6 Environmental Pathology

Chemical Injury
The two leading causes of illness and death in the United States are tobacco and alcohol use.
Chemical
Injury
The two leading causes of illness and death in the United States are tobacco and alcohol use.
Tobacco use
Table 6-1. Systemic Effects Associate !ith Tobacco "se
System Effects
Cardiovascular Acute myocardial infarction (AMI)
Sudden cardiac death
eri!heral vascular disease
"y!ertension
Central nervous system Stro#es$ intracerebral bleed% subarachnoid hemorrhage
&astrointestinal 'ro!haryngeal cancer$ s(uamous cell carcinoma
U!!er% mideso!hageal cancer$ s(uamous cell carcinoma
&astroeso!hageal reflu) disease$ decreases tone of lower eso!hageal s!hincter
*elayed healing of !e!tic ulcers
ancreatic cancer$ adenocarcinoma
&eneral +ow birth weight% fetal growth retardation
,eutro!hilic leu#ocytosis$ decreased activation of neutro!hil adhesion molecules
*ecreased concentration of ascorbic acid and -.carotenes
&enitourinary Cervical cancer$ s(uamous cell carcinoma
*ecreased testosterone in males
*ecreased estrogen in females
/idney cancer$ renal cell carcinoma
Urinary bladder cancer$ transitional cell carcinoma
Integument Increased facial wrin#ling
Musculos#eletal 'steo!orosis$ due to decreased estrogen in females and decreased testosterone in males
0es!iratory +aryngeal cancer$ s(uamous cell carcinoma
Chronic obstructive !ulmonary disease$ chronic bronchitis% em!hysema
+ung cancer$ s(uamous cell carcinoma% small cell carcinoma% some ty!es of adenocarcinoma
S!ecial senses *ecreased sense of smell and taste
1lindness$ macular degeneration
Cataracts
2. Tobacco is the leading cause of !remature death in the United States.
3. The rate of cigarette smo#ing is increasing in females and decreasing in males.
4. Chemical com!onents of tobacco
a. ,icotine
i. 0a!idly absorbed
ii. Most addictive chemical in tobacco smo#e
iii. Cotinine is the most im!ortant metabolite of nicotine.
Screening test in blood or urine for detecting nicotine
b. olycyclic hydrocarbons are the !rimary carcinogens.
5. Smo#eless tobacco (e.g.% chewing tobacco)
o Can cause nicotine addiction and cancer
2. assive (secondhand) smo#e inhalation
a. &reatest im!act on children
i. Increased ris# of res!iratory and middle ear infections
ii. 6)acerbates asthma
b. Increased ris# for lung cancer and coronary artery disease
7. Systemic effects associated with tobacco use
8. 1eneficial effects of smo#ing cessation
c. 0is# for cardiovascular disease
A!!roaches nonsmo#er after 27 years
bb 0is# for lung cancer
A!!roaches nonsmo#er after 27 years
bb 0is# for stro#e
A!!roaches nonsmo#er after 7 to 27 years
bb 'ther benefits
i. 0educed ris# for cancers of the mouth% laryn)% eso!hagus% !ancreas% and urinary
bladder
ii. Im!roved !ulmonary function regardless of severity of the disease
iii. 0educed ris# for !neumonia% influen9a% and bronchitis
Alcohol abuse
!age 2:;
!age 22:
!age 22:
!age 222
Table 6-#. Systemic Effects Associate !ith Alcohol Abuse
System Effects
Cardiovascular Congestive (dilated) cardiomyo!athy$ due to thiamine deficiency
"y!ertension$ vaso!ressor effects due to increase in catecholamines
Central nervous system
(C,S)
C,S de!ressant$ !articularly cerebral corte) and limbic system
<ernic#e=s syndrome$ confusion% ata)ia% nystagmus due to thiamine deficiency
/orsa#off=s !sychosis$ memory deficits due to thiamine deficiency
Cerebellar atro!hy$ due to loss of ur#in>e cells
Cerebral atro!hy$ due to loss of neurons
Central !ontine myelinolysis$ due to ra!id intravenous fluid correction of hy!onatremia in
an alcoholic
&astrointestinal 'ro!haryngeal and u!!er to mideso!hageal cancer$ s(uamous cell carcinoma
Acute hemorrhagic gastritis
Mallory.<eiss syndrome$ tear of distal eso!hagus due to retching
1oerhaave=s syndrome$ ru!ture of distal eso!hagus due to retching
6so!hageal varices$ caused by !ortal vein hy!ertension in alcoholic cirrhosis
Acute and chronic !ancreatitis
&eneral ?etal alcohol syndrome$ mental retardation% microce!haly% atrial se!tal defect
&enitourinary Testicular atro!hy$ decreased testosterone% decreased s!ermatogenesis
Increased ris# for s!ontaneous abortion
"emato!oietic ?olate deficiency$ decreased reabsor!tion in >e>unum@ macrocytic anemia
Ac(uired sideroblastic anemia$ microcytic anemia due to defect in heme synthesis
Anemia chronic disease$ most common anemia in alcoholics
"e!atobiliary ?atty liver% alcoholic he!atitis% cirrhosis
"e!atocellular carcinoma$ !ree)isting cirrhosis
Integument or!hyria cutanea tarda$ !hotosensitive bullous s#in lesions
Musculos#eletal 0habdomyolysis$ direct alcohol effect on muscle
eri!heral nervous system eri!heral neuro!athy$ due to thiamine deficiency
!age 222
!age 223
2. Alcohol metabolism
a. Absor!tion occurs in the stomach (37A)
b. Metabolism occurs in the stomach and liver
Alcohol dehydrogenase is the rate.limiting en9yme.
c. Im!ortant !roducts of alcohol metabolism
bb 0educed nicotinamide adenine dinucleotide (,A*")
Causes conversion of !yruvate to lactate
Causes conversion of acetoacetate to -.hydro)ybutyrate
Causes conversion of dihydro)yacetone !hos!hate to glycerol 4.
!hos!hate
bbb Acetyl coen9yme A (acetyl CoA)
Used to synthesi9e fatty acids for triglyceride synthesis
Used to synthesi9e #etoacids
b. Alcohol induction of the cytochrome .57: en9yme system
Increases alcohol metabolism% which increases the tolerance for alcohol
b. +egal blood alcohol limit for driving
0anges from B: to 2::mgCd+
bb 0is# factors for alcohol.related disease
a. Amount
b. *uration
c. ?emale se)
bb *ecreased gastric alcohol dehydrogenase levels
Causes higher alcohol levels in women than in men% even after drin#ing
the same amount of alcohol
bbb &enetic susce!tibility
3. Systemic effects associated with alcohol abuse
4. +aboratory findings in alcohol abuse
a. ?asting hy!oglycemia
6)cess ,A*" causes !yruvate (substrate for gluconeogenesis) to convert to
lactate.
d. Increased anion ga! metabolic acidosis
bb +actic acidosis
bbb -."ydro)ybutyric #etoacidosis
6)cess acetyl CoA is converted to -.hydro)ybutyrate.
b. 'ther findings
bb "y!eruricemia
+actic acid and -.hydro)ybutyric acid com!ete with uric acid for e)cretion
in the !ro)imal tubules.
bbb "y!ertriglyceridemia
Increased !roduction of glycerol 4.!hos!hate% the #ey substrate for
triglyceride synthesis in the liver
bbbb Serum as!artate aminotransferase (AST) greater than serum alanine
aminotransferase (A+T) in liver disease
Alcohol is a mitochondrial to)in that causes release of AST% which is
located in the mitochondria.
bvb Increased serum D.glutamyltransferase (&&T)
Alcohol induces hy!er!lasia of the smooth endo!lasmic reticulum
causing increased synthesis of &&T.
'ther drugs of abuse
Table 6-$. Selecte %rugs of Abuse an Their Effects
%rug %escri&tion To'ic Effects
Cocaine Stimulant Mydriasis% tachycardia% hy!ertension
Associated ris# of AMI% C,S infarction% !erforation of nasal se!tum
(intranasal use)
"eroin '!iate Miotic !u!ils% noncardiogenic !ulmonary edema (frothing from mouth)%
focal segmental glomerulosclerosis (ne!hrotic syndrome)
&ranulomatous reactions in s#in and lungs from material used to EcutE
(dilute) drug
Mari>uana
(Cannabis)F
T"C.containing
!sychoactive stimulant
0ed con>unctiva% eu!horia% delayed reaction time
MT 1y.!roduct of synthesis of
me!eridine
Irreversible ar#inson=s disease$ cytoto)ic to neurons in nigrostriatal
do!aminergic !athways
FUsed medically to decrease nausea and vomiting associated with chemothera!y and to decrease intraocular !ressure in glaucoma.
AMI% myocardial infarction@ C,S% central nervous system@ MT% 2.methyl.5.!henyl.2%3%4%8.tetrahydro!yridine@ T"C% G
;
.
tetrahydrocannabinol.
!age 223
!age 224
Sedatives% stimulants% hallucinogens
2. C,S effects of long.term drug abuse
a. *amage to neurotransmitter rece!tor sites
b. Cerebral atro!hy (e.g.% alcohol)
3. Com!lications of intravenous drug use (IH*U)
a. "e!atitis 1
b. "uman immunodeficiency virus ("IH)
c. Infective endocarditis
Caused by Staphylococcus aureus
d. Tetanus
Com!lication of Es#in !o!!ing
Adverse effects of thera!eutic drug use
Table 6-(. Averse )eactions Associate !ith Thera&eutic %rug "se
)eaction %rug*s+
,loo %yscrasias
A!lastic anemia Chloram!henicol% al#ylating agents
"emolytic anemia enicillin% methyldo!a% (uinidine
Macrocytic anemia Methotre)ate (most common)% !henytoin% oral contrace!tives% 7.fluorouracil
latelet dysfunction As!irin% other ,SAI*s
Thrombocyto!enia "e!arin (most common)% (uinidine
Cariac
Congestive cardiomyo!athy *o)orubicin% daunorubicin
Central -ervous System
Tinnitus% vertigo Salicylates
Cutaneous
Angioedema AC6 inhibitors
Maculo!a!ular rash enicillin
hotosensitive rash Tetracycline
Urticaria enicillin
.astrointestinal
"emorrhagic gastritis Iron% salicylates
/e&atic
Cholestasis 'ral contrace!tives% estrogen% anabolic steroids
?atty change Amiodarone% tetracycline% methotre)ate
"e!atic adenoma 'ral contrace!tives
+iver necrosis Acetamino!hen (most common)% isonia9id% salicylates% halothane% iron
Pulmonary
Asthma As!irin% other ,SAI*s
Interstitial fibrosis 1leomycin% busulfan% nitrofurantoin% methotre)ate
Systemic
*rug.induced lu!us rocainamide% hydrala9ine
AC6% angiotensin.converting en9yme@ ,SAI*% nonsteroidal anti.inflammatory drug.
!age 224
!age 225
2. Acetamino!hen
a. Conversion to free radicals in the liver
b. May result in damage to the liver (e.g.% fulminant he!atitis)
c. May result in damage to the #idneys (e.g.% renal !a!illary necrosis)
3. As!irin (acetylsalicylic acid) overdose
a. &eneral sym!toms
Tinnitus% vertigo% change in mental status (confusion% sei9ures)% tachy!nea
b. Acid.base disorders
bb 0es!iratory al#alosis may occur initially (within 23.35 hours)
*ue to direct stimulation of the res!iratory center
0es!iratory acidosis may occur as a late finding.
bbb Shift to metabolic acidosis with an increased anion ga!
'ccurs more often in children
bbbb Mi)ed !rimary res!iratory al#alosis and metabolic acidosis
'ccurs more often in adults
b. "y!erthermia
bb Salicylates damage the inner mitochondrial membrane.
bbb ')idative energy is released as heat% not as adenosine tri!hos!hate.
c. "emorrhagic gastritis% fulminant he!atitis
3. *isorders associated with e)ogenous estrogen without !rogestin
a. Cancer (adenocarcinoma)
6ndometrium% breast
b. Henous thromboembolism
bb 6strogen decreases synthesis of antithrombin III (ATIII).
ATIII normally neutrali9es coagulation factors.
bbb 6strogen increases synthesis of factors I (fibrinogen)% H% and HIII.
b. Intrahe!atic cholestasis with >aundice
c. Cardiovascular effects
Myocardial infarction (MI)% stro#e
bb *isorders associated with oral contrace!tives
o Contain estrogen and !rogestin
a. Cancer
bb 1reast (adenocarcinoma)
bbb Cervi) (s(uamous cell carcinoma)
b. Henous thromboembolism
bb Similar !athogenesis to estrogen without !rogestin
c. ?olate deficiency
bb *ecreases >e>unal reabsor!tion of folate
d. "y!ertension
bb *ue to increased synthesis of angiotensinogen
e. "e!atic adenoma
bb 0is# of intra!eritoneal hemorrhage
f. Intrahe!atic cholestasis with >aundice
g. Cholesterol gallstones
bb 6strogen increases cholesterol e)cretion in bile.
In>uries caused by environmental chemicals
Table 6-0. Environmental Chemicals an Associate To'ic Effects
Chemical Source To'ic Effects
Arsenic esticides% animal di!s *iarrhea% transverse bands in nails (Mee=s lines)% convulsions
S(uamous cell carcinoma of s#in% liver angiosarcoma% lung
cancer
Asbestos Insulation% roofing material rimary lung cancer% mesothelioma
1en9ene Solvent Acute leu#emia% a!lastic anemia
Carbon mono)ide Automobile e)haust% house
fires
"eadache (first sign)% cherry.red s#in% coma
*ecreased o)ygen saturation
Coral sna#e bite ,euroto)in$ binds to
!resyna!tic nerve terminals
and acetylcholine
Sna#e has Ered on yellowE bands
To)ic effects$ mydriasis% !aralysis% and res!iratory failure
Crotaline bite Henom cyto.hemo.neuroto)ic 0attlesna#e% co!!erhead% water moccasin
To)ic effects$ local edema% shoc#% disseminated intravascular
coagulation (*IC)
Cyanide "ouse fires Sei9ures
6thylene glycol Antifree9e
6nd !roduct$ o)alic acid
Increased anion ga! metabolic acidosis
Acute renal failure
Iso!ro!yl alcohol 0ubbing alcohol
6nd !roduct$ acetone
*ee! coma
Latrodectus biteF (blac#
widow s!ider)
,euroto)in ainful bite
Muscle cram!sCs!asms$ occur in thighs and abdomen and
simulate an acute abdomen
+ead +ead.based !aint% batteries%
metal casting
Microcytic anemia with coarse baso!hilic sti!!ling%
ne!hroto)icity in !ro)imal tubule
Loxosceles bite
I
(brown
recluse s!ider)
,ecroto)in ainless to mildly !ainful bite
ainful reddish blister with blue.white halo followed by
e)tensive s#in necrosis
Mercury ?ish% insecticides *iarrhea% constricted visual fields% ne!hroto)icity in !ro)imal
tubule
Methanol <indow.washing fluid
6nd !roduct$ formic acid
Increased anion ga! metabolic acidosis
1lindness due to o!tic atro!hy
'rgano!hos!hates esticides Miotic !u!ils% !aralysis
*ecreased serum and red blood cell cholinesterase levels
olyvinyl chloride lastics industry +iver angiosarcoma
Scor!ion sting ,euroto)in oisonous s!ecies in Southwestern deserts (Centruroides
s!.)
To)ic effects$ initially has !ainful sting followed by numbness%
hy!ertension% ascending motor !aralysis leading to death@
may cause acute !ancreatitis
Physical Injury
Mechanical in>ury
!age 228
!age 22J
2. Ty!es of s#in wounds
a. Contusion (bruise)
1lunt force in>ury to blood vessels with subse(uent esca!e of blood into tissue
b. Abrasion
Su!erficial e)coriation of the e!idermis
c. +aceration
Kagged tear with intact bridging blood vessels% nerves% and connective tissue
d. Incision
<ound with shar! margins with severed bridging blood vessels
3. &unshot wounds
a. Contact wounds
bb Stellate.sha!ed
bbb Contain soot and gun!owder (fouling)
b. Intermediate.range wounds
owder tattooing (sti!!ling) of the s#in around the entrance site
b. +ong.range wounds
No !owder tattooing
c. 6)it wounds
Ty!ically larger and more irregular than entrance wounds
bb Motor vehicle collisions
a. ?re(uently cause mechanical in>ury
b. ?re(uently alcohol.related
Mechanical in>ury
!age 228
!age 22J
2. Ty!es of s#in wounds
a. Contusion (bruise)
1lunt force in>ury to blood vessels with subse(uent esca!e of blood into tissue
b. Abrasion
Su!erficial e)coriation of the e!idermis
c. +aceration
Kagged tear with intact bridging blood vessels% nerves% and connective tissue
d. Incision
<ound with shar! margins with severed bridging blood vessels
3. &unshot wounds
a. Contact wounds
bb Stellate.sha!ed
bbb Contain soot and gun!owder (fouling)
b. Intermediate.range wounds
owder tattooing (sti!!ling) of the s#in around the entrance site
b. +ong.range wounds
No !owder tattooing
c. 6)it wounds
Ty!ically larger and more irregular than entrance wounds
bb Motor vehicle collisions
a. ?re(uently cause mechanical in>ury
b. ?re(uently alcohol.related
Thermal in>ury
Table 6-6. /eat Injuries1
Ty&e of Injury ,oy Tem&erature S2in 3ental Status
"eat cram!s 4J.:LC (;B.8L?) Moist and cool ,ormal
"eat e)haustion M4J.BLC (M2::L?) Sweating Minimally altered
"eat stro#e M5:LC (M2:5L?) *ry (anhidrosis) Im!aired consciousness
F"eat in>ury is e)acerbated by high humidity.
!age 22J
!age 22B
2. 1urns
a. ?irst.degree
i. ainful !artial.thic#ness burns (e.g.% sunburn)
ii. "eal without scarring
b. Second.degree
i. ainful !artial.thic#ness burns
ii. *amage to entire e!idermis
iii. 1lister formation
iv. Usually heal without scarring
c. Third.degree
i. ainless full.thic#ness burns
ii. 6)tensive necrosis of e!idermis and adne)a
iii. Scarring is inevitable.
/eloids (e)aggerated scars) commonly occur.
otential for develo!ing s(uamous cell carcinoma
iv. "ealing of e!ithelial surface
roliferation of residual e!ithelium located at burn margins and lining
adne)al structures
d. Com!lications
i. Infection
Se!sis due to Pseudomonas aeruginosa is the most common cause of
death.
ii. Curling=s ulcers (stomach)
3. "eat in>uries
4. ?rostbite
a. athogenesis
i. +ocali9ed tissue in>ury caused by direct damage (e.g.% ice crystalli9ation in cells)
ii. Indirect damage (e.g.% vasodilation% thrombosis)
b. Clinical findings
i. +oss of !ain sensation
ii. <a)y a!!earance
6lectrical in>ury
2. roduced by alternating current (AC) and direct current (*C)
a. AC is more dangerous than *C.
b. AC !roduces tetanic contractions
c. *C !roduces a single shoc#
3. <et s#in decreases resistance% which increases current.
4. *ry s#in increases resistance% which decreases current.
5. Tissue damage increases with increased voltage and duration of e)!osure.
7. Current moving from the left arm to the right leg
a. Most dangerous route% because it affects the heart
b. *eath results from cardiores!iratory arrest.
*rowning
2. Common cause of death in children from 2 to 25 years of age
3. Terms
a. *rowning refers to death by suffocation from immersion in li(uid.
b. ,ear drowning is defined as survival following as!hy)ia secondary to submersion.
c. <et drowning
i. ;:A of cases
ii. Initial laryngos!asm on contact with water followed by rela)ation and as!iration of
water
d. *ry drowning is characteri9ed by intense laryngos!asm without as!iration.
4. atho!hysiology
a. "y!o)emia with damage to central nervous system% heart% #idneys
b. +ung as!iration (fresh or salt water)
i. *amages ty!e II !neumocytes% which decreases surfactant !roduction
ii. *iffuse alveolar damage
c. As!hy)ia in dry drowning
d. +ung in>ury and hy!o)emia in wet drowning
5. Cold water drowning
a. Activates diving refle)
Shunts blood from the !eri!hery to the central core
b. "y!othermia decreases metabolic demand.
"igh altitude in>ury
2. &eneral
a. '3 concentration 32A
b. *ecreased barometric !ressure
c. "y!o)emic stimulus for res!iratory al#alosis
*ecrease in aco3 causes a corres!onding increase in ao3.
d. 0es!iratory al#alosis activates glycolysis
bb Increased synthesis of 3%4.bis!hos!hoglycerate
bbb 0ight.shifts '3.binding curve
Increases release of '3 to tissue
3. Acute mountain sic#ness
a. Usually occurs at above B::: feet (355:m) elevation
b. 0is# factors
bb Increased rate of ascent
bbb 6)treme altitude
c. Clinical findings
bb "eadache (most common)
bbb ?atigue% di99iness% anore)ia% insomnia
bbbb Acute !ulmonary edema
,oncardiogenic (e)udate)
bvb Acute cerebral edema
Ata)ia% stu!or% coma
d. Treatment
Immediate descent (if severe com!lications)
)aiation Injury
Ioni9ing radiation in>ury
!age 22;
!age 23:
6)am!les.).rays% D.rays
2. atho!hysiology
a. In>ury correlates with ty!e of radiation% cumulative dose% and amount of surface area
e)!osed.
b. *irect or indirect *,A in>ury occurs via formation of hydro)yl free radicals.
3. Tissue susce!tibility
a. Most radiosensitive tissues (highest mitotic activity)
i. +ym!hoid tissue (most sensitive)
ii. 1one marrow
iii. Mucosa of gastrointestinal tract% germinal tissue
b. +east radiosensitive tissues
i. 1one (least sensitive)
ii. 1rain% muscle% s#in
4. 0adiation effects in different tissues
a. "emato!oietic
i. +ym!ho!enia (first change)
ii. Thrombocyto!enia
iii. 1one marrow hy!o!lasia
b. Hascular
i. Thrombosis (early)% fibrosis (late)
ii. Ischemic damage
c. 6!idermal
i. Acute effects are erythema% edema% blistering
ii. Chronic effect is radiodermatitis
otential for s(uamous cell carcinoma
d. &astrointestinal
i. Acute effect is diarrhea.
ii. Chronic effects are adhesions with !otential for bowel obstruction.
5. Cancers caused by radiation
a. Acute leu#emia (most common)
b. a!illary carcinoma of the thyroid
c. 'steogenic sarcoma
Ioni9ing radiation in>ury
!age 22;
!age 23:
6)am!les.).rays% D.rays
2. atho!hysiology
a. In>ury correlates with ty!e of radiation% cumulative dose% and amount of surface area
e)!osed.
b. *irect or indirect *,A in>ury occurs via formation of hydro)yl free radicals.
3. Tissue susce!tibility
a. Most radiosensitive tissues (highest mitotic activity)
i. +ym!hoid tissue (most sensitive)
ii. 1one marrow
iii. Mucosa of gastrointestinal tract% germinal tissue
b. +east radiosensitive tissues
i. 1one (least sensitive)
ii. 1rain% muscle% s#in
4. 0adiation effects in different tissues
a. "emato!oietic
i. +ym!ho!enia (first change)
ii. Thrombocyto!enia
iii. 1one marrow hy!o!lasia
b. Hascular
i. Thrombosis (early)% fibrosis (late)
ii. Ischemic damage
c. 6!idermal
i. Acute effects are erythema% edema% blistering
ii. Chronic effect is radiodermatitis
otential for s(uamous cell carcinoma
d. &astrointestinal
i. Acute effect is diarrhea.
ii. Chronic effects are adhesions with !otential for bowel obstruction.
5. Cancers caused by radiation
a. Acute leu#emia (most common)
b. a!illary carcinoma of the thyroid
c. 'steogenic sarcoma
,onioni9ing radiation
2. Ultraviolet light 1 (UH1) is most damaging
a. athogenesis
i. yrimidine dimers distort the *,A heli)
ii. Inactivation of the TP53 su!!ressor gene
iii. Activation of the RAS oncogene
b. &eneral effects
i. Sunburn
ii. Actinic (solar) #eratosis
recursor of s(uamous cell carcinoma (3.7A of cases)
iii. Corneal burns from s#iing
c. Cancers
i. 1asal cell carcinoma (most common)
ii. S(uamous cell carcinoma% malignant melanoma
3. 6ffects of other ty!es of radiation
a. +aser radiation
Third.degree burns
b. Microwave radiation
S#in burns% cataracts% sterility
c. Infrared radiation
S#in burns% cataracts