Chemistry Flashcards
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
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
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)
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
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
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
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)
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
What does it mean if you see a bimodal albumin peak on SPEP?
This is seen in heterozygotes for albumin alleles
No clinical significance
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)
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
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
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
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!
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
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
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
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
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
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)
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
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
What are the positive acute phase reactants?
C3, CRP
A1AT, A2M
Ceruloplasmin
Fibrinogen
Haptoglobin
What are the negative acute phase reactant?
Albumin
Transthyretin
Retinol binding protein (RBP)
Transferrin
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
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
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
What are reasons for increased albumin on SPEP?
Dehydration
Diabetes insipidus
Prolonged tourniquet time
What proteins are represented by the beta region on SPEP?
Transferrin (beta 1)
LDL (beta 1-beta 2 interface)
IgA and C3 (beta 2)
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
BQ! What states cause a LOW anion gap?
low albumin +/or high Ig’s (myeloma, AIDS, cirrhosis)
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
What are the causes of anion gap metabolic acidosis?
“DUMPSALE”
Diabetic ketoacidosis
Uremia
Methanol
Paraldehyde
Salicylates
Alcoholic ketoacidosis
Lactic acidosis
Ethylene Glycol
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
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.
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
What clinical scenario would give you this pattern on urine protein electrophoresis?
Overflow proteinuria: M-spike
- often IgL - sometimes: intact Ig
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
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!
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
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?
What three tumor types cause hypercalcemia due to PTHrP production?
Squamous (any site), breast, renal
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
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
What tumor marker is not produced by Lewis negative patients because it is related to the Lewis antigen?
CA 19-9
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
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
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
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
What two poisons cause “arteriolization of venous blood” (increased venous oxygen content)?
cyanide and hydrogen sulfide poisoning
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
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
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
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
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
What is the DeRitis ratio?
AST:ALT ratio
Usually <1 but may be >1 in alcohol abuse and cirrhosis
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
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
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
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
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
What is δ (delta) bilirubin?
Bilirubin covalently bound to albumin forming after prolonged hyperbilirubinemia; very slowly excreted
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
What processes cause an unconjugated hyperbilirubinemia from excess conversion of heme?
Hemolysis (extravascular)
Ineffective hematopoiesis (intramedullary hemolysis)
Large hematoma (reabsorbed heme)
What processes cause an unconjugated hyperbilirubinemia from excess delivery of unconjugated bilirubin to liver?
Blood shunting (cirrhosis)
Right heart failure
What processes cause an unconjugated hyperbilirubinemia from poor uptake of unconjugated bilirubin into hepatocyte?
Gilbert’s syndrome
Drugs, esp rifampin and probenacid
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
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
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
What is bisalbuminemia?
A benign condition when someone has a variant albumin allele that results in two albumin spikes on electrophoresis
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
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
What type of cast is seen in this urine?
Hyaline cast
relatively nonspecific
renal disease, dehydration, heat related trauma or vigorous exercise
What type of cast is seen in this urine?
Red cell cast
specific for glomerulonephritis
What type of cast is seen in this urine?
White cell cast
typical of tubulointerstitial nephritis particularly pyelonephritis
What type of cast is seen in this urine?
Tubular cast
indicate ATN
What type of cast is seen in this urine?
granular cast
nonspecific
renal disease, dehydration, heat related trauma or vigorous exercise
What type of cast is seen in this urine?
waxy cast
severe renal disease
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
What type of cast is seen in this urine?
Fatty cast
maltese cross when polarized
indicate nephrotic syndrome
