Pathophysiology: Pathophysiology: Introduction to Basic Introduction to Basic

PathologyPathology

Lecture 1Lecture 1Dr. Karen RonquilloDr. Karen Ronquillo

Premed 2Premed 2

Basic PathophysiologyBasic Pathophysiology

Basic PathologyBasic Pathology Basic MicrobiologyBasic Microbiology

BacteriologyBacteriology

VirologyVirology

MycologyMycology

ImmunologyImmunology Basic PharmacologyBasic Pharmacology

What is Pathology?What is Pathology?

PathologyPathology

Branch of MedicineBranch of Medicine ““suffering’suffering’ Studies the underlying causes of Studies the underlying causes of

diseasesdiseases

““etiology”etiology” Mechanisms that result in the signs Mechanisms that result in the signs

and symptoms of the patientand symptoms of the patient

““pathogenesis”pathogenesis”

PathologyPathology

Bridge between basic science and Bridge between basic science and clinical practiceclinical practice

Divisions:Divisions:

General PathologyGeneral Pathology

Systemic PathologySystemic Pathology

The CellThe Cell

How do cells react to How do cells react to environmental stress?environmental stress?

HypertrophyHypertrophy HyperplasiaHyperplasia AplasiaAplasia HypoplasiaHypoplasia AtrophyAtrophy MetaplasiaMetaplasia

HypertrophyHypertrophy

Increase in protein synthesis/ Increase in protein synthesis/ organellesorganelles

Increase in size of cellsIncrease in size of cells

Increase in organ/tissue sizeIncrease in organ/tissue size

HypertrophyHypertrophy

HyperplasiaHyperplasia

Increase in NUMBER of cellsIncrease in NUMBER of cells

Increase in size of organ/tissueIncrease in size of organ/tissue

Similar end result as hypertrophySimilar end result as hypertrophy May occur with hypertrophyMay occur with hypertrophy

HyperplasiaHyperplasia

AplasiaAplasia

Failure of cell productionFailure of cell production

Agenesis or absence of an Agenesis or absence of an organ:fetusorgan:fetus

Loss of precursor cells:adultsLoss of precursor cells:adults

Technetium: scintigraphy

AplasiaAplasia

HypoplasiaHypoplasia

Decrease in cell productionDecrease in cell production

AtrophyAtrophy Decrease in mass of preexisting cellsDecrease in mass of preexisting cells

Smaller tissue/organSmaller tissue/organ Most common causes:Most common causes:

disusedisusepoor nutritionpoor nutritionlack of oxygenlack of oxygenlack of endocrine stimulationlack of endocrine stimulationagingaginginjury of the nervesinjury of the nerves

AtrophyAtrophy

MetaplasiaMetaplasia

Replacement of one tissue by Replacement of one tissue by another tissueanother tissue

Several forms:Several forms:

Squamous metaplasiaSquamous metaplasia

Cartilaginous metaplasiaCartilaginous metaplasia

osseous metaplasiaosseous metaplasia

myeloid metaplasiamyeloid metaplasia

MetaplasiaMetaplasia

Squamous to columnar change in cells

Barrett’s esophagusBarrett’s esophagus

What are the causes of What are the causes of injury/stress?injury/stress?

Hypoxic cell injuryHypoxic cell injury Free radical injuryFree radical injury Chemical cell injuryChemical cell injury

Hypoxic cell injuryHypoxic cell injury

Complete lack of oxygen/ decreased Complete lack of oxygen/ decreased oxygenoxygen

Anoxia or hypoxiaAnoxia or hypoxia Causes:Causes:

ischemiaischemia

anemiaanemia

carbon monoxide poisoningcarbon monoxide poisoning

decrease tissue perfusiondecrease tissue perfusion

poorly-oxygenated bloodpoorly-oxygenated blood

Hypoxic cell injuryHypoxic cell injury

Early stage Hypoxic cell Early stage Hypoxic cell injuryinjury

Decrease in production of ATPDecrease in production of ATP Changes in cell membraneChanges in cell membrane Cellular swellingCellular swelling

endoplasmic reticulumendoplasmic reticulummitochondriamitochondria

Ribosomes disaggregateRibosomes disaggregate Failure of protein synthesisFailure of protein synthesis Clumping of chromatinClumping of chromatin

Late stage Late stage

Cell membrane damageCell membrane damage

myelin blebsmyelin blebs

cell blebscell blebs

Cell DeathCell Death

Irreversible damage to the cell Irreversible damage to the cell membranesmembranes

Calcium influxCalcium influx Mitochondria calcifiesMitochondria calcifies Release of cellular enzymesRelease of cellular enzymes

lab exams for AST, ALT, CKMB, LDHlab exams for AST, ALT, CKMB, LDH Most vulnerable cells:Most vulnerable cells:

neuronsneurons

Cardiac enzymesCardiac enzymes

CKMB kitCKMB kit

Free radicals: superoxide and Free radicals: superoxide and hydroxyl radicalshydroxyl radicals

Seen in:Seen in:

normal metabolismnormal metabolism

oxygen toxicityoxygen toxicity

ionizing radiationionizing radiation

UV lightUV light

drugs/chemicalsdrugs/chemicals

ischemiaischemia

What will neutralize free What will neutralize free radicals?radicals?

Mechanisms to detoxify free Mechanisms to detoxify free radicalsradicals

GlutathioneGlutathione CatalaseCatalase Superoxide dismutaseSuperoxide dismutase Vitamin A, C, EVitamin A, C, E Cysteine, selenium, ceruloplasminCysteine, selenium, ceruloplasmin Spontaneous decaySpontaneous decay

Chemical InjuryChemical Injury

Carbon tetrachloride and liver Carbon tetrachloride and liver damagedamage

Morphologic patterns of cell Morphologic patterns of cell death:death:

NECROSIS AND APOPTOSISNECROSIS AND APOPTOSIS NecrosisNecrosis

sum of all the reactions seen in sum of all the reactions seen in an an injured tissue, leads to cell deathinjured tissue, leads to cell death

autolysis – cell’s enzymesautolysis – cell’s enzymes Heterolysis – extrinsic factorsHeterolysis – extrinsic factors

Types of necrosisTypes of necrosis

Coagulative necrosis Coagulative necrosis Liquefactive necrosisLiquefactive necrosis Caseous necrosisCaseous necrosis Gangrenous necrosisGangrenous necrosis Fibrinoid necrosisFibrinoid necrosis Fat necrosisFat necrosis

Coagulative necrosisCoagulative necrosis

Interruption of the blood supplyInterruption of the blood supply

Poor collateral circulationPoor collateral circulationheartheartkidneykidney

Characteristic nuclear Characteristic nuclear changeschanges

Coagulative necrosisCoagulative necrosis

Coagulative NecrosisCoagulative Necrosis

Liquefactive necrosisLiquefactive necrosis

Interruption of blood supplyInterruption of blood supply Enzymes liquefy the tissueEnzymes liquefy the tissue

BrainBrain Suppurative infectionsSuppurative infections

BacteriaBacteria

Liquefactive necrosisLiquefactive necrosis

Caseous necrosisCaseous necrosis

Coagulative + liquefactiveCoagulative + liquefactive ““cheese - like”cheese - like” Part of granulomatous inflammationPart of granulomatous inflammation Classic picture:Classic picture:

Tuberculosis Tuberculosis

Caseous necrosisCaseous necrosis

Gangrenous necrosisGangrenous necrosis

Interuption of the blood supply to the Interuption of the blood supply to the lower extremities or bowelslower extremities or bowels

2 types: 2 types:

1. Wet type: complicated by 1. Wet type: complicated by liquefactive necrosisliquefactive necrosis

2. Dry type: complicated by 2. Dry type: complicated by coagulative necrosiscoagulative necrosis

Gangrenous necrosis typesGangrenous necrosis types

Fibrinoid necrosisFibrinoid necrosis

Immune-mediated vascular damageImmune-mediated vascular damage Protein – like material in the blood Protein – like material in the blood

vessel wallsvessel walls

Fat necrosisFat necrosis

Traumatic fat necrosis: after injuryTraumatic fat necrosis: after injury

BreastBreast

ENZYMATIC FAT NECROSIS: ENZYMATIC FAT NECROSIS: PANCREASPANCREAS

APOPTOSISAPOPTOSIS

““falling away from”falling away from” Another cell death patternAnother cell death pattern ““Programmed cell death”Programmed cell death” Removal of cellsRemoval of cells Prevents neoplastic transformationPrevents neoplastic transformation

Necrosis versus apoptosisNecrosis versus apoptosis

Gross irreversible Gross irreversible cell injurycell injury

Passive form of cell Passive form of cell deathdeath

Does not require Does not require genes, protein genes, protein synthesissynthesis

Marked Marked inflammatory inflammatory reactionreaction

Physiologic Physiologic programmed cell programmed cell removalremoval

Active form of cell Active form of cell deathdeath

Requires genes, Requires genes, proteins, energyproteins, energy

No inflammatory No inflammatory reactionreaction

Genes affecting apoptosisGenes affecting apoptosis

Inhibits:Inhibits:

bcl-2bcl-2

Facilitates:Facilitates:

baxbax

p53p53

Morphological features in Morphological features in apoptosisapoptosis

Involves small clusters of cells onlyInvolves small clusters of cells only No inflammatory cellNo inflammatory cellss Cell membrane blebsCell membrane blebs Cytoplasmic shrinkageCytoplasmic shrinkage Chromatin condensationChromatin condensation Phagocytosis of apoptotic bodiesPhagocytosis of apoptotic bodies

Reversible Cellular changes Reversible Cellular changes

Fatty changeFatty change Hyaline changeHyaline change Accumulation of exogenous pigmentsAccumulation of exogenous pigments Accumulation of endogenous Accumulation of endogenous

pigmentspigments Pathologic calcificationsPathologic calcifications

Fatty changeFatty change

Liver, heart, kidneyLiver, heart, kidney Accumulation of intracellular Accumulation of intracellular

parenchymal triglyceridesparenchymal triglycerides

-increased transport-increased transport

-decrease mobilization-decrease mobilization

-decreased use-decreased use

-overproduction-overproduction

Fatty change: LIVERFatty change: LIVER

Hyaline changeHyaline change

Accumulation of hyalineAccumulation of hyaline HYPERTENSION; DIABETES MELLITUSHYPERTENSION; DIABETES MELLITUS ““glassy” appearanceglassy” appearance

Exogenous pigmentsExogenous pigments

LungsLungs

carboncarbon

silicasilica

iron dustiron dust Lead – PlumbismLead – Plumbism Silver - ArgyriaSilver - Argyria

Endogenous pigmentsEndogenous pigments

Bilirubin Hemosiderin

LipofuscinLipofuscin ““wear and tear” wear and tear”

pigmentpigment Elderly patientsElderly patients Liver, heartLiver, heart

Brown atrophyBrown atrophy

Pathologic calcificationsPathologic calcifications

Previously damages tissuesPreviously damages tissues

““dystrophic calcification”dystrophic calcification”

scarred heart valvesscarred heart valves

Pathologic calcificationsPathologic calcifications

Hypercalcemia Hypercalcemia

““metastatic calcification”metastatic calcification”

Question:Question:

A young woman was admitted due to a A young woman was admitted due to a bacterial infection. CT scan showed an bacterial infection. CT scan showed an abscess in her brain. What type of necrosis abscess in her brain. What type of necrosis would you expect to see?would you expect to see?

A.coagulativeA.coagulative B.CaseousB.Caseous C.LiquefactiveC.Liquefactive

Question:Question:

A 15 year old girl was brought into A 15 year old girl was brought into your clinic due to painful menses. She your clinic due to painful menses. She also said that her menstrual blood flow also said that her menstrual blood flow was heavy and had clumps of blood was heavy and had clumps of blood clots and tissues.Menstruation is clots and tissues.Menstruation is classified as:classified as:

A. ApoptosisA. Apoptosis B. Coagulative NecrosisB. Coagulative Necrosis C. Liquifactive NecrosisC. Liquifactive Necrosis