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