Gen Path Intro

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IntroductionIntroduction

totoPathologyPathology

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


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definition of Termsdefinition of Terms

PathologyPathologypathospathos suffering; diseasesuffering; diseaselogoslogos study; knowledgestudy; knowledge

-- branch of medicine concerned with determiningbranch of medicine concerned with determining

thethe nature & course of diseases by analyzing bodynature & course of diseases by analyzing bodytissues & fluidstissues & fluids

-- study of diseasesstudy of diseases


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General vs. Systemic/SpecialGeneral vs. Systemic/Special::

General PathologyGeneral Pathology disease mechanismsdisease mechanisms maymaybe common to several diseasesbe common to several diseases

Systemic/Special PathologySystemic/Special Pathologygenetic, cellular,genetic, cellular,molecular manifestations of specific diseasesmolecular manifestations of specific diseases

Anatomic/Surgical vs. ClinicalAnatomic/Surgical vs. Clinical

Anatomic/Surgical PathologyAnatomic/Surgical PathologyAutopsy; Biopsy;Autopsy; Biopsy;CytopathologyCytopathology

Clinical PathologyClinical Pathology

Hematology & Blood Banking;

Hematology & Blood Banking;Clinical Chemistry; Clinical Microscopy; Serology;Clinical Chemistry; Clinical Microscopy; Serology;

MicrobiologyMicrobiology


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Forensic PathologyForensic Pathology medicolegal investigationsmedicolegal investigations

Cardiovascular PathologyCardiovascular Pathology


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Autopsy/NecropsyAutopsy/Necropsymedical examination of amedical examination of adead human body, to determine cause ofdead human body, to determine cause ofdeath, diagnosis, or disease progressiondeath, diagnosis, or disease progression

BiopsyBiopsybiobio -- life ;life ; opsisopsis -- a viewinga viewing thethe

removal of a sample of tissue from a livingremoval of a sample of tissue from a livingperson for laboratory examination; primarilyperson for laboratory examination; primarilyfor the detection of Cancerfor the detection of Cancer

Excision biopsyExcision biopsy

Incision biopsyIncision biopsy

Fine needle aspiration biopsy (FNAB)Fine needle aspiration biopsy (FNAB)

Frozen section biopsyFrozen section biopsy


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ExfoliativeCytopathologyExfoliativeCytopathologymicroscopicmicroscopicexamination of cells in body tissues or bodyexamination of cells in body tissues or bodyfluids primarily to determine if they arefluids primarily to determine if they arecancerous; uses thecancerous; uses the PapanicolaouPapanicolaou methodmethodof staining, hence the term of staining, hence the term Pap smearPap smear

Clinical MicroscopyClinical MicroscopyHematology & Blood BankingHematology & Blood Banking

Serology & ImmunologySerology & Immunology

Microbiology/BacteriologyMicrobiology/BacteriologyClinicalChemistryClinicalChemistry


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FourAspects of a DiseaseFourAspects of a Disease

EtiologyEtiology cause /causes of the diseasecause /causes of the disease

PathogenesisPathogenesis development of the disease;development of the disease;

chronologicprogression ofpathologic changeschronologicprogression ofpathologic changesMorphologic changesMorphologic changes -- signs signs anatomic /anatomic /

histologic changes; objective; can be seen or measuredhistologic changes; objective; can be seen or measured

Functional derangements/ClinicalFunctional derangements/Clinical significancesignificance--symptomssymptoms subjective; what apatient feels;subjective; what apatient feels;

limitations onpatients normal activities;prognosislimitations onpatients normal activities;prognosis


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Cellular Pathology:Cellular Pathology:CellularAdaptationCellularAdaptation

Cellular Injury &Cell DeathCellular Injury &Cell Death

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


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CellularAdaptation;Cellular Injury;CellularAdaptation;Cellular Injury;

Cell DeathCell Death

NormalCellNormalCell

CellularCellular----------------------------------------ReversibleReversible------------------------------Cell DeathCell Death

AdaptationAdaptation InjuryInjury

AtrophyAtrophy FattyChangeFattyChange NecrosisNecrosis

HypertrophyHypertrophy Cloudy swellingCloudy swelling ApoptosisApoptosis

HyperplasiaHyperplasia

MetaplasiaMetaplasia


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TheCellCycleTheCellCycle

Labile cellsLabile cellscells thatcells thatnever leave the cell cycle;never leave the cell cycle;retain their mitotic abilityretain their mitotic ability

Permanent cellsPermanent cellscells thatcells thatleave the cell cycleleave the cell cyclepermanently; no mitoticpermanently; no mitoticabilityability

Stable cellsStable cellscells that havecells that havetemporarily left the celltemporarily left the cellcycle; mitotic ability iscycle; mitotic ability isretained but quiescent, mayretained but quiescent, mayoccur when neededoccur when needed

M= MITOSIS

G 1

G 2


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CellularAdaptationCellularAdaptation

HyperplasiaHyperplasiaincrease in number of cells throughincrease in number of cells through

cell divisioncell division

HypertrophyHypertrophyincrease in cell size due toincrease in cell size due toincrease in cellular componentsincrease in cellular components

AtrophyAtrophydecrease in cell size due to reduction indecrease in cell size due to reduction incell components; associated with increasedcell components; associated with increased

autophagic vacuoles & lipofuscin pigmentautophagic vacuoles & lipofuscin pigment

MetaplasiaMetaplasiachange from one adult cell type tochange from one adult cell type to

another due to chronic irritation; alwaysanother due to chronic irritation; always

pathologicpathologic


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CellularAdaptationCellularAdaptation

(cystic) hyperplasia

(squamous) metaplasia

atrophy

hypertrophy


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Cellular InjuryCellular Injury::

GeneralConsiderationsGeneralConsiderations

The structural & biochemical elements of the cell areThe structural & biochemical elements of the cell are

so closely interso closely inter--related that whatever the precise pointrelated that whatever the precise point

of initial attack, injury at one locus leads to wideof initial attack, injury at one locus leads to wide--

ranging secondary effectsranging secondary effectsMorphologic changes become apparent only whenMorphologic changes become apparent only when

some critical biochemical system has been derangedsome critical biochemical system has been deranged

Reactions of the cell to injurious stimuli depend on theReactions of the cell to injurious stimuli depend on thetype, duration, & severity of injury, as well as on thetype, duration, & severity of injury, as well as on the

type, state, & adaptability of the celltype, state, & adaptability of the cell


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Causes ofCellular InjuryCauses ofCellular Injury

HYPOXIAHYPOXIA

PHYSICALAGENTSPHYSICALAGENTS

CHEMICALAGENTS/DRUGSCHEMICALAGENTS/DRUGS BIOLOGICAGENTSBIOLOGICAGENTS

IMMUNOLOGIC REACTIONSIMMUNOLOGIC REACTIONS

GENETIC DERANGEMENTSGENETIC DERANGEMENTS NUTRITIONAL IMBALANCESNUTRITIONAL IMBALANCES


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CellularComponents/ProcessesCellularComponents/Processes

most vulnerable to Injurymost vulnerable to Injury

Cell membraneCell membraneSelective permeabilitySelective permeability

MitochondriaMitochondriaAerobic respiration /Aerobic respiration /Oxidative phosphorylationOxidative phosphorylation

RibosomesRibosomes//Rough Endoplasmic reticulumRough Endoplasmic reticulum

Protein synthesisProtein synthesis Nuclear chromatinNuclear chromatinGenetic material /Genetic material /

DNADNA control of cellular activitiescontrol of cellular activities


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Common Biochemical themes inCommon Biochemical themes in

Cellular InjuryCellular Injury

ATPATPdepletion & defects in Membranedepletion & defects in Membrane

permeabilitypermeability intracellular intracellularCalciumCalcium & loss of& loss of

Calcium homeostasisCalcium homeostasis

Oxygen & production of Oxygen Oxygen & production of Oxygen--derivedderivedfree radicalsfree radicals


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Free RadicalsFree Radicals

definitiondefinition chemical species that have a singlechemical species that have a singleunpaired electron in an outer orbital; extremelyunpaired electron in an outer orbital; extremelyreactive & unstable, can react with organic orreactive & unstable, can react with organic orinorganic chemicals, esp. cell membranes & nucleicinorganic chemicals, esp. cell membranes & nucleic

acidsacids HydroxylHydroxylOHOH;; Hydrogen peroxideHydrogen peroxide HH22OO22; Superoxide; Superoxide

OO22 ;; Nitric oxideNitric oxide NONO

actionsactions lipid peroxidation of cell membranes;lipid peroxidation of cell membranes;

denaturation of proteins; DNA

mutationdenaturation of proteins; DNA

mutation neutralized byneutralized byAntiAnti--oxidants (oxidants (vitE, vit C, sulfhydrilvitE, vit C, sulfhydril--containing compounds Cysteine, Glutathionecontaining compounds Cysteine, Glutathione--GSH,GSH,Albumin, Ceruloplasmin, Transferrin, SuperoxideAlbumin, Ceruloplasmin, Transferrin, Superoxidedismutase, GSHperoxidasedismutase, GSHperoxidase))


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ReversibleCellular InjuryReversibleCellular Injury

Fatty changeFatty changereplacement ofreplacement of

parenchymal cells by lipidparenchymal cells by lipid

dropletsdroplets-- most commonlymost commonlyseen in the liverseen in the liver

Cloudy swellingCloudy swelling

accumulation of wateraccumulation of waterwithin cellswithin cells -- mostmostcommonly seen in renalcommonly seen in renaltubular cells:tubular cells: groundgroundglassglassororcloudycloudy

histologic appearancehistologic appearance


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IrreversibleCellular Injury /Cell DeathIrreversibleCellular Injury /Cell Death

NECROSISNECROSIS

changes that occur inchanges that occur in

the irreversiblythe irreversibly

injured cellinjured cell --denaturation ofdenaturation of

proteinsproteins &&

subsequentsubsequentenzymaticenzymatic

digestiondigestion;; alwaysalwayspathologic; involves apathologic; involves a

group of cells;group of cells;

accompanied byaccompanied by

inflammationinflammation

APOPTOSISAPOPTOSISfalling offfalling off--chromatinchromatin

condensationcondensation &&subsequentsubsequentfragmentationfragmentation of theof thedead cell intodead cell intoapoptotic bodiesapoptotic bodies;;

physiologic orphysiologic orpathologic; maypathologic; mayoccur in a single cell;occur in a single cell;no inflammationno inflammation


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Patterns ofPatterns ofNecrosisNecrosis

Coagulative/CoagulationCoagulative/Coagulation cell shape iscell shape ispreserved; denaturation of cellular proteins;preserved; denaturation of cellular proteins;tombstone cellstombstone cells

Liquefactive/LiquefactionLiquefactive/Liquefaction amorphous necroticamorphous necrotic

debris due to hydrolytic enzymatic dissolution;debris due to hydrolytic enzymatic dissolution;typical of brain injury; abscesstypical of brain injury; abscess

Caseous/CaseationCaseous/Caseation coagulation, then incompletecoagulation, then incompletedissolution; typical ofTBdissolution; typical ofTB

Gangrenous/GangreneGangrenous/Gangrene coagulation + bacterialcoagulation + bacterialcontamination (varying degrees of liquefaction):contamination (varying degrees of liquefaction):wetwetorordrydry-- diabetic woundsdiabetic wounds

Fat NecrosisFat Necrosis:: TraumaticTraumatic breast; subcutaneousbreast; subcutaneousfat;fat; EnzymaticEnzymatic pancreatitispancreatitis


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Coagulative Necrosis /Liquefactive NecrosisCoagulative Necrosis /Liquefactive Necrosis


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Caseation NecrosisCaseation Necrosis


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Gangrenous NecrosisGangrenous Necrosis


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Traumatic & EnzymaticFat NecrosisTraumatic & EnzymaticFat Necrosis


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ApoptosisApoptosis

PhysiologicPhysiologic:: programmed destruction of cells during embryogenesis &programmed destruction of cells during embryogenesis &

organogenesis; developmental involution; programmedorganogenesis; developmental involution; programmedcell deathcell death

in adults, hormonein adults, hormone--dependent involution e.g. menopause,dependent involution e.g. menopause,postpost--partum, thymic involutionpartum, thymic involution

cell deletion in proliferating cell populations e.g. epithelialcell deletion in proliferating cell populations e.g. epithelialrenewalrenewal

PathologicPathologic:: cell death in tumors; cell death in viral injurycell death in tumors; cell death in viral injury death of immune cells; cytotoxicTdeath of immune cells; cytotoxicT--cell actioncell action

pathologic atrophy of hormonepathologic atrophy of hormone--dependent tissuesdependent tissues

in parenchymal organs due to duct obstructionin parenchymal organs due to duct obstruction


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ApoptosisApoptosis

Councilman bodies in Hepatitis


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PathologicCalcification:PathologicCalcification:deposition ofCalciumdeposition ofCalciumsalts + smaller amounts ofFe, Mg, & other mineral saltssalts + smaller amounts ofFe, Mg, & other mineral salts

DystrophicDystrophic in dead orin dead ordying tissues, regardless ofdying tissues, regardless ofCa levels, in the absence ofCa levels, in the absence of

abnormalC

a metabolismabnormalC

a metabolism atheromasatheromas

aging/damaged heartaging/damaged heartvalvesvalves

myocardial infarctsmyocardial infarcts

tuberculomastuberculomas

psammoma bodiespsammoma bodies

MetastaticMetastatic in vital or viablein vital or viabletissues when there istissues when there ishypercalcemia, almost alwayshypercalcemia, almost always

with some derangement ofC

awith some derangement ofC

ametabolismmetabolism

usually in interstitial tissuesusually in interstitial tissuesof blood vessels, kidneys,of blood vessels, kidneys,lungs, gastric mucosalungs, gastric mucosa

hyperCa: hyperparathyroidismhyperCa: hyperparathyroidismhyperthyroidism, systemichyperthyroidism, systemicsarcoidosis, vit D intoxicationsarcoidosis, vit D intoxicationAddisons dse, metastaticAddisons dse, metastatictumors, bone tumors, MMtumors, bone tumors, MM


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PathologicCalcificationPathologicCalcification

grossgross: fine white granules or clumps felt as gritty: fine white granules or clumps felt as gritty

deposits; crumbled chalk appearancedeposits; crumbled chalk appearance

microscopicmicroscopic: H & E: basophilic amorphous granular: H & E: basophilic amorphous granularor clumped deposits, intraor clumped deposits, intra-- or extraor extra-- cellular;cellular;

psammoma bodiespsammoma bodies lamellated circular Ca depositslamellated circular Ca deposits

seen inpapillary tumorsseen inpapillary tumors


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PathologicCalcificationPathologicCalcification

DystrophicDystrophic

calcificationcalcification

deposition ofdeposition ofCalciumCalcium

inin dead or dyingdead or dyingtissuestissues

MetastaticMetastatic

calcificationcalcificationdeposition ofdeposition ofCalciumCalcium

inin viable tissuesviable tissues -- duedue

toto hypercalcemiahypercalcemia


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IntracellularAccumulationsIntracellularAccumulations

intranuclear or cytoplasmicintranuclear or cytoplasmic

normal cellular constituent or abnormal substancenormal cellular constituent or abnormal substance

endogenous or exogenous abnormal substanceendogenous or exogenous abnormal substance may be apigment (endogenous or exogenous)may be apigment (endogenous or exogenous)

may be an infectiousproductmay be an infectiousproduct

accumulation may be due to overproduction,accumulation may be due to overproduction,inadequate metabolism & excretion, or bothinadequate metabolism & excretion, or both


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IntracellularAccumulationsIntracellularAccumulations

LipidsLipids accumulation of Triglycerides withinparenchymalaccumulation of Triglycerides withinparenchymalcellscells FattyLiver ofAlcoholism, Kwashiorkor, DM, Obesity, AnoxiaFattyLiver ofAlcoholism, Kwashiorkor, DM, Obesity, Anoxia

& Toxins& Toxins

may also occur in the Heart, Muscles, Kidneysmay also occur in the Heart, Muscles, KidneysProteinsProteins usually as rounded eosinophilic droplets, vacuoles,usually as rounded eosinophilic droplets, vacuoles,

massesmasses Hyaline droplets in kidneys(PCT) in dses with proteinuriaHyaline droplets in kidneys(PCT) in dses with proteinuria

Russell bodiesRussell bodies excess Igs in plasma cellsexcess Igs in plasma cellsCarbohydratesCarbohydrates Glycogen storage disordersGlycogen storage disorders

PigmentsPigments Lipofuscin, Hematin, Melanin, homogentisic acid,Lipofuscin, Hematin, Melanin, homogentisic acid,


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MiscellanyMiscellany

LysosomesLysosomes

HeterophagyHeterophagy ingestion of outside material by endocytosisingestion of outside material by endocytosis

AutophagyAutophagy intracellular material (e.g. senescentintracellular material (e.g. senescent

organelles) is sequestered into autophagic vacuolesorganelles) is sequestered into autophagic vacuoles Residual bodiesResidual bodies lysosomes with undigested debrislysosomes with undigested debris

LipofuscinLipofuscin yellowyellow--brown pigment granules that representbrown pigment granules that represent

undigested material from intracellular lipid peroxidationundigested material from intracellular lipid peroxidation

Smooth ER induction (Hypertrophy)Smooth ER induction (Hypertrophy) for detoxification fnfor detoxification fn Barbiturates, Steroids,Barbiturates, Steroids,

Carcinogenic hydrocarbons, insecticides, Alcohol, CCl4Carcinogenic hydrocarbons, insecticides, Alcohol, CCl4


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MiscellanyMiscellany

Mitochondria: alterations in size, shape, numberMitochondria: alterations in size, shape, number MegamitochondriaMegamitochondria very large due to increased metabolicvery large due to increased metabolic

demands e.g. in alcoholic hepatitis, nutritional deficienciesdemands e.g. in alcoholic hepatitis, nutritional deficiencies

Mitochondrial myopathiesMitochondrial myopathies -- in number, + abnormal cristae &in number, + abnormal cristae &

crystalloids seen in skeletal muscle disorderscrystalloids seen in skeletal muscle disorders increase in size & numberincrease in size & number in Oncocytomas of the salivaryin Oncocytomas of the salivary

glands, thyroids, parathyroids, kidneysglands, thyroids, parathyroids, kidneys

Cytoskeleton:Cytoskeleton: defects in cell locomotion & intracellular organelledefects in cell locomotion & intracellular organelle

movements e.g. Chediakmovements e.g. Chediak--Hegashi syndrome; immotile ciliaHegashi syndrome; immotile ciliasyndromesyndrome

accumulation of microtubules & intermediate filamentsaccumulation of microtubules & intermediate filaments

e.g. neurofibrillary tangles in Alzheimers diseasee.g. neurofibrillary tangles in Alzheimers disease


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Thank youThank you

&&

Good Day !Good Day !

Gen Path Intro

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