Clinical Chemistry (part 3) Flashcards
EC numerical code for ALP
3.1.3.1
Catalyze the hydrolysis of various phosphomonoesters at an alkaline pH (9.0 – 10.0) into alcohol and phosphate
ALP
ALP requires __ as an activator
Magnesium
Tissues sources of ALP
Liver, small intestine, kidney, bone, placenta
Diet may induce elevation in ALP activity of blood groups __ and __ individuals who are secretors
B and O
Not usually tackled ALP isoenzyme, but lectin may be used in electrophoresis to resolve it
Kidney ALP
Origin of ALP isoforms: genetic loci
Chromosome 1:
Chromosome 2:
Chromosome 1: Kidney, Liver, Bone
Chromosome 2: Intestinal, Placental
Normal ALP isoenzymes
Intestinal, placental, bone, liver
3 abnormal ALP isoenzymes (carcinoplacental ALPs)
Regan, Nagao, Kasahara
Abnormal ALP isoenzyme with the highest incidences is found in ovarian and gynecological cancers
Regan ALP
Abnormal ALP isoenzyme observed in pleural cancer and pancreatic and bile duct carcinomas
Nagao ALP
Abnormal ALP isoenzyme observed in hepatoma and GIT tumors
Kasahara ALP
Regan ALP is found in (4 carcinomas)
Lung cancer
Breast cancer
Ovarian cancer and gynecological
Colon cancer
Most heat-stable (including normal and abnormal ALP); Resist heat up to 60 deg C for 30 minutes
Regan ALP
Variant of Regan;
Found in metastatic carcinoma of pleural surfaces
Nagao
Most anodal ALP isoenzyme
Liver ALP
Least anodal ALP isoenzyme
Intestinal
Electrophoretic mobility of ALP isoenzymes towards the anode
Intestinal > Placental > Bone > Liver
3 methods to use to improve separation of bone and liver forms
- Neuraminidase
- Wheat germ lectin
- High resolution electrophoresis
Removes sialic acid
Neuraminidase
Bind other isoenzymes
Wheat germ lectin
Uses polyacrylamide gel and isoelectric focusing to remove multiple bands of ALP isoenzymes
High resolution electrophoresis
Heat stability is determined by heating serum at __
56 deg C for 10-15 minutes
Heat stability of ALP isoenzymes
Placental > Intestinal > Liver > Bone
Most heat-labile isoenzyme
Bone ALP
Most heat-stable of all normal ALP isoenzyme
Placental ALP
Regan ALP can resist heat up to ___
60 deg C for 30 minutes
After heat denaturation,
80% activity remains in: ___
20% activity remains in: ___
Placental
Bone
Inhibits placental, intestinal, Regan, and Nagao
L-phenylalanine
Inhibits liver and bone isoenzymes
Levamisol, L-homoarginine
Inhibits bone isoenzymes
2M urea
Inhibits Nagao isoenzyme
L-leucine
Denatures liver ALP rapidly than bone
20% ethanol
Enzyme often used in the evaluation of hepatobiliary disorders (obstructive conditions) and bone disorders
ALP
Highest elevation of Alp (5-10x ULN) is attributed to either __ or ___
Liver ALP or bone ALP
Biliary tract obstruction, biliary cirrhosis (type of ALP isoenzyme)
Liver ALP
Paget’s disease (Osteitis deformans), osteogenic sarcoma, hyperparathyroidism (type of ALP isoenzyme)
Bone ALP
Moderate ( up to 3x ULN) elevation of ALP is seen in:
Hepatocellular disorders – viral hepatitis and liver cirrhosis
ALP is elevated during pregnancy (3rd trimester until onset of labor) and normalizes after ___ of labor
6 days
ALP up to 3x ULN
Healing fractures and normal growth (children)
Decreased level of what enzyme is found in inherited condition of hypophosphatasia
ALP
Avoid hemolysis, ___ is 6 times more concentrated in RBCs than in serum
ALP
Run ALP asssays ASAP; ALP activity in serum increases __ at room temperature or refrigerated for several hours
3 – 10%
ALP values may be ___ higher following ingestion of a high-fat meal due to increase intestinal fraction
25%
Plasma should not be used - __, ___, ___ inhibit ALP activity
Citrate, oxalate, EDTA
Method of ALP determination
Bowers and Mc Comb
IFCC recommended method for ALP determination Szasz modification
Most specific method
Bowers and Mc Comb
Substrate used in the Bowers and Mc Comb of ALP determination
p-nitrophenyl phosphate
ALP isoenzyme found in extrahepatic biliary obstruction and intrahepatic cholestasis
Liver ALP
Optimum pH in Bowers and Mc Comb method for ALP determination
pH 10.5 at 30 deg C
Increased p-nitrophenol production is directly proportional to the activity of ALP in the sample; measured at ___
405 nm (yellow colored complex)
___ buffer is added to bind phosphorus in the sample (phosphorus inhibits ALP activity)
2-amino-2-methyl-1-propanol
Substrate and endproducts in Bessey, Lowry, Brock method of ALP determination
S: p-nitrophenyl phosphate
P: p-nitrophenol or yellow nitrophenoxide ion
“Bakit nahuli ng PNPP ang Bessey ko na nagnanakaw ng ALPo”
Substrate and endproducts in Huggins and Talalay (ALP determination)
S: Phenophthalein diphosphate
P: Phenolphthalein red
Substrate and endproducts in Moss (ALP determination)
S: Alpha naphthol phosphate
P: Alpha-naphthol
Substrate and endproducts in Klein, Babson, and Read (ALP determination)
S: Buffered phenolphthalein phosphate
P: Free phenolphthalein
Substrate and endproducts in Bodansky, Shinowara, Jones, Reinhart (ALP determination)
S: Beta-glycerophosphate
P: Inorganis phosphate + glycerol
Substrate and endproducts in King and Armstrong
S: Phenyl phosphate
P: Phenol
Gamma Glutamyl Transferase EC numerical code
2.3.2.2
Tissue sources of GGT
Kidneys, liver, prostate, pancreas
GGT present in the serum is predominantly derived from the __ tissue where it is concentrated in the lining of biliary ductules
Liver
Highest concentration of ALP and GGT
Biliary obstruction
In Myocardial infarction, the level of GGT is __
Normal
GGT in AMI
Occurs at 4th day
Peaks for another 4 days
If GGT is increased in MI, liver damage is secondary to __
Cardiac insufficiency
GGT is a sensitive indicator of hepatobilary disorders (biliary obstruction) ___ x ULN
5-30
Used to differentiate the source of ALP elevation
GGT
GGT is affected by enzyme-inducing drugs
Warfarin, phenobarbital, and phenytoin
GGT is slightly elevated in patients with ___
Diabetes mellitus
Hemolysis will not interfere with GGT
True
Preferred specimen for GGT
Serum
Anticoagulants that inhibit GGT activity
Citrate, oxalate, fluoride
Anticoagulant that causes turbidity in GGT determination
Heparin
GGT is stable with no loss of activity for ___ at ___
1 week at 4 deg C
Methodologies for GGT determination (3)
Szasz and Rosalki
Persijn and Van der Silk method
Goldberg method
IFCC recommended method for GGT determination
Optimum pH: 8.2
Subtrate: gamma-L-glutamyl-p-nitroanilide
Product: p-anilide (405-420 nm)
Szasz and Rosalki
Aka 5’-ribonucleotide phosphohydrolase
5’ nucleotidase
a metalloprotein with zinc as its integral component
5’ nucleotidase
More sensitive to metastatic liver disease than ALP
5’ nucleotidase
levels of 5’ NT after abdominal surgery
Increased
Similar to GGT, ___ is commonly used to determine the source of ALP elevation
5’ NT
Highest elevation of 5’NT is observed in ____
hepatobiliary disorders
Increased ALP, Normal GGT, Normal 5’NT
Pregnancy
Increased ALP, Increased GGT, Increased 5’NT
Hepatobiliary disorders
Increased ALP, Normal GGT, Normal 5’NT
Bone disorders
2 enzymes that can be used to estimate the degree r severity of liver cell damage
AST and GLD
___ elevation is observed in patients with hepatocellular disorder since GLD is a mitochondrial enzyme
GLD
4-5 x ULN in GLD:
Chronic hepatitis
2 x ULN in GLD:
liver cirrhosis
pronounced elevation of GLD is seen in ___
Halothane toxicity
Potential hepatotoxic drugs can lead to notable rise in ___ level
GLD
Type of GST with the highest concentration in the liver
Alpha
Evenly distributed in the liver acinus making it useful in determining all types of hepatocyte damage
GST
___ was found more valuable than AST in detecting early rejection episodes after liver transplant procedure
GST
True cholinesterase/ choline esterase I
Acetyl choline esterase
True cholinesterase is found in ___
RBCs
Enzyme that inhibits neurotransmission, and detection of neural tube defects
Acetyl choline esterase
Pseudocholinesterase
Serum cholinesterase/ butyryl cholinesterase
Only enzyme that decreased during infection or disease states
Pseudocholinesterase
Sensitive indicator of liver synthetic capacity
Pseudocholinesterase
In hepatitis, pseudocholinesterase is decreased by how many percent?
30 - 50%
In metastatic carcinoma and cirrhosis, pseudocholinesterase is decreased by how many percent?
50 -70%
Maker of organophosphate poisoning
Pseudocholinesterase
In surgical procedures, muslce relaxants are used. ___ is normally present to hydrolyze them
cholinesterase
EC numerical code of glycogen phoshorylase
Glycogen phosphorylase
Other names of glycogen phosphorylase
1,4-alpha-D-glucan (orthophosphate)
alpha-D-glucosyltransferase
3 isoenzymes of glycogen phosphorylase
GP-LL
GP-MM
GP-BB
GP found in liver and all other human tissues, except the heart, smooth muscle, and brain
GP-LL
GP found in adult skeletal muscle
GP-MM
GP found in human brain
GP-BB
EC numerical code of creatinine kinase
2.7.3.2
Catalyzes the transfer of phosphate to creatine
Creatinine kinase
Creatine + ATP –> creatinine phosphate +
ADP
Creatinine kinase requires __ and ___
Magnesium and thiol source (cysteine)
CK is inhibited by ___ and ___
Zinc and manganese
(excess magnesium can also inhibit CK)
CK is highly seen in what tissue source
striated muscle and heart muscle
__ and __ are devoid of CK actiivty
Erythrocytes and Liver
B subunit of CK is found in chromosome
14
M subunit of CK is found in chromosome
19
___ is responsible for rephosphorylation of ADP to ATP at pH 6.7 or pH 9.0
CK
It activates CK but present in minimal concentration because it is inhibitory
Magnesium
other sulfhydryl-binding reagent sulfhydryl compounds
- N-acetyl cysteine
- Dithiothreitol
- Glutathione
” The brain type “ CK
CK-BB
“The hybrid type” CK
CK-MB”
“The muscle type” CK
CK-MM
Tumor associated marker-prostatic carcinoma and other carcinomas
CK-BB
CK-BB is ___ (usually within 10 - 50 U/L) in carcinomas
> 5 U/L
Half-life of CK-BB
2-3 hours
CK type that is fastest to move to anode
CK-BB
CK type seen in acute myocardial infarction (1st to ride)
CK-MB
AMI in CK-MB
Rise within 4-8 hours
Peak at 12-24 hours
Returns to normal within 48-72 hours
CK-MB in the serum is derived only in __
myocardium
CK-MB that is >6% of the total CK is indicative of ___
myocardial damage
Half-life of CK-MB
12 hours
CK type seen in myocardial infarction and skeletal muscle disorders
CK-MM
Highest elevation of CK is seen in ___
Duchenne’s muscular dystrophy
Major isoenzyme of CK found in serum
CK-MM
Half life of CK-MM
15 hours
AMI markers
“MyTROPICAL”
Myoglobin
Troponin I
CK-MB
AST
LDH
20% if CK-MB is found in ___
Cardiac tissue
CK-MB concentration in healthy serum
<5 ug/L
More specific during myocardial damage
Troponins
2 atypical forms of CK
CK-MI
Macro-CK
Chromosome 15
Constitutes up to 15% of the total CK
CK-MI
Largely comprises CK-BB complexed with IgG
Some comprises CK-MM complexed with a lipoprotein
Macro-CK
CK is not present in RBCs, but ___, which catalyzes a similar reaction as that of CK is present - False increase in CK
adenylate kinase
CK is stored in ___
Dark
(since recent studies show that CK is inactivated by direct light exposure)
Removes adenylate kinase
adenosine monophosphate
specimen of choice for CK
Serum
(heparinized plasma can be used; other anticoagulants inhibit CK activity)
2 methodologies in CK determination
Tanzer-Gilvarg
Oliver-Rosalki
ATP + creatine –> ADP + creatine phosphate
ADP formed is reacted with pyruvate kinase and lactate dehydrogenase
PK: ADP + phosphoenol pyruvate –> ATP + pyruvate
LDH: pyruvate + NADH –> lactate and NAD
NADH absorbs light at 340 nm (pH 9.)
Tanzer-Gilvarg method
ADP + creatine phosphate –> ATP + creatine
ATP formed from the reaction is reacted with Hexokinase and G6PD
pH: 6.7
Reverse reaction that is 6x faster than forward reaction
Addition of adenosine monophosphate inhibits adenylate kinase
Oliver-Rosalki (reverse reaction)
EC Numerical code for Lactate dehydrogenase
1.1.1.27
Catalyzes the reversible conversion of lactate and NAD into pyruvate and NADH
Lactate + NAD –> pyruvate + NADH
LDH
pH of the forward reaction in LDH determination
8.8 - 9.8
pH of the reverse reaction in LDH determination
7.4 - 7.8
One of the components of LDH determination methods
Zinc
LD-M is found in chromosome
11
LD-H is found in chromosome
12
Most abundant and most heat-stable LD
LD-2
Least anodal and most cold-labile LD (4 deg C loss of activity)
LD-5
Normal LD pattern
LD2> LD1 > LD3 > LD4 > LD5
Electrophoretic mobility of LD
(least anodal to most anodal)
LD5 - LD4 - LD3 - LD2 - LD1
LD isoenzyme present in post-pubertal human testes (not found in human serum but in seminal fluid)
LD-X or LD-C
(XXXX or CCCC)
LD observed in arteriosclerotic cardiovascular failure
LD6
3 clinical significance of LDH
Hemolytic anemia
Hepatic and non-hepatic metastases
Myocardial infarction
LD is ___ x ULN in megaloblastic anemia (pernicious anemia)
50 (highest elevation)
LD flipped pattern (LD1 > LD2) is seen in
myocardial infarction
AMI in LD
Rises within 12-24 hours
Peaks at 48-72 hours
remains elevated for long periods of time
Returns to normal within 10 days
Specimen of choice for LD
Serum
(anticoagulant may inhibit LD activity)
LD is present __ times in RBCs than in serum
100 - 150
Moderate elevations of LD
Acute viral hepatitis
Cirrhosis
Slight elevations of LD is seen in
Biliary tract disease
2 methods of LD determination
Wacker (forward reaction)
Wroblewski and La Due (reverse reaction)
Measure enzymatic activity as lactate is converted to pyruvate
UV kinetic or colorimetric
Wacker method (LD determination)
Measures increase in absorbance at 340 nm as NAD is converted to NADH (LD determination)
Colorimetric method (Wacker)
Colorimetric method (Wacker):
Addition of phenazine methosulfate and nitroblue tetrazolium which reacts with NADH to produce a positive ___
blue-purple color
Colorimetric method (Wacker):
Addition of p-nitrophenylhydrazine (or 2,4-dinitrophenylhydrazine) which reacts with pyruvate producing phenylhydrazone – ___ color at alkaline pH measured at 440 or 525 nm
Golden brown
Measures enzymatic activity as pyruvate is converted to lactate
Measures the decrease in absorbance at 340 nm as NADH is converted to NAD
3 times faster than forward reaction of LD determination
Wroblewski and La Due (reverse reaction)
Catalyzes an early step in glycolysis for glucose
Aldolase
Highest level in skeletal muscle disease or injury, metastatic carcinoma of the liver, granulocytic leukemia
Aldolase
AMI in Aldolase
Rises 6-8 hours and stay elevated up to 3-4 days
RBC alsolase is __ times as high as the serum level
150
Specimen of choice of Aldolase determination
Plasma
(because of the possible release of platelet enzyme during clotting
3 tetramers of aldolase
ALD A - skeletal muscle
ALD B - WBC, Liver, Kidney
ALD C - Brain tissue
Acid orthophosphoric monoester phosphohydrolase
Acid phosphatase
factor conversion of ACP
860 - Total ACP
853 - Non-prostatic ACP
catalyze the hydrolysis of various phosphomonoesters at an optimal pH of below 7.0 (5.0 - 6.0)
acid phosphatase
Highest concentration in prostate and RBCs, mod amounts in bone, platelets, liver, and spleen
ACP
Isoenzymes of ACP and their location
Prostatic ACP - Chr 13
Bone ACP - Chr 19 (TRACP)
Lysosomal ACP - Chr 11
Erythrocytic ACP - Chr 2
Macrophage ACP - Chr 19
Metastatic carcinoma of the prostate
ACP
Enzyme used in the medico legal evaluation of rape (up to 4 days in vaginal washings)
ACP
TR-ACP is found in (3 conditions)
Bone diseases
Gaucher’s disease
Hairy cell leukemia (leukemic reticuloendotheliosis)
ACP is labile at room temperature - acidification of sample is needed (___ is used to achieve a pH of 6.2 to 6.6)
Acetate buffer (20 uL : 1 ml serum)
Preferred sample for ACP determination
Plasma
Preferred anticoagulant for ACP determination
Citrate
Anticoagulant that inhibits ACP
Fluoride
Anticoagulant that false decrease ACP
Heparin and oxalate
ACP isoenzyme that remains in the origin
Erythrocytic ACP
ACP isoenzyme that migrates the fastest
Prostatic ACP
Inhibits the activity of the prostatic ACP and Lysosomal ACP
L-tartrate
Formula for prostatic ACP
Prostatic ACP = Total ACP - Nonprostatic ACP
2% formaldehyde and 1 mM cupric sulfate solutions inhibit the activity of ___
erythrocytic ACP
Other methods for total ACP activity
Thymolphthalein monophosphate
Alpha-naphthyl phosphate
The substrate of choice for most endpoint reactions of Total ACP activity
Thymolphthalein monophosphate
Substrate of choice for most continuous monitoring assays of Total ACP activity
Alpha-naphthyl phosphate
6 other methods of ACP determination
Bodansky
Gutman, King, Armstrong
Hudson
Babson and Reed
Roy
Reitz, Guilbault
Bodansky subtrate and product;
nonspecific to prostatic ACP; lengthy assay
S: Beta-glycerophosphate
P: Glycerol
Gutman, King, Armstrong substrate and product;
non-specific to prostatic ACP
S: phenyl phosphate
P: Phenol
Hudson substrate and product;
non-specific to prostatic ACP; rapid assay
S: p-nitrophenyl phosphate
P: p-nitrophenol
Babson and Reed substrate and product;
less sensitive to prostatic ACP
S: Alpha-naphthyl phosphate
P: Alpha-naphthol
Roy (most specific) substrate and product;
most specific method for prostatic ACP; less interferences from bilirubin and hemoglobin
S: THymolphthalein monophosphate
P: Thymolphthalein
(has a strong absorbance at 590 nm)
Reitz, Guilbault substrate and product;
fluorescence method
S: 4-methylumbeliferonephosphate
P: methylumberliferone
Catalyzes the breakdown of starch and glycogen
Amylase (diastase)
Enzyme that requires calcium and chloride for activation
Amylase (diastase)
Smalles enzyme; only enzyme present in urine
Amylase
Highest tissue concentration of amylase
acinar cells of the pancreas and salivary glands
2 isoenzymes of amylase
P-amylase
S-amylase
Other name of P-amylase
Amylopsin
Other name of S-amylase
Ptyalin
Tissue source of P-amylase
Predominantly from pancreatic tissue
Tissue source of S-amylase
salivary glands
Electrophoretic mobility of P-amylase
Slowest towards the anode
Electrophoretic mobility of S-amylase
Fastest towards the anode
Presence in sample of P-amylase
Found in urine
Presence in sample of S-amylase
Found in serum
Acute pancreatitis (Amylase)
Rises within 2-12 hours
Peaks at 24 hours
Returns to normal within 3-5 days
Amylase 5 or more x ULN
Pancreatic pseudocyts
Morphine administration
Lung and ovarian tumors
Amylase 3-5 x ULN
Pancreatic carcinoma
Mumps
Perforated peptic ulcer
Ionizing radiation
Amylase can be detected in serum, urine, and __
peritoneal fluid
Saliva contains ___ times more amylase than serum
700
Red cells do not contain amylase (T/F)
T
__ and ___ falsely elevate amylase
Morphine and opiates
Macroamylasemia, lipemia, bilirubin ___, and insulin falsely decrease amylase
> 20 mg/dl
Urine samples for amylase determination
24-hour urine sample
adjusted to a pH of 7.0 (using either 0.1 N NaOH or 0.1 N HCl)
inhibits amylase activity
Calcium-binding anticoagulants
What is the level of amlase in patients with acute pancreatitis and hyperlipemia?
Normal
(since the excess AMY is inhibited by triglyceride)
nagcancel out kaya naging normal
4 methods of amylase determination
Saccharogenic
Amyloclastic
Coupled enzymatic reaction
Chromogenic
Amylase determination method
Sugar-generating;
Includes Folin-Wu and Somogyi-Nelson;
Measures reducing sugars produced by hydrolysis of starch;
“Sugar-cutting”
Saccharogenic
Amylase determination method;
Starch-cutting or iodometric method;
Includes method of Caraway;
Measures decrease in substrate concentration;
Starch + iodine –amylase–> dark blue colored compound;
endpoint: absence of blue starch-iodine complex
Reduction in the intensity of the blue colored compound is directly proportional to the activity of amylase
Amyloclastic
Amylase determination method;
Coupling of several enzyme systems;
Often used for automated procedures;
Substrate: matopentose or maltotetraose;
Optimal pH: 6.9;
Coupled enzymes used:
(1) amylase-glucosidase-glucoamylase
(2) amylase-glucosidase-hexokinase-G6PD
(most commonly used)
Coupled enzymatic reaction
Amylase determination method;
starch is bound to a chromogenic dye;
the complex is hydrolyzed by amylase releasing dye-substrate fragments;
increase in color intensity is proportional to the activity of amylase
Chromogenic
Hydrolyzes the ester linkages of fats to produce alcohol and fatty acids
Lipase
Primary tissue source of lipase
Pancreas
Clinical significance of lipase (2)
Acute pancreatitis
Chronic pancreatitis
Acute pancreatitis in Lipase
Rises within 4-8 hours
Peaks at 24 hours
Remains elevated for 5 days to 2 weeks
More sensitive enzyme in detecting acute pancreatitis
Lipase
Complete absence of lipase resulting to fat malabsorption and severe steatorrhea
Chronic pancreatitis
Result of hemolysis in lipase
False decrease
Cause of false increase lipase concentration
Bacterial contamination
3 methods of lipase determination
Cherrry and Crandall
Turbidimetric
Colorimetric
Substrate in Cherry and Crandall method that liberates fatty acids and measured by titration with NaOH after 24-hour incubation
Olive oil
Substrate in Cherry and Crandall that is used for a more pure form of triglycerides
Triolein
Used to determine the amount of acid released in Cherry and Crandall method of lipase determination
Copper salt
___ measurement of copper indicates the amount of fatty acids present corresponding to the level of enzyme activity
Colorimeteric
Simpler and more rapid of lipase determination;
measurement of rate of clearing as an estimate for lipase activity
Turbidimetric method
Coupled reactions with peroxidase or glycerol kinase of lipase determination
Colorimetric method
Tissue source of G6PD
RBC
For assessment of X-linked disorder of G6PD deficiency;
Decreased with hereditary disposition to hemolytic crises after ingestion of oxidant drugs
G6PD
In G6PD deficiency, ___ is used
Red cell hemolysate
G6PD excess uses this type of specimen
serum
Pseudocholinesterase is found in these tissue sources
Liver
Brain
Serum
Sensitive indicator of liver synthetic capacity;
insecticide poisoning;
organophosphate poisoning (Decrease in concentration)
Pseudocholinesterase
aka serum cholinesterase, butyrylcholinesterase;
used to hydrolyze muscle relaxants administered in surgical operations
Pseudocholinesterase
Enzymes used for pancreatic profile
LIpase, amylase
Enzymes used to assess hepatic disorders
AST, ALT, (GST, GGT)
Enzymes used to assess hepatobiliary disorders
ALT, GGT, 5’NT
Average water content of the human body
40% to 70% (45% to 75%)
(2/3 ICF, 1/3 ECF)
test measures the solute concentration of plasma
osmolality
In response to an increased plasma osmolality, ____ is secreted by the posterior pituitary gland stimulated by the hypothalamus
arginine vasopressin hormone (formerly ADH)
Normal plasma osmolality
275 - 295 mOsm/kg of plasma H2O
Determines state of hydration
Increased POV = dehydrated
Osmolality
Stimuli (increased BP and Plasma volume)
Prevents salt-induced hypertension and congestive heart failure
Natriuretic peptides
2 body water compartments
Extracellular compartment (1/3)
Intracellular compartment (2/3)
2 types of extracellular water compartment
Physiological
Transcellular
Plasma osmolality and __ are maintained within a narrow range
Sodium
Principal determinant of plasma osmolality
Sodium
Produced primarily in the atrium of the heart
Reduced venous pressure due to increase blood volume;
Increases vascular permeability;
Promotes natriuresis and diuresis;
Inhibits salt appetite, water intake, and ADH and cortisol secretion in the brain
Atrial Natriuretic peptide
More potent natriuretic and diuretic
Urodilatin
Produced primarily from the ventricles of the heart;
Has cardiovascular, natriuretic, and diuretic effects
Brain natriuretic peptide
Produced in the brain, vascular endothelial cells and renal tubules
Most potent vasodilator but has no natriuretic effect
C-type natriuretic peptide
Charged particles
Electrolytes
Electrolyte panel
Sodium
Potassium
Chloride
Bicarbonate
Anticoagulant of choice for electrolyte analysis
Heparin
Balance of charges (equal no. of cations and anions)
Electroneutrality
Major extracellular cation (90%)
largely determines the plasma osmolality
Sodium
sodium levels are mainly controlled by
Aldosterone
Sodium levels in blood is dependent on (4 factors)
- sodium intake and excretion
- renal regulation
- arginine vasopressin hormone
- aldosterone
PISO
Potassium In (2 molecules)
Sodium out (3 molecules)
Causes of hypernatremia
Increased water loss relative to sodium loss
Decreased water intake
Increased sodium intake or retention
Diabetes mellitus
Hyperaldosteronism
Causes of hyponatremia
Increased sodium loss
Increased water retention
Water imbalance
Hypoaldosteronism
Potassium deficiency
Ketonuria
Salt-losing nephropathy
Vomiting, diarrhea, SIADH
Primary intracellular cation
Potassium
NV or potassium
3.5 - 5.5 mmol/L
Only electrolyte clinically affected by hemolysis
Potassium
Involved in the proper transmission of nerve impulses
Potassium
Important for heart contraction - abnormal levels can lead to altered electrocardiographic patterns
Potassium
Causes of Hyperkalemia
Decreased renal excretion
Increased potassium intake
Hemolysis, thrombocytosis, prolonged tuorniquet applications, excessive fist clenching
Causes of hypokalemia
GI loss
Decreased potassium intake
Renal loss
Cellular shift (alkalosis, insulin overdose)
Major extracellular anion
Chloride
Counterion of sodium - to maintain electroneutrality
Chloride
Maintains water balance, osmotic pressure, and anion-cation balance in the ECF
Responsible for chloride shift
Chloride
Exchange mechanism between chloride and bicarbonate across RBC membrane
Chloride shift
Causes of hyperchloremia
Excess loss of bicarbonate
Renal tubular acidosis
Metabolic acidosis
Causes of hypochloremia
Prolonged vomiting
Diabetic ketoacidosis
Hypoaldosteronism
Salt-losing nephropathy
High serum bicarbonate
5th most abundant cation
Contributor to structure of bone and teeth;
Coagulation factor IV;
for proper contraction of heart muscles and a neurotransmission regulator
Calcium
Causes of hypercalcemia
Primary hyperparathyroidism
Familial hypocalciuric hypercalcemia
Ectopic secretion of PTH by neoplasms
Malignancy associated
Vitamin D intoxication
Thyrotoxicosis
Hypoadrenalism
Causes of hypocalcemia
Primary hypoparathyroidism
Severe hypomagenesemia
Pseudohypoparathyroidism
Vitamin D deficiency
Chronic renal failure
Fanconi’s syndrome
Rhabdomyolysis
Most reabsorbed in kidneys as CO2
Bicarbonate
Increased in metabolic alkalosis
Decreased in metabolic acidosis
Bicarbonate
Second most abundant anion in ECF
Account for more than 90% of the total CO2;
Major component of the buffering system in blood
Diffuses out of the cell in exchange for chloride
Bicarbonate
Regulation controlled largely by kidneys
PTH increases renal reabsorption and intestinal reabsorption
Aldosterone and thyroxine increase renal excretion
Magnesium
Increased in renal failure, acute diabetic acidosis, dehydration;
decreased in chronic alcoholism, malabsorption, severe diarrhea, pancratitis
Magnesium
Second most abundant intracellular cation
Low levels cause tetany
Magnesium
Kidneys play major role in regulation;
PTH decreases it while Vitamin D and GH increase its levels
Phosphate
Hyperphosphatemia
Acute or chronic renal failure
Neonates with increased intake
Increased breakdown of cells
Lymphoblastic leukemia
Hypophophostemia
Diabetic ketoacidosis
COPD
Asthma
Malignancies
Inflammatory bowel disease
Only electrolyte affected by diurnal variation
Highest levels in the late morning and lowest in the evening
Phosphate
Concentration of inorganic and organic phosphates in adults
60 grams
Electrolyte that is not specifically regulated;
Liver is the major organ that removes it
Lactate
Lactate is increased in :
Hypoxic conditions
(shock, MI, CHF, pulmonary edema, blood loss)
Metabolic origin
(DM, severe infection, leukemia, liver and kidney diseases, and toxins)
By-product of an emergency mechanism that produces a small amount of ATP when oxygen is severely diminished
Lactate
Specimen considerations in sodium determination
Serum, plasma, 24 hr urine, sweat, CSF
Formula for sodium determination
Na = CO2 + Cl + 10 or
Na = CO2 + Cl + 12
3 methodologies for Sodium determination
Flame Emission Photometry
Atomic Absorption Spectrophotometry
Ion Selective Electrode (most common method)
- emits light at 590 nm
Method wherein sodium produces yellow color when exposed to flame
- sodium emits light at 590 nm
- serum is diluted with high purity water (1:100 or 1:200)
Flame emission photometry
NV of serum sodium
135 to 145 mmol/L
Normal value of 24-hour urine sample (sodium)
40 to 220 mmol/day
NV of CSF serum
138 to 150 mmol/L
Specimen considerations for potassium
Serum/Plasma
No to prolonged tourniquet application
3 methods of potassium determination
Flame Emission photometry
AAS
ISE (most common method)
- emits light at 768 nm
In sodium determination using ISE, what is the membrane used?
Valinomycin
NV of serum potassium
3.4 to 5.0 mmol/L
NV of potassium in 24 hour sample
25 to 125 mmol/day
Electrolyte that has the most narrow reference range and is most strictly regulated by the body
Potassium
Anticoagulant of choice for chloride measurements
lithium heparin
4 methods of chloride determination
ISE
Amperometric-Colorimetric titration
Mercurimetric titration
Colorimetric method
Most commonly used method of chloride measurement
ISE
Membrane used in ISE for the determination of chloride
Combination of silver wire coated with AgCl
Principle of Amperomeric-Colorimetric titration of chloride measurement
Cotlove Chloridometer
Principle of mercurimetric method of chloride determination
Sshales and Schales method
What leads to a positive error in mercurimetric titration in chloride determination
Bromide
Uses mercuric thiocyanate and ferric nitrate to form ferric thiocyanate (red colored complex with a peak absorbance at 480 nm)
- used in autoanalyzer (Technicon) in chloride measurement
Colorimetric method
NV serum chloride
98 to 107 mmol/L
NV of chloride in 24 hr urine
110 to 250 mmol/day
In 24 hr urine calcium, the sample is acidified using ___
6M HCl (1ml per 100 ml urine)
- to prevent precipitation of calcium
2 methodologies in calcium determination
Orthocresolphthalein complexone
Arsenzo III
Conversion factor of calcium
0.25
A calcium chelator
-produces reddish complex (570 to 578nm)
-used in autoanalyzer (Hitachi and Dimension)
Orthocresolphthalein complexone
Method used in calcium measurement
- used in autoanalyzer (Vitros and Synchron)
Arsenzo III
NV of Total Calcium
Child: 2.20 - 2.70 mmol/L
Adult: 2.15 - 2.50 mmol/L
NV of Ionized calcium
Child: 1.20 - 1.38 mmol/L
Adult: 1.16 - 1.32 mmol/L
NV of 24 hour urine calcium
2.50 - 7.50 mmol/day
24 hour urine ___ is acidified with __
6M HCl
5 methods of magnesium measurement
-Colorimetric method
-Dye lake method
-Fluorometry
-AAS: Reference method
-ISE: most common
Magnesium measurement wherein the titan yellow dye (clayton yellow/thiazole yello) forms a red lake with magnesium)
Dye-lake method
NV for serum magnesium
0.63 - 1.0 mmol/L
Method for phosphate measurement
Fiske-Subbarow Method
Reagent used in Fiske-Subbarow method
Molybdate
NV for serum magnesium
Neonate: 1.45 - 2.91 mmol/L
Child: 1.45 - 1.78 mmol/L
Adult: 0.87 - 1.45 mmol/L
NV or 24 hour urine phosphate
13 - 42 mmol/day
Difference between unmeasured anions and unmeasured cations;
-useful in indicating an increase in one or more of the unmeasured anions in the serum
-serves as a form of quality control for the analyzer used to measure these electrolytes
Anion gap
Formula for anion gap
AG = Na - (Cl + HCO3) or
AG = (Na + K) - (Cl + HCO3)
NV of anion gap
7 - 16 mmol/L or
10 - 20 mmol/L
Increased AG
Methanol
Uremia
Diabetic ketoacidosis
Iron, inhalants, isoniazid. ibuprofen
Lactic acidosis
Ethylene glycol poisoning, ethanol ketoacidosis
Salicylates, starvation
Decreased AG
Hypoalbuminemia
Severe hypercalcemia
Multiple Myeloma
Instrument error
Substance that can yield a hydrogen ion when dissolved in water
Acid
Substance that can yield hydroxyl ion when dissolved in water
Base
The relative strength and ability of acids and bases to dissociate in water
Dissociation constant or ionization constant K value
5 Buffer systems
Bicarbonate
Ammonia-Ammonium
Protein
Phosphate
Hemoglobin
“BAPPH”
Important buffer of H in red blood cells
-binds and release H to facilitate its buffering effect
Hemoglobin Buffer System
Most abundant buffer in the ICF and blood plasma
-most circulating proteins have a negative charge capable of binding H
Protein Buffer System
Important buffer system in the secretion of H via urination
Ammonia-ammonium buffer system
If pH is too high:
(what is the response of the carbonic acid-bicarbonate buffer system)
HCO3 is excreted while H is reabsorbed
if pH is too low
(what is the response of the carbonic acid-bicarbonate buffer system)
H will be excreted while HCO3 is reabsorbed
Normal ratio of bicarbonate to carbonic acid
20:1
2 organs that play important roles in regulating blood pH
Lungs, kidneys
The interrelationship of lungs and kidneys in maintaining pH is depicted by the ___
Henderson-Hasselbach equation
(recall)
Important regulator of pH in the cytosol
- buffers acid in urine
-secretes excess H in the kidney tubule
-combines with HPO4 to produce H2PO4
Phosphate buffer system
___ is expressed in concentration of dissolved carbon dioxide
H2CO3
Concentration is controlled by the kidneys; Non-respiratory or “metabolic” component
HCO3
Concentration is controlled by the lungs;
- respiratory component
H2CO3
___ is computed by multiplying partial pressure of carbon dioxide (mmHg) by alpha (solubility coefficient of carbon dioxide)
dCO2
Normal average of pCO2 is equal to __
40 mmHg
THe solubility coefficient of CO2 is ___
0.03 mmol/K/ mmHg
the Pka is equal to 6.1, with a bicarbonate concentration of ___
24 mmol/L
The normal ratio of bicarbonate to carbonic acid, which is expressed in dCO2 is ___
20:1
The normal blood pH is 7.4. the normal range is from
7.35 to 7.45
Blood pH <7.35
acidosis
Blood pH >7.45
alkalosis
Action of the body to restore acid-base homeostasis whenever an imbalance occurs
-alters the factor not primarily affected by the pathologic process
Compensation
In metabolic/nonrespiratory acidosis or alkalosis: ____ compenstation
- response is short-term and often incomplete
Respiratory
In respiratory acidosis or alkalosis: ___ compensation
-response is slower but long term and potentially complete
Renal
If the pH has returned to the normal range, meaning the 20:1 ratio has been restored, it is considered ____
Fully compensated
If the pH is approaching the normal range, it is considered
Partially compensated
Due to a decreased bicarbonate level
Metabolic acidosis
Metabolic acidosis is caused by:
- Renal tubular acidosis
- Direct administration of acid-producing substances (ammonium chloride, calcium chloride)
- Excessive formation of organic acids (diabetic ketoacidosis, starvation)
- Excessive loss of bicarbonate (diarrhea)
Primary compensation for metabolic acidosis
lungs blow off CO2 to raise pH
Significant laboratory findings of metabolic acidosis
Decreased pH, normal pCO2, decreased HCO3
Due to decreased alveolar ventilation (hypoventilation)
Respiratory acidosis
Respiratory acidosis results to ___
hypercapnia
Respiratory acidosis is caused by:
- Lung diseases (COPD, bronchopneumonia)
- Hypoventilation caused by drugs (barbituates, morphine, alcohol)
- Mechanical obstruction or asphyxiation
- Asthma
- Severe pulmonary infection
Primary compensation of respiratory acidosis
Renal compensation (it takes days to weeks to complete)
Significant laboratory findings of respiratory acidosis
Decreased pH, increased pCO2, normal HCO3
Due to an increased bicarbonate level; ratio is greater than 20:1 because of increased HCO3
Metabolic alkalosis
Metabolic alkalosis is caused by:
- Excessive loss of acid (vomiting and nasogastric suctioning)
- Prolonged use of diuretics
- Excessive sodium bicarbonate administration
- Hyperaldosteronism and Cushing’s syndrome
- Ingestion of bicarbonate-producing salts (sodium, lactate, citrate, and acetate)
Primary compensation of metabolic alkalosis
lungs retain CO2 to lower pH
Significant laboratory findings of metabolic alkalosis
Increased pH, normal pCO2, Increased HCO3
Due to an increased alveolar ventilation (hyperventilation)
Respiratory alkalosis
Causes of respiratory alkalosis
- Hysteria
- Pulmonary emboli and pulmonary fibrosis
- Fever
- Increased in environmental temperature
- Drugs that stimulates respiratory center (salicylates)
- Congestive heart failure
Primary compensation of respiratory alkalosis
Renal compensation
Significant laboratory findings in respiratory alkalosis
Increased pH, decreased pCO2, normal HCO3
NV
Blood pH
pCO2
HCO3
pO2
Total CO2
Oxygen saturation
NV
Blood pH: 7.35 - 7.45
pCO2: 35 - 45 mmHg
HCO3: 22 - 26 mmol/L
pO2: 80 - 110 mmHg
Total CO2: 23 - 27 mmol/L
Oxygen saturation
3 methods for blood gas analysis
-Spectrophotometric (Co-oximeter)
-Blood Gas analyzers
-Stow-Severinghaus ISE method
-Enzymatic methods
Method for blood gas analysis that determines oxygen saturation and the actual percent of oxyhemoglobin
Spectrophotometric (Co-oximeter)
Method for blood gas analysis that use electrodes as sensing devices to measure pO2, pCO2, and pH
Blood Gas Analyzers
pO2 measurement is ___
amperometric
pCO2 measurement is ___
potentiometric
Method for blood gas analysis that measures total CO2 with the use of an acid reagent
Stow-Severinghaus ISE method
Method for blood gas analysis that use phosphoenolpyruvate carboxylase and malate dehydrogenase
Enzymatic methods
Preferred sample for blood gas analysis
Arterial blood
Air trapped in syringe for blood gas analysis leads to
increased pO2, decreased pCO2
Anticoagulant used in blood gas analysis and its corresponding concentration
Liquid heparin - 0.05 ml per ml of blood
If processing for blood gas analysis is delayed, what is the next course of action
Transport the specimen in chilling condition
Specialized organs capable of producing hormone
Endocrine system
3 structural classes of hormones
Steroid hormones
Protein hormones
Amine hormones
Site of production of steroid hormones
Adrenal glands, gonads, placenta
Chemical component of steroid hormones
Cholesterol
Carrier of steroid hormones
Protein
Examples of steroid hormones
Cortisol
Aldosterone
Testosterone
Estrogen
Progesterone
Site of production of protein hormones
Anterior pituitary, placenta, and parathyroid glands
Chemical component of protein hormones
Protein
Production and storage of protein hormones
Synthesized then stored in cell as secretory granules until needed
Examples of protein hormones
FSH
LH
TSH
hCG
Glucagon
Parathyroid hormone
GH
Prolactin
Site of production of amine hormones
Thyroid and adrenal glands
Chemical component of amine hormones
Amino acids
Examples of amine hormones
Epinephrine
Norepinephrine
Thyroxine
Triiodothyronine
Butterfly-shaped organ located on the posterior portion of the neck
Thyroid gland
ligament that separates the left and right lobes of the thyroid gland
isthmus
2 cell types of the thyroid gland
Follicular cells
Parafollicular cells
Produces metabolic hormones T3 and T4
Follicular cells
AKA perfollicular cells or C-cells; produces calcitonin
Parafollicular cells
T3 is composed of
MIT + DIT
-more biologically active
T4 is composed of
DIT + DIT
- greater concentration
Primary Hypothyroidism
(T3, T4, TSH levels)
Low T3 and T4 levels, Increased TSH levels
Secondary Hypothyroidism
Low T3, T4, and TSH levels
Primary hyperthyroidism
High T3 and T4 levels, low TSH levels
Secondary hyperthyroidism
High T3, T4, TSH levels
Basal metabolic rate and sympathetic response in hypothyroidism
Decreased
Hypothyroidism, weight ___
Gain
Temperature tolerance in hypothyroidism
Cold intolerance
Decreased sweating
GIT function in hypothyroidism
Constipation
Decreased appetite
Cardiovascular function in hypothyroidism
Decreased cardiac output
Bradycardia
Respiratory function in hypothyroidism
Hypoventilation
General appearance in hypothyroidism
Myxedema
Deep voice
Impaired growth (in children)
General behavior in hypothyroidism
Mental retardation (infant)
Mental and physical sluggishness
Somnolence
Basal metabolic rate and sympathetic response in hyperthyroidism
Increased
Weight in hyperthyroidism
Loss
Temperature tolerance in hyperthyroidism
Heat intolerance
Increased sweating
GIT function in hyperthyroidism
Diarrhea
Increased appetite
Cardiovascular function in hyperthyroidism
Increased cardiac output
Tachycardia and palpitation
Respiratory function in hyperthyroidism
Dyspnea
General appearance in hyperthyroidism
Exophthalmos
Decreased blinking
Enlarged thyroid
General behavior in hyperthyroidism
Restlessness
Irritability and anxiety
Hyperkinesis and wakefulness
-Decreased T3 and T4
-Decreased TSH
-Increased or Normal TRH
-TSH before administration is low
Secondary hypothyroidism
-Decreased T3 and T4
-Decreased TSH
-Decreased TRH
-TSH before administration is low
After administration is high
Tertiary hypothyroidism
Anti-microsomal antibodies (anti-thyroid peroxidase antibodies)
-Anti-thyroglobulin antibodies
-primary hypothyroidism
Hashimoto’s thyroiditis
Anti-TSH receptor antibodies
-primary hyperthyroidism
Grave’s disease
Major transport protein for T3 and T4 (approximately 70 - 75%)
Thyroid-Binding Globulin (TBG)
Percentage of T4 that is unbound
0.03 - 0.05%
Percentage of T3 that is free
0.5%
Which is more potent, T3 or T4?
T3
Other names of T4
Thyroxine
Methods for T4 measurement
RIA
Fluorometric enzyme immunoassay
Fluorescence polarization immunoassay (FPIA)
Other name of T3
Triiodothyronine
Methods for T3 determination
RIA
Microparticle enzyme immunoassay
Fluorometric enzyme immunoassay
THBR other names
Thyroid hormone binding ratio
T3 uptake test
T uptake test
Methods for THBR measurement
Resin uptake
RIA
Methods for FT4 determination
Equilibrium dialysis
Immunometric assay (chemiluminescence)
Methods for FT3 determination
RIA
FT4 index methods of measurement
Calculation from T4 and THBR
FT3 index method of measurement
Calculation from T3 and THBR
Methods for TSH measurement
RIA
Immunometric assay (IMA)
3 classes of steroid hormones
Mineralcorticoids
Glucocorticoids
Sex steroids
Function of mineralocorticoids
fluid and electrolyte balance
Function of glucocorticoids
glucose production and protein metabolism
Function of sex steroids
regulate sexual development and control many aspects of pregnancy
Hormone under mineralocorticoids
Aldosterone
3 hormones under glucocorticoids
Cortisol
Cortisone
11-deoxycortisol
3 hormones under sex steroids
Androgens
Estrogens
Progesterone
Most abundant hormone in post-menopausal women
Estrone (E1)
Most potent ; most abundant in pre-menopausal women
Estradiol (E2)
Metabolite of estradiol; estrogen found in maternal women; major estrogen secreted by placenta
Estriol (E3)
steroid transport protein that nonspecific and carries many steroids
albumin
Steroid transport protein that carries cortisol and derivatives; progesterone
Cortisol-binding globulin
Steroid transport protein for testosterone and estradiol
Sex hormone-binding globulin
3 colorimetric assays in steroid hormone analysis
Zimmerman reaction
Porter-Silber assay
Kober reaction
Measurement of 17-ketosteroids (metabolites of several precursors to cortisol) to assess androgen production by the adrenal glands
Zimmermann reaction
Primary reagent in Zimmermann reaction
m-dinitrobenzene in alcoholic KOH solution
Result of Zimmermann reaction
Purple color (520 nm)
For urine cortisol and derivatives (cortisone and 11-deoxycortisol)
Porter-Silber assay
Primary reagent in Porter-Silber assay
2,4-dinitrophenylhydrazine
Result of Porter-Silber assay
Yellow derivative (410 nm)
FOr urine estrogen determination: sufficiently sensitive to quantitate total urine estrogen during the middle and latter stages of pregnancy
Kober reaction
Primary reagent in Kober reaction
Strong aqueous sulfuric acid solution containing hydroquinone
Result of Kober reaction
Reddish-brown color (472 nm, 512 nm, and 556 nm)
Formed by the conversion of tyrosine
Catecholamines
2 best known catecholamines
epinephrine
norepinephrine
Catecholamines are synthesized and stored by the __
Chromaffin cells of the adrenal medulla
2 end products of catecholamine metabolism
Homovanillic acid
Vanillylmandelic acid
Method of determination of catecholamines
Pisano method
Colorimetric assay for total metanephrines
-involves extraction followed by colorimetric reaction
-conversion to vanillin (absorbance maximum at 360 nm) is accomplished through periodate oxidation
Pisano method
Increased levels of catecholamines are seen in
Pheochromocytoma
Neuroblastoma
Essential hypertension
Hypothyroidism
Diabetic acidosis
Cardiac disease
Burns
Septicemia
Depression
Decreased levels of catecholamines are seen in
Hyperthyroidism
long term diabetes mellitus
Involves analysis, assessment and evaluation of circulating concentrations of drugs in serum, plasma, or whole blood ;to ensure that a given dosage of drug produces maximal therapeutic benefit and minimal toxic side effects
Therapeutic Drug Monitoring (TDM)
Concerned with the application or administration of drugs to patients for the purpose of prevention and treatment of disease
Pharmacotherapeutics
Describe what the drug does to the body
Pharmacodynamics
Describe how drugs are received and handled by the body
Pharmacokinetics
The rate of administration is equal tot he rates of metabolism and excretion
Steady state
Refers to the serum concentration of drug established to achieve desired clinical effect
Therapeutic range
Drugs enter hepatic portal system first before entering the general circulation
First pass metabolism
Refers to the spread of drug from its point of entry throughout the systemic circulation and into various tissues
Drug distribution
Represents the time needed for the serum concentration of a drug to decrease by half
Half-life
preferred sample for TDM
Serum
Why are samples for TDM not collected in serum separator tubes
Drugs are reabsorbed in gel
Maximum specimen; collected 30 - 60 minutes after drug administration but may vary depending on the type of drug
Peak specimen
Minimum concentration; collected before administration of the next dose
Trough specimen
Laboratory results should contain 2 factors
Time of last dose
Time of extraction
Effective dose; predicted to be effective or have therapeutic benefit in 50% population
ED50
Toxic dose; predicted to produce toxic response in 50% population
TD50
Lethal dose; predict death in 50% of population
LD50
Refers to a constellation of clinical signs and symptoms that suggest a specific class of poisoning
Toxidromes
Most commonly abused chemical substance
Alcohol
Method of alcohol determination
Flame ionization gas chromatography
Headspace gas chromatography
Most ingested ethanol is converted to __
acetic acid
Alcohol is increased in __
GGT, AST, AST/ALT ratio (>2.0), increased HDL, MCV
Disinfectatn use for alcohol measurement
Benzalkonium chloride
Methods for cyanide determination
Photometric analysis
Headspace gas chromatography
Characteristic odor of cyanide
Bitter almonds
Cyanide binds to hemoglobin causing ___
hypoxia
Methods for carbon monoxide measurement
Gas chromatography
Spot test for CO exposure
Differential spectrophotometry
Colorless, tasteless, odorless gas;
common sources are car exhausts and cigarette
-Has 250 times greater affinity for hemoglobin compared to oxygen
-produces cherry red color of the blood
Carbon monoxide
Odor of garlic;
highly keratinophilic, carcinogenic;
specimen toxicity analysis include skin, hair, or nails
Arsenic
can cause toxic effects in brain and can lead to anemia
(measurement of blood level)
Lead
Previously used in sphygmomanometer, thermometers, and manometers
- toxicity: can alter proteins and cause severe kidney damage
Mercury
Found in pesticides and insecticides
Toxicity decreases cholinesterase
Organophosphatases
Sedative hypnotics drugs
Barbiturates
Benzodiazepines
Derived from the leaves of marijuana plant Cannabis sativa
Cannabinoids
Alkaloid found in a plant Erythroxylon coca
Cocaine
Structurally similar to serotonin; found in fungus Claviceps purpura
Lysergic Acid Drugs (LSD)
Stimulants and hallucinogen
Amphetamines
Produced directly by the tumor as an effect of the tumor in a healthy tissue
Tumor markers
Ideal characteristics of tumor markers
- Tumor specific
- Absent or present in very narrow range in healthy individuals
- Readily detectable in body fluid
Tumor marker for hepatic and testicular cancers
AFP
Tumor marker for pancreatic cancer
Amylase
Tumor marker for breast or ovarian cancer
BRCA-1
Tumor marker for ovarian cancer (treatment and recurrence)
CA 125
Tumor marker for breast cancer
CA 15.3, Cathepsin-D, Estrogen receptor , HER-2/neu
Tumor marker for gastric, pancreatic, and colorectal cancers
CA 19.9
Tumor markers for gastric and pancreatic cancers (treatment and recurrence)
CA 50
Tumor marker for breast cancer (treatment and recurrence)
CA 27-29
Tumor marker for medullary thyroid cancer
Calcitonin
Tumor marker for colorectal, stomach, breast, lung cancer (treatment and recurrence)
CEA
Tumor marker for small cell lung cancer, prostate cancer
CK-1
TUmor cancer for hepatoma
GGT
Tumor marker for urinary bladder cancer
Nuclear matrix protein (NMP)
Tumor markers for monitoring breast cancer
CA 15-3, HER-2/neu, CA 27-29
Tumor marker for monitoring ovarian cancer
CA 125
Tumor marker for monitoring pancreatic cancer
CA 19-9
