8-4 Cell Injury Flashcards
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Categories of Injury 1. Hypoxia/Anoxia 2. Chemical 3. Biological 4. Genetic 5. Aging (Destructive) 6. Immunologic 7. Physical 8. Nutritional -------------------------------------------------------------------------------------- B: During Dz, cells start to change their structure & function due to injury. This will manifest as signs & symptoms. Cells react to the injury in 4 ways:
1) Homeostasis: Physiologic response (tachycardia during exercise)
2) Adaptation: Cells change in size/shape/number in response to environmental changes. {Hyperplasia vs. Hypertrophy vs. Atrophy vs. Metaplasia}
3) [Reversible Cell Injury]: Sublethal (fat accumulating in liver cells post ethanol ingestion=steatosis OR [Cell Swelling])
4) [ iiReversible cell injury :-( ] = CELL DEATH (sustained ischemia causes myocardial infarction)
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CELL ADAPTATION: Cells change in number/size/shape in response to environmental changes. {Hyperplasia vs. Hypertrophy vs. Atrophy vs. Metaplasia}
- ------------ - Hyperplasia= Cells INC in (#) from growth factors that activate signaling pathways to stimulate cell proliferation or stem cell regeneration
Physiologic Example: During Pregnancy [glandular epithelium] of breast proliferates to prepare for breast feeding
PATHOLOGIC EXAMPLE: HIGH ESTROGEN CAN CAUSE PROLIFERATION OF [ENDOMETRIAL GLAND EPITHELIUM] = ENDOMETRIAL HYPERPLASIA
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CELL ADAPTATION: Cells change in number/size/shape in response to environmental changes. {Hyperplasia vs. Hypertrophy vs. Atrophy vs. Metaplasia}
- ------------ - HyperTrophy "I want a Bigger Trophy" = Individual Cells INC in ACTUAL SIZE
Physiologic Example: Athlete who repeatedly lifts weights will INC skeletal muscle mass
PATHOLOGIC EXAMPLE: PT WITH SYSTEMIC HTN WILL INC CARDIAC MUSCLE MASS BECAUSE HEART HAS TO WORK HARDER TO OVERCOME VASCULAR RESISTANCE
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CELL ADAPTATION: Cells change in number/size/shape in response to environmental changes. {Hyperplasia vs. Hypertrophy vs. Atrophy vs. Metaplasia}
- ------------ - Atrophy = Individual Cells DEC in actual SIZE smh because of cellular substance loss when DEC protein synthesis & metabolic activity and INC protein degradation occur
Physiologic Example: Cessation of menses and DEC endometrium growth in post-menopausal women due to lower estrogen level
PATHOLOGIC EXAMPLE: MUSCLES ATROPHY WHEN LEG IS PLACED IN CAST FOR BROKEN BONE
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CELL ADAPTATION: Cells change in number/size/shape in response to environmental changes. {Hyperplasia vs. Hypertrophy vs. Atrophy vs. Metaplasia}
- ------------ - Metaplasia = Occurs when 1 adult cell is substituted for another type of adult cell after the precursor cells have been reprogrammed for differentiation
PATHOLOGIC EXAMPLE:
1. [SIMPLE COLUMNAR EPITHELIUM] IN THE ENDOCERVIX CAN BE CONVERTED INTO [stratified squamous epithelium] IF THE CERVIX UTERI IS IRRITATED AND INFLAMED ENOUGH
- CIGARETTE SMOKERS WILL HAVE SQUAMOUS METAPLASIA OF THE BRONCHI COLUMNAR CELLS **This is Reversible :-) **
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Certain components of the cell are VULNERABLE to INJURY: A: Cell Membrane B: Mitochondria/Aerobic respiration C: Cellular Ca+ D: Integrity of genetic material
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These 4 biochemical changes during injury will determine the EXTENT of the injury and whether or not cell death will occur:
- Depletion of ATP
- O2 deprivation OR Generation of O2-dervied free radicals
- [Intracell Ca+ Concentration] and loss of Ca+ homeostasis
- Defective cell membrane permeability
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Hypoxic Injury Model
A: Cell Swelling is a structural change caused by abnormal INC water content. It is Reversible!
B: Etiology:
1. DEC O2 adversely affects oxidative phosphorylation in the cell—> DEC ATP from mitochondria—> [Na/K pump] stops working—> Na+ becomes trapped in the cell! —>Water passively moves into cell and swells it
- DEC ATP from mitochondria ALSO—> INC Cell Ca+—> [altered membrane permeability] and activation of [intracell enzymes]. Since the membrane is altered, these [intracell enzymes] leak out into [vascular compartment] and can be used by Docs for measurement
- DEC ATP from mitochondria ALSO—> [INC AnAerobic Glycolysis]—> Metabolic Acidosis
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Free Radical Injury Model
OXYGEN RELATED FREE RADICALS
A: Free radical is an atom/atoms with a single unpaired electron in outer orbit. They are unstable and reactive with cell components such as membrane and organelles. This rxn can cause iiReversible Damage!
A2: There are defensive cell mechanisms to [Free Radicals] such as [Antioxidants Vitamin C and E] and [intracell enzymes= catalase/superoxide dismutases/glutathione peroxidase]
B: Types of Free Radicals
1) O2 related: ROS (Reactive oxygen species) made during mitochondrial respiration. They’re typically degraded & removed. So at steady state they are at low concentrations.
1B: INC production of ROS can lead to excess [Free Radicals such as O2 superoxide / H202 / OH] and [oxidative stress].
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C: NON-OXYGEN RELATED FREE RADICALS
Ex: CCL3 from [carbon tetrachloride] when acetaminophen is metabolized.
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D: Mechanisms of Free Radical Injury include
-Lipid peroxidation of membrane
-Nonperoxidative mitochondrial damage
-Lesions in DNA
-Protein Cross-linking
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Chemical Injury
A: Chemicals can act in 2 ways:
1) Direct= mercury chloride poisoning
2) INdirect= acetaminophen is first converted into [carbon tetrachloride] before it causes damage
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iRReversible cell injury—> Cell Death that manifest as Necrosis.
A: Necrosis is the pathological process involving morphologic change in living tissue after it’s died. It happens due to enzymatic breakdown and protein denaturation. Necrosis is characterized by neutrophils (which infiltrate the dead tissue), and structural changes in nucleus & cytoplasm
B: H&E Stains (Hematoxalyin & Eosin) exploit cell changes during Necrosis. Necrotic cells show INC eosinophilia due to loss of cytoplasmic RNA. This means
- less [Blue Hematoxalyin]
- MORE [Red-Pink Eosin] since it binds to denatured cytoplasmic proteins
C: Hematoxalyin stains [RNA-rich-parts of cytoplasm] * [hyaline cartilage matrix] BLUE
D: Eosin stains [cytoplasm / connective tissue / extracell substances / RED or PINK
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A: [iRReversible Nuclear changes] during Necrosis appear in 1 out of the 3 patterns due to DNA breakdown
1. Karyolysis = basophilia of chromatin fade. This reflects loss of DNA from enzymatic degradation by endonucleases
- Pyknosis
- Karyorrhexis
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B: [iRReversible Nuclear changes] during Necrosis appear in 1 out of the 3 patterns due to DNA breakdown
1. Karyolysis
- Pyknosis= nuclear shrinkage & INC basophilia. Chromatin condenses into solid, shrunken basophilic mass. Pyknosis is also common in apoptosis along with DNA breakdown
- Karyorrhexis
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C: [iRReversible Nuclear changes] during Necrosis appear in 1 out of the 3 patterns due to DNA breakdown
1. Karyolysis
- Pyknosis
- Karyorrhexis= Pyknotic nucleus undergoes fragmentation and in a day or two..nucleus in necrotic cell TOTALLY DISAPPEARS. This is associated with [Coagulation Ischemic Necrosis] specifically
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A: [Coagulative Ischemic Necrosis] is often associated with ischemia and best appreciated in solid organs like the HEART & KIDNEY!
B: [Coagulative Ischemic Necrosis] is characterized by ghost-like remnants of cells that lack their nuclei.
B2: These cells’ cytoplasm STAINS PINK (Eosinophilia) due to membrane damage(allows RNA to leak out) and Eosin stains cytoplasm even when RNA has leaked out
