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Pulmonary Pathology

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Environmental Diseases Bill Becker, DO, MPH Clinical Associate Professor Dept of Pathology Ohio State University Objectives – Selected Environmental Diseases   Chemical agents – therapeutic & nontherapeutic – Lead Physical agents - burns  Radiation injury  Nutritional diseases – Protein energy malnutrition – Vitamin Deficiencies General – Environmental Disorders Injuries/disorders caused by chemical or physical agents  Related field – Occupational medicine – injuries that occur in the workplace  Regulatory agencies – EPA, FDA, OSHA, Consumer Products Safety Commission  General – Environmental Disorders Air pollution – both indoor & outdoor  Industrial exposures – coal, asbestos, metals  Tobacco smoke (don‟t smoke – please!)  Chemical agents  Physical agents  Electrical injury  Radiation injury  Nutritional diseases  Injury from Chemical Agents Occur by inhalation, ingestion, injection or absorption thru the skin  Est. 2 million exposures/yr in the US  Kids account for 61%  Common house items – cleaners, analgesics, cosmetics, plants, cold meds  CLADME  Injury by Therapeutic Agents Averse drug reactions are common (2%)  Relatively minor ADR‟s – rashes, GI upset  Major - anaphylaxis (penicillin is classic), blood clots, arrhythmias, hematologic (anemia, thrombocytopenia, leukopenia)  ADR‟s are also related to potency – anticancer meds  Injury by Therapeutic Agents  Aspirin – overdose may be accidental (kids) or intentional (adolescents/adults) Acetaminophen – OD with large ingestions (15-20 gms) – causes liver damage, may result in liver failure/death  Injury by Therapeutic Agents     Exogenous Estrogens – until 2002 HRT widely used for menopausal symptoms and prevention of osteoporosis Recent Women‟s Health Initiative data – long term use has ↑‟er risk of heart disease, breast ca, strokes & blood clots Short term use may have better risk-benefit relationship OCP‟s also have risks & benefits that should always be considered Injuries by Non-therapeutic Agents Lead Lead is found in urban air, soil, water, food, house dust, batteries, older paints & gasoline  Occupational lead – mining, foundries  85% of Pb is taken up by bones & teeth – it competes with Ca++ and interferes with remodeling process. “Lead lines”  Hyperpigmented gums – „blue line‟  Radiodense metaphyseal lines – lead poisoning Lead Pb blocks or hinders incorporation of Fe++ into hemoglobin ***  Develop anemia (microcytic, hypochromic)  Neurologic disturbances – range from mild to learning difficulties to sensory & motor deficits  Wristdrop and footdrop (adults)  Lead GI tract – colicky pain – severe, not localized  Kidneys – damages tubules, fibrosis, perhaps even renal failure  Public Health & EPA monitor Pb (10 g/dL)  – African American kids (11.2%) – Caucasian kids (2.3%)  Chelation therapy Drugs of Abuse (Non-therapeutic)    Sedative-hypnotic – EtOH, barbiturates, benzodiazepines CNS Stimulants – cocaine, amphetamines Opioids – heroin, morphine, methadone, codeine    Hallucinogens – LSD, PCP, mescaline, MDMA Inhalants – glue, toluene, paint thinner, gasoline, amyl nitrate, nitrous oxide Nonprescription drugs – analgesics, antihistamines, scopolamine, atropine Club Drugs    Used in bars, dance clubs, raves, trances Methamphetamines, LSD, Ketamine, MDMA (ecstasy), GHB, Rohypnol Bruxism – clenching of teeth – use of “e” Physical Agents Mechanical trauma – abrasions, contusions, lacerations, incisions, puncture wounds  Thermal injuries – body operates in temperature range of 31o to 41oC (89-106oF)  Hyperthermia (burns) – cause > 5000 deaths/yr in the US  Hypothermia – due to prolonged exposure to low temps  Burns – Important Factors ***  % of body surface area (rule of 9‟s) – Head & neck 9% – Trunk front 18%, trunk back 18% – Arms 9% each (hands are 1% each) – Legs 18% each – Perineum 1 % Burns – Important Factors *** Depth of the burn (full or partial thickness)  Potential for internal injuries from inhalation of fumes or hot gases  Age of the patient (elderly & very young)  How fast and how well is it treated?  Clinical Consequences of Burns If > 50% bsa involved – grave prognosis  Shock common when > 30-40% bsa involved  – Massive fluid shifts – hypovolemia – Infections – Pseudomonas spp. Candida – Electrolyte & nutrition (hypermetabolic)  Internal injuries – from fumes (CO, HCN) – Damages both URT & LRT – Acute respiratory distress syndrome (ARDS) Hyperthermia Due to prolonged exposure to ↑ ambient temperatures  Heat cramps – exercise w loss of fluids & e-lytes  Heat exhaustion – sudden onset of shock, CV system fails to adjust acutely to the hypovolemia, will usually recover spontaneously  Heat stroke – temps > 40oC, body core temp ↑’s, peripheral vasodilatation (pooling), ischemia, muscle necrosis (rhabdomyolysis), DIC, confusion, coma, seizures, high mortality rate  Hypothermia  Abnormally low core temperature – High humidity, wet clothes, vasodilatation (EtOH) all facilitate development of hypothermia Mild (core temp =) 32-35oC (89-95oF)  Moderate 28-32oC (82-89oF)  Severe < 28oC (< 82oF)  Bradycardia, atrial fibrillation, loss of consciousness  Hypothermia Frost bite – occurs when the temperature of the extremities falls below freezing  At the cellular level hypothermia may lead to cell damage (crystallization of water)  Indirect effect of chilling – vasoconstriction, edema, long term may cause atrophy & fibrosis  Radiation Injuries Sources – cosmic, ultraviolet, elemental (from the earth‟s crust – radon), medical (both diagnostic & therapeutic), industrial, nuclear power plants, weapons  Forms:  – Electromagnetic waves – x-rays & gamma rays – High energy neutrons and charged particles – alpha and beta particles, protons Radiation Injuries  Cellular mechanism of damage (***): – Direct damage to DNA – Indirect – production of free radicals that can damage membranes, nucleic acids and enzymes  Result may be reversible, may lead to cell death (apoptosis), nuclear changes (pyknosis), cytoplasm changes (membranes, mitochondria and EER) Radiation Injuries Rad (radiation absorbed dose) = the amount of energy absorbed per unit mass  Chest x-ray - < 0.2 rad  Mammography – 0.4 rad  Dental (bite) - < 0.4 rad  Occupational exposures should not exceed 400 mrem/yr (rem = rad w a quality factor)  Radiation Injuries Organ Systems effects:  Skin: damage occurs over time –  – Erythema (redness) at 2-3 days – Edema 2-3 wks – Blistering/desquamation 4-6 wks – Atrophy & neoplasias months to yrs Radiation Injuries  Hematopoietic/lymphoid tissues – sensitive – Lymphocytes  in hrs, rebound in wks/mo‟s – Lymph nodes & spleen shrink in size – PMN‟s  over 1-2 wks, rebound in 2-3 mo‟s Susceptible to infections ! – Platelets & RBC‟s also , take longer to rebound Radiation Injuries Gonads – both sexes – sensitive (sterility)  Lungs – sensitive d/t vascularity – pulmonary congestion & edema, ARDS  GI tract – v. sensitive – ulcers, strictures, later ‟d risk for cancer  Other – blood vessels – endothelial cell injury then fibrosis & narrowing (ischemia)  Total Body Radiation Effects Lethal range begins about 200 rad and at 700 rad death is certain w/o treatment Acute Radiation Syndromes (3):  Hematopoietic – 200-500 rad – GI sx‟s,  WBC‟s, infections, sepsis & bleeding  GI – 500-1000 rad – severe GI sx‟s, bloody diarrhea, shock, sepsis, death in 10-14 d  Cerebral - > 5000 rad – listlessness, drowsiness, seizures, coma, death in 14-36 hrs  Nutritional Diseases A branch of science that studies the qualitative and quantitative aspects of diet  Utilization of components required to maintain health  “Adequate diet” should provide CHO‟s, protein & fats for daily metabolic needs  Essential amino acids, fats, vitamins & minerals  Malnutrition    Primary – diet is deficient in 1 or more components Secondary – supply is OK, problem w absorption, storage, utilization, excessive losses or drug effects Causes of poor diet – SES, ignorance of needs, fads, acute illnesses (↑‟s BMR), self imposed diet restriction/habits (anorexia/bulimia), malabsorption syndromes (CF, Crohns), genetic diseases Protein-Energy Malnutrition (PEM)  Common in developing countries – Up to 25% of children affected – Major cause of morbidity in kids < 5 yrs Ways to assess nutritional status – body weight (compared to age, sex & height norms), rate of growth (charts)  2 major disorders: Marasmus & Kwashiorkor  Protein-Energy Malnutrition  2 functional protein compartments: – Somatic – skeletal muscles - more severely affected in marasmus – skinfold thickness – Visceral – liver - more severely affected in kwashiorkor – serum proteins (albumin & transferrin)  When weight falls to < 60% of normal – child has marasmus Marasmus Deficiency of caloric intake  Catabolize proteins (amino acids) for energy  Somatic protein compartment (sk muscle) is depleted. Sub Q fat depleted also.  – Visceral compartment is held in reserve  Extremities are emaciated, head looks out-ofproportion too large Marasmus Growth retardation  Anemia, multiple vitamin deficiencies  – Bone marrow may be hypoplastic   Immune deficiencies – esp T-cell defects – Infections are common – Thrush Serum albumin relatively normal (or sl ‟d)  Bradycardia, Body temperature ‟s Kwashiorkor Greater deficiency of protein than total calories, more severe than marasmus  PEM found in Africa & SE Asia  Visceral protein compartment is depleted  Low albumin – generalized edema  Weight is between 60-80% of normal but this is misleading because of the edema  Infant with Kwashiorkor Visible edema (puffiness) of the face, hands and legs From: Robbins Basic Pathology Kwashiorkor Skin changes – alternating zones of hyperpigmentation, desquamation & hypopigmentation (flaky paint)  Changes in hair texture & color  Liver – enlarged & fatty  – Lack of transport proteins Vitamin and mineral deficiencies  Immune system defects – infections  Growth retardation  Secondary Forms of PEM In the US can be found in chronic illness or hospitalized pts  Cachexia – a form of PEM seen in cancer patients  – Decreased appetite partly responsible – Increased catabolism – cytokine-mediated (IL-1, IL-6 and TNF) Vitamin Deficiency Common in person in lower SES  Usually a part of overall malnutrition  Fat-soluble (A, D, E, K)  – Require healthy intestinal mucosa, bile & pancreatic secretions for absorption – Are stored in body tissues (compare to watersoluble) – Inflammatory bowel disease (Crohn‟s), Cystic fibrosis, Alcoholic liver disease - ‟d absorption Vitamin A      1925 found to prevent night blindness 3 biologically active forms – retinol, retinal, and retinoic acid β-carotenes are found in yellow & leafy green veggies, some animal products (liver, fish, eggs, milk) Mainly stored in the liver, reserves for 6-12 months Released w carrier protein – retinol-binding protein Vitamin A  Functions: – Maintain vision in reduced light – Augments differentiation of specialized epithelial cells (mucus secreting epithelium) – Enhances immunity to infections (kids, measles) Vitamin A Deficiency Deficiency is worldwide – esp 3rd world countries  Early sign is impaired night vision  Persistent deficiency – Dry eyes (xerosis and xerophthalmia) which can lead to damage to the cornea and total blindness  Vitamin A Deficiency Epithelia of Respiratory & Urinary tracts are also affected – squamous metaplasia – increases risk for infections and stones  Impaired immunity – measles, pneumonia and infectious diarrhea  Vitamin A Toxicity  25,000 IU or more daily – Over use of vitamin supplements (read labels) – Topical retinoic acid (acne) – this is rare Acute – N/V, irritability, headache, blurred vision (papilledema symptoms)  Chronic – anorexia, hair loss, dry skin (itching), dry mucus membranes, fissured lips, fatigue, weight loss, bone/joint pain  The End !

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