1. ENVIRONMENTALENVIRONMENTAL
&&
NUTRITIONALNUTRITIONAL
PATHOLOGYPATHOLOGY

2. Environmental andEnvironmental and
Nutritional PathologyNutritional Pathology
 Environment and DiseaseEnvironment and Disease
 Common ExposuresCommon Exposures
 EnvironmentalEnvironmental
 OccupationalOccupational
 NutritionNutrition and Diseaseand Disease

3. Reported Occupational DiseasesReported Occupational Diseases
DiseaseDisease NumberNumber PercentagePercentage
Repeated traumaRepeated trauma 276,600276,600 6464
Skin disordersSkin disorders 57,90057,900 1313
Lung conditions due toLung conditions due to
toxic exposurestoxic exposures
20,30020,300 55
Physical injuryPhysical injury 16,60016,600 44
PoisoningPoisoning 5,1005,100 11
Lung disease due toLung disease due to
dustsdusts
2,9002,900 11
All other illnessesAll other illnesses 50,60050,600 1212
TotalTotal 430,000430,000 100100

4. Mechanisms of ToxicityMechanisms of Toxicity
 Threshold effectThreshold effect
 Absorption at portals of entryAbsorption at portals of entry
 ingestioningestion
 inhalationinhalation
 skin contactskin contact
 Distribution within the bodyDistribution within the body
 Metabolism and ExcretionMetabolism and Excretion
 Toxic effectsToxic 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

8. Dose-response CurveDose-response Curve

9. CommonCommon ExposuresExposures
 PersonalPersonal
 MedicationsMedications
 Outdoor Air PollutionOutdoor Air Pollution
 Indoor Air PollutionIndoor Air Pollution
 Industrial ExposuresIndustrial Exposures
 Agricultural HazardsAgricultural Hazards
 Natural ToxinsNatural Toxins
 Radiation InjuryRadiation Injury
 Physical InjuryPhysical Injury

10. TobaccoTobacco
 440,000 premature deaths/year in USA440,000 premature deaths/year in USA
 cancercancer
 cardiovascular diseasecardiovascular disease
 respiratory diseaserespiratory disease
 cerebrovascular diseasecerebrovascular disease
 $150 billion in health related costs$150 billion in health related costs
By farBy far the most preventable causethe most preventable cause
of death in the United Statesof 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 CigarettesRelative Risks for Current Smokers of Cigarettes
Disease or Condition MalesMales FemalesFemales
Coronary heart diseaseCoronary heart disease
Age 35–64Age 35–64 2.82.8 3.13.1
Age ≥ 65Age ≥ 65 1.51.5 1.61.6
Cerebrovascular lesionsCerebrovascular lesions
Age 35–64Age 35–64 3.33.3 44
Age ≥ 65Age ≥ 65 1.61.6 1.51.5
Aortic aneurysmAortic aneurysm 6.26.2 7.17.1
Chronic airways obstructionChronic airways obstruction 10.610.6 13.113.1
CancerCancer
Lip, oral cavity, pharynxLip, oral cavity, pharynx 10.910.9 5.15.1
EsophagusEsophagus 6.86.8 7.87.8
StomachStomach 22 1.41.4
PancreasPancreas 2.32.3 2.32.3
LarynxLarynx 14.614.6 1313
LungLung 23.323.3 12.712.7
CervixCervix 1.61.6
KidneyKidney 2.72.7 1.31.3
Bladder, other urinary organsBladder, other urinary organs 3.33.3 2.22.2

14. Cigarettes And The WorkplaceCigarettes And The Workplace
 Similar to asbestos exposure, cigarette smoke isSimilar to asbestos exposure, cigarette smoke is
synergistic with radon decay products in causingsynergistic with radon decay products in causing
lung cancerlung cancer
 Cigarette smoke exacerbates bronchitis, asthma,Cigarette smoke exacerbates bronchitis, asthma,
and pneumoconiosis associated with exposureand pneumoconiosis associated with exposure
to silica, coal dust, grain dust, cotton dust, andto silica, coal dust, grain dust, cotton dust, and
welding fumeswelding fumes

15. AlcoholAlcohol
 15 to 20 million alcoholics in the USA15 to 20 million alcoholics in the USA
 100,000 deaths/year due to alcohol100,000 deaths/year due to alcohol
abuseabuse
 Economic losses of $100 to $130Economic losses of $100 to $130
billion/yearbillion/year
 One to two drinks/day reducesOne 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?

16. Definition of Alcoholism
?

17. Effects of Blood Alcohol Levels in the Absence of ToleranceEffects of Blood Alcohol Levels in the Absence of Tolerance
Blood Level, mg/dLBlood Level, mg/dL Usual EffectUsual Effect
2020 Decreased inhibitions, a slightDecreased inhibitions, a slight
feeling of intoxicationfeeling of intoxication
8080 Decrease in complex cognitiveDecrease in complex cognitive
functions and motor performancefunctions and motor performance
200200 Obvious slurred speech, motorObvious slurred speech, motor
incoordination, irritability, andincoordination, irritability, and
poor judgmentpoor judgment
300300 Light coma and depressed vitalLight coma and depressed vital
signssigns
400400 DeathDeath
Harrison Internal Med, 16th
Ed

18. Metabolism Of EthanolMetabolism Of Ethanol
ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase
20%
80%

20. LEGAL INTOXICATION
0.08%

21. Widmark EquationWidmark Equation
 C = A / (W * r)C = A / (W * r)
 C = concentration of EtOH in mg/dlC = concentration of EtOH in mg/dl
 A = mass of alcohol ingested in gramsA = mass of alcohol ingested in grams
 density of ethanol = 0.8density of ethanol = 0.8
 W = body weight in gramsW = body weight in grams
 r = Widmark distribution for ethanolr = Widmark distribution for ethanol
 0.55 mL/ g body weight for females0.55 mL/ g body weight for females
 0.68 mL / g body weight for males0.68 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 kineticszero order kinetics
 Medical measurements use mg/dl in plasma, whereasMedical measurements use mg/dl in plasma, whereas
legal definitions use percentage (mass/volume) in wholelegal definitions use percentage (mass/volume) in whole
bloodblood
 to estimate the alcohol level in whole blood using the alcoholto estimate the alcohol level in whole blood using the alcohol
level in blood plasma, divide by 1.16level in blood plasma, divide by 1.16

22. Alcohol and the LiverAlcohol and the Liver
 Fatty ChangeFatty Change
 present in over 90% of binge and chronic drinkerspresent in over 90% of binge and chronic drinkers
 liver is enlarged but patient is asymptomaticliver is enlarged but patient is asymptomatic
 changes are reversible with cessation of drinkingchanges are reversible with cessation of drinking
 macrosteatosis w/o inflammation or necrosismacrosteatosis w/o inflammation or necrosis
 Alcohol hepatitisAlcohol hepatitis
 only between 10 - 15% of alcoholics will developonly between 10 - 15% of alcoholics will develop
alcoholic hepatitisalcoholic hepatitis
 may have systemic symptoms and jaundicemay have systemic symptoms and jaundice
 hepatocellular necrosis with Mallory bodies and PMNshepatocellular necrosis with Mallory bodies and PMNs
(central hyaline sclerosis)(central hyaline sclerosis)
 thought to be a precursor of cirrhosisthought to be a precursor of cirrhosis
 Alcoholic cirrhosisAlcoholic cirrhosis
 shrunken nodular liver with uniform small nodulesshrunken nodular liver with uniform small nodules
(micronodular cirrhosis)(micronodular cirrhosis)

23. Fatty Change BiochemistryFatty Change Biochemistry
 Catabolism of fat by peripheral tissues isCatabolism of fat by peripheral tissues is
increased, and there is increased delivery ofincreased, and there is increased delivery of
free fatty acids to the liverfree fatty acids to the liver
 An excess of NADH over NAD stimulatesAn excess of NADH over NAD stimulates
lipid biosynthesislipid biosynthesis
 Oxidation of fatty acids by mitochondria isOxidation of fatty acids by mitochondria is
decreaseddecreased
 Acetaldehyde forms adducts with tubulin andAcetaldehyde forms adducts with tubulin and
impairs function of microtubules, resulting inimpairs function of microtubules, resulting in
decreased transport of lipoproteins from thedecreased transport of lipoproteins from the
liverliver

28. Neurologic Manifestations of AlcoholismNeurologic Manifestations of Alcoholism
 Wernicke syndromeWernicke syndrome
 confusion, ataxia, and diplopia fromconfusion, ataxia, and diplopia from
ophthalmoplegiaophthalmoplegia
 damage to mammillary bodies, cerebellum anddamage to mammillary bodies, cerebellum and
periaqueductal gray matterperiaqueductal gray matter of the midbrainof the midbrain
 due to thiamine deficiencydue to thiamine deficiency
 may respond to prompt thiamine replacementmay respond to prompt thiamine replacement
 Korsakov syndromeKorsakov syndrome
 memory loss and confabulationmemory loss and confabulation
 results from thiamine deficiency and directresults from thiamine deficiency and direct
toxicitytoxicity

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 DrugsTherapeutic Drugs
(Medications)(Medications)
 Oral Contraceptives (BCPs)Oral Contraceptives (BCPs)
 Hormone Replacement Therapy (HRT)Hormone Replacement Therapy (HRT)
 AcetaminophenAcetaminophen
 AspirinAspirin

33. Oral Contraceptives (BCPs)Oral Contraceptives (BCPs)
 Breast cancer and other cancersBreast cancer and other cancers
 no increase in breast cancerno increase in breast cancer
 decrease endometrial and ovarian cancersdecrease endometrial and ovarian cancers
 increase in cervical cancer (?lifestyle induced)increase in cervical cancer (?lifestyle induced)
 Thromboembolic eventsThromboembolic events
 DVT and Pulmonary Embolism increasedDVT 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 diseaseCardiovascular disease
 with current low estrogen pills, risk of MI andwith current low estrogen pills, risk of MI and
atherosclerosis not increased in non-smoking women < 45 yatherosclerosis not increased in non-smoking women < 45 y
 ischemic stroke increased regardless of age or smokingischemic stroke increased regardless of age or smoking
 Liver tumorsLiver tumors
 benign hepatic adenomasbenign hepatic adenomas
 older women with prolonged useolder women with prolonged use
 may rupture and cause intra-abdominal bleedingmay rupture and cause intra-abdominal bleeding

34. Hormone Replacement Therapy (HRT)Hormone Replacement Therapy (HRT)
 CancerCancer
 in women with a uterus combined estrogen andin women with a uterus combined estrogen and
progestin Rx necessary to reduce endometrial cancerprogestin Rx necessary to reduce endometrial cancer
 WHI showed increased risk of breast cancer in womenWHI showed increased risk of breast cancer in women
who used HRT combined therapy for 5 yearswho used HRT combined therapy for 5 years
 Thromboembolic eventsThromboembolic events
 elevated approximated twofold in HRT users, especiallyelevated approximated twofold in HRT users, especially
within the first 2 yearswithin the first 2 years
 Cardiovascular diseaseCardiovascular disease
 WHI reported 29% increased risk of myocardialWHI reported 29% increased risk of myocardial
infarction, especially during the first year of combinedinfarction, especially during the first year of combined
HRT useHRT use

35. Acetaminophen (Tylenol)Acetaminophen (Tylenol)
 Does not affect cyclooxygenase so bleedingDoes not affect cyclooxygenase so bleeding
associated with aspirin does not occurassociated with aspirin does not occur
 Has analgesic and antipyretic actions but noHas analgesic and antipyretic actions but no
anti-inflammatory actionanti-inflammatory action
 Large doses may produce hepatic necrosisLarge doses may produce hepatic necrosis
 patients should not exceed recommended dosepatients should not exceed recommended dose
(4 grams/day)(4 grams/day)
 toxic dose in adults is 15 to 25 gmtoxic dose in adults is 15 to 25 gm
 dose should be reduced in children with fever ordose should be reduced in children with fever or
dehydrationdehydration

36. AspirinAspirin
 OverdoseOverdose
 respiratory alkalosis followed by metabolic acidosis thatrespiratory alkalosis followed by metabolic acidosis that
may be fatalmay 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, andmental confusion, drowsiness, nausea, vomiting, and
diarrheadiarrhea
 Inhibits cyclooxygenase (COX 1 & 2)Inhibits cyclooxygenase (COX 1 & 2)
 Erosive gastritis is a major cause of GI bleedingErosive gastritis is a major cause of GI bleeding
 May be implicated in Reye syndrome (fatty liverMay 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 poxespecially with influenza and chicken pox

37. Cox-1 and Cox-2 InhibitorsCox-1 and Cox-2 Inhibitors
 Cyclooxygenase 1Cyclooxygenase 1
 constitutively expressed and active in theconstitutively expressed and active in the
normal platelet (thromboxane A2)normal platelet (thromboxane A2)
 involved in synthesis of gastro-protectiveinvolved in synthesis of gastro-protective
prostaglandinsprostaglandins
 Cyclooxygenase 2Cyclooxygenase 2
 induced, especially in inflamed tissueinduced, especially in inflamed tissue
 in vessel wall produces prostacyclin (PGIin vessel wall produces prostacyclin (PGI22))
 Aspirin and other nonselective NSAIDSAspirin and other nonselective NSAIDS
inhibit both COX-1 and COX-2inhibit 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 PollutionIndoor Air Pollution
 Carbon Monoxide COCarbon Monoxide CO
 Nitrogen Dioxide NONitrogen Dioxide NO22
 Wood SmokeWood Smoke
 FormaldehydeFormaldehyde
RadonRadon
 Manufactured Mineral FibersManufactured Mineral Fibers
 BioaerosolsBioaerosols

40. RadonRadon
 Radon is a radioactive gas and a decayRadon is a radioactive gas and a decay
product of uraniumproduct of uranium
 It is widely distributed in the soil and isIt 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 emittersRadon decay products are alpha emitters
 10% of US homes have levels associated with10% of US homes have levels associated with
an increased risk of lung cancer and anan increased risk of lung cancer and an
estimated 10,000 lung cancers per year in theestimated 10,000 lung cancers per year in the
United States are due to radon. SmokingUnited States are due to radon. Smoking
elevates risk.elevates risk.
 Proper venting reduces the exposureProper venting reduces the exposure

41. LeadLead
 lead is classified as a heavy metal (otherslead is classified as a heavy metal (others
include mercury, arsenic, and cadmium)include mercury, arsenic, and cadmium)
 Source of exposureSource of exposure
 lead paintlead paint
 lead solder in plumbing (older houses)lead solder in plumbing (older houses)
 lead-glazed ceramicslead-glazed ceramics
 industrial exposureindustrial exposure
 Route of exposureRoute of exposure
 inhalation with industrial exposureinhalation with industrial exposure
 ingestion with household exposureingestion with household exposure

42. Lead Distribution and ExcretionLead Distribution and Excretion
 Lead is a divalent cation that is taken up byLead 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 yearsHalf-life of lead in bone is 30 years
 Blood accumulates 5% to 10% of lead, butBlood accumulates 5% to 10% of lead, but
lead is rapidly cleared from the bloodlead is rapidly cleared from the blood
 lead in blood indicates recent exposurelead in blood indicates recent exposure
 blood level does not allow the determination ofblood level does not allow the determination of
total body burdentotal body burden
 Remainder is distributed in the soft tissuesRemainder is distributed in the soft tissues
 Excretion is via the kidneysExcretion is via the kidneys

43. Effects of LeadEffects of Lead
 High affinity for sulfhydryl groupsHigh affinity for sulfhydryl groups
 inhibition of heme biosynthesis with hypochromicinhibition of heme biosynthesis with hypochromic
anemia and basophillic stippling of erythrocytesanemia and basophillic stippling of erythrocytes
 Competition with calcium ionsCompetition with calcium ions
 As a divalent cation, lead competes with calcium and isAs a divalent cation, lead competes with calcium and is
stored in bone.stored in bone.
 It also interferes with nerve transmission and brainIt also interferes with nerve transmission and brain
development.development.
 Inhibition of membrane-associated enzymesInhibition 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 ofpotassium ion pumps, leading to decreased survival of
red blood cells (hemolysis), renal damage, andred blood cells (hemolysis), renal damage, and
hypertension.hypertension.

44. Consequences
of lead
exposure

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 DosimetryRadiation Dosimetry
 Roentgen:Roentgen: unit of charge produced by x-rays or gammaunit of charge produced by x-rays or gamma
rays that ionize a specific volume of airrays that ionize a specific volume of air
 RADRAD (radiation absorbed dose):(radiation absorbed dose): the dose of radiationthe dose of radiation
that will produce absorption of 100 ergs of energy per gramthat will produce absorption of 100 ergs of energy per gram
of tissue; 1 gm of tissue exposed to 1 roentgen of gammaof tissue; 1 gm of tissue exposed to 1 roentgen of gamma
rays is equal to 93 ergsrays is equal to 93 ergs
 GrayGray (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 Gyabsorption 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)
 REMREM (radiation equivalent man):(radiation equivalent man): the dose of radiation thatthe dose of radiation that
causes a biologic effect equivalent to 1 rad of x-rays orcauses a biologic effect equivalent to 1 rad of x-rays or
gamma raysgamma rays
 SievertSievert (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 Sveffect 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 RadiationAcute Effects of Ionizing Radiation
 Free radical generationFree radical generation
 Ionizing radiation + HIonizing radiation + H220 → H0 → H3300++
+ OH·+ OH·
 DNA DamageDNA Damage
 double-stranded DNA breaks needed to kill celldouble-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 bondsphosphate bonds
 Tumor-suppressor geneTumor-suppressor gene p53p53 activationactivation
 cell cycle arrest in presence of damaged DNAcell cycle arrest in presence of damaged DNA
 repair of DNA damage or apoptosisrepair of DNA damage or apoptosis

51. Acute Whole Body RadiationAcute 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)
 HematopoieticHematopoietic
 200–600 REM200–600 REM
 Maximum neutrophil and platelet depression in 2 wkMaximum neutrophil and platelet depression in 2 wk
 GastrointestinalGastrointestinal
 600–1000 REM600–1000 REM
 Nausea, vomiting, diarrheaNausea, vomiting, diarrhea
 Hemorrhage and infection in 1–3 wkHemorrhage and infection in 1–3 wk
 Central nervous systemCentral nervous system
 >1000 REM>1000 REM
 Intractable nausea and vomitingIntractable nausea and vomiting
 Confusion, somnolence, convulsionsConfusion, somnolence, convulsions
 death in 14–36 hrdeath in 14–36 hr

52. Therapeutic RadiationTherapeutic Radiation
 External radiation is delivered to malignantExternal radiation is delivered to malignant
neoplasms at fractionated doses up to 40 toneoplasms at fractionated doses up to 40 to
70 Gy (4000 to 7000 rad), with shielding of70 Gy (4000 to 7000 rad), with shielding of
adjacent normal tissuesadjacent normal tissues
 Therapeutic radiation alone seems to addTherapeutic radiation alone seems to add
little risk of AML but can increase the risk inlittle risk of AML but can increase the risk in
people exposed to alkylating agentspeople exposed to alkylating agents
 Fatigue, nausea and vomiting frequentFatigue, nausea and vomiting frequent
 Bone marrow suppression may occurBone marrow suppression may occur
especially with chest or abdominal radiationespecially with chest or abdominal radiation

53. Delayed Radiation InjuryDelayed Radiation Injury
 Carcinogenesis (atom bomb survivors)Carcinogenesis (atom bomb survivors)
 myeloid leukemias peak 5 to 7 years after exposuremyeloid leukemias peak 5 to 7 years after exposure
 breast and thyroid cancers may show greater latencybreast and thyroid cancers may show greater latency
 no germline mutations noted in progeny of survivorsno germline mutations noted in progeny of survivors
 Vascular effectsVascular effects
 endothelial necrosis followed by intimal and medialendothelial necrosis followed by intimal and medial
fibrosisfibrosis
 capillaries may become thrombosed and obliterated orcapillaries may become thrombosed and obliterated or
ectaticectatic
 Parenchymal atrophy and fibrosisParenchymal atrophy and fibrosis

54. Radiation effects on TISSUE
 ACUTE (vasculitis, possibly “fibrinoid” necrosis)
 CHRONIC (fibrosis)

55. Physical InjuryPhysical Injury
 AbrasionAbrasion
 basically a scrapebasically a scrape
 superficial epidermis is torn off by friction or forcesuperficial epidermis is torn off by friction or force
 regeneration without scarring usually occursregeneration without scarring usually occurs

Laceration vs. IncisionLaceration vs. Incision
 a laceration is an irregular tear in the skin produced bya laceration is an irregular tear in the skin produced by
overstretching. The wound margins are frequently hemorrhagicoverstretching. The wound margins are frequently hemorrhagic
and traumatizedand traumatized
 an incision is made by a sharp cutting object. The margins ofan incision is made by a sharp cutting object. The margins of
the incision are usually relatively cleanthe incision are usually relatively clean
 ContusionContusion
 an injury caused by a blunt force that damages small bloodan injury caused by a blunt force that damages small blood
vessels and causes interstitial bleeding, usually withoutvessels and causes interstitial bleeding, usually without
disruption of the continuity of the tissue (disruption of the continuity of the tissue (cfcf 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. NUTRITIONNUTRITION & DISEASE& DISEASE
 Food SafetyFood Safety
 AdditivesAdditives
 ContaminantsContaminants
 Nutritional DeficienciesNutritional Deficiencies
 VitaminsVitamins
 MineralsMinerals
 ObesityObesity
 Diet and DiseaseDiet and Disease
 Chemoprevention of CancerChemoprevention of Cancer

68. Vitamin Deficiency and ExcessVitamin Deficiency and Excess
 Fat soluble vitaminsFat soluble vitamins
 A, D, E, KA, D, E, K
 readily stored in body fatreadily stored in body fat
 poorly absorbed in digestive disorders involvingpoorly absorbed in digestive disorders involving
malabsorbtion of fatmalabsorbtion of fat
 Water soluble vitaminsWater soluble vitamins
 remaining vitaminsremaining vitamins
 readily excreted in urinereadily excreted in urine
 Vitamin storesVitamin stores
 vitamins B-12 and A: stores sufficient for 1 yearvitamins B-12 and A: stores sufficient for 1 year
 folate and thiamine may become depletedfolate and thiamine may become depleted
within weeks when eating a deficient dietwithin weeks when eating a deficient diet

69. Vitamin D MetabolismVitamin D Metabolism
 Absorption of vitamin D in the gut orAbsorption of vitamin D in the gut or
synthesis from precursors in the skinsynthesis from precursors in the skin
 Binding to a plasma α1 -globulin (D-Binding to a plasma α1 -globulin (D-
binding protein) and transport to liverbinding protein) and transport to liver
 Conversion to 25-hydroxyvitamin D,Conversion to 25-hydroxyvitamin D,
25(OH)D (calcidol) by 25-hydroxylase in25(OH)D (calcidol) by 25-hydroxylase in
the liverthe liver
 Conversion of 25(OH)D to 1,25(OH)Conversion of 25(OH)D to 1,25(OH)22 DD
(calcitrol, Vitamin D3) by α1-hydroxylase(calcitrol, Vitamin D3) by α1-hydroxylase
in the kidney;in the kidney; biologically this is the mostbiologically this is the most
active form of vitamin Dactive form of vitamin D..

70. Functions of Vitamin DFunctions of Vitamin D
 Stimulates intestinal absorption of calciumStimulates intestinal absorption of calcium
and phosphorusand phosphorus
 Collaborates with PTH in the mobilizationCollaborates with PTH in the mobilization
of calcium from boneof calcium from bone
 Stimulates the PTH-dependent reabsorptionStimulates the PTH-dependent reabsorption
of calcium in the distal renal tubulesof calcium in the distal renal tubules
 1,25(OH)1,25(OH)22 D, the biologically active form ofD, the biologically active form of
vitamin D, is best regarded as a steroidvitamin D, is best regarded as a steroid
hormone which acts by binding to a high-hormone which acts by binding to a high-
affinity receptoraffinity receptor

72. Vitamin D DeficiencyVitamin D Deficiency
 Holick et al (2005) reported the results of aHolick et al (2005) reported the results of a
large North American study that assessedlarge North American study that assessed
the vitamin D status of postmenopausalthe vitamin D status of postmenopausal
women receiving therapy to treat or preventwomen receiving therapy to treat or prevent
osteoporosisosteoporosis
 52% of 1536 women had inadequate52% 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 2036% 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 DeficiencyVitamin D Deficiency
 Childhood: RicketsChildhood: Rickets
 epiphyses are openepiphyses are open
 cartilage overgrowthcartilage overgrowth
 Adults:Adults: osteomalaciaosteomalacia
 bone matrix is not calcifiedbone 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 KVitamin K
 Clotting factors VII, IX, and X andClotting factors VII, IX, and X and
prothrombin (II) all require carboxylation ofprothrombin (II) all require carboxylation of
glutamate residues for functional activityglutamate residues for functional activity
 anticoagulant coumadin is a Vitamin Kanticoagulant coumadin is a Vitamin K
antagonistantagonist
 Activation of anticoagulant proteins C and SActivation of anticoagulant proteins C and S
also requires glutamate carboxylationalso requires glutamate carboxylation
 SourcesSources
 endogenous intestinal bacterial floraendogenous intestinal bacterial flora
 dietdiet

76. Vitamin K DeficiencyVitamin K Deficiency
 CausesCauses
 fat malabsorptionfat malabsorption
 reduced gut bacterial florareduced gut bacterial flora
 administration of wide specturm antibioticsadministration of wide specturm antibiotics
 neonatal period before gut is colonizedneonatal period before gut is colonized
 liver disease with reduced recycling of vitamin Kliver disease with reduced recycling of vitamin K
 Effects of vitamin K deficiencyEffects of vitamin K deficiency
 bleeding diathesisbleeding diathesis
 estimated 3% prevalence of vitamin K-estimated 3% prevalence of vitamin K-
dependent bleeding diathesis among neonatesdependent bleeding diathesis among neonates
warrants routine prophylactic vitamin K therapywarrants routine prophylactic vitamin K therapy
for all newbornsfor all newborns