2 - Cell Injury, Adaptations, and Death 1 and 2 Flashcards
What are two things that cells/organs can adapt to?
- Physiologic stimuli/stress: normal stimuli such as hormones
- Pathologic stimuli/stress: modify structure or function to decrease or avoid injury or death; achieve a new “steady state” to preserve function
What types of injury can normal cells undergo?
Normal cells first undergo reversible injury, then if the injury is severe and progressive it will undergo irreversible injury, which causes necrosis or apoptosis.
What are three causes of cell injury?
- Hypoxia and ischemia: resulting in oxygen deprivation
- Toxins: pollutants, cigarette smoke, ethanol, drugs
- Infectious agents: viruses, fungi, bacteria, parasites
Other than hypoxia, toxins, and infectious agents, what are other etiologies of cell injury?
- Immunologic reactions: autoimmune disease, allergic rxns, hypersensitivity
- Genetic derangments
- Nutritional imbalances: protein/calorie imbalance
- Physical agents: trauma, temp exremes, radiation
- Aging
Define reversible cell injury? What is an example?
Stage of cell injury at which the injured cell can return to normal is damaging stim is removed.
Typical functional derangements and morph changes: failure of membrane pumps ot maintain homeostasis and accum of organelles and lipids in cell
What happens when there’s failure of membrane pumps ot maintain homeostasis and accum of organelles and lipids in cell occurs (reversibly injury)?
Distended ER, detached ribosomes, membrane blebs, loosening of intercellular attachments, swollen mito.
Enlargement of entire organ and cell swelling
At light microscope level: hydropic change or vacuolar degeneration, fatty change (primarily in cells dependent on fat metabolism).
What does a yellow “greasy” looking liver indicate? Why does this occur?
Steatosis (fat accum).
Hepatocytes are injured, resulting in an intracellular accum of triglycerides, liver enlargement, and elevated liver enzymes (leaked from injured cells)
What occurs cellularly during liver steatosis?
Intraecllular accumulation, in liposomes coalesce and push aside nucleus.
May impair cellular function (still reversible).
mild=no effect on cell function
severe=impairs cell function
*caused by toxins, obesity etc
What is necrosis? When does it occur?
Major pathway of cell death; uncontrolled“accidental” result of damage too severe for repair.
In response to: ischemia, toxin exposure, infections, trauma
What is regulated cell death and when does it occur?
Occurs with less severe injury when cells need to be eliminated as part of normal processes.
May be modified by therapeutic agents or genetic miutations.
Morphologically: apoptosis
What happens to the cell during necrosis?
- Membranes fall apart
- Enzymes leak out of lysosomes and cell
- Inflammation induced
- Cell is digested by enzymes leaked from lysosomes or from recruited leukocytes
Describe the morphology of cell necrosis?
- Cytoplasmic changes: increase eosinophilia, homogeneous cytoplasm, vacuolation
- Nuclear changes: pyknosis (shrinkage of pyknotic nuc), karyorrhexis (frag of pyknotic nucl), karyolysis (nuc basophihlia disappears due to digestion
- Dead cells: may be completely digested and disappear, debris phagocytosed, results in fatty acids that may calcify
What does this image represent?
Cell necrosis: cell and nucleus are shrunken, dead neurons visible
What is coagulative necrosis and what does it result from? Where does it occur?
Results from hypoxic or anoxic injury due to ischemia.
Persistence of dead cells with intact outlines but with loss of cellular details.
Occurs in solid organs (except the brain).
What is liquefactive necrosis and when is it commonly seen? What is an exception?
Complete digestion of dead cells - tissue dissolved by hydrolytic enzymes from lysosomes in WBCs
Commonly seen with bacterial and fungal infetions (microbes stim WBCs that release digestive enzymes)
Exception: brain infarcts result in liquefactive necrosis that’s swollen
What is caseous necrosis and what is it characteristic of?
Characteristic of tuberculous infection; gross appearance resembles cheese (crumbly/friable appearance)
Fragmented and coaulated cells with loss of tissue architecture (no cell outlines!).
Usually surrounded by a border of inflamm cells forming distinctive pattern called granuloma
What is gangrenous necrosis a term for? What are the different types?
Not a specific type but instead a term used for ischemic coagulative necrosis or lower or upper extremity.
Dry gangrene vs. wet gangrene: when bact. infection is present, the necrosis has liquefactive properties (wet).
Also used for severe necrosis of other organs (eg. gangrenous bowel/appendix/gallbladder)
In what case is fat necrosis typically seen?
Pancrease in acute pancreatitis: injury to pancrease releases lipase which liquifies and splits triglycerides.
-Fatty acid combines with Ca++ to form chalky white material (saphonification)
Can also occur as a result of trauma to fatty tissue which releases lipases and triglycerides
What is Fibrinoid necrosis and where does it occur?
Deposition of immune complexes (antigens/antibodies) in vascular wall.
Fibrin-like: bright pink amorphous appearance
Occurs in vasculitis syndromes - infectionof the vessel wall
What occurs in cell injury and death (apoptosis)? What are key features?
- Cells activate enzymes that degrade DNA and proteins
-
Key features (that contrast from necrosis)
- Plasma membrane is intact
- no leakage of contents
- fragments of cell are pinched off (apoptotic bodies)
- no inflammation (no significant PMNs or lymphocytes)
- cell fragments are consumed by macrophages
What are physiologic conditions that cause apoptosis? When can this occur?
- During embryogenesis
- Involution of hormone dependent tissues after hormone deprivation
- turnover of proliferative tissues
- death of leukocytes after inflamm response
- Elim of self-reactive lymphocytes
Controlled
What are pathologic conditions that cause apoptosis?
-
DNA damage
- if repair processes fail, apop is activated and cell dies
- radiation and chemo works via apop
- Accum of misfolded proteins (alzheimers)
- Cell injury induced by viral infections, induced by virus or host
What are three major mechanisms of apoptosis?
- Mitochondrial (intrinsic) pathway
- Death receptor (extrinsic) pathway
- Clearance of apoptotic cells
What is the mitochondrial (intrinsic) pathway mechanism for apoptosis?
- Cyt. C leaks from mito after BH3 sensors are activated and Bax and Bak are released.
- Cyt C. activates caspases.
What is the death receptor (extrinsic) pathway mechanism for apoptosis?
Cells expressing Fas ligand or TNF bind to cell surface “death receptors” and trigger caspase activation.
How are apoptotic cells cleared?
They express ligands for phagotye cell receptors and secrete factors that attract phagocytes.
Describe the morphology of apoptosis?
- Cytoplasmic eosinophilia.
- Chromatin condensation and aggregation - eventually karyorrhexis (frag of nucl and breal-up of chromatin into granules)
- Cell shrinkage with cytoplasmic blebs and apop bodies
- Phagocytosis without inflammation
Describe the cell size, nucleus, plasma membrane, cell contents, adjacent inflammation, and physiolog or pathologic role in cell necrosis?
Cell size: enlarged (swelling)
Nucleus: pyknosis, karorrhexis, karyolysis
Plasma membrane: disrupted
Cell contents: enzymatic digestion-may leak out of cell
Adjacent inflammation: frequent
Physiolog or pathologic role: invariably pathologic
Describe the cell size, nucleus, plasma membrane, cell contents, adjacent inflammation, and physiolog or pathologic role in cell apoptosis?
Cell size: Reduced (shrinkage)
Nucleus: fragmentation into nucleosome - size fragments
Plasma membrane: Intact: altered structure
Cell contents: Intact: may be released in apoptotic bodies
Adjacent inflammation: No
Physiolog or pathologic role: Often physiologic: eliminating unwanted cells; may be pathologic
What effect does ischemia have on mitochondrion?
Decreased oxidative phosphorylation > decreased ATP > decreased Na+ pump activity causeing ER swelling/cell swelling, and detachment of ribosomes causing decreased protein synthesis.
What is oxidative stress (causes apoptosis and/or necrotic cell death) and what causes it? What does it cause on a cellular level?
Cellular abnormalities induced by ROS
ROS production increased with radiation, UV light, X rays, toxins such as CCL4, and reperfusion of ischemic tissues.
Membrane damage, protein breakdown and misfolding, mutations.
In what type of cell death does mitochondrial dysfunciton occur?
Both necrotic and apoptotic cell death
What is the appearance of myofibers in someone with hypertrophy?
Increased myofiber width and enlarged nucleu.
Describe neurogenic atrophy in sksletal muscle?
Fibers shrink and myofibers disintegrate.
This is a pathologic process.
What happens to skeletal muscle in myopathy?
Hypertrophy AND atrophy occur in the same tissue.
What are two examples of epithelial metaplasia?
Ciliated columnar epithelium becomes squamous epithelium (trachea/bronchi of smokres)
Squamous epithelium becomes gastric/intestinal type epithelium (distal esophagus in ppl with reflux-_Barrett’s Esophagus_)
What ocurs with squamous metaplasia in the endocervix?
Columnar cells become squamous and increase the risk of HPV infection
What is ocuring when there’s an atherosclerotic plaque in arteries?
Cholesterol is deposited in the intima of the vessel, increasing the size of the intima.
What accumualtes in heart muscle, liver, and the brain and occurs predominantly with aging?
Lipofuscin: Indigestible material resulting from lipid peroxidation, “wear and tear” pigment.
What causes antracosis in the lung?
Carbon is inhaled and phagocytosed by alveolar mø and is transported to regional lymph nodes.
What is hemosiderin and what is it caused by?
Hemoglobin-derived pigment containing iron: looks yellow to golden brown.
Occurs locally where there’s been hemorrhage and causes systemic deposition with increased absorption of iron.
Found in many organs: liver, BM, spleen, lymph nodes.
Describe dystrophic pathologic calcification? In what types of tissue does it occer? What is its appearance and what are examples?
Non-viable, damaged or dying tissues with normal serum calcium.
Gross: white gritty deposits
Microscopically: basophilic
Exp: aortic valves in elderly, lymph nodes with old TB
Describe how metastatic pathologic calcification differs from dystrophic? In what tissues does it occur? What are common locations?
Occurs in normal tissues with hypercalcemia.
Common locations: interstitial tissues (lung, kidney, gasrtic mucosa)
