e nvironmental & n utritional d isease by dr jayalaxmi cb. presenter: dr abiodun mark.a

ENVIRONMENTAL & NUTRITIONAL DISEASE

By Dr Jayalaxmi CB.Presenter: Dr Abiodun Mark .A

OUTLINE

GENERAL MECHANISMS OF TOXICITY ENVIRONMENTAL POLLUTION EFFECTS OF TOBACCO EFFECTS OF ALCOHOL INJURY BY THERAPEUTIC DRUGS AND DRUGS OF

ABUSE INJURY BY PHYSICAL AGENTS NUTRITIONAL DISEASES

INTRODUCTION.

The term environment comprises of both the indoors, outdoors & occupational environment.

In each of these environments, the food, water & air are major determinants of our health.

Our personal environment on the other hand is influenced greatly by tobacco use, alcohol ingestion, therapeutic and non therapeutic uses of drugs and our diet.

ENVIRNOMENTAL DISEASE

The term environmental diseases refers to lesions and diseases caused by exposure to chemical or physical agents in the ambient, workplace, and personal environments, including diseases of nutritional origin.

Environmental diseases mostly came into public's attention after major disasters like:-Methyl isocyanate gas in Bhopal India in 1984.-Chernobyl nuclear disaster Ukraine 1986.-Mercury contamination in Japan 1960s.

TOXICITY OF CHEMICAL & PHYSICAL AGENTS.

Toxicology is defined as the science of poisons.

Toxicology studies the distribution, effects and mechanisms of action of toxic agents.

Approx 4 billion pounds of toxic chemicals including 72 million pounds of recognized carcinogens are produced in the united states annually.

TOXICITY OF CHEMICAL & PHYSICAL AGENTS: POISON

The definition of a poison is not an easy one.

Poison is a concept that is highly determined by dosage.

Paracelsus: “All substances are poison ,the right dose differentiates a poison from a remedy”

TOXICITY OF CHEMICAL & PHYSICAL AGENTS: XENOBIOTICS.

Xenobiotics - These are exogenous chemicals present in air, water, soil, and food.

Enter the body through skin, inhalation, and ingestion.

Some xenobiotics form inactive water soluble products called detoxification.

XENOBIOTICS MENTABOLISM:PHASE 1.

Xenobiotics are metabolized to form inactive water soluble products(detoxification) or are activated to toxic metabolites.

The reaction that converts xenobiotics into either nontoxic or toxic compounds occurs in 2 phase.

Phase I Reactions (Smooth ER), makes them less lipophilic by adding a direct polar group (Hydrolysis, oxidation, reduction) Cytochrome P-450-dependent monooxygenase

system Flavin-containing monooxygenase system Peroxidase-dependent co-oxidation

XENOBIOTICS MENTABOLISM:PHASE II

Phase II Reactions, combines them with other polar substances Glucuronidation Biomethylation Sulfation Glutathione conjugation

CYTOCHROME P-450 ENZYME SYSTEM. The most important catalyst in phase1 is Cytochrome P-450

enzyme system, they detoxify or activate xenobiotics to cause cellular injury.

The enzymatic effect of CYP on xenobiotics sometimes causes the generation of free radicals which can damage cells & tissues.

Carbon tetrachloride Toxic trichloromethyl (liver)

Generation of a DNA binding metabolite from Benzo-a-pyrene, a carcinogen present in cigarette.

There is a great variation in the activity of CYPs among individuals.

ENVIRONMENTAL POLLUTION.

Metals Industrial Exposures Agricultural Hazards Natural Toxins Radiation Injury Physical Injury

ENVIRONMENTAL POLLUTION:OUTDOOR AIR POLLUTION: OZONE (O3)

The interaction of UV radiation and oxygen in the stratosphere causes ozone formation which then accumulates in the ozone layer.

The ozone layer offers a protective effect to life on earth by absorbing the dangerous UV rays.

The ozone layer has decreased in size over the years due to use of aerosols.

This has lead to a ban in the use of CFC as aerosol propellants.

In contrast to the good ozone, ozone that accumulates in the lower atmosphere is a very pernicious air pollutant.

Ozone toxicity is dues to its free radical mediated injury, mostly on the lungs.

ENVIRONMENTAL POLLUTION:OUTDOOR AIR POLLUTION: CARBON MONOXIDE

Air pollutants, accidental & suicidal death Automotive engines, industrial, cigarette smoke Colorless, tasteless, odorless, and non-irritating.

Toxicity: At low levels, forms carboxyhemoglobin producing hypoxia ischemia in CNS death.

Clinical Manifestation Headache, nausea, confusion Acute poisoning Cherry-red skin color and mucous

membranes due to high carboxyhemoglobin Chronic poisoning Hypoxia, Ischemic changes in the

CNS(Basal ganglia) Treatment – O2

ENVIRONMENTAL POLLUTION:OUTDOOR AIR POLLUTION: SULPHUR DIOXIDE.

Sources:- Burning charcoal and oil, paper mills, power plants

When it releases into air converts into sulfuric acid.

Effects Irritation in the nose and throat.

ENVIRONMENTAL POLLUTION: OUTDOOR AIR POLLUTION :PARTICULATE MATTER (SOOT)

Sources:- Coal and oil fired power plants

Particulate matter soot less than 10 micrometer diameter is most harmful

Clinical features-Inflammation of lung, asthma attacks, irritation of eyes and nose, myocardial ischemia, scrotal cancer.

EFFECTS OF AIR POLLUTANTS ON LUNG

Acute toxicity Irritate the bronchi Pulmonary edema Allergic reaction Asthmatic attacks Chronic lung disease Pneumoconiosis Cancer

ENVIRONMENTAL POLLUTION: INDOOR AIR POLLUTION: RADON

Radon is a radioactive gas and a decay product of uranium.

It is widely distributed in the soil and is prevalent in homes (especially in basements)

Radon decay products are alpha emitters.

Increased risk of lung cancer due to radon. Smoking elevates risk.

Proper venting reduces the exposure.

METALLIC ENVIRONMENTAL POLLUTANTS: LEAD

Lead is classified as a heavy metal (others include mercury, arsenic, and cadmium)

Naturally occurring elementSource of exposure lead paint lead solder in plumbing (older houses) lead-glazed ceramics industrial exposure

Route of absorption inhalation with industrial exposure ingestion with household exposure

Lead poisoning also occurs in:-Painters Batteries House paints Gasoline Flaking lead paint in older houses Mines, foundries and spray paints.

LEAD DISTRIBUTION AND EXCRETION Half-life of lead in bone is 30 years

lead in blood indicates recent exposure.

Remainder is distributed in the soft tissues.

Excretion is via the kidneys.

A more permeable blood-brain barrier in children creates a high susceptibility to brain damage.

Lead poisoning effects Behavior & learning problems, Lower IQ & Hyperactivity, Slowed growth, Hearing problems, Anemia

EFFECTS OF LEAD

High affinity for sulfhydryl groups Inhibition of heme

synthesis hypochromic anemia and basophilic stippling of erythrocytes

Competition with calcium ions.

Inhibition of membrane-associated enzymes.

Lead interferes with normal remodeling of cartilage also it delays the healing of fractures.

WHAT ARE THE SIGNS OF LEAD POISONING?

Lead lines on the gums.

Lead lines in the epiphyses of long bones.

Anemia (microcytic hypochromic) develops due to the inhibition of hematopoiesis.

A characteristic finding is basophilic stippling of erythrocytes.

Lead colic: severe and extremely difficult to localize abdominal pain.

Peripheral demyelization neuropathies: this manifests via wrist drops and foot drops.

Kidneys: decreases the excretion of uric acid leading to gout.

Basophillic Stipling

Consequences of lead exposure

METALLIC ENVIRONMENTAL POLLUTANTS: MERCURY POISONING

Minamata disease (Industrial disaster)

Cerebral palsy, mental retardation, deafness and blindness

It is caused mainly by Mercury Methyl Exposure to industrial power plants, cave paintings,

dental amalgams, Contaminated fish, contaminated rivers and

streams.

Intracellular glutathione exhibits protective mechanism against the effects of mercury toxicity with CNS and kidney damage.

METALLIC ENVIRONMENTAL POLLUTANTS ARSENIC POISONING

Historically “Murder Weapon” (Royal family)

Found in soil and water , also in agricultural products and wood preservatives, herbicides.

It usually causes lung and skin cancer.

Chronic exposure causes hyperkeratosis and hyperpigmentation and development of basal and squamous cell carcinoma of skin.

OCCUPATIONAL HAZARDS

Pneumoconiosis – Inhalation of mineral dusts causing lung diseases

Coal workers pneumoconiosis: Asbestosis Silicosis Berylliosis Bysinossis. Bagasossis.

PNEUMOCONIOSES Non-neoplastic lung reaction to inhalation of

mineral, other inorganic and organic dusts

4 major - coal dust, silica, asbestos, beryllium.

concentration size and shape of particles (1-5µm) chemical character of dust concurrent smoking

COAL WORKERS' PNEUMOCONIOSIS Spectrum of findings in coal workers

Asymptomatic anthracosis simple coal workers' pneumoconiosis (little

pulmonary dysfunction) - slight fibrosis, non-progressive

Progressive massive fibrosis (lung function compromised) - fibrous nodules (up to 2 cm) - sometimes coalesce - "black lung", central necrosis.

Clinically - breathlessness, cough sometimes associated with rheumatoid arthritis - Caplan's syndrome (rapidly developing nodular pulmonary lesions)

SILICOSIS

Inhalation of crystalline silica

Crystalline forms

Most prevalent chronic occupational disease in the world

very heavy exposure - acute silicosis (generalized accumulation of lipoproteinaceous material within alveoli)

Decades of exposure - stone cutting, foundry work, ceramics, sandblasting.

Pulmonary hypertension, cor pulmonale.

Eggshell calcifications in LN

BERYLLIOSIS

Exposure in mining and fabrication, aerospace workers.

Massive dose - acute pneumonitis

Protracted exposure - pulmonary and systemic granulomatous disease closely mimicking sarcoidosis.

Progressive course with fatal outcome; in some patients remission and spontaneous disappearance.

VINYL CHLORIDE.

Associated with Angiosarcoma of the liver.

Mostly found among plastic factory workers.

TOBACCO.

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

The main culprit is cigarette smoking, but smokeless tobacco is also harmful.

Tobacco smoking is the single most common cause of preventable mortality.

Passive smoking is also injurious to health.

Tacky the brown material in the cigarette smoke gives brown stain to teeth and fingers.

TOBACCO EFFECT.

Nicotine receptors in the brain and, through the release catecholamine's, the increase in heart rate and blood pressure, and the increase in cardiac contractility and output.

Cessation of smoking greatly reduces within 5 yrs the overall mortality and risk of death from cardiovascular diseases.

Carcinogenic substances in tobacco smoke are:Tar, Benzopyrene, Polycyclic hydrocarbons, Nitrosamines

DISEASES RELATED TO SMOKING INCLUDE:-

Heart & blood vessels:

Cigarette smoking is risk factor with hypertension and hypercholesterolemia coronary artery disease and arteriosclerosis.

Myocardial infarction and stroke in women who take oral contraceptives.

Lung: 1. Chronic bronchitis

(irritation & ↑ mucus production)

2. Emphysema (recruitment of leukocytes with ↑local elastase production

3. Cancer of lung, bronchogenic carcinoma

TOBACCO EFFECTS.

GIT: Tobacco use also

increases the prevalence of peptic ulcers.

Smoking impairs healing of ulcers and increases the likelihood of recurrence.

Smoking may also increase pyloric reflux

Other associated problems:

low birth weight.

Increased incidence of spontaneous abortion.

Premature rupture of the membranes.

Placenta previa

Abruptio placentae

ALCOHOL Ethanol consumption in moderation is

generally not harmful, but excessive amount causes serious physical and psychological damage.

Stats: 100, 000 deaths annually due to Alcohol consumption U.S.

Legal blood concentration 80mg/dL or 0.08%.

The legal definition of drunken drive Blood alcohol concentration of 80mg to

100 mg– 200 mg/dl drowsiness– 300 mg/dl Stupor– 400 mg/dl Profound anesthesia (may be fatal)

ALCOHOL

Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase in the gastric mucosa and liver, and by cytochrome P-450 ( xenobiotic-metabolizing enzyme CYP2E1) and catalase in the liver.

Acetaldehyde is converted to acetic acid by aldehyde dehydrogenase.

When alcohol is present in the blood at high concentrations, it competes with other CYP2E1 substrates and may delay the catabolism of other drugs

GENETIC VARIATION.

Asians have low content of ALDH (Acetaldehyde dehydrogenase) leads to flushing, tachycardia, nausea hyperventilation.

Women has decreased levels of alcohol dehydrogenase cause high levels of alcohol in the blood.

EFFECTS OF ALCHOHOL.

Fatty accumulation (Hepatic steatosis) in the liver is because of excess of NADH.

The NAD is converted to NADH (Nicotinamide adenine dinucleotide)

The NAD is needed for fatty acid oxidation in liver & conversion of lactate to pyruvate.

In fatty liver, fat droplets seen in cytoplasm of hepatocytes.

Lactic acidosis. Hyperurecemia Increase in beta OHB Hypoglycemia due to decrease in

oxaloacetate due to more generation of lactate from pyruvate.

CHRONIC ALCOHOLISM

Liver: -Hepatic injury leading to chronic liver disease

1. Fatty liver 2. alcoholic hepatitis 3. Cirrhosis (15-

20%) 4.HCC.

Using cytochrome P450 system in metabolism of ethanol, will generate reactive oxygen species causing lipid peroxidation of cell membrane.

ALCOHOLIC HEPATITIS

Alcoholic hepatitis can produce fever, liver tenderness, and jaundice.

On histologic examination, there are focal areas of hepatocyte necrosis and cell injury manifest by fat accumulation and alcoholic hyaline, or Mallory bodies. Neutrophils accumulate around foci of necrosis.

ALCOHOLIC CIRRHOSIS

Ethanol and its metabolites are directly toxic to hepatocytes with chronic ethanol use.

10% to 15% of alcoholics develop irreversible liver damage, or alcoholic cirrhosis.

Characterized by a hard, shrunken liver with formation of micronodules regenerating hepatocytes surrounded by dense bands of collagen.

Perisinusoidal fibrosis occurs initially, with deposition of collagen by perisinusoidal stellate cells (Ito cells)

Alcoholic cirrhosis is a serious, potentially fatal disease accompanied by:– Weakness– Muscle wasting– Ascites– Gastrointestinal hemorrhage– Coma

NEUROLOGIC EFFECT OF CHRONIC ALCHOHOLISM.

Korsakoff syndrome: Some alcoholics

with poor nutrition develop the severe memory loss.

This is believed to result from a combination of direct toxicity and thiamine deficiency.

Wernicke syndrome Ataxia, disturbed

cognition, ophthalmoplegia, and nystagmus.

Chronic thiamine deficiency contributes to degeneration of nerve cells, reactive gliosis, and atrophy of the cerebellum and peripheral nerves

CARDIOVASCULAR EFFECTS OF CHRONIC ALCOHOLISM. Chronic ethanol abuse can cause Dilated

Cardiomyopathy.

Hypertension is also more common in chronic alcoholics, Secondary to the vasopressor effects of ethanol triggered by increased release of catecholamines.

Moderate consumption of redwine (one to two drinks per day) show a protective effect of ethanol on the cardiovascular system.

At this level of consumption, drinkers show increased levels of high-density lipoprotein and decreased platelet aggregation.

EFFECT OF ALCOHOL ON GASTROINTESTINAL TRACT.

Acute gastritis: due to a direct toxic effect of ethanol on the stomach.

Chronic users are vulnerable to acute and chronic pancreatitis: – Pancreatic acinar destruction leads to impaired intestinal absorption of nutrients and contributes to vitamin deficiencies.

Bleeding from gastritis, gastric ulcer, or Esophageal Varices (Cirrhosis)

Reflux esophagitis (Mallory-Weiss Syndrome)

EFFECT ON REPRODUCTIVE SYSTEM

Chronic ethanol use leads to testicular atrophy and decreased fertility in both men and women.

Women who drink alcohol also have an increased risk of spontaneous abortion.

EFFECT ON DEVELOPING FETUS. Fetal Alcohol Syndrome A tragic consequence

characterized by growth and developmental defects, including microcephaly .

Maxillary hypoplasia, ASD, short palpebral fissure and mental retardation.

The pathogenesis of fetal alcohol syndrome is not entirely clear. It is hypothesized that acetaldehyde, a metabolite of ethanol crosses the placenta and damages the fetal brain