Cellular Injury & Adaptation
5 general types of cellular adaptation to injury?
***induced by direct stimulation or activation of cell surface receptors driving downstream changes*** 1. Hypertrophy - increase in size. 2. Hyperplasia - increase in number. 3. Atrophy - decrease in size. 4. Metaplasia - fundamental change in differentiation of STEM CELL type. 5. Displasia - abnormal cytological structure.
Examples of cellular injury related to free radicals?
1. CCl4 toxin - used in dry cleaning, metabolized by P450 to CCl3 radical 2. NO 3. H/R injury following ischemia
5 manifestations of cellular injury?
1. General cell swelling 2. Mitochondrial swelling 3. Plasma membrane blebbing BUT INTACT 4. Condensed chromatin - pyknosis 5. Autophagy
5 general causes of cellular injury?
1. H/I 2. Physical agents 3. Chemical agents 4. Infection 5. Immunogenic 6. Genetic derangement 7. Endocrine derangement
Intracellular accumulation related to cellular injury/defective metabolism?
1. Steatosis - lipid accumulation 2. Mallory's hyaline - degeneration of cytoskeleton filaments 3. Systemic Fe overload - hemochromatosis (genetic) or acquired (RBC transfusion) 4. Anthracotic pigment - HC fragment w/i Macrophage from inhaled soot/smoke 5. Lipofuscin pigment accumulation - protein wear and tear.
Immunogenic cell danage
Anaphylaxis, autoimmune reactions.
Dysplasia
Cancer
Chemical cell damage
Cyanide, arsenic --> disruption of metabolism and ATP depletion.
Endocrine cell damage
Estrogen --> hypertrophy/hyperplasia --> liver damage.
True/False: Ischemic injury is NOT associated with inflammation?
False - Ischemia results in the production of cytokines and increased expression of adhesion molecules, thus promoting neutrophil influx in reperfusion injuries.
True/False: The most common type of cellular injury is exposure to toxin?
False - ischemic & hypoxic injury is most common.
Physical cell damage
Heat, cold, mechanical injury, pressure, electricity (ion gradient).
Hallmark of reversible cellular injury?
Intact cell membrane with blebbling (cytoplasmic leaking) & ATP depletion.
Hypoxia & ischemia cell damage
Ischemia causes more damage, more quickly than hypoxia. Characteristic increase in lactic acid and necrosis.
All of the following are reversible cellular injuries, except: plasma membrane blebbing, impaired protein synthesis, karyorrhexis, mitochondiral dysfunction, pyknosis?
Karyorrhexis = nuclear fragmentation, not reversible.
Which of the following is not a general cause of cellular injury: auto-immure reaction, viral infection, Tylenol OD, Drowning?
NONE
All of the following generate ROS, except: membrane oxidation, protein oxidation, DNA oxidation, depletion of scavenger.
None
Hyperplasia
Physiologic - breast dev. during puberty, lactation during pregnancy (hormonal), liver regeneration (functional). Pathologic - loss of p53 control, increased estrogen with obesity leading to endometrial hyperplasia and cancer.
Atrophy
Physiologic - uterus shrinking post-menopause (hormonal), embryogenesis. Pathologic - decreased: nutritional supply, workload, blood supply, oxygen supply leading to cellular starvation/disruption.
Hypertrophy
Physiologic: lifting weight, uterine growth during pregnancy (hormonal), myocardial hypertrophy with exercise. Pathologic: myocardial hypertrophy secondary to increased afterload.
Metaplasia
Physiological - cervix cells altered from columnar to stratified squamous at the external os during puberty. Pathologic - smoking causes delicate ciliated columnar cells of RE to more durable stratified squamous epithelium, Barrett esophagus in GERD from stratified squamous to columnar with mucin secreting goblets.
In alcoholic liver injury, accumulation of lipid vacuoles results from defective metabolism of endogenous substance while Mallory's hyaline represents accumulation of abnormal endogenous substance?
True
True/False: Hypoxic injury occurs secondary to insufficient oxygenation of tissue (respiratory failure) and ischemic injury occurs secondary to loss of blood supply (arterial occlusions/impeded venous drainage)?
True
True/False: ROS are produced in large amounts by leukocytes, particularly neutrophils and macrophages, as mediators for destroying microbes, dead tissue & other exogenous species?
True
True/False: Rapid bursts of ROS are produced by leukocytes during inflammation. This occurs by a multiprotein complex that uses NADPH oxidase for the reaction?
True
True/False: Squamous metaplasia in uterine cervix is physiologic while squamous metaplasia in respiratory epithelium is pathologic?
True
True/False: The two phenomena that consistently characterize irreversibility of cell damage are the inability to reverse mitochondrial dysfunction (lack of oxidative phosphylation and ATP generation) even after resolution of injury and profound membrane disturbance?
True
Genetic cell damage
UV, XRT, translocation of oncogene, replication of oncogene cassette.
Infectious cell damage
Viruses, bacteria, fungi, parasite.
