2. Environmental andEnvironmental and
Nutritional PathologyNutritional Pathology
Environment and DiseaseEnvironment and Disease
CommonCommon ExposuresExposures
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
ThresholdThreshold effecteffect
AbsorptionAbsorption at portals of entryat portals of entry
ingestioningestion
inhalationinhalation
skin contactskin contact
DistributionDistribution within the bodywithin the body
MetabolismMetabolism andand ExcretionExcretion
ToxicToxic effectseffects
5. 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
8. 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
9. 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. 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.
12. 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
13. Cigarettes And The WorkplaceCigarettes And The Workplace
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
14. 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
16. 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. 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 cirrhosis, 10-25% of A.H.thought to be a precursor of cirrhosis, 10-25% of A.H.
will go to cirrhosiswill go to cirrhosis
Alcoholic cirrhosisAlcoholic cirrhosis
shrunken nodular liver with uniform small nodulesshrunken nodular liver with uniform small nodules
(micronodular cirrhosis)(micronodular cirrhosis)
19. 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
20.
21.
22.
23.
24. Neurologic Manifestations of AlcoholismNeurologic Manifestations of Alcoholism
Wernicke syndromeWernicke syndrome
confusion, ataxia, and diplopia fromconfusion, ataxia, and diplopia from
ophthalmoplegiaophthalmoplegia
damage todamage to mammillary bodiesmammillary bodies,, cerebellumcerebellum andand
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 direct toxicityresults from thiamine deficiency and direct toxicity
25.
26. 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
27. 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
29. Oral Contraceptives (BCPs)Oral Contraceptives (BCPs)
Increased risk of cervical cancer. Decreased ovarian andIncreased risk of cervical cancer. Decreased ovarian and
endometrial cancer.endometrial cancer.
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
30. 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 showedWHI showed increased risk of breast cancerincreased risk of breast cancer in womenin women
who used HRT combined therapy for 5 yearswho used HRT combined therapy for 5 years
Thromboembolic eventsThromboembolic events
elevated approximated twofoldelevated approximated twofold in HRT users, especiallyin HRT users, especially
within the first 2 yearswithin the first 2 years
Cardiovascular diseaseCardiovascular disease
WHI reportedWHI reported 29% increased risk of myocardial29% increased risk of myocardial
infarctioninfarction, especially during the first year of combined, especially during the first year of combined
HRT useHRT use
31. 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
HasHas analgesic and antipyretic actions but noanalgesic and antipyretic actions but no
anti-inflammatory actionanti-inflammatory action
Large doses may produceLarge doses may produce hepatic necrosishepatic 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
32. AspirinAspirin
Chronic aspirin toxicity (salicylism)Chronic aspirin toxicity (salicylism)
headache, dizziness, ringing in the earsheadache, dizziness, ringing in the ears
((tinnitustinnitus), mental confusion, drowsiness,), mental confusion, drowsiness,
nausea, vomiting, and diarrheanausea, vomiting, and diarrhea
Inhibits cyclooxygenases (COX 1 & 2)Inhibits cyclooxygenases (COX 1 & 2)
Erosive gastritis is a major cause of GIErosive gastritis is a major cause of GI
bleedingbleeding
May be implicated in Reye syndrome (fattyMay be implicated in Reye syndrome (fatty
liver with encephalopathy) in children < 15liver with encephalopathy) in children < 15
years old, especially with influenza andyears old, especially with influenza and
chicken poxchicken pox
33. Cox-1 and Cox-2 InhibitorsCox-1 and Cox-2 Inhibitors
Cyclooxygenase 1 (inhib of COX-1 isCyclooxygenase 1 (inhib of COX-1 is BADBAD))
constitutively expressed and active in the normalconstitutively expressed and active in the normal
platelet (thromboxane A2)platelet (thromboxane A2)
involved in synthesis of gastro-protectiveinvolved in synthesis of gastro-protective
prostaglandinsprostaglandins
Cyclooxygenase 2 (inhib of COX-2 isCyclooxygenase 2 (inhib of COX-2 is GOODGOOD))
induced, especially in inflamed tissueinduced, especially in inflamed tissue
in vessel wall produces prostacyclin (PGIin vessel wall produces prostacyclin (PGI22))
Aspirin and other nonselective NSAIDS inhibitAspirin and other nonselective NSAIDS inhibit
both COX-1 and COX-2both COX-1 and COX-2
35. Indoor Air PollutionIndoor Air Pollution
Carbon Monoxide COCarbon Monoxide CO
Nitrogen Dioxide NONitrogen Dioxide NO22 ((from acid rainfrom acid rain))
Wood SmokeWood Smoke
FormaldehydeFormaldehyde
RadonRadon
Manufactured Mineral FibersManufactured Mineral Fibers
BioaerosolsBioaerosols
36. 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
37. Lead Distribution and ExcretionLead Distribution and Excretion
Lead is taken up by bone and developingLead is taken up by bone and developing
teeth in children (80% to 85%)teeth in children (80% 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
38. Effects of LeadEffects of Lead
High affinity for sulfhydryl groupsHigh affinity for sulfhydryl groups
inhibition of heme biosynthesis with hypochromic anemiainhibition of heme biosynthesis with hypochromic anemia
and basophillic stippling of erythrocytesand 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 of redpotassium ion pumps, leading to decreased survival of red
blood cells (hemolysis), renal damage, and hypertension.blood cells (hemolysis), renal damage, and hypertension.
41. 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
42. 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
43. 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
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
44. Delayed Radiation InjuryDelayed Radiation Injury
Carcinogenesis (atom bomb survivors)Carcinogenesis (atom bomb survivors)
myeloid leukemias peak 5 to 7 years aftermyeloid leukemias peak 5 to 7 years after
exposureexposure
breast and thyroid cancers may show greaterbreast and thyroid cancers may show greater
latencylatency
Vascular effectsVascular effects
endothelial necrosis followed by intimal andendothelial necrosis followed by intimal and
medial fibrosis, often the endothelial cells lookmedial fibrosis, often the endothelial cells look
quite plump and atypical, as do the fibroblasts!quite plump and atypical, as do the fibroblasts!
capillaries may become thrombosed andcapillaries may become thrombosed and
obliterated or ectaticobliterated or ectatic
Parenchymal atrophy and fibrosisParenchymal atrophy and fibrosis
46. 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)
47.
48. GUNSHOT WOUND
Entrance Vs. Exit
Far range Vs. Close range
NOT CLOSE
RANGE
CLOSE RANGE
(POWDER BURNS)
EXIT WOUNDS are
generally SLOPPIER than
ENTRANCE WOUNDS
49. HYPER-THERMIA
HEAT
CRAMPS: Electrolyte loss via sweat (Na+, K+)
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. In this case true “SHOCK” would be
a better term than “STROKE”
50. HYPO-THERMIA
Often in setting of
homelessness or alcoholism
or both
< 90º often fatal, assoc. w.
BRADYCARDIA
ATRIAL FIBRILLATION
51. LIGHTNING/ELECTRICAL
ELECTRIC DISTURBANCES
NEURAL (because nerve is such an EXCELLENT
conductor of electricity)
EKG (like reverse cardioversion)
THERMAL INJURY, depends upon a particular
tissue’s RESISTANCE to electrical flow
“LIGHTNING” MARKS
53. ALTITUDE ILLNESS
Caused by LOW Oxygen Tension
HIGH ALTITUDES (>4000 m [12,000 feet])
OBTUNDATION
INCREASED CAPILLARY PERMEABILITY
ACUTE PULMONARY EDEMA (HAPE)
Q: What is the name of the base camp at Mt. Everest
A: Pulmonary Edema
54. 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
55. 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
56. NUTRITIONNUTRITION & DISEASE& DISEASE
Food SafetyFood Safety
AdditivesAdditives
ContaminantsContaminants
Nutritional DeficienciesNutritional Deficiencies
VitaminsVitamins
MineralsMinerals
ObesityObesity
Diet and DiseaseDiet and Disease
Chemoprevention of CancerChemoprevention of Cancer
57. Vitamin Deficiency and ExcessVitamin Deficiency and Excess
Fat soluble vitaminsFat soluble vitamins
A,A, DD, E,, E, KK
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 stores (fat stores longer than water)Vitamin stores (fat stores longer than water)
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
58. 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..
59. 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
60.
61. 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
62.
63. 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
64. 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
65. 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
All of these topics are notoriously inadequate but represent things you should “know” as they pertain to pathology. Each one is a full course in itself.
An occupational disease is any chronic ailment that occurs as a result of work or occupational activity. OSHA keeps reams of statistics.
This is actually not a bad diagram, fairly logical.
The threshold is the dose at which toxic effects are noted clinically. Below this dose, no adverse effects are noted (sub threshold). This is a basic Pharm 101 graph. The 50% line means HALF of controls will respond. (Similar to an LD50 in rats or humans)
Note well, the last bullet point!
Two good general percentages to remember well.
Many people living in denial (i.e., alcoholics) are violently opposed to defining alcoholism at >2* drinks per day, so probably the TRUEST definition of alcoholism is subjective but involves impairment and degradation of family and social relationships. Most alcoholics living in denial devote most of their brilliant brain power proving to themselves and the world that they are NOT alcoholics.
Note this is NOT a percent, but an actual concentration in mg/dL. Many common devices use a BAC, (Blood Alcohol Concentration, or Blood Alcohol Content) often expressed as a PERCENT. Generally the mg/dL numbers and the BAC numbers are the same except for three decimal points.
Remember this number if you drive.
Note this is a spectrum, which generally progresses with continued drinking: FATTY LIVER ALCOHOL HEPATITIS CIRRHOSIS
Factors of fatty change, all relatively DIFFERENT!
Liver with extensive macrovessicular fat. Nearly all of the hepatocytes in this field are filled with a large clear lipid vacuole. The vacule is clear because the fat has been removed in tissue processing. If you estimate that 50% of the histologic cross area of this slide is “clear”, i.e., “fat”, and the liver weighs, say 2000 gm. (normal = 1400-1800), then you can say 1000 gms are fat, right? Ans:YES
Point out the microvesicular and macrovescicular fat.
Liver with alcoholic hyaline (Mallory bodies), fatty change, and focal hepatocyte necrosis and inflammation. They are highly eosinophilic and thus appear pink on H&E stain. The bodies themselves are made up of intermediate keratin filament proteins that have been ubiquinated, or bound by other proteins such as heat shock proteins, or p62. What is the main difference between alcoholic and viral hepatitis? FAT! Point out the Mallory body!
There are nodules of regenerated hepatocytes (R)surrounded by fibrous bands (F). This pattern of regeneration and repair results from a previous episode or episodes of hepatocellular necrosis which destroyed liver heptocytes and their architectural framework. Alternatively there may have been chronic and ongoing necrosis of hepatocytes. Residual hepatocytes eventually regenerate in nodules surrounded by fibrosis. Does it seem like the central veins are gone? Answer: YES This is often the part where I ask everybody to stand up, but we already did!
Often the term Wernicke-Korsakov syndrome is used to include features of BOTH, but Korsakov is much more serious and much more likely due to direct toxicity rather than just thiamine deficiency, I guess you can say it is. a SPECTRUM. KORSAKOV is WORSE!
Point out periaqueductal grey matter, and “mammillary bodies”, involved in recognition memory and smell.
Pathologists have often made the comment, “Gee, every time I do a cirrhosis autopsy, the arteries seem so remarkably clean”? I dread telling you this.
Estrogens/NSAIDS as exposures, not at all intended to replace a first class pharm course.
COMMON COOMMON concerns almost all
Previous teaching was that estrogen had a cardio-protective effect since it raises high density lipoproteins (HDL, good cholesterol). This is an example of how the use of a surrogate marker can be misleading. *WHI = Women’s Health Initiative, part of NIH
A notable exception to the ischemia centrolobular, toxicity periportal rule of thumb.
ASPIRIN inhibits BOTH Cox-1 AND Cox-2
Eicosenoid pathways. Don’t be spooked by the biochemistry and terminology, only look at the important stuff.
The body often thinks PB++ is really Ca++, an understandable misunderstanding!
Basophilic stippling is RIBOSOMES, gingival “lead” lines are at tooth-gingiva brder, x-ray “lead” lines are the densities at the metaphyses
The first bullet point might answer the question, “How much whole body radiation can kill you?”
Rad:Gy::REM:Sv Everything that can CURE cancer, can cause it too! Gamma knife?
Vascular damage and parenchymal atrophy are seen with therapeutic radiation. A whole body exposure sufficient to cause these changes would be lethal before these changes could appear.
Does it look there there is atherosclerotic “plaque” also on the right? Ans: NO
Injuries can be considered as “exposures” too, to keep in tune with the rest of this chapter.
1) Abrasion (Scrape) 2) Laceration (NOT incision) 3) Contusion (Blunt Trauma), can be INTERNAL too.
Lightning marks are not that common in lightning electrocution, but when you see them, they are practically diagnostic. Would electricity damage non-conducting soft tissues like fat, worse than conducting soft tissues like muscle? Ans: YES
The three different ways pressure changes can be damaging and even fatal.
Related to air/tissue interfaces chiefly.
This is a medical school course in itself, greatly amplified with confusion and deceit and greed, because of commercialism! But we should emphasize the few points that we will not cover elsewhere.
Gut + skin liver kidneys
Name 3 ways Vit-D puts Calcium into the blood: 1,2,3 Gi Bone Kidney
Osteoporosis strongly linked to Vit-D, but remember: Osteoporosis is NOT loss of bone Ca++ , it’s loss of bone MASS
Hypocalcemia is the main trigger of PTH
“ malacia” in pathology usually means “softening”, NOT evil. The main difference between childhood Vit-D deficiency (rickets), and adult Vit-D deficiency (osteomalacia) is cartilage overgrowth vs. bone softening. What is a rosary? (Hail Mary, full of grace…….)