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Flashcards in Chemistry Deck (171):
1

What lab value may be increased postprandially in people that are Lewis positive group B or O secretors?

Alkaline phosphatase (intestinal)

Medications (OCPs, NSAIDs) may elevate Alk Phos levels

2

Which liver disease:

1) is associated with marked polyclonal increase in IgG?

2) is associated with marked polyclonal increase in IgM?

1) Autoimmune hepatitis

2) Primary biliary cirrhosis

3

What are reasons for decreased albumin on SPEP?

Malnourishment (used to assess nutritional status)

Inflammatory states (negative acute phase reactant)

Liver disease

Increased catabolism: inc T4, pregnancy or steroids

Loss: nephrosis, burn, protein losing enteropathy

Fluid retention (SIADH)

4

What are reasons for increased or decreased alpha 1 band on SPEP?

Increased: Acute inflammatory states (acute phase reactant)

Decreased: alpha 1 anti-trypsin deficiency, HDL def and aged serum

5

1) What are the reasons for increased alpha 2 band on SPEP?

2) What two other proteins are represented in the alpha 2 band?

1) Relative concentration elevated in liver and renal disease; large size prevents its loss in nephrotic syndrome leading to a relative 10 fold rise in concentration

2) Ceruloplasmin (decreased in Wilson's disease, acute phase reactant) and Haptoglobin (binds free hemoglobin, acute phase reactant)

*NOTE low ceruloplasmin is not detectable with SPEP

6

What major protein is represented in the beta 1 region and what would cause this spike to increase?

Transferrin

It is markedly increased in iron deficiency

7

What major proteins are represented in the beta 2 region?

IgA and C3

*Fibrinogen, usually absent from serum, may be present in the beta-gamma interface when there is incomplete clotting (a possible pseudo M spike)

8

What major proteins are represented in the gamma region (gamma 1 and gamma 2)?

Gamma 1: gamma globulins

Gamma 2: CRP (acute phase reactant)

*CRP normally 2-3 mg/L but high level CRP elevation (>10 mg/L) usually indicates active inflammation such as collagen vascular disease, infection, etc and low level CRP elevation (3-10 mg/dL) is indicative of cellular stress and correlated with higher all cause mortality, poor outcome following cardiovascular events

9

What does it mean if you see a bimodal albumin peak on SPEP?

This is seen in heterozygotes for albumin alleles

No clinical significance

10

What pattern would you see on SPEP in a patient with nephrotic syndrome?

Loss of small serum proteins, particularly albumin, while large proteins are retained

Result is a decrease in all bands except alpha 2 (too big so it's retained)

11

What pattern would you see on SPEP in a patient with acute inflammation?

Decreased albumin

Increased alpha 1 and alpha 2

Normal-to-increased gamma globulins

12

What condition causes beta gamma briding on SPEP?

Indicative of cirrhosis cause by increased serum IgA

Additional features include hypoalbuminemia and blunted alpha 1 and alpha 2 bands

13

If the basal triglyceride level is elevated, what two clinical scenarios can cause this "pseudo-hypertriglyceridemia"?

DKA
Glycerol kinase def.
- (glycerol –GK-- > glycerol-3-phosphate)

These people aren't metabolizing TGs correctly

14

What is Friedewald equation (which you MUST KNOW for boards)?

LDL-C = TC – HDL-C – Tg/5* (*estimates VLDL-C)

If TG >400, it is invald!

15

What is Osler guy's helpful tip for remembering the different lipid disorders and what is elevated in them?

Increased TG: Types I (chylomicrons), IV (VLDL) and V (chylomicrons and VLDL)

Increased LDL: Types IIA (LDL)

Increased TG and LDL: Types IIB (LDL and VLDL) and III (IDL and remanant lipoproteins

16

What are the causes of type I hyperlipidemia (chyolmicronemia)?

Lipoprotein Lipase Deficiency: AR, rare, onset in infancy

Apo CII Deficiency: ligand for lipoprotein lipase, AR, rare, onset in childhood

SLE: acquired, autoantibody against lipoprotein lipase

17

What are the acquired and genetic causes of type IV hyperlipemia (increased VLDL)?

Genetic

Insulin resistance: insulin receptor mutation, lipodystrophy

Familial hypertriglyceridemia

Familial combined hypertriglyceridemia 

Inborn errors of metabolism:glycogen storage disease

Acquired 

Insulin resistance: increased VLDL production, decreased VLDL clearance, decreased activity of LPL (includes obesity, met syn, diabetes, Cushing, acromegaly, pheo, steroids)

Liver disease

Renal disease

Hypothyroidism

18

What are the genetic causes of type IIA hyperlipemia and what particle is involved?

LDL

Monogenic disorders
Familial hypercholesteromia
Familial hyperapo-B-lipoproteinemia
AR familial hypercholesteromia
Familial combined hyperlipidemia
Polygenic disorders
Polygenic hypercholesterolemia

19

What are the acquired causes of type IIA hyperlipidemia and what particle is involved?

Liver disease (e.g.,biliary tract disease*)

*in biliary tract disease, there is a lipoprotein called LpX which can falsely elevate both LDL and HDL
Renal disease (e.g., nephrosis)
Endocrine (hypothyroidism, diabetes mellitus)
Drugs - glucocorticoids, androgens

20

What are the causes of type IIB hyperlipidemia and what are the particles involved?

LDL & VLDL

Similar to HLP IIA
except: Familial hyperapo-Blipoproteinemia: HLP IIA only
(no incr. in VLDL)

21

What are the causes and particles involved in type III hyperlipidemia?

LDL and remnant lipoproteins

Happens if somone is homozygous for Apo E2/E2 AND has an environmental stressor that makes them hyperlipidemic such as:
- EtOHism
- DM
- Renal disease
- Liver disease

22

What is the one genetic cause of low lipoproteins that you MUST KNOW for boards and how is it inherited, what particles are low and what are the clinical features?

Abetalipoproteinemia

Autosomal recessive failure of apo B production
- very low Tg & chol
- Very low: VLDL & LDL
HDL: preserved (lacks apo B)
Clinical: acanthocytes
developmental failure in infancy
fat malabsorption

23

What are the positive acute phase reactants?

C3, CRP
A1AT, A2M
Ceruloplasmin
Fibrinogen
Haptoglobin

24

What are the negative acute phase reactant?

Albumin
Transthyretin
Retinol binding protein (RBP)
Transferrin

25

What is the one body fluid where you can see a band in the pre-albumin peak on serum protein electrophoresis?

CSF

Also has a "2nd form" of beta which represents CSF transferrin

Hallmarks of CSF:

Prealbumin spike

Double transferrin (B1) peak from asialated transferrin aka Tau protein

26

What proteins are represented in the prealbumin peak on SPEP?

Retinal Binding Protein (RBP) which transports VitA

and

Transthyretin which is a T4 transporter

*prealbumin is an indicator of nutritional status (half like 48 hours) and is a neg acute phase reactant

27

What are significant causes of decreases in RBP or
transthyretin (which are seen in the pre-albumin peak on SPEP)?

RBP: malnutrition

Transthyretin: malnutrition and nephrosis

*why would nephrosis be a prothrombotic state if you are losing proteins? You are also losing anti-coag like antithrombin 3

28

What are reasons for increased albumin on SPEP?

Dehydration
 Diabetes insipidus
 Prolonged tourniquet time

29

What proteins are represented by the beta region on SPEP?

Transferrin (beta 1)

LDL (beta 1-beta 2 interface)

IgA and C3 (beta 2)

30

What are the primary and secondary cause of hypogammaglobulinemia on SPEP?

Primary:

XLA (Brutons agammaglobulinemia),
CVID (common variable immunodeficiency)
IgA (w/ IgG subclass: sinopulm/GI infections)
Hyper-IgM syndrome (CD40L--on T cells,CD40--on B cells, NEMO, AID)

Secondary:

Loss (nephrosis, burn, protein losing enteropathy)
Various forms of immunosuppresion
Chemotherapy for cancer
Irradiation for cancer
Immunosuppression for organ tx/AI Dz
Light chain disease

31

BQ! What states cause a LOW anion gap?

low albumin +/or high Ig’s (myeloma, AIDS, cirrhosis)

32

BQ! In the basic metabolic panel, what is actually being measured in testing for bicarbonate?

Total CO2 content = bicarbonate + carbonic acid + carbamino compounds;
usually 1-2 mmol/L higher than true bicarbonate

33

What are the causes of anion gap metabolic acidosis?

"DUMPSALE"

Diabetic ketoacidosis
 Uremia
 Methanol
 Paraldehyde
 Salicylates
 Alcoholic ketoacidosis
 Lactic acidosis
 Ethylene Glycol

34

What is the most common cause of inborn error in urea synthesis?

Ornithine transcarbamoylase

Only enzyme encoded on the X chromosome so this will affect boys

35

What clinical scenario would give you this pattern on urine protein electrophoresis?

Glomerular proteinuria:
Albumin +/- transferrin (ß globulin)

 

A normal UPE would just have an albumin peak.

36

What clinical scenario would give you this pattern on urine protein electrophoresis?

Tubular proteinuria:
Albumin + alpha-2 + beta

*can occur in heavy metal poisoning, Wilson's disease, etc

If there is an alpha 2 band on the urine protein electrophoresis, it will be due to a tubular problem because with glomerular issues, alpha 2 is too big to filter through even in damage so other proteins will be increased but not alpha 2

37

What clinical scenario would give you this pattern on urine protein electrophoresis?

Overflow proteinuria: M-spike
- often IgL - sometimes: intact Ig

38

What test should you do if you have an infant you think has an inborn error of metabolism?

Benedict's copper reduction reaction to detect
nonglucose reducing sugars 

Classic disorders: Galactosemia and Hereditary Fructose Intolerance

39

BQ!!!! The boards LOVE to ask about Gilbert's syndrome. What impaired metabolism do they have?

mild impairment UDP-GT, (TA7
in promoter instead of the usual 6 that most people have); gene common 1/6, syndrome (jaundice at times of stress) less so (5% M, < 1% F); impairs irinotecan metab. important because this is a chemo agent so if these people get cancer, must know about this!

40

BQ! They ask about this ALL THE TIME!

What changes in thyroid function do you see in someone who is sick (ie acute illness)?

ACUTE: TSH normal, T4 normal, T3 low, increased rT3

Chronically: TSH normal, rT3 increased, T4 and T3 low

41

Boards LOVES to ask about metyrapone testing so what is the idea behind the test?

Metyrapone blocks 11-hydroxylase (last step in cortisol synthesis); normal response is for cotrisol to fall, but ACTH and 11-deoxycortisol to rise (the latter by at least 7 ug/dL).

Therefore if 11-deoxycortisol levels do not rise and remains less than 7 µg/dl and ACTH rises, then it is highly suggestive of adrenal insufficiency, if neither 11-deoxycortisol nor ACTH rise it is highly suggestive of an impaired HPA axis at either the pituitary or hypothalamus.

This is used to diagnose Addision's and it is almost never used because why would you want to lower cortisol levels in someone you suspect having Addisons which could throw them into Addisonian crisis?

42

What three tumor types cause hypercalcemia due to PTHrP production?

Squamous (any site), breast, renal

43

What disorder is a primary (familial) cause of low HDL?

Tangier disease

autosomal recessive disorder that shows low cholesterol, normal to increased TG, absent HDL, and absence of Apo A1

Cholestrol esters deposit in the tonsils, lymph nodes, vasculature, and spleen

Corneal opacities develop

44

What patients lack HbA1C (need to keep in mind if you are testing for or monitoring diabetes)? What can you measure instead?

Pregnancy

Hemoglobinopathies where HgbA is absent (HbSS, CC, SC, etc)

Can measure fructosamine (glycosalated albumin)

*not actual fructose, the chemical structure just resembles

Splenectomy and Iron deficiency patients with have increased A1C

45

What tumor marker is not produced by Lewis negative patients because it is related to the Lewis antigen?

CA 19-9

46

What 2 tumor markers are different epitopes of the same antigen which is the protein product of the breast cancer associated MUC1 gene?

CA27.29 and CA15-3

both are elevated in 60-70% of women with advanced stage breast cancer and like CEA in colon cancer it is elevated in 25% of localized disease and 70% of advanced

These are also high in liver disease

47

What are 2 urine tumor markers that can be used to test for urothelial carcinoma?

  • NMP22 which detects a nuclear matrix protein called NuMA (nuclear mitotic appartus) that is released from the nuclei of tumor cells when they die
  • BTA (bladder tumor antigen test) detects complement factor H and complent factor H related proteins (CFH-rp) in the urine

These are best suited for ruling out recurrent low grade disease

48

What are the quad screen findings regarding hCG, inhibin, AFP and estriol in:

1) Down's

2) Trisomy 18

3) neural tube defects

1) INCREASED hCG and inhibin, DECREASED estriol and AFP

2) ALL DECREASED

3) INCREASED AFP, DECREASED estriol, NORMAL inhibin and hCG

49

What is the only marker of fetal lung maturity that is NOT affected by either meconium or blood?

Phosphatidylglycerol concentration

The caveat is that this is a late marker of maturity so it's utility in assessing maturity in premature babies is limited but it is still not affected by meconium or blood

*Meconium falsely decreases the L:S ratio

* lamellar body count is another test used and >50,000 indicates maturity but blood contamination decreases the count and meconium increases it

50

What two poisons cause "arteriolization of venous blood" (increased venous oxygen content)?

cyanide and hydrogen sulfide poisoning

51

What is the most reliable means of assessing arsenic levels in suspected poisoning?

Quantatative 24 hour urinary arsenic excretion

Blood arsenic levels are not reliable

 

52

1) What are the bone formation markers?

2) What are the bone resorption markers?

1) PINP, osteocalcin, and bone alkaline phosphatase

*relatively small circadian variability compared to bone resorption markers

2) CTX (C terminal telopeptide) and NTX

*substantial circadian variability

53

What over the counter medication is known to falsely elevate serum chromogranin A levels by stimulating its secretion?

Proton pump inhibitor

*kidney failure also falsely elevates chromogranin A levels

54

What is the D-xylose test and what does it evaluate?

Purpose is to differentiate enteric causes of malabsorption (ileal causes) from pancreatic causes (tumor, fibrosis and surgery)

Patient is given oral dose of D-xylose after an overnight fast and then it is measured in the urine.

If the etiology is pancreatic, the xylose levels will be elevated in the urine (passed from gut to urine ok because this sugar does not require pancreatic enzymes for absorption).

If cause is enteric, very little to no xylose will be absorbed and therefore little to no levels in urine.

Kidney disease will effect this test

55

What heavy metal poisoning can masquerade as a pheochromocytoma and why does it do this?

Mercury poisioning

It inhibits catechol-O-methyltransferase which is a major enzyme in the metabolism of catecholamines, resulting in hypertension, tachycardia and sweating so must do imaging and 24 hour catecholamine testing to determine etiology

56

What is the DeRitis ratio?

AST:ALT ratio

Usually <1 but may be >1 in alcohol abuse and cirrhosis

57

What organs normally have LD1 and LD2?

heart, red blood cells and kidneys

*SO FLIPPED LD ratio can be due to MI, hemolysis OR renal infarction

Normal LD ratios in blood: LD2>LD1>LD3>LD4>LD5

Normal LD ratios in CSF:  LD1>LD2>LD3>LD4>LD5

58

What organs normally have LD4 and LD5?

Liver and skeletal muscle

Normal LD ratios in blood: LD2>LD1>LD3>LD4>LD5

Normal LD ratios in CSF:  LD1>LD2>LD3>LD4>LD5

59

What organs normally have LD3?

Lung, spleen, lymphocytes and pancreas

Normal LD ratios in blood: LD2>LD1>LD3>LD4>LD5

Normal LD ratios in CSF:  LD1>LD2>LD3>LD4>LD5

60

What organs have concentrated alkaline phosphatase and what method can you use to tell them apart?

Especially concentrated in bone, liver, intestine and placenta

Current practice usually measure GGT or 5'nucleotidase to confirm hepatobiliary origin

Traditional methods:

Heat/urea inhibition = bone AlkPhos

L-phe inhibition = Placenta or Intestinal AlkPhos

61

What is the Regan isoenzyme?

Observed in a small proportion of people with malignant disease

Thought to be re-expression of placental alk phos gene in tumor cells

62

What is δ (delta) bilirubin?

Bilirubin covalently bound to albumin forming after prolonged hyperbilirubinemia; very slowly excreted

63

How is bilirubin measured?

Without an accelerator (alcohol), mainly conjugated bilirubin is measured (direct reaction)

Accelerators permit unconjugated bilirubin to react as well providing total bilirubin

Different between total and direct is unconjugated (indirect) bilirubin

64

What processes cause an unconjugated hyperbilirubinemia from excess conversion of heme?

Hemolysis (extravascular)

Ineffective hematopoiesis (intramedullary hemolysis)

Large hematoma (reabsorbed heme)

65

What processes cause an unconjugated hyperbilirubinemia from excess delivery of unconjugated bilirubin to liver?

Blood shunting (cirrhosis)

Right heart failure

66

What processes cause an unconjugated hyperbilirubinemia from poor uptake of unconjugated bilirubin into hepatocyte?

Gilbert's syndrome

Drugs, esp rifampin and probenacid

67

What processes cause an unconjugated hyperbilirubinemia from impaired conjugation of bilirubin in hepatocyte?

Crigler-Najjar syndrome

Deficiency of a conjugation enzyme UDP-glucuronsyl transferase 1A1 (UGT1A1)

Hypothyroidism

68

What processes cause a conjugated hyperbilirubinemia from impaired transmembrane secretion of conjugated bilirubin into canaliculus (hepatocellular jaundice)?

Hepatitis/hepatic injury

Endotoxin (sepsis)

Pregnancy (estrogen)

Drugs: estrogen, cyclosporine

Dubin-Johnson syndrome

Rotor syndrome

69

What processes cause a conjugated hyperbilirubinemia from impaired flow of conjugated bilirubin through canaliculi and bile ducts (cholestatic jaundice)?

Intrahepatic: PBC, medication, alcohol, pregnancy, sepsis

Extrahepatic: PSC, tumor, stricture, stone, AIDS choledochopathy

70

What defines pathologic neonatal jaundice?

May appear in the first 24 hours

May continue rising beyond 1 week of age 

Total bili exceeds 12 mg/dL

Rises quickly, with single day increases of >5 mg/dL

Conjugated (direct) bili exceeds 2 mg/dL

71

There are 3 main non-invasive tests to diagnose pancreatic exocrine dysfunction, how do they work and what is considered positive?

1) 72 hour fecal fat quantitation

2) Spot fecal fat

3) Stool elastase 1 and stool chymotrypsin

1) high fat diet for 6 days (3 days prior to test and 3 days during test); in exocrine deficiency, fecal fat often exceeds >20 g/day

2) sudan black staining of a random stool sample; considered positive when there are >6 droplets of fat per high power field

3) both are decreased in insufficiency

*Invasive testing involves collection of exocrine products after CCK is administered IV

72

What are the amylase, CEA and CA 19-9 levels in:

pseudocyst

increased amylase

normal CEA

increased CA 19-9

73

What are the amylase, CEA and CA 19-9 levels in:

serous cystadenoma

solid pseudopapillary tumor

ALL DECREASED IN BOTH

74

What are the amylase, CEA and CA 19-9 levels in:

MCN

normal amylase

increased CEA

increased CA 19-9

75

What are the amylase, CEA and CA 19-9 levels in:

IPMN

increased amylase

increased CEA

normal-to-increased CA 19-9

76

There are 3 main types of CK and 2 subtypes of CK. What are they, where are they found and how do they separate on electrophoresis?

CK1 (BB): fast migrating found primarily in BRAIN

CK2 (MB): found in skeletal mm (1% MB) and cardiac mm (30% MB)

CK3 (MM): found in skeletal mm (99%) and cardiac mm (70%)

Macro CK (macro CK type 1): migrates between MM and MB and may be found in healthy elderly women

Mitochondrial CK (macro CK type 2): slowest migrating and may be found in patients with advanced malignancy

77

Which is more stable, BNP or NT-proBNP?

NT-proBNP

it has a half life of 1-2 hours whereas BNP's half life is 20 minutes

78

What is bisalbuminemia?

A benign condition when someone has a variant albumin allele that results in two albumin spikes on electrophoresis

79

What are all the represented proteins on serum protein electrophoresis?

*I realize this is super broad question but I wanted a card to put a figure with the whole SPEP represented

80

On SPEP, if there is a spike in the alpha 2-beta interface, what is this from?

Usually empty but if there is a spike there, it is hemoglobin (hemolysis)

81

If there is a spike in the beta 1- beta 2 interface, what is this from?

LDL

82

What is carbohydrate deficient transferrin a marker of?

Alcohol use

83

How are cryoglobulines detected and what are the 3 types?

Detection: blood is drawn at 37C until clotted, then centrifuged at 37C. The serum is then placed at 4C for at least 3 days, then centrifuged at 4C. Any precipiate that forms is a cryoglobulin; the cryopreciptate can then be washed and subjected to electophoresis and immunofixation for characterization

Type I: monoclonal Igs associated with myeloma or Waldenstrom's

Type II: mixture of monoclonal IgM and polyclonal IgG; the IgM has rheumatoid factor activity (anti IgG); most common type of cryoglobulin

Type III: mixture of two polyclonal Igs, typically IgG and IgM; the IgM has rheumatoid factor activity

84

How does hyperglycemia affect sodium levels?

There is a true physiologic shift in sodium ions into the extracellular space, producing HYPOnatremia that is real but unrelated to any intrinsic defect in sodium homeostasis

The degree of change in sodium conc attributable to glucose can be calculated by:

1.6 x (serum glucose - 100) / 100

Hypertonic (>295 mOsm/kg) hyponatremia suggests marked hyperglycemia but may also be seen in patients given mannitol in order to reduce ICP

85

How does renal tubular acidosis affect potassium levels?

Nearly all cases of RTA cause HYPERkalemia

The main exception is Type I and II where the potassium is LOW

*RTA Type I also shows HYPOnatremia

86

What electrolyte can be low with a large villous adenoma of the GI tract?

Potassium

87

What happens to potassium levels in DKA?

There is an initial HYPERkalemia (as in most acidotic states) but correction of DKA results in profound hypokalemia and supplementation must be given

88

How is calcium affected by acidotic and alkalotic states?

Acidosis DECREASES the binding of calcium to albumin so free calcium will INCREASE but total is normal

Alkalosis INCREASES the binding of calcium to albumin so free calcium will DECREASE but total is normal

*with decreased albumin, TOTAL calcium is decreased while free calcium is normal

89

What urinary marker is increased in hyperparathyroidism (other than phosphate)?

Urinary cAMP

90

What is tertiary hyperparathyroidism?

After long periods of secondary hyperparathyroidism, autonomous parathyroid function may develop

Seen in post renal transplant

91

What malignancies are associated with hypercalcemia secondary to PTH related protein (PTHrP)?

SCC

Myeloma

Breast CA

Islet cell tumors

Paraganglioma

RCC

HCC

T-ALL

Small cell of ovary (hypercalcemic type)

92

What gene is responsible for familial hypocalciuric hypercalcemia?

CASR gene on 3q

93

What electrolyte is affected in:

1) Hypothyroidism

2) Hyperthyroidism

1) Hyponatremia

2) Hypercalcemia

94

What are the two biologically active forms of PTH?

Intact PTH and N-terminal PTH (short half lives; 5 min)

Non active types: Mid-region PTH and C-terminal PTH (long half lives; 36 hours)

95

What are the ECG findings with low and high calcium levels?

Hypercalcemia: Peaked T waves

Hypocalcemia: Lengthening of QT interval and low voltage T waves

96

What is magnesium's affect on PTH levels?

Prolonged or marked hypomagnesemia is capable of suppressing PTH secretion

Mild transient hypomagnesemia may actually cause increased PTH secretion

97

What is an easy way to remember what type of acid base disturbance is present?

In metabolic acidosis/alkalosis: pH and bicarb go in same direction

In respiratory acidosis/alkalosis: pH and bicarb go in opposite directions

 

98

What are the causes of increased osmol gap WITH metabolic acidosis?

Methanol

Propylene glycol

Ethylene glycol

Paraldehyde

Ethanol (sometimes)

99

What are the causes of increased osmol gap WITHOUT metabolic acidosis?

Isopropanol

Glycerol

Sorbitol

Mannitol

Acetone

Ethanol (sometimes)

100

What substance is freely filtered by the glomerulus and completely reabsorbed by the proximal tubule and is a strong predictor of cardiovascular mortality in patients with chronic renal disease?

Cystatin C

101

What is the definition of significant proteinuria?

>300 mg/day

102

What is the definition of chronic kidney disease?

GFR <60

Stage 1: albuminuria without decreased GFR (>90)

Stage 2: albuminuria with a mild decrease in GFR (60-89)

Stage 3: moderate decrease in GFR (30-59)

Stage 4: severe decrease in GFR (15-29)

Stage 5: renal failure (<15)

103

What are the lab parameters seen in prerenal azotemia?

BUN:Cr >20:1

High urine specific gravity and osmolarity

FE Na <1%

FE urea <35%

104

What are the lab parameters in renal azotemia?

BUN:Cr <20:1

Low urine specific gravity and osmolarity

FE Na >1%

FE urea >35%

105

Describe:

1) quad screen

2) 1st trimester test

3) serum integrated screen

4) sequential screen

1) Performed at 18 weeks and measures hCG, AFP, estriol and inhibin A (sensitivity for Downs syndrome is 78%)

2) Performed at 10-13 weeks and measures hCG, plasma associated protein A (PAPP-A) and nuchal fold translucency. When combined with maternal age, overall sensitivity is 83%

Downs will have DECREASED PAPP-A, INCREASED hCG and INCREASED nuchal translucency

3) combines the above two and when combined with maternal age and nuchal fold thickness, overal sensitivity is 88%

4) risk is initially based on 1st trimester results if high and if these results do not indicate high risk, then the risk is reported based on the integrated results

106

What are the physiologic changes (lab wise) in pregnancy?

Estrogen causes increase in TBG (so increased T3 and T4)

Relative insulin resistance in early 3rd trimester from hPL which has antiinsulin effects similar to growth hormone

LABS INCREASED: fibrinogen, trigylcerides and urine protein (doubles)

LABS DECREASED: albumin, total calcium, creatinine, BUN, Hct and Hgb (dilutional)

107

What are the metabolites of:

1) ethylene glycol

2) isopropanol

3) methanol

1) oxalate and glycolate

2) acteone

3) formate and formaldehyde

108

What key enzymes does lead inhibit and hence responsible for its toxicity?

delta-ALA-dehydratase and ferrochelatase

leading to the accumulation of the precursor protoporphyrin (free erythrocyte protoporphyrin or FEP) which binds to available zinc, yielding zinc protoporphyrin (ZPP)

Both FEP and ZPP are increased in lead toxicity (and in iron deficiency)

*inhibits sodium channel ATPase leading to increased osmotic fragility and shortened red cell survivial

Basophilic stippling results from inhibition of 5'nucelotidase, an enzyme whose function is to break down RNA

109

What is the mechanism of cyanide poisoning?

Inhibits cytochrome 3a thus uncoupling the elctron transport system

causes severe lactic acidosis and oxygen deposition in the blood (hence cherry red color)

Cyanide is rapidly metabolized to thiocyanate (test for this)

Treatment: sodium nitrite and amyl nitrite which forms methemaglobin which while bind available cyanide in addition to sodium thiosulfate which will rapid convert cyanide to thiocyanate

110

How is the mortality risk of salicylate poisoning determined?

6 hour plasma salicylate concentration >130 mg/dL have a high fatality rate

111

What is the mechanism for arsenic toxicity and how is this tested?

Inhibits oxidative production of ATP

Most reliable test is a quantitative 24 hour urine arsenic excretion; blood arsenic level is HIGHLY unreliable

112

Poisoning with what substance is responsible for acrodynia and erethism and what is this?

Mercury

Acrodynia (Feer syndrome): autonomic manifestations (sweating, hemodynamic instability) and a desquamative erythematous rash on the plams and soles

Erethism: personality changes, irritability and fine motor disturbances

Test by measuring 24 hour urine collection for elemental mercury; whole blood or hair analysis for organic

113

What is the most common form of primary hypercholesterolemia and what are the causes of secondary?

Familial hypercholesterolemia (Type IIa) which is an AD deficiency of LDL receptors or LDL recepor activity

Secondary: hypothyroidism, diabetes, nephotic syndrome, cholestasis, cyclosporine, thiazide diuretics or loop diuretics

114

In terms of lipids, what is the vehicle for transport into the bloodstreem and what is the vehicle for transport into somatic cells?

Ingested lipids are internalized by small bowel enterocytes and packaged into chylomicrons which transports lipid from enterocytes to hepatocytes into which they are endocytosed via apoE

In liver, cholesterol and TG undergo additional metabolism before being packaged into VLDL which is the vehicle for transport into blood

In blood, TG in VLDL undergoes progressive hydrolysis by the endothelium bound lipoprotein lipase producing IDL and eventually LDL

LDL is the main vehicle for transporting cholesterol from the blood to somatic cells where LDL undergoes endocytosis mediated by LDL receptor and ApoB100

115

MANY chemistry assays are linked to detection of the conversion of NAD to NADPH. What wavelength does this happen?

*according to ASCP lecture, if you see wavelength on boards just pick this answer because so many things use it!

340nm

116

What is Whipple's triad?

Insulinomas typically present with this triad:

hypoglycemic symptoms

plasma glucose <45

relief of symptoms with glucose administration

117

What is the diagnostic criteria for gestational diabetes following a 75g oral glucose tolerance test?

Fasting: > 95 mg/dL

1 hour: > 180 mg/dL

2 hour: > 153 mg/dL

118

What are some causes of false positive and false negative results on a fecal occult (guiac) test?

False positive: NSAID use, consumption of heme (in meat), consumption of peroxidase (turnips and horseradish)

False negative: excessive vitamin C consumption

119

What variant of AFP is more specific for HCC and is more associated with aggressive forms?

L3 variant of AFP

120

What markers are elevated in neuroblastoma?

Urine vanillylmandelic acid (VMA) and homovallillic acid (HMA)

HVA is the final metabolic product of dopamine while VMA is the final product of norepinephrine and epinephrine

Neuron specific enolase, LDH and ferritin are nonspecific markers that be be used to follow disease activity

121

What are the antibodies seen in:

1) Grave's disease

2) Hashimoto's

1) thyroid stimulating Abs (TSI) aka long acting thyroid stimulating Abs (LATS)

Antimicrosomal Abs found in 60% and anithyroglobulin Abs in 30%

2) antitissue peroxidase and antithyroglobulin Abs (>90%)

TSI not seen in Hash

 

122

What are TSH levels in hypothyroidism due to pituitary disease?

You would think they are decreased but actually they are normal-to-high because of production of a messed up version of TSH which doesn't work but we measure it

123

What are the lab values seen in euthyroid sick syndrome?

This is abnormal thyroid function tests in a euthyroid patient suffering from a nonthyroidal illness

Acutely: Normal T4 and TSH, decreased T3 and increased rT3

Chronically: decreased T3 and T4, normal TSH, increased rT3

INCREASED rT3 is the key! If you see this, think euthyroid sick sydrome!

124

What is amiodarone's effect on the thyroid?

Amiodarone is largely unpredictable but a general rule of thumb is in developed (iodine rich) parts of the world it causes HYPOthyroidism and in underdeveloped (iodine poor) places it causes HYPERthyroidism

125

What are the manifestations and lab values of congenital adrenal hyperplasia?

21-hydroxylase (MC) and 11 hydroxylase (2nd MC) deficiency

Gene for 21-hydroxylase is found on 6p21.3 within the HLA complex

21 hydroxylase: Affected patients have increased 17-hydroxyprogesterone, decreased cortisol, increased ACTH, increased androgens, increased 17-ketosteroids and decreased aldosterone and elevated urinary pregnanetriol

11 hydroxylase: elevated serum 11-deoxycortisol and deoxycorticosterone

21: virilization, salt wasting

11: virilization and hypertension

*remember if there is a 1 as the second number, there is virilization and if there is a 1 as the first number there is hypertension

126

What lab value confirms GH hypersecretion?

IGF-1 consistently elevated in hypersecretion

Normal IGF-1 excludes GH excess

127

With hypothalamus stimulation, how is prolactin different from the other pituitary hormones and how is it effected when there is severed connection between the hypothalamus and pituitary?

Prolactin is unique in that is does not have a dedicated stimulator for its release; the hypothalmus produces a potent INHIBITOR (dopamine)

If connections between the hypothalamus and pituitary are severed, ALL anterior pituitary hormones decrease (due to lack of stimulation) except prolaction which markedly increases due to lack of inhibition

128

SIADH is caused by many tumors but what drug causes it?

small cell CA of lung, pancreatic adenoCA and intracranial tumors 

interstitial lung disease and cerebral trauma

CHLORPROPAMIDE (a drug in the sulfonylurea class used to treat type 2 diabetes)

129

What causes browish black urine?

Alkaptonuria

Metemoglobinuria

130

What causes blue/green urine?

Pseudomonas infection

131

What inhibits several urine dipstick tests including glucose, hemoglobin, bilirubin, nitrite and leukocyte esterase?

Ascorbate

132

What is the copper sulfate method (Benedict reaction)?

This is a urine test for glycosuria (glucose) that underlies the Clinitest procedure

It detects all reducing substances (substances that will reduce copper salts) including glucose, lactose, fructose, galactose and pentose

133

What two things are possible false positive sources of leukocyte esterase?

Trichomonas and eosinophils

134

What is the normal pH of urine?

6.0

In renal tubular acidosis, the urine is inappropriately alkaline relative to the pH of blood and the kidneys cannot acidify the urine beyond 6.5

135

Oxaluria is increased in what two conditions?

Patients with Crohn's disease who have undergone small bowel resection or small bowel bypass

Patients who ingest excessive amounts of oxalate (rhubarbs, spinach and nuts)

136

What crystals are seen in:

1) acidic urine

2) alkaline urine

1) triple phosphate (struvite) and calcium

2) urate

137

What type of cast is seen in this urine?

Hyaline cast

relatively nonspecific

renal disease, dehydration, heat related trauma or vigorous exercise

138

What type of cast is seen in this urine?

Red cell cast

specific for glomerulonephritis

139

What type of cast is seen in this urine?

White cell cast

typical of tubulointerstitial nephritis particularly pyelonephritis

140

What type of cast is seen in this urine?

Tubular cast

indicate ATN

141

What type of cast is seen in this urine?

granular cast

nonspecific

renal disease, dehydration, heat related trauma or vigorous exercise

142

What type of cast is seen in this urine?

waxy cast

severe renal disease

143

What type of cast is seen in this urine?

Broad cast

hyaline, granular or waxy casts that are unusually broad and indicated end stage renal disease corresponding to widely dilated collecting ducts in advanced atrophy

144

What type of cast is seen in this urine?

Fatty cast

maltese cross when polarized

indicate nephrotic syndrome

145

What lab value is used to assess the integrity of the blood brain barrier?

Albumin

When intact, the CSF:serum albumin ratio is >1:230

146

What test is more sensitive and specific for detecting oligoclonal bands in MS compared to electrophoresis?

Isoelectric focusing (IEF)

90% sensitivity and 95% specificity

147

What type of viral meningitis characteristically has decreased CSF glucose (which is unusual for viruses)?

HSV encephalitis

148

What are the leukocyte count, protein levels, leukocyte type and glucose levels in the CSF with:

1) bacterial meningitis

2) viral meningitis

3) fungal and mycobacterial meningitis

1) Bacterial: leukocyte count 1,000 to 10,000, protein >100, polys predominate, glucose <40

2) Viral: leukocyte count 50-500, protein 20-100, polys early and lymphs late, glucose normal

3) Fungal and mycobacterial: leukocyte count 50-500, protein 20-100, lymphs predominate, glucose <50

149

What lab value is elevated in tuberculosis pleural effusion?

Adenosine deaminase (ADA)

TB causes an overwhelming lymphocytic effusion with very few mesothelial cells present

150

What is the difference between a chylous effusion and a pseudochylous effusion?

Chylous: caused by lymphatic obstruction caused by malignancy (lymphoma and bronchgenic CA), trauma, surgery, infection, sarcoidosis, and LAM of the lung

milky, lymphocytes and TG > 110 wtih chylomicrons by electrophoresis

Pseudochylous: gradual accumulation of lipids from cellular breakdown in conditions such as TB, rheumatoid pleural effusions and myxedema

milky, mixed leukocytes and cholesterol crystals, TGs <50 and no chylomicrons on electrophoresis

151

What is the serum ascites gradient used to evaluate?

Distinguishing portal hypertension related ascites from others

this is the difference between albumin measured in serum and that measured in ascited fluid

in portal HTN, the gradient is >1.1 g/dL

152

What are the crystals in gout and pseudogout and how do they polarize?

Gout: monosodium urate, needle shaped and have NEGATIVE birefringence (means yeLLow when paraLLel and blue when perpendicular)

Pseudogout: calcium pyrophosphate, rods or rhomboid shape and have POSITIVE birefringence (yellow when perpendicular and blue when parallel)

153

In evaluating myocardial infarction, when do troponin I and CKMB appear and dissapear?

Troponin I or T: Appears in 4-8 hours, peaks at 1-2 days, and may remain elevated for 7-10 days
CKMB: Appears in serum in 4-8 hours, peaks at 18-24 hours, declines to baseline over 48-72 hours

154

What is the most active form of Vit D?

 1,25(OH)D is the most active form

Vit D increases calcium and phosphate

155

What tissue has the highest concentration of AST?

Cardiac mm

then liver, skeletal mm, kidney and brain in decreasing order

156

What percentage of calcium is bound to albumin?

50%

157

Most pituitary hormones have a shared alpha unit and unique beta subunit except?

ACTH

158

Poisoning by what agent leads to an elevated lactate, increased serum glucose, and decreased arterial venous oxygen gap?

Cyanide

Having a normal serum lactate almost definitively excludes cyanide poisoning

159

What substance is not directly measured and is instead estimated in the Friedwald equation by dividing TG by 5?

VLDL

160

Do right or left sided colon cancers have higher levels of CEA?

Left sided

161

What test provides the best evidence for death caused by anaphylaxis?

serum beta tryptase

162

What is the correct order of drawing blood tubes?

1) blood cultures 2) plain tubes 3) citrate tubes 4) other
additives (e.g. EDTA)
-Not infrequently, if proper order of draw is not followed, contamination of next tube with purple top additive (potassium EDTA) leads to:
– Markedly increased potassium
– Decreased Ca2+, Mg2+ (chelated by EDTA), decreased enzyme activity for enzymes requiring cations (alkaline phosphatase, creatine kinase)

163

What are the consequences of prolonged storage of blood samples at room temp?

– Factor VIII degraded -> increased PTT (non-heparin
containing specimens)
– Platelets release platelet factor 4 (PF4) which neutralizes
heparin -->decreases PTT (heparin containing specimens)
– Plain tubes (red top) --> increased potassium (cellular leak)
– Increased phosphorus (cellular leak)
– Increased ammonia (protein breakdown)
– Glucose falls 3-5% per hour at room temperature (glycolysis)

164

What are the consequences of increased storage of blood samples at 4C?

– Increased potassium (Na-K pump inhibited)
– Factor VII activated -> shortens PT

165

What is the relationship between platelets and postassium?

Platelets release potassium when clotting occurs
– Serum K > plasma K
– Thrombocytosis can lead to increased serum Ks
(~0.1 mmol/L for each 100K of platelets)

166

What is a widely used inexpensive test for albumin (not electrophoresis)?

Dye Binding

– Widely used, inexpensive, and easy to automate
– Albumin binds to dye, causing shift in dye’s
absorbance
– Bromocresol green (BCG) and bromocresol purple
(BCP)
– BCP more accurate for low albumin levels (<2.0)

167

What are the lab findings in Wilson's disease?

Exhibit low serum CER (<10 mg/dl).
Measurement: Immunoassay. However, this test is not
specific (poor liver function, nephrotic syndrome can also lead to reduced levels)
Low plasma copper: Due to low CER
Elevated urine copper: Due to increase in filterable

168

What can cause a false positive for PCP on urine drug screen?

dextromethorphan

169

What is the most reliable indicator for evidence of rape by an aspermic male?

Acid Phosphatase

170

What is iodine-131-labeled albumin used to determine?

Plasma volume

171

BQ! Why does the immunoassay for quinidine report a higher value than HPLC?

HPLC will separate out the metabolites while the immunoassay will count them all as quinidine.