Cell injury Flashcards
Defenition of cell injury
**A Variety of stresses the cell encounters as a change in external or internal environment causing morphological &/or functional chnages. **
The cellular response depends on ……… & ……..
1- Type of cell or tissue involved
2- extent & type of injury
What are types of cellular responses ?
1. Cellular adaptations
2. reversible Cell injury
3. Irreversible CI
4. Intracellular accumulations
In reversible CI, when the stress is …… to ……., the cell ……..
mild
moderate
may recover
In Irreversible CI, the stress is ……………, ………. may occur
severe, persistent
cell death (necrosis // Apotosis
Def of Cellular addaptations
def & types
Reversible changes in size, type, phenotype, metabolic activity or functions of cell in response to a stimuli (chnage in the environment).
There are 4 types :
1. Hypertrophy
2. Atrophy
3. Hyperplasia
4. Metaplasia
diff betw physiologic adaptations & Pathologic ones
- **Physiologic adaptations : ** represent responses of cell to normal stimulations as hormones or endogenous chemical mediators
- Pathologic Adaptations :represent responses of cell to stress allowing to modulate its structure & functions => escape injury.
Def of Atrophy
decrease in size of a normal organ due to decrease in size of its cells w/ or w/o decrease in nb of cells.
Diff betw Atrophy // Aplasia // Agenesis
- **Atrophy : **decrease in size of a normal organ due to decrease in size of its cells w/ or w/o decrease in nb of cells.
- **Aplasia : **extreme failure of develop. so only rudimentary tissue is present.
- **Agenesis : **Complete absence of an organ.
Atrophic cells are dead ?
No, they have diminished function but not dead.
…………. death may be induced by the same signals as Atrophy leading to decrease in nb.
Apoptotic death
EX of Physiologic Atrophy
Atrophy of
1. Lymphoid tissue, thymus, appendix
2. Brain & Heart w/ aging
3. gonads after menopause
EX of Pathologic Atrophy
- Disuse Atrophy: wasting of muscles of the limb immobilized
- Neuropathic Atrophy: Neuropathic due to loss of innervation => wasting of muscles (ex : traumatic nerve injury & poliomyelitis)
- Endocrine Atrophy: Loss of trophic hormones (hormones secreted by pituitary) (EX: hypopituitarism may lead to atrophy of thyroid, adrenal, gonads)
- Pressure Atrophy: Large aortic aneurysm => atrophy of vertebral bodies not intervertebral discs.
- Atrophy due to lack of nutrients: severe protein-calorie malnutrition (EX: Marasmus), => muscle atrophy.
disuse atrophy: not using muscles enough, body start break them down
Atrophy Pathogenesis (mechanism by w the lesions are produced)
Decrease in cells size due to :
decrease in protein synthesis
Increase in protein degradation
Atrophy Morphologic features
- Organ is small as cells are small due to reduction in cell organelles (mitochondira, ER, Myofil.)
- Numerous Autophagic vacuoles w/ cell debris => residual bodies EX: lipofuscin pigment granules in brown atrophy
Def of Hypertrophy
Increase in size of organ due to increase in size of its cells
Occurs in Non dividing cells (permenant cells)
EX of Physiologic Hypertrophy :
- Uterine smooth muscle hypertrophy during pregnancy (may be accompainied by Hyperplasia)
- Skeletal m. in athletes
EX of Pathologic Hypertrophy :
Hypertrophic left ventricle: in systemic Hypertension or Reduced aortic valve outflow
Hypertrophy Pathogenesis
Cells become larger dur to :
Increase in protein synthesis
Decrease in protein degradation
Hypertrophy Morphologic Features
Organ is large & heavy due to increase if size in muscle fibers as well as of nuclei
Def of hyperplasia
Increase in size of an organ due to increase in nb of its cells
Occurs in Labile & Stable cells
EX of Physiologic Hyperplasia :
-
Hormonal Hyper.:
Hyperplasia of :
Breast during puberty, during pregnancy & lactation /// pregnant uterus - Compensatory Hyper.: following the removal of a part of sn organ or a conttralateral organ i paired organs. EX: Regeneration of liver following hepatectomy
EX of Pathologic Hyperplasia :
Hormonal (due to excessive hormonal stimulation):
1. Increase estrogen stimulation unopposed by progestrone as in *Fibrocystic breast disease (mammary hyper.) /// Endometrial Hyper. *
2. Prostatic Hyperplasia in old age
3. Thyroid Hyperplasia (Goiter) due to increase TSH (thyroid stimulating Hormone)
Epithelial due to chronic irritation or inflammation: as in Bilharizial cystitis.
Hyperplasia Pathogenesis
Cells increase in nb by proliferation of stem cells & parenchymal cells.
Diff betw Hyperplasia & Neoplasia
Both are icrease in nb of cells but
Hyperplasia: controlled & reversible, but pathologic hyperplasia may be the soil of neoplastic proliferation.
**Neoplasia **: uncontrolled & Irreversible => tumors
Deff of Metaplasia
- Reversible change in w one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type, w/o crossing histogenetic boundries.
- Occurs in response to chronic irritation & inflammation.
Metaplasia Pathogenesis
genetic reprogramming of epithelial stem cells or UMCs in CT.
Although metaplastic changes lead to stronger epithelium it may be less well-specialized. Explain
**Squamous metaplasia in Respiratory epithelium will result in deprivation of mucus secretion & ciliary clearence => infection. **
Metaplasia may revert back in case of …………. /// but in case of …………… it may lead to malignant transformation
- Absence of stimulus
- Persistent stimulus
EX of Epithelial Metaplasia
Metaplasia types : Epithelial & mesenchymal
Squamous metaplasia **
1. From *Pseudostratified Columnar ciliated epithelium: in bronchi in chronic bronchitis in chronic smokers
2. From Simple columnar epithelium : in gall Bladder in chronic cholecystitis w/ cholelithiasis (gall bladder stones fromation trapping the bile in the duct).
3. From transitional epithelium* : in urinary bladder & renal pelvis in stones & chronic infection as schistosomiasis (caused by parasitic worms).
Columnar metaplasia:
Barrett’s esophagus: change from normal squamous epithelium in the distal part of esophagus in case of Chronic reflux Esophagitis
EX of Mesenchymal Metaplasia
- Osseous: In muscles in myositis ossoficans
- Cartilagenous: in long-standing fibrosis as capsule of spleen in chronic venous congestion.
What are causes of cell injury ?
Genetic Causes :
1- Deficiency of proteins as enzymes functions.
2- Accumulation of damaged DNA => cell Death
Acquired causes :
1. Hypoxia: has 3 causes :
A. Ischemia => reduced B. Supply
B. Ht & Lung diseases => Dminished blood oxygenation
C. Anemia, CO poisoning => diminished oxygen carrying capacity.
2. Physical Agents : trauma, T, Radiation, Pressure …
3. Chemical : poisons, organic & inorganic environ. agents, Therapeutic drugs.
4. Infectuous : virsus, parasites, bacteria….
5. Immunologic : hypersens. reactions, Autoimmune
6. Nutritonal Imbalances :
A. Nutritunal Deficency due to : Overall deficiency (Starvation) /// Protein calorie (marasmus,, Kwashiorkor), or minerals (anemia).
B. Nutritunal Excess : obesity, Diabetes Mellitus, Atherosclerosis, Ht Disease, Hypertension.
CO => attaches to HB prevent its attachment to O2.
Cell injury may result in a state of reversible or irreversible injury depending on …………….. & ………………
- **Type, duration & severity of agents: **
A small dose of a chemical agent or brief ischemia => reversible cell injury. BUT, a large dose or persistent ischemia => Cell Death. - **Type, Status & Adaptability of the target cell: **
Skeletal muscle can endure hypoxic injury for 2-3 h,
Cardiac muscle => 20-30 mins
Brain 4-6 mins.
What are the mechanisms of Cell injury ?
- ATP depletion
- Mitochodrial damage
- Nuclear damage
- Plasma memb. damage
- Generation of reactive oxygen species
- Loss of Ca++2 Homeostasis.
Explain ATP depletion
Cause & Consequences
ATP depletion may be caused by ischemia that diminishs the oxidative phosphorylation in mitochodria causing =>
1. Failure of Na+ pump => influx of Na+ & efflux of K+ => swelling
2. Failure of Ca2+ pump => its influx => damaging effects on cellular components.
3. Increases Anaerobic glycolysis => accumulation of Lactic acid => decrease Ph => damage enzymes + clumping of chromatin.
4. Detachment of ribososmes from rER => decrease in protein synthesis => damage to mitochodrial & plasma memb. => cell death.
Explain Mitochodrial Damage
- Increase cytosolic Ca2+, ROS (reactive O2 species) & Hypoxia: appear as vacuoles & amorphous Calcium deposits. This damage affects oxifative phosphorylation w/ ATP depletion & generations of ROS => Necrosis.
- **Decreased survival signals, Irrepairable DNA or Protein damage : **=> increase in permeability of mitochodrial memb => leaking of cytochrome C into cytop. => Apoptosis.
Explain loss of Ca2+ Homeostasis
Cause & Consequences
**Causes: ** Ischemia (ATP depletion => failure of Ca2+ pump) , Certain toxins => increase intracellular Ca2+.
Consequences Activation of enzymes as :
1. Phospholipases & Proteases => CM damage.
2. Endonucleases => DNA & Chromatin fragmentation
3. ATPase => ATP depletion.
4. Caspases => Apoptosis.
Explain Accumulation of reactive O2 species (ROS)
/O2 derived free radicals
Def & Causes & Consequences
**Def: **Chemical species w/ unpaired electron in their outer orbit, produced during Mitochondria respiration & energy generation, & degraded by cellular defense systemes (SOD & Glutathione superoxidase).
Causes : Cell injury => accumulation of these ROS (superoxide, H2O2, Hydroxyl).
**Consequences : **
1. CM damage due to lipid peroxidations.
2. Protein oxidation => loss of enzymatic activity.
3. DNA damage.
Explain Memb. damage
**Causes : **
Increase in Cytosolic Ca2+ => activation of endogenous phospholipases => degradation of phospholipids causing memb damage of Cell, Lysosomes & Mitochondria.
Consequences :
1. Loss of osmotic balance
2. Loss of cellular components depleting energy stores
3. Lysosomal memb damage => leakage of its Hydrolytic enzymes => their activation in cytosol as acidic Ph & lack of O2 => Cell death.
Morphologic feature following the memb. damage
Dead cells are further replaced by phospholipids masses calles myelin figures that will be phagocytosed by macrophages or form Ca+2 soaps
During Memb. damage, Leaked enzymes can also
mark ” the cell type damaged. Explain.
As reflected by elevated serum level of specific izoenzymes as :
Creatine Kinase & Troponins in case of Myocardial infarction.
Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase in case of **liver **problem.
Explain nuclear damage
Cause : Activated lysosomal enzymes such as proteases & endonucleases.
This damage can occur in 3 forms :
Pyknosis => condensation of nucleus w becomes dark basophilic
Karyorrhexis => Fragmentation of nucleus into bits dispersed in cytopl.
Karyolysis => Dissolution of the nucleus.
What is morphology of reversible CI ?
2 processes
- Hydropic change
- Fatty change
What can distinguish betw irreversible from reversible CI ?
- Inability of the cell to reverse mytochondrial dysfunction on reperfusion (restoration of Blood Flow to a certain organ) & Reoxygenation
- Disturbance in CM function.
Explain the Hydropic change during reversible CI
DEF, Pathogenesis, Features, ultrastructural changes
Def:accumulation of water within the cytoplasm also known as Cloudy swelling (cytopl appears cloudy), & Vacuolar degeneration (due to cytopl vaculations).
Pathogenesis
Impairment distribution of Na & K at the level of the CM => accumulation of Na inside w/ efflux of K => swelling.
Morphological Features
Grossly : specialized organs as Heart, Kidney, Pancreas, Liver are enlarged + cut surface is bulged outwards & slightly pale.
Microscopically : Cells are swollen, capillaries are compressed, small clear vacuoles repreenting distended cisternea of ER.
ultrastructural changes
1. CM alterations : blunting, blebs, loss of microvilli
2. Mitochondrial swelling
3. Distention of rER w/ detachment of ribosomes
4. Nuclear alterations w/ chromatin clumping
5. Looseneing of intercellular attachment.
What cellular adaptations may lead to Neoplasia if persistent ?
hyperplasia & Metaplasia
