Chapter 2 - Cell Injury Flashcards
Mild cell injury (Cellular stress)
Induces cells to alter and adapt without dying, due to disruption of cellular homeostasis
- An interruption or alteration of cell function
Reactions to injury or cellular stress
- May be reversible or irreversible
- May result in recovery, adaptation or death
- Vary with: 1.) Injury type
2. ) Duration and severity of injury
3. ) Type of cell
4. ) Current state or health of the cell
Functions of the cell most vulnerable to injury
From immediate to long term…
- Aerobic respiration: the most important energy source, no oxygen = no ATP
(Hypoxia - most common injury cause) - Cell membrane integrity
- Enzyme and structural proteins synthesis
- Genetic integrity
Intracellular accumulations
Require mild injury or stress for at least a few weeks
Acute mild injury or stress
- Intracellular edema
- Steatosis
Intracellular edema
Water accumulation (hydrophobic change = cloudy swelling)
- Due to interference with cellular metabolism > decreased ATP > sodium potassium pump failure > loss of selective permeability of cell membrane > influx of sodium and water into cell
- Reversible if source of stress is removed early enough; if not, this will eventually result in death
Steatosis
Fat accumulation (“fatty change” or “fatty degeneration”)
- Interference in cellular metabolism may result in: decreased export of fat from cell or increased production of fat
- Reversible if source of stress is removed early enough; if not will eventually result in cell death
- Chronic alcoholism: fatty liver due to stress of alcohol consumption
Chronic mild injury or stress
- Cholesterol accumulation
- Protein accumulation
- Glycogen accumulation
- Pigment accumulation
- Calcification
- Hyaline deposits
Cholesterol accumulation
The most extensive and damaging accumulation
- First appears in macrophages and smooth muscle cells in arterial wall
- Later accumulates into large, extracellular pools in the arterial wall
Protein accumulation
Proteins are misfolded and nonfunctional
- Alpha 1 anti-trypsin deficiency: genetic degeneration with protein clumps in hepatocytes
- Mallory bodies: protein clumps due to alcoholic liver disease
- Alzheimer disease: neuronal protein plaque accumulations
Glycogen accumulation
Storage form of glucose in the liver and muscles
- Diabetes: high blood glucose causes liver and kidney cells to be stuffed with glycogen
Pigment accumulation
Soluble, visible substances
- Lipofuscin
- Melanin
- Carbon
- Hemosiderin and ferritin
- Bilirubin
- Tattoos
Lipofuscin
Residue of worn out organelles (“wear and tear” pigment)
- Golden brown granules are most common pigment accumulation
- Result of aging or long term, low-grade cell stress
- Brain neurons, myocardial muscles cells, and hepatocytes
- Usually does not interfere with cell function
Melanin
Normal pigment, usually good
- Normal body pigment, brown granule a basal cells in epidermis
- Increased deposit seen with:
• excess sun
• various metabolic skin diseases, or tumors (melanoma)
Carbon
- Acquires as dust from the environment (exogeneous)
- Black granules
- Deposits and lung are called anthracosis (not due Bacillus anthracis)
- Usually doesn’t interfere with cell function
Hemosiderin and ferritin
Iron storage molecules
- Important and hemoglobin and iron metabolism
- Dark brown granules
- Deposits and lungs are called hemosiderosis
• May indicate there is underlying disease
• May interfere with cell function or cause cell death
Bilirubin
“Red” bile: orange or yellow color
- Break down product of hemoglobin from dying RBC’s
- Processed and excreted by the liver
- Excess amounts in tissue result in a yellow color (jaundice or icterus)
Tattoos
Ink pigments into skin where dermal macrophages (Langerhan cells) engulf and persist for a lifetime
Calcification
Calcium compounds and tissue
- Normal in bones and teeth
- Abnormal calcification
• Dystrophic calcification: deposits in damaged or dead tissue
• Metastatic calcification: deposits in living tissue due to cancer disorder
Hyaline deposits
A collective term meaning anything that looks pink in structureless (amorphous) under the microscope
- Fibrin, collagen, amyloid (starch-like)
Adaptations to mild injury or stress
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
- Anaplasia
Atrophy
Decrease cell size
- Cell or organ loses substance in and attempt to survive changing circumstances
- Causes: • Disuse atrophy - not used
• Loss of innervation (EMS won’t prevent, only slows down atrophy)
• Diminished blood supply (ischemia)
• Loss of endocrine simulation
• Chronic inflammation
Hypertrophy
Increase cell size, not number of cells
- Usually from increased functional demand “compensatory hypertrophy”
• Skeletal muscles in a bodybuilder
• Heart in patient with hypertension (systematic)
• Kidney enlargement following removal of other kidney - Hormonal stimulation: breast enlargement after delivery due to prolactin
Hyperplasia
Increase number of cells
- Usually from increased functional demand
• Skin callus: following repeated use or trauma
• Uterine smooth muscle: during pregnancy
• Increased liver cells following loss of liver tissue - Hormonal stimulation: thyroid gland following stimulation by the pituitary
*** Note on hypertrophy and hyperplasia
Frequently occur together if cells have the ability to divide
- Cardiac muscle cells don’t divide, so they can only hypertrophy
- Both are controlled processes that don’t stop when stimulus ceases
Metaplasia
Change of cell type
- Change from one mature cell type to another mature cell type
- Usually a change from a more sensitive cell type to a better able to survive a particular stress
- Like dysplasia it is reversible if irritation is removed
Dysplasia
Disarrangement of cells, usually associated with epithelia
- Replacement abnormal cells with abnormal, usually following chronic irritation
- First stage in development of malignancy
- Reversible if irritation is removed
Anaplasia
Formation of malignant tumors or neoplasms (not benign tumors)
- Tissue organization breaks down beyond dysplasia or metaplasia
- Undifferentiated cells: do not resemble tissue of origin (nonfunctional)
• Benign tumor show slight anaplasia if cells are semi-differenciated - Uncontrolled cell division: density dependent cell division lost
- Irreversible
Typical cancer progression
Normal > dysplasia > anaplasia
Lung cancer progression
Normal > metaplasia > dysplasia anaplasia
Connective tissue cancers progression
Normal > anaplasia
- No warning
Severe injury and cell death
- Autolysis
- Necrosis
Autolysis
Self digestion, when the whole body is dead
- Cell damage leads to release of interest cellular enzymes > break down adjacent structures
- Usually refers to sell death in the context of an individual, cell death in a dead body
Necrosis
Pathological cell death, localized
- Coagulation necrosis
- Liquefication necrosis
- Caseous necrosis
- Fat necrosis
Coagulation necrosis
Makes tissue more solid than normal
- Cells are dead but overall cell outlines remain intact for a while, nuclei don’t show
• Often called a “ghost town” appearance
• Eventually dead cells are removed by the body’s clean up system and replaced by scar tissue - Infarct
Infarct
Ischemic death usually resulting from a loss of blood supply
- Most common cause of coagulation necrosis
- Myocardial infarction
Liquefication necrosis
Dead tissue rapidly dissolves into fluid, eventually cleaned up and leaves a hole
- Suppurative (pus forming) bacterial infections (abscesses, boils, puss)
- Death of tissue with powerful hydrolytic enzymes (brain infarction)
Caseous necrosis
Dead tissue becomes crumbly amorphis debris “cheese like”
- Usually result of infection by organisms that elicit a granulomatous inflammatory response (tuberculosis)
Fat necrosis
Result of damage by lipase (pancreatic enzyme) associated with “pancreatic ez”
- Lipase breaks triglycerides into fatty acids
- Fatty acids combine with calcium to make chalky “soaps” (saponification: one form of dystrophic calcification)
- Calcium soaps can be visible on radiographs, mimic calcium deposits in breast cancer
- Fatty tissues die and become firm, white, and chalky
Biologic aging
- Aging
- Apoptosis
Aging
Normal physiological process distinct from disease
- Cell lifespan
- Telomere
- Progeria
Cell lifespan
Have about 50 generations
Telomere
Cap of nucleotides on the end of each DNA strand
• Each replication: telomere loses a few nucleotides, like a clock ticking
• Telomere gone: cell no longer replicates and dies
Progeria
Rapid aging disease, “early geriatrics”, increased speed with high stress
Apoptosis
Normal, physiologic, planned cell death
- Epidermis: cells are genetically programmed to commit suicide after a few days
- GI tract: epithelial cells are actively dividing to replace cells programmed to die
