MTH64-203E: Environmental & Nutritional Diseases (1/2024) PDF

MTH64-203E: Pathology for MT-inter students (1/2024) ENVIRONMENTAL AND NUTRITIONAL DISEASES Dr. Kritsada Pruksaphon...

MTH64-203E: Pathology for MT-inter students (1/2024) ENVIRONMENTAL AND NUTRITIONAL DISEASES Dr. Kritsada Pruksaphon School of Allied Health Sciences Walailak University 12 August 2024 Modified from Assist. Prof. Dr. Saruda Kuraeiad  LEARNING OBJECTIVES After finish this topic, student be able to:  Understand the harmful effect of environmental pollutants on human health  Identifies sign and/or symptom caused by environment pollutants  Understand the harmful effect of chemical: tobacco and alcohol  Understand injury induced by therapeutic drugs and addictive  Understand injury induced by physical agents  Understand and classification of malnutrition  Identifies sign and/or symptom caused by vitamin deficiency  Understand the pathogenesis of disease caused by vitamin deficiency OUTLINE OF THIS TOPIC Environment and Nutritional disease Environmental disease Nutritional disease Pollution: Air, Metal Malnutrition Tobacco Protein-energy, Anorexia, Bulimia Alcohol Vitamin deficiency Drug injury and drug abuse Obesity Physical injury Diet and cancer  ENVIRONMENTAL DISEASE  Lesion and disease cause by exposure to chemical and physical agents in the ambient, workplace, and personal environments including disease of nutritional origin. U1 www.worldwildlife.org news.thomasnet.com Carbon monoxide and hemoglobin www.cnn.com biology.tutorvista.com https://www.doctorstock.com/image/I0000b.E0XsVm7pQ GENERAL MECHANISM OF TOXICITY Human exposure to pollutants Pollutants contained in air, water and soil are absorbed through the lungs, GI tract, and skin Transport to various through the bloodstream Stored/metabolized/excreted Or activate into toxic compound METABOLISM OF DESTROYING TOXIC SUBSTANCES Xenobiotic = exogenous chemicals ENVIRONMENTAL DISEASES Pollution: Air, Metal Tobacco: Cigarette smoking Alcohol Drug and drug abuse Physical injury  AIR POLLUTION  Ozone  Tobacco smoke  Nitrogen dioxide  Carbon dioxide  Sulfur dioxide  Asbestos  Acid aerosols  Wood smoke www.nature.org.au  Particulates  Radon  Bioaerosols  PM 10/2.5 8 U2 https://my.clevelandclinic.org/health/diseases/4375-lung-cancer https://www.thaipost.net/main/detail/60568 METALS AS ENVIRONMENTAL POLLUTANTS Lead, mercury, arsenic, and cadmium are the heavy  Lead metals most commonly associated with harmful  Mercury effects in human populations  Arsenic  Cadmium Heavy metals is ?? LEAD  Lead exposure  Lead contamination in air and food  Pathologic features of lead poisoning  House paints (old house) and Toys*** U3  Blood: microcytic hypochromic anemia, basophilic stippling  Soil contamination and gasoline  Nervous system: Memory loss,  80-85% absorbed lead is taken up by bone and Encephalopathy, mental deterioration developing teeth  5-10% absorbed lead remains in the blood  GI tract: Abdominal pain  Other : distribute throughout soft tissue  Kidney: Chronic tubulointerstitial disease  Bone: radiodense deposits in epiphyses LEAD Basophilic stippling radiodense deposits in epiphyses Lead line Basophilic stippling U4 MERCURY Diseases -Minamata disease U5 - Cerebral palsy, deafness, blindness, and major CNS defects in children exposed in the uterus ARSENIC U6 Diseases  Acute toxicity - central nervous systems, often progressing to death (interference with mitochondrial oxidative phosphorylation)  Chronic exposure - hyperpigmentation and hyperkeratosis. thaipublica.org These alterations may be followed by the development of basal and squamous cell carcinomas www.mne.eng.psu.ac.th CADMIUM  Used mainly in nickel-cadmium batteries Diseases -Kidney damage -Skeletal abnormalities, osteoporosis and osteomalacia -Itai-itai (ouch-ouch) U7 Itai-itai disease https://www.researchgate.net/publication/273123192_Environmental_Toxicity_of_Cadmi um_and_Health_Effect/figures?lo=1 INDUSTRIAL AND AGRICULTURAL EXPOSURES  Organic solvents--chloroform and carbon tetrachloride, are found in degreasing and dry cleaning agents and paint removers Acute exposure - dizziness and confusion, leading to CNS depression and coma  Benzene and 1,3-butadiene - leukemia  Polycyclic hydrocarbons (from tar and soot) -- carcinogen CIGARETTE SMOKING: TOBACCO AND CANCER  Tobacco and Cancer Organ-Specific Carcinogens in Tobacco Smoke  70% of all lung cancers Organ Carcinogen Lung, larynx Polycyclic aromatic hydrocarbons*** U8  30% of all cancers 4-(Methylnitrosoamino)-1-(3-pyridyl)-1-buta-none (NNK) Polonium 210 Esophagus N'-Nitrosonornicotine (NNN) Pancreas NNK (?) Bladder 4-Aminobiphenyl, 2-naphthylamine Oral cavity Polycyclic aromatic hydrocarbons, NNK, NNN (smoking) Oral cavity (snuff) NNK, NNN, polonium 210 Data from Szczesny LB, Holbrook JH: Cigarette smoking. In Rom WH (ed): Environmental and Occupational Medicine, 2nd ed. Boston, Little, Brown, 1992, p. 1211. CIGARETTE SMOKING: TOBACCO AND CANCER ALCOHOL EFFECTS OF BLOOD ALCOHOL LEVELS IN THE ABSENCE OF TOLERANCE Blood Level, Usual Effect mg/dL Decreased inhibitions, a slight feeling 20 of intoxication Decrease in complex cognitive 80 functions and motor performance Obvious slurred speech, motor 200 incoordination, irritability, and poor judgment safeandsoberalli ance.blogspot.c 300 Light coma and depressed vital signs om 400 Death Harrison Internal Med, 16th Ed Metabolism of Ethanol U9 https://www.stronger247.com/topic/12146/anyone-have-bad-reaction-to-alcohollolpic/ Asian flush syndrome Oxidation of ethanol to acetaldehyde by three different routes, and the generation of acetic acid. Note that oxidation by alcohol dehydrogenase (ADH) 19 takes place in the cytosol; the cytochrome P-450 system and its CYP2E1 isoform are located in the ER (microsomes), and catalase is located in peroxisomes. Oxidation of acetaldehyde by aldehyde dehydrogenase (ALDH) occurs in mitochondria. ALCOHOL AND THE LIVER  Fatty Change  present in over 90% of chronic drinkers  Alcohol hepatitis  between 10-15% of alcoholics will develop alcoholic hepatitis  Alcoholic cirrhosis FATTY CHANGE BIOCHEMISTRY  Catabolism of fat by peripheral tissues is increased, and there is increased delivery of free fatty acids to the liver.  An excess of NADH over NAD stimulates lipid biosynthesis.  Oxidation of fatty acids by mitochondria is decreased.  Acetaldehyde forms adducts with tubulin and impairs function of microtubules, resulting in decreased transport of lipoproteins from the liver. ALCOHOLISM  Wernicke syndrome U10  due to thiamine (Vit B1) deficiency  Korsakov syndrome  memory loss and confabulation nursingcrib.com  Mechanisms of Disease Caused by Ethanol Abuse Organ System Lesion Mechanism Liver Fatty change Toxicity Acute hepatitis Alcoholic cirrhosis Nervous system Wernicke syndrome Thiamine deficiency Korsakoff syndrome Toxicity and thiamine deficiency Cerebellar Nutritional deficiency degeneration Peripheral neuropathy Thiamine deficiency Cardiovascular Cardiomyopathy Toxicity system Hypertension Vasopressor 23  Mechanisms of Disease Caused by Ethanol Abuse Organ System Lesion Mechanism Gastrointestinal Gastritis Toxicity tract Pancreatitis Toxicity Skeletal muscle Rhabdomyolysis Toxicity Reproductive Testicular atrophy ? system Spontaneous ? abortion Fetal alcohol Growth retardation Toxicity syndrome Mental retardation 24 Birth defects Therapeutic Drugs (Medications) 25 THERAPEUTIC DRUGS (MEDICATIONS)  Oral Contraceptives  Hormone Replacement Therapy (HRT)  Acetaminophen  Aspirin  Addictives ORAL CONTRACEPTIVES  Cancers  Increase in cervical cancer (lifestyle induced)  Thromboembolic events  DVT and Pulmonary Embolism increased  Cardiovascular disease menopausemoxie.com  Ischemic stroke increased regardless of age or smoking  Liver tumors  Benign hepatic adenomas monitorhealthcare.com HORMONE REPLACEMENT THERAPY (HRT)  Cancer  WHO showed increased risk of breast cancer in women who used HRT combined therapy for 5 years  Thromboembolic events  elevated approximated two-fold in HRT users, especially within the first 2 years  Cardiovascular disease  WHI reported 29% increased risk of myocardial infarction, especially during the first year of combined HRT use ACETAMINOPHEN (PARACETAMOL)  Has analgesic and antipyretic actions but no anti- inflammatory action  Large doses may produce hepatic necrosis  ASPIRIN U11  Inhibits Cyclooxygenase (COX 1 & 2)  Chronic aspirin toxicity (salicylism)  Headache, dizziness, ringing in the ears (tinnitus), mental confusion, drowsiness, nausea, vomiting, and www.oknation.net diarrhea  Erosive gastritis is a major cause of GI bleeding Figure 2-16 Generation of arachidonic acid metabolites and their roles in inflammation. The molecular targets of action of some anti-inflammatory drugs are indicated by a red X. COX, cyclooxygenase; HETE, hydroxyeicosatetraenoic acid; HPETE, hydroperoxyeicosatetraenoic acid. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 15 August 2005 06:35 PM)  ADDICTIVE Cocaine  Potent stimulant of the central nervous system  Cocaine produces a sense of intense euphoria and mental alertness U12  The effect of cocaine on neurotransmission.  inhibits reuptake of the neurotransmitters dopamine and norepinephrine*** in the central and peripheral nervous systems ADDICTIVE Heroin  Heroin is an addictive opioid derived from the poppy plant and is closely related to morphine.  Heroin is a depressant HEROIN - MECHANISM OF ACTION Act on: Opioid receptor mu (µ), kappa (κ), delta (δ) Receptor (G-protein couple receptor) Ca2+ K+ efflux cAMP influx Inhibit substance-P release from neuronal cells Inhibit pain transmission  ADDICTIVE Marijuana  Marijuana acts as both stimulant and depressant  PHYSICAL INJURY U13 Abrasion Laceration vs. Incision Contusion THERMAL BURNS  1st, 2nd, 3rd, 4th “Degree”  FULL vs. PARTIAL Thickness  Survival  Degree (i.e., Depth)  Respiratory Tract Involvement  AGE reference.medscape.com  Immune System THERMAL BURNS HYPERTHERMIA  Heat Cramps: Electrolyte loss via sweat  Heat Exhaustion: Water depletion and lack of cardiovascular compensation  Heat “Stroke”: Extensive peripheral vasodilatation, i.e., “shocky”, very serious, T>40ºC, over 40ºC have been reported, high mortality. HYPERTHERMIA LIGHTNING/ELECTRICAL  Electric disturbances  Thermal injury, depends upon a particular tissue’s resistance to electrical flow  “LIGHTNING” marks Ionizing Radiation Nutritional Diseases 43 NUTRITIONAL DISEASES  Too little nutrient  Too much nutrient  Isolated deficiency is rare  How did it come to happen  Dietary related  Refined out of diet  Absorption problem  Utilization UNDERNUTRITION Marasmus Kwashiorkor Anorexia nervosa and bulimia Vitamin and mineral deficiencies MARASMUS U14 Severe reduction in caloric intake*** < 60% normal weight Growth retardation Stunting Loss of subcutaneous fat Muscular atrophy KWASHIORKOR  Protein deprivation  60-80% normal body weight  Edema  CNS  Skin and hair  U15 ANOREXIA NERVOSA AND BULIMIA www.geronguide.com minesgreencircle.wordpress.com SPECIFIC VITAMIN DEFICIENCIES Water soluble vitamins Fat soluble vitamins - B-complex  A, D, E, & K -C  Readily stored in body fat - Readily excreted in urine  Pancreatic insufficiency - Dietary absence  Liver disease - GI related  Multiple deficiencies  Problems of absorption Vitamin stores Vitamins B-12 and A: stores sufficient for 1 year Folate and thiamine may become depleted within weeks when eating a deficient diet VITAMIN A  Retinol  Retinaldehyde  retinoic acid  carotenoids  VITAMIN A FUNCTION AND IT’S DEFICIENCY Functions of Vit. A: maintain normal vision in reduced light important role in differentiation of mucus-secreting epithelial enhance immunity to infection Eyes: rod cells in retina night blindness - Squamous metaplasia Mucus-secreting - Keratinizing epi. columnar epi. Keratinizing metaplasia (mucous cell >>epithelial cell): Bitot spots (keratin debris), corneal ulcer, keratomalacia (คอร์ เนี ยร์ อ่อนตัวและเป็ นแผล)  Vitamin A deficiency Bitot Spot Keratomalacia Night blindness 52 VITAMIN D U16 Vitamin D is synthesized in the skin and some food source and need to sunlight (UV) Exposure 1) increases intestinal absorption of calcium and phosphate 2) stimulating reabsorption of calcium and phosphate in the distal renal tubules 3) it mobilizes bone mineral VITAMIN D DEFICIENCY 1. Decrease in substrate for renal hydroxylase 2. Deficient absorption of Ca and P from gut 3. Decrease in serum Ca and P 4. Hypocalcemia activates parathyroid gland 5. Mobilizing Ca and P from bone 6. PTH>>wasting P in urine 7. Impair mineralization in bone VITAMIN D DEFICIENCY  Rickets in children - Bow leg (ขาโก่ง) - Knock-knee (ขาถ่าง)  Osteomalacia in adults - Fractures  Excess of vitamin D leads to - Hypercalcemia VITAMIN E Tocopherols---antioxidant in cell membranes  Vit.E Polyunsaturated fatty acid VITAMIN K Phylloquinone Menaquinones Menadione VITAMIN K  The cofactor for the carboxylation of glutamate residues in the postsynthetic modification of proteins to form the unusual amino acid-carboxyglutamate (Gla)  Blood-clotting system (Factors VII, IX, and X, and proteins C and S) Vitamin K deficiency VITAMIN B COMPLEX  Water soluble  Green vegetables  Cereals  Deficiency states  - Starvation  - Refinement of food  - Alcoholics  VITAMIN B1 Metabolism of carbohydrates THIAMIN DEFICIENCY=beriberi VITAMIN B2 (RIBOFLAVIN)  Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) = mitochondrial respiratory chain  Deficiency=Desquamation and inflammation of the tongue, angular stomatitis (ปากนกกระจอก)  U17 VITAMIN B3 (NIACIN) Nicotinic acid and nicotinamide ADP-ribosylation = DNA repair mechanism DEFICIENCY=PELLAGRA (3D)*** - dermatitis - dementia - diarrhea VITAMIN B6 Pyridoxine, pyridoxal, pyridoxamine  Amino acid metabolism  Deficiency disease is rare VITAMIN B9 (FOLATE) Megaloblastic anemia Tetrahydrofolate-carry one-carbon fragments Function: purine, pyrimidine synthesis, nucleic acid synthesis VITAMIN B12 Cobalamins Coenzyme in methionine synthesis which is coordinated with folate  Vitamin B12 is absorbed bound to intrinsic factor Megaloblastic anemia BIOTIN (B7) Acetyl-CoA carboxylase Biotin also has a role in regulation of the cell cycle, acting to biotinylate key nuclear proteins. en.wikipedia.org ASCORBIC ACID (VITAMIN C) Copper-containing hydroxylases  U18 ASCORBIC ACID (VITAMIN C)  Citrus and veggies  Function – Water soluble free radical scavenger – Helps absorb Fe and Cu (in reduced state) – Collagen metabolism  Hydroxylation of lysine and proline  Scurvy**** (ลักปิ ดลักเปิ ด) OVERNUTRITION Increased body weight, due to adipose accumulation When food-derived energy chronically exceeds energy expenditure Genetic, environmental, and psychological factors involved Obesity  WHAT ARE WAYS TO MEASURE OBESITY?  BMI: >30 obese, 25-29 overweight  Skin fold thickness  Waist to hip circumference ratios WHAT ARE THE DISEASES ASSOCIATED WITH OBESITY? Hypertension Type 2 diabetes Increase in risk of hypertension in normotensive person is proportional Hyperinsulinemia and insulin to increase in weight resistance Describe liver and biliary tree Atherosclerosis Hypoventilation syndrome Osteoarthritis: wear and tear on joints Cancer and obesity ATHEROSCLEROSIS AND OBESITY  Abnormal lipids increase risk of coronary artery disease  Low HDL  Hypertriglyceridemia LIVER AND BILIARY TREE AND OBESITY  Cholelithiasis: increase in total body cholesterol, turnover, and augmented biliary excretion of cholesterol in bile predisposes to formation of cholesterol stones HYPOVENTILATION SYNDROME (PICKWICKIAN SYNDROME) AND OBESITY  Hypersomnolence associated with apnea during sleep, polycythemia, right sided heart failure ACTIVE LEARNING / ASSIGNMENT  Classroom assignment (Next week, after finish the lecture of General pathology of infectious diseases)  Post test (Quiz) in WU e-learning (until 20 August 24, 23.59)  Topic summary report in WU e-learning (until 25 August 24, 23.59) THANK YOU