cell adaptations cell injury cell death dr.samina qamar ap pathology
DESCRIPTION
OBJECTIVES Understand 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, CytoskeletonTRANSCRIPT
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.