8/9/2019 genPathEnv

1/81

Environmental PathologyEnvironmental Pathology

Ma. Minda Luz M. Manuguid, M.D.Ma. Minda Luz M. Manuguid, M.D.

8/9/2019 genPathEnv

2/81

Environmental PathologyEnvironmental Pathology

Disorders of nutritionDisorders of nutrition Air pollutionAir pollution Chemical & drug injuriesChemical & drug injuries

Physical injuries

infectious diseaseinfectious disease

8/9/2019 genPathEnv

3/81

N utritional DiseaseN utritional Disease

MALNUTRITIONMALNUTRITION-- usually used as ausually used as asynonym of Undernutrition, but may besynonym of Undernutrition, but may be

caused by dietary excesses as well.caused by dietary excesses as well.

Undernutrition is globally the mostUndernutrition is globally the mostimportant category of Environmentalimportant category of Environmental

DiseaseDisease OvernutritionOvernutrition-- predisposes to illnesses &predisposes to illnesses &

increased mortalityincreased mortality

8/9/2019 genPathEnv

4/81

Etiology ofEtiology ofmalnutritionmalnutrition

Primary: lack of foodPrimary: lack of food-- esp. Proteinesp. Protein

Secondary:Secondary:

Reduced intakeReduced intake-- poor dentition; dysphagia;poor dentition; dysphagia;systemic dses w/ anorexia; bizarre/restrictedsystemic dses w/ anorexia; bizarre/restricteddiets; Anorexia nervosadiets; Anorexia nervosa

MalabsorptionMalabsorption-- biliary/pancreatic dses;biliary/pancreatic dses;enteric malabsorption syndromes;enteric malabsorption syndromes;pernicious anemia (vit B12 malabsorption)pernicious anemia (vit B12 malabsorption)

8/9/2019 genPathEnv

5/81

Secondary MalnutritionSecondary Malnutrition Increased requirementsIncreased requirements-- rapid growth periods (infancy,rapid growth periods (infancy,

childhood, adolescence); pregnancy; trauma/woundchildhood, adolescence); pregnancy; trauma/woundhealing; burns; excessive losses (enteropathies,healing; burns; excessive losses (enteropathies,

nephropathies)nephropathies) Special categoriesSpecial categories-- TPN (total parenteral /iV nutrition);TPN (total parenteral /iV nutrition);

drug interference with absorption; genetic metabolicdrug interference with absorption; genetic metabolicdisordersdisorders

******Overt morphologic lesions are relatively lateOvert morphologic lesions are relatively latemanifestations & may be preceded for long periods ofmanifestations & may be preceded for long periods oftime by functional deficitstime by functional deficits.***.***

8/9/2019 genPathEnv

6/81

Protein-Calorie malnutrition /

Protein-Energy malnutritionworldwide incidenceworldwide incidence

mostly affects childrenmostly affects children

KwashiorkorKwashiorkor-- mainlyProtein deficiencymainlyProtein deficiency

MarasmusMarasmus-- mainly Carbohydrate deficiencymainly Carbohydrate deficiency

common features:common features: growth failure;growth failure;

impairment of the immune response &impairment of the immune response &increased susceptibility to infections;increased susceptibility to infections;

anemia; hypoplastic bone marrowanemia; hypoplastic bone marrow

thymus & lymph node atrophythymus & lymph node atrophy

8/9/2019 genPathEnv

7/81

Kwashiorkor & MarasmusApathyApathy;; AnorexiaAnorexia

moonfacemoonface-- round,round,edematousedematous

AnasarcaAnasarca bipedalbipedalpitting edemapitting edema-- lowlowserum Albuminserum Albumin

Fatty hepatomegalyFatty hepatomegaly

Flaky paint skinFlaky paint skinlesionslesions

Flag signFlag sign on hairon hair

GI mucosal atrophyGI mucosal atrophy

AlertnessAlertness;;HungerHunger

old mans faceold mans face--pinched, wizenedpinched, wizened

skin & bones,skin & bones,broomstick limbsbroomstick limbs--muscle wasting; loss ofmuscle wasting; loss ofsubcutaneous fatsubcutaneous fat

Cerebral atrophy;Cerebral atrophy;reduced number ofreduced number ofneuronsneurons

Other organ atrophyOther organ atrophy

8/9/2019 genPathEnv

8/81

Kwashiorkor& Marasmus

flaky paint dermatosis cerebral atrophy

flag sign-hair reduced number of

Ascites; intestinal parasitism neurons

8/9/2019 genPathEnv

9/81

Nutritional excess: Obesity

too much foodtoo much foodand/or too littleand/or too little

activityactivity Storage of excessStorage of excess

calories in fat depotscalories in fat depots

GeneticGenetic

predispositionpredisposition--minimal roleminimal role

8/9/2019 genPathEnv

10/81

Obesity Insulin resistanceInsulin resistance Diabetes mellitus IIDiabetes mellitus II

HypertensionHypertension

Coronary heart dse.Coronary heart dse.

HyperlipidemiaHyperlipidemia

Cholesterol gallstonesCholesterol gallstones

OsteoarthritisOsteoarthritis,, esp. kneesesp. knees

Pickwickian syndromePickwickian syndrome

Excess mortalityExcess mortality

assoc w/ breast,colon CAassoc w/ breast,colon CA

8/9/2019 genPathEnv

11/81

Vitamins

Vitamins are organic micronutrients essentialVitamins are organic micronutrients essentialfor health ; they act as critical catalytic cofor health ; they act as critical catalytic co--

factors or prosthetic groups on enzymes in vitalfactors or prosthetic groups on enzymes in vitalmetaboloic reactionsmetaboloic reactions

FatFat--soluble vitamins : vit A, vit D, vit E & vit Ksoluble vitamins : vit A, vit D, vit E & vit K

WaterWater--soluble Vitamins : vit C, vit B1, B2, B6,soluble Vitamins : vit C, vit B1, B2, B6,B12, Niacin, Panthotenic acid; Biotin; Folic acidB12, Niacin, Panthotenic acid; Biotin; Folic acid

8/9/2019 genPathEnv

12/81

Fat-solubleVitamins:

A, D, E, K need fat, bile salts, & pancreatic enzymesneed fat, bile salts, & pancreatic enzymes

to be absorbed in the GITto be absorbed in the GIT

can be stored in the bodycan be stored in the body

can give rise to toxicity syndromescan give rise to toxicity syndromes

not easily destroyed bynot easily destroyed by cooking

8/9/2019 genPathEnv

13/81

Fat-soluble vitamins: ADEK

vitamin A Vitamin AVitamin A-- retinol; retinoic acid; retinalretinol; retinoic acid; retinal

sourcessources: eggs, butter, meat, whole milk, fish: eggs, butter, meat, whole milk, fish

liver; carotenoids, includingliver; carotenoids, including --carotene, incarotene, inleafy green & yellow vegetables: spinach,leafy green & yellow vegetables: spinach,carrots, sweet potatoes, squashcarrots, sweet potatoes, squash

actionaction: maintains integrity of mucosal: maintains integrity of mucosal

membranes; needed in vision, esp. dark vision;membranes; needed in vision, esp. dark vision;enhances immunity to infections esp. inenhances immunity to infections esp. inchildren; is an antichildren; is an anti--oxidant (antioxidant (anti--cancer)cancer)

storagestorage: Liver: Liver

8/9/2019 genPathEnv

14/81

Vitamin A deficiency NyctalopiaNyctalopia-- night blindnessnight blindnessusually the firstusually the first

symptomsymptom

Squamous metaplasiaSquamous metaplasia of mucosaeof mucosae

X

erophthalmiaX

erophthalmia-- conjunctival keratinizationconjunctival keratinization KeratomalaciaKeratomalacia-- corneal softening & ulcerationcorneal softening & ulcerationcorneal scarringcorneal scarring blindnessblindness

itots spotsBitots spots-- graygray--white plaques of piledwhite plaques of piled--upup

squamous cellssquamous cells Follicular hyperkeratosisFollicular hyperkeratosis;;AcneAcne

Impaired immunityImpaired immunityin chidren,in chidren, susceptibility tosusceptibility toinfections, esp. measlesinfections, esp. measles

8/9/2019 genPathEnv

15/81

H ypervitaminosis A Headaches; nausea; vomiting; diarrhea;Headaches; nausea; vomiting; diarrhea;

irritability; drowsiness; alopeciairritability; drowsiness; alopecia Lymphadenopathy; immunologicLymphadenopathy; immunologic

abnormalitiesabnormalities

Bony hyperostosisBony hyperostosis Hypercarotenemia; yellowHypercarotenemia; yellow--orangeorange

discoloration of skin but not the scleraediscoloration of skin but not the sclerae In infants: premature closeure of fontanelsIn infants: premature closeure of fontanels

Synthetic retinoids given to pregnant womenSynthetic retinoids given to pregnant womenpredispose to congenital malformations of thepredispose to congenital malformations of thechild.child.

8/9/2019 genPathEnv

16/81

V itamin D

Vitamin DVitamin D Ergosterol; CalcitriolErgosterol; Calcitriol

sourcessources::

endogenousendogenous synthesis in skin exposed tosynthesis in skin exposed toUV light:UV light: 77--dehydrocholesteroldehydrocholesterolvit Dvit D

exogenous/dietaryexogenous/dietary: deep sea fish; grains;: deep sea fish; grains;fortified dairy productsfortified dairy products

actionsactions: maintenance of adequate Calcium: maintenance of adequate Calcium& Phosphate levels for normal bone& Phosphate levels for normal bonemineralizationmineralization

8/9/2019 genPathEnv

17/81

Vitamin D : deficiency & excess

deficiencydeficiency: Inadequate bone mineralization;: Inadequate bone mineralization;

in childrenin children-- RicketsRickets inadequate provisionalinadequate provisionalcalcification of epiphyseal cartilagecalcification of epiphyseal cartilage impairedimpaired

bone growth = bowleggedness, pigeon breastbone growth = bowleggedness, pigeon breastdeformity, Harrisons groovedeformity, Harrisons groove

inin adults- OsteomalaciaOsteomalacia osteopeniaosteopenia------

susceptibility to fractures, most often of thesusceptibility to fractures, most often of the

vertebrae, hips, wrists, ribsvertebrae, hips, wrists, ribsExcessExcess:: Hypercalcemia:Hypercalcemia:

metastatic calcificationmetastatic calcification

renal calculirenal calculi

8/9/2019 genPathEnv

18/81

V itamin E Vitamin EVitamin E-- tocopherols; tocotrienols; mosttocopherols; tocotrienols; most

potent ispotent is --tocopheroltocopherol

sourcessources: vegetables; grains & their oils; fish,: vegetables; grains & their oils; fish,

nutsnutsactionaction: ANTI: ANTI--OXIDANTOXIDANT-- protects cellularprotects cellular& subcellular polyunsaturated membrane& subcellular polyunsaturated membrane

fatty acidsfatty acidsabsorptionabsorption: requires fat: requires fat

storagestorage: adipose tissue; liver, muscle: adipose tissue; liver, muscle

8/9/2019 genPathEnv

19/81

V itamin E

deficiency & excess Vitamin E deficiency:Vitamin E deficiency: spinocerebellar degenerationspinocerebellar degeneration-- dysarthria;dysarthria;

ophthalmoplegia; ataxia; loss of position & vibrationophthalmoplegia; ataxia; loss of position & vibration

sense; loss of pain sensationsense; loss of pain sensation Skeletal muscle changesSkeletal muscle changes-- to absent tendon reflexesto absent tendon reflexes

Hemolytic anemia in infantsHemolytic anemia in infants

Pigmented retinopathyPigmented retinopathy

Vitamin E excess:Vitamin E excess: gastrointestinal disturbancesgastrointestinal disturbances

8/9/2019 genPathEnv

20/81

Vitamin K

*sources:*sources:

EndogenousEndogenous --made in the body by normalmade in the body by normalintestinal bacterial flora (acidophilus)intestinal bacterial flora (acidophilus)

ExogenousExogenous-- green leafy vegetables, liver, milk,green leafy vegetables, liver, milk,vegetable oils, egg yolks, tomatoes, whole grains,vegetable oils, egg yolks, tomatoes, whole grains,seaweed, oats and meat.seaweed, oats and meat.

*storage: Liver & Bones**storage: Liver & Bones*

*actions : needed in the formation of clotting*actions : needed in the formation of clottingfactors II, VII, IX, X (Prothrombin complex);factors II, VII, IX, X (Prothrombin complex);also maintains normal bone densityalso maintains normal bone density

8/9/2019 genPathEnv

21/81

Vitamin K

deficiency & excess deficiencydeficiency::

APCD: acquiredProthrombin complexAPCD: acquiredProthrombin complex

deficiencydeficiency-- in infants purely breastfed &in infants purely breastfed &born at home & in adults on antibioticborn at home & in adults on antibiotictherapytherapy-- bleeding diathesisbleeding diathesis-- into skin,into skin,

umbilicus, visceraumbilicus, viscera toxicitytoxicity: rare: rare-- flushing, sweating,flushing, sweating,

jaundice and anemiajaundice and anemia

8/9/2019 genPathEnv

22/81

Water-soluble vitamins:

vit B complex & vit C easily lost during cooking and processing.easily lost during cooking and processing. excess quantities of most, except vits B6 & B12, are notexcess quantities of most, except vits B6 & B12, are not

stored by the body & are readily excreted in urine, sostored by the body & are readily excreted in urine, so

foods bearing them must be consumed frequentlyfoods bearing them must be consumed frequently generally nontoxic when present in excess of needs,generally nontoxic when present in excess of needs,although symptoms may be reported in people takingalthough symptoms may be reported in people takingmegadoses of niacin, vitamin C, or pyridoxine (vit B6).megadoses of niacin, vitamin C, or pyridoxine (vit B6).

all the B vitamins function as coenzymes or cofactors,all the B vitamins function as coenzymes or cofactors,assisting in the activity of important enzymes andassisting in the activity of important enzymes andallowing energyallowing energy--producing reactions to proceed normally.producing reactions to proceed normally.

any deficiency mostly affects growing or rapidlyany deficiency mostly affects growing or rapidlymetabolizing tissues such as skin, blood, the digestivemetabolizing tissues such as skin, blood, the digestivetract, and the nervous systemtract, and the nervous system

8/9/2019 genPathEnv

23/81

V itamin B1: Thiamine SourcesSources: Pork/pork products, beef, liver,: Pork/pork products, beef, liver,

yeast/baked products, enriched and whole grainyeast/baked products, enriched and whole graincereals, nuts & seeds, milk, leafy greencereals, nuts & seeds, milk, leafy green

vegetablesvegetables

DeficiencyDeficiency:: dry Beri Beri:dry Beri Beri: anorexia, weight loss, weakness,anorexia, weight loss, weakness,peripheral neuropathyperipheral neuropathy

wet Beriwet Beri--beriberi: anasarca; high: anasarca; high--output cardiac failureoutput cardiac failure(dilated, flabby heart)(dilated, flabby heart)

WernickeWernicke--Korsakoff syndromeKorsakoff syndrome: in chronic alcoholics:: in chronic alcoholics:staggered gait, crossed eyes, dementia, disorientation,staggered gait, crossed eyes, dementia, disorientation,memory lossmemory loss

ToxicityToxicity: none reported: none reported

8/9/2019 genPathEnv

24/81

V itamin B2: Riboflavin

SourcesSources: Milk, eggs, mushrooms, whole grains,: Milk, eggs, mushrooms, whole grains,enriched grains, green leafy vegetables, yeast,enriched grains, green leafy vegetables, yeast,liver, and oily fishliver, and oily fish

deficiencydeficiency:: AriboflavinosisAriboflavinosis: inflammation of: inflammation oftongue (tongue (glossitisglossitis), cracks at corners of mouth), cracks at corners of mouth((cheilosischeilosis), stomatitis, dermatitis,), stomatitis, dermatitis,

conjunctivitis, growth retardation, cornealconjunctivitis, growth retardation, cornealvascularization, nerve damagevascularization, nerve damage

toxicitytoxicity: none reported: none reported

8/9/2019 genPathEnv

25/81

Vit B3: Nicotinic acid /

Niacin /Niacinamide SourcesSources: meat, poultry (chicken), fish (tuna, salmon),: meat, poultry (chicken), fish (tuna, salmon),

yeast, enriched and whole grain breads and cereals,yeast, enriched and whole grain breads and cereals,peanuts, mushrooms, milk, and eggs (tryptophan)peanuts, mushrooms, milk, and eggs (tryptophan)

Deficiency:

PELLAGRA:

Deficiency:

PELLAGRA:diarrheadiarrhea

dermatitisdermatitisdementiadementia

*Long*Long--term deficiencyterm deficiencyleads to central nervous systemleads to central nervous system

dysfunction manifested as confusion, apathy,dysfunction manifested as confusion, apathy,disorientation, and eventually coma and death.disorientation, and eventually coma and death.

toxicitytoxicity: flushing of skin, itching, nausea & vomiting,: flushing of skin, itching, nausea & vomiting,and liver damage occurs at intake over 35 mg/day fromand liver damage occurs at intake over 35 mg/day fromsupplementssupplements

8/9/2019 genPathEnv

26/81

V it B5: Pantothenic acid

sourcessources : widely distributed in foods;: widely distributed in foods;watercress; broccoli; alfalfa sprouts;watercress; broccoli; alfalfa sprouts;mushroomsmushrooms

actionaction: incorporated in coenzyme A, as co: incorporated in coenzyme A, as co--factor in carboxylation reactionsfactor in carboxylation reactions

deficiencydeficiency: rare: muscle cramps; poor: rare: muscle cramps; poorconcentration; teeth grinding; nausea &concentration; teeth grinding; nausea &

vomitingvomiting

toxicitytoxicity: none reported: none reported

8/9/2019 genPathEnv

27/81

V itamin B6: Pyridoxine

sourcessources: meat, fish, poultry, spinach, potatoes,: meat, fish, poultry, spinach, potatoes,bananas, avocados, sunflower seeds, eggs, wholebananas, avocados, sunflower seeds, eggs, wholegrains, fortified breads & cereals, legumesgrains, fortified breads & cereals, legumes

actionsactions:: natural antinatural anti--depressant; needed in balancingdepressant; needed in balancingproteins, in hormone production, & in balancing theproteins, in hormone production, & in balancing thesex hormonessex hormones

deficiencydeficiency: dermatitis, cheilosis, glossitis, peripheral: dermatitis, cheilosis, glossitis, peripheralneuropathy (tingling hands), anemia, convulsion,neuropathy (tingling hands), anemia, convulsion,depression, confusion, decline in immune function,depression, confusion, decline in immune function,

water retention, nervous irritabilitywater retention, nervous irritability toxicitytoxicity: none from foods, but excess intake above 100: none from foods, but excess intake above 100

mg/day from supplements causes neuropathy (nervemg/day from supplements causes neuropathy (nervedestruction) and skin lesionsdestruction) and skin lesions

8/9/2019 genPathEnv

28/81

V itamin B8: Biotin

sourcessources: Whole grains, eggs, nuts and seeds,: Whole grains, eggs, nuts and seeds,widely distributed in small amountswidely distributed in small amounts

actionaction: cofactor in carboxylation reactions: cofactor in carboxylation reactions deficiencydeficiency: Infants: dermatitis, convulsions,: Infants: dermatitis, convulsions,

hair loss (alopecia), neurological disorders,hair loss (alopecia), neurological disorders,impaired growthimpaired growth

toxicitytoxicity: none known: none known

8/9/2019 genPathEnv

29/81

Folic acid /Folate

sourcessources: ready: ready--toto--eat breakfast cereals,eat breakfast cereals,enriched grain products, green vegetables,enriched grain products, green vegetables,liver, legumes, orangesliver, legumes, oranges

actionsactions: transfer & utilization of C units in DNA: transfer & utilization of C units in DNAsynthesis; maturation of RBCsynthesis; maturation of RBC

deficiencydeficiency: megaloblastic (macrocytic) anemia,: megaloblastic (macrocytic) anemia,abdominal pain, diarrhea, birth defects inabdominal pain, diarrhea, birth defects in

babies of deficient pregnant womenbabies of deficient pregnant women

toxicitytoxicity: none (up to 5 mg/day);: none (up to 5 mg/day);

8/9/2019 genPathEnv

30/81

V it B12: Cobalamin /

Cyanocobalamin sourcessources: meat, fish (tuna, sardines); poultry, oysters,: meat, fish (tuna, sardines); poultry, oysters,

readyready--toto--eat fortified breakfast cereals, eggs, fermentedeat fortified breakfast cereals, eggs, fermenteddairy products (cheese, yogurt, etc)dairy products (cheese, yogurt, etc)

actionsactions: help recycle folate coenzymes involved in the: help recycle folate coenzymes involved in thesynthesis of DNA and RNA; help in the normalsynthesis of DNA and RNA; help in the normalformation of red blood cellsformation of red blood cells

deficiencydeficiency::Pernicious AnemiaPernicious Anemia: macrocytic anemia;: macrocytic anemia; CombinedCombineddegeneration of posterolateral spinal cord tracts:degeneration of posterolateral spinal cord tracts:paresthesia (tingling and numbness in limbs), tenderparesthesia (tingling and numbness in limbs), tendermuscles, difficulty walking, loss of bowel and bladdermuscles, difficulty walking, loss of bowel and bladdercontrol, dementiacontrol, dementia

toxicitytoxicity: none reported: none reported

8/9/2019 genPathEnv

31/81

Choline for many years not considered a vitamin;for many years not considered a vitamin;

however, research now shows that production inhowever, research now shows that production inthe body is not enough to cover requirements.the body is not enough to cover requirements.CholineCholine is not considered a B vitamin because itis not considered a B vitamin because it

does not have a coenzyme function and thedoes not have a coenzyme function and theamount in the body is much greater than other Bamount in the body is much greater than other Bvitamins.vitamins. helps maintain the structural integrity ofhelps maintain the structural integrity of

membranes surrounding every cell in the bodymembranes surrounding every cell in the body

can play a role in nerve signaling, cholesterolcan play a role in nerve signaling, cholesteroltransport, and energy metabolism.transport, and energy metabolism.

widely found in foods, so it is unlikely that awidely found in foods, so it is unlikely that adietary deficiency will occur.dietary deficiency will occur.

8/9/2019 genPathEnv

32/81

V itamin C: Ascorbic acid sourcessources: citrus fruits, strawberries, guavas, peppers,: citrus fruits, strawberries, guavas, peppers,

greens, broccoli, tomatoesgreens, broccoli, tomatoes actions:actions:AntiAnti--oxidant: protects membranes, antioxidant: protects membranes, anti--aging,aging,

antianti--cancer; Collagen synthesis: proper wound healing,cancer; Collagen synthesis: proper wound healing,

integrity of blood vessel walls; Biosynthesis ofintegrity of blood vessel walls; Biosynthesis ofneurotransmitters, Carnitine biosynthesis; Immunologicneurotransmitters, Carnitine biosynthesis; Immunologicfunctionfunction

deficiencydeficiency:: SCURVYSCURVY: in adults: in adults-- fatigue, poor woundfatigue, poor woundhealing, pinpoint hemorrhages around hair follicles onhealing, pinpoint hemorrhages around hair follicles on

back of arms & legs, bleeding gums & joints; in childrenback of arms & legs, bleeding gums & joints; in children--hemorrhages,hemorrhages, skin purpura over lower legsskin purpura over lower legs, gingival, gingivalswelling, perifollicular hyperkeratotic papular rash,swelling, perifollicular hyperkeratotic papular rash,scorbutic rosary (abnormal osteoid)scorbutic rosary (abnormal osteoid)

toxicitytoxicity: megadoses over 2 g/day cause nausea,: megadoses over 2 g/day cause nausea,abdominal cramps, diarrhea, uricosuriaabdominal cramps, diarrhea, uricosuria

8/9/2019 genPathEnv

33/81

Minerals

inorganic elements that originate in the earth andinorganic elements that originate in the earth andcannot be made in the bodycannot be made in the body

play important roles in various bodily functionsplay important roles in various bodily functions

necessary to sustain life and maintain optimal health,necessary to sustain life and maintain optimal health,and thus are essential nutrients.and thus are essential nutrients.

provide structure to bones and teeth and participate inprovide structure to bones and teeth and participate inenergy production, the building of protein, bloodenergy production, the building of protein, blood

formation, and several other metabolic processesformation, and several other metabolic processes

Most of the minerals in the human diet come directlyMost of the minerals in the human diet come directlyfrom plants and water, or indirectly from animal foodsfrom plants and water, or indirectly from animal foods

8/9/2019 genPathEnv

34/81

Major& Trace

minerals Sodium (Na)Sodium (Na)

Potassium (K)Potassium (K)

Chloride (Cl)Chloride (Cl)

Calcium (Ca)Calcium (Ca)

Magnesium (Mg)Magnesium (Mg)

Phosphorus (P)Phosphorus (P)

Sulfur (S)Sulfur (S)

Iron (Fe)Iron (Fe)

Copper (Cu)Copper (Cu)

Chromium (Cr)Chromium (Cr) Fluoride (Fl)Fluoride (Fl)

Iodine (I)Iodine (I)

Manganese (Mn)Manganese (Mn)

Molybdenum (Mo)Molybdenum (Mo) Selenium (Se)Selenium (Se)

Zinc (Zn)Zinc (Zn)

8/9/2019 genPathEnv

35/81

Major minerals : functions NaNa,, KK,, ClCl ::fluid balancefluid balance :regulated by charged sodium and:regulated by charged sodium and

chloride ions in the ECF and potassium in the ICF, and bychloride ions in the ECF and potassium in the ICF, and bysome other electrolytes across cell membranes. Tightsome other electrolytes across cell membranes. Tightcontrol is critical for normal muscle contraction, nervecontrol is critical for normal muscle contraction, nerve

impulse transmission, heart function, and blood pressure.impulse transmission, heart function, and blood pressure. SodiumSodium plays an important role in the absorption of otherplays an important role in the absorption of other

nutrients, such as glucose, amino acids, and water.nutrients, such as glucose, amino acids, and water.

ChlorideChloride is a component of hydrochloric acid, anis a component of hydrochloric acid, an

important part of gastric juice (an acidic liquid secreted byimportant part of gastric juice (an acidic liquid secreted byglands in the stomach lining) and aids in food digestion.glands in the stomach lining) and aids in food digestion.

Potassium and sodiumPotassium and sodium act as cofactors for certainact as cofactors for certainenzymes.enzymes.

8/9/2019 genPathEnv

36/81

Major minerals: functions

CalciumCalcium,, magnesiummagnesium, and, and phosphorusphosphorus are essential forare essential forthe development and maintenance of bones and teeth;the development and maintenance of bones and teeth;& needed for maintaining cell membranes and& needed for maintaining cell membranes and

connective tissue.connective tissue. Several enzymes, hormones, and proteins that regulateSeveral enzymes, hormones, and proteins that regulate

energy and fat metabolism requireenergy and fat metabolism require calciumcalcium,, magnesiummagnesiumand/orand/or phosphorusphosphorus to become active.to become active.

CalciumCalcium also aids in blood clotting.also aids in blood clotting.

SulfurSulfur is a key component of various proteins andis a key component of various proteins andvitamins and participates in drugvitamins and participates in drug--detoxifying pathwaysdetoxifying pathwaysin the body.in the body.

8/9/2019 genPathEnv

37/81

Trace minerals: Iron

sourcessources::beef esp. liver, chicken, rice, broccoli,beef esp. liver, chicken, rice, broccoli,canned tuna, wheat germ, tofu, boiled egg,canned tuna, wheat germ, tofu, boiled egg,molasses, cooked musselsmolasses, cooked mussels

actionsactions:: necessary for the production of normalnecessary for the production of normalhemoglobin, & therefore, normal RBChemoglobin, & therefore, normal RBC deficiencydeficiency::Microcytic hypochromic anemiaMicrocytic hypochromic anemia;;

cold intolerance; poor wound healing; alopecia;cold intolerance; poor wound healing; alopecia;

koilonychia; atrophic glossitis; reversible losskoilonychia; atrophic glossitis; reversible lossof cognitive function; malaise;of cognitive function; malaise; immunity immunity excessexcess:: Hemochromatosis: bronze diabetesHemochromatosis: bronze diabetes

8/9/2019 genPathEnv

38/81

Trace minerals: Copper

sourcessources:: nuts, sunflower seeds, lobster, greennuts, sunflower seeds, lobster, greenolives, wheat bran, liver, cocoa, oysters, blackolives, wheat bran, liver, cocoa, oysters, blackpepper, blackstrap molassespepper, blackstrap molasses

actionsactions:: needed for hemoglobin synthesis,needed for hemoglobin synthesis,normal iron metabolism, maintenance of bloodnormal iron metabolism, maintenance of blood

vessels, bone, nerves,vessels, bone, nerves, deficiencydeficiency:impaired bone calcification,:impaired bone calcification,

hypochromic anemia not responsive to Ironhypochromic anemia not responsive to Irontherapy, neutropeniatherapy, neutropenia

excessexcess : Wilsons disease: liver cirrhosis, with: Wilsons disease: liver cirrhosis, withCopper depositionCopper deposition

8/9/2019 genPathEnv

39/81

Trace minerals: Selenium

sourcessources:: meat, liver, oysters, wheat germ, yeast,meat, liver, oysters, wheat germ, yeast,pumpkin seeds, alfalfa, wild yampumpkin seeds, alfalfa, wild yam

actionsactions :: antianti--oxidant; part of glutathioneoxidant; part of glutathioneperoxidaseperoxidase;;

deficiencydeficiency :: Keshan diseaseKeshan disease;; muscle pain &muscle pain &tenderness in TPNtenderness in TPN;; KashinKashin--Beck diseaseBeck disease

toxicitytoxicity:: hair loss, abnormal nails, peripheralhair loss, abnormal nails, peripheralneuropathy, dermatitis, nausea, diarrhea,neuropathy, dermatitis, nausea, diarrhea,fatigue, irritability, garlic breathfatigue, irritability, garlic breath

8/9/2019 genPathEnv

40/81

Trace minerals: Zinc

sourcessources::brazil nuts, seafood, poultry, red meat,brazil nuts, seafood, poultry, red meat,grains, eggs, garlic; oats, brown rice, vegetablesgrains, eggs, garlic; oats, brown rice, vegetables(soil)(soil)

actionsactions:: component of hundreds of enzymescomponent of hundreds of enzymes

deficiencydeficiency::AAcrodermatitis enteropathica;crodermatitis enteropathica;maternal deficiencymaternal deficiency-- fetal malformations &fetal malformations &low birth weightlow birth weight

toxicitytoxicity::very rare: microcytosis, neutropenia,very rare: microcytosis, neutropenia,impaired immunity, vomiting, diarrheaimpaired immunity, vomiting, diarrhea

8/9/2019 genPathEnv

41/81

Fluoride, Iodine, Chromium,

Manganese, Molybdenum FluorideFluoride-- (Fl)(Fl) --prevention ofprevention of

cavitiescavities

IodineIodine-- (I)(I) -- necessary fornecessary forthyroid hormone productionthyroid hormone production ChromiumChromium (Cr)(Cr)-- needed forneeded for

proper carbohydrateproper carbohydratemetabolismmetabolism

ManganeseManganese-- (Mn)(Mn)-- componentcomponentof enzymes, e.g. superoxideof enzymes, e.g. superoxidedismutasedismutase

MolybdenumMolybdenum-- (Mo(Mo)) --enzymeenzymecomponentcomponent

deficiency states:deficiency states:

FlFl-- dentalCariesdentalCaries II -- Goiter /Goiter /

HypothyroidismHypothyroidism Cr, Mn, MoCr, Mn, Mo --

MetabolicMetabolicderangementsderangements

8/9/2019 genPathEnv

42/81

Air Pollution Daily, we inhale from 10,000Daily, we inhale from 10,000--20000 liters of20000 liters of

air, bearing myriad pollutantsair, bearing myriad pollutants-- gases,gases,bacteria, fibers, particlesbacteria, fibers, particles

e.g. ozone, nitrous dioxide, radon, cigarettee.g. ozone, nitrous dioxide, radon, cigarette

smoke, coal dust, silica, asbestossmoke, coal dust, silica, asbestos etiologic factorsetiologic factors: population explosion;: population explosion;

improper garbage disposal; burning of certainimproper garbage disposal; burning of certainchemicals;chemicals; no. of no. ofautomobiles (automobiles (exhaust)exhaust)

somesome consequencesconsequences: destruction of atmospheric: destruction of atmosphericOzone; greenhouse effect (global warming)Ozone; greenhouse effect (global warming)--loss of vegetation, loss of rain forestsloss of vegetation, loss of rain forests

8/9/2019 genPathEnv

43/81

Air Pollution: adverse consequences

Destruction of atmosphericDestruction of atmospheric OzoneOzonebybychlorofluorocarbonschlorofluorocarbons (CFCs),(CFCs), nitrogennitrogen

dioxidedioxide (NO2), &(NO2), &bromidebromide//brominebromineradicalsradicals

Global warming / the greenhouseGlobal warming / the greenhouse

effect:effect: CO2, CFCs, NO2CO2, CFCs, NO2,,methanemethane in thein theatmosphere traps infrared waves/heat onatmosphere traps infrared waves/heat onthe earths surfacethe earths surface

8/9/2019 genPathEnv

44/81

Air Pollution: Patterns of Lung injury

Acute/Chronic InflammationAcute/Chronic Inflammation

HypersensitivityPneumonitisHypersensitivityPneumonitis

EmphysemaEmphysema

AsthmaAsthma

PneumoconiosisPneumoconiosis

NeoplasiaNeoplasia

direct cell injurydirect cell injury

immunologic injuryimmunologic injury

enhanced proteolysisenhanced proteolysis

allergic/irritant effectallergic/irritant effect

fibrotic reactions causedfibrotic reactions caused

by cytokines releasedby cytokines released

from macrophages & otherfrom macrophages & otherrecruited leukocytesrecruited leukocytes

mutagenic & promotingmutagenic & promoting

effectseffects

8/9/2019 genPathEnv

45/81

Air Pollution: Tobacco smoking

the single most preventable cause of premature deaththe single most preventable cause of premature deathin developed countriesin developed countries

adverse effects are much greater than those of all otheradverse effects are much greater than those of all other

pollutants combinedpollutants combined damages not only the principal smokers but alsodamages not only the principal smokers but alsoinnocent bystanders (innocent bystanders (passivepassive smokers)smokers)

quantitation:quantitation:no. of packs smoked per day x no. of years smokingno. of packs smoked per day x no. of years smoking

= no. of pack= no. of pack--yearsyearse.g. pack a day x 10 yrs = 5 packe.g. pack a day x 10 yrs = 5 pack--yearsyears

** The higher the number of pack** The higher the number of pack--years, the greater theyears, the greater therisks of smoking.**risks of smoking.**

8/9/2019 genPathEnv

46/81

Adverse effects of Smoking

coronary heart diseasecoronary heart disease leading toleading to myocardialmyocardialinfarctioninfarction (MI)(MI)-- no.1 cause of death related tono.1 cause of death related tocigarette smokingcigarette smoking

CancerCancer of theof the LungLung Chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease(COPD):(COPD): emphysemaemphysema,, chronic bronchitischronic bronchitis Systemic arteriosclerosisSystemic arteriosclerosis

Peptic ulcerPeptic ulcer OtherOther Cancers: larynx, esophagus, kidney,Cancers: larynx, esophagus, kidney,pancreas, urinary bladderpancreas, urinary bladder

8/9/2019 genPathEnv

47/81

Adverse effects of Cigarette smoking

on unborn children of mothers who smoke:on unborn children of mothers who smoke:increased incidence of low birth weight,increased incidence of low birth weight,prematurity, stillbirth, spontaneous abortion, &prematurity, stillbirth, spontaneous abortion, &

infant mortalityinfant mortality on passive smokers: increased risk of lungon passive smokers: increased risk of lung

cancer, cardiovascular disease, particularly MI,cancer, cardiovascular disease, particularly MI,& lower respiratory tract illness; possible& lower respiratory tract illness; possible

retardation of physical & intellectualretardation of physical & intellectualmaturation in infants & childrenmaturation in infants & children

******The safest cigarette is the unsmoked one***The safest cigarette is the unsmoked one***

8/9/2019 genPathEnv

48/81

cessation of Smoking/exposure

immediate decrease in irritation, inflammation,immediate decrease in irritation, inflammation,& hyper& hyper--responsiveness of airways, includingresponsiveness of airways, includingcessation ofcessation ofsmokers coughsmokers cough

slow decrease in excess mortality, returning toslow decrease in excess mortality, returning tobaseline in about 20 yearsbaseline in about 20 years

risk of MI begins to decline within a year, butrisk of MI begins to decline within a year, buttakes 5takes 5--20 yrs. to approach that of non20 yrs. to approach that of non--smokerssmokers

risks of lung CA & laryngeal CA start to declinerisks of lung CA & laryngeal CA start to declinew/in 1w/in 1--2 yrs, but remain slightly increased even2 yrs, but remain slightly increased evenafter 30 yrs.after 30 yrs.

8/9/2019 genPathEnv

49/81

Air pollution: Carcinogenic effects

AgentAgent ArsenicArsenic

AsbestosAsbestos

BenzeneBenzene BetaBeta--naphthylaminenaphthylamine

CadmiumCadmium

ChromiumChromium

NickelNickel UraniumUranium

Vinyl chlorideVinyl chloride

Type of CancerType of CancerSkin, lung, liverSkin, lung, liver

Mesothelioma, lungMesothelioma, lung

Myelogenous leukemiaMyelogenous leukemia

Urinary bladderUrinary bladder

Prostate, kidneyProstate, kidney

Nasal cavity, sinus, lungNasal cavity, sinus, lung

Nasal cavity, sinus, lungNasal cavity, sinus, lungLungLung

Liver angiosarcomaLiver angiosarcoma

8/9/2019 genPathEnv

50/81

Chemical & drug injuries

***All chemicals & drugs are capable of causing***All chemicals & drugs are capable of causinginjury or death.***injury or death.***

accidental exposureaccidental exposure

selfself--administrationadministration accidental overdoseaccidental overdose

nonnon--medical use of street drugsmedical use of street drugs

unanticipated result of selfunanticipated result of self--administered oradministered orprescribed use of standard medicines.prescribed use of standard medicines.

exaggeration of an intended pharmacologicexaggeration of an intended pharmacologiceffect or an accompanying side effecteffect or an accompanying side effect

8/9/2019 genPathEnv

51/81

Adverse drug reactions (ADRs)

any response to a drug that is noxious & unintended,any response to a drug that is noxious & unintended,occuring at doses used in humans for prophylaxis,occuring at doses used in humans for prophylaxis,diagnosis, or therapy, excluding failure to accomplishdiagnosis, or therapy, excluding failure to accomplish

the intended purpose; [mechanisms: direct toxicity tothe intended purpose; [mechanisms: direct toxicity tocells; immunologic/idiosyncratic reactions; or due tocells; immunologic/idiosyncratic reactions; or due toimmunologic / hormonal host defenses]immunologic / hormonal host defenses]

Predictable ADRs: known sidePredictable ADRs: known side--effects; doseeffects; dose--related,related,severity depends on route of administrationseverity depends on route of administration

Unpredictable ADRs: unanticipated, usuallyUnpredictable ADRs: unanticipated, usuallyimmunologic, idiosyncratic; dose & route ofimmunologic, idiosyncratic; dose & route ofadministration do not affect the severityadministration do not affect the severity

8/9/2019 genPathEnv

52/81

Therapeutic agents

ANALGESICSANALGESICS AspirinAspirin

Aspirin + PhenacetinAspirin + Phenacetin

NSAIDS (nonNSAIDS (non--steroidal antisteroidal anti--inflammatory drugs):inflammatory drugs):Ibuprofen, Diclofenac,Ibuprofen, Diclofenac,

Acetaminophen/ParacetamolAcetaminophen/Paracetamol

ANTIMICROBIALSANTIMICROBIALS

ANTIANTI--NEOPLASTIC AGENTSNEOPLASTIC AGENTS AntiAnti--metabolitesmetabolites

ImmunosuppressivesImmunosuppressives

8/9/2019 genPathEnv

53/81

Therapeutic agents: aspirin

Therapeutic dose: 0.5Therapeutic dose: 0.5--1.0 gm./day1.0 gm./day Lethal dose: 2Lethal dose: 2--4 gm./day in children4 gm./day in children

1010--30 gm./day in adults30 gm./day in adults

Acute toxicity: initial alkalosisAcute toxicity: initial alkalosis------ fluid & electrolytefluid & electrolyteimbalanceimbalance------ metabolic acidosismetabolic acidosis------ deathdeath Chronic toxicity: (3 gm/day): dizziness, nausea,Chronic toxicity: (3 gm/day): dizziness, nausea,

vomiting, diarrhea, drowsiness, hallucinations,vomiting, diarrhea, drowsiness, hallucinations,convulsions, comaconvulsions, coma

Known effects: analgesic; antiKnown effects: analgesic; anti--platelet aggregation;platelet aggregation;gastric irritantgastric irritant------ acute erosive gastritisacute erosive gastritis

Unpredictable ADRs: hypersensitivity: rashes,Unpredictable ADRs: hypersensitivity: rashes,urticaria, exfoliative dermatosesurticaria, exfoliative dermatoses

8/9/2019 genPathEnv

54/81

Therapeutic agents: analgesics

Aspirin + PhenacetinAspirin + Phenacetin Toxicity: nephropathy : renal papillary necrosisToxicity: nephropathy : renal papillary necrosis

NSAIDS:NSAIDS: known side effect: gastric irritation;known side effect: gastric irritation; UADR: hypersensitivityUADR: hypersensitivity

Acetaminophen:Acetaminophen: therapeutic dose: 0.5 gm q 4 hrs.(up to 3gm/day)therapeutic dose: 0.5 gm q 4 hrs.(up to 3gm/day)

toxic dose: 15toxic dose: 15--25 gm;25 gm; toxicity: nausea, vomiting, diarrhea; shock; hepatictoxicity: nausea, vomiting, diarrhea; shock; hepatic

injuryinjury pathology: hepatic necrosis; renal/myocardialpathology: hepatic necrosis; renal/myocardial

damagedamage

8/9/2019 genPathEnv

55/81

Therapeutic agents: anti-neoplastics

AntiAnti--metabolitesmetabolites Bone marrow suppressionBone marrow suppression

GI mucosal injuryGI mucosal injury

Hair follicle injuryHair follicle injury

ImmunosuppressionImmunosuppression

Nonlethal mutationsNonlethal mutations

Initiation of some form of CancerInitiation of some form of Cancer

ImmunosuppressivesImmunosuppressives susceptibility to infections, esp. opportunistic susceptibility to infections, esp. opportunistic

risk of malignant lymphoma risk of malignant lymphoma

8/9/2019 genPathEnv

56/81

Therapeutic agents:

antimicrobials/antibiotics HypersensitivityHypersensitivity

rashes, urticaria, exfoliative dermatosesrashes, urticaria, exfoliative dermatoses

anaphylaxisanaphylaxis

Emergence of microbial resistanceEmergence of microbial resistance

supersuper--infectionsinfections

Eradication of normal floraEradication of normal flora vitamin K deficiencyvitamin K deficiency------ bleeding diathesisbleeding diathesis

8/9/2019 genPathEnv

57/81

Common adverse drug reactions &

major offenders BLOOD (DYSCRACIAS)BLOOD (DYSCRACIAS)

GranulocytopeniaGranulocytopenia Aplastic anemiaAplastic anemia PancytopeniaPancytopenia Hemolytic anemiaHemolytic anemia thrombocytopeniathrombocytopenia

CNSCNS Tinnitus, dizzinessTinnitus, dizziness Acute dystonic reactionsAcute dystonic reactions

Parkinsons syndromeParkinsons syndrome CUTANEOUSCUTANEOUS

UrticariaUrticaria PetechiaPetechia Exfoliative dermatitisExfoliative dermatitis

BLOOD DYSCRACIASBLOOD DYSCRACIAS AntiAnti--neoplasticsneoplastics ImmunosuppressantsImmunosuppressants ChloramphenicolChloramphenicol QuinidineQuinidine MethyldopaMethyldopa

CNSCNS SalicylatesSalicylates Phenothiazine antipsychoticsPhenothiazine antipsychotics

SedativesSedatives CUTANEOUSCUTANEOUS

SulfonamidesSulfonamides HydantoinHydantoin AntiAnti--neoplasticsneoplastics

8/9/2019 genPathEnv

58/81

Common adverse drug reactions &

major offenders CARDIACCARDIAC

ArrhythmiasArrhythmias CardiomyopathyCardiomyopathy

HEPATICHEPATIC Fatty changeFatty change CholestasisCholestasis Hepatocellular damageHepatocellular damage

PULMONARYPULMONARY Acute PneumonitisAcute Pneumonitis Interstitial fibrosisInterstitial fibrosis AsthmaAsthma

CARDIACCARDIAC TheophyllineTheophylline HydantoinHydantoin Doxorubicin, DaunorubicinDoxorubicin, Daunorubicin

HEPATICHEPATIC TetracyclineTetracycline Chlorpromazine, EstrogensChlorpromazine, Estrogens Halothane, Acetaminophen,Halothane, Acetaminophen,

INHINH

PULMONARYPULMONARY SalicylatesSalicylates NitrofurantoinNitrofurantoin Busulfan, BleomycinBusulfan, Bleomycin

8/9/2019 genPathEnv

59/81

Common adverse drug reactions &

major offenders RENALRENAL

GlomerulonephritisGlomerulonephritis

TubulointerstitialTubulointerstitial

nephritisnephritis Acute tubular nephritisAcute tubular nephritis

SYSTEMICSYSTEMIC

AnaphylaxisAnaphylaxis

Lupus erythematosusLupus erythematosussyndromesyndrome

RENALRENAL

PenicillaminePenicillamine

Phenacetin, SalicylatesPhenacetin, Salicylates

Aminoglycosides,Aminoglycosides,Cyclosporine,Cyclosporine,Amphotericin BAmphotericin B

SYSTEMICSYSTEMIC

Penicillin, AspirinPenicillin, Aspirin

Hydralazine,Hydralazine,ProcainamideProcainamide

8/9/2019 genPathEnv

60/81

Common agents implicated in

fatal reactions Tricyclic antiTricyclic anti--

depressantsdepressants

AlprazolamAlprazolam

Ipramine, DesipramineIpramine, Desipramine

NortriptylineNortriptyline

AcetaminophenAcetaminophen

HalothaneHalothane AspirinAspirin

CNS depressionCNS depression

Hepatic necrosisHepatic necrosis

Hepatic necrosisHepatic necrosis

Metabolic acidosis; FluidMetabolic acidosis; Fluid& Electrolyte imbalance& Electrolyte imbalance

8/9/2019 genPathEnv

61/81

8/9/2019 genPathEnv

62/81

Non-medical use of street drugs

Cocaine: alkaloid extractCocaine: alkaloid extractfrom the leaves of thefrom the leaves of theCocaCoca plant: pureplant: pure-- Crack;Crack;Cocaine hydrochlorideCocaine hydrochloride

Heroin: opiate derivedHeroin: opiate derivedfrom thefrom the PoppyPoppy plant;plant;the most hazardousthe most hazardous

street drugstreet drug-- producesproducesTrue Addiction (physicalTrue Addiction (physicaldependence)dependence) & intense& intensefear of withdrawal (Illfear of withdrawal (Illdie without it)die without it)

potent CNS stimulant;potent CNS stimulant;cardiorespiratorycardiorespiratorytoxicity; perinataltoxicity; perinatalmorbidity & mortality;morbidity & mortality;but

but effective localeffective localanestheticanesthetic

Feelings of wellFeelings of well--being,being,tranquility, sedation;tranquility, sedation;multisystem toxicity;multisystem toxicity;infections, granulomas;infections, granulomas;sudden death fromsudden death fromoverdoseoverdose

8/9/2019 genPathEnv

63/81

Non-therapeutic chemicals

Ethyl Alcohol:Ethyl Alcohol: AcetaldehydeAcetaldehyde10 gm in 12 oz beer, 4 oz unfortified wine, or 1.5 oz 8010 gm in 12 oz beer, 4 oz unfortified wine, or 1.5 oz 80--

proof liquorproof liquor

rapidly absorbed in the stomach & small intestinesrapidly absorbed in the stomach & small intestines

Metabolized by the liverMetabolized by the liver at the rate of 10gm/hrat the rate of 10gm/hrAcute intoxication: mainly affects the CNS & StomachAcute intoxication: mainly affects the CNS & Stomach

2020--30mg/dL= powerful depressant effect on cortical30mg/dL= powerful depressant effect on corticalinhibitory centers= loss of inhibitions= party inhibitory centers= loss of inhibitions= party syndrome; Euphoria; disordered cognitive & motorsyndrome; Euphoria; disordered cognitive & motorfunctionsfunctions

100mg/dL= legal level of intoxication= Ataxia100mg/dL= legal level of intoxication= Ataxia

200200--250mg/dL= narcosis= drowsiness250mg/dL= narcosis= drowsiness

300300--400mg/dL= coma; profound anesthesia; death400mg/dL= coma; profound anesthesia; death

8/9/2019 genPathEnv

64/81

Non-therapeutic agents:

ethyl alcohol

Chronic Alcoholism: induces injuries in all tissuesChronic Alcoholism: induces injuries in all tissuesLiverLiver -- most commonly & severely affected= fattymost commonly & severely affected= fatty

change, acute hepatitischange, acute hepatitis------ CirrhosisCirrhosis

CNSCNS Wernickes encephalopathyWernickes encephalopathy-- ataxia, globalataxia, globalconfusion, ophthalmoplegia, loss of neuropil &confusion, ophthalmoplegia, loss of neuropil &demyelination (vit B1 def) &demyelination (vit B1 def) & Korsakoff syndromeKorsakoff syndrome--profound memory deficit both recent & remote;profound memory deficit both recent & remote;cerebellar degeneration; cerebral atrophycerebellar degeneration; cerebral atrophy

Fetal Alcohol Syndrome: microcephaly, cardiac defects,Fetal Alcohol Syndrome: microcephaly, cardiac defects,mental deficiency, facial malformationsmental deficiency, facial malformations

Misc.: neuropathies; congestive cardiomyopathy;Misc.: neuropathies; congestive cardiomyopathy;frequency of cancer in the larynx, oropharynx, esophagus,frequency of cancer in the larynx, oropharynx, esophagus,rectum, lungrectum, lung

8/9/2019 genPathEnv

65/81

Uncommon potentially fatal

nontherapeutic agents ARSENICARSENIC-- in rat poison,in rat poison,

fruit sprays, weed killer;fruit sprays, weed killer;binds sulfhydrilbinds sulfhydril

CARBON MONOXIDECARBON MONOXIDE--odorless, tasteless, inodorless, tasteless, incigarette smoke, fossilcigarette smoke, fossilfuel exhaustfuel exhaust

CARBONCARBONTETRACHLORIDE &TETRACHLORIDE &CHLOROFORMCHLOROFORM

Nausea, vomiting,Nausea, vomiting,visceral hemorrhages,visceral hemorrhages,liver & lung CAliver & lung CA

Systemic asphyxia: 1%Systemic asphyxia: 1%fatal in 10fatal in 10--20 min, 7%20 min, 7%fatal in 5 min: cherry redfatal in 5 min: cherry reddiscoloration of mucosaediscoloration of mucosae

Centrilobular necrosis,Centrilobular necrosis,Liver; renal ATNLiver; renal ATN

8/9/2019 genPathEnv

66/81

Uncommon potentially fatal

nontherapeutic agents CYANIDECYANIDE-- gas causes deathgas causes death

within minutes; saltswithin minutes; salts(100mg), within hours;(100mg), within hours;antidote: Nitriteantidote: Nitrite

INSECTICIDESINSECTICIDES Chlorinated hydrocarbons:Chlorinated hydrocarbons:

chlordane, Aldrin, DDTchlordane, Aldrin, DDT

Organophosphates: Malathion,Organophosphates: Malathion,Pyrophosphates, DimpylatePyrophosphates, Dimpylate

Polychlorinated biphenyls:Polychlorinated biphenyls:PCBsPCBs

Histotoxic hypoxia; bindsHistotoxic hypoxia; bindscytochrome oxidasecytochrome oxidase--cherry red discoloration,cherry red discoloration,

bitter almond odorbitter almond odor

InsecticidesInsecticides Toxic neuronal injuryToxic neuronal injury

hyperexcitability,delirium,hyperexcitability,delirium,convulsions, comaconvulsions, coma

Muscle twitching, flaccidMuscle twitching, flaccidparalysis, cardiacparalysis, cardiac

arrhythmiasarrhythmias Chloracne, impotence,Chloracne, impotence,

infertilityinfertility

8/9/2019 genPathEnv

67/81

Uncommon potentially fatal

nontherapeutic agents KEROSENEKEROSENE-- accidentalaccidental

ingestion or inhalation ofingestion or inhalation offumesfumes

LEADLEAD-- paint, water (pipes),paint, water (pipes),newsprint, pottery glazes,newsprint, pottery glazes,gas exhaust, tin cans,gas exhaust, tin cans,moonshine whiskey,moonshine whiskey,occupational exposureoccupational exposure

MERCURYMERCURY-- contaminatedcontaminatedfish, grain,fungicides,fish, grain,fungicides,dermatologic ointments,dermatologic ointments,interior latex paintsinterior latex paints

FulminantFulminantbronchopneumonia; lipoidbronchopneumonia; lipoidpneumonia; CNSpneumonia; CNSdepressiondepression

Lead colic; lead line onLead colic; lead line ongums; basophilic stipplinggums; basophilic stipplingof RBC; anemia;of RBC; anemia;encephalopathy;encephalopathy;demyelinating neuropathydemyelinating neuropathy

Eosinophilic globules inEosinophilic globules inrenal tubules; neuronalrenal tubules; neuronaltoxicity; gingival deposits;toxicity; gingival deposits;Minamata dseMinamata dse--

blindness, hearing loss,blindness, hearing loss,spasticity, paralysisspasticity, paralysis

8/9/2019 genPathEnv

68/81

Uncommon potentially fatal

nontherapeutic agents METHANOLMETHANOL-- in solvents,in solvents,

paint removers, & antipaint removers, & anti--freeze; toxic metabolite isfreeze; toxic metabolite is

FormalinFormalin POISONOUS MUSHROOMSPOISONOUS MUSHROOMS

Amanita muscariaAmanita muscaria rarelyrarelylethal; active metabolite islethal; active metabolite ismuscarinmuscarin

Amanita phalloidesAmanita phalloides deathdeathrate is 30rate is 30--50%; active50%; activemetabolite is amanitinmetabolite is amanitin

Metabolic acidosis; CNSMetabolic acidosis; CNSdepression; retinaldepression; retinalganglion necrosis=ganglion necrosis=

blindnessblindness MUSHROOMSMUSHROOMS

ImmediateImmediateparasympathomimeticparasympathomimeticeffects: salivation, sweating,effects: salivation, sweating,miosis, bradycardia,miosis, bradycardia,

hypotension, GI Sxhypotension, GI Sx Cardiovascular collapse;Cardiovascular collapse;

convulsions, coma, ATN,convulsions, coma, ATN,centrilobular necrosiscentrilobular necrosis

8/9/2019 genPathEnv

69/81

Poisonous mushroomsPoisonous mushrooms

Amanita muscaria Amanita phalloides

8/9/2019 genPathEnv

70/81

Physical injury

Mechanical forceMechanical force

Soft tissue injuries:Soft tissue injuries:contusions,contusions,lacerations, avulsions,lacerations, avulsions,

Bone injuries:Bone injuries:fracturesfractures

Head injuries; coup &Head injuries; coup &

contrecontre--coup injuries,coup injuries,concussion,concussion,contussioncontussion

8/9/2019 genPathEnv

71/81

Physical injury

Temperature changesTemperature changes Hyperthermia:Hyperthermia:

Heat stroke= peripheral vasodilatation, hypotension, CNSHeat stroke= peripheral vasodilatation, hypotension, CNSdysfunctiondysfunction

Exertional= hyperK, metabolic acidosis, myoglobinuria, acuteExertional= hyperK, metabolic acidosis, myoglobinuria, acuterenal failure, DICrenal failure, DIC

Burns= partial & full thickness = plasma transudation,Burns= partial & full thickness = plasma transudation,hypovolemia, shock; sepsis:hypovolemia, shock; sepsis:Pseudomonas aeruginosa;Pseudomonas aeruginosa;CCurlings ulcers, DIC, ATN,urlings ulcers, DIC, ATN,

Smoke inhalation: ARDS, pulmonary edema, alveolar hgeSmoke inhalation: ARDS, pulmonary edema, alveolar hge

Hypothermia:Hypothermia: local freezing= Frostbitelocal freezing= Frostbite ischemic necrosisischemic necrosis

Systemic hypothermia= circulatory failureSystemic hypothermia= circulatory failure-- markedmarkedvasoconstriction, slowing of metabolismvasoconstriction, slowing of metabolism

8/9/2019 genPathEnv

72/81

Burns

8/9/2019 genPathEnv

73/81

Physical injury

Changes in Atmospheric pressureChanges in Atmospheric pressure Blast injury: Air blastBlast injury: Air blast-- bomb explosions;bomb explosions;

Immersion blastImmersion blast-- underwaterunderwater

Altitude sickness: hypoxic injury;Altitude sickness: hypoxic injury;

chronicchronic-- anemiaanemia

Caisson diseaseCaisson disease

Electrical injuryElectrical injury Factors: DC less harmful than AC; duration of exposure,Factors: DC less harmful than AC; duration of exposure,

amperage/voltage, path of currentamperage/voltage, path of current-- resistance of tissues, waterresistance of tissues, watercontentcontent

Lightning: arborizing burns, organ rupture, fractures,Lightning: arborizing burns, organ rupture, fractures,hemorrhageshemorrhages

FlashoverFlashover

8/9/2019 genPathEnv

74/81

Physical injury Ionizing RadiationIonizing Radiation-- physical transfer ofphysical transfer of

energy from its site of origin to the biologicenergy from its site of origin to the biologictargets, inducing ionization of its atoms:targets, inducing ionization of its atoms:

Electromagnetic waves: xElectromagnetic waves: x--rays, gamma raysrays, gamma rays Particles : neutrons & charged particlesParticles : neutrons & charged particles-- alpha,alpha,

beta, protons, mesons, deuteronsbeta, protons, mesons, deuterons

Sources of Radiation:Sources of Radiation:

background: galactic/solar cosmic rays, incl.background: galactic/solar cosmic rays, incl.UV, natural terrstrial radionucleidesUV, natural terrstrial radionucleides

manman--made: diagnostic & therapeuticmade: diagnostic & therapeutic

8/9/2019 genPathEnv

75/81

Physical injury

Quantitation of Radiation:Quantitation of Radiation:RR-- roentgenroentgenrr radrad-- also called a centigray (cGy)= energyalso called a centigray (cGy)= energy

absorption of 100 ergs/gm of tissue (0.01 joule/kg)absorption of 100 ergs/gm of tissue (0.01 joule/kg)GG gray = 100 radsgray = 100 radsCiCi -- curiecurie

Linear energy transfer (LET)Linear energy transfer (LET) Relative biologic effectiveness (RBE)Relative biologic effectiveness (RBE) Mechanisms of Radiation injury:Mechanisms of Radiation injury:

Target theory: direct damage to DNATarget theory: direct damage to DNAIndirect action theory: radiolysis of cellular water,Indirect action theory: radiolysis of cellular water,

production of free radicals= damage to DNA & cellproduction of free radicals= damage to DNA & cellmembranesmembranes

8/9/2019 genPathEnv

76/81

Radiation injury--raysrays ionizing particlesionizing particlesxx--raysrays ,, , protons, etc., protons, etc.

IONIZATION & EXCITATIONIONIZATION & EXCITATION heatheat

Oxygen effectOxygen effect CHEMICAL CHANGECHEMICAL CHANGE free radicalsfree radicals

BIOLOGIC CHANGE (DNA damage) DNA repairBIOLOGIC CHANGE (DNA damage) DNA repair

malignantmalignant mutationsmutations inhibition of inhibition oftransformationtransformation cell divisioncell division

CANCERCANCER GENETIC EFFECTSGENETIC EFFECTS CELL DEATHCELL DEATH

8/9/2019 genPathEnv

77/81

Radiation injury

Biologic effects of RadiationBiologic effects of Radiation Effects are in direct proportion to mitotic/reproductive activityEffects are in direct proportion to mitotic/reproductive activity Various types of radiation differ in penetrability & pattern ofVarious types of radiation differ in penetrability & pattern of

deposition of energydeposition of energy Oxygen effects: amplifies low LET radiation damage; induces freeOxygen effects: amplifies low LET radiation damage; induces free

radical production; fixation of radiant injuries/lesions which wouldradical production; fixation of radiant injuries/lesions which wouldotherwise be reparableotherwise be reparable

Cellular: swelling, nuclear & cytoplasmic chromatin clumping,Cellular: swelling, nuclear & cytoplasmic chromatin clumping,abnormal mitoses, aneuploidy, mitochondrial distortion, ERabnormal mitoses, aneuploidy, mitochondrial distortion, ERdegeneration; endothelial swelling, thrombosis, hemorrhagedegeneration; endothelial swelling, thrombosis, hemorrhage

Organ atrophy, esp. GI mucosa & hair folliclesOrgan atrophy, esp. GI mucosa & hair follicles Lymphopenia w/in hours, granulocytopenia w/in 1 week; Anemia;Lymphopenia w/in hours, granulocytopenia w/in 1 week; Anemia;

ThrombocytopeniaThrombocytopenia Radiodermatitis: thin, atrophic skin; hyperRadiodermatitis: thin, atrophic skin; hyper-- or deor de--pigmentationpigmentation Pulmonary interstitial fibrosisPulmonary interstitial fibrosis Sterility: Ovaries more severely affected than TestesSterility: Ovaries more severely affected than Testes

8/9/2019 genPathEnv

78/81

Susceptibility to radiation injury

High: lymphoid, hematopoietic,High: lymphoid, hematopoietic,spermatogonia, ovarian folliclesspermatogonia, ovarian follicles

Fairly high: GI & mucosal epithelia, hairFairly high: GI & mucosal epithelia, hairfollicles, lung; latefollicles, lung; late--kidneykidney

Medium: GIT wall, endothelium, glandularMedium: GIT wall, endothelium, glandularepitheliumof the breast & pancreas, u.bladderepitheliumof the breast & pancreas, u.bladderepithelium, growing cartilage, bone, normalepithelium, growing cartilage, bone, normal

brainbrain Low: mature bone; mature cartilage; muscle;Low: mature bone; mature cartilage; muscle;

peripheral nervesperipheral nerves

8/9/2019 genPathEnv

79/81

Radiation injury

BrainBrain-- adultadult--resistant; embryonicresistant; embryonic--neuronal/glial destructionneuronal/glial destruction

SkinSkin-- erythema; edema; depigmentation;erythema; edema; depigmentation;

atrophy; canceratrophy; cancer LungsLungs-- edema; ARDS; interstitial fibrosis;edema; ARDS; interstitial fibrosis; Lymph nodesLymph nodes-- atrophy; fibrosisatrophy; fibrosis GITGIT-- mucosal injury, ulceration, fibrosis of wallmucosal injury, ulceration, fibrosis of wall

GonadsGonads-- destruction of germ cellsdestruction of germ cells Blood & Bone marrowBlood & Bone marrow-- thrombocytopenia,thrombocytopenia,

granulocytopenia, anemia: pancytopeniagranulocytopenia, anemia: pancytopenia

A h l b d di i

8/9/2019 genPathEnv

80/81

Acute whole body radiation 1010--50 rads: no obvious effect; minor blood changes50 rads: no obvious effect; minor blood changes

5050--100 rads: vomiting & nausea for 1 day in 5100 rads: vomiting & nausea for 1 day in 5--10%; fatigue;10%; fatigue;transient reduction in lymphocytes & neutrophilstransient reduction in lymphocytes & neutrophils

100100--200 rads: vomiting & nausea for 1 dayin 20200 rads: vomiting & nausea for 1 dayin 20--50%; about50%; about50% reduction in lymphocytes & neutrophils50% reduction in lymphocytes & neutrophils

200200--350 rads: vomiting & nausea in nearly all; anorexia,350 rads: vomiting & nausea in nearly all; anorexia,

diarrhea, minor hemorrhages; about 20% die w/in 2diarrhea, minor hemorrhages; about 20% die w/in 2--6 wks6 wksafter exposure; convalescence is about 3 mos.up to 75%after exposure; convalescence is about 3 mos.up to 75%reduction in all circulating blood elementsreduction in all circulating blood elements

350350--550 rads: about 50% die w/in 1 month; convalescence is550 rads: about 50% die w/in 1 month; convalescence isabout 6 mos.about 6 mos.

550550--750 rads: vomiting & nausea in all w/in 4 hrs; up to 100%750 rads: vomiting & nausea in all w/in 4 hrs; up to 100%die; few survivors convalesce for 6 mosdie; few survivors convalesce for 6 mos

1000 rads: vomiting & nausea in all w/in 11000 rads: vomiting & nausea in all w/in 1--2 hrs; all die w/in2 hrs; all die w/indaysdays

5000 rads: almost immediate incapacitation; all die w/in 1 week5000 rads: almost immediate incapacitation; all die w/in 1 week

Th kTh k

8/9/2019 genPathEnv

81/81

Thank youThank you

very much !very much !