3 - Environmental Diseases

environment

• encompasses the outdoor, indoor, and occupational environments shared by small and large populations, and our own personal environment.

• in each of these environments, the air we collectively breathe, the food and water we consume, and exposure to toxic agents are major determinants of our health.

• our personal environment is greatly influenced by tobacco use, alcohol ingestion, therapeutic and non therapeutic drug consumption, and diet.

environmental diseases

conditions caused by exposure to chemical or physical agents in the ambient, workplace, and personal environment, including diseases of nutritional origin

Environmental, Occupational, Iatrogenic, Self-administered

Sources of Exposure

close contact

described by the WHO as talking to a person less than 1 meter for 15 minutes or more for the past 24 hours

Mechanisms of Toxicity

• Corrosive, tissue destruction (acids, alkali)

  • desiccation (drying out)

  • protein destruction

  • protein denaturation

  • hydrolysis

  • fat saponification

• Inhibition of enzyme activity

  • example: cyanide-> inhibits cytochrome oxidase

• Alternate metabolic pathways

  • ethanol: NAD/NADH

• Disturbances of homeostasis

  • steroids: immune system

  • aspirin: acidosis

• Mutagenesis

• Carcinogenesis

acids, alkali

Mechanisms of Toxicity

• Corrosive, tissue destruction (________, ________)

  • desiccation (drying out)

  • protein destruction

  • protein denaturation

  • hydrolysis

  • fat saponification

• Inhibition of enzyme activity

  • example: cyanide-> inhibits cytochrome oxidase

• Alternate metabolic pathways

  • ethanol: NAD/NADH

• Disturbances of homeostasis

  • steroids: immune system

  • aspirin: acidosis

• Mutagenesis

• Carcinogenesis

cyanide

Mechanisms of Toxicity

• Corrosive, tissue destruction (acids, alkali)

  • desiccation (drying out)

  • protein destruction

  • protein denaturation

  • hydrolysis

  • fat saponification

• Inhibition of enzyme activity

  • example: ________-> inhibits cytochrome oxidase

• Alternate metabolic pathways

  • ethanol: NAD/NADH

• Disturbances of homeostasis

  • steroids: immune system

  • aspirin: acidosis

• Mutagenesis

• Carcinogenesis

ethanol

Mechanisms of Toxicity

• Corrosive, tissue destruction (acids, alkali)

  • desiccation (drying out)

  • protein destruction

  • protein denaturation

  • hydrolysis

  • fat saponification

• Inhibition of enzyme activity

  • example: cyanide-> inhibits cytochrome oxidase

• Alternate metabolic pathways

  • ________: NAD/NADH

• Disturbances of homeostasis

  • steroids: immune system

  • aspirin: acidosis

• Mutagenesis

• Carcinogenesis

steroids

Mechanisms of Toxicity

• Corrosive, tissue destruction (acids, alkali)

  • desiccation (drying out)

  • protein destruction

  • protein denaturation

  • hydrolysis

  • fat saponification

• Inhibition of enzyme activity

  • example: cyanide-> inhibits cytochrome oxidase

• Alternate metabolic pathways

  • ethanol: NAD/NADH

• Disturbances of homeostasis

  • ________: immune system

  • aspirin: acidosis

• Mutagenesis

• Carcinogenesis

aspirin

Mechanisms of Toxicity

• Corrosive, tissue destruction (acids, alkali)

  • desiccation (drying out)

  • protein destruction

  • protein denaturation

  • hydrolysis

  • fat saponification

• Inhibition of enzyme activity

  • example: cyanide-> inhibits cytochrome oxidase

• Alternate metabolic pathways

  • ethanol: NAD/NADH

• Disturbances of homeostasis

  • steroids: immune system

  • ________: acidosis

• Mutagenesis

• Carcinogenesis

Inhalation Toxins Related to Farming

(Inhalation Toxins Related to Farming)

• Organic dusts (hypersensitivity pneumonitis)

  • moldy hay (Farmer’s Lung)

  • bird droppings (bird breeders lung)

• Pesticides

  • organophosphate (acetycholine esterase inhibitors)

  • organochlorine (DDT, chlordane)

• Herbicides (paraquat, diquat, dioxin)

• Fertilizer (ammonia)

hypersensitivity pneumonitis

Inhalation Toxins Related to Farming

• Organic dusts (________ ________)

  • moldy hay (Farmer’s Lung)

  • bird droppings (bird breeders lung)

• Pesticides

  • organophosphate (acetycholine esterase inhibitors)

  • organochlorine (DDT, chlordane)

• Herbicides (paraquat, diquat, dioxin)

• Fertilizer (ammonia)

moldy hay, bird droppings

Inhalation Toxins Related to Farming

• Organic dusts (hypersensitivity pneumonitis)

  • ___________ (Farmer’s Lung)

  • ___________ (bird breeders lung)

• Pesticides

  • organophosphate (acetycholine esterase inhibitors)

  • organochlorine (DDT, chlordane)

• Herbicides (paraquat, diquat, dioxin)

• Fertilizer (ammonia)

organophosphate, organochlorine

Inhalation Toxins Related to Farming

• Organic dusts (hypersensitivity pneumonitis)

  • moldy hay (Farmer’s Lung)

  • bird droppings (bird breeders lung)

• Pesticides

  • ____________ (acetycholine esterase inhibitors)

  • ____________ (DDT, chlordane)

• Herbicides (paraquat, diquat, dioxin)

• Fertilizer (ammonia)

paraquat, diquat, dioxin

Inhalation Toxins Related to Farming

• Organic dusts (hypersensitivity pneumonitis)

  • moldy hay (Farmer’s Lung)

  • bird droppings (bird breeders lung)

• Pesticides

  • organophosphate (acetycholine esterase inhibitors)

  • organochlorine (DDT, chlordane)

• Herbicides (__________, __________, __________)

• Fertilizer (ammonia)

ammonia

Inhalation Toxins Related to Farming

• Organic dusts (hypersensitivity pneumonitis)

  • moldy hay (Farmer’s Lung)

  • bird droppings (bird breeders lung)

• Pesticides

  • organophosphate (acetycholine esterase inhibitors)

  • organochlorine (DDT, chlordane)

• Herbicides (paraquat, diquat, dioxin)

• Fertilizer (___________)

Tobacco

• Tobacco Smoking

• _________ is the most common exogenous cause of human cancers, being responsible for 90% of lung cancers.

cigarette smoking

• Tobacco Smoking

• The main culprit is _________ _______, but smokeless tobacco (snuff, chewing tobacco, etc.) is also harmful to health and an important cause of oral cancer

second-hand smoke

• Tobacco Smoking

• passive tobacco inhalation from the environment (“_________ _____”) can cause lung cancer in nonsmokers

Tobacco Smoking

• 400,000 deaths/yr

• 50 Million smokers in US

• Smoke composition

  • carcinogens (polycyclic HC, β-naphthylamine, nitrosamines)

  • Irritants and toxins – ammonia, formaldehyde, oxides of nitrogen

  • CO

  • Nicotine

polycyclic HC, B-naphthylamine, nitrosamines

• smoke composition

• 3 carcinogens

ammonia, formaldehyde, oxides of nitrogen

• smoke composition

• 3 irritants and toxins

carbon monoxide (CO)

• smoke composition

• component of smoke that can displace oxygen in hemoglobin

nicotine

• smoke composition

• among the components, __________ is the one causing the addiction

tetrahydrocannabinol (THC)

• VAPE content/E cigarette

• a psychoactive component of the marijuana plant, which may contain vitamin E acetate for vaping purposes

formaldehyde

• VAPE content/E cigarette

• a gas often used in building materials, manufactured wood, adhesives, and other materials

cadmium

• VAPE content/E cigarette

• metal found in batteries

arsenic

• VAPE content/E cigarette

• a poisonous substance that is often used to kill rodents

carcinogens

• The number of potentially noxious chemicals in tobacco smoke is extraordinary.

• Tobacco contains between 2000 and 4000 substances, more than 60 of which have been identified as ____________.

Cessation

• ____________ of smoking greatly reduces, within 5 years, the overall mortality and the risk of death from cardiovascular diseases.

• Lung cancer mortality decreases by 21% within 5 years, but the excess risk lasts for 30 years

Mercury

• Heavy Metal Toxic Agents

• focal GI ulceration and severe renal damage

Arsenic

• Heavy Metal Toxic Agents

• associated with angiosarcoma

Iron

• Heavy Metal Toxic Agents

• hemosiderosis

Lead

• Heavy Metal Toxic Agents

• inhibits heme synthesis, CNS function, kidneys, GI

• 2-11% of children in US exceed 10 μg/dL

• Subclinical lead poisoning may occur in children exposed to levels of lead below 10 μg/dL, causing low intellectual capacity, behavioral problems such as hyperactivity, and poor organizational skills

• indications of lead poisoning

  • lead lines: gingiva

  • basophilic stippling

  • acute tubular necrosis

Subclinical lead poisoning

• Heavy Metal Toxic agent

• lead

• ___________ _____ _________may occur in children exposed to levels of lead below 10 μg/dL, causing low intellectual capacity, behavioral problems such as hyperactivity, and poor organizational skills.

Ethanol

• Organic Alcohols

• 1/3 of Americans characterized as heavy drinkers

• CNS depressant

• legally intoxicated >100 mg/dL

• Nearly 50% of fatal MVA

Methanol

• Organic Alcohols

• toxic metabolites inhibit hexokinase, may cause blindness

Ethylene glycol

• Organic Alcohols

• antifreeze, ATN

mallory body

it is present in alcoholic hepatitis when the liver is abused

Antibiotics

• Adverse Effects of therapeutic Drugs

• Drug resistance- due to poor drug compliance

• Fatal aplastic anemia- chloramphenicol

Sulfonamides

• Adverse Effects of therapeutic Drugs

• Immune complex diseases

• Crystallization of the sulfonamides within the renal collecting system

• BM failure

• Acute self-limiting hemolytic anemia

Analgesics

• Adverse Effects of therapeutic Drugs

• Aspirin

  • GI bleeding

  • Reye`s syndrome- microvesicular fatty change in the liver and encephalopathy

  • Allergic reaction

Aspirin

• GI bleeding

• Reye`s syndrome- microvesicular fatty change in the liver and encephalopathy

• Allergic reaction

Reye`s syndrome

• aspirin

• microvesicular fatty change in the liver and encephalopathy

Mechanical force

• Physical Injuries

• abrasion

• laceration

• incision

• contusion

Gunshot wounds

• Physical Injuries

• entry wound

• exit wound

abrasion

• Mechanical force

• gasgas

• can be open

• have minor scratches

laceration

• Mechanical force

• irregular open wound caused by blunt instrument

incision

• Mechanical force

• clean cut wound brought about by knife or any sharp edge

contusion

• Mechanical force

• bruise, close wound

thermal injury

• Both excessive heat and excessive cold are important causes of injury.

• Burns are the most common cause of thermal injury

• 80% caused by fire or scalding

• Scalding- major cause of injury in children

scalding

• thermal injury

• major cause of injury in children

• due to hot liquid or gas

The clinical significance of a burn injury depends on the following factors

(The clinical significance of a burn injury depends on the following factors:)

• Depth of the burns

• Percentage of body surface involved

• Internal injuries caused by the inhalation of hot and toxic fumes

• Promptness and efficacy of therapy, especially fluid and electrolyte management and prevention or control of wound infections

superficial burns

• classification of burns

• formerly known as first-degree burns

• are confined to the epidermis

partial thickness burns

• classification of burns

• formerly known as second-degree burns

• involve injury to the dermis

full-thickness burns

• classification of burns

• formerly known as third-degree burns

• extend to the subcutaneous tissue

• may also involve damage to muscle tissue underneath the subcutaneous tissue (these were known formerly as fourth-degree burns)

fourth-degree burns

• classification of burns

• full-thickness burns

• may also involve damage to muscle tissue underneath the subcutaneous tissue (these were known formerly as ____________________)

first degree burns

• classification of burns

• redness that subsides within a few hours/days

second degree burn

• classification of burns

• blisters

• there’s elevation & fluid inside

• there’s too much pain because the nerves are exposed

third degree burns

• classification of burns

• painless because the nerves are already burnt

• this is more severe because the tissues involved are deeper and you can already see the bones, cartilages, and muscles burnt

Shock, sepsis, respiratory insufficiency

• _________, _________, and _________ _________ are the greatest threats to life in burn patients.

  • burns of more than 20% of the body surface, there is a rapid (within hours) shift of body fluids into the interstitial compartments, both at the burn site and systemically, which can result in hypovolemic shock.

  • Because protein from the blood is lost into interstitial tissue, generalized edema, including pulmonary edema, can be severe.

hypovolemic shock

• Shock, sepsis, and respiratory insufficiency are the greatest threats to life in burn patients.

  • burns of more than 20% of the body surface, there is a rapid (within hours) shift of body fluids into the interstitial compartments, both at the burn site and systemically, which can result in __________ _______.

  • Because protein from the blood is lost into interstitial tissue, generalized edema, including pulmonary edema, can be severe.

pulmonary edema

• Shock, sepsis, and respiratory insufficiency are the greatest threats to life in burn patients.

  • burns of more than 20% of the body surface, there is a rapid (within hours) shift of body fluids into the interstitial compartments, both at the burn site and systemically, which can result in hypovolemic shock.

  • Because protein from the blood is lost into interstitial tissue, generalized edema, including ___________ ______, can be severe.

burn site

ideal for the growth of microorganisms; the serum and debris provide nutrients, and the burn injury compromises blood flow, blocking effective inflammatory responses.

Pseudomonas aeruginosa

most common organism affecting burns

S. aureus, Candida species

antibiotic-resistant strains of other common hospital-acquired bacteria and fungi

24 to 48

Injury to the airways and lungs may develop within ____ to ____ hours after the burn and may result from the direct effect of heat on the mouth, nose, and upper airways or from the inhalation of heated air and noxious gases in the smoke.

Water-soluble gases

_____________, such as chlorine, sulfur oxides, and ammonia, may react with water to form acids or alkalis, particularly in the upper airways, producing inflammation and swelling, which may lead to partial or complete airway obstruction.

chlorine, sulfur oxides, ammonia

Water-soluble gases, such as ________, ________ ________, and ________, may react with water to form acids or alkalis, particularly in the upper airways, producing inflammation and swelling, which may lead to partial or complete airway obstruction.

Lipid-soluble gases

________________, such as nitrous oxide and products of burning plastics, are more likely to reach deeper airways, producing pneumonitis.

nitrous oxide

Lipid-soluble gases, such as _______________ and products of burning plastics, are more likely to reach deeper airways, producing pneumonitis.

Hyperthermia

Prolonged exposure to elevated ambient temperatures can result in heat cramps, heat exhaustion, and heat stroke.

Heat cramps

• Hyperthermia

• result from loss of electrolytes via sweating.

• Cramping of voluntary muscles, association with vigorous exercise, is the hallmark.

Heat exhaustion

• Hyperthermia

• is probably the most common hyperthermic syndrome.

• Its onset is sudden,

• with prostration (total exhaustion) and collapse

• results from a failure of the cardiovascular system to compensate for hypovolemia, secondary to water depletion.

• After a period of collapse, which is usually brief, equilibrium is spontaneously re-established.

Heat stroke

• Hyperthermia

• associated with high ambient temperatures, high humidity, and exertion. Thermoregulatory mechanisms fail, sweating ceases, and the core body temperature rises to more than 40°C, leading to multi-organ dysfunction that can be rapidly fatal.

• The underlying mechanism is marked generalized vasodilation, with peripheral pooling of blood and a decreased effective circulating blood volume. Hyperkalemia, tachycardia, arrhythmias, and other systemic effects are common.

• Necrosis of the muscles (rhabdomyolysis) and myocardium may occur as a consequence of the nitrosylation of the ryanodine receptor type 1 (RYR1) in skeletal muscle. [40] RYR1 is located in the sarcoplasmic reticulum and regulates the release of calcium into the cytoplasm.

• Inherited mutations in RYR1 occur in the condition called malignant hyperthermia, characterized by a rise in core body temperature and muscle contractures in response to exposure to common anesthetics.

ryanodine receptor type 1

• Heat stroke

• Necrosis of the muscles (rhabdomyolysis) and myocardium may occur as a consequence of the nitrosylation of the _________________________ (RYR1) in skeletal muscle. [40] RYR1 is located in the sarcoplasmic reticulum and regulates the release of calcium into the cytoplasm.

• Inherited mutations in RYR1 occur in the condition called malignant hyperthermia, characterized by a rise in core body temperature and muscle contractures in response to exposure to common anesthetics.

malignant hyperthermia

• Heat stroke

• Necrosis of the muscles (rhabdomyolysis) and myocardium may occur as a consequence of the nitrosylation of the ryanodine receptor type 1 (RYR1) in skeletal muscle. [40] RYR1 is located in the sarcoplasmic reticulum and regulates the release of calcium into the cytoplasm.

• Inherited mutations in RYR1 occur in the condition called ___________________, characterized by a rise in core body temperature and muscle contractures in response to exposure to common anesthetics.

Hypothermia

• Prolonged exposure to low ambient temperature

• a condition seen all too frequently in homeless persons.

  • low humidity

  • wet clothing

• dilation of superficial blood vessels resulting from the ingestion of alcohol hasten the lowering of body temperature.

two mechanisms of hypothermia

(two mechanisms of hypothermia):

• Direct effects

  • mediated by physical disruptions within cells by high salt concentrations caused by the crystallization of intra- and extracellular water.

• Indirect effects

  • resulting from circulatory changes, which vary depending on the rate and duration of the temperature drop.

  • Slowly developing chilling may induce vasoconstriction and increased vascular permeability, leading to edema and hypoxia.

  • Such changes are typical of “trench foot.”

Direct effects

• Hypothermia causes injury by two mechanisms

• mediated by physical disruptions within cells by high salt concentrations caused by the crystallization of intra- and extracellular water

Indirect effects

• Hypothermia causes injury by two mechanisms

• resulting from circulatory changes, which vary depending on the rate and duration of the temperature drop.

• Slowly developing chilling may induce vasoconstriction and increased vascular permeability, leading to edema and hypoxia.

• Such changes are typical of “trench foot.”

trench foot

condition developed in soldiers who spent long periods of time in water-logged trenches during the First World War (1914–1918), frequently causing gangrene that necessitated amputation (the only protection was to cover the feet with whale-oil grease as insulation).

whale-oil

• TRENCH FOOT

• condition developed in soldiers who spent long periods of time in water-logged trenches during the First World War (1914–1918), frequently causing gangrene that necessitated amputation (the only protection was to cover the feet with ________-______ grease as insulation).

with sudden, persistent chilling

• hypothermia

• (With sudden, persistent chilling):

  • the vasoconstriction and increased viscosity of the blood in the local area- cause ischemic injury and degenerative changes in peripheral nerves.

  • the vascular injury and increased permeability with exudation become evident only after the temperature begins to return to normal.

  • during the period of ischemia, hypoxic changes and infarction of the affected tissues may develop (e.g., gangrene of toes or feet).

gangrene

• is the death of tissue in part of the body

• foul-smelling discharge

• surface and subsurface discoloration