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- 2. Environmental and Environmental and Nutritional Pathology Nutritional Pathology Environment and Disease Environment and Disease Common Exposures Common Exposures Environmental Environmental Occupational Occupational Nutrition Nutrition and Disease and Disease
- 3. Reported Occupational Diseases Reported Occupational Diseases Disease Disease Number Number Percentage Percentage Repeated trauma Repeated trauma 276,600 276,600 64 64 Skin disorders Skin disorders 57,900 57,900 13 13 Lung conditions due to Lung conditions due to toxic exposures toxic exposures 20,300 20,300 5 5 Physical injury Physical injury 16,600 16,600 4 4 Poisoning Poisoning 5,100 5,100 1 1 Lung disease due to Lung disease due to dusts dusts 2,900 2,900 1 1 All other illnesses All other illnesses 50,600 50,600 12 12 Total Total 430,000 430,000 100 100
- 4. Mechanisms of Toxicity Mechanisms of Toxicity Threshold effect Threshold effect Absorption at portals of entry Absorption at portals of entry ingestion ingestion inhalation inhalation skin contact skin contact Distribution within the body Distribution within the body Metabolism and Excretion Metabolism and Excretion Toxic effects Toxic effects
- 5. Xenobiotic Mechanisms Phase I Reactions (Smooth ER), makes them less lipophilic by adding a direct polar group Cytochrome P-450-dependent monooxygenase system Flavin-containing monooxygenase system Peroxidase-dependent cooxidation Phase II Reactions, combines them with other polar substances Glucuronidation Biomethylation Glutathione conjugation
- 7. Contents of Toxic Waste Dumps Acetone DDT, DDE, DDD Aldrin/Dieldrin 1,1 and 1,2-Dichloroethane Arsenic Lead Barium Mercury Benzene Methylene chloride 2-Butanone Nickel Cadmium Pentachlorophenol Carbon tetrachloride Polychlorinated biphenyls Chlordane Tri- and Tetrachloroethylene Chloroform Toluene Chromium Vinyl Chloride Cyanide Zinc
- 9. Common Common Exposures Exposures Personal Personal Medications Medications Outdoor Air Pollution Outdoor Air Pollution Indoor Air Pollution Indoor Air Pollution Industrial Exposures Industrial Exposures Agricultural Hazards Agricultural Hazards Natural Toxins Natural Toxins Radiation Injury Radiation Injury Physical Injury Physical Injury
- 10. Tobacco Tobacco 440,000 premature deaths/year in USA 440,000 premature deaths/year in USA cancer cancer cardiovascular disease cardiovascular disease respiratory disease respiratory disease cerebrovascular disease cerebrovascular disease $150 billion in health related costs $150 billion in health related costs By far By far the most preventable cause the most preventable cause of death in the United States of death in the United States
- 11. Tobacco and Cancer 70% of all lung cancers 30% of all cancers
- 12. Organ-Specific Carcinogens in Tobacco Smoke Organ Carcinogen Lung, larynx Polycyclic aromatic hydrocarbons 4-(Methylnitrosoamino)-1-(3-pyridyl)-1-buta-none (NNK) Polonium 210 Esophagus N'-Nitrosonornicotine (NNN) Pancreas NNK (?) Bladder 4-Aminobiphenyl, 2-naphthylamine Oral cavity (smoking) Polycyclic aromatic hydrocarbons, NNK, NNN 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.
- 13. Relative Risks for Current Smokers of Cigarettes Relative Risks for Current Smokers of Cigarettes Disease or Condition Males Males Females Females Coronary heart disease Coronary heart disease Age 35–64 Age 35–64 2.8 2.8 3.1 3.1 Age ≥ 65 Age ≥ 65 1.5 1.5 1.6 1.6 Cerebrovascular lesions Cerebrovascular lesions Age 35–64 Age 35–64 3.3 3.3 4 4 Age ≥ 65 Age ≥ 65 1.6 1.6 1.5 1.5 Aortic aneurysm Aortic aneurysm 6.2 6.2 7.1 7.1 Chronic airways obstruction Chronic airways obstruction 10.6 10.6 13.1 13.1 Cancer Cancer Lip, oral cavity, pharynx Lip, oral cavity, pharynx 10.9 10.9 5.1 5.1 Esophagus Esophagus 6.8 6.8 7.8 7.8 Stomach Stomach 2 2 1.4 1.4 Pancreas Pancreas 2.3 2.3 2.3 2.3 Larynx Larynx 14.6 14.6 13 13 Lung Lung 23.3 23.3 12.7 12.7 Cervix Cervix 1.6 1.6 Kidney Kidney 2.7 2.7 1.3 1.3 Bladder, other urinary organs Bladder, other urinary organs 3.3 3.3 2.2 2.2
- 14. Cigarettes And The Workplace Cigarettes And The Workplace Similar to asbestos exposure, cigarette smoke is Similar to asbestos exposure, cigarette smoke is synergistic with radon decay products in causing synergistic with radon decay products in causing lung cancer lung cancer Cigarette smoke exacerbates bronchitis, asthma, Cigarette smoke exacerbates bronchitis, asthma, and pneumoconiosis associated with exposure and pneumoconiosis associated with exposure to silica, coal dust, grain dust, cotton dust, and to silica, coal dust, grain dust, cotton dust, and welding fumes welding fumes
- 15. Alcohol Alcohol 15 to 20 million alcoholics in the USA 15 to 20 million alcoholics in the USA 100,000 deaths/year due to alcohol 100,000 deaths/year due to alcohol abuse abuse Economic losses of $100 to $130 Economic losses of $100 to $130 billion/year billion/year One to two drinks/day reduces One to two drinks/day reduces incidence of coronary artery disease* incidence of coronary artery disease* * What kind of person would put this kind of bullet on a powerpoint? A. Drinker? B) Non-Drinker?
- 17. Effects of Blood Alcohol Levels in the Absence of Tolerance Effects of Blood Alcohol Levels in the Absence of Tolerance Blood Level, mg/dL Blood Level, mg/dL Usual Effect Usual Effect 20 20 Decreased inhibitions, a slight Decreased inhibitions, a slight feeling of intoxication feeling of intoxication 80 80 Decrease in complex cognitive Decrease in complex cognitive functions and motor performance functions and motor performance 200 200 Obvious slurred speech, motor Obvious slurred speech, motor incoordination, irritability, and incoordination, irritability, and poor judgment poor judgment 300 300 Light coma and depressed vital Light coma and depressed vital signs signs 400 400 Death Death Harrison Internal Med, 16th Ed
- 18. Metabolism Of Ethanol Metabolism Of Ethanol ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase 20% 80%
- 21. Widmark Equation Widmark Equation C = A / (W * r) C = A / (W * r) C = concentration of EtOH in mg/dl C = concentration of EtOH in mg/dl A = mass of alcohol ingested in grams A = mass of alcohol ingested in grams density of ethanol = 0.8 density of ethanol = 0.8 W = body weight in grams W = body weight in grams r = Widmark distribution for ethanol r = Widmark distribution for ethanol 0.55 mL/ g body weight for females 0.55 mL/ g body weight for females 0.68 mL / g body weight for males 0.68 mL / g body weight for males Elimination of ethanol = 0.015%/h (15mg/dl/h) Elimination of ethanol = 0.015%/h (15mg/dl/h) zero order kinetics zero order kinetics Medical measurements use mg/dl in plasma, whereas Medical measurements use mg/dl in plasma, whereas legal definitions use percentage (mass/volume) in whole legal definitions use percentage (mass/volume) in whole blood blood to estimate the alcohol level in whole blood using the alcohol to estimate the alcohol level in whole blood using the alcohol level in blood plasma, divide by 1.16 level in blood plasma, divide by 1.16
- 22. Alcohol and the Liver Alcohol and the Liver Fatty Change Fatty Change present in over 90% of binge and chronic drinkers present in over 90% of binge and chronic drinkers liver is enlarged but patient is asymptomatic liver is enlarged but patient is asymptomatic changes are reversible with cessation of drinking changes are reversible with cessation of drinking macrosteatosis w/o inflammation or necrosis macrosteatosis w/o inflammation or necrosis Alcohol hepatitis Alcohol hepatitis only between 10 - 15% of alcoholics will develop only between 10 - 15% of alcoholics will develop alcoholic hepatitis alcoholic hepatitis may have systemic symptoms and jaundice may have systemic symptoms and jaundice hepatocellular necrosis with Mallory bodies and PMNs hepatocellular necrosis with Mallory bodies and PMNs (central hyaline sclerosis) (central hyaline sclerosis) thought to be a precursor of cirrhosis thought to be a precursor of cirrhosis Alcoholic cirrhosis Alcoholic cirrhosis shrunken nodular liver with uniform small nodules shrunken nodular liver with uniform small nodules (micronodular cirrhosis) (micronodular cirrhosis)
- 23. Fatty Change Biochemistry Fatty Change Biochemistry Catabolism of fat by peripheral tissues is Catabolism of fat by peripheral tissues is increased, and there is increased delivery of increased, and there is increased delivery of free fatty acids to the liver free fatty acids to the liver An excess of NADH over NAD stimulates An excess of NADH over NAD stimulates lipid biosynthesis lipid biosynthesis Oxidation of fatty acids by mitochondria is Oxidation of fatty acids by mitochondria is decreased decreased Acetaldehyde forms adducts with tubulin and Acetaldehyde forms adducts with tubulin and impairs function of microtubules, resulting in impairs function of microtubules, resulting in decreased transport of lipoproteins from the decreased transport of lipoproteins from the liver liver
- 28. Neurologic Manifestations of Alcoholism Neurologic Manifestations of Alcoholism Wernicke syndrome Wernicke syndrome confusion, ataxia, and diplopia from confusion, ataxia, and diplopia from ophthalmoplegia ophthalmoplegia damage to mammillary bodies, cerebellum and damage to mammillary bodies, cerebellum and periaqueductal gray matter periaqueductal gray matter of the midbrain of the midbrain due to thiamine deficiency due to thiamine deficiency may respond to prompt thiamine replacement may respond to prompt thiamine replacement Korsakov syndrome Korsakov syndrome memory loss and confabulation memory loss and confabulation results from thiamine deficiency and direct results from thiamine deficiency and direct toxicity toxicity
- 30. 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 degeneration Nutritional deficiency Peripheral neuropathy Thiamine deficiency Cardiovascular system Cardiomyopathy Toxicity Hypertension Vasopressor
- 31. Mechanisms of Disease Caused by Ethanol Abuse Organ System Lesion Mechanism Gastrointestinal tract Gastritis Toxicity Pancreatitis Toxicity Skeletal muscle Rhabdomyolysis Toxicity Reproductive system Testicular atrophy ? Spontaneous abortion ? Fetal alcohol syndrome Growth retardation Toxicity Mental retardation Birth defects
- 32. Therapeutic Drugs Therapeutic Drugs (Medications) (Medications) Oral Contraceptives (BCPs) Oral Contraceptives (BCPs) Hormone Replacement Therapy (HRT) Hormone Replacement Therapy (HRT) Acetaminophen Acetaminophen Aspirin Aspirin
- 33. Oral Contraceptives (BCPs) Oral Contraceptives (BCPs) Breast cancer and other cancers Breast cancer and other cancers no increase in breast cancer no increase in breast cancer decrease endometrial and ovarian cancers decrease endometrial and ovarian cancers increase in cervical cancer (?lifestyle induced) increase in cervical cancer (?lifestyle induced) Thromboembolic events Thromboembolic events DVT and Pulmonary Embolism increased DVT and Pulmonary Embolism increased adds to other risk factors (e.g. Factor V Leiden) adds to other risk factors (e.g. Factor V Leiden) Cardiovascular disease Cardiovascular disease with current low estrogen pills, risk of MI and with current low estrogen pills, risk of MI and atherosclerosis not increased in non-smoking women < 45 y atherosclerosis not increased in non-smoking women < 45 y ischemic stroke increased regardless of age or smoking ischemic stroke increased regardless of age or smoking Liver tumors Liver tumors benign hepatic adenomas benign hepatic adenomas older women with prolonged use older women with prolonged use may rupture and cause intra-abdominal bleeding may rupture and cause intra-abdominal bleeding
- 34. Hormone Replacement Therapy (HRT) Hormone Replacement Therapy (HRT) Cancer Cancer in women with a uterus combined estrogen and in women with a uterus combined estrogen and progestin Rx necessary to reduce endometrial cancer progestin Rx necessary to reduce endometrial cancer WHI showed increased risk of breast cancer in women WHI showed increased risk of breast cancer in women who used HRT combined therapy for 5 years who used HRT combined therapy for 5 years Thromboembolic events Thromboembolic events elevated approximated twofold in HRT users, especially elevated approximated twofold in HRT users, especially within the first 2 years within the first 2 years Cardiovascular disease Cardiovascular disease WHI reported 29% increased risk of myocardial WHI reported 29% increased risk of myocardial infarction, especially during the first year of combined infarction, especially during the first year of combined HRT use HRT use
- 35. Acetaminophen (Tylenol) Acetaminophen (Tylenol) Does not affect cyclooxygenase so bleeding Does not affect cyclooxygenase so bleeding associated with aspirin does not occur associated with aspirin does not occur Has analgesic and antipyretic actions but no Has analgesic and antipyretic actions but no anti-inflammatory action anti-inflammatory action Large doses may produce hepatic necrosis Large doses may produce hepatic necrosis patients should not exceed recommended dose patients should not exceed recommended dose (4 grams/day) (4 grams/day) toxic dose in adults is 15 to 25 gm toxic dose in adults is 15 to 25 gm dose should be reduced in children with fever or dose should be reduced in children with fever or dehydration dehydration
- 36. Aspirin Aspirin Overdose Overdose respiratory alkalosis followed by metabolic acidosis that respiratory alkalosis followed by metabolic acidosis that may be fatal may be fatal Chronic aspirin toxicity (salicylism) Chronic aspirin toxicity (salicylism) headache, dizziness, ringing in the ears (tinnitus), headache, dizziness, ringing in the ears (tinnitus), mental confusion, drowsiness, nausea, vomiting, and mental confusion, drowsiness, nausea, vomiting, and diarrhea diarrhea Inhibits cyclooxygenase (COX 1 & 2) Inhibits cyclooxygenase (COX 1 & 2) Erosive gastritis is a major cause of GI bleeding Erosive gastritis is a major cause of GI bleeding May be implicated in Reye syndrome (fatty liver May be implicated in Reye syndrome (fatty liver with encephalopathy) in children < 15 years old, with encephalopathy) in children < 15 years old, especially with influenza and chicken pox especially with influenza and chicken pox
- 37. Cox-1 and Cox-2 Inhibitors Cox-1 and Cox-2 Inhibitors Cyclooxygenase 1 Cyclooxygenase 1 constitutively expressed and active in the constitutively expressed and active in the normal platelet (thromboxane A2) normal platelet (thromboxane A2) involved in synthesis of gastro-protective involved in synthesis of gastro-protective prostaglandins prostaglandins Cyclooxygenase 2 Cyclooxygenase 2 induced, especially in inflamed tissue induced, especially in inflamed tissue in vessel wall produces prostacyclin (PGI in vessel wall produces prostacyclin (PGI2 2) ) Aspirin and other nonselective NSAIDS Aspirin and other nonselective NSAIDS inhibit both COX-1 and COX-2 inhibit both COX-1 and COX-2
- 38. 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) © 2005 Elsevier
- 39. Indoor Air Pollution Indoor Air Pollution Carbon Monoxide CO Carbon Monoxide CO Nitrogen Dioxide NO Nitrogen Dioxide NO2 2 Wood Smoke Wood Smoke Formaldehyde Formaldehyde Radon Radon Manufactured Mineral Fibers Manufactured Mineral Fibers Bioaerosols Bioaerosols
- 40. Radon Radon Radon is a radioactive gas and a decay Radon is a radioactive gas and a decay product of uranium product of uranium It is widely distributed in the soil and is It is widely distributed in the soil and is prevalent in homes (especially in basements) prevalent in homes (especially in basements) Radon decay products are alpha emitters Radon decay products are alpha emitters 10% of US homes have levels associated with 10% of US homes have levels associated with an increased risk of lung cancer and an an increased risk of lung cancer and an estimated 10,000 lung cancers per year in the estimated 10,000 lung cancers per year in the United States are due to radon. Smoking United States are due to radon. Smoking elevates risk. elevates risk. Proper venting reduces the exposure Proper venting reduces the exposure
- 41. Lead Lead lead is classified as a heavy metal (others lead is classified as a heavy metal (others include mercury, arsenic, and cadmium) include mercury, arsenic, and cadmium) Source of exposure Source of exposure lead paint lead paint lead solder in plumbing (older houses) lead solder in plumbing (older houses) lead-glazed ceramics lead-glazed ceramics industrial exposure industrial exposure Route of exposure Route of exposure inhalation with industrial exposure inhalation with industrial exposure ingestion with household exposure ingestion with household exposure
- 42. Lead Distribution and Excretion Lead Distribution and Excretion Lead is a divalent cation that is taken up by Lead is a divalent cation that is taken up by bone and developing teeth in children (80% bone and developing teeth in children (80% to 85%) to 85%) Half-life of lead in bone is 30 years Half-life of lead in bone is 30 years Blood accumulates 5% to 10% of lead, but Blood accumulates 5% to 10% of lead, but lead is rapidly cleared from the blood lead is rapidly cleared from the blood lead in blood indicates recent exposure lead in blood indicates recent exposure blood level does not allow the determination of blood level does not allow the determination of total body burden total body burden Remainder is distributed in the soft tissues Remainder is distributed in the soft tissues Excretion is via the kidneys Excretion is via the kidneys
- 43. Effects of Lead Effects of Lead High affinity for sulfhydryl groups High affinity for sulfhydryl groups inhibition of heme biosynthesis with hypochromic inhibition of heme biosynthesis with hypochromic anemia and basophillic stippling of erythrocytes anemia and basophillic stippling of erythrocytes Competition with calcium ions Competition with calcium ions As a divalent cation, lead competes with calcium and is As a divalent cation, lead competes with calcium and is stored in bone. stored in bone. It also interferes with nerve transmission and brain It also interferes with nerve transmission and brain development. development. Inhibition of membrane-associated enzymes Inhibition of membrane-associated enzymes Lead inhibits 5'-nucleotidase activity and sodium- Lead inhibits 5'-nucleotidase activity and sodium- potassium ion pumps, leading to decreased survival of potassium ion pumps, leading to decreased survival of red blood cells (hemolysis), renal damage, and red blood cells (hemolysis), renal damage, and hypertension. hypertension.
- 47. “RADIATION” T ½ Curie vs. Becqerel IONIZING vs. NON-IONIZING PARTICULATE vs. NON-PARTICULATE (Photons) ENERGY: Kev, Mev (~Wavelength) Linear Energy Transfer (LET), Relative Biologic Effect (RBE) LD50@60d
- 48. This is the single most RADIOSENSITIVE CELL In your body
- 49. Radiation Dosimetry Radiation Dosimetry Roentgen: Roentgen: unit of charge produced by x-rays or gamma unit of charge produced by x-rays or gamma rays that ionize a specific volume of air rays that ionize a specific volume of air RAD RAD (radiation absorbed dose): (radiation absorbed dose): the dose of radiation the dose of radiation that will produce absorption of 100 ergs of energy per gram that will produce absorption of 100 ergs of energy per gram of tissue; 1 gm of tissue exposed to 1 roentgen of gamma of tissue; 1 gm of tissue exposed to 1 roentgen of gamma rays is equal to 93 ergs rays is equal to 93 ergs Gray Gray (Gy): the dose of radiation that will produce (Gy): the dose of radiation that will produce absorption of 1 joule of energy per kilogram of tissue; 1 Gy absorption of 1 joule of energy per kilogram of tissue; 1 Gy corresponds to 100 rad (SI unit for absorbed dose) corresponds to 100 rad (SI unit for absorbed dose) REM REM (radiation equivalent man): (radiation equivalent man): the dose of radiation that the dose of radiation that causes a biologic effect equivalent to 1 rad of x-rays or causes a biologic effect equivalent to 1 rad of x-rays or gamma rays gamma rays Sievert Sievert (Sv): the dose of radiation that causes a biologic (Sv): the dose of radiation that causes a biologic effect equivalent to 1 Gy of x-rays or gamma rays; 1 Sv effect equivalent to 1 Gy of x-rays or gamma rays; 1 Sv corresponds to 100 rem (SI unit) corresponds to 100 rem (SI unit)
- 50. Acute Effects of Ionizing Radiation Acute Effects of Ionizing Radiation Free radical generation Free radical generation Ionizing radiation + H Ionizing radiation + H2 20 → H 0 → H3 30 0+ + + OH· + OH· DNA Damage DNA Damage double-stranded DNA breaks needed to kill cell double-stranded DNA breaks needed to kill cell (mammalian cells can repair single stranded (mammalian cells can repair single stranded breaks) breaks) cross-linking of DNA strands, cleavage of sugar- cross-linking of DNA strands, cleavage of sugar- phosphate bonds phosphate bonds Tumor-suppressor gene Tumor-suppressor gene p53 p53 activation activation cell cycle arrest in presence of damaged DNA cell cycle arrest in presence of damaged DNA repair of DNA damage or apoptosis repair of DNA damage or apoptosis
- 51. Acute Whole Body Radiation Acute Whole Body Radiation LD50 @ 6 wks 2.5 to 4.0 Gy (250 to 400 rad) LD50 @ 6 wks 2.5 to 4.0 Gy (250 to 400 rad) Hematopoietic Hematopoietic 200–600 REM 200–600 REM Maximum neutrophil and platelet depression in 2 wk Maximum neutrophil and platelet depression in 2 wk Gastrointestinal Gastrointestinal 600–1000 REM 600–1000 REM Nausea, vomiting, diarrhea Nausea, vomiting, diarrhea Hemorrhage and infection in 1–3 wk Hemorrhage and infection in 1–3 wk Central nervous system Central nervous system >1000 REM >1000 REM Intractable nausea and vomiting Intractable nausea and vomiting Confusion, somnolence, convulsions Confusion, somnolence, convulsions death in 14–36 hr death in 14–36 hr
- 52. Therapeutic Radiation Therapeutic Radiation External radiation is delivered to malignant External radiation is delivered to malignant neoplasms at fractionated doses up to 40 to neoplasms at fractionated doses up to 40 to 70 Gy (4000 to 7000 rad), with shielding of 70 Gy (4000 to 7000 rad), with shielding of adjacent normal tissues adjacent normal tissues Therapeutic radiation alone seems to add Therapeutic radiation alone seems to add little risk of AML but can increase the risk in little risk of AML but can increase the risk in people exposed to alkylating agents people exposed to alkylating agents Fatigue, nausea and vomiting frequent Fatigue, nausea and vomiting frequent Bone marrow suppression may occur Bone marrow suppression may occur especially with chest or abdominal radiation especially with chest or abdominal radiation
- 53. Delayed Radiation Injury Delayed Radiation Injury Carcinogenesis (atom bomb survivors) Carcinogenesis (atom bomb survivors) myeloid leukemias peak 5 to 7 years after exposure myeloid leukemias peak 5 to 7 years after exposure breast and thyroid cancers may show greater latency breast and thyroid cancers may show greater latency no germline mutations noted in progeny of survivors no germline mutations noted in progeny of survivors Vascular effects Vascular effects endothelial necrosis followed by intimal and medial endothelial necrosis followed by intimal and medial fibrosis fibrosis capillaries may become thrombosed and obliterated or capillaries may become thrombosed and obliterated or ectatic ectatic Parenchymal atrophy and fibrosis Parenchymal atrophy and fibrosis
- 54. Radiation effects on TISSUE ACUTE (vasculitis, possibly “fibrinoid” necrosis) CHRONIC (fibrosis)
- 55. Physical Injury Physical Injury Abrasion Abrasion basically a scrape basically a scrape superficial epidermis is torn off by friction or force superficial epidermis is torn off by friction or force regeneration without scarring usually occurs regeneration without scarring usually occurs Laceration vs. Incision Laceration vs. Incision a laceration is an irregular tear in the skin produced by a laceration is an irregular tear in the skin produced by overstretching. The wound margins are frequently hemorrhagic overstretching. The wound margins are frequently hemorrhagic and traumatized and traumatized an incision is made by a sharp cutting object. The margins of an incision is made by a sharp cutting object. The margins of the incision are usually relatively clean the incision are usually relatively clean Contusion Contusion an injury caused by a blunt force that damages small blood an injury caused by a blunt force that damages small blood vessels and causes interstitial bleeding, usually without vessels and causes interstitial bleeding, usually without disruption of the continuity of the tissue ( disruption of the continuity of the tissue (cf cf ecchymosis) ecchymosis)
- 57. Adult Mortality Rates in the United States, Ages 25–44, in 1998 Rate per 100,000 population Cause Hispanic Black White Unintentional injuries 33.4 40.1 31.6 Cancer 16.8 38.0 25.3 Homicide 13.1 36.2 4.7 Human immunodeficiency virus 12.1 43.3 4.8 Heart disease 10.3 43.5 18.3 Suicide 7.8 — 17.0 Total 130.2 303.7 139.4 Data from CDC Fact Book, 2000/2001, Department of Health and Human Services, Centers for Disease Control and Prevention.
- 58. GUNSHOT WOUND Entrance Vs. Exit Far range Vs. Close range
- 59. BURNS 1st , 2nd , 3rd , 4th “Degree” FULL vs. PARTIAL Thickness Survival PERCENT of body using the rule of NINES DEGREE (i.e., Depth) Respiratory Tract Involvement AGE Speed of access to Burn Unit Immune System (Pseudomonas, S. aureus, Candida)
- 60. HYPER-THERMIA HEAT CRAMPS: Electrolyte loss via sweat EXHAUSTION: Water depletion and lack of cardiovascular compensation “STROKE”: Extensive peripheral vasodilatation, i.e., “shocky”, very serious, T>106º, over 110º have been reported, high mortality.
- 61. HYPO-THERMIA Often in setting of homelessness or alcoholism or both < 90º often fatal, assoc. w. BRADYCARDIA ATRIAL FIBRILLATION
- 62. LIGHTNING/ELECTRICAL ELECTRIC DISTURBANCES NEURAL EKG THERMAL INJURY, depends upon a particular tissue’s RESISTANCE to electrical flow “LIGHTNING” MARKS
- 63. ATMOSPHERIC PRESSURE Altitude Illness Blast Injuries Decompression Injuries
- 64. ALTITUDE ILLNESS Caused by LOW Oxygen Tension HIGH ALTITUDES (>4000 m) OBTUNDATION INCREASED CAPILLARY PERMEABILITY ACUTE PULMONARY EDEMA (HAPE) Q: What is the name of the base camp at Mt. Everest A: Pulmonary Edema
- 65. BLAST INJURIES RELATED TO RAPID ATMOSPHERIC PRESSURE CHANGES LUNGS VISCERA, especially GAS filled viscera Rupture, Hemorrhage, etc. IMMERSION BLAST also possible, causing more of a total body compression syndrome
- 66. DECOMPRESSION Related to GAS SOLUBILITY in divers ascending rapidly, especially the more NON-SOLUBLE gasses, like NITROGEN, and, to a lesser extent, XENON AIR EMBOLISM is the common pathology ACUTE: “BENDS” (peri-articular), acute “CHOKES” (lungs), acute “STAGGERS” (inner ear), acute CHRONIC: ASEPTIC NECROSIS: humeri, femurs
- 67. NUTRITION NUTRITION & DISEASE & DISEASE Food Safety Food Safety Additives Additives Contaminants Contaminants Nutritional Deficiencies Nutritional Deficiencies Vitamins Vitamins Minerals Minerals Obesity Obesity Diet and Disease Diet and Disease Chemoprevention of Cancer Chemoprevention of Cancer
- 68. Vitamin Deficiency and Excess Vitamin Deficiency and Excess Fat soluble vitamins Fat soluble vitamins A, D, E, K A, D, E, K readily stored in body fat readily stored in body fat poorly absorbed in digestive disorders involving poorly absorbed in digestive disorders involving malabsorbtion of fat malabsorbtion of fat Water soluble vitamins Water soluble vitamins remaining vitamins remaining vitamins readily excreted in urine readily excreted in urine Vitamin stores Vitamin stores vitamins B-12 and A: stores sufficient for 1 year vitamins B-12 and A: stores sufficient for 1 year folate and thiamine may become depleted folate and thiamine may become depleted within weeks when eating a deficient diet within weeks when eating a deficient diet
- 69. Vitamin D Metabolism Vitamin D Metabolism Absorption of vitamin D in the gut or Absorption of vitamin D in the gut or synthesis from precursors in the skin synthesis from precursors in the skin Binding to a plasma α1 -globulin (D- Binding to a plasma α1 -globulin (D- binding protein) and transport to liver binding protein) and transport to liver Conversion to 25-hydroxyvitamin D, Conversion to 25-hydroxyvitamin D, 25(OH)D (calcidol) by 25-hydroxylase in 25(OH)D (calcidol) by 25-hydroxylase in the liver the liver Conversion of 25(OH)D to 1,25(OH) Conversion of 25(OH)D to 1,25(OH)2 2 D D (calcitrol, Vitamin D3) by α1-hydroxylase (calcitrol, Vitamin D3) by α1-hydroxylase in the kidney; in the kidney; biologically this is the most biologically this is the most active form of vitamin D active form of vitamin D. .
- 70. Functions of Vitamin D Functions of Vitamin D Stimulates intestinal absorption of calcium Stimulates intestinal absorption of calcium and phosphorus and phosphorus Collaborates with PTH in the mobilization Collaborates with PTH in the mobilization of calcium from bone of calcium from bone Stimulates the PTH-dependent reabsorption Stimulates the PTH-dependent reabsorption of calcium in the distal renal tubules of calcium in the distal renal tubules 1,25(OH) 1,25(OH)2 2 D, the biologically active form of D, the biologically active form of vitamin D, is best regarded as a steroid vitamin D, is best regarded as a steroid hormone which acts by binding to a high- hormone which acts by binding to a high- affinity receptor affinity receptor
- 72. Vitamin D Deficiency Vitamin D Deficiency Holick et al (2005) reported the results of a Holick et al (2005) reported the results of a large North American study that assessed large North American study that assessed the vitamin D status of postmenopausal the vitamin D status of postmenopausal women receiving therapy to treat or prevent women receiving therapy to treat or prevent osteoporosis osteoporosis 52% of 1536 women had inadequate 52% of 1536 women had inadequate [25(OH)D] levels (<30 ng/mL) [25(OH)D] levels (<30 ng/mL) 36% and 18% had levels less than 25 and 20 36% and 18% had levels less than 25 and 20 ng/mL, respectively. ng/mL, respectively. Holick MF et al: J Clin Endocrinol Metab 90:3215, 2005
- 74. Vitamin D Deficiency Vitamin D Deficiency Childhood: Rickets Childhood: Rickets epiphyses are open epiphyses are open cartilage overgrowth cartilage overgrowth Adults: Adults: osteomalacia osteomalacia bone matrix is not calcified bone matrix is not calcified vs osteoporosis (matrix reduced) vs osteoporosis (matrix reduced) ADULTS CHILDREN (RICKETS) OSTEOMALACIA 1) Bone fractures that happen with very little injury 2) Muscle weakness 3) Widespread bone pain, especially in the hips
- 75. Vitamin K Vitamin K Clotting factors VII, IX, and X and Clotting factors VII, IX, and X and prothrombin (II) all require carboxylation of prothrombin (II) all require carboxylation of glutamate residues for functional activity glutamate residues for functional activity anticoagulant coumadin is a Vitamin K anticoagulant coumadin is a Vitamin K antagonist antagonist Activation of anticoagulant proteins C and S Activation of anticoagulant proteins C and S also requires glutamate carboxylation also requires glutamate carboxylation Sources Sources endogenous intestinal bacterial flora endogenous intestinal bacterial flora diet diet
- 76. Vitamin K Deficiency Vitamin K Deficiency Causes Causes fat malabsorption fat malabsorption reduced gut bacterial flora reduced gut bacterial flora administration of wide specturm antibiotics administration of wide specturm antibiotics neonatal period before gut is colonized neonatal period before gut is colonized liver disease with reduced recycling of vitamin K liver disease with reduced recycling of vitamin K Effects of vitamin K deficiency Effects of vitamin K deficiency bleeding diathesis bleeding diathesis estimated 3% prevalence of vitamin K- estimated 3% prevalence of vitamin K- dependent bleeding diathesis among neonates dependent bleeding diathesis among neonates warrants routine prophylactic vitamin K therapy warrants routine prophylactic vitamin K therapy for all newborns for all newborns