CELL INJURY CELL ADAPTATION CELL DEATH - SRM … · 2015-11-07 · CONCEPTS IN CELL INJURY • Cell...
Transcript of CELL INJURY CELL ADAPTATION CELL DEATH - SRM … · 2015-11-07 · CONCEPTS IN CELL INJURY • Cell...
Chapter 1
CELL INJURYCELL DEATH
CELL ADAPTATIONS
M.G.Rajanandh, Dept. of Pharmacy Practice, SRM College of Pharmacy, SRM University.
CONCEPTS IN CELL INJURY
• Cell injury results from a disruption of one or more of the cellular components that maintain cell viability.
• The clinical signs and symptoms are severalsteps removed from the biochemical changesassociated with cell injury.
• Cell injury is common to all pathologic processes.
CONCEPTS IN CELL INJURY
• Cell injury may be reversible, result in cell adaptation, or lead to cell death.
– Biochemical alterations occur prior to morphologic changes.
– The result of cell injury is determined, in part, by the intensity,duration and/or the number of exposures to an etiologic agent.
– The result of cell injury is determined, in part, by the celltype and its physiologic state.
• Injury at one point induces a cascade of effects.
CONCEPTS IN CELL INJURY
• The clinical signs and symptoms are severalsteps removed from the biochemical changesassociated with cell injury.
• Cell injury is common to all pathologic processes.
CAUSES OF CELL INJURY -THE PATIENT’S VIEW
• Hypoxia• Infectious agents• Physical injury• Chemicals/drugs
• Immune response• Genetic derangement• Nutritional imbalance
HYPOXIC INJURY
Cerebral infarction Myocardial infarction
Renal atrophy
• Cell injury results from a disruption of one or more of the cellular components that maintain cell viability.
CONCEPTS IN CELL INJURY
• Divergent factors can act at the same point on the cell to induce cell injury.
CELL INJURY - THE CELL’S PERSPECTIVE
CONCEPTS IN CELL INJURY
• Injury at one point induces a cascade of effects.
• The clinical signs and symptoms are severalsteps removed from the biochemical changesassociated with cell injury.
• Cell injury results from a disruption of oneor more of the cellular components thatmaintain cell viability.
MECHANISMS OF CELL INJURY
• Hypoxia / Ischemia Model
• Generation of Reactive Oxygen Species
• Increased Cytoplasmic Ca++
HYPOXIA - ISCHEMIA MODELBlood Clot
⇓ O2
⇓ Oxidative Phosphorylation
⇓ATP
Impaired function of the plasma membrane
ATP-dependentNa+ pump
⇑ Glycolysis
Detachment ofribosomes
HYPOXIA - ISCHEMIA MODEL
Detachmentof ribosomes
⇑ Glycolysis ⇓pH
⇓ GlycogenStores
⇓ ProteinSynthesis
LipidDeposition
ChromatinClumping
REACTIVE OXYGEN SPECIES
02
Fe+2 Fe+3SODO2 H2O2 OH + OH
2GSHGlutathione GlutathionePeroxidase Reductase
GSSH
H20CELL INJURY
Ca++ INDUCED CELL INJURY
Ca++Ca++ Ca++
⇑Cytoplasmic ionic Ca++
ATPase Phospholipase Protease Endonuclease
⇓ATP ⇓Phospholipids Protein DNADisruption Damage
OTHER CAUSES OF CELL MEMBRANE INJURY
• Complement - C5-C9 MAC• Cytotoxic T Cells - perforin• Virus• Bacterial Endotoxins and Exotoxins• Drugs
CONCEPTS IN CELL INJURY
• Cell injury may be reversible, result in a cell adaptation, or lead to cell death.
– Biochemical alterations occur prior to morphologic changes.
– The result of cell injury is determined, in part, by the intensity,duration and/or the number of exposures to an etiologic agent.
– The result of cell injury is determined, in part, by the celltype and its physiologic state.
• Injury at one point induces a cascade of effects.
OUTCOMES OF CELL INJURY
REVERSIBLE CELL DEATH CELLADAPTATIONS
NORMAL CELL
CELL INJURY / CELL STRESS
ACUTE CHRONIC
REVERSIBLE CELL INJURY
• Oftentimes is an acute process.
• Cell injury of short duration and minimal intensity.
• Causes include: ischemia, exposure to toxins, infectious agents, and thermal injury.
• Plasma membrane injury leads to increased intracellular Na+ that leads to an isosmotic gain in water and cell swelling.
NECROSIS• Morphologic types of necrosis
– Coagulative– Liquifactive– Caseous– Enzymatic (fat)
• The type of necrosis is dependent upon patterns of enzymatic degradation of cells and extracellular matrix, the type of necrotic debris, and by bacterial products when present.
APOPTOSIS MAINTAINS HOMEOSTASIS
• Embryogenesis
• Normal cell turnover– cells with short half-life– tissue involution due to loss of growth
factor stimulation
• Immune function– Elimination of autoreactive T cells– NK and CTL killing
APOPTOSIS AND DISEASE
• Too Much Apoptosis
toxin induced liver injury
AIDS
ischemia
neurodegenrative diseases
myelodysplasia
APOPTOSIS AND DISEASE
• Inhibition of Apoptosis
various viral diseases - e.g. Herpes, poxvirus, and adenovirus
cancer - e.g. follicular lymphoma, andcarcinomas of the breast, prostate and ovaries
autoimmune diseases - SLE
MORPHOLOGY OF APOPTOSIS
Progressive cell shrinkageChromatin condensation
Plasma membrane blebbingApoptotic bodiesPhagocytosis - no inflammation
MECHANISMS OF APOPTOSIS
NECROSIS VS. APOPTOSIS
NECROSIS APOPTOSIS
Stimuli Pathologic PhysiologicPathologic
Morphology Multiple cellsCell swellingCell lysis
Single cellCell shrinkageChromatinCondensationApoptotic bodies
Host response Inflammation No inflammation
CAUSES OF CHRONIC CELL INJURY
•Ischemia, hormones, infections, chemicals/drugs, trauma, etc.
•Strength of the insult may be minimal.
•Duration of stress is prolongedas compared to acute cell injury.
Alteration in cell differentiation with concurrent alteration of
tissue/organ function.
METAPLASIA
CELLULAR ADAPTATIONS
• Alterations in cell size
• Alterations in cell number
• Alterations in cell differentiation
• Abnormal intracellular accumulations
METAPLASIA
Barrett's Esophagus