2/13/2014 1 Environmental & Nutritional Pathology นายแพทย ดร.ณตพล ศุภณัฐเศรษฐกุล ภาควิชาพยาธิวิทยา คณะแพทยศาสตร มหาวิทยาลัยนเรศวร 3 มีนาคม 2557 Topics • Environmental pathology – General mechanism of Toxicity – Environmental pollution – Effects of Tobacco – Effects of Alcohol – Injury by Physical agent • 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.
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2/13/2014
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Environmental &
Nutritional Pathology
นายแพทย ดร.ณตพล ศุภณัฐเศรษฐกุล
ภาควิชาพยาธิวิทยา
คณะแพทยศาสตร มหาวิทยาลัยนเรศวร 3 มีนาคม 2557
Topics • Environmental pathology
– General mechanism of Toxicity – Environmental pollution – Effects of Tobacco – Effects of Alcohol – Injury by Physical agent
• 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.
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General Mechanisms of Toxicity
• “Toxicology” = The science of poison
• “Poison” basically depends on dosage
• “All substances are poisons” (Paracelsus 16th 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. 1-1. 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
• Chemicals, drugs, alcohol are primarily metabolized by this enzyme system
Environmental Pollution
• Air pollution : “smog” (Ozone, Nitrogen dioxide, Sulfur dioxide,
• 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.
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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.)
Smoking cessation
“Greatly reduces the risk of death from
Lung cancer”
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
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.)
Laceration wound Contusion
Abrasion wound
Cut wound, Incised wound
Stab wound, Puncture 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
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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.
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.
Mineral deficiencies • Iron : Hypochromic microcytic anemia • Zinc : Acrodermatitis enteropathica, growth
• Efferent : feeding behavior + energy expenditure (TRH and autonomic pathway)
Food–derived energy > energy expenditure Storage as triglycerides in adipose tissue (insulin effect) - Daily requirement : 2000 – 3000 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 = 655 + (9.5 x Wt.) + (1.8 x Ht.) – (4.7 x age)