Introduction to Basic Pathology; Cellular Reaction to Injuries

Introduction to Basic Pathology; Cellular Reaction to Injuries`
Dr. ROOPAPathophysiology Premed 2

Basic Pathophysiology
Basic PathologyBasic MicrobiologyBacteriologyVirologyMycologyImmunologyBasic Pharmacology

What is Pathology?

Pathology
Branch of MedicineStudies the underlying causes of diseasesetiologyMechanisms that result in the signs and symptoms of the patientpathogenesis

Pathology
Bridge between basic science and clinical practicestudy of sufferingDivisions:General PathologySystemic Pathology

The Cell

How do cells react to environmental stress?
HypertrophyHyperplasiaAplasiaHypoplasiaAtrophyMetaplasia

Hypertrophy
Increase in protein synthesis/ organelles

Increase in size of cells

Increase in organ/tissue size

Hypertrophy

Hyperplasia
Increase in NUMBER of cells

Increase in size of organ/tissue

Similar end result as hypertrophyMay occur with hypertrophy

Hyperplasia

Aplasia
Failure of cell production

Agenesis or absence of an organ:fetusLoss of precursor cells:adults

Aplasia

Hypoplasia
Decrease in cell production

Atrophy
Decrease in mass of preexisting cells

Smaller tissue/organMost common causes:disusepoor nutritionlack of oxygenlack of endocrine stimulationaginginjury of the nerves

Atrophy

Metaplasia
Replacement of one tissue by another tissueSeveral forms:Squamous metaplasiaCartilaginous metaplasiaosseous metaplasiamyeloid metaplasia

Metaplasia

DEFINITION- DYSPLASIA
Dysplasia means disordered growth, most commonly seen in squamous epithelial cells following chronic injury.

What are the causes of injury/stress?
Hypoxic cell injuryFree radical injuryChemical cell injury

Hypoxic cell injury
Complete lack of oxygen/ decreased oxygenAnoxia or hypoxiaCauses:ischemiaanemiacarbon monoxide poisoningdecrease tissue perfusionpoorly-oxygenated blood

Hypoxic cell injury

Early stage Hypoxic cell injury
Decrease in production of ATPChanges in cell membraneCellular swellingendoplasmic reticulummitochondriaRibosomes disaggregateFailure of protein synthesisClumping of chromatin

Late stage
Cell membrane damagemyelin blebscell blebs

Cell Death
Irreversible damage to the cell membranesCalcium influxMitochondria calcifiesRelease of cellular enzymesMost vulnerable cells:neurons

Free radicals: superoxide and hydroxyl radicals
Seen in:normal metabolismoxygen toxicityionizing radiationUV lightdrugs/chemicalsischemia

Mechanisms to detoxify free radicals
GlutathioneCatalaseSuperoxide dismutaseVitamin A, C, ECysteine,glutathione, selenium, ceruloplasminSpontaneous decay

Chemical Injury
Carbon tetrachloride and liver damage

NECROSIS AND APOPTOSIS
Necrosissum of the morphologic changes that follow cellular death in the tissue or organs.Mainly 2 processes cause the morphologic changes of necrosis;Denaturation of proteinsEnzymatic digestion of organelles n other cytosolic components.

Autolysis cell digestion due to hydralytic enzymes derived from dead cells.Heterolysis ; derived from invading inflammatory cells.

Types of necrosis
Coagulative necrosis Liquefactive necrosisCaseous necrosisGangrenous necrosisFibrinoid necrosisFat necrosis

Coagulative necrosis
Interruption of the blood supplyCommonest form of necrosisPoor collateral circulationheartkidneyCharacteristic nuclear changespyknosiskaryorrhexiskaryolysisdisappearance of a nuclei

NUCLEAR CHANGES
Karyolysis- disintegration and dissolution of a cell nucleus when a cell diesDue to DNA se activity Basophilia of chromatin fade

NUCLEAR CHANGES
Pyknosis a degenerative state of the cell nucleus-Nuclear shrinkage - Increased basophiliaKaryorrhexis nuclear fragmentation within 1 or 2 days nucleus disappears.

Coagulative Necrosis

Liquefactive necrosis
Is typically found in the brain or in an abscess. Tissue is softened through the action of enzymes released from brain or in the case of an abscess, PMN.

Liquefactive necrosis

Caseous necrosis
Coagulative + liquefactivecheese - likePart of granulomatous inflammationClassic picture:Tuberculosis

Caseous necrosis

Gangrenous necrosis
Interuption of the blood supply to the lower extremities or bowelsWet type: complicated by liquefactive necrosisDry type: complicated by coagulative necrosis

Gangrenous necrosis

Fibrinoid necrosis
Immune-mediated vascular damageProtein like material in the blood vessel walls

Fat necrosis
Traumatic fat necrosis after injuryBreastEnzymatic fat necrosis after inflammationPancreas

FAT NECROSIS

APOPTOSIS
-Programmed cell deathOccurs when a cell dies through the activation of an internal suicide program.This is mainly useful in eliminating the unwanted cells with minimal disruption of the surronunding tissue.Can be seen mainly in the elimination of unwanted cells during embryogenesis.

Necrosis versus apoptosis
Gross irreversible cell injuryPassive form of cell deathDoes not require genes, protein synthesisMarked inflammatory reaction
Physiologic programmed cell removalActive form of cell deathRequires genes, proteins, energyNo inflammatory reaction

Genes affecting apoptosis
Inhibits:bcl-2

Facilitates:baxp53

Morphological features in apoptosis
Involves small clusters of cells onlyNo inflammatory cellsCell membrane blebsCytoplasmic shrinkageChromatin condensationPhagocytosis of apoptotic bodies

*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*