Chemistry Flashcards
Anion gap calculation
Na - Cl - HCO3
Should not exceed 12 normally
Osmotic gap calculation
2Na + BUN/3 + Glucose/20
Should not exceed 10 normally
Ketones in DKA
About 80% are beta-hydroxybutyrate, which is not detected by nitroprusside technique. Converted to acetoacetate/acetone which are detected (may have transient increase with treatment)
Causes of anion-gap metabolic acidosis
Methanol Uremia Diabetic ketoacidosis Propylene glycol Isoniazid Lactate Ethanol Salicylates
Causes of non-anion-gap metabolic acidosis
Bicarbonate losses (diarrhea, renal tubular acidosis)
Water distribution
TBW is 60% water
2/3 of water is intracellular, 1/3 is extracellular
1/4 of extracellular water is intravascular (1/12 overall)
Pseudohyponatremia
Spurious hyponatremia seen on indirect ISE methods where an assumed 93% water content is incorrect in the settings of patient hyperlipidemia or paraproteinemia.
FENa
(Urine sodium * Plasma creatinine) / (Urine creatinine * plasma sodium)
If low (1%), reabsorption is functional.
Causes of hypernatremia
Almost always dehydration or diabetes insipidus
Causes of hyponatremia
Overhydration, SIADH
Wasting states (nephrotic syndrome, cirrhosis)
Pseudohyperkalemia
Can be caused by hemolysis, collection into EDTA tube, clenching during phlebotomy or small needles.
Causes of ture hyperkalemia
Hypoaldosteronism
Renal tubular acidosis
Renal failure
CEA
Nonspecific family of surface glycoproteins expressed in many cancers (GI). Can be used for monitoring, not screening or diagnosis.
May transiently increase during chemotherapy. Higher in smokers.
AFP
First expressed in yolk sac, then fetal liver (12wk).
Expressed in many tumors, but L3 variant is somewhat specific for HCC.
Can also be elevated in regenerative states, but very high levels suggest tumor.
PSA
Prostatic specific antigen. Binds alpha-2-macroglobulin and alpha-1-antichymotrypsin
Levels of 4-10 are gray; look at free or pro-PSA levels (low % suggest cancer)
CA15-3
CA19-9
CA125
CA15-3: Breast (MUC1, also CA27.29)
CA19-9: Lewis A, pancreatic cancer. Can be elevated in cholestasis.
CA125: Ovarian epithelial tumors (except mucinous)
Whipple triad
Glucose <45mg/dL, symptoms of hypoglycemia, reversal with glucose administration
DM diagnostic criteria
- Symptoms
2. Either fasting glucose > 126, random >200, 75g OGTT >200, or A1C > 6.5%,
Detection of diabetes in hemoglobinopathies
Cannot rely on A1C due to shortened RBC lifespan. Look at FRUCTOSAMINE
Microalbuminuria
Predicts diabetic nephropathy. Precedes decline in GFR.
Start checking annually after T2DM diagnosis, or +5yrs for T1DM.
Creatinine clearance
Urine volume * urine creatinine [] / plasma creatinine
MDRD formula
Calculates eGFR from Creatinine while considering age, gender, and ethnicity
T3RU test
Measures TBG by incubating patient serum and radiolabeled T3 with a resin.
Circulating thyroglobulin
Can be used as a marker of residual disease in thyroid cancer (PTC, FTC)
So too can anti-thyroglobulin antibodies, which are sometimes seen.
What causes increases or decreases in TBG?
Increases: Estrogen (pregnancy)
Decreases: Cirrhosis, nephrotic syndrome…
Note that TBG does not strongly affect free T3/T4 levels.
Thyroid hormone potencies
T3 > T4 > rT3 (inactivated)
Diurnal pituitary hormones
CRH/ACTH highest upon waking
GH/GHRH highest upon sleeping
Diagnosis of hypercortisolism
Screen with urine free cortisol (24hr) or 1mg overnight suppression
Confirm with LOW-DOSE dexamethasone suppression test
Identify secondary hypercortisolism with ACTH level, HIGH-DOSE dexamethasone suppression
Diagnosis of adrenal insufficiency
Urine free cortisol
Cosyntropin test
Metyrapone
Blocker of 11-hydroxylase, prevents cortisol production
Aldosterone testing
Aldosterone:renin ratio >10 suggests hyperaldosteronism
Lateralize with petrosal sinus sampling
Plasma and urine catecholamine metabolites…
Pheochromocytoma: Check urinary fractionated catecholamines or plasma metanephrines
Neuroblastoma: Check urine HMA/VMA levels
Note: 5-HIAA is derived from serotonin, levels elevated in carcinoid syndrome
Prolactin signaling
Inhibited by dopamine from hypothalamus. May be the only normal hormone in panhypopituitarism.
Can be promoted by HYPOTHYROIDISM.
High-molecular weight forms may be specific for prolactinoma.
Bilirubin lab analysis
Direct bilirubin: Diazo method, does not use any accelerants (only detects conjugated)
Total bilirubin: Diazo method, uses caffeine or methanol to detect all.
Gilbert’s disease
UGT1A1 mutation resulting in mildly reduced bilirubin conjugation. Flares with illness, benign.
Reduced metabolism of IRINOTECAN
Dubin-Johnson
Mutation of organic anion transporter. Results in direct hyperbilirubinemia and pigmentation of organs
Liver enzymes
AST: Nonspecific, also see in skeletal and cardiac muscle (elevated in exercise)
ALT: More specific for liver
GGT: Cholestatic marker, fairly specific
LDH: Non-specific, fast clearing
Liver autoantibodies
AMA - PBC, especially PDC-M3 variant ASMA - Type 1 AIH Anti-LKM - Type 2 AIH Anti-soluble liver antigen - Type 3 AIH pANCA - PSC
Wilson’s disease
ATP7B transporter defect with resultant tissue accumulation of copper.
When not active/fulminant, low ceruloplasmin & copper. Otherwise note hemolysis
Hereditary hemochromatosis
XXXXXX
DeRitis Ratio
AST:ALT
Normally ALT > AST, but in alcohol, Wilson, cirrhosis, the ratio is reversed
Lactate dehydrogenase fractions
Normally LD2 > LD1 (both very common).
LD1 elevation / flipped ratio can be seen in acute infarctions or hemolysis.
Alkaline phosphatase
Many isoenzymes, can be distinguished by electrophoresis or heat inactivation
“Bone burns, liver lingers”.
Regan isozyme - Placenta, tumors
Biliprotein
Bilirubin + albumin; accumulates in cholestatic states and takes days to clear.
Amylase
Elevated in pancreatitis, sialadenitis (lipase normal), macroamylasemia (spurious complex)
Less specific than lipase.
Needs calcium as a chelator, do not draw in blue/lavender tops.
D-xylose test
Measures gut absorptive capacity (not pancreatic exocrine function)
Fecal elastase
Superior to fat analysis or fecal chymotrypsin to assess pancreatic exocrine function
Must be performed on well-formed stools.
Troponins
Complex consists of cardiac troponins C (calcium), I, T (tropomyosin).
C: Same in cardiac and skeletal
I: Specific.
T: Specific.
CK-MB, myoglobin
CK-MB: Outdated MI marker.
Myoglobin: Totally nonspecific, but fast to rise and fast to fall.
NT-proBNP
Superior to biologically active BNP or ANP. Reflects systolic (not diastolic dysfunction)
MI diagnosis
Troponin >99th percentile
One of: Symptoms, EKG abnormality, or wall motion abnormality
ACE
Can be elevated in sarcoidosis
Macro CK Mitochondrial CK (macro CK type 2)
Macro CK: Immunoglobulin complex seen in some elderly women
Mitochondrial CK: SUggestive of some advanced malignancies.
hsCRP
Predictor for development of acute coronary syndrome
JUPITER study
Cryoglobulinemias
Type I: Monoclonal only; associated with lymphoproliferative disorders
Type II: Monoclonal and polyclonal component; associated with HCV
Type III: Polyclonal only; associated with autoimmune disorders
Calcium assay
Colorimetric assay
Ionized assay
Urinary CAMP
Increased in hyperparathyroidism
Forms of parathyroid hormone
Intact - Active, short-lived
N-terminal - Active, short-lived
C-terminal - Inactive, long-lived
Co-oximetry
Uses 4 wavelengths of light
Distinguishes oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, methemoglobin
Does not detect sulfhemoglobin
FSH/LH secretion
Responds to continuous GNRH secretion (continuous inhibits)
Surge in ovulation. Estrogen predominates in follicular phase, progesterone in luteal phase.
Estrogens
E1: Estrone, mostly post-menopausal
E2: Estradiol, most potent
E3: Estriol, placental/pregnancy
AMH
Produced by granulosa cells, marker of ovarian reserve. Elevated in PCOS due to failure of selection of a dominant follicle.
hCG in pregnancy
Doubles every two days (if normal intrauterine)
Peaks at end of third trimester, holds through pregnancy
Takes 2 weeks postpartum to clear
*Hyperglycosylated form predominates in early pregnancy
First trimester screen
hCG, PAPP-A, nuchal thickness.
For down syndrome.
Quad screen
hCG / Inhibin / Estriol / AFP
t21: + / + / - / -
t18: - / - / - / -
NT defect: AFP elevated
MSAFP
If >2.5 MoM, high risk of birth defects.
LOW in t21!
Markers of fetal lung maturity
LS ratio of 2.5:1 (less lecithin suggests immaturity)
PG concentration
Lamellar body count (more = mature)
Pregnancy marker changes
eGFR increases»_space; lower creatinine, BUN. Proteinuria, glucosuria
Increased fibrinogen, (relatively) decreased albumin
Dilutional anemia despite increase in red cell mass
Lipoprotein compositions
Chylomicrons: Triglycerides.
VLDL: Triglycerides.
LDL: Cholesterol, Apo-B100
HDL: Cholesterol, Apo-A
Friedewald calculations
VLDL is estimated as TG/5.
LDLc = TC - HDL - VLDL
Abetalipoproteinemia
Low triglycerides and low cholesterol.
ACANTHOCYTES on peripheral smear.
Developmental delay, fat malabsorption…
Frederickson phenotypes of hyperlipidemias
I - Hyperchylomicronemia (TGs, LPL or ApoC2 def)
II - A (LDL), B (VLDL, LDL)
III - ApoE2/E2
IV - VLDL, associated with insulin receptor mutations and lipodystrophy
V - Chylomicrons, VLDL
LPL effect
LCAT effect
CETP effect
LPL: Hydrolyzes VLDL to form IDL/LDL
LCAT: Transfers lipids to HDL
CETP: Exchanges lipids between HDL and lower density particles
Tangier disease
Autosomal recessive disorder of absent HDL.
ATP III recommended targets
TC: <200
LDL: Optimal <100, near optimal 100-129, borderline 130-159
HDL: <40 low, >60 high
GDM testing
2-step: 50g OGTT (target X), then 100g OGTT (target Y
1-step: 75g OGTT (target 180, 153 at 1, 2 hours)
Fecal occult blood testing
Guaiac based testing prone to false-positives (NSAIDs, red meat, peroxidase (horseradish)) and false-negatives (Vitamin C consumption)
Immunochemical based methods are less affected.
Euthyroid sick syndrome
Low T3, T4
Elevated rT3?
Nomral TSH.
Just peripheral inactivation of thyroid hormone. Thyroid function is normal.
T3RU
Measures available binding sites on thyroid binding globulins.
Mix patient sample with radioactive iodine (binds available sites), then resin-adsorb and see how much radioactive iodine remains.
High residual levels means few binding sites (hyperthyroidism). Low residual levels in hypothyroidism.
High-dose dexamethasone suppression
Distinguishes pituitary corticotroph adenoma (Cushing disease) which should suppress from ectopic ACTH production (does not suppress).
Granulosa cells - Hormonal profile
Secretes both steroid hormones (testosterone, estrogen, etc) and peptide hormones (AMH, inhibin).
May have elevated AFP serum levels (not CA-125!)
Confirmatory test for Conn syndrome
Isotonic large volume saline infusion»_space; failure to suppress aldosterone
Gestational thyrotoxicosis
Elevated bHCG levels cross-react on TSH receptor. Should co-occur with hyperemesis gravidarum
CTX, NTX
Bone resorption markers.
High variability according to diet, circadian rhythm
Pseudohypoparathyroidism
Peripheral resistance to PTH.
Associated with GNAS (McCune-Albright)
Apt test
Distinguishes fetal hemoglobin from adult; fetal hemolysate resists denaturing in 1% NaOH
IBD serologies
Crohn’s: Anti-saccharomyces cerevisiae (ASCA)
UC: pANCA (as in PSC)
Schilling test
Test for failure of B12 absorption. Give oral load of radiolabeled B12, inject non-radiolabeled. Measure urine.
Done in stages with progressive replacement of IF, pancreatic enzymes
Celiac serology
TTG is best test for diagnosis
Anti-endomysial IgA (EMA) may disappear after diet improvements
Carbohydrate-deficient transferrin
Old, shitty test for alcohol abuse
Non-HBV hepatitis serologies
Anti-HAV: Total for screen, IgM for confirm
Anti-HCV: IgG only (no IgM)
Hyperviscosity
Falsely depresses most assays/analytes
Timing of cardiac biomarkers
Myoglobin rises and falls first
CK-MB and troponins all have similar timing (detectable in 4-6 hrs, peak in 10-24hrs)
Skin sweat chloride test
Gold standard for CF diagnosis.
Performed using coulometric titration
Grey-tops
Contains sodium fluoride to halt in-tube glycolysis. For glucose measurements.
Jaffe reaction
Detects creatinine by forming a chromogen (alkaline picrate). Affected by interfering substances ~520nm.
Convert urea to BUN
Divide by molar ratio of nitrogen to urea molar weight– 60/28, or divide by 2.14.
Pseudohypokalemia
Can be seen in some leukemic specimens; cells (especially blasts) may take up extracellular potassium
Fatty- acid oxidation defects
Usually present with hypoglycemia and low ketones (cannot mobilize fat stores)
Most common urea cycle defects
Most common organic acidemias
Urea cycle: Ornithine transcarbamylase deficiency (X-linked recessive)
Organic acidemias: Methylmalonic, priopionic acidemias
Transient hyperkalemias
Exercise
Shift to upright positioning (third-spacing of free water)
Familial hyperkalemia
Familial hypocalciuric hypocalcemia
FH: Autosomal dominant defect of RBC membrane»_space; leakage in storage
FHH: Benign condition of decreased urine calcium excretion»_space; as name suggests
RTAs
Type 1: Distal. Poor hydrogen excretion means urine cannot acidify. Alkaline urine. Hyperchloremic.
Type 2: Proximal. Failure to reabsorb bicarb, but distal compensation can acidify urine. Hyperchloremic.
Type 4: Failure of aldosterone. Hyperkalemic! Acidic urine.
Pseudohypoparathyroidism
Renal disease
Low calcium, high potassium
High parathyroid hormone
NAD+, NADH absorption
NAD: 260nm
NADH: 340nm
Can see interference with lactic samples or high LDH samples
Rickets
Low calcium, LOW PHOSPHATE, high PTH
Procalcitonin
Inflammatory marker that is suggestive of bacterial infection
Testosterone testing
Immunoassays (insensitive, only use in men or when high levels are expected)
Mass spec (for women, children, tumors?)
Triglyceride testing
Relies on hydrolysis of glycerol; false elevations may be seen in hyperglycerolemic states (glycerol kinase deficinecy)
