9/20/2011 1 Environmental pathology พยาธิวิทยาสิ่งแวดลอม นพ.จตุวิทย หอวรรณภากร ว.ว. (พยาธิกายวิภาค) ว.ว. (นิติเวชศาสตร) ภาควิชาพยาธิกายวิภาคและนิติเวชศาสตร คณะแพทยศาสตร มหาวิทยาลัยนเรศวร Definition It is the study of disease caused by exposure to harmful external agents. A. Toxic agents B. Physical damage
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Acetaminophen (Tylenol) • Does not affect cyclooxygenase so bleeding associated with aspirin does not occur
• Has analgesic and antipyretic actions but no anti‐inflammatory action
• Large doses may produce hepatic necrosis – patients should not exceed recommended dose (4 grams/day)
– toxic dose in adults is 15 to 25 gm – dose should be reduced in children with fever or dehydration
Aspirin • Overdose
– respiratory alkalosis followed by metabolic acidosis that may be fatal
• Chronic aspirin toxicity (salicylism) – headache, dizziness, ringing in the ears (tinnitus), mental confusion, drowsiness, nausea, vomiting, and diarrhea
• Analgesic nephropathy (renal papillary necrosis) • Erosive gastritis is a major cause of GI bleeding • May be implicated in Reye syndrome (fatty liver with encephalopathy) in children < 15 years old, especially with influenza and chicken pox
• Mycotoxin alfatoxin liver cancer • Phytotoxin solanine neurotoxin • Animal toxin venoms snakes, bees tetrodotoxin puffer fish
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Physical Injury • Abrasion
– basically a scrape – superficial epidermis is torn off by friction or force – regeneration without scarring usually occurs
• Laceration vs. Incision – a laceration is an irregular tear in the skin produced by overstretching. The wound margins are frequently hemorrhagic and traumatized
– an incision is made by a sharp cutting object. The margins of the incision are usually relatively clean
• Contusion – an injury caused by a blunt force that damages small blood vessels and causes interstitial bleeding, usually without disruption of the continuity of the tissue (cf ecchymosis)
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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)
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.
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HYPO‐THERMIA • Often in setting of homelessness or alcoholism or both –< 90º often fatal, assoc. w.
• BRADYCARDIA • ATRIAL FIBRILLATION
LIGHTNING/ELECTRICAL • ELECTRIC DISTURBANCES
– NEURAL – EKG
• THERMAL INJURY, depends upon a particular tissue’s RESISTANCE to electrical flow
– HIGH ALTITUDES (>4000 m) – OBTUNDATION – INCREASED CAPILLARY PERMEABILITY – ACUTE PULMONARY EDEMA (HAPE)
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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
DECOMPRESSION • Related to GAS SOLUBILITY in divers ascending rapidly, especially the more NON‐SOLUBLE gasses, like NITROGEN, and, to a lesser extent, XENON
a. Vitamin A b. Vitamin D c. Vitamin C (Ascorbic Acid)
5. OBESITY a. General Consequences b. Obesity and Cancer
6. DIETS, CANCER, AND ATHEROSCLEROSIS a. Diet and Cancer b. Diet and Atherosclerosis
1. Dietary Insufficiency • Primary malnutrition = components are missing from the diet • Secondary malnutrition = nutrients is adequate
– But insufficient intake, malabsorption, impaired utilization or storage, excess loss, or increased need for nutrients
– More than 50% of elderly residents in nursing homes – Risk of mortality =five‐fold
• ↓subcutaneous fat in the arms, chest wall, shoulders • wasting of the quadriceps & deltoid • ankle or sacral edema
• Conditions lead to dietary insufficiencies 1. Poverty 2. Infections 3. Acute and chronic illnesses PEM associated with advanced cancers and AIDS 4. Chronic alcoholism deficiency of several vitamins 5. Ignorance and failure of diet supplementation in infants, adolescents, and
pregnant women 6. Self‐imposed dietary restriction Anorexia nervosa, bulimia 7. Other causes GIT diseases and malabsorption syndromes, genetic diseases,
specific drug therapies
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2. Protein Energy Malnutrition (PEM)
Kwashiorkor Cachexia
• Who = children • Where =low‐income countries • How bad = major factor in the high child death rates in under 5 years age • Determined by • 1. body mass index (BMI)
– Malnutrition =less than 16 kg/m2 – Normal =18.5 to 25 kg/m2
Cachexia • Risk groups = patients with AIDS or advanced cancers
– 50% of cancer patients (gastrointestinal, pancreatic, and lung cancers) are cachectic
– responsible for about 30% of cancer deaths • Characterized by =weight loss, fatigue, muscle atrophy, anemia, anorexia, and
edema • Mortality = related to atrophy of the diaphragm and other respiratory muscles • Causes of cachexia = not known • Mechanism= Cachetic agents secreted by tumors
– 1. PIF (proteolysis‐inducing factor) = excreted in the urine of patients – 2. LMF (lipid‐mobilizing factor)= cause fatty acid oxidation – 3. pro‐inflammatory cytokines = TNF and Il‐2, Il‐6 – PIF &cytokines = production of two muscle‐specific ubiquitin ligases, MuRF1
(muscle RING finger‐1) and MAFBx (muscle atrophy F‐box, or atroglin‐1) NF‐κB‐induced activation of the ubiquitin proteasome pathway contributors to muscle atrophy
– Loss of dystrophin also lead to skeletal muscle breakdown (latest information)
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3. Anorexia and Bulimia
Features Anorexia Bulimia Body weight loss marked No Frequency Less common More common Mortality high Low Prognosis Worse better Amenorrhea (↓GnRH ↓ LH, FSH ovarian failure)
Yes Less common (hormone levels – normal)
cardiac arrhythmia and sudden death (hypokalemia)
Yes Yes
Blood Anemia, lymphopenia, and Hypoalbuminemia
-
Bone density
+ -
Skin changes (dry and scaly), Lanugo hair
Yes -
Pulmonary aspiration of gastric contents esophageal and gastric cardiac rupture
No Yes
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4. Vitamin deficiencies & Toxicities
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4. Vitamin deficiencies & Toxicities Vitamin A • Group of related compounds =retinol (vitamin A alcohol), retinal (vitamin A
aldehyde), and retinoic acid (vitamin A acid) • Sources
– liver, fish, eggs, milk, and butter (preformed vitamin A) – Yellow and leafy green vegetables ‐carrots, squash, and spinach (provitamins)
• Absorption = requires bile, pancreatic enzymes • Storage= in liver Ito cells as Retinol esters; last for at least 6 months • Retinoic acid = important in epithelial differentiation and growth • Functions
– Maintenance of normal vision = rhodopsin in the rods is synthesed from retinol – Cell growth and differentiation = retinoic acid receptors (RARs) and (RXR) bind
to retinoic acid encode receptors for growth factors, tumor suppressor genes, and secreted proteins; deficiency lead to squamous metaplasia
– Metabolic effects of retinoids =(RXR) form heterodimers with (PPARs), and vitamin D receptors ( important in adipogenesis and obesity)
– Host resistance to infections = viatmin A reduce morbidity and mortality from infections (diarrhea & Measles)
– Photoprotective and antioxidant agents =β‐carotene & carotenoids ( used in Rx of acute promyelocytic leukemia, severe acne and ,psoriasis)
4. Vitamin deficiencies & Toxicities‐ Vitamin A
• Mmm
• Deficiency states = malnourished children with infections; Adults with malabsorption syndromes
• Vitamin A Toxicity = mega doses – acute hypervitaminosis A = headache, dizziness, vomiting, stupor, and blurred
vision (pseudotumor cerebri). – Chronic toxicity = weight loss, anorexia, nausea, vomiting, and bone and joint pain
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4. Vitamin deficiencies & Toxicities
• Vitamin D Fat soluble vitamin Maintains adequate plasma levels of calcium & phosphorus Vitamin D deficiency can result from: • ↓ in the diet • malabsorption syndrome • ↓ synthesis in the skin • defective vitamin D metabolism Vitamin D deficiency states: • Rickets (children) • Osteomalacia (adults)
• Hypervitaminosis D – In adults = bone pain and hypercalcemia – In children =metastatic calcifications of soft tissues such as the
kidney
. Vitamin deficiencies & Toxicities • Vitamin C
Water soluble vitamin No endogenous synthesis of vitamin C in humans. Principal functions: • required for hydroxylation of lysine & proline – residues in procollagen: ↓ hydroxylation ⇒ ↓ – cross‐linking ⇒ ↓ tensile strength • free radical scavenger
Vitamin C deficiency is due to ↓ in the diet Vitamin C deficiency state ‐ scurvy • impaired wound healing • hemorrhages • skeletal changes
• Vitamin C Toxicity
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5 &6. Obesity, Diet, Cancer, Atherosclerosis • #1 epidemic in the USA!!!
• Because obesity plays a role in many chronic diseases, it is important to define, recognize and understand it’s causes.
• Measurements of Fat accumulation: – a) Body Mass Index (kg/m2) ‐ normal 25 is normal. > 27 imparts health risks.
– b) Skinfold measurements
– c) Various body circumferences (waist:hip ratio).
• Etiopathogenesis
• Not completely understood.
• “Disorder of energy balance”.
• Generally: calories in = energy expended (when weight stable).
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5 &6. Obesity, Diet, Cancer, Atherosclerosis
• Concept of “lipostat”‐L =
– a) leptin – leptin receptor system‐LR
• Dysfunction within the L‐LR system
• a) leptin resistance in tissues
• b) neuropeptide Y excess
– Leptin gene polymorphism
• Leptin – also important in
– a) puberty
– b) development of 2nd sexual characteristics
• Other dysfunction/s in hypothalamic/pituitary/end‐organ axis