

Albumin constitutes ~2/3 of total plasma protein and has a half-life of 17 days.

Answer 292

Analbuminemia is a rare AR disorder manifested by the absence or severe reduction of circulating serum albumin. Analbuminemic individuals usually have surprisingly minimal findings, since the absence of albumin is partially compensated for by an increase of other serum proteins, such as globulins, transferrin, and coagulation factors. The main clinical symptoms include mild edema and occasionally chronic fatigue or lipodystrophy, especially in women, while the most common biochemical signs are gross hyperlipidemia with hypercholesterolemia and elevated LDL-cholesterol levels. The finding of a low albumin concentration during routine SPEP, with normal liver function and no GI or renal protein loss, suggests the clinical diagnosis. This needs to be confirmed by the molecular diagnosis, based on the identification of the causative mutation within the albumin (ALB) gene by DNA sequence analysis.

Answer 293

Hepatic synthetic function is poorly reflected in the albumin, since only in end-stage liver disease is serum albumin noticeably decreased. The greatest decrements in serum albumin are seen in protein-losing conditions such as protein-losing enteropathy and nephrotic syndrome.

Answer 294

In non-diabetic individuals, up to 8% of albumin is normally glycosylated nonenzymatically in the serum. In diabetics with poor control, up to 25% becomes glycosylated.

Answer 295

Prealbumin. Due to its sparseness, however, it is not normally seen on traditional SPEP and seen only faintly on high-resolution SPEP.

Answer 296

T4 and T3 circulate in the blood bound to 3 different binding proteins: thyroxine-binding globulin (TBG), prealbumin (AKA thyroxine-binding prealbumin (TBPA) AKA transthyretin (TTR)), and albumin. TBG carries 70% of the circulating T4 and T3 due to its high affinity. Prealbumin binds to ~10-15% of the hormones (mostly T4), and albumin binds to the remaining 10-15%.

Answer 297

Prealbumin crosses the blood-brain barrier and is actively secreted into the CSF by the choroid plexus.

Answer 298

The prominent "prealbumin" band that is often seen in heparinized patients results from an alteration in beta-lipoprotein such that it migrates in the prealbumin range.

Answer 299

Alcohol use, renal dysfunction and drugs (corticosteroids and other hormones, high-dose NSAIDs). .

Answer 300

Alpha-1-lipoprotein (a constituent of HDL) is found at the albumin/alpha-1 interface. Beta-lipoprotein (a constituent of LDL) is found at the beta-1/beta-2 interface.

Answer 301

SPEP can be used to screen for AAT deficiency, in which the serum will display a markedly diminished alpha-1 band.

Answer 302

Alpha-1 antitrypsin is usually the major component of the alpha-1 band. Alpha-1 acid glycoprotein (orosomucoid) is usually a minor component of the alpha-1 band but a major component of the increased alpha-1 band seen in acute inflammation.

Answer 303

A falsely normal or increased ceruloplasmin may be seen in inflammatory states (ceruloplasmin is an acute phase reactant) or pregnancy. Decreased ceruloplasmin is seen with Wilson disease, hepatic failure, malnutrition, and Menke syndrome.

Answer 304

Alpha-2 macroglobulin, haptoglobin, and ceruloplasmin.

Answer 305

This area is usually empty, but hemoglobin, usually absent from serum, may be present here when there is a hemolysis, giving a possible pseudo-M-spike.

Answer 306

No. Haptoglobin is a protein that binds free hemoglobin.

Answer 307

The haptoglobin genetic locus at 16q22 is polymorphic with two classes of alleles: type 1 and type 2. Based on these 2 alleles, the 3 haptoglobin phenotypes/protein products are: Hp 1-1, Hp 2-1, and Hp 2-2. The 2-2 phenotype is an independent risk factor for CV disease in DM.

Answer 308

The half-life of haptoglobin is 3.5 days, and the half-life of the haptoglobin-hemoglobin complex is ~10 minutes. The haptoglobin-hemoglobin complex is removed by binding to the CD163 receptors on the surface of macrophages and monocytes.

Answer 309

The major biologic function of haptoglobin is to bind hemoglobin in an equimolar ratio with very high affinity to prevent hemoglobin-mediated renal parenchymal injury and loss of iron following intravascular hemolysis. In addition, haptoglobin can inhibit prostaglandin synthesis and is believed to have anti-inflammatory and antioxidant properties in the body.

Answer 310

Transferrin is the major beta globulin and makes up the beta-1 band. Transferrin may be high in iron deficiency, giving a possible pseudo-M-spike. Beta-lipoprotein, a constituent of LDL, is seen at the beta-1/beta-2 interface. The beta-2 band is made up of IgA (runs beta-2 to gamma), CRP (runs beta-2 to gamma), and complement. Also, fibrinogen, usually absent from serum but may be present with incomplete clotting, may straddle the beta/gamma interface, giving a possible pseudo-M-spike.

Answer 311

Fibrinogen is supposed to be absent from serum, most of it having been consumed in the clot. However, if the specimen clots incompletely (such as in a heparinized patient), fibrinogen may be seen in the SPEP straddling the beta/gamma interface and misinterpreted as an M protein. Other causes of fibrinogen in serum include patients with dysfibrinogenemia, APL/APLS syndrome, liver disease, or vitamin K deficiency.

Answer 312

Absolute ethanol can be used in vitro to selectively precipitate fibrinogen and obviate this interference.

Answer 313

Hemoglobin, usually absent from serum, may be present at the alpha-2/beta interface when there is hemolysis, Transferrin (beta-1 band) can be increased in iron deficiency. Fibrinogen, usually absent from serum, may be present in the beta-2 band when there is incomplete clotting.

Answer 314

Transferrin is decreased in acute inflammation, then increased in chronic inflammation. Gamma globulings are normal to decreased in acute inflammation then increased in chronic inflammation.

Answer 315

Chronic inflammatory state, iron deficiency, pregnancy, estrogen therapy.

Answer 316

The blood-brain barrier transports transferrin into the CSF, but not before modifying a percentage of it to make asialated transferrin (so-called Tau protein), while the rest of it is unmodified. Thus, the double transferrin peak that is one of the hallmarks of CSF protein electrophoresis.

Answer 317

CRP is produced in the liver. Its name derives from its reaction with Streptococcal capsular (C) polysaccharide.

Answer 318

The physiological role of CRP is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system. CRP binds to phosphocholine on microbes and damaged cells and enhances phagocytosis by macrophages. Thus, CRP participates in the clearance of necrotic and apoptotic cells.

Answer 319

Normal CRP level: 10 mg/L (usually indicative of active inflammation).

Answer 320

Normal serum has a nearly invisible pre-albumin band and a very large albumin band. This is followed by a small peaked alpha-1 band, an alpha-2 band, a bimodal beta, and a broad gamma.

Answer 321

In nephrotic syndrome due to minimal change disease, there is an especially selective loss of albumin (selective proteinuria). In other forms of nephrotic syndrome, nearly all proteins are lost, including gamma globulins. However, in all types of nephrotic syndrome, larger protein molecules are retained. The result is dimming of all the electrophoretic bands, most prominently the albumin band, with the conspicuous exception of the alpha-2 band which contains the large protein alpha-2 macroglobulin.

Answer 322

The acute phase reactants account for an increase in the alpha-1 and alpha-2 bands. Albumin is slightly decreased. Initially, the gamma globulins are unchanged, but with prolonged inflammation, these are polyclonally increased.

Answer 323

Beta-gamma bridging (attributed mainly to increased serum IgA) is the hallmark of cirrhosis. Additional features include hypoalbuminemi and blunted alpha-1 and alpha-2 bands.

Answer 324

In ~5% of sera with an M-protein, two M-proteins are present (biclonal gammopathy). Biclonal gammopathies are typically detected when two different heavy or light chain classes of M-proteins are detected on immunofixation (eg, an IgA kappa M-protein and an IgM lambda M-protein in the same patient). Sometimes, the presence of monomers and polymers of a single M-protein may produce two spikes on the SPEP and can resemble a biclonal gammopathy (this should be considered monoclonal rather than biclonal).

Answer 325

Usually within the gamma region, but may be in beta-gamma, beta, or alpha-2.

Answer 326

The monoclonal gammopathies (paraproteinemias or dysproteinemias) are a group of disorders characterized by the proliferation of a single clone of plasma cells, which produces an immunologically homogeneous immunoglobulin commonly referred to as a paraprotein or monoclonal protein (M-protein or M-component, where the "M" stands for monoclonal). The M-protein can be an intact immunoglobulin (ie, containing both heavy and light chains) or can be composed of only light chains or (rarely) only heavy chains.

Answer 327

Hypogammaglobulinemia may be congenital, sex-linked, and/or part of a combined immunodeficiency state. It may also be acquired, as in multiple myeloma (~10% of patients), primary amyloidosis (~20% of patients), chronic lymphocytic leukemia, lymphoma, corticosteroids, or nephrotic syndrome.

Answer 328

Panhypogammaglobulinemia occurs in ~10% of patients with multiple myeloma. Most of these patients have a Bence Jones protein (monoclonal free kappa or lambda light chains) in the urine, but lack intact immunoglobulins in the serum. Panhypogammaglobulinemia occurs in ~20% of patients with primary amyloidosis, often associated with a nephrotic pattern (mainly albumin with nonselective globulin loss) in the urine.

Answer 329

Waldenström macroglobulinemia, with increased concentrations of IgM, is the most common cause of hyperviscosity, but hyperviscosity can also occur in patients with high concentrations of monoclonal IgA or IgG. Serum viscosity should be determined whenever the monoclonal IgM protein spike is >4 g/dL or the IgA or IgG protein spike is >6 g/dL.

Answer 330

Serum viscosity is normally in the range of 1.5 to 1.8 centipoise (cp). Many patients have symptoms when the viscosity is >4 cp and most have symptoms when the viscosity reaches 6 to 7 cp.

Answer 331

The CSF normally contains essentially all the proteins present in serum, although in smaller quantities. The most characteristic features of the normal CSF electrophoresis are a prominent pre-albumin band and a double beta (transferrin) band. Additional subtler features are a dim albumin and alpha-2 band.

Answer 332

A diagnosis of multiple sclerosis is supported by finding oligoclonal bands (several distinct bands in the gamma region reflective of several clonal immunoglobulins). These bands should be absent from the patient's serum, run concurrently, to be specific.

Answer 333

Elevations in oligoclonally expanded immunoglobulin concentrations in the CSF, termed oligoclonal bands, may occur in any disorder that disrupts the blood-brain barrier. Oligoclonal bands may also be caused by intrathecal production of IgG, and the presence of such bands is a diagnostic criterion for multiple sclerosis. Other diseases that can cause oligoclonal bands in the CSF include infections (eg, nervous system Lyme disease), autoimmune diseases, brain tumors, and lymphoproliferative diseases.

Answer 334

Glomerular proteinuria is due to increased filtration of macromolecules (such as albumin) across the glomerular capillary wall. On UPEP there are strong albumin, alpha-1 and beta bands. Very large proteins, due to the persistence of some filtering function, and very small proteins due to tubular absorption, do not make their way into urine. This leaves the protein in between these, most notably albumin, AAT, and transferrin.

Answer 335

Weak albumin band and strong alpha-1 and beta bands. This pattern results from the impaired tubular reabsorption of low molecular weight proteins normally filtered freely by the glomerulus and almost completely reabsorbed in the proximal tubules, such as alpha-2-macroglobulin, beta-2-microglobulin, and Ig light chains.

Answer 336

Increased excretion of LMW proteins can occur with marked overproduction of a particular protein, leading to increased glomerular filtration and excretion. This is almost always due to immunoglobulin light chains in multiple myeloma but may also be due to lysozyme (in acute myelomonocytic leukemia), myoglobin (in rhabdomyolysis), or free hemoglobin (in intravascular hemolysis) that is not bound to haptoglobin. In these settings, the filtered load is increased to a level that exceeds the normal proximal reabsorptive capacity.

Answer 337

Cryoglobulin is present when proteins precipitate from an individual's serum and plasma, and cryofibrinogen refers to the precipitate from plasma only. Cryoglobulins are either immunoglobulins or a mixture of immunoglobulins and complement components. Cryofibrinogen is typically composed of a mixture of fibrinogen, fibrin, fibronectin, and fibrin split products.

Answer 338

The presence of isolated monoclonal Ig (typically IgG or IgM, less commonly IgA or free immunoglobulin light chains) is the criterion for classification as a type I CG. The proportion of patients with a type I CG accounts for 5-25% of cases. The hematologic diagnoses are typically Waldenström's macroglobulinemia or multiple myeloma.

Answer 339

A mixture of polyclonal Ig in association with a monoclonal Ig, typically IgM or IgA, with rheumatoid factor activity defines type II CG. This type of CG, also called essential mixed cryoglobulinemia, accounts for 40-60% of cases. Type II CGs are often due to persistent viral infections, particularly hepatitic C and human immunodeficiency virus infections.

Answer 340

Mixed cryoglobulins consisting of polyclonal immunoglobulins characterize type III CGs. 40-50% of all CG cases are type III, and these are often secondary to connective tissue diseases.

Answer 341

Arginine vasopressin (AVP), the naturally occurring ADH in humans, is an octapeptide similar in structure to oxytocin. AVP is synthesized in the cell bodies of neurons in the supraoptic and paraventricular nuclei of the anterior hypothalamus and travels along the supraopticohypophyseal tract into the posterior pituitary. Here, it is stored in secretory granules in association with a carrier protein, neurophysin, in the terminal dilatations of secretory neurons that rest against blood vessels.

Answer 342

The major stimuli for AVP secretion are hyperosmolality and effective circulating volume depletion, which are sensed by osmoreceptors and baroreceptors, respectively. Osmoreceptors are specialized cells in the hypothalamus that perceive changes in the extracellular fluid (ECF) osmolality. Baroreceptors are located in the carotid sinus, aortic arch, and left atrium; these receptors participate in the nonosmolar control of AVP release by responding to a change in effective circulating volume.

Answer 343

SIADH consists of hyponatremia, inappropriately elevated urine osmolality (>100 mOsm/kg), and decreased serum osmolality in a euvolemic patient. There is continued renal excretion of sodium. The hyponatremia is corrected by fluid restriction. SIADH should be diagnosed when these findings occur in the setting of otherwise normal cardiac, renal, adrenal, hepatic, and thyroid function; in the absence of diuretic therapy; and in absence of other factors known to stimulate ADH secretion, such as hypotension, severe pain, nausea, and stress.

Answer 344

Pseudohyponatremia (from hyperglycemia, hyperlipidemia, hyperproteinemia). True hyponatremia with hypovolemia: renal losses (diuretics, medullary renal disease, Addison's disease, RTA type I) or extrarenal losses (GI losses, third spacing). True hyponatremia with euvolemia: SIADH, psychogenic polydipsia, drugs with ADH-like effect. True hyponatremia with hypervolemia: CHF, cirrhosis, nephrotic syndrome.

Answer 345

Inadequate potassium intake. Increased potassium excretion (mineralocorticoid excess (endogenous or exogenous), hyperreninism (renal artery stenosis), osmotic diuresis (mannitol, hyperglycemia), increased gastrointestinal losses, drugs, genetic disorders). Transcellular shifts (alkalosis, correction of DKA, refeeding, hypothermia).

Answer 346

Congenital adrenal hyperplasia (11-beta hydroxylase or 17-alpha hydroxylase deficiency). Glucocorticoid-remediable hypertension. Bartter syndrome. Gitelman syndrome. Liddle syndrome. Gullner syndrome. Glucocorticoid receptor deficiency. Hypokalemic periodic paralysis. Thyrotoxic periodic paralysis (TTPP). Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome).

Answer 347

The most common cause for metabolic acidosis with hypokalemia is GI loss (eg, diarrhea, laxative use). Other less common etiologies include renal loss of potassium secondary to renal tubular acidosis (types I and II?) or salt-wasting nephropathy.

Answer 348

To convert serum ethanol level to BAC, move the decimal point 3 places to the left. Example, a 100 mg/dL serum ethanol level is equivalent to a 0.10 (g/dL) BAC, or 0.10% (weight/volume). This means that one tenth of a percent of a person's blood volume is alcohol or that a person has 1 part alcohol per 1000 parts blood.

Answer 349

Blood alcohol concentration in serum or plasma is 1.2x higher than in whole blood.

Answer 350

Ethanol is absorbed primarily in the small intestine and secondarily in the stomach. It is eliminated mostly by metabolism in the liver, with the remainder excreted through urine, exhaled breath, and sweat.

Answer 351

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Metabolism at high alcohol concentrations follows zero order kinetics (independent of time and concentration of the drug). In the initial metabolic pathway, ADH breaks down alcohol into the toxic metabolite acetaldehyde. Small amounts of ADH are also found in other organs such as the stomach. This metabolite is further broken down to acetate by ALDH. Acetate is fed into the Krebs cycle and eventually broken down to water and carbon dioxide.

Answer 352

An estimate for blood alcohol level would be each ounce of whisky, 12 ounces of beer, or 5 ounces of wine raises blood alcohol level by 15-25 mg/dL. Peak is reached anywhere between 30 minutes (if consumption in fasting state) to 3 hours after the last drink. Metabolism is anywhere from 10-30 mg/dL/hour and depends upon a multitude of factors.

Answer 353

Clinical prediction rules for predicting the severity of (non-gallstone) acute pancreatitis. AT ADMISSION: Age in years >55. WBC count >16,000 cells/uL. Blood glucose >200 mg/dL. Serum AST >250 IU/L. Serum LDH >350 IU/L. WITHIN 48 HOURS: Hematocrit fall of 10% or more. BUN increase by 5 mg/dL or more in spite of fluids. Serum calcium level 6 L. pO2 4 mEq/L. INTERPRETATION: If score is 3 or more, severe pancreatitis is likely, and if score is less than 3, severe pancreatitis is unlikely. Alternatively, score of 0-2 = 2% mortality, 3-4 = 15% mortality, 5-6 = 40% mortality, and 7-8 = 100% mortality.

Answer 354

The effect of PTH on renal tubules causes increased calciium reabsorption and increased phosphate excretion.

Answer 355

This is because PTH has a dual effect on renal tubules, where there is increased calcium reabsorption and increased phosphate excretion.

Answer 356

Primary hyperparathyroidism is caused by solitary parathyroid adenoma in 90%, 4-gland hyperplasia in 9%, and carcinoma in 1%.

Answer 357

The locus on chromosome 11 that, in germline form, leads to MEN1 has been found to contain somatic mutation in ~25% of sporadic parathyroid adenomas.

Answer 358

The most common mediator of this syndrome is PTHrP (parathyroid hormone-related protein).

Answer 359

An increased nephrogenous cAMP in the presence of normal PTH is highly suggestive of humoral hypercalcemia of malignancy.

Answer 360

PTH causes increased calcium reabsorption and increased phosphate excretion. Vitamin D causes increased calcium reabsorption and increased phosphate reabsorption.

Answer 361

The histiocytes of sarcoidal granulomas appear to have the capacity to activate vitamin D to the active form (1,25 dihydroxy vitamin D). This phenomenon is rarely seen in other types of granulomatous disease.

Answer 362

There are three major mechanisms by which hypercalcemia of malignancy can occur: osteolytic metastases with local release of cytokines (including osteoclast activating factors); tumor secretion of parathyroid hormone-related protein (PTHrP); and tumor production of 1,25-dihydroxyvitamin D (calcitriol). Additionally, some tumors cause ectopic secretion of PTH.

Answer 363

Osteolytic metastases: breast cancer, multiple myeloma, lymphoma, leukemia. Humoral hypercalcemia (PTHrP): squamous cell carcinoma (lung, head and neck), RCC, breast cancer, bladder carcinoma, ovarian carcinoma, non-Hodgkin lymphoma, CML, leukemia, lymphoma. Tumor production of calcitriol: lymphoma (Hodgkin, non-Hodgkin, lymphomatosis/granulomatosis), ovarian dysgerminoma.

Answer 364

Hypercalcemia in patients with osteolytic metastases is primarily due to increased bone resorption and release of calcium from bone (is mediated by osteoclasts and is not a direct effect of tumor cells). Hypercalcemia in patients with tumors secreting PTHrP is due to both increased bone resorption and distal renal tubular calcium reabsorption. In patients with tumoral production of 1,25-dihydroxyvitamin D, hypercalcemia is the result of a combination of increased bone resorption and intestinal calcium absorption.

Answer 365

Increased production of 1,25-dihydroxyvitamin D (calcitriol) is the cause of almost all cases of hypercalcemia in Hodgkin lymphoma and approximately one-third of cases in non-Hodgkin lymphoma. An occasional patient with Hodgkin lymphoma, however, has hypercalcemia due to PTHrP (humoral hypercalcemia of malignancy), as do some with non-Hodgkin lymphoma.

Answer 366

Patients with mild hypercalcemia (calcium 14 mg/dL [3.5 mmol/L]), there is often progression of these symptoms.

Answer 367

PTH is synthesized as a 115- amino acid polypeptide called pre-pro-PTH, which is cleaved within parathyroid cells at the N-terminal portion first to pro-PTH (90 amino acids) and then to PTH (84 amino acids). The latter is the major storage, secreted, and biologically active form of the hormone. Calcium regulates not only the release but also the synthesis and degradation of PTH, in all its molecular forms.

Answer 368

In addition to intact PTH, some inactive C-terminal fragments and small amounts of active N-terminal fragments of PTH are present in the parathyroid glands. During hypocalcemia, intracellular degradation of PTH decreases, and mostly PTH 1-84 is secreted; in comparison, during hypercalcemia mostly biologically inactive C-terminal fragments of PTH are secreted.

Answer 369

Circulating immunoreactive PTH in normal subjects comprises: intact PTH (5-30%), C-terminal fragments (70-95%), and N-terminal fragments (small percentage).

Answer 370

Intact PTH: +, short (plasma half-life of 2-4 min). N-terminal PTH: +, short. Mid-region PTH: -, long. C-terminal PTH: -, long (plasma half-life 5-10x longer than intact PTH).

Answer 371

Acidosis increases the proportion of free calcium by competing for binding sites on albumin. Likewise, alkalosis decreases free calcium.

Answer 372

If the total serum calcium is low but the ionized calcium is normal, it is called pseudohypocalcemia. If the total serum calcium is high in the setting of a normal ionized calcium, it is called pseudohypercalcemia.

Answer 373

~40% is bound to albumin in a ratio of 0.8 mg/dL (0.2 mmol/L or 0.4 meq/L) of calcium per 1.0 g/dL (10 g/L) of albumin. ~45% circulates as physiologically active ionized (or free) calcium. ~15% is bound to multiple organic and inorganic anions such as sulfate, phosphate, lactate, and citrate.

Answer 374

The equation used to measure corrected calcium in cases of hypo/hyperalbuminemia is: Corrected (Ca) = Measured total (Ca) + (0.8 x [4.5 - (alb)]). Or, 0.8 mg/dL Ca per 1g/dL protein. While this formula often provides a good estimate of the ionized calcium, its use should be avoided in patients with acid-base disturbances, renal insufficiency, liver disease, and neonates.

Answer 375

Squamous epithelium and lactating breast epithelium.

Answer 376

PTH-mediated: primary hyperparathyroidism, familial (MEN-I and -IIa, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia), tertiary hyperparathyroidism. PTH-independent: hypercalcemia of malignancy, vitamin D intoxication, chronic granulomatous disorders, medications (thiazide diuretics, lithium, teriparatide, theophylline toxicity, excessive vitamin A), miscellaneous (hyperthyroidism, acromegaly, pheochromocytoma, adrenal insufficiency, immobilization, parenteral nutrition, milk-alkali syndrome).

Answer 377

Activating mutations: autosomal dominant hypocalcemia (also called autosomal dominant hypoparathyroidism) (ADH), ADH with features of Bartter's syndrome. Inactivating mutations: familial hypocalciuric hypercalcemia (FHH1; also called familial benign hypercalcemia), neonatal (NHPT) and neonatal severe primary hyperparathyroidism (NSHPT), and occasionally familial isolated hyperparathyroidism.

Answer 378

Renal failure (impaired calcitriol production, hyperphosphatemia). Decreased calcium intake. Calcium malabsorption (vitamin D deficiency, bariatric surgery, celiac disease, pancreatic disease (fat malabsorption)). Renal calcium loss (idiopathic hypercalciuria, loop diuretics). Inhibiton of bone resorption (bisphosphonates, hungry bone syndrome).

Answer 379

4 main categories: Low PTH (hypoparathyroidism). High PTH (secondary hyperparathyroidism in response to hypocalcemia). Drugs. Disorders of magnesium metabolism.

Answer 380

Low PTH (hypoparathyroidism): genetic disorders, post-surgical (thyroidectomy, parathyroidectomy, radical neck dissection), autoimmune, infiltration of the parathyroid gland (granulomatous, iron overload, metastases), radiation-induced destruction of parathyroid glands, hungry bone syndrome, HIV infection. High PTH (secondary hyperparathyroidism in response to hypocalcemia): vitamin D deficiency or resistance, parathyroid hormone resistance, renal disease, loss of calcium from the circulation (hyperphosphatemia, tumor lysis, acute pancreatitis, osteoblastic metastases, acute respiratory alkalosis, sepsis or acute severe illness. Drugs. Disorders of magnesium metabolism.

Answer 381

Secondary hyperparathyroidism (AKA pseudohypoparathyroidism) is due to peripheral resistance to the action of PTH. The PTH level is normal to high, calcium level is low, and phosphate is high. This persistent hyperparathyroid state produces marked activation of osteoclasts in bone, leading to so-called brown tumors of bone (renal osteodystrophy).

Answer 382

Mild transient deccreases in serum magnesium cause increased PTH secretion (an attempt on the part of the parathyroids to maintain the balance of divalent cations). However, persistent or marked hypomagnesemia causes PTH resistance (when the hypomagnesemia is milder) or inhibits PTH secretion (when the hypomagnesemia is more severe), leading to hypoparathyroidism.

Answer 383

Metabolic disorders are due to excessive intake, excessive production, or too little renal elimination of an acid or base; the primary change is in (HCO3-). Compensation in primary metabolic disorders involves buffers and alterations in pulmonary handling of CO2.

Answer 384

The Henderson–Hasselbalch equation describes the derivation of pH as a measure of acidity (using pKa, the negative log of the acid dissociation constant) in biological and chemical systems. pH = pKa + log(base/acid).

Answer 385

pH = 7.4. pKa = 6.1. Base = [bicarb] = 24. Acid = dissolved PaCO2 = 0.03 x PaCO2 = 0.03 x 40 = 1.2. Substituting these into the equation, 7.4 = 6.1 + log(24/1.2) = 6.1 + 1.3 = 7.4. The body makes every attempt to maintain the validity of this equation. Since it must maintain a pH of 7.4 and the pK is a constant, it can only alter [bicarb] and PaCO2, and so the ratio of these must remain 20:1.

Answer 386

ABG analyzers use a pH electrode, a PaCO2 electrode, and a PaO2 electrode to measure these variables directly. They usually also derive a % saturation of oxygen through a calculation that assums a normal hemoglobin oxygen affinity.

Answer 387

Pulse oximeters measure hemoglobin oxygen saturation directly by measuring the absorbance of transdermally transmitted light. It emits two wavelengths of light: one that deoxyhemoglobin absorbs, and one that oxyhemoglobin absorbs.

Answer 388

The co-oximeter is a spectrophotometric dvice that measures absorbance of multiple wavelengths of light. It is thus able to measure (not calculate) the proportions of oxyhemoglobin, deoxyhemoglobin, methemoglobin, and carboxyhemoglobin. Oxygen saturation is then the ratio of oxyhemoglobin to the total.

Answer 389

Co-oximetry.

Answer 390

Anion gap = [Na] - ([Cl] + [HCO3]). Normal = <12.

Answer 391

Corrected anion gap = [Na] - ([Cl] + [HCO3]) + 2.5(4-albumin).

Answer 392

Osmolal gap = osm measured - (2[Na] + [Glu]/18 + BUN/2.8). Normal = <10.

Answer 393

A comparison of the delta bicarb and the delta anion gap. These changes should be essentially 1:1 (within +/- 2) in simple acid-base disorders. A delta-delta greater than that is indicative of a complex disorder.

Answer 394

Metabolic acidosis: pH and [HCO3] go same direction (bicarb usually 44 mmHg). Metabolic alkalosis: pH and [HCO3] go same direction (bicarb usually >25 mEq/L). Respiratory alkalosis: pH and [HCO3] go opposite direction (pCO2 usually <40 mmHg).

Answer 395

Metabolic acidosis: for each 1.3 mEq fall in [HCO3], the pCO2 decreases by 1.0 mmHg. Metabolic alkalosis: for each 0.6 mEq rise in [HCO3], the pCO2 increases by 1.0 mmHg. Acute respiratory alkalosis or acidosis: for each 1 mmHg change in pCO2, the [HCO3] changes by 0.1 in the same direction. Chronic respiratory alkalosis or acidosis: for each 1 mmHg change in pCO2, the [HCO3] changes by 0.4 in the same direction.

Answer 396

With increased AG (>12): ketoacidosis (diabetic, starvation, EtOH-associated), lactic acidosis, D-lactic acidosis, ingestions (methanol, ethylene glycol, diethylene glycol, propylene glycol, salicylate, toluene (if early or if kidney function is impaired)), pyroglutamic acid (5-oxoproline), CKD/uremia. With normal AG (<12): diarrhea or other intestinal losses, ureteral diversion, ketoacidosis posttreatment, carbonic anhydrase inhibitors, type 1 (distal) RTA, type 2 (proximal) RTA, type 4 RTA (hypoaldosteronism), toluene ingestion (if late and if renal function is preserved - dut to excretion of sodium and potassium hippurate in the urine), CKD and tubular dysfunction (but relatively preserved GFR).

Answer 397

Toluene ingestion causes increased AG if early after ingestion or if kidney function is impaired. It causes normal AG if late after ingestion and if renal function is preserved - due to excretion of sodium and potassium hippurate in the urine.

Answer 398

With anion gap metabolic acidosis: ingestion (ethylene glycol, methanol, formaldehyde, paraldehyde); lactic acidosis; diabetic ketoacidosis; alcoholic ketoacidosis; end-stage CKD (GFR <10 mL/min) without regular dialysis. Without metabolic acidosis: ingestion (ethanol, isopropyl alcohol, diethyl ether); infusion of nonconductive glycine, sorbitol, or mannitol solutions; severe hyperproteinemia; severe hyperlipidemia.

Answer 399

Chloride responsive: diuretic therapy, vomiting, NGT suction, villous adenoma, carbenicillin, contraction alkalosis. Chloride resistant: hyperaldosteronism, Cushing syndrome, exogenous steroids, licorice (glyccrhizic acid), Bartter syndrome, milk-alkali syndrome.

Answer 400

Pheochromocytomas and most sympathetic paragangliomas are often associated with clinical symptoms, while only a small percentage of parasympathetic paragangliomas are symptomatic. Parasympathetic paragangliomas often lack tyrosine hydroxylase, the enzyme required for catecholamine synthesis, and are therefore usually nonfunctional.

Answer 401

The biochemical profiles of tumors associated with mutations of genes encoding succinate dehydrogenase subunits, (collectively referred to as SDHx; x refers to all subunits, SDHA refers to subunit A, etc) are characterized by dopamine and/or norepinephrine production. VHL-related tumors are associated with norepinephrine production. RET- and NF1-related tumors are associated with epinephrine production.

Answer 402

Catecholamines (dopamine, norepinephrine, and epinephrine) are not continuously secreted in normal conditions, and undergo intracellular methylation by the tumor cells the produce them. Biochemical testing for the O-methylated metabolites of dopamine, norepinephrine, and epinephrine (methoxytyramine, normetanephrine, and metanephrine, respectively) in plasma and/or urine is therefore superior to measurement of the parent catecholamines.

Answer 403

Urea, individual amino acids, urate, creatinine, and ammonia. Urea is the largest component of NPN.

Answer 404

Urea is freely filtered and partially reabsorbed by the nephron; this reabsorption has the consequence that BUN always slightly underestimates GFR.

Answer 405

Reabsorption increases with hypovolemia; thus BUN underestimates GFR even more in hypovolemic states.

Answer 406

The creatinine concentration was classically determined, and is still often determined, by the Jaffe reaction - alkaline picrate forms a colored complex with creatinine. Alternative enzymatic (using creatinase) and colorimetric assays are available.

Answer 407

Creatinine is derived from the metabolism of creatine in skeletal muscle and from dietary meat intake. It is released into the circulation at a relatively constant rate. Creatinine is freely filtered across the glomerulus and is neither reabsorbed nor metabolized by the kidney. However, approximately 10 to 40 percent of urinary creatinine is derived from tubular secretion by the organic cation secretory pathways in the proximal tubule, with the quantity secreted increasing with increasing serum creatinine concentration. At all serum concentrations, creatinine slightly overestimates GFR.

Answer 408

BUN underestimates GFR. Cr overestimates GFR.

Answer 409

ClCr = UCr x VUr / PCr. Where UCr is urine creatinine in mg/dL, VUr is volume of urine in mL/24 hrs, and PCr is plasma creatinine in mg/dL. But this formula is overly simplistic and the MDRD study equation is the most widely recommended formula now.

Answer 410

Nonlinearity and nonglomerular influences upon creatinine. Nonlinearity: The inverse relationship between GFR and Cr is nonlinear. Mild to moderate degrees of GFR impairment do not cause appreciable increases in Cr concentration; only when GFR is about half of normal does creatinine rise precipitously and begin to linearly reflect changes in GFR. Nonglomerular influences upon creatinine: The serum Cr concentration is increased by muscle mass/activity/injury and protein intake; it is decreased by age; it is influences by race, age, sex, and numerous medications.

Answer 411

The MDRD equation has been studied and validated in adult Caucasian and African American populations with impaired kidney function (GFR

Answer 412

4, based on if the lab reports serum Cr in mg/dL (conventional units) or umol/L (SI units), and whether the lab uses a Cr assay that has been (traceable) or has not been (original (non-traceable)) calibrated to be traceable to an isotope dilution mass spectometry (IDMS) method.

Answer 413

The result given by the Modification of Diet in Renal Disease Study equation is multiplied by 0.742 if the patient is female and by 1.210 is the patient is African American.

Answer 414

mL/min/1.73m^2.

Answer 415

When BUN and Cr are elevated but the ratio is maintained, it is suggestive of intra-renal disease (GN and TIN) - renal azotemia. When the ratio is elevated, is suggests prerenal azotemia (poor renal perfusion) or postrenal azotemia (renal obstruction). A decreased BUN/Cr is rare and may result from dietary protein insufficiency or severe liver disease.

Answer 416

Cystatin C is a cysteine protease inhibitor produced by nearly all cells in the body that is freely filtered by the glomerulus, not reabsorbed, and is metabolized by the proximal tubular epithelium.

Answer 417

Normal proteinuria does not exceed 150 mg/day and consists mainly of Tamm-Horsfall protein and minute amounts of albumin.

Answer 418

The urine protein assay is sensitive to all kinds of protein (albumin, globulins, Bence-Jones), and its lower limit of detection is about 3 mg/dL.

Answer 419

The urine dipstick test is most sensitive to albumin (but not enough to detect microalbuminuria); it is not sensitive to globulins or even to very high levels of Bence-Jones protein. The lower limit of detection of the urine dipstick test for albumin is 18 mg/dL.

Answer 420

3 mg/dL, 18 mg/dL, and 0.3 mg/dL, respectively.

Answer 421

The albumin:creatinine ratio is reported in mg/g, and the protein:creatinine ratio is reported in mg/mg.

Answer 422

Bence-Jones protein and hook effect (a false negative result with certain immunoassays due to very high concentrations of a particular analyte).

Answer 423

The hook effect or the prozone effect is a false negative result with certain immunoassays due to very high concentrations of a particular analyte. The hook effect mostly affects one-step immunometric assays, such as two-site immunoassays in which both the capture and detection antibody are added simultaneously, free analyte and analyte bound to labelled antibody compete for the limited number of antibody-binding sites and in the presence of higher analyte concentration will decrease rather than increase label bound to the solid phase.

Answer 424

Interferences that alter the measurable analyte concentration in the sample: Hormone binding proteins. Pre-analytical factors, e.g., anticoagulants, sample storage. Autoanalyte antibodies. Interferences that alter antibody binding: Heterophile antibodies. Human anti-animal antibodies. High-dose hook effect.

Answer 425

Crossreactivity: All, but primarily competitive assays. Hook effect: Nephelometric, turbidimetric, and immunometric assays. Antibody interference: All, but primarily immunometric assays. Signal interference: All. Matrix effects: All.

Answer 426

Tubular dysfunction, since these proteins are freely filtered by the glomerulus then completely reabsorbed by the normally functioning proximal convoluted tubule.

Answer 427

CKD is defined as the presence of kidney damage (usually detected as urinary albumin excretion of ≥30 mg/day, or equivalent) OR decreased kidney function (defined as eGFR <60 mL/min per 1.73 m^2) for three or more months, irrespective of the cause. The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease/injury.

Answer 428

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines stage according to: cause of disease, 6 categories of eGFR (G stages), and 3 categories of albuminuria (A stages).

Answer 429

Prerenal - As an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons. Renal/Intrinsic - In response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage. Postrenal - From obstruction to the passage of urine. While this classification is useful in establishing a differential diagnosis, many pathophysiologic features are shared among the different categories.

Answer 430

The most common cause of renal/intrinsic acute kidney injury is ATN, the most common causes of which are ischemia and nephrotoxins.

Answer 431

In these patients, fractional excretion of urea can be a useful alternative.

Answer 432

Prerenal ARF: A lack of findings or isolated hyaline casts. GN: Dysmorphic RBCs and RBC casts. ATN: Pigmented casts. TIN: Leukocytes (in the absence of infection - sterile pyuria), WBC casts, and/or eosinophils.

Answer 433

Bilirubin levels normally peak at 23-25 weeks' gestation in unaffected fetuses.

Answer 434

It predicts the severity of hemolytic disease of the newborn based on amniotic fluid bilirubin levels. On semilog paper, absorbances are plotted against wavelength. A straight line is drawn from the point at 350 nm to the point at 550 nm. This line reflects the theoretical plot if there were no pigments in the fluid. The difference between the line and the actual absorbance at 450 nm is the delta OD450, which reflects the bilirubin concentration. The delta OD450 is plotted against the EGA on a Liley chart, and results fall into zones I, II, or III.

Answer 435

A result in Zone I indicates mild or no disease. Fetuses in zone I are usually followed with amniocentesis every 3 weeks. A result in zone II indicates intermediate disease. Fetuses in low Zone II are usually followed by amniocentesis every 1-2 weeks. A result above the middle of Zone II may require transfusion or delivery. Patients with results in zone I or low zone II can be allowed to proceed to term, at which point labor should be induced. In most cases, patients in the middle of zone II can progress to 36-38 weeks of gestation. If results are in zone III or rising in zone II, deliver immediately for EGA >36 wks, and consider intrauterine transfusion otherwise.

Answer 436

hCG is a glycoprotein heterodimer composed of an alpha and a beta chain. The alpha subunit is identical to that found in TSH, FSH, and LH. The predominant methodologies involve immunoassay directed against the beta subunit. The concentration is expressed in mIU/mL and ng/mL (100 mIU = 8 ng).

Answer 437

False negative hCG can occur with urine testing, especially if the urine is dilute. When there is high suspicion, the negative urine hCG is confirmed with a serum hCG test. False positive hCG can occur due to heterophile antibody interference. The measurement can be repeated on a different analyzer, pretreat sample with a heterophile binding reagent, or run serial dilutions.

Answer 438

A false-positive hCG result that is a consequence of interference of heterophil antibodies with standard assays for hCG. A diagnosis of “phantom” hCG should be suspected in patients with a negative urine and a positive serum hCG. Apart from pregnancy, heterophil bridging antibodies in immunometric hCG assays can cause falsely elevated levels in patients with gestational trophoblastic diseases, choriocarcinoma, testicular germ cell tumors and IgA deficiencies.

Answer 439

hCG becomes detectable 6-8 days following conception (about the time of implantation), when levels are 10-50 mIU/mL. The hCG level doubles every 2 days until 1200 mIU/mL at 10 weeks. The level doubles every 3 days between 1200 to 6000 mIU/mL. The level doubles every 4 days above 6000 until it peaks near the end of the first trimester around 10,000 (800 ng/mL). After delivery, hCG normally remains detectable for 2 weeks.

Answer 440

hCG becomes detectable 6-8 days following conception (about the time of implantation), when levels are 10-50 mIU/mL.

Answer 441

After delivery, hCG normally remains detectable for 2 weeks. The disappearance of hCG after term pregnancy is best viewed as triphasic, with rapid, medium, and slow half-lives of 3.6 hrs, 18 hrs, and 53 hrs.

Answer 442

Multiple gestations, polyhydramnios, eclampsia, erythroblastosis fetalis.

Answer 443

If a normal hCG dynamic is not seen, this suggests an abnormal pregnancy. Specifically, if serum hCG does not rise at least 66% in 48 hrs, or if the hCG falls during this time, this suggests an ectopic pregnancy or nonviable IUP. However, a normal rate of rise can be seen in 15% of ectopics, and an abnormal rate of rise can be seen in 15% of normal IUP.

Answer 444

With transabdominal US, a gestational sac should be detectable when the hCG >6000 mIU/mL. When the hCG is >1400 mIU/mL, the absence of an IUP detectable by transvaginal US is 90% specific for an ectopic.

Answer 445

A serum progesterone level >25 ng/mL virtually assures an IUP. Levels <5 ng/mL are strongly (almost 100%) predictive of an abnormal pregnancy. However, most patients fall somewhere in between these thresholds.

Answer 446

2 weeks. 4 weeks. 4-6 weeks. Up to 10 weeks.

Answer 447

After evacuation of a molar pregnancy, hCG levels must be monitored weekly until undetectable for 3 consecutive weeks. It is then measured monthly for 1 year.

Answer 448

Triple screen - 70%, Quad test - 80%. Integrated screen - 85%. Integrated screen combined with US nuchal fold thickness - >90%.

Answer 449

Triple screen: hCG, AFP, unconjugated estriol. Quad test: the components of the triple screen plus dimeric inhibin A. Integrated screen: PAPP-A and hCG are measured in the 1st trimester; AFP, unconjugated estriol, and dimeric inhibin A are measured in the 2nd trimester; then the data are combined.

Answer 450

The improved performance of the Quad test comes mainly from amelioration of the effects of inaccurate gestational age which plague the triple screen.

Answer 451

In diabetic mothers, unconjugated estriol and hCG are mildly decreased. In mothers who smoke, unconjugated estriol and hCG are decreased, while AFP is increased.

Answer 452

All 3 components (uE, hCG, AFP) are decreased.

Answer 453

hCG increased, AFP and uE decreased. Also, dimeric inhibin A is increased.

Answer 454

AFP increased, uE decreased, hCG normal. With increased AFP, if an US confirms gestational age and excludes overt anatomic abnormalities, multiple gestations, or fetal demise, then amniocentesis is performed to obtain amniotic fluid for AFP and AChE.

Answer 455

2-3% of maternal serum AFPs are elevated on prenatal screening; of these, 10% are due to an actual NTD. The sensitivity of MSAFP screening is 90% - the sensitivity is worse for multiple gestations (30%).

Answer 456

MSAFP rises progressively during the 1st and 2nd trimesters. Adjustments to the MSAFP interpretation are made for maternal weight, race, number of fetuses, and maternal diabetes. Increased maternal weight can have a dilutional effect on the AFP, providing a falsely low value. Levels are much higher in multiple gestations, and much lower in maternal diabetes.

Answer 457

>2.0 MOM is considered abnormal in maternal diabetes, and >4.5 MOM is considered abnormal in twin gestations.

Answer 458

NTDs. Omphalocele and gastroschisis. Renal anomalies. Sacrococcygeal teratoma. Cystic hygroma. Hydrops fetalis. Turner syndrome. Bowel obstruction. Twins. Wrong gestational age. Fetal demise. Fetal-maternal hemorrhage.

Answer 459

Maternal serum hCG is ~2x higher than normal in Down syndrome.

Answer 460

Trisomy 18 (Edward syndrome). Smith-Lemli-Optiz syndrome. Inherited (fetal) deficiencies of steroid sulfatase.

Answer 461

Dimeric inhibin A is a glycoprotein produced by the placenta. In a Down syndrome fetus, DIA is increased to an average of 1.9 MOM.

Answer 462

Fetal fibronectin is a protein found normally at the placental fetomaternal interface. Cervicovaginal fluid contains fetal fibronectin briefly during early gestation, after which time it is absent until just before labor. The absence of fetal fibronectin has very high NPV and can exclude impending preterm birth. A positive result suggests the onset of preterm labor, but the overall PPV is low.

Answer 463

Mature type II pneumocytes produce a mixture of phospholipids composed predominantly of lecithin. The vast majority of lecithin is disaturated phosphatidylcholine (DSPC). Lesser amounts of phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and sphingomyelin also comprise lecithin.

Answer 464

It is an issue for gestation between 34 to 37 weeks. Prior to 34 weeks, fetal lung maturity is unlikely, and the risk of RDS is very high. After 37 weeks the risk of RDS is exceedingly low, and fetal lung maturity testing is generally not indicated, except in the presence of poorly controlled maternal diabetes.

Answer 465

Lecithin/sphingomyelin ratio. Phosphatidylglycerol concentration. Foam stability. Lamellar body number density. Disaturated phosphatidylcholine concentration. Fluorescence polarization assay.

Answer 466

Lecithin increases with gestational age, while sphingomyelin remains at a relatively constant 2% of total surfactant phospholipid. Until 26 wks, the ratio is 1:1. After that, the L:S ratio increases until 2:1 is reached around 35 wks. This ratio is generally taken to indicate fetal lung maturity. Above 2:1, 2% of premature infants will develop RDS. Below 2:1, nearly 60% will.

Answer 467

In DM, a ratio of 2:1 does not ensure FLM. The phosphatidylglycerol concentration is more reliable in this senario. The presence of meconium falsely decreases the L:S ratio. The presence of blood normalizes the L:S ratio to ~1.5. The CV of the L:S ratio is high.

Answer 468

Phosphatidylglycerol concentration.

Answer 469

PG is first detected around 36 wks and its presence is indicative of FLM. Neither blood nor meconium interfere with PG determinations, making it the test of choice when the only available specimen is a contaminated one. PG can be measured by TLC or agglutination.

Answer 470

When pulmonary surfactant is present in amniotic fluid in sufficient concentration, the fluid is able to form a highly stable film that can support the structure of a foam. The amniotic fluid is serially diluted with ethanol, and the highest concentration of ethanol at which a complete ring of bubbles is seen is the foam stability index (FSI). An FSI greater than 0.47 is considered indicative of fetal lung maturity.

Answer 471

Surfactant lamellar bodies are about the size of platelets, and the platelet channel of a cell counter can be used to quantify them. An LBND greater than 50,000/mL is predictive of maturity.

Answer 472

An alternative to the L/S ratio is to determine the DSPC concentration, the major component of lecithin, directly. Since it doesn't rely on a ratio with sphingomyelin, it is unaffected by meconium and blood contamination.

Answer 473

This is now the most commonly used method; it is rapid and at least as predictive of FLM as the L/S, with considerably lower CV. A fluorescence polarization value less than 260 is considered mature. Values greater than 290 are considered immature. If these is less than 0.5% blood, results are unaffected. Greater amounts tend to lower high values and raise low values. Even in the presence of blood, values less than 230 are considered mature.

Answer 474

Albumin: dec 1 g/dL. Total calcium: dec 10%. Creatinine: dec 0.3 mg/dL. Fibrinogen: inc 1-2 g/L. Albumin: dec 0.5-1 g/dL. BUN: dec 50%. Urine protein: inc to approximately double. Amylase: inc 50-100%. Hct: dec 4-7%. Hgb: dec 1.5-2 g/dL.

Answer 475

Fibrinogen: inc 1-2 g/L. Urine protein: inc to approximately double. Amylase: inc 50-100%.

Answer 476

There are increased circulating fatty acids and serum triglycerides are increased by about 40%. Also, a low-level ketosis is often seen.

Answer 477

Decreased albumin and total protein result from hemodilution. Increased transport proteins such as TBG result from increased estrogen. Increased GFR is due to increased blood volume and is reflected in decreased BUN, Cr, and urate. Increased insulin resistance is due to hPL, which has anti-insulin effects similar to GH.

Answer 478

Until the mid-2nd trimester, glucose tolerance actually improves. After that, however, relative insulin resistance emerges, reflected in prolonged elevations in postprandial serum glucose. The most important cause of this is hPL, which has anti-insulin effects similar to GH.

Answer 479

Sodium and potassium remain relatively constant throughout pregnancy. Calcium falls slightly throughout pregnancy.

Answer 480

Complement levels are low in SLE flare and normal in PIH.

Answer 481

Hypothyroidism. In pregnancy there is increased demand placed upon the thyroid due to an estrogen-driven increase in TBG and the TSH-like stimulatory effect of hCG. Patients with borderline thyroid function or those with borderline availability of iodine will be unable to meet these demands.

Answer 482

Transient hyperthyroidism of hyperemesis gravidarum, due to high levels of hCG.

Answer 483

Serum bile acids (chenodeoxycholic acid, deoxycholic acid, and cholic acid) are increased, often to levels 10x the upper limit of normal.

Answer 484

Parental karyotyping (karyotyping of an abortus is often indicated as well). Endometrial bxs may be obtained to exclude luteal phase defect (endometrial histology that is 2 or more days discrepant with dates). Endometrial culture may be obtained to exclude subclinical infection with U. urealyticum or C. trachomatis. Thyroid function tests. Tests for lupus anticoagulants.

Answer 485

The acute subtype (which is the most common subtype) has hypercalcemia the most frequently. Hypercalcemia is less common in the lymphomatous subtype and is absent in the chronic, smoldering, and cutaneous subtypes.

Answer 486

Vd = D / C, where D is the quantity of an administered dose, and C is the resulting measured plasma concentration. A drug's Vd is usually expressed in liters.

Answer 487

Cocaine: 1 hr, 24-72 hrs, benzoyl ecgonine methyl ester. Heroin: 3 min, 72 hrs, 6-acetyl morphine. Amphetamines: 30 min, 72 hrs, norepinephrine and phenylacetone. PCP: 30 min, 72 hrs, hydroxylated and glucuronated. Cannabis: 8 hrs, weeks, delta-9-THC-COOH.

Answer 488

Due to skeletal muscle effects, the specificity of both myoglobin and CK-MB is lower in cocaine-induced AMI, but the specificity of troponin I is equally good.

Answer 489

pH suspicious if less than 4.5 or greater than 8.0. Specific gravity suspicious for dilution if 500 ug/mL.

Answer 490

Because both propoxyphene and its major metabolite (norpropoxyphene) cause a quinidine-like interference with sodium channels.

Answer 491

It can be ingested, injected, or smoked. It exerts its effects through blocking catecholamine re-uptake. The behavioral manifestations are characteristically fluctuating, thought to be a reflection of the marked lipid solubility of PCP, resulting in fluctuating blood levels.

Answer 492

The effects of intoxication include hyperpnea, hypertension, and tachycardia. The behavioral manifestations fluctuate from periods of calm and sedation to periods of marked agitation, aggression, and incoordination. Horizontal nystagmus is often present and provides a clue to PCP use. Severe intoxication may present instead with hypoglycemia, hypotension, bradycardia, hypopnea, AMS, seizures, or life-threatening hyperthermia. Rhabdomyolysis may be induced by PCP. Leukocytosis is a frequent nonspecific finding.

Answer 493

0.4% - coma and death.

Answer 494

Whole blood should be submitted in sodium fluoride and potassium oxalate to prevent both increases (due to fermentation) and decreases in ethanol concentration. Use of alcohol swabs on the venipuncture site should be avoided.

Answer 495

This method is fairly specific for ethanol and doesn't measure other alcohols such as methanol.

Answer 496

GGT is increased in heavy drinkers (more than 4 drinks a day for more than 4 weeks). And 4 or more weeks of abstinence are usually required for normalization of GGT.

Answer 497

CDT is at least as sensitive and probably more specific than GGT. CDT levels require only 1-2 weeks of heavy consumption before levels are raised, whereas 4 weeks is needed for elevated GGT levels. Because the 2 analytes are not highly correlated, their use in parallel enhances the sensitivity of detection of heavy alcohol consumption.

Answer 498

Women produce more CDT under natural conditions and may produce less CDT in response to heavy drinking.

Answer 499

MCV is increased in heavy alcohol consumption. Its sensitivity and specificity are modest, and at least 4-8 weeks of consumption are required to produce a measurable effect.

Answer 500

Signs: hyperthermia, dry skin, flushing, altered mental status, psychosis ("hot as a hare, dry as a bone, red as a beet, mad as a hatter"), mydriasis, constipation. Agents: atropine, antihistamines, tricyclics, scopolamine.

Answer 501

Signs: salivation, lacrimation, urination, diarrhea, GI cramps, emesis ("SLUDGE"); diaphoresis, miosis, wheezing. Agents: organophosphates, pilocarpine, carbamate.

Answer 502

Signs: hypertension, tachycardia, mydriasis, anxiety, hyperthermia. Agents: amphetamines, cocaine, pseudoephedrine, ephedrine, PCP.

Answer 503

Sedatives signs: altered mental status, slurred speech, hypopnea/apnea. Sedatives agents: barbiturates, alcohols, opiates. Narcotics signs: altered mental status, hypopnea/apnea. Narcotics agents: opiates.

Answer 504

Ephedrine/pseudoephedrine are adrenergic only. LSD is hallucinogenic only. The rest are both adrenergic and hallucinogenic.

Answer 505

Toxicology screening. Calculation of the anion gap. Calculation of the osmolar gap. Measurement of blood gases. Measurement of urinary pH.

Answer 506

Some common conditions may lower the anion gap or mask a mildly increased anion gap. Chief among these is hypoalbuminemia; for every 1 gram decrease in albumin, there is a 2.5 mEq decrease in the anion gap.

Answer 507

Acetaminophen, salicylates, ascorbate, hydrogen sulfide, ethylene glycol, methanol, ethanol, formaldehyde, carbon monoxide, nitroprusside, epinephrine, paraldehyde.

Answer 508

Sodium, glucose, and BUN normally account for all but about 5-10 mOsm of the serum osmolarity (normal 285-295 mOsm/L).

Answer 509

Serum osmolarity is generally measured by freezing point depression osmometry, and this method will measure most alcohols. However, the less commonly used vapor pressure method does not detect ethanol and methanol (? "vapor pressure method is less useful particularly in methanol, isopropyl alcohol, and ethylene glycol poisoning"); thus, these two agents will not give an osmolal gap if vapor pressure osmometry is used.

Answer 510

The oxygen saturation gap is the difference between the saturation given by co-oximeter and by the ABG analyzer. Normally, the difference between these two determinations should be less than 5. Confusingly, the term oxygen saturation gap is sometimes also used to refer to the difference between the % oxyhemoglobin given by the pulse oximeter and by the ABG analyzer.

Answer 511

The ABG analyzer is likely to give a falsely normal (falsely high) reading. Furthermore, there will be a difference between % oxyhemoglobin given by the ABG analyzer and that given by the co-oximeter.

Answer 512

The presence of carboxyhemoglobin, methemoglobin, sulfmethemoglobin, or cyanohemoglobin.

Answer 513

When abnormal hemoglobins are present, they will absorb light and give a falsely high reading to either the oxyhemoglobin or the deoxyhemoglobin, often in difficult to predict ways. For example, in methemoglobinemia, oxygen saturation by pulse oximetry may be falsely high in severe methemoglobinemia and falsely low in mild methemoglobinemia. Carboxyhemoglobin has a maximal absorption similar to oxyhemoglobin, leading to a falsely high oxyhemoglobin by pulse oximetry.

Answer 514

Cyanide and hydrogen sulfide poisoning.

Answer 515

Generally, the limits of urinary pH manipulation are 4.5 to 7.5 under conditions of enhanced acidification and alkalinization. Agents whose pKa are well outside this range (pKa 8) tend to be unaffected by these maneuvers.

Answer 516

Ethanol, methanol, isopropyl alcohol, ethylene glycol, propylene glycol, glycerol, acetone, mannitol, radiocontrast media, hypermagnesemia.

Answer 517

A toxic alcohol (methanol, isopropanol, ethylene glycol) ingestion is suspected if the osmolal gap exceeds 10, and suspected strongly if it exceeds 20. Direct lab tests for methanol and ethylene glycol are not available in most places, so the osmolal gap is used as a surrogate marker.

Answer 518

2[Na] + [BUN] / 2.8 + [glucose] / 18 + [ethanol] / 4.6.

Answer 519

Ethanol -/+, methanol +, isopropanol -, ethylene glycol +.

Answer 520

Ethanol -/+, methanol -, isopropanol +, ethylene glycol -. Of note, isopropanol is metabolized to acetone, which is a ketone. However, some laboratories will measure β-hydroxybutyrate concentrations when “serum ketones” are requested. Acetone is the predominant ketone generated by metabolism of isopropanol, and serum β-hydroxybutryate concentrations remain low even following large ingestions.

Answer 521

Ethylene glycol is metabolized to glycolate, glyoxylate, and oxalate. The parent alcohol (ethylene glycol itself) is relatively nontoxic. The glycolate is responsible for the CNS manifestations and for the anion gap acidosis. Oxalate binds calcium to produce calcium oxalate, which is deposited in tissues, with the process often resulting in hypocalcemia. ARF is primarily due to glycolate-induced damage to tubules, although tubule obstruction from precipitated oxalate crystals may contribute.

Answer 522

Methanol is metabolized to formaldehyde and formate. The parent alcohol (methanol itself) is relatively nontoxic. Formate causes retinal injury with optic disc hyperemia, edema, and eventually permanent blindness, as well as ischemic or hemorrhagic injury to the basal ganglia. These changes are postulated to result from disruption of mitochondrial function. The metabolites result in the anion gap acidosis and osmolal gap.

Answer 523

Acetone. It is responsible for the marked ketosis that is present in most isopropyl alcohol ingestions. Acetone causes less sedation than the parent alcohol, so steady improvement in the patient's level of consciousness is the expected clinical course.

Answer 524

Methanol and ethylene glycol are both primary alcohols, which are oxidized (via alcohol dehydrogenase and then aldehyde dehydrogenase) to carboxylic acids (formic acid in the case of methanol and glycolic, glyoxylic, and oxalic acids in the case of ethylene glycol). These acid metabolites cause the severe toxicity characteristic of methanol and ethylene glycol poisoning. Isopropyl alcohol is a secondary alcohol which is metabolized to a ketone (via alcohol dehydrogenase), rather than an aldehyde. Ketones cannot be oxidized to carboxylic acids. As a result, only very limited acidemia can occur; isopropyl alcohol is considerably less toxic than methanol or ethylene glycol.

Answer 525

Ethanol competitively inhibits the formation of the metabolites of methanol (formate and formaldehyde) and ethylene glycol (glycolate, glycoxylate, and oxalate). Concurrent ethanol use delays the development of increased anion gap metabolic acidosis. In such instances, the elevated osmolal gap may be the only clue to the correct diagnosis.

Answer 526

Lead enters the body through inhalation and ingestion. About 95% of ingested lead is distributed in erythrocytes and bone. Some also goes to the kidney where it is toxic to renal tubular cells.

Answer 527

It nonspecifically binds to and inhibits enzymes bearing sulfhydryl groups, and it is directly toxic to mitochondria.

Answer 528

Among the enzymes inhibited are many of the key enzymes involved in heme synthesis, particularly delta-ALA-dehydratase and ferrochelatase. This leads to an accumulation of the immediate precursor of heme, protoporphyrin (free erythrocyte protoporphyrin). FEP binds non-enzymatically to available zinc, yielding zinc protoporphyrin. Lead inhibits sodium channel ATPases, leading to increased osmotic fragility and shortened RBC survival.

Answer 529

FEP and ZPP are both increased in lead poisoning and iron deficiency.

Answer 530

The final step in biosynthesis of heme, in which iron is incorporated into protoporphyrin (catalyzed by ferrocheletase, which is inhibited by lead), is further inhibited by a deficiency of iron, resulting in reduction of circulating levels of hemoglobin. Also, in an attempt to upregulated intestinal absorption of iron, there is the unintended effect of increased absorption of lead.

Answer 531

Lead absorption is inversely proportional to chronologic age. In general, approximately 30-50% of lead ingested by children is absorbed, compared with approximately 10% of that ingested by adults. The elimination half-life of lead in adult human blood has been estimated to be 1 month, whereas in children it may be as high as 10 months.

Answer 532

Hematologic manifestations of lead toxicity include microcytic and hypochromic anemia.

Answer 533

Mitochondrial toxicity leads to reduced ATP available to drive the numerous ATP-dependent channels involved in renal tubular epithelial function. Then end-result is aminoaciduria, glycosuria, and phosphaturia (similar to Fanconi renal syndrome). Leads inclusions are detectable ultrastructurally as highly electron-dense founded intracellular bodies.

Answer 534

The CDC recommendation, made in 1978 and still upheld today, is that a blood lead level greater than or equal to 10 ug/dL should be considered elevated.

Answer 535

Their advantage is they can be performed on capillary blood samples and they easily detect moderate to severe lead toxicity. One further advantage is that blood lead levels tend to misleadingly "rebound" during treatment, so that the FEP and ZPP can be used to distinguish this phenomenon from a true increase in lead toxicity.

Answer 536

Atomic absorption spectrophotometry is the preferred method for screening for lead toxicity. It is capable of detecting lead levels below the 10 ug/dL threshold. A venous sample is necessary for this determination, as capillary blood obtained from heel- or finger-sticks can give erroneous results. Furthermore, a repeat for confirmation of any abnormal screening test is advised.

Answer 537

CaNa-EDTA test is designed to assess the degree to which lead will be mobilized by chelation therapy. An IV dose of CaNa-EDTA is given, followed by an 8-hour urine collection, and the amount of lead excreted in the urine is determined. This test is sometimes administered prior to initiation of chelation therapy.

Answer 538

At low levels (10-20 ug/dL), environmental interventions may be all that is indicated. Beyond that, both environmental intervention and chelation are indicated. A level >70 ug/dL is considered an indication for inpatient monitoring and treatment. Chelators include dimercaprol (also known as British antilewisite or BAL), CaNa-EDTA, D-penicillamine, and succimer.

Answer 539

False. CO has greater avidity for fetal hemoglobin, putting infants and fetuses at greater risk for CO poisoning.

Answer 540

Normal nonsmokers: 0.4-2%. Normal smokers: 2-6%. Mild symptoms (dyspnea on exertion): 10-20%. Severe symptoms (intoxication, headache, lethargy, loss of consciousness): 20-50%. Coma and death: >50%.

Answer 541

It is produces during the breakdown of heme. Endogenous production usually results in Hb-CO levels of 1% or less. CO is also generated in the hepatic metabolism of dichloromethane (methylene dichloride), found in paint and varnish removers.

Answer 542

The half-life of CO depends on the oxygen tension. On room air it is about 6 hrs, while on 100% O2 it is 1 hr.

Answer 543

A light blue tiger is stopped at a red light. The light turns green and the tiger moves out into the intersection, where he is hit by a lavender car. The tiger turns dark blue then gray as he is dying, and the other driver pees himself. Light blue ("sea" blue for citrate) - tiger (serum separator) - red (nothing) - green (heparin) - lavender (EDTA) - dark blue (EDTA) - gray (sodium fluoride) - yellow (citrate).

Answer 544

Initially (phase I) there may be mild nausea and abdominal discomfort, which is self-limited and abates over a matter of hours. Later, often days later (usually over 24 hrs), there is progressive liver injury (phase II). This leads to fulminant hepatic failure (phase III), after which there is resolution (phase IV) in 4 days to 2 weeks in the form of complete recovery, liver transplant, or death.

Answer 545

It predicts hepatotoxicity/determines the need for NAC therapy/need for ICU admission in acetaminophen overdose (single acute ingestion) by relating serum acetaminophen concentration to time of ingestion. As there are no early symptoms that predict acetaminophen toxicity, poisoning severity following an acute ingestion is quantified by plotting a timed serum acetaminophen concentration on the modified Rumack-Matthew nomogram. Serum concentrations drawn before four hours may not represent peak values (4 hrs is the time it takes for full absorption), and should not be used.

Answer 546

The nomogram stratifies patients into probable hepatic toxicity, possible hepatic toxicity, and no hepatic toxicity. NAC is indicated for patients in the first 2 categories. ICU admission is indicated for patients in the first category.

Answer 547

The nomogram should only be used after a single acute acetaminophen ingestion; It cannot be used for ingestions that occurred greater than 24 hours prior to presentation, repeated supratherapeutic oral ingestions, or iatrogenic intravenous overdose. Also, serum acetaminophen level should be obtained four or more hours after an ingestion to ensure that a peak level has occurred.

Answer 548

A dose over 150 mg/kg. Also, any single acetaminophen level over 5 ug/mL places the patient at high risk for hepatic necrosis.

Answer 549

The liver handles acetaminophen in 2 main pathways. Most of the drug is conjugated with glucuronide or sulfate to form nontoxic metabolites. A small amount is metabolized by the P450 system into the toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI is normally detoxified by gluathione, but glutathione reserves are quickly overwhelmed in toxic ingestions. Furthermore, any agent that induces the P450 system increases the proportion of acetaminophen processed to NAPQI, enhancing toxicity. Chronic ethanol use, for example, has this effect.

Answer 550

The toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI is normally detoxified by gluathione, but glutathione reserves are quickly overwhelmed in toxic ingestions.

Answer 551

NAPQI induces centrilobular (zone 3) hepatic necrosis with periportal sparing. Its formation within hepatocytes makes the liver the primary target, but other organs may be affected.

Answer 552

Cyanide binds to and inhibits cytochrome a3, thus uncoupling the electron transport system. This results in diminished oxygen-dependent metabolism and severe anion gap metabolic (lactic) acidosis. Oxygen accumulates in the blood, giving rise to a bright cherry red skin color.

Answer 553

In cyanide toxicity, the patient's breath often has an odor of bitter almonds due to the presence of HCN gas. However, only about 50% of the population is capable of detecting this odor.

Answer 554

Cyanide levels can be measured, but cyanide is quickly metabolized to thiocyanate. Thiocyanate persists for a long period of time and is more reliable for the diagnosis of cyanide exposure.

Answer 555

While not specific, all patients exposed to cyanide should have an elevated serum lactate and an anion gap metabolic acidosis. Furthermore, the plasma lactate concentration correlates linearly with the cyanide concentration, and a normal lactate essentially excludes the diagnosis. There will usually be an elevated serum glucose (due to decreased utilization). Co-oximetry will show a decrease in the arterial-venous oxygen gap.

Answer 556

A decrease in the arterial-venous oxygen gap (due to decreased utilization) is seen. Also, the co-oximeter can specifically measure carboxyhemoglobin and methemoglobin, removing them from the DDx.

Answer 557

Administration of sodium nitrite and amyl nitrite leads to formation of methemoglobin, which binds available cyanide. Next, sodium thiosulfate is administered, which reacts with cyanohemoglobin to form thiocyanate, a harmless compound that can be cleared by the kidneys.

Answer 558

AL and AA types. AL type is a systemic primary amyloidosis seen often in the setting of multiple myeloma. AA type is a systemic secondary amyloidosis seen in the setting of chronic inflammation, such as RA or chronic infections.

Answer 559

AL - lambda or kappa light chains (lambda 3x more common), systemic primary amyloidosis. AA - apo SAA, systemic secondary amyloidosis. AH - IgG1, systemic heavy chain amyloidosis. ATTR - transthyretin, systemic hereditary or de novo amyloidosis (polyneuropathy or cardiomyopathy). AGel - gelsolin, Finnish familial amyloidosis. AApoA1 - apoA1, familial amyloid polyneuropathy. A(beta2)M - beta2-microglobulin, systemic amyloidosis found with chronic dialysis. A(beta) - A beta protein precursor, localized cerebral amyloid.

Answer 560

Serum iron concentration, transferrin % saturation, and ferritin are all high. Often, due to intramedullary hemolysis associated with ineffective erythropoiesis, there is hyperbilirubinemia, high LDH, and a drop in serum haptoglobin.

Answer 561

This has been attributed to a secondary increase in PTH, as well as resistance of the tissues to the effect of calcitonin.

Answer 562

Aspirin directly stimulates the respiratory center in the medulla oblongata, promoting respiratory alkalosis. Also, aspirin uncouples oxidative phosphorylation and inhibits the Krebs cycle, shunting energy production towards anaerobic pathways with accumulation of organic acids including lactic acid and ketoacids, promoting metabolic acidosis.

Answer 563

The gaseous form -arsine gas- is the most toxic form of arsenic, capable of producing acute renal failure, hemolysis, and death within 24-48 hrs.

Answer 564

Ingested arsenic is excreted in urine, with most of the remainder distributed into skin, nails, and hair.

Answer 565

Arsenic inhibits the oxidative production of ATP. Thus, initial toxicity is manifested in dividing tissue such as GI mucosa, with nausea, vomiting, bloody diarrhea, and abdominal pain. The marrow is affected, causing cytopenias (with erythrocyte basophilic stippling similar to that seen in lead toxicity). Chronic toxicity results in peripheral neuropathy, nephropathy, skin hyperpigmentation and hyperkeratosis (particularly palms and soles) and transverse Mees lines in the nails.

Answer 566

Samples for the diagnosis of chronic intoxication may include fingernails, hair, or urine. The most reliable test is a quantitative 24 hr urinary arsenic excretion; however, this result may be misleadingly elevated due to recent seafood ingestion. A blood arsenic level is highly unreliable, as the substance is rapidly cleared from circulation. Arsenic detection in hair and nails may reflect prolonged exposure.

Answer 567

Tricyclic antidepressants exert their effect by blocking reuptake of dopamine and epinephrine from the synaptic space. There are also anticholinergic effects, more or less profound depending upon the particular agent (strongest for amitriptyline).

Answer 568

CNS: sedation, coma, seizures. Cardiac: tachycardia, hypotension, conduction abnormalities (V tach and V fib, particularly when QRS prolongation is present). A QRS interval longer than 0.16 sec is strongly associated with arrhythmia, while a QRS interval longer than 0.1 sec is associated with a high risk of seizures.

Answer 569

Qualitative (urine) and quantitative (serum) TCA testing have limited therapeutic and prognostic utility in the acute setting. Significant illness can occur at drug concentrations not classically described as toxic, especially in children and in patients taking TCAs on a chronic basis. In addition, a positive qualitative test only indicates use, not overdose, and multiple drugs, including carbamazepine, diphenhydramine, cyclobenzaprine, and quetiapine cross-react with qualitative immunoassays, potentially yielding false positive results. Quantitative serum concentrations are not only poor predictors of systemic toxicity, due to the kinetic changes described above, but are usually not available within a clinically relevant time frame.

Answer 570

Both inhibit acetylcholinesterase but binding to the enzyme and rendering it nonfunctional and causing the muscarinic toxidrome (DUMBELS - Defecation, Urination, Miosis, Bronchorrhea/Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation).

Answer 571

Direct measurement of RBC AChE activity provides a measure of the degree of toxicity. Sequential measurement of RBC AChE activity (if rapidly available) may also be used to determine the effectiveness of oxime therapy in regeneration of the enzyme. RBC AChE activity can also be helpful in evaluating chronic or occupational exposure. An assay for plasma (or pseudo-) cholinesterase activity is more easily performed, but does not correlate well with severity of poisoning and should not be used to guide therapy. Alternatively, metabolites can be detected in urine for up to 1 week after exposure.

Answer 572

Conditions that result from chronic exposure to mercury. Other names for acrodynia are hydrargyria, mercurialism, erythredema, erythredema polyneuropathy, Pink's disease, Bilderbeck's disease, Selter's disease, Swift's disease, Swift-Feer disease, and Feer syndrome. Another name for erethism is erethism mercurialis.

Answer 573

Acrodynia results from chronic exposure to mercury and occurs most often in infants and young children. Symptoms include irritability, photophobia, polyneuritis, autonomic manifestations (sweating, hemodynamic instability), and a desquamative erythematous rash on the palms and soles. It is associated with increased urinary catecholamines and can in many ways mimic pheochromocytoma. The presentation may also be similar to Kawasaki disease.

Answer 574

Since mercury blocks the degradation pathway of catecholamines (it is suggested to inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-o-methyl transferase), epinephrine excess causes profuse sweating, tachycardia, salivation and elevated blood pressure. There are increased amounts of vanillylmandelic and homovanillic acid in urine.

Answer 575

Erethism (from French erethisme - abnormal irritability or responsiveness to stimulation) is a neurological disorder resulting from chronic exposure to mercury. Symptoms include irritability, depression, personality changes, memory loss, delirium, and fine motor disturbances.

Answer 576

Mercury exists in elemental (liquid), inorganic, and organic forms, which are characterized by different toxic properties. Elemental (vapor) and organic forms are toxic to the central nervous system and the fetus, whereas inorganic forms of mercury may affect the kidneys. Mercury also exists in different oxidation states and can form a number of organomercuric compounds. These physical properties contribute to the considerable toxicity observed with mercury. Dental amalgam fillings are the most common exposure to elemental and inorganic mercury, and fish are the most common exposure to organic mercury.

Answer 577

Pulmonary absorption of mercury vapor (elemental form) is high; however, this form of mercury is only poorly absorbed from the GI tract and across the skin. The kidney is the major site of deposition for mercury derived from inhalation exposure of mercury vapor. A significant fraction of the mercury vapor taken into the lung is eliminated via exhalation; most of the absorbed mercury is eliminated in the feces. GI absorption of inorganic mercury is on the order of 15 percent. The kidney is the major site of deposition for inorganic mercury compounds. Organic mercury compounds such as methylmercury are highly absorbed from the GI tract and later de-alkylated. The kidney, hair, and CNS are major sites of deposition. Organic mercury readily crosses the placenta, causing severe neurologic impairments in the fetus.

Answer 578

Clinical manifestations include paresthesias around the mouth, peripheral neuropathy, tremor, malaise, constriction of the visual field, deafness, and ataxia. The fetus is particularly vulnerable (organic mercury crosses the placenta readily), even if the pregnant mother shows no signs of toxicity.

Answer 579

While blood levels are useful for more acute exposures, long-term exposures are best reflected in hair mercury measurements. Organic mercury is easily absorbed and retained by the body; it has a half-life in blood of about 44 days, which makes blood tests useful measures of acute exposure. The blood level correlation with chronic organic mercury toxicity is more variable.

Answer 580

Inorganic mercury redistributes to other body tissues; thus, its levels in the blood are accurate only after an acute ingestion. Excretion of mercury in urine (24 hour urine collection) is a good indicator of inorganic and elemental mercury exposure but is unreliable for organic mercury because this is eliminated mostly in the feces. In cases of chronic mercury toxicity, the urinary mercury measurement may be falsely low.

Answer 581

When there is a change in dose, a change in the patient's renal function, or a change in concomitantly administered medications.

Answer 582

Digoxin is primarily excreted by the kidneys and has a long half-life of around 36 hours.

Answer 583

Samples for digoxin levels should be drawn about 8 to 12 hrs after the last dose, ideally about 8 to 10 days after a dose change.

Answer 584

Hypokalemia, hypercalcemia, hypomagnesemia, hypoxia, hypothyroidism, quinidine, and calcium channel blockers.

Answer 585

Quinidine, in addition to enhancing end-organ effects of digoxin, frees digoxin from protein binding sites and impairs digoxin clearance.

Answer 586

They are endogenous or exogenous substances that cross-react with antidigoxin antibodies and falsely elevate serum digoxin concentrations, interfering in interpretation of results for therapeutic digoxin monitoring. Falsely lower digoxin values due to the presence of DLISs have been reported as well.

Answer 587

Elevated DLIS concentrations are encountered in patients with volume-expanded conditions such as uremia, essential hypertension, liver disease, and preeclampsia. They are also seen in neonates, pregnant women, and renal failure.

Answer 588

Procainamide is cleared predominantly by the liver. Procainamide is metabolized by hepatic acetyltransferase to N-acetylprocainamide (NAPA), which has pharmacologic activity of its own (in making dosing decisions, the sum of procainamide and NAPA is considered). NAPA is cleared predominantly by the kidneys.

Answer 589

Pocainamide (hepatic clearance) is metabolized to N-acetylprocainamide (NAPA) (renal clearance), which is also biologically active. The rate of conversion to NAPA is determined by the concentration of hepatic acetyltransferase, which is genetically determined. So-called fast acetylators, who have genetically high levels of acetyltransferase, have higher levels of NAPA.

Answer 590

Procainamide, hydralazine, minocycline, diltiazem, penicillamine, isoniazid (INH), quinidine, anti-tumor necrosis factor (TNF) alpha therapy (most commonly with infliximab and etanercept), interferon-alfa, methyldopa, chlorpromazine, and practolol.

Answer 591

Mainly by the kidneys.

Answer 592

Ideally, the gentamicin peak specimen is drawn 30 min after the completion of a dose, and the trough specimen is drawn immediately before a dose.

Answer 593

Quinidine, disopyramide, and procainamide. They function by blocking sodium and potassium channels in cardiac conduction fibers.

Answer 594

Cinchonism, a syndrome which may include tinnitus, high-frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium has been associated with quinidine use. Usually associated with chronic toxicity, this syndrome has also been described after brief exposure to a moderate dose in sensitive patients.

Answer 595

Cinchonism (tinnitus, hearing loss, vertigo, blurred vision), AMS, widening of the QRS complex, prolonged QT interval, and hypotension (without compensatory tachycardia).

Answer 596

Quinidine is cleared by the liver. Quinidine levels are not routinely used to predict toxicity; the ECG is more reliable in this regard. It is important to check and correct electrolyte levels.

Answer 597

Early manifestations: ocular dysmotility (particularly horizontal gaze nystagmus), ataxia, and incoordination. Severe toxicity: AMS and cardiac conduction disturbances.

Answer 598

It is thought that this discrepancy and the arrhythmogenic effects of IV intoxication are due to the propylene glycol diluent instead of phenytoin.

Answer 599

AKA dilantin embryopathy or fetal dilantin syndrome. A congenital syndrome resulting from in utero phenytoin exposure. It occurs in <10% of exposed fetuses. It is characterized by IUGR, microcephaly, mental retardation, nail and distal phalanx hypoplasia, midfacial hypoplasia, hypertelorism, flattened philtrum, and shortened nose.

Answer 600

Following initiation or a change in dose, since the half-life for lithium varies from 8-40 hrs (depending largely on age and renal function), steady state conditions would be expected in 2-8 days, and checking levels after a period of 3-7 days is recommended. Several guidelines have been proposed for routine monitoring (patients who are stable on therapy), with a range of recommended intervals of 1-3 mos. For routine monitoring, a sample should be taken at 12 hrs following the last dose.

Answer 601

Amiodarone levels should not necessarily be routinely monitored in the stable patient. In this situation, many advocate the use of other monitors such as the function of organs known to be affected by amiodarone toxicity or the monitoring of desethylamiodarone (an amiodarone metabolite) or the amiodarone to desethylamiodarone ratio.

Answer 602

Pulmonary toxicity (1% annually), thyroid toxicity (hypothyroidism 5-15%, hyperthyroidism 1-2%), hepatotoxicity (0.6%), peripheral neuropathy (0.3%). Thus, at baseline and every 6 mos it is recommended that there be thyroid and liver function testing, in addition to annual CXR and ECG.

Answer 603

Amiodarone reduces the clearance of warfarin, and can thereby prolong the INR. This effect is usually fully manifest by 7 wks of co-treatment, so that close INR monitoring needs only be carried out for that period of time. Amiodarone increases digoxin concentrations, and doses of digoxin must be reduced while closely monitoring digoxin concentrations.

Answer 604

Cholesterol, triglyceride, and phospholipid.

Answer 605

Chylomicrons, VLDL, IDL, LDL, HDL.

Answer 606

Ingested lipid are internalized by small bowel enterocytes and packaged into chylomicrons, which have a low density due to a large triglyceride component. The chylomicron is the lipoprotein that transports lipid from enterocytes to other somatic cells, particularly hepatocytes, into which they are endocytosed via apolipoprotein E.

Answer 607

In the liver, cholesterol and triglyceride undergo additional metabolism before being packaged, for secretion into the blood, into VLDL, which has a low density due to a large triglyceride component, and is the vehicle for transport of triglyceride to somatic cells.

Answer 608

VLDL is the vehicle for transport of triglyceride to somatic cells. LDL is the vehicle for transport of cholesterol to somatic cells.

Answer 609

In the blood, the TG in VLDL undergoes progressive hydrolysis by the endothelium-based enzyme lipoprotein lipase. Over time, enough TG is removed from VLDL to increase its density to that of IDL and, eventually, LDL.

Answer 610

The typical LDL particle has lost most of its TG and a good bit of its apolipoproteins C and E, leaving predominantly phospholipid, cholesterol, and apolipoprotein B-100.

Answer 611

LDL is the main vehicle for transporting cholesterol to somatic cells, where LDL particles undergo endocytosis mediated by the LDL receptor and apolipoprotein B-100.

Answer 612

The liver produces a class of lipoproteins called HDL that contain a small amount of lipid, mainly phospholipid and cholesterol, the enzyme lecithin cholesterol acyl transferase (LCAT), and apolipoproteins, especially apolipoprotein A-1. The function of HDL is to scavenge cholesterol from the periphery and returning it to the liver.

Answer 613

Chylomicrons: origin. VLDL: pre-beta. IDL: pre-beta/beta. LDL: beta. HDL: alpha.

Answer 614

Chylomicrons and VLDL: triglyceride. IDL, LDL, and HDL: cholesterol.

Answer 615

Chylomicrons: 1%. VLDL: 8%. IDL: 15%. LDL: 20%. HDL: 50%.

Answer 616

Chylomicrons: B-48, A-1, C, E. VLDL: B-100, C, E. IDL: B-100, E. LDL: B-100. HDL: A-1, C, E.

Answer 617

Chylomicrons: 0.95 g/mL, 1%. VLDL: 1.0 g/mL, 8%. IDL: 1.02 g/mL, 15%. LDL: 1.04 g/mL, 20%. HDL: 1.10 g/mL, 50%.

Answer 618

LDL does. IDL: 1.02 g/mL average density, 15% protein. LDL: 1.04 g/mL average density, 20% protein.

Answer 619

LDL and VLDL are calculated. LDL is calculated, usually using the Friedewald equation = total cholesterol - HDL - TG/5. VLDL is often estimated as TG/5 (when expressed in mg/dL) or TG/2.2 (when expressed in mmol/L).

Answer 620

LDL is calculated, usually using the Friedewald equation = total cholesterol - HDL - TG/5. VLDL is often estimated as TG/5 (when expressed in mg/dL) or TG/2.2 (when expressed in mmol/L).

Answer 621

Measurement is carried out by a sequence of enzymatic reactions, a dye product of which is measured spectrophotometrically.

Answer 622

When TG is greater than 400 mg/dL, chylomicrons are present, or there is beta-VLDL characteristic of the very rare type III dyslipidemia. The Friedewald calculation for LDL is also not valid in these 3 situations.

Answer 623

HDL is usually measured by an enzymatic sequence similar to that for total cholesterol or TG, after removal of non-HDL lipoproteins. The initial removal step may take the form of selective precipitation by manual chemical pretreatment, followed by a cholesterol determination performed on the supernatant. This method may also require ultracentrifugation to remove VLDL and chylomicrons when they are increased. Alternatively, in what are called homogeneous assays (which are amenable to automation, without a manual step), a polymer, detergent, or enzyme is used to inactivate non-HDL cholesterol, followed by a cholesterol determination.

Answer 624

When TG is greater than 400 mg/dL, chylomicrons are present, or there is beta-VLDL characteristic of the very rare type III dyslipidemia. The VLDL estimation of TG/5 (when expressed in mg/dL) or TG/2.2 (when expressed in mmol/L) is also not valid in these 3 situations.

Answer 625

Ultracentrifugation, electrophoresis, and homogeneous assays.

Answer 626

Ultracentrifugation is a tedious and technically difficult technique not well-suited for routine use, but it does remain the gold standard for method comparison. In a way similar to SPEP, lipoproteins can be subjected to electrophoresis on agarose gel then scanned densitometrically to give quantitative results. Current techniques yield fairly reliable quantitation; furthermore, they provide a display that can be analyzed visually to help classify lipid disorders. However, due to the labor and expertise required, it is not suitable for routine use in all labs. Homogenous assays employ detergents to block or dissolve all but LDL, permitting direct enzymatic measurement of LDL cholesterol. These assays can be automated.

Answer 627

Lipoprotein electrophoresis is performed on a gel in a manner similar to protein electrophoresis, and stained with a fat stain such as Oil Red O or Sudan Black B. Chylomicrons do not move from the point of application. LDL migrates in the beta region, VLDL in the pre-beta region, and HDL in the alpha region. This is why LDL is often referred to as beta-lipoprotein and HDL as alpha-lipoprotein. This method is employed as a basis for qualitative analysis of lipoprotein classes but is not suitable for quantitative analysis.

Answer 628

Overnight refrigeration produces characteristic patterns in plasma, depending on the lipoprotein profile. The presence of a creamy layer atop the plasma indicates the presence of excess chylomicrons. Turbidity or opacity of the plasma below this indicates abundant VLDL. Even when present in excess, LDL and HDL do not visibly alter the plasma.

Answer 629

The major classes of dyslipidemia have been conventionally classified by patterns of elevation in lipoproteins and lipids according to the Fredrickson phenotype. A variety of defects, some of which are familial, can produce these disorders. The phenotypes are I, IIa, IIb, III, IV, and V.

Answer 630

I: Chylomicrons; TGs. IIa: LDL; Cholesterol. IIb: LDL and VLDL; TGs and cholesterol. III: VLDL and chylomicron remnants (? IDL); TGs and cholesterol. IV: VLDL; TGs. V: Chylomicrons and VLDL; TGs and cholesterol.

Answer 631

Familial LPL deficiency: I. Familial apo- C-II deficiency: I or V. Familial hypercholesterolemia: IIa. Apolipoprotein E deficiency: IIb. Familial dysbetalipoproteinemia: III. Familial combined hyperlipidemia: II or IV. Familial hypertriglyceridemias: IV or V.

Answer 632

It is seen when there is abnormally high LDL or IDL; that is, whenever the cholesterol is too high. It is not a prominent feature when only the TG is elevated.

Answer 633

Eruptive xanthomas, presenting as crops of yellow pruritic papulonodules, are seen with elevated TG (chylomicrons or VLDL). Tendinous (tuberous) xanthomas are seen near the knees or elbows and appear when there are simultaneous elevations in TG and cholesterol (elevated IDL). Xanthelasma are yellow periorbital papules that are associated with high cholesterol (LDL).

Answer 634

Acute pancreatitis is associated with elevated TG (chylomicrons or VLDL), particularly when greater than 5-10 mmol/L.

Answer 635

Familial LPL deficiency: chol+, TG+++. Familial apo- C-II deficiency: chol+, TG+++. Familial hypercholesterolemia: chol+++, TG normal to +. Apolipoprotein E deficiency: chol+++, TG+++. Familial dysbetalipoproteinemia: chol+++, TG+++. Familial combined hyperlipidemia: chol+, TG+. Familial hypertriglyceridemias: chol+, TG+++.

Answer 636

Hypothyroidism, DM, nephrotic syndrome, cholestasis, cyclosporine, thiazide diuretics, or loop diuretics.

Answer 637

Familial hypercholesterolemia, an autosomal dominant deficiency in LDL receptors.

Answer 638

Heavy alcohol consumption, obesity, DM, hepatitis, pregnancy, renal failure, beta blockers, isotretinion, corticosteroids, nephrotic syndrome, and gout.

Answer 639

Familial combined hyperlipidemia, familial LPL deficiency, familial apo C-II deficiency, and familial hypertriglyceridemia.

Answer 640

Severe examples of DM, hypothyroidism, or nephrotic syndrome. Also, type III hyperlipidemia, thiazides, loop diuretics, and beta blockers.

Answer 641

Familial combined hyperlipidemia.

Answer 642

A low level of HDL cholesterol, defined as less than 35 mg/dL, is an independent risk factor for premature atherosclerosis. A high HDL, greater than 70 mg/dL, is protective.

Answer 643

Low cholesterol, normal to increased TG, absent HDL, and absence of APO-A1. Cholesterol esters deposit in the tonsils, lymph nodes, vasculature, and spleen, and corneal opacities develop.

Answer 644

The National Cholesterol Education Program (NCEP) has been providing guidelines for cholesterol testing and treatment since 1988. Their most recent guidelines are the 3rd Adult Treatment Panel (ATP III). ATP III recommends a fasting lipoprotein profile (TG, TC, HDL, LDL) (in a non-fasting patient, the TGs and calculated LDL-C are not considered valid). The ATP III also recommends specific cholesterol and LDL targets.

Answer 645

TC: desirable less than 200, borderline 200-239, high greater than 240. LDL: optimal less than 100, near optimal 100-129, borderline 130-159, high 160-189, very high greater than 190. HDL: low less than 40, high greater than 60.

Answer 646

CHD or CHD risk equivalents (10 yr risk greater than 20%): less than 100 mg/dL. 2 or more risk factors (10 yr risk 20% or less): less than 130 mg/dL. 0 to 1 risk factors (almost all people with 0 to 1 risk factors have a 10 yr risk less than 10%): less than 160 mg/dL.

Answer 647

Human placental lactogen, also called somatomammotropin, has anti-insulin effects and is responsible for the relative glucose intolerance of pregnancy.

Answer 648

Insulin is synthesized as proinsulin, a single amino acid chain 51 amino acids long. Though it is a single polypeptide chain, by convention the first (amino terminus) several amino acids are called the B-chain, the next several amino acids are called the C-peptide, and the carboxy-terminal amino acids are called the A-chain. Disulfide bonds form between the A and B chains, and the C-peptide is proteolytically cleaved posttranslationally to make insulin. When islet cells are induced to secrete, they secrete disulfide-linked A-B chains (insulin) and C-peptide simultaneously.

Answer 649

Because insulin is rapidly metabolized compared to C-peptide.

Answer 650

When blood is left in an unseparated test tube, glycolysis will reduce the glucose by 5-10 mg/dL/hr depending on the temperature and white cell count. Fluoride added to the tube will arrest this process for 24 hrs.

Answer 651

(5-15?) to up to 30 min.

Answer 652

Insulin, sulfonylureas, alcohol, quinine, salicylates, haloperidol, beta blockers, quinolones, pentamidine, ACE inhibitors, IGF-1).

Answer 653

Fasting hypoglycemia is the abnormal gradual-onset of hypoglycemia occurring following a prolonged fast or prolonged exercise. Reactive hypoglycemia is the abnormal rapid-onset of hypoglycemia following a meal.

Answer 654

Kidneys. Therefore, C-peptide is raised in renal impairment.

Answer 655

In patients with insulinomas, the absolute insulin concentration may be normal, but it is inappropriately high for the degree of hypoglycemia. Thus, the diagnosis depends on the insulin:glucose ratio, which is often greater than 180 with insulinoma, whereas normal is less than 0.25. Also useful are proinsulin levels, which will be greater than 25% (or up to 90%) of that of immunoreactive circulating insulin, whereas normal is less than 10%.

Answer 656

Anti-insulin Abs can be raised in response to exogenous insulin, but this is rare in the era of human (recombinant?) insulin administration. Anti-insulin Abs may rarely occur in patients never exposed to exogenous insulin, and may cause reactive hypoglycemia (autoimmune insulin syndrome). Also, anti-insulin Abs may be found rarely in patients with insulinoma.

Answer 657

Hyperglycemia more commonly than hypoglycemia.

Answer 658

Non-ketotic hypoglycemia suggests the presence of insulin-like activity and may be seen in autoimmune hypoglycemia, liver failure, or starvation. All other causes of hypoglycemia are associated with ketosis.

Answer 659

Insulinoma. Nesidioblastosis. ILGF-like hormone secreting tumors (sarcomas, HCC). Advanced malignancy. Anti-insulin receptor antibodies. Autoimmune insulin syndrome. Post-gastric surgery. Drug induced (insulin, sulfonylureas, alcohol, quinine, salicylates, haloperidol, beta blockers, quinolones, pentamidine, ACE inhibitors, IGF-1). Critical illness such as hepatic/renal/cardiac failure, sepsis, inanition (def: an exhausted condition resulting from lack of food and water or a defect in assimilation; starvation). Hormone deficiency (cortisol, glucagon and epinephrine in insulin-deficient DM). Inborn errors of metabolism (glycogen storage disease, hereditary fructose intolerance, galactosemia, carnitine deficiency). Starvation. Accidental, surreptitious, or malicious hypoglycemia.

Answer 660

Insulin. Islet cells. Glutamic acid decarboxylase (GAD65). ZnT8 (zinc transporter of islet beta cells). Insulinoma-associated protein 2 (IA-2 and IA-2 beta).

Answer 661

Impaired glucose tolerance (IGT) – OGTT (75 g oral glucose load) results in a two-hour plasma glucose of 140 to 199 mg/dL (7.8 to 11.0 mmol/L). Impaired fasting glucose (IFG) – FPG 100 to 125 mg/dL (5.6 to 6.9 mmol/L).

Answer 662

FPG 126 mg/dL (7.0 mmol/L) or greater. A1C 6.5% or greater. 2 hr plasma glucose 200 mg/dL (11.1 mmol/L) or greater in an OGTT. Random (or "casual") plasma glucose 200 mg/dL (11.1 mmol/L) or greater in the presence of symptoms. The diagnosis based on one of the above findings must be confirmed on a subsequent day by repeat measurement, repeating the same test for confirmation.

Answer 663

FPG less than 100 mg/dL (5.6 mmol/L). Fasting is defined as no caloric intake for at least eight hours.

Answer 664

Screening can be performed at the first prenatal visit for high-risk women, where a FPG of 126 mg/dL or random plasma glucose of 200 mg/dL is diagnostic of GDM. In the absence of early screening/testing or if early screening/testing is negative, universal screening is performed at 24 to 28 weeks of gestation. There are numerous approaches from numerous organizations: one step vs. two steps, 75g vs 100g oral glucose load, 2 hr test vs 3 hr test.

Answer 665

6-12 wks postpartum.

Answer 666

Hg A1C testing is used to monitor glycemic control. The frequency of testing is often individualized, but the ADA recommends testing at least twice a yr in stable patients and more frequently in others, and recommends the A1C be less than 7%. Adult patients are screened annually for lipid disorders. Testing for microalbuminuria is performed annually. The serum Cr is measured annually for calculation of eGFR. Magnesium levels should be checked periodically, since hypomagnesemia is a common problem in diabetics, and appears to complicate glycemic control.

Answer 667

Hyperglycemia (glucose at least 200 mg/dL; normoglycemic DKA is rare), ketosis, and metabolic acidosis (venous pH less than 7.30 or bicarbonate less than 15 mmol/L) are the usual requirements for the diagnosis of DKA. Occasionally the diagnosis is made solely on the basis of the typical clinical presentation coupled with urine dipstick findings of glycosuria and ketonuria.

Answer 668

Acetone, acetoacetic acid, and beta-hydroxybutyrate. These are in a dynamic balance with one another and undergo continual interconversion.

Answer 669

The nitroprusside technique, a semi-quantitative method that is sensitive to acetone and acetoacetic acid but not beta-hydroxybutyrate. In normal circumstances, these are present in roughly equimolar concentrations. When "ketones" are measured, actually only a small fraction of serum ketones are being measured.

Answer 670

Acetone, acetoacetic acid, and beta-hydroxybutyrate are the major serum ketones. These are in a dynamic balance with one another and undergo continual interconversion, and in normal circumstances these are present in roughly equimolar concentrations. In DKA, due to an altered metabolic milieu, acetone and acetoacetic acid account for 20% of serum ketones and beta-hydroxybutyrate accounts for 80%.

Answer 671

Ketones are measured by the nitroprusside technique, a semi-quantitative method that is sensitive to acetone and acetoacetic acid but not beta-hydroxybutyrate. The apparent increase in "ketones" is due to beta-hydroxybutyrate being converted to the other two forms as total serum ketones decrease.

Answer 672

HHNC is about one-tenth as common as DKA but has a mortality rate 10 times that of DKA (mortality rate of HHNC varies from 15% to 50%).

Answer 673

There is a typical clinical presentation as well as extreme hyperglycemia (at least 600 mg/dL, usually greater than 1000 mg/dL), hyperosmolarity (greater than 330 mOsm/L), and essentially normal bicarbonate and ketones.

Answer 674

There are several definitions for the metabolic syndrome, but The National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) is the most widely used. 2005 criteria define the metabolic syndrome as the presence of any 3 of these 5 traits: Abdominal obesity, defined as a waist circumference in men 102 cm (40 in) or greater and in women 88 cm (35 in) or greater. Serum triglycerides 150 mg/dL (1.7 mmol/L) or greater or drug treatment for elevated triglycerides. Serum HDL cholesterol less than 40 mg/dL (1 mmol/L) in men and less than 50 mg/dL (1.3 mmol/L) in women or drug treatment for low HDL-C. Blood pressure 130/85 mmHg or greater or drug treatment for elevated blood pressure. Fasting plasma glucose 100 mg/dL (5.6 mmol/L) or greater or drug treatment for elevated blood glucose.

Answer 675

Ethylene glycol: anion gap acidosis +, osmolal gap +, no increase in ketones. Metabolized by alcohol dehydrogenase initially into glycolic acid, then to oxalate. The glycolic acid is responsible for the CNS manifestations and for the anion gap acidosis. The oxalate binds calcium to produce calcium oxalate, which is deposited in tissues and can be found in renal tubules and urine. Methanol: anion gap acidosis +, osmolal gap +, no increase in ketones. Metabolized by alcohol dehydrogenase to formaldehyde then formic acid. These metabolites result in ocular toxicity and the anion gap acidosis. Isopropyl alcohol: no anion gap acidosis, osmolal gap +, no increase in ketones. Is metabolized to acetone. Ethanol will have -/+ anion gap acidosis, osmolal gap +, and -/+ increase in ketones. Direct laboratory tests for methanol and ethylene glycol are not widespread, so the osmolal gap is a surrogate marker; ingestion is suspected if the osmolal gap exceeds 10, and is strongly suspected if it exceeds 20.

Answer 676

Na: serum values decrease after death; vitreous values stable until onset of putrefaction. Cl: serum values decrease after death; vitreous values stable. K: serum and vitreous values increase after death. BUN/Cr: both serum and vitreous values are stable after death.

Answer 677

Exudates have increased vascular permeability, high protein and cell debris, and a specific gravity greater than 1.020. Transudates have normal vascular permeability, low protein and a specific gravity less than 1.020.

Answer 678

Phase I (non-synthetic reactions) - modification (oxidation, reduction, hydrolysis). Phase II (synthetic reactions) - conjugation (methylation, sulphation, acetylation, glucuronidation). Some classification systems also include a... Phase III - excretion/further modification and excretion.

Answer 679

TSH, FSH, LH, and hCG. The first 3 are synthesized by the anterior pituitary, while hCG is synthesized by placental trophoblastic cells during pregnancy. The unique beta subunit of all four protein hormones provides biological specificity. The beta subunit of hCG is closely related to the beta subunit of LH, and both hormones bind to the LH receptor, which reflects the physiologic role of both hormones

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