Environmental & Nutritional Pathology. Topics. Environment Diseases 2/13/2014

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1 Environmental & Nutritional Pathology Topics Environmental pathology General mechanism of Toxicity Environmental pollution Effects of Tobacco Effects of Alcohol Injury by Physical agent 3 ม นาคม 2557 นายแพทย ดร.ณตพล ศ ภณ ฐเศรษฐก ล ภาคว ชาพยาธ ว ทยา คณะแพทยศาสตร มหาว ทยาล ยนเรศวร Nutritional deficiencies Protein Energy Malnutrition Vitamin Deficiencies Mineral Deficiencies Obesity Environment Diseases = Conditions caused by exposure to chemical or physical agents in the environment [outdoor, indoor, occupational, personal (tobacco, alcohol, drug) environment] Figure 8-1 Human exposure to pollutants. Pollutants contained in air, water, and soil are absorbed through the lungs, GI tract, and skin. In the body they may act at the site of absorption but are generally transported through the bloodstream to various organs, where they may be stored or metabolized. Metabolism of xenobiotics may result in the formation of water-soluble compounds that are excreted or in activation of the agent, creating a toxic metabolite. 1

2 General Mechanisms of Toxicity Toxicology = The science of poison Poison basically depends on dosage All substances are poisons (Paracelsus 16 th century) Xenobiotics = Exogenous chemicals Figure 8-2 Xenobiotic metabolism. Xenobiotics can be metabolized to nontoxic metabolites and eliminated from the body (detoxification). However, their metabolism may also result in activation of the chemical leading to formation of a reactive metabolite that is toxic to cellular components. If repair is not effective, short- and long-term effects develop. (Based on Hodgson E: A Textbook of Modern Toxicology, 3rd ed. Fig Hoboken, New Jersey, John Wiley & Sons, 2004.) Metabolism of Xenobiotics Cytochrome P-450 system in liver (ER) Detoxification and excretion Toxic metabolites reactive oxygen species (ROS) Cellular injury and cell death Environmental Pollution Air pollution : smog (Ozone, Nitrogen dioxide, Sulfur dioxide, Carbon monoxide, particulate matter) Metals as Environmental Pollutants (Lead, Mercury, Arsenic, Cadmium) Chemicals, drugs, alcohol are primarily metabolized by this enzyme system 2

3 Carbon monoxide (CO) An air pollutants and important cause of death from accidents and suicide (nonirritating, colorless, tasteless, odorless gas) Imperfect oxidation of cabonaceous material: car exhaustion, wood furnace, etc. Binds hemoglobin with high affinity (Carboxyhemoglobin) and cause systemic asphyxiation with CNS depression, lethal coma in 5 minutes 20-30% saturation = systemic hypoxia 60-70% saturation = unconsciousness and death Heavy Metal Lead: paint, Encephalopathy and Mental deterioration in children, bone defect, anemia Mercury: Contaminated fish and dental amalgams, CNS defect (cerebral palsy, deafness, blindness), Minamata disease Arsenic: soil and water, GI, cardio and CNS disturbance with hyperpigmentation of skin Cadmium: soil, batteries, obstructive lung disease and kidney damage, itai-itai in postmenopausal women (osteoporosis, osteomalacia associated with renal disease) 3

4 Effects of Tobacco Tobacco smoke contains >2,000 compounds Nicotine Tobacco addiction Strong carcinogen: Polycyclic aromatic hydrocarbon, nitrosamine, aromatic amines, especially Lung Cancer Effects of Tobacco Important risk factor for atherosclerosis, MI, cerebrovascular accident (stroke) Predispose to emphysema, chronic bronchitis, chronic obstructive disease Maternal smoking increases the risk of abortion, premature birth, intrauterine growth retardation Figure 8-6 Adverse effects of smoking: the more common are in bold face. 4

5 Smoking cessation Greatly reduces the risk of death from Lung cancer Figure 8-7 The risk of lung cancer is determined by the number of cigarettes smoked. (Modified from Stewart BW, Kleihues P [eds]: World Cancer Report, Lyon, IARC Press, 2003.) Effects of Alcohol Drawsiness at blood level 200 mg/dl...เมา Alcohol is oxidized to acetaldehyde in the liver by alcohol dehydrogenase and acetate used in respiratory chain in mitochondria Acute effects: CNS depression, Fatty liver, gastritis, diuresis, dehydration, metabolic acidosis, hyperventilation By law เมาส ราตามกฎหมาย ปร มาณ alcohol ในกระแส เล อดมากกว า 50 mg/dl (ว ดโดยการเป าออกมาทาง ลมหายใจ) จ าค กไม เก น 3 เด อน หร อปร บต งแต 2,000-10,000 บาท หร อ ท งจ าท งปร บ (พรบ.จราจรทางบก พ.ศ. 2522) จ าค กไม เก น 1 ป หร อปร บต งแต 5,000-20,000 บาท หร อท งจ าท งปร บ และพ กใช ใบอน ญาตข บข ไม น อย กว า 6 เด อน หร อเพ กถอนใบอน ญาต (ฉบ บท 7 พ.ศ. 2550) (รอลงอาญา+ค มประพฤต ) ไวน 2 แก ว, เบ ยร ปกต 2 กระป อง, ไลท เบ ยร 4 กระป อง, ส รา 6 ฝา เป นต น 5

6 - ถ าการกระท าความผ ดตามวรรคหน งเป นเหต ให ผ ได ร บอ นตรายแก กายหร อ จ ตใจผ กระท าต องระวางโทษจ าค กต งแต หน งป ถ งห าป ปร บสองหม นบาทถ ง หน งแสนบาท และให ศาลส งพ กใช ใบอน ญาตข บข ของผ น นม ก าหนดไม น อยกว า หน งป หร อเพ กถอนใบอน ญาตข บข - ถ าการกระท าความผ ดตามวรรคสองเป นเหต ให ผ อ นได ร บอ นตรายสาห ส ผ กระท า ต องระวางโทษจ าค กต งแต สองป ถ งหกป และปร บต งแต ส หม นบาทถ งหน งแสนสอง หม นบาท และให ศาลส งพ กใช ใบอน ญาตข บข ของผ น นม ก าหนดไม น อยกว าสองป หร อ เพ กถอนใบอน ญาตข บข - ถ าการกระท าความผ ดตามวรรคสองเป นเหต ให ผ อ นถ งแก ความตาย ผ กระท าต อง ระวางโทษจ าค กต งแต สามป ถ งส บป และปร บต งแต หกหม นบาทถ งสองแสนบาท และ ให ศาลส งเพ กถอนใบอน ญาตข บข Effects of Alcohol Chronic alcoholism: alcoholic hepatitis, cirrhosis, portal hypertension, esophageal varice, gastric ulcer, cardiomyopathy, pancreatitis, Thiamine deficiency, hepatocellular carcinoma, and oral cancer Fetal alcohol syndrome: microcephaly, growth retardation, unusual facial feature, reduction in mental functions Fetal Alcohol Syndrome Growth retardation, Mental retardation, Unusual facial feature Drugs or Medications Adverse drug reaction (NSAIDs, paracetamol, Antibiotics, etc.) Drug abuse (Cocaine, Heroin, Marijuana, LSD, Ectasy, Ice, Sedatives, Anxiolytics, Antitussive) 6

7 Injury by Physical Agents Mechanical trauma (Abrasion, Laceration, Contusion, Cut wound, Puncture wound) Thermal injury (Burns, Heat stroke, Hypothermia) Electrical injury (burns, cardiac failure) Radiation injury Laceration wound Contusion Figure 8-12 A, Laceration of the scalp: the bridging strands of fibrous tissues are evident. B, Contusion resulting from blunt trauma. The skin is intact but there is hemorrhage of subcutaneous vessels, producing extensive discoloration. (From the teaching collection of the Department of Pathology, University of Texas Southwestern Medical School, Dallas, Texas.) Abrasion wound Cut wound, Incised wound Radiation Injury Direct injury to DNA mutation neoplastic transformation Indirect injury by generating free radicals from water or molecular oxygen in the body Rapidly dividing cells are very sensitive (germ cells, bone marrow, GI tract) Vascular damage and sclerosis ischemic necrosis and replacement by fibrous tissue Stab wound, Puncture wound 7

8 Figure 8-13 Effects of ionizing radiation on DNA and their consequences. The effects on DNA can be direct or, most importantly, indirect, through free-radical formation. Figure 8-15 Overview of the major morphologic consequences of radiation injury. Early changes occur in hours to weeks; late changes occur in months to years. ARDS, acute respiratory distress syndrome. Topics Environmental pathology Nutritional deficiencies Protein Energy Malnutrition Anorexia Nervosa and Bulimia Vitamin Deficiencies Mineral Deficiencies Obesity Nutritional Requirement An aequate diet should provide: 1. Energy, in the form of carbohydrates, fats, proteins 2. Essential (as well as nonessential) amino acids and fatty acids as building blocks 3. Vitamins and minerals function as coenzymes and hormones in vital metabolic pathways 8

9 ภาวะท พโภชนาการ (Malnutrition) Primary malnutrition : missing from the diet Secondary malnutrition : adequate nutrients supply, but malnutrition may result from - Malabsorption - Impaired nutrient use or storage - Excess nutrient losses - Increased need for nutrients (GI diseases, chronic wasting diseases, acute critical illness) Common Causes Poverty (homeless, aged, children) Ignorance (infants, adolescents, pregnant women) Chronic alcoholism Acute and chronic illnesses (trauma, burn, cancer, etc.) Self-imposed dietary restriction Protein - Energy malnutrition (PEM) - PEM refers to a range of clinical syndrome characterized by an inadequate dietary intake of protein and calories to meet the body s needs. - Primary (children) and Secondary (illness) PEM - Two polar forms: - Marasmus, - Kwashiorkor 9

10 1. Marasmus. - Severe reduction in caloric intake (ขาดพล งงานมากกว า) - Reduction in body weight > 60% - Most common during the first year of life - Use somatic protein component & subcutaneous fat as a source of energy very thin - Serum albumin levels are either normal or only slightly reduced - Growth retardation, multivitamin deficiencies, anemia, immune deficiency 2. Kwashiorkor - More severe form of malnutrition than marasmus - Mainly occur in children 6 months to 3 years of age - Occurs when protein deprivation is relatively greater than the reduction in total calories (ขาดโปรต นมากกว า) - Loss of visceral protein component - Hypoalbuminemia generalized edema - Fatty change of liver - Skin lesion : hypo-and hyperpigmentation, desquamation - Hair change : overall loss of color or alternating band (flag sign), straightening, loss of firm attachment to the scalp - Multivitamin deficiencies, anemia, immune deficiency Secondary PEM. Syndrome Clinical setting Time course Clinical features Laboratory findings Prognosis 1. marasmuslike PEM Chronic illness (e.g., cancer, chronic lung disease,) Months History of weight loss, muscle wasting, absent subcutaneous fat Normal or mildly reduced serum proteins Variable; depends on underlying disease 2. kwashiorkorlike PEM Acute, catabolic illness (e.g., severe trauma, burn, sepsis) Weeks Normal fat and muscle, edema, easily pluckable hair Serum albumin < 2.8 gm/dl poor 10

11 Vitamin Deficiencies and Toxicities Fat soluble vitamins A, D, E, K Deficiency due to abnormal fat absorption Accumulate and toxicity Water soluble vitamins B1, B2, B3, B6, B12, C, Folate Other names, diseases Other names Ascorbic acid Niacin Pyridoxine Calciferol Cobalamin Retinoic acid Thiamine Riboflavin Tocopherol Phylloquinone Folic acid Vitamin deficiencies Bitot s spot, Keratomalacia Rickets, Osteomalacia Beri beri, Wernicke-Korsakoff syndrome Scurvy, impaired collagen synthesis Bleeding diathesis Neural tube defect Pellagra (3Ds) Angular stomatitis, cheilosis Megaloblasic anemia with neurologic symptoms Vitamin A Deficiency : night blindness : Bitot s spot (small plaques of keratin debris), keratomalacia (corneal ulcer and destruction), xerophthalmia (dry eye), total blindness : Squamous metaplasia 2 o pulmonary infection, KUB stone (keratin debris) 11

12 Vitamin D 1, 25 (OH)2 D is the active form of vitamin D (synthesis from kidney by α1-hydroxylase) Function : stimulate intestinal absorption of Ca and P. : collaborates with parathyroid hormone (PTH) in the mobilization of Ca from bone, and reabsorption of Ca in the distal renal tubules 12

13 Vitamin D deficiency Rickets : is a softening of bones in children potentially leading to fracture and deformity Vitamin D and calcium deficiencies from severe malnutrition Osteomalacia : same condition occurred in adult Vitamin B1 (thiamine) Function : maintains neural membranes and normal nerve conduction, especially peripheral nerve Deficiency : most common in chronic alcoholism, result in syndromes of - dry beriberi (polyneuropathy) - wet beriberi (heart failure, peripheral edema) - Wernicke Korsakoff Syndrome (Encephalopathy and psychosis) Vitamin B2 (Riboflovin) - cheilosis (cheilitis, angular stomatitis): first + most characteristic sign (crack + fissure at the angles) - Glossitis : tongue atrophy, red-blue discoloration - Eye change : interstitial keratitis, corneal vascularization, corneal ulcer - Scaling dermatitis : nasolabial folds and cheek (butterfly distribution), scrotal, vulva 13

14 Vitamin B3 (Niacin) - an essential component of NAD + and NADP - Pellagra (3 D s): - Dermatitis sharply demarcated scaling and desquamation of exposure area, bilaterally symmetry - Diarrhea caused by atrophy of the gastrointestinal epithelium - Dementia results from neuron degeneration in the brain, and in the spinal cord Vitamin B12 (Cobalamin) - Coenzyme in the DNA synthetic pathway (as well as folic acid) - Vit.B12 + R-binder(saliva) protease (pancreas) vit.b12 + intrinsic factor (gastric parietal cell) absorb at ileum 14

15 Vitamin B12 ผ ป วยท ม การผ าต ดกระเพาะอาหาร ผ ป วย Chronic atrophic gastritis (autoantibody to IF, parietal cell, IFR) Strictly vegetarian Megaloblastic anemia Macrocytic RBC with Hypersegmented neutrophil Anemia with neurological changes Folate - Coenzyme in the DNA synthetic pathway - Absorb at proximal jejunum - Deficiency : Neural tube defects in the developing fetus (first few weeks postconception) Vitamin C (Ascorbic acid) -Function : hydroxylation of procollagen, antioxidant -Deficiency : impaired synthesis of collagen (bone and vessel) Morphology -Scurvy in growing child - Hemorrhagic diathesis (bleeding tendency) - Cartilagenous overgrowth widening of epiphysis and inadequate synthesis of osteoid - Impaired wound healing and local infection -Skin lesions : perifollicular hemorrhage, hyperkeratotic, papular rash 15

16 Mineral deficiencies Iron: Hypochromic microcytic anemia Zinc: Acrodermatitis enteropathica, growth retardation, infertility Iodine: Goiter and hypothyroidism Selenium : Myopathy, rarely cardiomyopathy Manganese : Muscle weakness, neurologic defects, hypopigmentation, abnormal collagen cross-linking Figure 8-22 Major consequences of vitamin C deficiency caused by impaired formation of collagen. They include bleeding tendency because of poor vascular support, inadequate formation of osteoid matrix, and impaired wound healing. Obesity Mesurement : Body mass index (BMI) = Wt (kg)/ht(m) 2 : Body fat percentage (skin fold measurement) and lean body weight BMI : normal = kg./m 2 : overweight = kg./m 2 : obesity > 30.0 kg./m 2 M/SylPjdnnHQs/s1600/anemia+symptoms.png 16

17 Neurohumoral mechanism เป นกลไกการควบค มการเผาผลาญพล งงาน Afferent (humoral) signals : leptin (adipose tissue), insulin, ghrelin(stomach) Hypothalamus Efferent : feeding behavior + energy expenditure (TRH and autonomic pathway) Food derived energy > energy expenditure Storage as triglycerides in adipose tissue (insulin effect) - Daily requirement : kcal/d. - Daily energy expenditure = Basal energy expenditure (BEE) +Activities. BEE man = 66 + (13.7 x Wt.) + (5 x Ht.) (6.8 x age) BEE woman = (9.5 x Wt.) + (1.8 x Ht.) (4.7 x age) Factors contributing to obesity : 1. Genetic predisposition 2. Decreased lipid utitization : aging, defective thermogenesis, inactivity, underexcercising 3. Sociocultural environment : stress, emotional, disturbances 4. Diseases : hypothalamic disorder. : hypothyroidism. : Cushing s syndrome. : Polycystic ovary syndrome. 17

18 Exercise more than 3 times per week 1. Aerobic exercise = moderate intensity + long duration (20 45 min.) use oxegen to burn fat Cardiovascular protection 2. Anaerobic exercise = high intensity + short duration. glycogenolysis + muscular hypertrophy ข อม ลเพ มเต ม ส าน กงานกองท นสน บสน นการสร างเสร มส ขภาพ โครงการคนไทยไร พ ง กรมอนาม ย กระทรวงสาธารณส ข /khonthairaipung.html ส าน กโภชนาการ กรมอนาม ย กระทรวงสาธารณส ข References ส ภรณ พงศะบ ตร, บรรณาธ การ, ต าราพยาธ ว ทยาท วไป., ภาคว ชาพยาธ ว ทยาและน ต เวชศาสตร, โกลบอลพร นท, 2551, หน า , Kumar V., Abbas A. K., Fausto N., Robbins and Cotran Pathologic Basis of Disease, 7 th edition., Elsevier Saunders, 2005, p ,