Forensic Toxicology Exam 2

Purpose of blood

Transport nutrients & waste throughout body

Types of blood cells

Erythrocytes, leukocytes, and platelets

Plasma

Liquid part of blood

Plasma contains

Proteins (Albumin, fibrinogen and globulin), water, salts, nutrients carried in blood

Purpose of erythrocytes (red blood cells)

Carry oxygen to tissues

Hemoglobin

Contains iron which binds with oxygen

Cause of anemia

Low RBC count, low hemoglobin concentration, deformed RBC

Results of anemia

Decreased oxygen availability

Purpose of Leukocytes (WBC’s)

Defend against infectious agents (bacteria, parasites, etc.)

Types of leukocytes

Neutrophil, eosinophil, basophils, lymphocytes, monocytes

Neutrophil

Active phagocyte and 1st responder. Increase in number during infection

Eosinophil

Kill larger parasites and allergens

Basophils

Cause infection response. Release histamine → Dilating blood vessels

Lymphocytes

B= produce antibodies

T= Respond to antibodies on foreign tissue

Monocytes

Largest and most active phagocytes. Used for chronic, widespread infections

Platelets

Fragments of multinucleate cells, initiate clotting cascade by clinging to broken vessel walls

Hematoxicology definition

The study of adverse effects of exogenous chemicals on blood and blood-forming tissues

Hematoxicology vs toxic effect

First is the primary toxicity, where one or more blood components are directly affected or secondary. The second is consequence of other tissue injury or systemic disturbances

Hematopoiesis

The production of blood cells – highly regulated sequence of events by which blood cell precursors proliferate and differentiate

Where does hematopoiesis take place in fetus?

Liver, spleen, bone marrow, lymph nodes

Where does hematopoiesis take place in adults?

Bone marrow and proximal limbs

Erythrocyte is involved

as carrier and/or reservoir for drugs and toxins

Hemoglobin transports

oxygen and carbon dioxide between lungs and tissues

Normal survival of erythrocytes in circulation is

~120 days

Hemostasis

Stoppage of bleeding or blood flow through an organ

How can xenobiotics harm platelets?

Cause low platelet levels and interferes with their function

Thrombocytopenia is due to

decreased production or increased destruction of platelets

Toxicologists

Detect and identify the presence of drugs and poisons in body fluids, tissues, and organs

What are toxicologists more frequently asked to determine?

The presence of alcohol in the body

What is the most widely abused drug in wester countries?

Alcohol

Metabolism

Body breaks down one chemical into chemicals that are easier for it to eliminate

Steps of metabolism

1. Absorption

2. Distribution

3. Elimination

Maximum Blood Alcohol Content (BAC)

may not be reached until 2-3 hours after time of consumption – more likely within 30-90 min. from final drink until absorption process is complete

Alcohol will become uniformly distributed throughout

The watery portion of the body at complete absorption – 2/3 of body volume

Henry’s Law applied

When a volatile chemical is dissolved in a liquid & is brought to equilibrium with air, there is a fixed ratio between the concentration of the volatile compound in air & its concentration in the liquid & this ratio is constant for a given temperature.

During period of alcohol absorption, alcohol concentration within arterial (oxygenated) blood will be considerably _____ than in venous (deoxygenated) blood

Higher

Breathalyzer Test

A device used for collecting and measuring the alcohol content of alveolar breath

Field Sobriety Test

Normally performed to ascertain the degree of the suspect’s physical impairment and whether or not an evidential test is justified

A screening test gives

quick insight into the likelihood that a specimen contains a drug substance.

Positive results arising from a screening test are tentative at best and must be verified with a

confirmatory test

Most widely used screening tests of blood for alcohol

Thin-layer chromatography, gas chromatography, and immunoassay

Why are added precautions needed when collecting and preserving blood in postmortem samples

We must account for bacterial action so collect from a number of different body sites

Acidic Drugs

Extracted from an acidified water solution with organic solvents such as chloroform

Examples of acidic drugs

Barbiturates and aspirin

Alkaline (basic) drugs

Extracted from alkaline water solution with organic solvents

Examples of alkaline drugs

Phencyclidine, Methadone, Amphetamines, Cocaine

How do we test for heavy metal poisons?

Reinsch Test; will develop a silvery or dark coating on the copper

CO binds with hemoglobin

carbonylhemoglobin

The liver is the main organ where

exogenous chemicals are metabolized and eventually excreted

Liver

First organ to encounter nutrients, drugs, toxicants, waste product. Efficient function extract these materials from blood for use, storage or excretion into bile

Main parts of liver

Lobule and acinus

Blood entering acinus is

oxygen-depleted from portal vein (60-70% of blood flow) + oxygenated blood from hepatic artery (30-40%)

Major type of cells in sinusoids

Endothelial, kupffer, stellate (Ito)

What fluid is produced by the liver

Bile

Bile functions are essential for

• Uptake of lipid nutrients from small intestine

• Protection of the small intestine from oxidative results

• Excretion of endogenous & xenobiotic compounds

enterohepatic cycling

when compounds are delivered back to liver

Types of hepatobiliary injury

Fatty liver, canalicular cholestasis, bile duct damage, sinusoidal disorders, fibrosis and cirrhosis, tumors

Ways the liver can die

Necrosis or apoptosis

Necrosis

Cell swelling, leakage, nuclear disintegration, influx of inflammatory cells. Detected by associated plasma (or serum) for specific enzymes

Apoptosis

Cell shrinkage, nuclear fragmentation, lack of inflammation cells

Canalicular Cholestasis

Decrease in the volume of bile formed or impaired secretion of specific solutes into bile (yellow eyes)

Fibrosis and cirrhosis

Accumulation of extensive amounts of collagen fibers, in response to direct injury or inflammation

Tumors

Derived from hepatocytes, bile duct cells, stem cells. Sinusoidal lining cells cause highly malignant tumors

Respiratory tract is divided into what oronasal passages

Upper respiratory tract (airway passages above neck) and lower respiratory tract (airway passages and lung parenchyma below the pharynx)

Oronasal passages sensory functions

• Nasal epithelia metabolizes foreign substances by cytochrome P450 enzyme

• Humans can distinguish between more than 5000 odors

• Detection of odor can be protective – avoidance behavior

• Chemosensory function

Proximal airway and portion of nasal passage covered by pseudostratified respiratory epithelium containing specialized cells

ciliated, mucous and basal cells

Gas exchange occurs in alveoli

85% of total lung volume

How many alveoli in adult lungs

300-500 million alveoli

Principal lung function

ventilation, perfusion, diffusion

Ventilation

During inhalation: fresh air moved into lung through upper respiratory tract into terminal units when thoracic cage enlarges and diaphragm moves downward

Perfusion

Lung receives entire output from right ventricle. Substantial amounts of toxic chemicals can be delivered to lung via blood

Diffusion

Gas exchange takes place across entire alveolar surface, meaning contact with toxin or toxicant occurs over an area ~140m2. Damage can be disruption of this process by collection of liquid in alveolar space and disruption of pulmonary surfactant system

Critical factors to consider how deep gas penetrates

1. Solubility

2. Diffusivity

3. Metabolism/reactivity in respiratory issues

4. Breathing rate (dictates volume)

What is critical in determining region affected (in lungs)

Particle size

Particles deposit by

• Impaction

• Interception

• Sedimentation

• Diffusion

• Electrostatic deposition

Particle Clearance

Rapid removal lessens time available to cause damage to pulmonary tissue or permit absorption

Types of particle clearance

• Nasal (wiping)

• Tracheobronchidal (Phlegm)

• Alveolar clearance (alveolar macrophage)

Acute responses to lung damage

• Trigeminally mediated airway reflexes

• Bronchoconstriction

• Pulmonary edema

Trigeminally mediated airway reflexes

Certain gases and vapors stimulate nerve endings in nose causing change in breathing patterns

Bronchoconstriction

Provoked by irritants, causes decrease in airway diameter and increase in resistance to airflow; chest tightness, coughing

Pulmonary Edema

Alveolar epithelial and endothelial cell perturbation and cell inflammation

Chronic responses to lung damage

• Chronic obstructive pulmonary disease (Progressive airflow obstruction, bronchitis)

• Lung cancer

• Asthma

• Pulmonary Fibrosis (Increased amounts of collagen)

General points that allow understanding of actions of neurotoxicants

Privileged status of NS with maintenance of biochemical barrier between brain/blood. Transmission of info via synapses

What protects the NS from adverse effects from toxicants

Blood-brain barrier (BBB)

How is the BBB at birth?

Incomplete, which predisposes infants to have brain injuries

Axonal Transport

Impulses are conducted over great distances at rapid speed – provide information about environment to organism

Axonal Degeneration

Characterized by loss of cell body and all processes

Neuronopathy

Neuronal cell body lethal injury causes degeneration process

Axonopathy

When injury at axon level – axon may degenerate while neuronal cell body continues survival

Patterns of neurotoxic injury

Neuronopathy, axonopathy, myelinopathy, Some forms of toxicity are due to interruption of the process of neurotransmission

myelinopathis

Toxicity interferes with myelin formation

Neurotoxicity

altered conduction & propagation of nerve impulses and changes in functions such as behavior, performance, conditioning

Functions of the NS

• Motor

• Sensory

• Autonomic

• Cognitive

Mechanisms of neurotoxicity targets

• Neuron

• Axon

• Myelinating cell

• Neurotransmitter System

Functional assessments of NS

• Test for motor activity

• Electrophysiological (nerve conduction velocity)

• Cardiovascular status

Neuropathies

Certain toxicants specific for neurons – results in injury or death

Neuron loss

irreversible, degeneration of all cytoplasmic extensions, dendrite and axons

Example of neuron toxicants

Methyl mercury

Primary site of toxicity (NS) (axonopathies)

Axon

Axon degenerates with

myelin surrounding it, neuron cell body remains intact