Cell Injury, Adaption, Death Flashcards
What are the two means of stimulation for cellular adaption?
Physiologic Stress - normal part of physiology
Pathologic Stress - abnormal
What are responses to nonlethal stimuli either by physiologic or injurous?
- Hyperplasia
- Hypertrophy
- Atrophy
- Metaplasia
What are the results of cell injury via ischemia, chemical injury, or infection?
Cell Injury:
- Acute Reversible
- Irreversible with necrosis and apoptosis
What are the differences between Labile, Stable, and Permanent cells?
Labile cells = continuously growing, surface epithelial
- bladder, skin, GI, bronchials, etc
Stable Cells = Quiescent, minimal division, but have the ability to if need be in response to injury.
- Liver, kidney, pancreas, endothelial cells
Permanent Cells = Do not divide, nonproliferative
- Neurons and Cardiac
Example of both types of hypertrophy?
- Physiologic: athletic muscles
- Pathologic: cardiac hypertrophy leading to HTN
What are both types of Hyperplasia and examples?
Physiologic: Hormonal - puberty
Pathologic: Endometrial hyperplasia, excessive stimulation by growth factors
Increased risk of cancer
What are examples of both types of Atrophy?
Reduction in size of cells, not related to death.
Physiologic: loss of hormonal stimulation
Pathologic: Broken arm/CVA, atrophy
What is metaplasia?
The change of one cell type to another in various locations based upon stimulation.
When does metaplasia occur and common locations?
Typically epithelial metaplasia, columnar to squamous or squamous to gastric epithelium, etc.
Bronchi of smokers (change from columnar)
Distal Esophagus in GERD to gastric cells
What are male and female versions of hyperplasia?
- Endometrial Hyperplasia
- Benign Prostatic Hyperplasia
- HPV skin warts/lesions
What is the common appearance of the tissue with hyperplasia?
Increased number of glands and nodes within the tissue due to the increased number of cells
What is the only organ that can undergo hyperplasia and hypertrophy?
Uterus, during pregnancy.
What is the biggest concern regarding metaplasia?
Increased risk of cancer of that tissue
What is the difference between ischemia and hypoxia?
Hypoxia is inadequete blood oxygenation such as in Asthma, COPD
Ischemia is lack of blood supply to a certain site such as in blood clots or injury
What are the two types of cell death and how are they different?
Necrosis
- primarily pathologic and associated with inflammation
Apoptosis
- usually physiologic without associated injury, can still be pathologic though
What are the characteristics of necrosis?
Enlarged cell with nucleus pyknosis, karyorrhexis, karyolysis
Disrupted plasma membrane
Enzymatic digestion/leaking out of cell (Troponin)
Frequent surrounding inflammation
Pathogenic
What are the characteristics of apoptosis?
Reduction in size of the cell
Fragmentation of the nucleus, membrane remains intact
Contents of cell intact and released as apoptotic bodies
No inflammation
Usually physiologic, but sometimes pathologic
What are the characteristics of reversible changes?
Fatty Change, lipid vacuoles in cytoplasm, usually occurs in cells with lipid metabolism ie. Liver
Cellular Swelling, membrane blebs/distended ER
Example: Cirrhotic Liver
What point does the cellular changes become irreversible?
When the organelles and cell membrane rupture
What are common causes of these type of reversible changes?
Alcohol, Obesity, Anorexia, DM, viral infections
Why does the liver become fatty with chronic alcohol use?
- impairment of microsomal and mitocondrial functions (where fat is broken down)
- decreased fatty acid oxidation
- increased fatty acid metabolism from peripheral
What are the most common types of necrosis?
Coagulative Caseous Liquefactive Fat Gangrenous Fibrinoid
What kind of necrosis happens to solid organs after anoxia or ischemia?
Coagulative
Not the brain though
What kind of necrosis has complete digestion of tissue dissolved by hydrolytic enzymes?
Liquefactive Necrosis, – Known as Abscess
ie. Pyelonephritis
Most common with bacterial and fungal infections
(Brain undergoes this necrosis after infarction)
What necrosis type of necrosis is used to describe coagulative necrosis in distal extremities?
Gangrenous Necrosis
Wet = infected as well
Dry = noninfected
What type of necrosis has loss of cell outlines and surrounded by inflammatory cells?
Caseous Necrosis, which is typical of TB granulomas
What kind of necrosis can occur with chronic alcoholism and pancreatitis?
Fat Necrosis, build of fat on fatty organs
–Also repeated trauma to fatty tissue–
What kind of necrosis occurs in result to deposits of immune complexes on vascular walls?
Fibrinoid Necrosis - is Vasculitis syndromes
What are common mechanisms of injury to a cell?
- Mitocondrial damage, deplete ATP
- Increased membrane permeability
- Increased ROS and DNA damage
- Increased Ca+2 causing inapproriate activation/inactivation
What are two results of depleted ATP?
- cellular and organelle swelling due to influx of cations
- clumping of chromatin due to lowered pH because of glycolysis producing acid
What is a key result of mitocondrial injury?
Leaking and production of ROS and pro-apoptotic proteins
What factors contribute to cellular injury?
Type of injury, hypoxia or ischemia
Duration of injury
Severity, partial or complete ischemia
Type of cells affected (neuron>cardiac>skeletal)
What is reperfusion injury?
When there was ischemia and flow is restored, which causes a large influx of ROS causing additional cellular damage + inflammatory response = further damage
What are the typical signs of apoptosis of a cell?
- Reduction in size
- Cellular contents do not leak
- No inflammation
What are common physiologic reasons of apoptosis?
embroyogenesis, elimination of T-cells, death of inflammatory cells, etc
What are the causes of apoptosis of cells?
- DNA damage from radiation/chemo
- accumulation of misfolded proteins, Alz disease
- Viral infection damage
- organ atrophy due to obstruction
What are the morphologies of apoptosis?
- Cytoplasmic eosinophilia
- Condensation of chromatin
- cell shrinkage
- cytoplasmic blebs
- phagocytosis without inflammation signs
What are the two pathways for apoptosis?
Intrinsic, Bcl-2 proteins induce mito to release pro-apoptotic factors cytochrome-c activating caspases
Extrinsic, Death receptor, activating caspases
What are the characteristics of dystrophic calcification?
Build up of calcium in non-viable and damaged tissue
Normal body calcium levels, white gritty deposits
Basophilic, blue color stain
Common Locations: Aortic valves, vessel lumens, lymphnodes
How is metastatic calcification different than dystrophic?
- Normal tissues will be effected due to body having hypercalcemia. Increased PTH, Vit D, causing renal failure and destruction of bone.
Locations: lungs, kidney, gastric tissues
How do cells undergo aging?
Chronic nonlethal damage over time, ROS damage, progressive shortening of telomeres.
Decreased cellular survival and homeostasis