Cell death, Injury Flashcards
What are the stages in cell response to stress and injury?
Homeostasis: normal cells have a fairly narrow range of function or steady state
Adaptation: excess physiologic or pathologic stress may force the cell to a new steady state
Injury: Too much stress exceeds the cell’s adaptive capacity
Three groups of cells on the basis of proliferative capacity and relation to the cell cycle
1) Continuously dividing cells (labile cells)
2) Quiescent Cells ( Stable Cells)
3) Non-dividing cells ( Permanent Cells)
Labile Cells
Follow the cell cycle; undergo mitosis; continue to proliferate throughout life; replace cells that are continuously being destroyed
Quiescent Cells
Demonstrate a low level of replication; neither cycling nor dying, re-enter the cycle in reponnse to an appropriate stimulus; are in G0 and can be stimulated into G1
Non-dividing or Permanent Cells
Have exited the cell cycle; cannot undergo mitotic division in postnatal life
Adaptations: Physiologic vs. Pathologic
Physiologic adaptations: Responses of cells to normal stimulation by hormones or endogenous chemical mediators
Pathologic adaptations: responses to stress that all cells to modulate their structure and function and this escape injury
Hypertrophy
An increase in the size of cells resulting in enlargement of organ size. Bigger cells no new cells and can be trigger by trophic hormones growth factors or mechanical stretch .
Occurs in cells incapable of dividing and has degenerative changes.
Hyperplasia
An increase in the number of cells resulting in an increase in size or weight of an organ or tissue due to increased number of cells.
Occurs in cells capable of dividing and can have hormonal hyperplasia and compensatory hyperplasia.
Caused by excesses of hormones or growth factors acting on target cells.
Ex: Abnormal menstrual bleeding, benign prostatic hyperplasia, thyroid hyperplasia, hyperplasia of the endometrium
Atrophy
Shrinkage in the size of the cell by loss of cell substance resulting in decreased protein synthesis and increased protein degradation. During early development embryonic structures undergo atrophy
Atrophy: Pathologic
Common causes include:
1) Disuse atrophy
2) Denervation
3) Hypoperfusion: reduced blood supply
4) Inadequate Nutrition: protein calorie malnutrition
Atrophy: Cell and Organ Effects
Degradation: Reduced tissue mass & function
Autophagy: self-eating starved cells eat their own components in an attempt to survive
Brown atrophy: Tissue discoloration from lysosomal accumulation of residual bodies
Decreased Hormonal Stimulation
Senile atrophy: Aging
Fibrotic Occlusion: secretory ducts
Pressure: Compression by a tumor
Metaplasia
One cell type is replaced by another by reprogramming of stem cells
Myeloid Metaplasia
Extramedullary Hematopoiesis: Proliferation of Hematopietic tissue in sites other than bone marrow such as spleen and liver
Causes of Cellular Injury
Hypoxia: the most common cause of injury and occurs when lack of oxygen prevents the cell from synthesizing sufficient ATP by aerobic oxidation
Pathogens: can injure the body by direct infection of cells, production of toxins, or host inflammatory response
What is the mechanism of cellular injury in hypoxia and ischemia?
Decrease intracellular generation of ATP which leads to failure of many energy-dependent cellular systems such as the ion pumps and depletion of glycogen stores
Causes of Cellular Injury continued…
1) Immunologic reaction
2) Congenital disorders are inherited genetic mutations
3) Chemical injury can occur with drugs, poisons
4) Nutritional or vitamin imbalance
5) Physical forms of injury
6) Aging: alterations in replicative and repair abilities
Mechanisms of Cellular Injury
1) Decreased ATP
2) Mitochondrial damage
3) Increased intracellular calcium
4) Increased free radicals
5) Increased cell membrane permeability
Reversible vs. Irreversible Cell Injury
Reversible Cell Injury= decreased oxidative phosphorylation, ATP depletion, cellular swelling
Irreversible cell injury= cell lysis= cell death= mitochondrial irreversibility , membrane damage, lysosomal digestion,
nuclear degeneration
Irreversible cell injury
1) Severe membrane damage: allows massive influx of calcium into the cell
2) Marked mitochondrial dysfunction: produces mitochondrial swelling
3) Rupture of the lysosomes: causes release of lysosomal digestive enzymes
4) Nuclear changes: can include pyknosis degeneration and condensation of nuclear chromatin
Necrosis
Cell lysis, membrane pores, perforin-mediated cell killing.
Mechanisms of injury: ATP depletion, mitochondrial damage, calcium influx, oxidative stress
Apoptosis: Cell death
Cell size: Shrunken reduced
Nucleus: Fragmentation into nucleosome-size fragments
Plasma membrane: Intact Altered structure & lipid orientation
Cellular contents: Intact, released apoptotic bodies
Inflammation: no
Role: Physiologic, pathologic
Necrosis
Cell size: Swollen enlarged Nucleus: Pyknosis, Karyorrhexis, Plasma membrane: Dsirupted Cellular contents: Enzymatic digestion, leakage out Inflammation: Frequent Role: Pathologic
Cell Injury Phenomenon
Reversible
1) Cellular swelling: failure of ion pumps,
2) Fatty Change
Irreversible
1) Mitochondrial dysfunction cannot be corrected
2) Profound membrane function disturbances
Mechanisms of Damage: Membrane permeability
1) Plasma membrane damage leads to loss of osmotic balance
2) Lysosomal membrane injury results in leakage of their enzymes into the cytoplasm and activation of the acid hydrolases in the acidic intracellular pH of the injured
3) Activation of lysosomes Ribonucleases, DNases, Proteases, Glucosidases, and other enzymes leads to enzymatic digestion of cell components, and cell death by necrosis
