Lecture 2: Cell Injury and Cell Death Flashcards
Be able to list several causes or agents of cell injury
Physical –> temp, pressure, radiation
Chemical –> drugs, toxins, pesticides, poison, CO
Biological –> biological toxins, microorganisms
Metabolic and nutrition alterations –> nutrition deficiency, lack of blood supply
Cell aging –> loss of repair mechanisms
genetic defects –> single AA substitution ( eg. trisomy 21)
Immune response –> autoimmune disease, allergy
Define and give appropriate physiological and pathological examples of cellular
adaptation
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
Atrophy
Decrease in cell size
–> can be due to lack of nutrition and proteins = allows the cells to survive better in lower mass
–> degradation of cellular proteins play a key role, and there are two mechanisms:
- lysosomes: intracellular organelles that have digestive enzymes that degrade molecules from the inside and the outside of the cell
- Ubiquitin- proteasome: cytosolic and nuclear proteins are tagged with the 76 AA protein, ubiquitin, and the tagged protein are degraded via proteasome (ubiquitin is not degraded, it is recycled)
–> can be both pathologic and physiologic
–> pathologic = disuse of some muscles (eg. skeletal muscles), so cells decrease in size (can be following loss of nerve input to the muscle)
–> physiologic = normal aging such as loss brain cell with age and their shrinkage
Hypertrophy
–> the increase of the size of cells
–> can be due to increase of synthesis of cellular proteins
–> can be physiologic and pathologic
–> physiologic = increase in size of uterine smooth muscles during pregnancy in response to estrogen hormone, or increase of size of skeletal muscles due to weight training
–> pathologic = increase in size of cardiac muscle fibers in response to increased workload because of systemic hypertension
Hyperplasia
–> the increase in number of cells via cell division
–> can be both physiologic and pathologic
–> physiologic = increase in number of uterine smooth muscles during pregnancy in response to estrogen hormone, or compensatory hyperplasia when a portion of tissue is removed (eg. if part of liver is removed, cells divide to recover and fill in the gap)
–> pathologic = excessive stimulation of estrogen in pregnancy can result in endometrial hyperplasia
Metaplasia
–> cells change to different cell types in response to a long-term change in environment
–> can be physiologic or pathologic
–> eg. change of cells from ciliated columnar cells to squamous cells in smokers bronchi
- ciliated cells are more fluid so they help clean the mucus, while squamous cells are more solid so they don’t clean mucus
dysplasia
–> when cells grow in an abnormal and disorganized way
–> can be caused by hyperplasia and metaplasia = can lead to neoplasia
–> always pathologic
Define and contrast reversible versus irreversible cell injury
These ways of cells adapting to a change in the body can be either reversible or irreversible. if the changes in the cells function and morphology is mild and still early in time, then that can be reversible. However, if the change of cell function and morphology remains for a long period of time, it can not change back, so it becomes irreversible.
–> note that changes in cell function can be observed quickly while changes in morphology take time to be observed
Be able to describe the cellular changes that characterize reversible cell injury
(e.g., cellular swelling/hydropic degeneration; fatty change).
–> caused by changes that lead to either cellular/hydropic swelling or fatty change
–> cellular/ hydropic swelling is the increase in volume of cell characterized by a large, pale cytoplasm and a normally located nucleus (nucleus that is still working). This is a result of impairment of maintaining proper ion concentration (Na+) in the cytoplasm. This is because agents can impair the Na+/K+ ATPase, which leads to high conc. of Na+ inside the cell. As a result, water also accumulates inside the cell to maintain iso-osmotic conditions => the cell swells. Mitochondria may also swell, cisternae if ER can be dilated and blebs may form on the plasma membrane
–> fatty change is a result of abnormal accumulation if triglycerides inside the cell
–> if the stimulus is removed, all these changes are reversible and the cell will go back to its normal state
Be able to describe the cellular changes that take place in irreversible cell
injury leading to necrosis (e.g., within the nucleus - pyknosis, karyorrhexis and
karyolysis; within the cytoplasm - eosinophilia).
–> if an overwhelming injury occurs where the cell can’t adapt, the cell dies ==> necrosis (nucleus starts dissolving)
–> can result because of inability to reverse mitochondrial dysfunction and sever disruption of membrane functions
–> necrosis is characterized by certain structural changes:
- intense eosinophilia (pinkness) of cytoplasm
- pyknosis (shrinkage) of the nucleus
-karyorrhexis ( pyknotic fragments of the nucleus)
-Karyolysis (dissolution) of the nucleus
Describe coagulative, liquefactive, fat, caseous, and gangrenous necrosis and be able
to give an example of each.
coagulative: most common form of necrosis. all morphology changes stated above are seen. cells appear liek ghosts of themselves (no nucleus) where the basic structural outline of coagulated cell persists for several days. typical with ischemia, eg in heart (myocardial cells)
liquefactive: rapid loss of architecture of tissue and digestion of dead cells. most often seen in CNS. Typical with bacterial damage
caseous: soft, friable, “cheesy-like” material. Characteristic of tuberculosis
fat: specific to fat (adipose) tissue. released enzymes digest fat that complexes with calcium to form chalky-white deposits. eg. pancreatitis; damage to breast tissue
gangrenous necrosis: also called wet gangrene. used to refer to a coagulative necrosis (frequently of a limb) when there is superimposed infection with a liquefactive component.
–> if necrotic tissue dries out (without infection component) it becomes dark black and mummified => called “dry gangrene”
Apoptosis
Apoptosis is the programmed cell death. It is an energy-dependent process specifically designed to switch off unwanted and damaged cells and eliminate them. Therefore, it can be physiologic (eg. during embryogenesis when forming fingers and toes, or during menstrual cycle), or pathologic (following radiation injury, in some cancers)
Apoptotic cells initiate their death by activating proteases known as caspases that break down the nucleus and cytoskeleton. Nucleus collapse and cells shrink and are cleaves into a membrane-bound clump enclosing organelles (apoptotic body). The membrane bound material is recognized and engulfed by phagocytes.
Define and contrast apoptosis and necrosis. Be able to describe the morphological
changes that characterize each.
The magnitude and type of injurious stimulus determines if the cell should undergo necrosis or apoptosis –> if more severe then the cell undergoes apoptosis, and if it is an immune-mediated damage it undergoes apoptosis. The amount of ATP in the cell also plays a key role, if there is severe depletion of ATP then cell can’t undergo apoptosis
Induction
Apoptosis
- physiological and pathological
Necrosis
- pathological
Extent
Apoptosis
- single cells
Necrosis
-cell groups
Biochemical events; mechanisms
Apoptosis
- gene activated; energy dependent fragmentation of DNA by endogenous endonucleases and cleaved into regular fragments (laddering); breakdown of cytoskeleton by proteases
Necrosis
- impairment or cessation of ion homeostasis; depletion of ATP; influx of sodium, water and calcium, irregular DNA fragmentation; cell membrane damage; may be mediated by free radicals
Cell membrane integrity
Apoptosis
- maintained
Necrosis
-lost
Morphology
Apoptosis
- cell shrinkage; fragmentation to form apoptotic bodies with dense chromatin
Necrosis
- cell swelling and lysis; swelling and disruption of organelles; nucleus; pyknosis, karyorrhexis, karyolysis
Inflammatory response
Apoptosis
-none
Necrosis
-yes
Fate of dead cells
Apoptosis
-ingested (phagocytosed) by macrophages
Necrosis
- ingested (phagocytosed) by neutrophils and macrophages
Describe the mechanism of cell injury and/or death in response to decreased oxygen.
Partially reduced or reactive oxygen species are identified as a likely cause of cell injury. They can be formed via the action of ionizing radiation; during reperfusion of tissues following ischemia; excess oxygen presence, and in inflammatory cells. They posses a free electron which is highly reactive; it can initiate lipid peroxidation which results in loss of membrane integrity, cross-link essential proteins, damage DNA or form secondary damaging ROS. Because these molecules are formed during regular metabolism and oxygen respiration, the body has several mechanism to detoxify the,: spontaneous decay (superoxide breaks down in presence of water into oxygen and hydrogen peroxide), superoxide dismutase ( converts superoxide to hydrogen peroxide and oxygen), catalase ( converts hydrogen peroxide to oxygen and water) or glutathione peroxidase ( reduction of hydrogen peroxide to water. Endogenous or exogenous antioxidants such as vitamins A, C and E can help offer some protection against these free radicals. when these endogenous systems become overwhelmed, damage occurs
Provide examples of physiological (e.g., lipofuscin, melanin) and pathological
intracellular accumulations (e.g., fatty change).
Under normal conditions, cells store fats, glycogen, vitamins and mineral for use in metabolism. They also store products of turnover as endogenous pigments such as degraded phospholipids as the golden-brown granules of “wear-and-tear” pigment, lipofuscin, which increases with age particularly in heart, lungs and brain. Also stores melanin, and insoluble brown-black pigment found in skin cells and in certain brain cells. Also stores hemosiderin, iron rich brown pigment derived from the breakdown of red blood cells. In hemosiderosis, the excess iron storage can damage vital organs. The most common exogenous pigment is carbon which is inhaled and deposited in tracheobronchial lymph nodes and lung tissue. Many inherited disorders of metabolism can lead to abnormal accumulation of metabolites.
Fatty change or steatosis is linked to intracellular accumulation of fat either because of increased delivery of fat onto the cells, an impairment of fat metabolism or decreased synthesis of apolipoproteins for transport out of the cell. Vacuoles form in cytoplasm that can join to form a large vacuole that displaces the nucleus. The liver is susceptible to fat change because it is where most fats are stored and metabolized, but it may also occur in heart, kidney, skeletal muscle and other organs as a result of exposure to toxins, protein malnutrition or starvation, diabetes, obesity and anoxia, and alcohol abuse (most common in Canada). Can be reversible is stimulus is removed
Neoplasia
An abnormal, uncontrolled growth of cells that can be benign or malignant
Benign Tumors
These are well differentiated, localized, non-invasive. Eg. Papilloma, adenoma
