Medical Technology Board Examination Notes 4

 

Globulin		Soluble: Hydrocarbon solvents Weak salt solution Insoluble: Water Saturated salt solution Concentrated salt solution
Prothrombin time		Differentiates intrahepatic disorder (prolonged PT) from extrahepatic obstructive liver disease (normal PT)
Albumin		Inversely proportional to the severity of the liver disease
Hepatic cirrhosis		Low total protein + low albumin
Bromcresol green		Most commonly used dye for albumin
Bromcresol purple		Most specific dye for albumin
Other dyes for albumin		Hydroxyazobenzene benzoic acid (HABA) Methyl orange (MO)
Nephrotic syndrome		Albumin excretion: 20-30 g/day
Analbuminemia		(-) albumin
Bisalbuminemia		EP: 2 albumin bands Therapeutic drugs in serum
Inverted A/G ratio		Hepatic cirrhosis (IgA) Multiple Myeloma (IgG) Waldenström’s macroglobulinemia (IgM) Chronic inflammation
Bilirubin		Derived from hemoglobin myoglobin, catalase and cytochrome oxidase
Heme oxygenase		Protoporphyrin à Biliverdin
Biliverdin reductase		Biliverdin àB1
Urobilinogen		Deconjugated bilirubin
Bilirubin 1		Non-polar bilirubin Free/Slow bilirubin
Bilirubin 2		Polar bilirubin One-minute/prompt bilirubin Regurgitative bilirubin
Delta bilirubin		Bilirubin tightly bound to albumin Delta bilirubin = TB-DB+IB
Jaundice		Bilirubin >2 or 3 mg/dL
Pre-hepatic jaundice		Hemolytic B1 = increased B2 = normal UG = increased UB = negative
Hepatic jaundice		Hepatocellular B1 = increased B2 = increased UG = increased UB = positive ALT = increased AST = increased
Post-hepatic jaundice		Obstructive B1 = normal B2 = increased UG = decreased/negative UB = positive ALP = increased GGT = increased Cholesterol = increased
Gilbert’s syndrome		Bilirubin transport deficit (uptake) B1 = increased B2 = decreased
Crigler-Najjar syndrome		Conjugation deficit Type I = total UDPGT deficiency Type II = partial UDPGT deficiency B1 = increased B2 = decreased Danger: Kernicterus Bile is colorless
Dubin-Johnson syndrome & Rotor syndrome		Bilirubin excretion deficit Blockade of excretion into the canaliculi TB = increased B2 = increased
Lucey-Driscoll syndrome		Circulating inhibitor of bilirubin conjugation B1 = increased
Methods (Bilirubin)		Free from hemolysis and lipemia Store in the dark Measured ASAP or w/in 2-3 hours
Van den Berg reaction		Diazotization of bilirubin
Evelyn and Malloy method		Accelerator: Methanol Diazo rgts: Diazo A (0.1% Sulfanilic acid + HCl) Diazo B (0.5% Sodium nitrite) Diazo blank (1.5% HCl) (+) pink to purple azobilirubin Affected by hemolysis
Jendrassik and Grof		Candidate reference method Accelerator: Caffeine sodium benzoate Buffer: Sodium acetate Ascorbic acid: terminates the initial reaction and destroys the excess diazo rgt Not falsely elevated by hemolysis Total bilirubin is measured 15 minutes after adding methanol or caffeine soln
Bilirubin		Absorbs light maximally at 450nm
Rosenthal White method		Double collection method Collection: -After 5 mins (50% dye retention) -After 30 mins (0% dye retention)
Mac Donald method		Single collection method Collection: -After 45 mins (+/- 5% dye retention)
Ammonia		From deamination of amino acids Elevated levels are neurotoxic and often associated w/ encephalopathy and acetaminophen poisoning Diagnosis of hepatic failure and Reye’s syndrome In severe liver disorder: áNH3 à circulation à brain (conv. to glutamine) à increases pH à compromise the Kreb’s cycle à Coma due to lack of ATP for the brain
Methods (Ammonia)		Specimen: Heparin or EDTA plasma Fasting is required Avoid smoking Prolonged standing of specimen: increased NH3 due to deamination Place on iced water immediately Avoid hemolysis
Kjeldahl (Digestion) method		Specimen à PFF N2 ----------(hot conc. H2SO4 + CuSO4 + Hg + Selenium)----------> NH3
Nesslerization of ammonia		NH3 + K2Hg2I2 ----------(Gum Ghatti)----------> NH2Hg2I2 End color: Yellow (low to moderate N2) Orange brown (high N2)
Berthelot reaction		NH3 + Phenol + Hypochlorite -----(Na Nitroprusside)-----> Indophenol blue
Normal Values (Liver Function Tests)		Total protein = 6.5-8.3 g/dL Albumin = 3.5-5.0 g/dL Globulin = 2.3-3.5 g/dL α1-globulin = 0.1-0.3 g/dL α2-globulin = 0.6-1.0 g/dL β-globulin = 0.7-1.1 g/dL γ-globulin = 0.8-1.6 g/dL Total bilirubin = 0.2-1.0 mg/dL Indirect bilirubin = 0.2-0.8 mg/dL Direct bilirubin = 0-0.2 mg/dL Urobilinogen: Urine = 0.1-1.0 Ehrlich units/2hrs (or 0.54 Ehrlich units/day) Stool = 75-275 Ehrlich units/100g feces (or 75-400 Ehrlich units/24hrs) Ammonia = 19-60 μg/dL
Enzymes
Enzyme concentration		Serum á Enzyme concentration = á reaction rate
Substrate concentration		Reagent If enzyme > substrate, á substrate = á reaction rate
Saturation kinetics		When substrate concentration reaches a maximal value, higher concentration of substrate no longer results in increased rate of reaction
Cofactors		Nonprotein entities
Coenzymes		Organic compound Ex. NADP á Coenzyme = á Velocity
Activators		Inorganic ions Alters spatial configuration of the enzyme for proper substrate binding Ex. Ca2+ (#1 activator), Zn2+ (LDH), Cl- (AMS), Mg2+ (CK, ALP)
Metalloenzymes		Inorganic ion attached to a molecule Ex. Catalase, cytochrome oxidase
Inhibitors		Interferes with the enzymatic reactions
Competitive inhibitor		Binds to the active site of an enzyme Reversible (Substrate > Inhibitor)
Noncompetitive inhibitor		Binds to the allosteric site (cofactor site) Irreversible
Uncompetitive inhibitor		Binds to the enzyme-substrate complex á Substrate = áES = áInhibition
Isoenzymes		Same catalytic reactions but slightly different molecular structures Fractionation of isoenzymes
Temperature		37’C = optimum temperature for enzyme activity áTemperature = áReaction rate (ámovement of molecules)
40-50’C		Denaturation of enzymes
60-65’C		Inactivation of enzymes
Temperature coefficient (Q10)		For every 10OC increase in temperature, there will be a two-fold increase in enzyme activity
pH		Most physiologic reactions occur in the pH range of 7-8
Storage		Enzymes: -20’C = for longer period of time Substrate and Coenzymes: 2-8’C LDH (LD4 & 5): Room temperature
Hemolysis		Mostly increases enzyme concentration
Lactescence or milky specimen		Decreases enzyme concentration
Enzyme nomenclature		1st digit: classification 2nd and 3rd digits: subclass 4th digit(s): serial number
Enzyme classification		“OTHLIL” Oxidoreductases Transferases Hydrolases Lyases Isomerases Ligases
Oxidoreductases		Redox reaction Dehydrogenases: -Cytochrome oxidase -LDH -MDH -Isocitrate dehydrogenase -G-6-PD
Transferases		Transfer of a chemical group other than hydrogen from 1 substrate to another Kinases, Transaminases, Aminotransferases: -CK -GGT -AST -ALT -OCT
Hydrolases		Hydrolysis/splitting by addition of water Esterases: -ACP -ALP -CHS -LPS Peptidases: -Trypsin -Pepsin -LAP Glycosidases: -AMS -Galactosidases
Lyases		Removal of groups w/o hydrolysis (product contains double bonds) Aldolase Decarboxylases: -Glutamate decarboxylase -Pyruvate decarboxylase -Tryptophan decarboxylase
Isomerases		Intramolecular arrangements Glucose phosphate isomerase Ribose phosphate isomerase
Ligases		Joining of 2 substrate molecules Synthases
Active site		Water-free cavity Where the substrate interacts
Allosteric site		Cavity other than the active site May bind regulatory molecules
Prosthetic group		Coenzyme that is bound tightly to the enzyme
Holoenzyme		Apoenzyme + Prosthetic group
Zymogen/proenzyme		Inactive form of enzyme
Emil Fisher’s/Lock and Key theory		Shape of the key (substrate) must fit into the lock (enzyme)
Kochland’s/Induced fit theory		Based on the substrate binding to the active site of the enzyme Acceptable theory
Enzyme kinetics		Enzymes catalyze reactions by lowering the activation energy level that the substrate must reach for the reaction to occur
Absolute specificity		Enzyme combines w/ only 1 substrate and catalyzes only 1 reaction
Group specificity		Enzymes combine w/ all the substrates in a chemical group
Bond specificity		Enzymes reacting w/ specific chemical bonds
Zero-order reaction		Reaction rate depends only on enzyme concentration Independent on substrate concentration
First-order reaction		Reaction rate is directly proportional to substrate concentration Independent on enzyme concentration
Measurement of enzyme activity		Change in substrate concentration Change in product concentration Change in coenzyme concentration
International Unit		1 micromole of substrate/minute
Katal Unit		1 mole of substrate/second
Nonkinetic assay		Absorbance is made at 10-second intervals for 100 seconds
Alkaline Phosphatase		pH = 10.5 405nm Electrophoresis: (+) Liver ß Bone (Regan) ß Placenta ß Intestine (-) Heat fractionation: (Δ Stable) Regan ß Placenta ß Intestine ß Liver ß Bone (Δ Labile)
Phenylalanine		Inhibits Regan, placental and intestinal ALP
L-leucine		Inhibits Nagao ALP
Levamisole		Inhibits liver and bone ALP
3M urea		Inhibits bone ALP
Methods (ALP)		Low temperature = Increased ALP 1. Bowers and McComb (PNPP) – IFCC recommended 2. Bessy, Lowry and Brock (PNPP) 3. Bodansky, Shinowara, Jones, Reinhart = BGP (beta glycerophosphate) 4. King and Armstrong = PP (phenylphosphate) 5. Klein, Babson & Read = Buffered PPP (phenolphthalein phosphate) 6. Huggins and Talalay = PPDP (phenolphthalein diphosphate) 7. Moss = ANP (alpha naphthol phosphate)
Increased ALP		Sprue Hyperparathyroidism Rickets (children) and osteomalacia (adults)
Acid Phosphatase		pH = 5.5 405nm Sources: Prostate (major), RBC, platelets, bone
Prostatic ACP		Inhibited by L-tartrate ions
RBC ACP		Inhibited by cupric and formaldehyde ions
Methods (ACP)		Room temperature (1-2 hrs) = decreased ACP Thymolphthalein monophosphate = specific substrate, substrate of choice (endpoint) Alpha-naphthyl phosphate = preferred for continuous monitoring methods 1. Gutman and Gutman = PP 2. Shinowara = PNPP 3. Babsonm Read and Phillips = ANP (continuous monitoring) 4. Roy and Hillman = Thymolphthalein monophosphate (endpoint)
Aspartate Aminotransferase (AST/SGOT)		pH 7.5 340nm Sources: Cardiac tissue > Liver > Skeletal muscle > Kidney, pancreas, RBCs
Alanine Aminotransferase (ALT/SGPT)		pH 7.5 340nm Major Source: Liver
Methods (AST and ALT)		1. Karmen method = Kinetic 2. Reitman and Frankel = Endpoint -Color developer: DNPH -Color intensifier: 0.4N NaOH
Increased Transaminases		DeRitis ratio (ALT:AST) >1.0 = Acute hepatitis (Highest) á20x = viral or toxic hepatitis Moderate elevation = chronic hepatitis, hepatic cancer, IM Slight elevation = Hepatic cirrhosis, alcoholic hepatitis, obstructive jaundice
Amylase		Smallest enzyme (appears in urine) Earliest pancreatic marker P3: most predominant pancreatic AMS isoenzyme in AP Isoenzymes: S-type (ptyalin): anodal P-type (amylopsin): cathodal
Methods (AMS)		Samples w/ high activity of AMS should be diluted w/ NaCl to prev. inactivation Salivary AMS = inhibited by wheat germ lectin Substrate: Starch
Saccharogenic		Reducing sugars produced Classic reference method (SU)
Amyloclastic		Degradation of starch
Chromogenic		Increase in color intensity
Coupled-enzyme		Continuous-monitoring technique
Lipase		Late marker (AP) Most specific pancreatic marker
Methods (LPS)		Substrate: Olive oil/Triolein 1. Cherry Crandal (Reference method) 2. Tietz and Fiereck 3. Peroxidase coupling (most commonly used method)
Lactate dehydrogenase		Lacks specificity RBC: 150x LDH than in serum Sources: LD1 (α-HBD) and LD2 = Heart, RBC, Kidneys LD3 = pancreas, lungs, spleen LD4 an LD5 = liver and muscle LD6 = alcohol dehydrogenase
Methods (LDH)		1. Wacker method (forward/direct) = pH 8.8, 340 nm, most commonly used 2. Wrobleuski LaDue (reverse/indirect) = pH 7.2, 2x faster 3. Wrobleuski Cabaud 4. Berger Broida
10-fold increase (LDH)		Hepatic carcinoma and toxic hepatitis
2-3x URL		Viral hepatitis and cirrhosis
Creatine Kinase		Isoenzymes: CK-BB = most anodal, brain CK-MB = myocardium (20%) CK-MM = least anodal, skeletal and smooth muscles (Major, 94-100%)
Duchenne’s muscular dystrophy		Total CK: 50x URL (highest)
CK-MB		Most specific indicator of myocardial damage (AMI) Not elevated in angina
Methods (CK)		1. Tanzer-Gilbarg (forward/direct) = pH 9.0, 340nm 2. Oliver-Rosalki/ Rosalki & Hess (reverse/indirect) = most commonly used method, faster reaction; pH 6.8, 340nm
Adenylate kinase		Inside RBCs Interferes w/ CK assay Inhibited by adenosine monophosphate
N-acetylcysteine		Activate CK
Liver cells and RBC		Do not contain CK
Cleland’s reagent and glutathione		Partially restore lost activity of CK
Electrophoresis		Reference method for CK
CK relative index (CKI)		CKI (%) = CK-MB/Total CK x 100
Aldolase		Isoenzymes: Aldolase A = Skeletal muscles Aldolase B = WBC, liver, kidney Aldolase C = brain tissue
5’ Nucleotidase		Marker for hepatobiliary diseases and infiltrative lesions of the liver Methods: 1. Dixon and Purdon 2. Campbell, Belfield and Goldberg
GGT		Located in the canaliculi of the hepatic cells Differentates the source of an elevated ALP level Sensitive indicator of occult alcoholism Increased: Obstructive jaundice Alcoholic hepatitis (most sensitive)
Methods (GGT)		Substrate: gamma-glutamyl-p-nitroanilide 1. Szass 2. Rosalki and Tarrow 3. Orlowski
Cholinesterase/ Pseudocholinesterase		Monitor effects of relaxants (succinylcholine) after surgery Marker for organophosphate poisoning (Low CHS) Methods: 1. Ellman technic 2. Potentiometric
Angiotensin-Converting Enzyme		A.k.a. peptidyldipeptidase A or Kininase II Converts angiotensin I à angiotensin II (lungs) Indicator of neuronal dysfunction (Alzheimer’s disease – CSF)
Ceruloplasmin		Ferrooxidase enzyme
Ornithine carbamoyl transferase		For hepatobiliary diseases
G-6-PD		Drug induced hemolytic anemia (primaquine, antimalarial drug)
Normal Values (Enzymes)		ALP = 30-90 U/L ACP: Total ACP (male) = 2.5-11.7 U/L Prostatic ACP = 0-3.5 ng/mL AST = 5-37 U/L ALT = 6-37 U/L AMS = 60-180 SU/dL (95-290 U/L) LPS = 0-1.0 U/mL LDH: Forward = 100-225 U/L Reverse = 80-280 U/L
Acute Myocardial Infarction Markers
	Myoglobin		Troponin T	Troponin I	CK-MB	AST	LD
Rise	1-3 h		3-4 h	3-6 h	4-8 h	6-8 h	12-24 h
Peak	5-12 h		10-24 h	12-18 h	12-24 h	24 h	48-72 h
Normalize	18-30 h		7 d (10-14 d)	5-10 d	48-72 h	5 d	10-14 d
Acute Pancreatitis Markers
	Amylase				Lipase
Rise	2-12 h				6 h
Peak	24 h				24 h
Normalize	3-5 d				7 d
Electrolytes
Electroneutrality		Equal no. of cations and anions Balance of charges
40-75%		Average water content of the human body
ECF		1/3 of total body water
ICF		2/3 of total body water
Normal plasma		93% water (Plasma: 13% > Whole blood) 7% solutes: (Increased in dehydration) -Proteins -Glucose -NPN -Lipids -Ions
Vasopressin deficiency		Excretion of 10-20L H2O everyday
Volume and Osmotic regulation		Sodium Potassium Chloride
Electrolytes		EC = Na+ > Cl- > HCO3- > Ca2+(5th) > iPO4 IC = K+ > Mg2+(4th)
Myocardial rhythm and contractility Neuromuscular excitability		Potassium Calcium Magnesium
Cofactors (enzyme)		Calcium Magnesium (CK) Zinc Chloride (AMS) Potassium
ATPase ion pump		Magnesium
Production and use of ATP from glucose		Magnesium Phosphate
Acid-base balance		Bicarbonate
Replication of DNA and translation of mRNA		Magnesium
Sodium		Major contributor of osmolality (92%, together w/ Chloride and Bicarbonate) á100 mg/dL glucose = â1.6 mmol/L sodium
Aldosterone		áSodium âPotassium = â Magnesium
Atrial natriuretic factor		â Sodium
Hypernatremia		Excess water loss Decreased water intake Hyperaldosteronism (Conn’s disease) Hypothalamic disease (Chronic hypernatremia)
Hyponatremia		Renal failure SIADH (increased water retention) Marked hemolysis (dilutional effect) <125 mmol/L = severe neuropsychiatric symptoms
Thirst		Major defense against hyperosmolality and hypernatremia 1-2% water deficit = severe thirst 150-160 mEq/L Na+ = Moderate deficit of water >165 mEq/L Na+ = Severe water deficit
Pseudohyponatremia (artifactual)		Hyperlipidemia (turbidity) Hyperproteinemia
Methods (Na+)		1. FEP 2. AAS 3. ISE = Glass aluminum silicate 4. Colorimetry = Albanese Lein
Potassium		Concentration in RBC is 105 mmol/L Reciprocal relationship with H+
Specimen Considerations (K+)		0.5% hemolysis = á 0.5 mmol/L Gross hemolysis = á 30% Serum K+ > Plasma K+ by 0.1-0.7 mmol/L  because of platelets (clot) á10-20% in muscle activity á0.3-1.2 mmol/L = mild to moderate exercise á2-3 mmol/L = vigorous exercise; fist clenching
Hyperkalemia		Decreased resting membrane potential à incr. contractility à lack of muscle excitability Decreased renal excretion (Dehydration, renal failure, Addison’s disease) Acidosis (DM) Muscle injury Spironolactone
Hypokalemia		Increased resting membrane potential  à arrhythmia Leads to hypomagnesemia Vomiting Diuretics Cushing’s syndrome Alkalosis Insulin overdose
pH and K+		â pH by 0.1 = á K+ by 0.2-1.7 mmol/L
Methods (K+)		Lithium heparin plasma = preferred 1. FEP 2. AAS 3. ISE = Valinomycin gel 4. Colorimetry = Lockhead and Purcell
Chloride		Chief counter ion of sodium in ECF
Specimen Considerations (Cl-)		Chloride methods measure bromide and iodide âCl- = áHCO3-
Methods (Cl-)		1. Schales and Schales: -Mercurimetric titration -Diphenylcarbazone -Excess Hg++ -(+) Blue violet 2. Whiterhorn Titration method -Mercuric thiocyanate -Reddish complex 3. Ferric perchlorate 4. Cotlove chloridometer -Coulometric amperometric titration -Excess Ag++ 5. ISE -Ion exchange membrane -Tri-n-octylpropylammonium chloride decanol
Hyperchloremia		Renal tubular acidosis Metabolic acidosis Diabetes insipidus (Dehydration) Prolonged diarrhea
Hypochloremia		Prolonged vomiting (âHCl) Aldosterone deficiency (âNa+ = âCl- = áK+) Metabolic alkalosis (áHCO3- = âCl-) Marked hemolysis (dilutional effect)
Calcium		99% à Bones 1% à ECF Absorbed in the duodenum Absorption is favored at an acidic pH
3 Forms of Calcium		50% = Free/Ionized/Unbound/Active Calcium 40% = Protein-bound (Albumin) 10% = Complexed with anions
Vitamin D3		á Ca2+ = á absorption (intestine) and reabsorption (kidney)
PTH		á Ca2+ = á resorption (bone) and reabsorption (kidney)
Calcitonin		â Ca2+ = á urinary excretion (major net loss of calcium)
Practical considerations (Ca2+)		Serum = specimen of choice â Albumin (1g/dL) = â Ca2+ (0.8 mg/dL)
Hypercalcemia		Acidosis (Ca2+: from Bones à Blood) Cancer Hyperthyroidism Milk-alkali syndrome
Hypocalcemia		Tetany Alkalosis (Ca2+: from Blood à Bones) Acute pancreatitis (Ca2+: binds to damage pancreatic tissues)
Primary hypocalcemia		Low PTH Parathyroid gland disease
Secondary hypocalcemia		High PTH Renal failure (á excretion)
Methods (Ca2+)		1. Clark Collip precipitation method -(+) Oxalic acid -Renal calculi 2. Ferro Ham Chloranilic acid precipitation method -(+)Chloranilic acid 3. Colorimetric = Ortho-Cresolphthalein complexone dyes -Dye: Arzeno III -8-hydroxyquinoline = chelates (inhibits) Mg2+ 4. EDTA titration method (Bachra, Dawer and Sobel) 5. AAS = Reference method 6. ISE = Liquid membrane 7. FEP
Inorganic Phosphorus		85% à Bones 15% à ECF (iPO4) Maximally absorbed in the jejunum (Ca2+: duodenum) Trancellular shift: Once absorbed inside cells, it no longer comes out à used for energy production Dirunal variation: á late morning, â evening Organic phosphate = principal anion within cells Inorganic phosphate = part of the blood buffer (Measured in the clin.lab.)
3 Forms of Inorganic Phosphorus		55% = Free 35% = Complexed with ions 10% = Protein-bound
PTH		â PO4 = á Ca2+
Calcitonin		á PO4 = â Ca2+
Growth hormone		á PO4 (renal reabsorption)
Practical considerations		Fasting is required (Nonfasting: â PO4)
Hyperphosphatemia		Hypoparathyroidism Renal failure Hypervitaminosis D
Hypophosphatemia		Alcohol abuse = most common cause Primary hyperparathyroidism Avitaminosis D (Rickets, Osteomalacia)
Methods (iPO4)		Most accurate: unreduced phosphomolybdate formation (340nm) 1. Fiske Subbarow Method (Ammonium molybdate method) -Reducing agents: Pictol, Elon, Senidine, Ascorbic acid -(+) Phosphomolybdenum blue
Magnesium		53% à Bones 46% à Muscles and soft tissues 1% à Serum and RBC Vasodilator
3 Forms of Magnesium		55% = Free/Ionized/Physiologically active 30% = Protein-bound 10% = Complexed with ions
PTH		áMg2+ = á Ca2+ = â PO4
Aldosterone (& Thyroxine)		âMg2+ = â K+ = á Na+
Hypermagnesemia		Addison’s disease Chronic renal failure
Hypomagnesemia		Acute renal failure Chronic alcoholism
Methods (Mg2+)		1. Calmagite -(+) Reddish-violet complex 2. Formazen dye method -(+) Colored complex 3. Magnesium Thymol blue method -(+) Colored complex 4. AAS = reference method 5. Dye-lake Method -Titan Yellow dye (Clayton Yellow or Thiazole yellow)
Bicarbonate		90% of the total CO2
Chloride shift		HCO3- diffuses out of the cell in exchange for Cl- to maintain ionic charge neutrality w/in the cell
Anion Gap		Difference between unmeasured anions and unmeasured cations QC for ISE
Increased AG		Uremia/renal failure Ketoacidosis Lactic acidosis Methanol poisoning Ethanol poisoning Ethylene glycol poisoning Salicylate poisoning
Decreased AG		Hypoalbuminemia Hypercalcemia Hyperlipidemia Multiple myeloma
Cystic Fibrosis (Mucoviscidosis)		Defective gene: Cystic fibrosis transmembranous conductance regulator (Chromosome 7) Miconeum ileus (Infants) Foul-smelling stool URT infection á Na+ and Cl-
Pilocarpine		Sweat inducer
Gibson & Cooke pilocarpine iontophoresis		Reference method (Sweat sodium and chloride)
Iron		Prooxidant 3-5g = Total body iron Ferrous = Hgb Ferric = Transferrin and Ferritin
Methods (Iron)		1. Colorimetric = HCl and Ferrozine -(+) Blue color 2. Anodic stripping voltammetry
Increased iron		Hemochromatosis Viral hepatitis Non-IDA
Decreased iron		IDA Malnutrition Chronic infection
TIBC		UIBC + Serum Iron Increased: IDA, hepatitis, iron-supplemented pregnancy Decreased: Non-IDA, nephrosis
UIBC		TIBC – Serum iron Measure of reserve iron binding capacity of transferrin
% Transferrin Saturation		Index of iron storage Increased: Iron overdose, hemochromatosis, sideroblastic anemia Decreased: IDA (lowest), malignancy, chronic infection
Transferrin		TIBC (μg/dL) x 0.70 = mg/dL
Note		Sodium 1/α Potassium Potassium 1/α Hydrogen ion Potassium α Magnesium Magnesium α Calcium Calcium 1/α Inorganic phosphate Chloride 1/α Bicarbonate
Normal Values (Electrolytes)		Sodium: Serum = 135-145 mmol/L [Critical: 160 mmol/L and 120 mmol/L] CSF = 136-150 mmol/L Potassium: Serum = 3.5-5.2 mmol/L [Critical: 6.5 mmol/L and 2.5 mmol/L] Chloride: Serum = 98-107 mmol/L Sweat = 5-40 mmol/L [Critical: >65 mmol/L] Calcium: Total = 8.6-10 mg/dL (adult) and 8.8-10.8 mg/dL (child) Ionized = 4.6-5.3 mg/dL (adult) and 4.8-5.5 mg/dL (child) [Critical: <7.5 mg/dL] Inorganic Phosphate: Adult = 2.7-4.5 mg/dL Child = 4.5-5.5 mg/dL Magnesium: Serum = 1.2-2.1 mEq/L Anion Gap: w/ K+ = 10-20 mmol/L w/o K+ = 7-16 mmol/L Iron: Male = 50-160 μg/dL Female = 45-150 μg/dL TIBC: Adult = 245-425 μg/dL >40 y.o. = 10-250 μg/dL NB and Child = 100-200 μg/dL % Transferrin Saturation = 20-50%
Blood Gases and pH
Regulation of Acid-Base balance		Lungs and Kidneys CO2 + H2O <--(Carbonic anhydrase)--> H2CO3 H2CO3 <-------(Carbonic anhydrase)--> H+ + HCO3-
20:1		HCO3-: H2CO3 ratio
4:1		HPO4: H2PO4 ratio
Expanded Henderson-Hasselbalch equation		pH = 6.1 + log [Total CO2 – (pCO2 x 0.03)]                                          pCO2 x 0.03
Chloride-isohydric shift		Buffering effect of hemoglobin
pCO2		Index of efficiency of gas exchange Increased: Barbiturates, morphine, alcohol, heparin (á12-15%)
pO2		Reflects the availability of the gas in blood but not its content Excessive O2 supply à acidosis
Metabolic Acidosis		Causes: -Bicarbonate deficiency -DKA (normochloremic acidosis) -Renal failure -Diarrhea (âHCO3-) Compensation: Hyperventilation Compensated: â HCO3- + âpCO2 + pH <7.4
Metabolic Alkalosis		Causes: -Bicarbonate excess -Vomiting (âCl-) -Hypochloremia -Hypokalemia Compensation: Hypoventilation Compensated: á HCO3- + ápCO2 + pH >7.4
Respiratory Acidosis		Causes: -CO2 excess (Hypoventilation) -COPD -Drug overdose (morphine, barbiturates, opiates) Compensation: Bicarbonate retention Compensated: á HCO3- + â pCO2 + pH <7.4
Respiratory Alkalosis		Causes -CO2 loss (Hyperventilation) Compensation: Bicarbonate excretion Compensated: â HCO3- + â pCO2 + pH >7.4
Full compensation		pH à normal range
Partial compensation		pH à near normal
Buffer base		All forms of base that will titrate hydrogen ions
Methods for Blood Gases and pH		Specimen: Arterial blood Blood gas analyzers: meas. pH, pCO2, pO2
Factors affecting Blood gases & pH measurements		For every á1OC above 37OC: â pH by 0.015 â pO2 by 7% á pCO2 by 3% Bacterial contamination: consume O2 (âpO2) Excess heparin (acid MPS) = âpH Air exposure (bubbles): ápO2 = 4 mmHg/2mins âpCO2 = 4 mmHg/2mins
Methods (Blood gases & pH)		1. Gasometer a. Van Slyke b. Natelson -Mercury: produce vacuum -Caprylic alcohol: anti-foam reagent -Lactic acid -NaOH -NaHSO3 2. Electrodes a. pH = potentiometry -Silver-silver chloride electrode (Reference electrode) -Calomel electrode [Hg2Cl2] (Reference electrode) b. pCO2 = Severinghaus electrode (potentiometry) c. pO2 = Clark electrode (polarography-amperometry)
Whole blood total CO2		Dissolved CO2 + H2CO3 + HCO3-
Transcutaneous electrodes		Continuous monitoring of pO2 Directly placed on the skin
Blood gas QC		Min. requirement: -1 sample every 8 hours -3 levels of control (acidosis, normal, alkalosis) every 24 hours
Normal Values (Blood gases and pH)		pH = 7.35-7.45 pCO2 = 35-45 mmHg Total CO2: WB arterial = 19-24 mmol/L WB venous = 22-26 mmol/L HCO3- = 21-28 mEq/L pO2 = 81-100 mmHg [Hypoxemia:] -Mild (61-80 mmHg) -Moderate (41-60 mmHg) -Severe (40 mmHg or less) O2 saturation = 94-100%
Endocrinology
Endocrine		Hormone à blood circulation à specific receptor
Paracrine		Hormone à interstitial space à adjacent cell
Autocrine		Hormone à self-regulation
Juxtacrine		Hormone à direct cell-to-cell contact
Exocrine		Hormone à gut
Neurocrine		Hormone à neurons à extracellular space
Neuroendocrine		Hormone à neurons à nerve endings
Glycoproteins		FSH, hCG, TSH, LH
Polypeptides		ACTH, ADH, GH, angiotensin, calcitonin, CCK, gastrin, glucagons, insulin, MSH, oxytocin, PTH, PRL, somatostatin
Steroids		Precursor: cholesterol Aldosterone, cortisol, estrogen, progesterone, testosterone, vitamin D
Amines		Derived from amino acids Catecholamines, T3, T4
Hypothalamus		Connected to the posterior pituitary by the infundibulum stalk Hypophyseal hormones: TRH, GnRH, GH-IH, GH-RH, PIF
Pineal gland		Melatonin: decreases pigmentation of the skin
Pituitary gland		Master Gland Located in the sella turcica or Turkish saddle
Anterior Pituitary (Adenohypophysis)		True endocrine gland Hormones: PRL, GH, FSH, LH, TSH, MSH, ACTH
GH (Somatotropin)		Most abundant of all pituitary hormones Structurally similar to PRL and HPL Markedly elevated during deep sleep
Dwarfism		Decreased GH
Acromegaly		Increased GH
GH deficiency tests		1. Insulin tolerance test = Gold standard (Confirmatory test) 2. Arginine stimulation test = 2nd confirmatory test
Tests for Acromegaly		1. Somatomedin C or insulin-like growth factor I (Screening) -Increased: Acromegaly -Decreased: GH deficiency 2. OGTT (Confirmatory) -75g glucose
FSH		Spermatogenesis
LH		Helps Leydig cells to produce testosterone (male) Ovulation (female) Synthesis of androgens, estrogens, and progesterone
TSH (Thyrotropin)		Stimulates thyroid gland to produce T3 and T4 Increased: 1’ hypothyroidism, 2’ hyperthyroidism Decreased: 1’ hyperthyroidism, 2’ hypothyroidism, 3’ hypothyroidism
ACTH  (Corticotropin)		Highest: 6-8 AM Lowest: 6-11 PM Not allowed to have contact with glass because it adheres to glass surface Collect blood in plastic tubes
Prolactin		Initiation and maintenance of lactation Inhibited by Dopamine Highest: 4AM and 8AM, and 8PM and 10PM Increased: Menstrual irregularity, infertility, amenorrhea, galactorrhea
Panhypopituitarism		From pituitary tumor (adenoma) or Ischemia
Pituitary ischemia (Shechan’s)		Hemorrhage or shock in a pregnant female at the time of deliver
Posterior pituitary (Neurohypophysis)		Release but not produce oxytocin and vasopressin
Oxytocin		Uterine contraction and milk ejection
ADH/AVP (Arginine vasopressin)		H2O reabsorption (DCT and CD) Stimulus: Increased plasma osmolality (>295 mOsm/kg), decreased blood vol. Promotes factor VII and vWF release
Overnight water deprivation test (Conc. test)		Diagnostic test for ADH
Neurogenic DI		True Diabetes Insipidus Failure of the pituitary gland to secrete ADH
Nephrogenic DI		Failure of the kidneys to respond to normal or elevated ADH
SIADH		Syndrome of inappropriate ADH Sustained production of ADH Decreased urine volume Low plasma osmolality Low serum electrolytes
Thyroid Gland		Butterfly-shaped 2 lobes = connected by the isthmus
Follicle		Fundamental structural unit of the thyroid gland
Follicular cells		Secrete T3 and T4
Parafollicular or C cells		Secrete calcitonin
Thyroglobulin		Preformed matrix containing tyrosyl groups Stored in the follicular colloid of the thyroid gland
Thyroid hormone Biosynthesis		1. Trapping of Iodine 2. Iodination: I2 à Tyrosine ring à MIT and DIT 3. Condensation: MIT+DIT=T3 / DIT+DIT=T4 4. Release: T3/T4 à Blood circulation 5.  Transport of T3/T4 by proteins
Protein-bound hormones		Metabolically inactive Biologically inert Do not enter cells Storage sites
Free hormones (FT3/FT4)		Physiologically active Readily enters cells
Reverse T3 (rT3)		From removal of one iodine from T4 (product of T4 metabolism) Metabolically inactive
I2 intake <50 μg/day		Deficiency of hormone secretion
T3		3,5,3’-Triiodothyronine Most active thyroid hormonal activity 75-80% is produced from the tissue deiodination of T4 Diagnosis of T3 thyrotoxicosis
T4		3,5,3’5’-Tetraiodothyronine Principal secretory product All originated in the thyroid gland
TBG		Transports 70-75 of TT4, and majority of T3
TBPA (Transthyretin)		Transports 15-20% of TT4 No affinity for T3
TBA		Transports T3 and 10% of T4
Thyroid autoantigens		TPO Tg TSHR
Thyroid disorders		Screening is recommended when a person reaches 35 yrs old and every 5 yrs thereafter
Primary hyperthyroidism		á T3 and T4 â TSH
Secondary hyperthyroidism		á T3 and T4 á TSH
T3 Thyrotoxicosis (Plummer’s disease)		á T3 N-T4 â TSH
Graves’ disease (Diffuse toxic goiter)		1’ Hyperthyroidism Most common cause of thyrotoxicosis (autoimmune) Women > Men Anti-TSH receptor
Riedel’s thyroiditis		Thyroid à woody or stony-hard mass
Subclinical hyperthyroidism		No symptoms N-T3 and T4 â TSH
Subacute granulomatous/ Subacute nonsuppurative/ De Quervain’s thyroditis		Hyperthyroidism Painful thyroiditis Neck pain, low-grade fever (-) anti-TPO, á ESR and Tg
Hypothyroidism		Treatment: Levothyroxine
Primary hypothyroidism		â T3 and T4 á TSH
Hashimoto’s disease (Chronic autoimmune thyroiditis)		Most common cause of 1’ hypothyroidism Thyroid is replaced by a nest of lymphoid tissue (T cells) Goiter (+) anti-TPO á TSH
Myxedema coma		Severe form of 1’ hypothyroidism Peculiar nonpitting swelling of the skin Skin is infiltrated by mucopolysaccharides “Puffy” face, thin eyebrows
Secondary hypothyroidism		â T3 and T4 â TSH
Tertiary hypothyroidism		â T3 and T4 â TSH â TRH
Congenital hypothyroidism (Cretinism)		Mental retardation (child) Screening: âT4 Confirmatory: áTSH
Subclinical hypothyroidism		N-T3 and T4 á TSH
TRH stimulation test		Most specific and sensitive test for diagnosing thyroid disease Confirm borderline cases and euthyroid Graves’ disease á: 1’ hypothyroidism â: Hyperthyroidism
Radioactive Iodine Uptake (RAIU)		Measure the ability of the thyroid gland to trap iodine
Thyroglobulin (Tg) assay		Postoperative marker of thyroid cancer á: Untreated and metastatic differentiated thyroid cancer, hyperthyroidism â: Hypothyroidism, thyrotoxicosis factitia
rT3		Assess borderline or conflicting laboratory results
Free Thyroxine Index (FT4I)		Indirectly assesses the level of FT4 in blood Equilibrium relationship of bound T4 and FT4 Reference method: Equilibrium dialysis FT4I = TT4 x T3U(%) or TT4 x THBR                       100
TT3, FT3, FT4		FT4 test: differentiates drug induced TSH elevation and hypothyroidism TT3 or FT3: confirm hyperthyroidism Reference method (FT4): Equilibrium dialysis
T3 Uptake test		Measures the number of available binding sites of the thyroxine binding proteins (TBG) á TBG = â T3U â TBG = á T3U
TBG test		Confirm results of FT3 or FT4 or abnormalities in the relationship of TT4 and THBR test Estrogen: áTBG Androgen: âTBG
Fine-needle aspiration		Most accurate tool in the evaluation of thyroid nodules
Recombinant Human TSH		Test patients w/ thyroid cancers for the presence of residual or recurrent dis.
Tanned Erythrocyte Hemagglutination method		Test for anti-Tg disorders
Serum calcitonin test		Marker for familial medullary thyroid carcinoma
FT4 and TSH		Best indicators of thyroid status
FT3 and FT4		More specific indicators of thyroid function than meas. of total hormone Not affected by TBG
Euthyroid sick syndrome		Acutely ill but without thyroid disease â T3 and T4 N/á TSH á rT3
Parathyroid gland		4 parathyroid glands Smalles endocrine gland
PTH		Hypercalcemic hormone á Ca2+ (bone resorption and renal reabsorption) and Mg2+ â iPO4
1’ hyperparathyroidism		Defective: Parathyroid gland Most common cause of hypercalcemia Parathyroid adenoma á PTH and iCa2+ Hypercalciuria Phosphaturia à Hypophosphatemia If goes undetected à severe demineralization (osteitis fibrosa cystica)
2’ hyperparathyroidism		In response to âCa2+ Hyperplasia of all 4 glands Causes: Vit. D deficiency and chronic renal failure á PTH â Ca2+
3’ hyperparathyroidism		Occurs w/ 2’ hyperparathyroidism (â Ca2+) Autonomous function of hyperplastic PT glands or PT adenoma á PO4 Calcium phosphates precipitate in soft tissues
Hypoparathyroidism		Accidental injury of the PT glands (neck) during surgery Autoimmune parathyroid destruction â PTH = â Ca2+
Hyperparathyroidism		Acidosis
Hypoparathyroidism		Alkalosis
Adrenal glands		Pyramid-shaped Above the kidneys Adrenal cortex = outer (yellow) Adrenal medulla = inner (dark mahogany) Has prime effects on blood pressure
Adrenal cortex		Major site of steroid hormone production G cells: convert cholesterol à pregnenolone
CPPP ring		17-carbon skeleton derived from cholesterol
3 layers (Adrenal cortex)		1. Zona Glomerulosa = Mineralocorticoids (Aldosterone) 2. Zona Fasciculata = Glucocorticoids (Cortisol) 3. Zona Reticularis = Weak androgens (androstenedione, DHEA)
Cortisol		Gluconeogenesis à hyperglycemia The only adrenal hormone that inhibit the secretion of ACTH Anti-inflammatory and immunosuppressive Diurnal: á 6-8AM / â 10PM-12AM Urinary metabolites: 17-OHCS and 17-KGS
Porter-Silber method		Meas. 17-OHCS Rgt: DNPH in H2SO4 + Alcohol (+) Yellow
Zimmerman reaction		Meas. 17-KGS Rgt: m-dinitrobenzene (+) Reddish purple Oxidation procedure: Norymberski (Na+ bismuthate)
Pisano method		For quantitating metanephrines and normetanephrines
Kober reaction		For estrogen Rgt: H2SO4 + hydroquinone (+) Reddish brown color
Cushing’s syndrome (Hypercortisolism)		Excessive production of cortisol and ACTH Overuse of corticosteroids Buffalo hump Hyperglycemia Hypertension Hypercholesterolemia â Lymphocytes
Screening tests (Cushing’s)		1. 24-hour urine free cortisol test 2. Overnight dexamethasone suppression tests = Most widely used (1mg) 3. Salivary cortisol test
Confirmatory tests (Cushing’s)		1. Low-dose dexamethasone suppression test (0.5mg) 2. Midnight plasma cortisol 3. CRH stimulation test
Addison’s disease (1’ Hypocorticolism)		Primary adrenal insufficiency â Cortisol and aldosterone á ACTH (+) Hyperpigmentation Screen: ACTH Stimulation Test
2’ Hypocorticolism		Secondary adrenal insufficiency Hypothalamic-pituitary insufficiency â ACTH Test: ACTH Stimulation test
ACTH Stimulation test (Corsyntropin stimulation test)		Corsyntropin: synthetic coritsol and aldosterone stimulator Differentiates: 2’ adrenal insufficiency (âACTH) from 3’ adrenal insufficiency (á ACTH)
Metyrapone test		Metyrapone: inhibitor of 11 β-hydroxylase Measures the ability of the pituitary gland to respond to declining levels of circulating cortisol, thereby secrete ACTH Alternative diagnostic or confirmatory test for 2’ or 3’ adrenal insufficiency (+): âACTH
24-hour urine free cortisol		Most sensitive and specific screening test for excess cortisol production because plasma cortisol is affected by diurnal variation Methods: HPLC or GC-MS
HPLC-MS		Reference method for measuring urinary free cortisol
ITT (Insulin tolerance test)		Gold standard for 2’ and 3’ hypocorticolism Confirms borderline response to ACTH stimulation test
Serum ACTH		Differentiates: Cushing’s disease (áACTH) Cushing’s syndrome (0-ACTH)
áACTH		á17-OHCS and 17-KS
Congenital Adrenal Hyperplasia		Enzyme deficiencies: 1.) 21-hydroxylase = most common 2.) 11 β-hydroxylase = 2nd most common 3.) 3β-hydroxysteroid dehydrogenase-isomerase 4.) C-17,20-lyase/17α-hydroxylase â Cortisol á ACTH á Androgens (hirsutism, virilization, amenorrhea, pseudohermaphroditism)
Aldosterone (Aldo)		Electro-regulating hormone á Na+ and Cl- â K+ and H+ â at night 18-hydroxysteroid dehydrogenase: enzyme needed for aldosterone synthesis
Conn’s disease (1’ hyperaldosteronism)		Aldosterone-secreting adrenal adenoma Screen: Plasma Aldo conc./Plasma renin activity ratio (PAC/PRA ratio) -(+): >50 ratio Confirm: Saline suppression test -(+): >5 ng/dL aldosterone
2’ Hyperaldosteronism		Excessive production of renin
Liddle’s syndrome		Pseudohyperaldosteronism Resembles 1’ aldosteronism clinically â Aldosterone (-) Hypertension
Bartter’s syndrome		Bumetanide-sensitive chloride channel mutation á Aldosterone and Renin
Gitelman’s syndrome		Thiazide-sensitive transporter mutation á Aldosterone
Hypoaldosteronism		Destruction of the adrenal glands Glucocorticoid deficiency 21-hydroxylase deficiency
Postural stimulation test		Test for aldosterone
Florinef		Synthetic mineralocorticoid
Weak androgens		Precursors for the production of more potent androgens and estrogens Precursors: Pregnenolone and 17-OH pregnenolone Examples: DHEA and androstenedione Bound to steroid hormone binding globulin (SHBG) á: Virilization (pseudohermaphroditism)
DHEA (Dehydroepiandrosterone)		Principal adrenal androgen Converted to estrone
Adrenal medulla		Chromaffin cells: secrete catecholamines Precursor: L-tyrosine Norepinephrine/Epinephrine ---(Monoamine oxidase and Catechol-0-methyl-transferase)---> Metanephrines and VMA
9:1		Norepinephrine: Epinephrine ratio
Norepinephrine		Primary amine á in CNS Metabolites: -3-methoxy-4-hydroxyphenylglycol (MHPG) = Major metabolite -VMA
Epinephrine		Secondary amine Most abundant medullary hormone “Flight or fight hormone” Metabolites: -Vanillylmandelic acid (VMA) = Major metabolite -Metanephrines -Normetanephrines -HVA
Dopamine		Primary amine From the decarboxylation of 3,4-Dihydroxyphenylalanine (DOPA) Major metabolite: Homovanillic acid (HVA)
Pheochromocytoma		Tumors of the adrenal medulla áCatecholamines Classic “Spells”: tachycardia, headache, chest tightness, sweating, hypertension
Clonidine test		Differentiates: Pheochromocytoma (Catecholamines not suppressed) from Neurogenic hypertension (50% decreased in catecholamines)
Neuroblastoma		áNorepinephrine (Children) á urinary HVA, VMA or both and dopamine
Methods (Catecholamines)		Specimen: 24-hr urine and plasma 1. Chromatography: HPLC or GC-MS 2. RIA: sensitive screening test ->2000pg/mL = diagnostic for pheochromocytoma
Estrogens		Estrone = áPostmenopausal women Estradiol = áPremenopausal women (most potent, secreted by the ovary) Estriol = áPregnancy (placenta)
Markers for Down Syndrome		âAFP âUnconjugated Estriol áhCG áInhibin A
Karyotyping or FISH typing		Test for Down syndrome (amniotic fluid)
Progesterone		Produced mainly by the corpus luteum Det. whether ovulation has occurred áLuteal phase
Tests for menstrual cycle dysfunction and anovulation		Estrogen Progesterone FSH LH
Tests for female infertility		hCG PRL FT4 TSH FSH LH Estradiol Progesterone
Pancreas (Exocrine)		Digestive enzymes (AMS, LPS) Acinus: functional secretory unit
Pancreas (Endocrine)		Hormones: Alpha cells (20-30%) = glucagon Beta cells (60-70%) = insulin Delta cells (2-8%) = somatostatin
hCG		Produced by the syncytiotrophoblasts (placenta) Maintain progesterone production by the corpus luteum
Human placental lactogen (HPL)		Stimulates development of mammary gland Increases maternal plasma glucose levels Diagnosis of intrauterine growth retardation
Gastrin		Secreted by G cells (stomach) Stimulates parietal cells to secrete HCl Stimulus: Amino acid áZollinger-Ellison syndrome âPernicious anemia
Serotonin (5-hydroxytryptamine)		Synthesized by argentaffin cells (GIT) Metabolite: 5-HIAA
5-HIAA		Diagnostic marker for carcinoid syndrome Test: Ehrlich’s aldehyde test = (+) purple color
Somatostatin		A.k.a. GH-IH Inhibitor of GH, glucagon and insulin
1’ amenorrhea		Menstruation having never occurred
2’ amenorrhea		Absence of menses for 6 months
Cushing’s disease		Abnormal increased secretion of ACTH
Cushing’s syndrome		Chronic excessive production of cortisol by the adrenal cortex -Large doses of glucocorticoids -Pituitary tumor (áACTH) = most common cause
Gynecomastia		Development of breast tissue in males
Hirsutism		Excessive hair growth w/ a male distribution pattern in a female Most common endocrine disorder in women
Mullerian agenesis		Congenital malformation or absence of the fallopian tubes, uterus or vagina N-FSH, LH and testosterone
Nonthyroidal illness		Illness that do not directly involve the thyroid gland
Sipples syndrome (MEN II)		Medullary carcinoma of the thyroid Pheochromocytoma Parathyroid adenoma
Stein-Leventhal syndrome		Mild hirsutism w/ normal menses to excessive hirsutism w/ amenorrhea
Thyroid stones		A.k.a. thyroid crisis Life-threatening Uncontrolled thyrotoxicosis
Normal Values (Endocrinology)		T3: Adult = 80-200 ng/dL Children 1-14 y.o. = 105-215 ng/dL T4: Adult = 5.5-12.5 μg/dL Neonate = 11.8-22.6 μg/dL T3U = 25-35%
Therapeutic Drug Monitoring
Mixed function oxidase (MFO) system		Biochemical pathway responsible for the greatest portion of drug metabolism
Intravenous route		100% bioavailability
Liberation		Drug à Release
Absorption		Drug à Blood (most: by passive diffusion)
Distribution		Drug à Tissues
Metabolism		Drug à Chemical modification
Excretion		Drug à metabolites à excreted
Bioavailable fraction (f)		Fraction of the dose that reaches the blood
Vd of a drug		Dilution of the drug after it has been distributed in the body
First-pass hepatic metabolism		Drugs à Liver à Decreased bioavailability
First order elimination		Linear relationship bet. the amt. of drug eliminated per hour and the blood level of drug
Pharmacodynamics		Relationship bet. drug concentration at the target site and response of the tissues
Pharmacokinetics		Relationship bet. drug dose and drug blood level
Pharmacogenomics		Study of genes that affect the performance of a drug in an individual
Therapeutic index		Ratio bet. the minimum toxic and maximum therapeutic serum conc.
Trough concentration		Lowest concentration of a drug obtained in the dosing interval Drawn immediately (or 30 mins) before the next dose
Peak concentration		Highest concentration of a drug obtained in the dosing interval Drawn one hour after an orally administered dose (except digoxin)
Cardioactive Drugs
Class I		Rapid Na+ channel blockers (Procainamide, Lidocaine, Quinidine)
Class II		Beta receptor blockers (Propanolol)
Class III		K+ channel blockers (Amiodarone)
Class IV		Ca2+ channel blockers (Verapamil)
Digoxin		Tx: CHF
Lidocaine (Xylocaine)		Local anesthetic 1’ product of hepatic metabolism: MEGX (monoethylglycinexylidide)
Quinidine		Common formulations: Quinidine sulfate and Quinidine gluconate
Procainamide (Pronestyl)		Hepatic metabolite: NAPA (N-acetylprocainamide) Toxic effect: reversible lupus-like syndrome
Disopyramide		Substitute for quinidine Anticholinergic effects
Propanolol		Tx: angina pectoris
Amiodarone (Cordarone)		Iodine-containing drug
Verapamil		Tx: angina, hypertension, supraventricular arrhythmias
Antibiotics
Aminoglycosides		Tx: Gram (-) bacterial infections Nephrotoxic and ototoxic
Vancomycin		Tx: Gram (+) cocci and bacilli Toxic effects: “Red man syndrome” Nephrotoxic and ototoxic
Antiepileptic Drugs
Phenobarbital		Long acting barbiturate Enhances bilirubin metabolism Inactive proform: Primidone
Phenytoin (Dilantin)		Injectable proform: fosphenytoin
Valproic acid (Depakene)		Tx: petit mal and grand mal
Carbamazepine (Tegretol)		Tx: grand mal
Ethosuximide (Zarontin)		Drug of choice for controlling petit mal seizure
Gabapentin (Neurontin)		Similar to neurotransmitter GABA
Others (Antiepileptic)		Topiramate Lamotrigine (Lamictal) Felbamate
Psychoactive Drugs
Lithium		Tx: Bipolar disorders (Manic depression)
Tricyclic antidepressantas (TCA)		Imipramine Amitriptyline Doxepin Nortriptyline Tradazone
		Major metabolite: Desipramine
Fluoxetine (Prozac)		Blocks reuptake of serotonin Tx: Obsessive-compulsive disorders
Bronchodilator
Theophylline		Tx: Asthma and other COPD
Anti-inflammatory and Analgesic Drugs
Salicylates/Aspirin (Acetylsalicylic acid)		Antiplatelet (inhibits cyclooxygenase) Method: Trinder assay
Acetaminophen (Tylenol)		Hepatotoxic
Ibuprofen		Lower risk of toxicity than salicylates and acetaminophen
Neuroleptics (Antipsychotic major tranquilizers)
Neuroleptics		Block the action of dopamine and serotonin Tx: Schizophrenia 2 classes: -Phenothiazines (chlorpromazine) -Butyrophenones (haloperidol) Examples: -Risperdal -Olonzapine (Zyprexa) -Quetiapine (Seroquel) -Aripiprazole (Abilify)
Immunosuppressants		Cyclosporine Tacrolimus (FK-506) Rapamycin (Sirolimus) Mycophenolate mofetil Lefluamide
Chemotherapeutic agents		Busulfan Methotrexate
Toxicology
Toxic Agents
Alcohols (%w/v)		Common CNS depressants
0.01-0.05		No obvious impairment, some changes observable on performance testing
0.03-0.12		Mild euphoria, decr. inhibitions, some impairment of motor skills
0.09-0.25		Decr. inhibitions, loss of critical judgment, memory impairment, decr. rxn time
0.18-0.30		Mental confusion, dizziness, strongly impaired motor skills (slurred speech)
0.27-0.40		Unable to stand/walk, vomiting, impaired consciousness
0.35-0.50		Coma and possible death
≥0.10		Presumptive evidence of driving under influence of alcohol
Ethanol (Grain alcohol)		Most common abused drug Ethanol à Acetic acid Major metabolic pathway: Ethanol ------(Alcohol Dehydrogenase)------> Acetaldehyde Testing: Use benzalkonium chloride as antiseptic
Methanol (Wood alcohol)		Cause blindness Methanol à Formaldehyde à Formic acid (liver)
Isopropanol (Rubbing alcohol)		Liver metabolism: Isopropanol à Acetone
Ethylene glycol (1,2-ethanediol)		Antifreezing agent Ethylene glycol à Oxalic acid and glycolic acid (+) Monohydrate calcium oxalate crystals
Carbon Monoxide		Colorless, odorless, tasteless gas Has 210x greater affinity than O2 for Hgb “Cherry-red” color of the face and blood Specimen: EDTA whole blood Method: Co-oximetry  (HbCO measurement)
Cyanide		Binds to iron (ferric and ferrous) containing substances like hemoglobin and cytochrome oxidase “Odor of bitter almonds” Antidote: Sodium thiosulfate, amyl and sodium nitrite
Arsenic		“Odor of garlic” “Metallic taste” Hair and nails: “Mees lines” Method: Reinsch test (Flat black)
Cadmium		Significant environmental pollutant (+) GGT in urine sample
Lead		Blocks D-ALA synthase and Ferrocheletase “Wrist drop or Foot drop” manifestation Tx: EDTA and dimercaptosuccinic acid (DMA) – remove lead áFree erythrocyte protoporphyrin (+) Basophilic stippling (course)
Mercury		Amalgamate: mix or merge w/ other substances Specimen: -Whole blood (organic mercury) -Urine (inorganic mercury) Method: Reinsch test (Silvery gray)
Drugs of Abuse
Opiates		Morphine Codeine Heroin Methadone
Tranquilizers		Diazepam (Valium) Oxazepam
Barbiturates: Sedative Hypnotics		Phenobarbital Pentobarbital Amobarbital
Dopaminergic pathway stimulants		Cocaine Benzoylecgonine Amphetamine
Hallucinogens		Phencyclidine Lysergic acid diethylamide Tetrahydrocannabinol Methaqualone
Amphetamines		Increase mental alertness (“Uppers”) MDMA (methylenedioxymethamphetamine) = ecstasy Methamphetamine  HCl = shabu
Annabolic steroids		Improves athletic performance by increasing muscle mass
Cannabinoids		Marijuana and hashish
Tetrahydrocannabinol (THC)		Psycoactive substance of marijuana Urinary metabolite: 11-nor-deltatetrahydrocannabinol (THC-COOH)
Cocaine (Crack)		Alkaloid salt Admin: Insufflation of IV or by inhalation/snorting Derived from coca plant (erythroxylon) Cardiac toxicity Prozac: inhibit the action of cocaine Urine metabolite: benzoylecgonine
Opiates		From opium poppy Heroin Morphine Codeine Methadone Major metabolites: N-acetylmorphine (heroin) and morphine Antagonist: Nalaxone (Narcan)
Phencyclidine (Angel dust or angel hair)		Hallucinogen Admin: Ingestion or inhalation Major metabolite: Phencyclidine HCl
Sedative hypnotics		Barbiturates (Secobarbital, pentobarbital, Phenobarbital) Benzodiazopines: Diazepam (Valium), Lorazepam (Ativan), Chlordiazepoxide (Librium) Major metabolite (barbiturates): Secobarbial
Lysergic acid diethylamide (LSD, Lysergide)		“Undulating vision” “Bad trip” – panic reactions
Methaqualone (Quaalude)		Pyramidal signs (Hypertonicity, hyperreflexia, myoclonus)
Vitamins
Vitamins		Water soluble: B1, B2, B3, B5, B6, B9, B12, Biotin, C, Carnitine Fat soluble: A, D, E, K
Vitamin A		CN: Retinol Def: Night blindness
Vitamin E		CN: Tocopherol Def: Mild hemolytic anemia, RBC fragility
Vitamin D2 Vitamin D3		CN: Ergocalciferol, Cholecalciferol (D2), 1,25-dihydroxycholecalciferol (D3) Def: Rickets (young), Osteomalacia (adult)
Vitamin K		CN: Phylloquinones, Menaquinones Def: Hemorrhage
Vitamin B1		CN: Thiamine Def: Beriberi, Wernicke-Korsakoff syndrome
Vitamin B2		CN: Riboflavin Def: Angular stomatitis, dermatitis, photophobia
Vitamin B3		CN: Niacin/Niacinamide/Nicotinic acid/Nicotinamide Def: Pellagra (dermatitis, disorientation, weight loss)
Vitamin B5		CN: Panthotenic acid Def: Depressed immune system, muscle weakness
Vitamin B6		CN: Pyridoxine, Pyridoxal Def: Facial seborrhea
Vitamin B9		CN: Folic acid, Pteroylglutamic acid Def: Megaloblastic anemia
Vitamin B12		CN: Cyanocobalamin Def: Megaloblastic anemia, neurologic abnormalities
Vitamin C		CN: Ascorbic acid Def: Scurvy
Biotin		Def: Dermatitis
Carnitine		Def: Muscle weakness, fatigue