CELL ADAPTATIONS CELL INJURY CELL DEATH DR.SAMINA QAMAR AP PATHOLOGY

CELL ADAPTATIONSCELL ADAPTATIONS

CELL INJURYCELL INJURY

CELL DEATHCELL DEATH

DR.SAMINA QAMARDR.SAMINA QAMAR

AP PATHOLOGY.AP PATHOLOGY.

OBJECTIVESUnderstand the concepts of cellular growth

adaptations---Hyperplasia, Hypertrophy, Atrophy, Metaplasia, Dysplasia

Reversible, irreversible cell injury

OBJECTIVESUnderstand the pathologic mechanisms at

the SUB-cellular level---ATP, Mitochondria, Ca++, Free Radicals, Membranes

Understand and differentiate the concepts of APOPTOSIS and NECROSIS

Understand SUB-cellular responses to injury---Lysosomes, Smooth endoplasmic reticulum, Mitochondria, Cytoskeleton

OBJECTIVESIdentify common patterns of cellular

swelling and fatty change.Cell aging

To maintain a steady state of structure and function is

HOMEOSTASIS

Cellular response to injury

• Non-lethal injury: cell will adapt• Hypoxia, chemical injury, infection:

Reversible injury will result in fatty change. Irreversible injury will result in death

• Repeated Injury: cellular aging

ADAPTATIONS: Non-lethal injury.

• Altered/changed steady state in structure and function of cell.

• WHY: In response to physical/ pathological stimuli. Increased or decreased stimulation or any irritation.

The –plasia brothers• HYPER-• HYPO- (A-)• NORMO-

• META-

• DYS-• ANA-• “Frank” ANA-

HYPER-PLASIAIN-CREASE IN NUMBER OF CELLS, if they can divide.

Examples: Endometrium,breast,liver.

The –trophy brothers• HYPER-• HYPO- (A-)

• DYS-

HYPER-TROPHYIN-CREASE IN SIZE OF CELLS

Examples:Myocardium, Myometrium, Muscle

Hypertrophy v/s Hyperplasia.

Can both occur simultaneously?

A-TROPHY*?DE-CREASE IN SIZE OF CELLS? YES

SHRINKAGE IN CELL SIZE DUE TO LOSS OF CELL

SUBSTANCE

ATROPHY• DECREASED WORKLOAD• DENERVATION• DECREASED BLOOD FLOW• DECREASED NUTRITION• AGING (involution)• PRESSURE• “EXHAUSTION”

Examples: Brain, Muscle.

METAPLASIA• A SUBSTITUTION of one NORMAL

CELL or TISSUE type, for ANOTHER– COLUMNAR SQUAMOUS (Cervix)– SQUAMOUS COLUMNAR

(Esophagus)– FIBROUS BONE

–WHY?

Examples: Respiratory epithelium, Barrett’s, myositis ossificans.

Dysplasia: disorganized epithelium.

Dysplasia:

Normal-hyperplasia-dysplasia-carcinoma.

CELL DEATH

CELL DEATHWhat is DEATH?

–DEATH is IRREVERSIBLE–But in cell its either reversible or irreversible.

• APOPTOSIS vs. NECROSIS

REVERSIBLE CHANGES

• REDUCED oxidative phosphorylation

• ATP depletion• Cellular “SWELLING”

IRREVERSIBLE CHANGES

• MITOCHONDRIAL IRREVERSIBILITY

• IRREVERSIBLE MEMBRANE DEFECTS

• LYSOSOMAL DIGESTION

REVERSIBLE = INJURY

IRREVERSIBLE = DEATH

SOME INJURIES CAN LEAD TO DEATH IF PROLONGED

and/or SEVERE enough

CELL DEATH• APOPTOSIS (“normal”

death) programmed death.• NECROSIS (“premature”

or “untimely” death

Death is of two types

INJURY CAUSES (REVERSIBLE)Hypoxia, (decreased O2)

PHYSICAL Agents

CHEMICAL Agents

INFECTIOUS Agents

Immunologic

Genetic

Nutritional

CHEMICAL INJURY• “Toxic” Chemicals, e.g CCl4 • Drugs, e.g tylenol• Dose Relationship• Free radicals, organelle, DNA

damage

INJURY MECHANISMS (REVERSIBLE)DECREASED ATP

MITOCHONDRIAL DAMAGE

INCREASED INTRACELLULAR CALCIUM

INCREASED FREE RADICALS

INCREASED CELL MEMBRANE PERMEABILITY

What is Death?What is Life?

•DEATH is–IRREVERSIBLE MITOCHONDRIAL

DYSFUNCTION–PROFOUND MEMBRANE

DISTURBANCESLIFE is……..??? Till death hasn’t

occurred.

DEATH:ELECTRON MICROSCOPY

B-Microvillus incorporated in cell,Blebs extruded from cell.C- Mitochondrial swelling.

DEATH:PINK INLIGHT MICROSCOPY

Nuclei

LIQUEFACTIVE NECROSIS, BRAIN

FIBRINOID NECROSIS

APOPTOSIS: falling off.

•NORMAL (preprogrammed)

•PATHOLOGIC (associated with Necrosis)

“NORMAL” APOPTOSIS• Embryogenesis • Hormonal “Involution”• Cell population control, e.g.,

“crypts”• Post Inflammatory “Clean-up”• Elimination of “HARMFUL” cells• Cytotoxic T-Cells cleaning up

“PATHOLOGIC” APOPTOSIS

• “Toxic” effect on cells, e.g., chemicals, pathogens

• Duct obstruction• Tumor cells• Apoptosis/Necrosis spectrum

APOPTOSIS MORPHOLOGY

• DE-crease in cell size, i.e., shrinkage• IN-crease in chromatin concentration,

i.e., hyperchromasia, pyknosis karyorhexis karyolysis

• IN-crease in membrane “blebs”• Phagocytosis

SHRINKAGE/HYPERCHROMASIA

Karryorhexis, karryolysis.

PHAGOCYTOSIS

Damaged/necrotic cells can accumulate fat: Fatty change

• Commonly occurs in Liver, heart.• Due to defective uptake, catabolism or

secretion of lipid.• Severe fatty change can alter cellular

structure and function.• Seen in diabetes, alcoholism, obesity.

LIPID LAW•ALL Lipids are YELLOW grossly and WASHED out (CLEAR) microscopically

FATTY LIVER

FATTY LIVER

CELL AGING• It is due to progressive decline in cellular

function resulting from exposure to exogenous influences.

• Cell can undergo limited number of divisions and goes into non-dividing or senescence phase.

• Accumulation of metabolic and genetic changes that damage DNA.

TELOMERES

• Telomeres are sequences of DNA present at ends of chromosomes. They become shorter with every division.

• Once shortened they cannot protect ends of chromosome and appear as damaged DNA.

• Cell goes into cell cycle arrest.