Week 1: Cell Injury & Death Flashcards
cellular changes that occur with apoptosis (3)
Defined fragmentation of DNA
Formation of distinct structures called apoptotic bodies
No inflammatory response, cells removed by phagocytosis
define apoptosis
cell death due to physiological turnover, programmed cell death; can be stimulated by physiologic or pathologic stimuli
changes in nucleus during necrosis (3 - define each)
karyolysis: DNA is degraded by lysing of the nucleus
pykinosis: nucleus shrinks in size
karyorrhexis: nucleus becomes fragmented
define necrosis
cell death by injury, involves autodigestion and may initiate an inflammatory response
define gas gangrene
occurs when infection is caused by clostridium spp., anaerobic bacteria that produce toxins that damage CT and cause gas
define wet gangrene
occurs when necrotic tissue is infected with bacteria and phagocytic cells are recruited – releasing enzymes that lead to liquefactive process
define dry gangrene
coagulative necrosis
cellular changes due to fat necrosis
saponification = formation of soap by fatty acids, triglycerides, calcium, magnesium and sodium
where does fat necrosis occur?
pancreas, breast, peritoneal cavity
define fat necrosis
occurs due to abnormal release of pancreatic enzymes that enter other structures. lipases cause specific cellular dissolution
cell changes that occur with caseous necrosis
- Necrotic debris not digested completely by hydrolases
2. Tissues appear soft and granular (white and cheesy)
causes of caseous necrosis
limited # of agents
common cause = TB
define caseous necrosis
combination of coagulative and liquefactive necrosis
cell changes with liquefactive necrosis (2)
- Digestion of the cell remains
- Associated with abscess (pus) formation
examples of liquefactive necrosis
- Characteristic of hypoxic death in CNS cells – rich in hydrolytic enzymes and lipids
- Characteristic of focal bacterial infections, which involve hydrolases from phagocytic neutrophils
liquefactive necrosis is the consequence of: _____ or _____
autolysis (destruction from within the cell) or heterolysis (destruction from outside of the cell)
cell changes that occur in coagulative necrosis (3)
- cell outline preserved
- acidosis denatures proteins
- protein denaturation causes coagulation
what is coagulative necrosis and in which organs does it occur?
cell death due to hypoxia and/or ischemia
found in the heart, kidneys and adrenal gland
characteristic of hypoxic death in all cells except brain cells
How does calcium influx affect mitochondria and the nucleus, leading to cell death?
mitochondria: disrupts normal cellular metabolism
nucleus: gene transcription and nucleases are modulated by the calcium which leads to apoptosis
how do ROS contribute to cell injury/death?
ROS work similarly as free radicals - damage cell membranes
how do ROS form under stress?
increase in ROS levels occurs under oxidative stress
how does a cell normally protect against ROS?
- superoxide dismutase converts superoxide to hydrogen peroxide
- catalase converts hydrogen peroxide to oxygen and water
consequences of free radical injury (4)
- damage cell membranes
- inactivate enzymes
- damage nucleic acids
- form reactive oxygen species
how are free radicals made?
made during normal cellular metabolism, can be increased or decreased by physiologic or pathologic stimuli
define free radical injury
damage due to unpaired electrons that interact with lipids and proteins
consequences of hypoxic injury (1)
due to need for anaerobic respiration in place of aerobic, lactic acid builds up and the pH becomes more acidic
3 major mechanisms of cellular injury
- injury by free radicals
- hypoxic injury
- disruption in calcium homeostasis
define pathogenesis
cellular response to disease
define etiology
underlying cause of disease
What are the general consequences of structural or metabolic changes or derangements on cell function? (3)
- Changes a cell’s ability to carry out vital functions
- Changes can spread across cells, impacting the function of tissue and potentially the organ
- Can compromise the health of an individual
general role of environment in cell injury
nutrients must outweigh waste products for the cell to function properly
How are accumulations of substances created by cells undergoing stress used by a pathologist to understand cell injury; and, give an example of the pathophysiological consequences of these accumulations?
- Can be used to determine extent of cell stress/adaptation, hallmarks of cell injury
- Consequences – may interfere with metabolic or physical functions; may initiate an inflammatory response that can lead to organ enlargement
What types of substances can accumulate in cells undergoing stress? (8)
- Lipids: heart and liver
- Glycogen: liver and skeletal muscle
- Pigments
- Melanin: skin
- Hemosiderin: bloodstream (hgb, iron)
- Bilirubin: liver - Lipofuscin: result of degenerating membranes – phospholipids and proteins form a fine granular golden-brown pigment
- Minerals: calcium
- Hyaline change: protein
examples of dysplasia and cancer (3)
- Epidermal actinic keratosis – hyperplastic squamous epithelium
- Ulcerative colitis - mucous cells in colon are subject to dysplasia due to chronic inflammation
- dysplastic cells can be found in the uterine cervix if cancerous processes are present
relationship between dysplasia and cancer - how does dysplasia affect the appearance of cells (3)
- Change in cell size and shape
- Nuclear enlargement, irregularity and hyperchromatism
- A disarray in the arrangement of cells within the epithelium
A smoker experiences lung changes that are associated with which type of cellular adaptation?
metaplasia - affects columnar ciliated epithelial cells, which turn into flat squamous cells. this disrupts the normal function of the mucus elevator and allows for particles to enter the lungs that would normally be excreted. this could cause changes that lead to cancer
causes of hyperplasia
Response to physiologic or pathologic stimuli, depends on cell’s ability to divide
causes of hypertrophy (2)
hormonal stimulation (pregnancy) increased functional demand (working out)
outcome of hypertrophy
initial increase in functional capacity, but over time the organ will not be able to continue to compensate for the workload (cardiac hypertrophy)
pathologic vs. physiologic causes of atrophy
Pathologic: due to pathologic stimuli
Physiologic: due to changes in functional demands on a cell
causes of atrophy
disuse syndrome, denervation, ischemic atrophy
define atrophy
decrease in size of tissue or organ due to reduction in cell size
define dysplasia
disordered growth and maturation of a cell component within a tissue
define metaplasia
mature cell types replaced by a less mature cell type
define hypertrophy
increase in size of cells
define hyperplasia
increase in number of cells
Two normal causes of cell death
Apoptosis & Necrosis
define karyorrhexis
irreversible cell death characterized by fragmentation of the nucleus
Define karyolysis
irreversible cell death characterized by lysing of nucleus due to action of DNAase & RNAse
General changes associated with cell injury (4)
- excessive cell swelling
- disruption to organelles
- autophagy by lysosomes
- karyolysis or karyorrhexis
How does reversible injury progress to irreversible
Reversible injury can progress to irreversible if stress continues before resolution
What is meant by adaptation?
Cells are able to adapt to increase work demands or threats to survival by changing their size, number and form
What is the “normal” process of adaptation?
Normal adaptation occurs in response to an appropriate stimulus and ceases once the need for adaptation is ceased
When do cells undergo adaptation?
when there is a change in the internal environment
define homeostasis
Purposeful maintenance of a stable internal environment by coordinated physiologic processes that oppose change
