Target Organ Toxicity (TOXI FINAL)

stratified squamous epithelium, mucociliated epithelium, olfactory cells

Nasal cells include (3)

CYP450, FMO (Flavin containing Monooxygenase)

Metabolic capability of Nasal cells

Mucociliated epithelium; Ciliated cells, mucous cells, serous cells

Tracheo-bronchial cells include (4)

Terminal bronchioles

Mucociliated epithelium with clara cells distal bronchioles and alveolar ducts.

Type 1 and Type 2 (32/51)

Alveolar cells contains what type of epithelium cells

Ventilation

gas exchange: inhale and exhale

70-80 cc of blood per heartbeat (75 ml per heartbeat)

Right ventricle output of blood per heartbeat

Diffusion

exchange of gases across alveolar surface

12-20 BPM

Normal respiratory rate

Less

The more water soluble, the ______ penetration to deep lung.

nose

SO2 has higher water solubility, deposited mainly in the ______ and is largely non-toxic.

alveoli

O3 and NO2 have lower water solubility and is deposited in the ____ and are toxic

Dosimetry

measure the delivered dose to target tissue, toxic response depends on site of deposition

Interception

edge of particle contacts a surface typical with fibers

Impaction

Common in nasopharyngeal regions and at bifurcations

Sedimentation

Smaller bronchi, bronchioles, and alveolar spaces

Diffusion

Submicrometer particles: Brownian movement

Wiping, Blowing, Swallowed

Defense mechanism against toxicants (CLEARANCE) NASAL

macrophage mediated

macrophages engulf particles and deposit them on mucociliary escalator or enter the lymphatic system

Defense mechanism against toxicants (CLEARANCE) LOWER RESPIRATORY TRACT:

Mucociliary escalator

trapping particles in mucous

upward beating of cilia on airway epithelial cells

material is expelled or swallowed

Defense mechanism against toxicants (CLEARANCE) TRACHEOBRONCHIAL

Airway reactivity

contraction of smooth muscle in lung in response to irritants

Pulmonary edema

thickened alveolar-capillary barrier due to acute lung injury

Cell necrosis

acidic or alkaline agents alter membrane permeability, leading to cell death

Cell proliferation

type I cells replaced by transformed type II cells in response to acute lung injury

ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide

Inhalation exposure direct GASES

Chlorine gas, cadmium oxide, acid aerosol

Inhalation exposure direct VAPORS, FUMES, AEROSOLS

grains, wood cedar bark, benzopyrenes, endotoxin-containing compounds

Inhalation exposure direct ORGANIC PARTICULATES

nickel compounds, vanadium compounds, asbestos fibers, silica

Inhalation exposure direct INORGANIC PARTICULATES

cigarette smoke, diesel engine exhaust, coal tar aerosols, PM2.5/PM10

Inhalation exposure direct: MIXTURES

Paraquat

Inhalation exposures indirect: widely used herbicide causes fibrosis of type I and Type II cells

Inhalation exposures indirect: a natural alkaloid causes hyperplasia of capillary endothelial ce

Chemotherapeutic agents

Inhalation exposure indirect: bleomycin, cyclophosphamide causing fibrosis

Depression or stimulation of the CNS

the effects of OD and poisoning on the respiratory system on the CNS

Lung parenchyma invol

effects of OD and poisoning in the RS by aspiration and/or chemical pneumonitis, fibrosis, interstitial disease, atelectasis, and pulmonary edema

Pleural disease

long term exposure to toxic inhalations can lead to

chest wall disturbances

disturbances with substances that produce paralysis of diaphragm and intercostal muscles

Pulmonary fibrosis

increases the amount of collagen fibers in alveolar interstitium causes fibroblast proliferation, increased collagen synthesis or deposition, decreased collagen degradation.

Pulmonary fibrosis (silicosis)

Agent silica can cause

Pumona

Coal particles (anthracite) can cause

asbestosis

lung cancer

malignant mesothelioma

what effects does the agent asbestos cause (3)

Tobacco smoke

Air pollution

Agents of chronic bronchitis

mucous gland hypertrophy

goblet cell metaplasia

Mechanism of Chronic bronchitis

Asthma

lack of control of airway smooth muscle causing muscle shortening, caused by agents such as dander, pollens, fumes, dusts, and gases

tobacco smoke

Agents that cause emphysema

Influential factor

elastase break down lung elastin, toxicants accelerate the process. Is influenced by alpha 1 -antiprotease

Emphysema

neutrophil (and perhaps alveolar macrophage) elastases can break down lung elastin and thus cause ________

Hypersensitivity Pneumonitis

What does the agent Organic dusts cause typically common in farmers

Shaver’s disease, interstitial fibrosis

Aluminum cause what lung disease

lung cancer

bronchitis

laryngitis

Arsenic cause what lung disease (3)

berylliosis

beryllium causes what lung disease

byssinosis

cotton dust cause what lung disease

siderotic lung disease

silver finisher’s lung

hematite miner’s lung

arc welder’s lung

Iron oxides causes what lung disease

Immunotoxicology

study of adverse effects on the immune system resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and, in some instances, biological materials.

Specificity

Memory

Ability to distinguish self from non-self

(3) cardinal characteristics of immune system

bone marrow= B cell production

thymus= T cell production

Primary classification of the immune system (2)

Spleen

Lymph nodes

Peyer’s patches

BIOLOGICAL SIEVES

Secondary classification of the immune system: lymphoid tissue

SALT

MALT

GALT

BALT
NALT

Cells lining the genitourinary tract

Tertiary (effector sites) classification of the immune system (6)

Lynmphocyte

are clonally distributed with respect to antigen specificity, each clone has a unique membrane receptor for antigen.

Cytokine producing cells

a type of T effector cells that augments macrophage function and other aspects of protective immunity.

effector cells and regulatory cells

T cells can divide and differentiated into (2)

plasma cells (synthesis and secretion of antibody)

B cells can be divided and differentiated into

B cell

secrete antibodies that defend against extracellular pathogens found in the Humoral

T cells

defend against infected cells, and is cell mediated

immediate type

Type 1 hypersensitivity

Type 2 Hypersensitivity

delayed hypersensitivity cell

Type 4 hypersensitivity

Langerhan’s/ dendri

In the inductions of sensitization the hapten-carrier complex is processed by_______

I step

Mast cell degranulation release pre formed mediators of inflammation and lung hypersensitivity (immune system step)

complement fixes to complement receptors on target cell membrane, including lysis Antibody (IgG) is directed against foreign Ag (immune

Step III

Chemotactic factors attract inflammatory cells to site. , local issues damaged by lysosomal enzymes released by phagocytes (immune system step)

Step IV

Induction of sensitization, hapten penetrates the epidermis and forms a comlex with a protein carrier, The hapten-carrier complex is processed by Langerhans’/Dendritic cells. (immune system step)

Hemolytic anemia

Methyldopa clinical manifestation associated with autoimmunity

SLE like syndrome

Hydralazine, Isoniazid, Procainamide clinical manifestation associated with autoimmunity

Autoimmune hepatitis

Halothane clinical manifestation associated with autoimmunity

Scleroderma-like syndrome

Vinyl chloride clinical manifestation associated with autoimmunity

Glomerular neuropath

mercury clinical manifestation associated with autoimmunity

Scleroderma

silica clinical manifestation associated with autoimmunity

Symptoms

vary from redness, itching and small blisters to widespread blisters that overlap forming very large fluid filled blisters

Hematotoxicology

The study of adverse effects of drugs, non-therapeutic chemicals and other agents in our environment on blood and blood-forming tissues

Neutrophil

Basophil

Eosinophil

3 granulocytes formed

Sideroblastic anemia

production of protoporphyrinogen III and protoporphyrin IX leads to

parameters useful in establishing the presence of anemia

PICE = Pyrazinamide, Isoniazid, Cycloserine, Chloramphenicol, Ethanol

Xenobiotics associated with sideroblastic anemia

B12 deficiency (Folate),

PENC = PAS, Ethanol, Neomycin, Ethanol

PPPCS+ Phenytoin, Primidone, Phenobarbital, Sulfsalazine

Xenobiotics associated with megaloblastic anemia

Aplastic

Life-threatening disorder characterized by peripheral blood pancytopenia, reticulocytopenia and bone marrow hypoplasia

Chloramphenicol

Gold

Penicillin

PTU

Indomethacin

Carbon tetrachloride

Streptomycin

Allopurinol

Drugs and chemicals associated with the development of aplastic anemia

Nitrites, Nitrates

Nitrobenzene

benzocaine

Lidocaine

Dapsone

amyl nitrate

Nitroglycerin

Sulfonamide

Phenacetin

Primaquine

Nitric oxide

Metoclopramide

Silver nitrate

Xenobiotics associated with methemoglobinemia

Homotropic effects

the slow but consistent oxidation of heme iron to the ferric state to form methemoglobin

C

if methemoglobin exceeds 5-10%

left shift

increase (alkalosis)

left shift pH

fetal haemoglobin

left shift (type of haemoglobin)

temperature- increase

2.3 BPG - increase

p(CO)2 - increase

pH- decrease (acidosis)

type of haemoglobin- adult haemoglobin

right shift

presence of schistocytes (fragmented RBCs) in the peripheral blood

March hemoglobinuria

destruction of RBCs during vigorous exercise or marching

Infectious Diseases

malaria, babesiosis, clostridial infections cuasing alterations in erythrocytes survival