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Interpret the following results:

1.) pH = 7.25

pCO2 = 35 mm Hg

HCO3 = 15 mmol/L

Uncompensated metabolic acidosis

Uncompensated respiratory acidosis

Partially compensated metabolic acidosis

partially compensated respiratory acidosis

2.) pH = 7.30

pCO2 = 50 mm Hg

HCO3 = 25 mmol/L

Uncompensated respiratory acidosis

Uncompensated metabolic acidosis

Partially compensated metabolic acidosis

partially compensated respiratory acidosis

3.) pH = 7.32

pCO2 = 30 mm Hg

HCO3 = 18 mmol/L

Partially compensated metabolic acidosis

Partially compensated respiratory acidosis

Fully compensated respiratory acidosis

Uncompensated respiratory acidosis

4.) pH = 7.30

pCO2 = 49 mm Hg

HCO3 = 30 mmol/L

Partially compensated respiratory acidosis

Partially compensated metabolic acidosis

Delayed specimen analysis

uncompensated respiratory acidosis

5.) pH = 7.47

pCO2 = 38 mm Hg

HCO3 = 29 mmol/L

Uncompensated metabolic alkalosis

uncompensated respiratory alkalosis

Partially compensated metabolic alkalosis

Partially compensated respiratory alkalosis

6.) pH = 7.50

pCO2 = 18 mm Hg

HCO3 = 24 mmol/L

Uncompensated respiratory alkalosis

Uncompensated metabolic alkalosis

Partially compensated respiratory alkalosis

Partially compensated metabolic alkalosis

7.) pH = 7.49

pCO2 = 52 mm Hg

HCO3 = 32 mmol/L

Partially compensated metabolic alkalosis

partially compensated respiratory alkalosis

uncompensated metabolic alkalosis

uncompensated respiratory alkalosis

8.) pH = 7.48

pCO2 = 33 mm Hg

HCO3 = 20 mmol/L

Partially compensated respiratory alkalosis

Partially compensated metabolic alkalosis

Delayed specimen analysis

Specimen received in lab on ice

Match each analyte to it's reference range. *All answers may not be used*

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Specimen integrity

Specimens must be given on lyophilized heparin whole blood samples.
They must be analyzed as soon as possible or the sample will become acidic
ASAP or acidic
Must not be exposed to air or have any bubbles or it will become more basic
bubbles(air)=basic

provide a couple of questions that give scenario such as - An ABG sample had accidently been delivered to the wrong department through your hospital's tube system. 1 hour following the time of draw, the specimen was received into the lab for analysis. The instrument reports the following results:
ph 7.24
pco2 52
hco3 28
How would you interpret these results

Patient has uncompensated respiratory acidosis

Patient has partially compensated respiratory acidosis

Delayed specimen analysis, increased bicarb

Delayed specimen analysis, decreased pH

Interpret the following results:
pH 7.53
pco2 31
hco3 32

partially compensated metabolic alkalosis

Partially compensated respiratory alkalosis

Specimen exposed to air, rerun

Specimen analysis delay, rerun

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ABG interpretation is typically based off the 3 analytes: pH, pco2, and hco3(bicarb)

Begin by determining if the pH results indicate acidosis or alkalosis:

Acidosis = pH<7.35

indicates a higher H+ concentration

Alkalosis = pH>7.45

indicates a lower H+ concentration

Next, determine if the cause of is of metabolic or respiratory origin:

Metabolic - change in bicarbonate due to a renal or metabolic function

Respiratory - change in pco2 due to a ventilation or respiratory component

Lastly, determine if the state of compensation:

Fully compensated - blood pH is normal

Partially compensated - pco2 or bicarb are moving in a direction to counter act the disorder

**Remember: Hco3 is an acid, bicarb is a base.

To compensate acidosis, bicarb must increase and pco2 decrease

To compensate alkalosis, pco2 must increase and bicarb decrease

Uncompensated - Neither pco2 or bicarb are shifting to bring blood pH back to equilibrium
Ex: pH < 7.35 = Acidosis
pco2 = 53
bicarb = 25
**High pH and pco2 indicate acidosis which is not being compensated whatsoever because the base didn't increase to counter-act the acid.

**Flowchart**

A much easier to way interpret blood gas is by using the acronym/mnemonic ROME!

R - Respiratory

O - Opposite

M - Metabolic

E - Equal

Look at the direction of pH. up or down, then look at

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ph
pco2
hco3

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Risk Factors

Positive - increase the chance for disease

Negative - decrease the chance for disease

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Manganese

In steel production and dry cell batteries

Manganese-rich foods include:  whole grains foods, nuts, leafy vegetables, soy products, and teas

Clinical significance:

Acts as a nonspecific enzyme activator and is an essential constituent of metalloenzymes

Deficiencies characterized by blood clotting defects, hypocholesterolemia, dermatitis, and elevated calcium, phosphorus, and alkaline phosphatase

Toxicity associated with neurological symptoms resembling Parkinson disease

Specimen:

Whole blood

Methods:

Atomic absorption spectrophotometry

ICP-MS

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Chromium

Used in manufacturing and released into the environment as industrial waste, and found in processed meats, whole grain products, green beans, broccoli, and some spices

Clinical significance:

Helps maintain normal metabolism of glucose, fat, and cholesterol

Deficiencies are characterized by glucose intolerance, glycosuria, hypercholesterolemia, impaired fertility, and decreased sperm counts

Toxicity is associated with cancer, severe dermatitis, and skin ulcers

Specimen:

Plasma, serum, or urine

Care must be taken to avoid exposure to stainless steel

Methods:

Atomic absorption spectrophotometry

Inductively Coupled Plasma-MS

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Copper
Absorption:

50 – 80 % of ingested copper is absorbed in the duodenum and stomach

Clinical significance:

Plays an important role in iron metabolism

Ceruloplasmin

The major copper containing protein in plasma

Copper Deficiency - Menkes syndrome:

An extreme form of copper deficiency

Steely-hair syndrome (kinky or twisted brittle hair)

Defect in copper transport and storage

Copper toxicity - Wilson’s disease:

Usually occurs 6 – 40 years of age

Copper accumulates in the liver, brain, kidney, and cornea

Causes cirrhosis, neurological disorders, and Kayser-Fleischer rings (green-brown discoloration) in the cornea

Laboratory assessment of Copper
Specimen:

Serum or plasma

Methods:

Copper- Atomic absorption spectrophotometry, photometric methods

Ceruloplasmin- photometric methods, immmunonephelometry

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Zinc

Absorption

20 – 30% of ingested zinc is absorbed

Mostly in the duodenum and proximal jejunum

Clinical significance

Essential to enzyme activity

Wound healing

Deficiencies cause retardation of growth and skeletal maturation

Interferes with copper absorption

Laboratory assessment of Zinc
Specimen:

Serum or plasma

Avoid hemolysis

Method:

Atomic Absorption Spectrophotometry

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Lab markers:

↑ serum iron

↓ TIBC

↓ transferrin

↑ % saturation

↑ ferritin

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Causes:

Iron poisoning

Hereditary hemochromatosis

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Lab markers:

↓ serum iron

↑ TIBC

↑ transferrin

↓ % saturation

↓ ferritin

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Causes:

Increased blood loss

Decreased dietary iron intake

Decreased release from ferritin

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Ferritin

Sensitive indicator of iron deficiency

Methodology:

Measured by immunochemical methods

ELISA

Chemiluminescent techniques

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Transferrin

Methodology:

Measured by immunochemical methods -  nephelometry.

Calculated:

transferrin (mg/dL) = 0.70 x TIBC

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% saturation

The ratio of serum iron to TIBC

Total iron divided by TIBC X 100

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Formula for calculated TIBC:

TIBC(µg/dL) = transferrin (mg/dL) x 1.25

Calculated TIBC can be slightly lower than actual TIBC due to iron bound by proteins other than transferrin

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TIBC

Amount of iron that could be bound by saturating transferrin and other minor iron-binding proteins in the sample

Specimen: same as iron

Methodology:

Add sufficient Fe+3 to saturate the binding sites on transferrin

Excess Fe+3 are removed by precipitating them out and centrifuging

Remaining solution contains iron bound proteins that can be analyzed for total iron content

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Laboratory evaluation of iron
Specimen:

Serum or heparin plasma

No oxalate, citrate, or EDTA - bind to the Fe ions

No hemolysis

Early morning specimen recommended due to diurnal variation

Methodology:

Fe+3 is released from transferrin by acidification and complexed with a color reagent to be read spectrophotometrically

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Transferrin – intracellular transport system to deliver iron to tissue such as bone marrow for heme synthesis

Ferritin – the major iron storage compound

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Absorption:

~10% of dietary iron is absorbed in the intestines

Most dietary iron is in the form Fe+3 and must be reduced to Fe+2 by agents such as Vitamin C to be absorbed

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Vitamin K deficiency: Hemorrhagic episodes

Due to:

Antibiotic therapy

Sterile gut of infants with minimal passage of vitamin K through breast milk

Vitamin K antagonists – Coumadin therapy

Elevated levels of Vitamin K:

Rarely seen in adults.

Large doses cause hyperbilirubinemia in infants

Laboratory assessment

Vitamin K not assayed

Prothrombin time

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Vitamin K

Function:

Essential for the formation of prothrombin and at least 5 other coagulation proteins (factors VII, IX, and X and proteins C and S)

Helps to convert precursor forms of these coagulation proteins to functional forms in the liver

50% of the vitamin K requirement is synthesized by intestinal bacteria

Dietary sources:  cabbage, cauliflower, spinach, and other leafy vegetables, pork, liver, soybeans, and vegetable oils

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Vitamin E deficiency:
Seen in:

Very low birth weight infants.

Patients who do not absorb fat normally (CF patients)Hemolytic anemia.

Premature infants are commonly supplemented with vitamin E to stabilize RBCs

Laboratory Assessment

α-tocopherol, the most biologically active form

HPLC

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Vitamin E
Functions:

Powerful antioxidant

Strengthens cell membranes

As an antioxidant, has been approved to be used to delay progress of Alzheimer’s

Dietary sources: fresh leafy vegetables, egg yolk, peanuts, vegetable oil, and margarine

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Elevated levels of vitamin D

Toxic

Hypercalcemia

Hypercalcuria.

Leads to calcium deposits in soft tissue and irreversible renal and cardiac damage

Due to:

Hyperparathyroidism

Hypophosphatemia

Pregnancy

Laboratory assessment

2 metabolic forms routinely measured

1,25(OH)2D3  - useful in diagnosing primary hyperparathyroidism, different types of rickets, when monitoring pts with chronic renal failure, and assessing pts on Vitamin D therapy

25(OH)D3  - major circulating form of Vitamin D, useful in nutritional assessment and intoxication

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Vitamin D deficiency:

Up to 75% of the world’s population is vitamin D deficient

Rickets- impairs the body’s ability to absorb calcium, causing poor bone development and a deformation of the skeleton in children.

Osteomalacia = vitamin D deficiency in adults, under mineralization of bone matrix in bone remodeling

Caused by malnutrition, vegetarian diet, malabsorption (small bowel disease & pancreatic insufficiency), chronic renal failure, hepatobiliary disease, obesity, anticonvulsant drugs, sun avoidance, and hypoparathyroidism

Those living in the northern hemisphere are more likely to have low levels of vitamin D  due to decreased sun exposure.

Dark skin reduces vitamin D synthesis.

Decreased levels lead to secondary hyperparathyroidism (calcium lost from bones)

Symptoms:

Fatigue, generalized aches, muscle weakness, increased bone fractures

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Vitamin D
Function:

Essential for development and maintenance of skeletal integrity and for calcium and phosphate homeostasis

Necessary for the body to absorb calcium

Exposure to sunlight triggers synthesis of vitamin D in the skin

Minimum UV exposure = 2 hours/day

Dietary sources:  major dietary source is from commercially prepared milk

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Vitamin A deficiency:

Most common among young children in non-industrialized countries

Due to insufficient dietary intake, chronic fat malabsorption, impaired liver functions

Leads to night blindness, and when prolonged, may cause total blindness

Elevated levels of Vitamin A

Toxic

Liver damage

Due to:

Excessive ingestion of Vitamin A

Ingestion of large amounts of liver or fish oils

Laboratory assessment

Retinol measurements by HPLC

Premature infants are treated with Vitamin A as preventative measure due to their:

Lower serum retinol.

Lower hepatic stores of retinol

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Vitamin A
Functions:

Essential for vision, cellular differentiation, growth, reproduction, and immune system function.

Associated with retinol

Stored in the liver

Dietary sources: fruits, vegetables, liver, and fish oils

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Pantothenic Acid Deficiency:  unlikely

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Pantothenic Acid

First designated as Vitamin B5 and later changed to pantothenic acid (Greek for “everywhere”).

Function: component of Coenzyme A

Dietary Sources:  widely distributed in foods – animal sources, legumes, whole grain cereals, egg yolk, kidney, liver, and yeast

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Biotin Deficiency: uncommon, seen with prolonged consumption of raw egg whites, in TPN (total parenteral nutrition) without biotin supplementation, and in patients with a genetic deficiency of biotinidase

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Biotin

Function: cofactor for carboxylation reactions.

Large doses can interfere with some immunoassay testing

Dietary sources:  liver, kidney, pancreas, eggs, yeast, and milk.

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Deficiency: pernicious anemia (megaloblastic anemia)  resulting from lack of intrinsic factor

Schilling test - Patient receives a small, oral dose of radiolabeled vitamin B12 and unlabeled B12

Serum and urine are collected at intervals, and labeled B12 is measured

Pts who cannot absorb vitamin B12 will have low levels of the labeled B12 in their blood and urine

Deficiency can also occur with a strict vegetarian diet, infection with fish tapeworm, as the result of malabsorption diseases or with folate deficiency

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Vitamin B12 (Cobalamin)

Refers to a large group of cobalt-containing compounds

Intrinsic factor, binding protein secreted from the stomach, is necessary for intestinal absorption of B12

Function:

Coenzyme in enzymatic reactions necessary for hematopoiesis and fatty acid metabolism

Dietary sources: animal products such as meat, eggs, and milk

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Folate deficiency:

Caused by:

Alcoholism

Malabsorption syndromes

Carcinoma

Liver disease

Chronic hemodialysis

Hemolytic and sideroblastic anemias

Certain anticonvulsants and other drugs

Major clinical symptom: megaloblastic anemia

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Folate (Folic Acid)
Function:

Play critical roles in cell division and protein synthesis

Closely related to vitamin B12 metabolically

The hematologic changes that result from deficiency of either vitamin B12 or folate are indistinguishable

Dietary source: Green leafy vegetables, fruits, organ meats, and yeast
Dietary supplementation of folate in pregnancy reduces the incidence of   fetal neural tube defects

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Niacin deficiency: Pellagra

Associated with diarrhea, dementia, dermatitis, and death

May result from alcoholism or low tryptophan diet

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Niacin (B3)

Requirement is met by the conversion of diet derived amino acid tryptophan to niacin

Given therapeutically to reduce cholesterol and triglyceride levels

Large therapeutic doses causes flushing of the skin and vasodilation

Function:

A component of the two coenzymes NAD and NADP

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Vitamin B6 deficiency:

Rarely occurs alone, most commonly seen in individuals deficient in several B vitamins

Patients at risk for deficiency:

Uremia

Liver disease

Absorption syndromes

Chronic alcoholism

malignancies

High doses are said to relieve PMS symptoms and depression, and reduce the pain of carpal tunnel syndrome.

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Vitamin B6 (Pyridoxine)

A complex of 3 related compounds

Function:

Metabolism of amino acids and lipids.

Maintaining the functional integrity of the brain

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Vitamin B2 deficiency:

Occurs with other nutritional deficiencies, alcoholism, and chronic diarrhea and malabsorption

A well-nourished person’s body stores enough riboflavin to prevent deficiency for 5 months

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Vitamin B2 (Riboflavin)

Function: A component of 2   coenzymes that catalyze a variety of oxidation-reduction reactions

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Vitamin B1  deficiency: Beriberi

Typically found in underdeveloped countries of the world

Chronic alcoholics with decreased intake, impaired absorption

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Vitamin B1 (Thiamine)

Functions: coenzyme in carbohydrate metabolism

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Vitamin C deficiency: Scurvy

Characteristics: hemorrhagic disorders: swollen, bleeding gums, impaired wound healing and anemia.

High intakes of vitamin C :

Readily excreted in the urine

Associated with very few adverse reactions

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Vitamin C (Ascorbic acid)

Has to be acquired by diet

Major dietary source:  Citrus fruits and vegetables

Functions:

Stabilization of collagen

Synthesis and hydroxylation of procollagen

Without enough Vitamin C, collagen becomes weak and easily degraded

Increase intestinal absorption of iron

Anti-oxidant

Loses an electron to reduce free radicals and protect cells from oxidative damage

May optimize the immune response by enhancing leukocyte functions

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Vitamin Classifications
Water-soluble

Soluble in aqueous environments

Cytoplasm and extracellular fluids

Cleared by the kidneys readily excreted in the urine and less likely than fat-soluble vitamins to accumulate to toxic levels in the body

Retained in the body for only short periods.

Include:  Vitamins B1, B2, B6, B12, C, and  Niacin and  Folic acid

Fat-soluble

Stored in the liver and adipose tissue

More likely to accumulate to toxic levels than water-soluble vitamins.

Retained in the body for longer periods

Include: Vitamins A1, D, E, and K

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Vitamin assessment
Biochemical assessment of vitamin status

1. Directly measure concentration of vitamin, its precursor or its metabolites in body fluids and tissues

2. Indirect measurements (or functional assays) of the vitamins

Quantitate vitamin levels by evaluating enzymatic activity or a physiologic response in which the vitamin is necessary

Diagnosis of vitamin deficiency:

A combination of dietary history, physical examination, and laboratory measurements

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Functions:

Serve as cofactors in enzymatic reactions

Antioxidants that protect cells from damage by scavenging free radicals

Vitamins C, E, and beta carotene

Calcium and phosphate-regulator

Part of the visual pigment rhodopsin

vitamin A

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Definition:
Essential organic molecules that may be:

supplied by the diet

synthesized by the body or its intestinal flora

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Meconium

Greenish-black newborn’s stool formed in utero starting at 16-20 weeks gestation

Made of amniotic fluid, mucous, bile, and cells shed from the intestinal tract

Generally passed 24-48 hours after birth

Provides in utero drug exposure for several months – detects drug use during the 2nd and 3rd trimesters

Easy and non-invasive

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Sweat

Easy and non-invasive

Tamper resistant collection devices

May be collected as liquid perspiration on sweat wipes or with a sweat patch

Sweat patch – waterproof and tamper resistant and can be worn for several weeks

Expensive

Large variation in sweat production

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Hair

Longest detection window – good for long-term exposure

Difficult to adulterate

Stable sample (mummified or exhumed bodies)

Collecting 1.5 inches from the back of the head represents approximately 90 days

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Oral fluid

Easy, non-invasive

Difficult to adulterate

Methods less established and expensive

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Benzodiazepines

Tranquilizers including: Diazepam (Valium), Librium, and Lorazepam (Ativan).

Same toxic affects as barbiturate

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Barbiturates

Tranquilizers including: phenobarbital, secobarbital, and pentobarbital.

Toxic affects include:

Hypotension

Lethargy

Slurred speech

Respiratory depression

Coma

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Phencyclidine (PCP)

Stimulant, depressant, anesthetic, and hallucinogenic properties.

Can be detected in heavy users up to 30 days following last use

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Opiates

Derived from the opium poppy

capable of analgesia, sedation, and anesthesia

Morphine, codeine, opium, heroin, Dilaudid, Percodan, Demerol, methadone, oxycodone, fentanyl, and Darvon as well as other opiates are readily detected in most urine drug methods

Heroin is metabolized to morphine.

Overdose causes:

Respiratory acidosis due to respiratory center depression

Increases in serum indicators of cardiac damage

Death caused by cardiopulmonary failure

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Cocaine

An effective anesthetic in therapeutic concentrations, a potent CNS stimulator in higher concentrations

Rapidly metabolized to benzylecgonine

Benzylecgonine can be detected in urine only within 2-3 days following a single use and up to 20 days after the last dose in chronic abusers

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CBD

Hemp contains low amounts of THC and more CBD (98%) while marijuana is higher in THC and lower in CBD.

Trace amounts of THC are found in CBD products.

Can’t differentiate marijuana use from CBD use.

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Cannabinoids

Group of psychoactive compounds found in marijuana

THC (tetrahydrocannabinol) is the most potent and abundant

Cannabinoid metabolites may remain detectable in urine for up to 2-3 weeks following marijuana use

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Anabolic steroids

Group of compounds related chemically to the male sex hormone, testosterone

Chronic abuse causes:

Enlargement of the heart

Toxic hepatitis

Accelerated atherosclerosis

Testicular atrophy, sterility, and impotence in males

Masculine traits, a reduction in breast tissue, and sterility in females

Identification is limited to chromatographic methods with GC/MS being most commonly used

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Amphetamine and methamphetamine

Stimulants used therapeutically for narcolepsy and ADD

Amphetamine-like compounds

MDMA (ecstasy) – amphetamine derivative

Routine drug screening by immunoassay of a urine specimen will usually not test positive

Patient history, presenting symptoms, and patient behavior with confirmation by GC/MS

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Assay Methods
Immunochemical methods

EMIT (enzyme multiplied immunoassay technique)

FPIA (fluorescence polarization immunoassay)

TLC (thin layer chromatography)- advantage: no instrumentation is required.

Either test for a specific drug (THC- tetrahydrocannabinol) or a class of drugs (opiates or barbiturates)

GC/MS is the most widely accepted method for confirmation

Specimen: Urine

Contains a high concentration of drugs or metabolites, easy to obtain

Most drugs excreted in urine

Many drugs are detectable in urine but not readily detectable in serum

Gastric aspirate or lavage specimens are appropriate only in recent drug ingestion or if a urine specimen cannot be obtained.

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Urine drug screening useful in:

Evaluation of drug overdose

Management of drug addiction

Employee screening

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Qualitative screens include:

Amphetamines

THC

Cocaine

Opiates

PCP

Barbiturates

Benzodiazepines

Methadone

Oxycodone

Screening procedures:

Rapid, simple, qualitative procedures intended to detect specific substances or classes of toxins

Good analytic sensitivity, lack specificity

Negative results can rule out a drug, but  positives should be confirmed by a more specific method

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Spot tests and dipsticks are available when specimen integrity cannot detect an adultered specimen

AdultaCheck 4

AdultaCheck 6

Intect 7

Can test for creatinine, nitrite, glutaraldehyde, pH, SG, bleach and PCC

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Adulterants
3 common ways of cheating on a drug test:

Substituting with a synthetic urine or purchased drug-free urine

Drinking a commercially available product to flush out drugs

Adding an adulterant in vitro to the specimen after collection

Synthetic urine is difficult to detect due to its similar pH, creatinine, and SG to normal urine

ID a normal constituent in urine not found in synthetic, i.e. cortisol

Flush-out drugs

Fluids or tablets + large amounts of water to dilute urine dilutes drugs for negative results but lowers creatinine below the cutoff

Commercial products added after urine collection

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Monitor for alterations by specimen integrity:

pH  should be 4.0-10.0

Temperature should be 90.5-98.9°F

Creatinine should be 15-20 mg/dL

Specific gravity should be 1.005-1.030

Chain-of custody should be established

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Drugs of Abuse screening

Important concerns

Integrity of specimen collection

Patient identification

Specimen identification

Prevention or detection of specimen adulteration

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Acetaminophen (Tylenol)

Overdose associated with severe hepatotoxicity

Alcoholic patients are more susceptible to acetaminophen toxicity(metabolize more rapidly)

Specimen

serum

Methods for analysis: HPLC, immunoassay

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Most common chromogenic assay:

Trinder reaction- reacts salicylate with ferric nitrate to form a colored complex that is then read spectrophotometrically

Specimen: serum

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Salicylates

Aspirin (acetylsalicylic acid)

Produce a syndrome of combined respiratory alkalosis (causing hyperventilation) and metabolic acidosis (an acid)

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Mercury

Acute ingestion of soluble mercury salts produces corrosive GI and kidney toxicity

Chronic poisoning due to industrial or other exposure to elemental mercury vapor or organic mercury compound is associated with neurological toxicity

Specimen:

blood, urine, or hair

Assay method:

atomic absorption spectrophotometry

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Lead

Sources of poisoning:

Most commonly, ingestion of old lead containing paint by children

Industrial exposure.

Improperly glazed pottery

Produces multiple effects on the nervous and hematopoietic systems

Synthesis of heme pigments is inhibited, increased reticulocyte counts and basophilic stippling appear on the clinical hematologic picture.

Specimen:

Whole blood- specimen of choice

Hair

Urine

Most common method: atomic absorption w/ whole blood

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Cadmium

Metal found in many industrial processes and cathodal material of nickel-cadmium batteries

Binds proteins and accumulates in the kidney

Associated with significant nephrotoxicity

Specimen: whole blood or urine

Method for analysis: atomic absorption

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Arsenic

Associated with exposure to or ingestion of arsenic-containing pesticides

Binds to enzymes, therefore inhibits key metabolic processes

Non-specific arsenic poisoning symptoms due to the capability of arsenic to bind to many proteins of the body

Specimen

Serum - least useful specimen to establish exposure to arsenic since the half-life in blood is only 4 to 6 hours

Urine - specimen of choice for recent exposure

Hair and nail keratin strongly attracts arsenic - best specimen to determine long term exposure. “Mees’ Lines”

Method for analysis: atomic absorption

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Cyanide

Can exist as gas, solid, or solution

Expresses toxicity by binding to heme iron

Symptoms of low level exposure include:

Headaches, dizziness, and respiratory depression

Progress to seizure, coma, and death

Analysis using ISE methods

Intoxication can occur in house fires.

Liberated from the combustion of products containing carbon and nitrogen

Antidote = IV administration of hydroxycobalamin

May interfere with spectrophotometric COHb resulting in falsely low levels

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COHB Levels

Normal levels of COHB:  1-3%

Smokers levels: 5-15%

Levels about 15-20% produce symptoms

Levels of about 40-70% produce confusion/unconsciousness

Levels 70-80% are usually fatal

Treatment: 100% oxygen therapy

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COHB Analysis

Spectrophotometry- co-oximetry for carboxyhemoglobin

Gas chromatography

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Colorless, odorless, and tasteless gas

Binds irreversibly to hemoglobin and promotes O2 release

Hemoglobin has a 200 times greater affinity for CO than for oxygen

Specimen:

whole blood

arterial for acute

venous is acceptable for chronic CO exposure

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Alcohol toxicity primarily related to metabolites

Ethanol → Acetaldehyde → Acetate

Isopropanol → Acetone

Methanol → Formaldehyde → Formic Acid

Ethylene Glycol → Oxalate and Formic Acid

Can be detected by an increase in the osmolal gap

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Ethylene glycol

Anti-freeze

Metabolized to formic acid and oxalic acid

May result in CNS depression, hypertension, and renal failure

Quantitated using GLC

Treatment: same as methanol

Affinity of ADH for ethanol is 100 times greater than its affinity for ethylene glycol

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Isopropanol

Rubbing alcohol

Metabolized to acetone by hepatic ADH

May result in severe ethanol-like symptoms that may persist for an extended period

Quantitated using GLC

Treatment: hemodialysis for severe intoxication

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MEOH intoxication treatment
Goal: prevent metabolism of MeOH in the presence of ADH

Based on the strong preference that ADH has for ethanol (the affinity of ADH for ethanol is 10 times greater than its affinity for methanol)

Treatment:

IV ethanol and treatment with diuretic agents

Fomepizole – very expensive

Dialysis

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Quantitated using GLC

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Methanol (MEOH)

Common solvent, found in paint thinners, gas line antifreeze, racing fuel

Metabolized to formaldehyde and formic acid by hepatic ADH (alcohol dehydrogenase)

Formation of formic acid → severe acidosis which may lead to death, and optic neuropathy

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Ranges
Ethanol levels of 50-100 mg/dL:

Produce intoxication with euphoria or sedation

Levels of 150-250 mg/dL:

Produce stupor

Levels of 300-400 mg/dL or above:

Can produce coma and death

Chronic abusers may tolerate higher levels

Conversion between mg/dL and  %  (weight per volume)

Move the decimal point 3 places (ex. 100 mg/dL = 0.10 %)

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Gas chromatography

Reference method

Dilution of the serum or blood sample with a saturated solution of sodium chloride in a closed container

Volatiles within the liquid specimen partition into the air space of the closed container

Sampling of this head space provides quantitation of ethanol as well as methanol and isopropanol

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Enzymatic ETOH analysis

In the presence of alcohol dehydrogenase (ADH) and NAD+ as the coenzyme

Alcohol is oxidized to acetaldehyde and NAD+ is reduced to NADH

Reaction above

The increase in absorbance with the formation of NADH is directly proportional to the concentration of ethanol in the specimen

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Ethanol (ETOH)

Specimen:

serum

plasma

whole blood

breath analysis

sodium fluoride = anticoagulant of choice

Serum alcohol levels ~15% higher than whole blood levels due to water content

Venipuncture site should be cleaned with an alcohol-free disinfectant

Specimens must be capped at all times to avoid evaporation

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Toxicology: The study of poisons

Poison: Any substance that causes a harmful effect on exposure

Exposure to toxin agents:

Intentional suicide attempts (50%)

Accidental exposure (30%)

Homicide or occupational exposure (20%)

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Definition:

Study of genetic variation in the context of variable response to drugs

Drugs tailor-made for individuals and adapted to each person's own genetic makeup.

Patient responsiveness

Aid in dosing

Avoidance of toxicity

Warfarin therapy/CYP2C9

Slowed or impaired metabolism genes

Tricyclic antidepressants/HTR2A

Receptor genes

Cytochrome P450

Enzyme that plays a major role in drug metabolism in the liver

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Cause potential interference with IFE and SPE

May cause interference in transfusion medicine

Daratumumab (anti-CD38) causes panreactivity in antibody screens

Dithiothreitol – reducing agent to fix the antibody screen

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Indications for mAbs:

Hematologic malignancies

Solid tumors

Autoimmune disorders

Asthma

Inflammatory bowel disease

Allograft rejection

Infectious organisms

Drug reversal

Osteoporosis

Hypercholesterolemia

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>100 approved by the FDA

mAbs can be targeted against:

A cell surface antigen

A plasma protein or drug

An infectious organism

Examples:

Remdezivir – Covid-19

Adalimumab – autoimmune disease

Daratumumab – multiple myeloma

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Methotrexate

Interferes with normal cellular metabolism by inhibiting the synthesis of DNA

Serum concentrations are used to evaluate the dosage of leucovorin needed to counteract the cytotoxic effects of methotrexate

Leucovorin is administered to reverse the actions of methotrexate at a specific time after its infusion