Env'tal and nutritional disease

1. Environmental disease Environmental disease Dr Daniel Kassie Assistant professor of pathology

2. Environmental disease Environmental disease • Environmental disease refer to conditions that are caused by exposure to chemical or physical agents in the ambient work place and personal environmental • Includes diseases • Alcohol and cigarrete related disorders • Therapeutic and recreational drug use • Exposure to different ambient gases like carbon monoxide • Poisoning by different chemical • Electrical and flame Burns • Excess exposure to high and low temperature

3. Terminology Terminology • Toxicology is defined as the science of poisons. • It studies the distribution, effects, and mechanisms of action of toxic agents • Definition of poisonisn’t straight forward Paracelsus in the 16th century Stated “all substances are poisons; the right dosage differentiates a poison from a remedy” • Xenobiotics are exogenous chemicals in the environment that may be absorbed by the body through inhalation, ingestion, or skin contact

4. • Ones absorbed, Xenobiotics might act at site of absorption or transported somewhere. • Most are metabolized to form water soluble product (Detoxification) or some might be activated to form toxic metabolite : Activation • Excretion of this chemicals usually occur through faces, urine and air • Some might accumulate in fat, bone tissue, brain …

6. • The reactions that metabolize xenobiotics into nontoxic products or that activate xenobiotics to generate toxic compounds occur in two phases. • In phase I reactions, chemicals undergo hydrolysis, oxidation, or reduction. • Products of phase I reactions are often metabolized into water- soluble compounds through phase II reactions, which include glucuronidation, sulfation, methylation, and conjugation with glutathione

7. Cytochrome P450 All organ very active in the liver ER

8. Environmental pollution : Air pollution Environmental pollution : Air pollution Carbon Monoxide poising • Nonirritating, colorless, tasteless, odorless gas • Vehicles, cigarette, charcoal • Important cause of accidental and suicidal death. • In small closed garage, A vehicle can produce a coma lethal dose of carbon monoxide with in 5 minute • CO is a systemic asphyxiant that kills by binding to hemoglobin and preventing oxygen transport. • Hemoglobin has a 200-fold greater affinity for CO than for O2

9. • Carboxy hemoglobin is unable to carry oxygen – Hypoxia – CNS depression – people unaware of the plight and unable to help themselves • Chronic form of CO poisoning, Stable carboxy hgb is formed – accumulate in life threatening amount – usually cause hypoxic damage to the brain particularly basal ganglia • In acute poisoning generalized cherry-red color of the skin and mucous membranes • Early presentation and treatment with 100% oxygen

11. Metals as Environmental Pollutants Lead poisoning • Readily absorbed metal that binds to sulfhydryl groups in proteins and interferes with calcium metabolism, leading to hematologic, skeletal, neurologic, GI, and renal toxicities. • Permeable BBB makes children more susceptible to lead poising

12. • 80% to 85% taken up into developing teeth and into bone, competes with calcium, binds phosphates, and has a half-life of 20 to 30 year • Peripheral neuropathy in adult • CNS damage more common in children , leading to Lower IQ, growth retardation, seizure, blindness, psychosis and coma • Lead has a high affinity for sulfhydryl groups and interferes with two enzymes involved in heme synthesis (aminolevulinic acid dehydratase and delta ferrochelatase) - MCHC

14. Occupation exposure

15. EFFECTS OF TOBACCO • Tobacco is the most common exogenous cause of human cancers, being responsible for 90% of lung cancers • Majority are due to smoking, other include chewing or snuff tobacco • Tobacco has risk of cancer both for smoker or people exposed to secondary smoke • Causes around 4 million deaths per year (Most due to CVD or COPD) • Smoking is the most important cause of preventable human death • Cessation is also associated with significant decrease in ROM.

16. At age 70 , Difference in survival is 8 years

17. • A number of noxious substance are found in tobacco are vast

18. Nicotine • Alkaloid, highly addictive substance • Binds to receptor In brain stimulate release of catecholamines • Responsible for increased HR,BP, Cardiac output and contractility • The most common diseases caused by cigarette smoking involve the lung and include emphysema, chronic bronchitis, and lung cancer

19. Mechanism of tobacco induced disease • Direct irritant effect on the tracheobronchial mucosa • Increase production of mucous, increase recruitment of inflammatory cells, increase elastase production in neutrophils (Hence : Emphysema) • Carcinogenesis : Polycyclic hydrocarbons and nitrosamine are potent increases the risk for oral, laryngeal, esophageal, gastric, lung, bladder ca

20. Mechanism of tobacco induced disease Atherosclerosis and myocardial infarction • Due to increased platelet aggregation, endothelial damage, Lung disease reduced oxygen exchange worsening narrowed supply • Has multiplicative effect when patient has HTN,DM and hypercholesteremia Smoking increase risk of spontaneous abortion, preterm labor , IUGR • Children exposed to smoke has increased risk of asthma and respiratory illness Passive smoke inhalation : Relative risk for lung ca is 1.3x than non exposed

21. Health consequence of smoking summary

22. Effect of Alcohol Effect of Alcohol • Despite all the attention given to illegal drugs, alcohol abuse is a more widespread hazard and claims many more lives. • Fifty percent of adults in the Western world drink alcohol, and 5% to 10% have chronic alcoholism • After ingestion, Absorbed at stomach and intestine and distributed equally through out the body in direct proportion to blood level • DUI is considered after 80 mg/dl (3 beer, 150 ml liquor, 500ml wine)

23. • Drowsiness occurs at 200 mg/dL, stupor at 300 mg/dL, and coma, with possible respiratory arrest at much higher level (>500) • Chronic alcoholics develop tolerance and metabolize alcohol at a higher rate than normal and hence show lower peak levels of alcohol

24. Alcohol metabolism Alcohol metabolism Only involved at higher volume Interfere with drug metabolism PCM, cocaine use this enzyme Only 10-15 percent

25. Toxic effects of ethanol metabolism Toxic effects of ethanol metabolism • Depletion of NAP+ and increase of NADPH interfere with fatty acid oxidation (needs NAD+) resulting in fatty liver and increased NADPH/NAD+ ratio leads to lactic acidosis • Acetyldehyde toxicity : unpleasant reaction like flushing,tachychardia and hyperventilation • Alcohol cause endotoxin release from intestinal flora – stimulat white blood cells – elicit inflammation and damages organs • ROS generation : Exact mechanism isn’t understood but free radical induced damage through the cytochrome P450 enzyme

26. Acute severe intoxication • CNS depression : Affects subcortical region that modulate cerebral cortical activity : Leads to disordered function motor/intellectual and cortex • At higher dose medullary function are suppressed • Damage to GI : Causes ulcer and acute gastritis • Liver : Even with moderate consumption result in fat droplet accumaltion and liver cell damage

27. Chronic alcoholism Chronic alcoholism Liver • Fatty liver, alcoholic hepatitis and cirrhosis • Cirrhosis is associate with portal hypertension and increased risk of HCC Gastrointestinal tract • Esophageal and gastric ulcer • Bleeding from the ulcer or veins due to Portal hypertension

28. Chronic alcoholism Chronic alcoholism Neurologic effect • Thiamin deficiency : Resulting in peripheral neuropathy and Wernicke - Korsakoff syndrome (Amnesia) • Wernicke syndrome : Acute form, present with gait abnormality, ophthalmoplegia and memory loss • Korsakoff syndrome : Chronic form, Memory loss and confabulation • Cerebral atrophy, cerebellar degeneration Pancreas • Acute and chronic pancreatitis

29. Chronic alcoholism Chronic alcoholism CVS • Increases risk of atherosclerosis • Dilated cardiomyopathy Effect on Fetus • Cause fetal alcohol syndrome Carcinogenesis • Increases the risk of oral, esophageal, liver and breast cancer Malnutrition

30. Injury by commonly used therapeutic drug Injury by commonly used therapeutic drug Acetaminophen (Paracetamol) • mostly conjugated in the liver with glucuronide or sulfate. • About 5% or less is metabolized to NAPQI (N-acetyl-p-benzoquinoneimine) through the hepatic P-450 system. • Large dose leads to accumulation of NAPQI : Depletes GSH (Removes ROS) and coagulates hepatocyte protein and cause centrilobular hepatic necrosis • Recommended dose for adult is less than 4gm. Toxic dose is 15-25 mg

31. Asprin • respiratory alkalosis develops, followed by a metabolic acidosis that often proves fatal • Fatal doses may be as little as 2 to 4 g in children and 10 to 30 g in adults • Chronic aspirin toxicity (salicylism): >3 gm /day • headache, dizziness, ringing in the ears (tinnitus), difficulty in hearing, mental confusion, drowsiness, nausea, vomiting, and diarrhea. • Convulsion or coma. • Cause acute erosive gastritis • Blocks COX enzyme – That produce TXA2 – Plt aggregation inhibited - petichae

32. Combined Oral contraceptives • Decreases the risk endometrial cancer, ovarian cancer and mildly increases risk of cervical cancer • No association with breast cancer • Increases chance of thromboemobolic event • Increases risk of hepatic adenoma • Increases risk of cardiovascular disease in woman > 35,smoker

33. INJURY BY PHYSICAL AGENTS Mechanical Trauma : Following RTA, fall down stick injuries, bullets • Abrasion : produced by scraping or rubbing the skin surface, which damages the superficial layer • Contusion : bruise, is a wound usually produced by a blunt trauma and is characterized by damage to a vessel and extravasation of blood • Laceration : Tear or disruptive stretching of tissue caused by the application of force by a blunt object • Incised wound : One inflicted by a sharp instrument • Perforating wounds

35. Thermal burn Thermal burn The clinical severity of burns depends on the following important variables: • Depth • Percentage of body surface involved • internal injuries inhalation of hot and toxic fumes are present • Promptness and efficacy of therapy, especially fluid and electrolyte management and prevention or control of wound infections

36. Thermal injuries Thermal injuries Thermal Burns • 1st degree burn-involves the epidermis only • 2nd degree burn-involves the epidermis and dermis • 3rd degree burn-involves the subcutaneous tissue • 4th degree burn-involves bones and muscles • full-thickness burns are white or charred, dry, and anesthetic ( destruction of nerve endings), • partial-thickness burns, depending on the depth, are pink or mottled, blistered, and painful • Shock ,sepsis and respiratory failure are the greatest treats of life

38. Hyperthermia • Prolonged exposure to elevated ambient temperatures can result in heat cramps, heat exhaustion, or heat stroke. • Heat cramps : result from loss of electrolytes through sweating. Cramping of voluntary muscles is the hallmark sign. Heat-dissipating mechanisms are able to maintain normal core body temperature.

39. Heat exhaustion • The most common hyperthermic syndrome. • Its onset is sudden, with prostration and collapse, and it 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 reestablished if the victim is able to rehydrate.

40. Heat stroke : Elderly with CVD or young patient with severe physical stress • Associated with high ambient temperatures and high humidity. • Thermoregulatory mechanisms fail, sweating ceases, and core body temperature rises. • > 40 °C : grave prognostic sign, and the mortality rate 50%. • Peripheral vasodilation with peripheral pooling of blood - decreased BV • Necrosis of the muscles and myocardium, arrythemia, DIC may occur

41. Malignant hyperthermia • Not caused by exposure to high temperatures. • genetic condition mutations RYR1 : control calcium levels in skeletal muscle cells. • In affected individuals, exposure to certain anesthetics during surgery may trigger a rapid rise in calcium levels in skeletal muscle, which in turn leads to muscle rigidity and increased heat production. • Mortality rate of approximately 80% if untreated • 5% if the condition is recognized and muscle relaxants administered

42. Hypothermia • Homeless alcoholic • At about 32°C, loss of consciousness occurs, followed by bradycardia and atrial fibrillation at lower core temperatures Mechanism of injury • Direct injury : Physical disruption, crystallization of water • Indirect effect : vasoconstriction,increased permiablity, increased viscosity, ischemia increased edema – Gangrene

43. Electrical Burn • Result from contact with • Low voltage (home and work place) or • High voltage (high power lines) • Two types of injury 1. Burns 2. ventricular fibrillation or cardiac and respiratory center failure resulting from disruption of normal electrical impulse

44. Nutritional disease Nutritional disease

45. Nutritional disease Nutritional disease Malnutrition • Inadequate intake of protein and calories or deficiencies in the digestion or absorption of protein resulting loss of fat and muscle, and generalized body weakness • In the other spectrum, obesity, results in increased risk of DM,HTN and Atherosclerosis with its complication

46. Dietary insufficiency • Appropriate diet should have • Adequate energy in forms of protein, carbohydrates, fat, • Contain adequate amino acid and fat for synthesis of protein and lipids • Adequate mineral and vitamin which are important coenzymes and hormones • primary malnutrition : one or all are missing due to reduced intake • Secondary malnutrition : Impaired absorption, utilization, storage, excess loss or increased need for nutrients

47. Conditions that lead to malnutrition • Poverty • Acute or chronic illness • Chronic alcohol consumption : Usually thiamin and folate deficiency • Ignorance or failure of diet supplementation : Pregnancy, Iodine • Self imposed dietary restriction : Bulimia, anorexia • Other causes : GI disease, pancreatic disease, drugs, inadequate TPN …..

48. Severe acute malnutrition (SAM) • WHO defines SAM Weight for height ratio below three standard deviation below normal • One of the major cause of under five children. • SAM can present in clinical range of syndromes • Marasmus : Affects primary somatic compartment, skeletal muscle • Kwashiorkor : Affects (deplets) primarily visceral compartment, Liver

49. Diagnosis • Straight forward in severe form, In mild to moderate form • Standard weight for height tables • Mid upper arm circumference • Skin fold thickness • Serum protein level • In addition to reduced intake, Abnormal gut microbiome is implicated recently as additional factor in pathogenies of SAM

50. Marasmus • Develops when the diet is severely deficient in calories • Considered marasmus when weight is reduced 60 percent for age, sex and height. • Suffers from growth retardation, Loss of muscle mass and subcutaneous adipose tissue due to catabolism and utilization • Visceral protein compartment is preserved, serum albumin is either normal or mildly reduced