Exam 1 Flashcards by Allison Aufderhaar

Origin of a disease; understanding this can lead to prevention

Etiology

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mechanism of a disease (from normal to abnormal); can develop disruptions in this process to treat disease.

Pathogenesis

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Cellular injury results from _____

a disruption of one or more cellular components that maintain cellular viability.

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When do the first clinical signs/symptoms of disease show up?

Far removed from the start of the morphologic and biochemical changes associated with cell injury.

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Injury in one part of the cell can ____.

induce a cascade of effects.

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Cell injury results in?

cell adaptation
cell death
or can be reversed

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What are some causes of cell injury?

oxygen deprivation
infectious agents - bacteria, viruses, fungi, and parasites
physical agents - trauma, electricity, pollutants, burns, UV light, radiation
chemical agents and drugs - tobacco, alcohol, poisons, Rx/OTC drugs
immunologic reactions - allergies and autoimmune disease
genetic derangement - genetic mutations, chromosome abnormalities
nutritional imbalance - obesity, malnutrition, vitamin defeciency

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Cellular structures that maintain cell viability -

plasma membrane
mitochondria
nucleus
macromolecular synthesis (proteins, nucleotides, carbs, lipids)

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What biochemical mechanisms can be disrupted during cell injury? (hint: think about the cellular structures that maintain cell viability)

ATP depletion
generation of ROS (oxidative stress)
loss of calcium homeostasis
altered plasma membrane permeability
mitochondrial damage
DNA/protein damage

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Cell injury by reduced energy production is caused by ___?

decreased oxygen or no oxygen

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Decreased Oxygen

hypoxia

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No oxygen

anoxia

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What causes reduced oxygen levels?

impaired absorption of oxygen
decreased blood flow
disease of blood or blood vessels
inadequate oxygenation of the blood

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decreased blood flow

ischemia

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Decreased oxygen impairs ___ ____ in the mitochondria

oxidative phosphorylation

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What is a side effect in the cell of a decrease in ATP?

plasma membrane’s ability to maintain homeostasis reduces –> increased net gain of solute and isosmotic gain in cytoplasmic water

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If the cell has an isosmotic gain (influx in sodium, thus influx of water) what does that lead to?

cell swelling w/ formation of cell surface blebs
swelling of mitochondria
dilation of ER

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What happens if the ER dilates?

detachment of ribosomes from the RER. —> decrease in protein synthesis so you get increased lipid deposition

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If oxidative phosphorylation is reduced, what other energy producing pathway kicks in?

glycolysis

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What happens if glycolysis is increased?

lactic acid and inorganic phosphates produced which decreases intracellular pH leading to chromatin clumping

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reduced substrate for ATP production

hyperglycemia

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How are ROS generated in the body?

via normal endogenous oxidative reactions in the plasma membrane, mitochondria, cytoplasm, and peroxisomes

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If ROS are generated in the body, what is associated with it?

inflammation
oxygen toxicity
chemicals
irradiation
aging

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What is considered an ROS?

superoxide
hydrogen peroxide
hydroxyl radicals

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How does ROS damage cells?

lipid peroxidation protein cross-linking react with thymidine and guanine to induce single strand DNA breaks

You can reduce the effects of ROS by blocking their initiation or inactivating them.

True

How do you inactivate/prevent ROS intracellularly?

superoxide dismutase catalase glutathione peroxidase

How do you inactivate/prevent ROS extracellularly?

vitamins E, A, C and serum proteins that bind free iron and copper

How is cytoplasmic calcium maintained?

protein sequestration in the cytoplasm, mitochondria, and ER

What is a final common pathway of cell injury?

increased cytoplasmic calcium

What degradative enzymes are activated from high levels of calcium?

phospholipases proteases endonucleases ATPase

What are other causes of cell membrane injury?

``` complement - C5 - C9 membrane attack complex cytotoxic T-cells - perforin viral bacterial endotoxins and exotoxins chemicals ```

Degree of cell injury depends on ______.

cell type and its physiologic state

Etiologies of reversible cell injury?

toxins infectious agents hypoxia thermal injury

characteristics of reversible cell injury?

acute in nature | cell injury is of short duration and minimal intensity

What two types of morphology are associated with reversible cell injury?

hydropic (water retention) and fatty (steatosis- organelles retain fat)

What are the two morphologic forms of cell death?

necrosis | apoptosis

___ ____ leads to the release of cellular components into the extracellular environment.

cell death

ROS cause ___ - ____ breaks in DNA.

Single-stranded, cause >30 different base modifications in both purines and pyrimidines. Thymidine and guanine are major sites

What are some morphological changes that occur during necrosis?

Cell swells protein denaturation yielding a glassy homogenous pink staining cytoplasm organelle breakdown --> vacuolated cytoplasm nuclei changes: karyolysis, pyknosis/karyorrhexis/total loss inflammation - acute or granulomatous

Type of necrosis present depends on....?

the patterns of enzymatic degradation and bacterial products present

Most common form of necrosis (cytoplasmic proteins are coagulated) nucleus is lost, but the eosinophilic outline of the cell is retained for a short time prior to the inflammatory response

Coagulative Necrosis

Tissue is totally digested via lysosomal enzymes during acute inflammation associated w/ focal bacterial or fungal infections seen in the central nervous system pus/purulence

Liquefactive Necrosis

Associated w/ M. tuberculosis tissue has white, cheesy appearance microscopically - amorphous pink granular material w/in a ring of granulomatous inflammation loss of tissue aritecture

Caseous Necrosis

Common in trauma to the breast or in pancreatitis adipose tissue has chalky white-yellow appearance dead adipocytes give a "soap-bubble" appearance histologically

Fat Necrosis

Programed cell death

apoptosis

Morphologic features of apoptosis

cell shrinks chromatin condensation followed by framentation apoptotic bodies form phagocytosis of the apoptotic bodies w/o significant inflammatory response

Mechanism of apoptosis

``` intrinsic program death signals - Fas ligand binds to Fas receptor removal of trophic signals (hormones) ROS, radiation, and toxins effect of cytotoxic T-cells ```

What are the 2 pathways of apoptosis?

direct signaling - Fas lignad, TNF binding | regulation of mitochondrial permeability

What serves as an on off switch that regulates mitochondria permeability?

Bcl 2 gene family * Bcl-2 and bcl-x inhibit apoptosis * Bax and bak stimulate apoptosis

What disrupts the inhibitory effect of Bcl-2 function, favoring apoptosis?

Cytochrome-c

Mitochondria release ___ which activates certain enzymes to execute apoptosis.

calcium

What is caused by transgutaminases in response to calcium release?

cross-link cytoplasmic proteins

What is caused by endonucleases in response to calcium release?

cleavage of DNA at the linker regions between nucleosomes

How are dead cells removed?

phagocytosis by neighboring cells and macrophages

How do cells adapt in response to injury?

change in size (atrophy or hypertrophy), number (hyperplasia) or differentiation (metaplasia), intracellular accumulations

What leads to cellular adaptations?

chronic cell injury

decrease in cell size and function

atrophy

What causes cellular atrophy?

``` decrease in workload loss of innervation decreased blood supply (ischemia) inadequate nutrition decreased trophic signals aging local pressure ```

What do atrophic cells look like?

shrunken and reduced in structural components

an increase in cell size associated with increase in functional capacity

hypertrophy

Can hypertrophy be accompanied with hyperplasia?

yes organ size may increase too.

What causes cellular hypertrophy?

responses to trophic signals normal hormone stimulation - for smooth muscle hypertrophy in pregnant uterus abnormal hormone stimulation - anabolic steroids to increase muscle size or overproduction of TSH due to iodine deficiency (goiter) response to increased function - increased skeletal muscle use; increased workload of cardiac muscle

increase in the number of cells in a tissue or organ

hyperplasia

What cells proliferated during hyperplasia?

epithelial or stromal cells

What stimulates cell proliferation?

hormones or cytokines (trophic factors)

Hyperplasia may increase the risk for neoplasmic transformation.

true

What causes hyperplasia?

hormones | growth factors

What hormones stimulate hyperplasia?

endometrial glandular cells during menstrual cycle gynecomastia erythrocyte hyperplasia following ectopic production of renal cell carcinoma

hyperplasia of the breast in men

gynecomastia

How does wound healing display hyperplasia?

connective tissues and epithelial cells divide

What causes lymph node hyperplasia?

lymphocyte hyperplasia from chronic inflammation and immune response

Are calluses due to hyperplasia?

yes, epidermal hyperplasia

Can chronic inflammation cause hyperplaisa?

yes

one adult cell type is replaced by another adult cell type in response to chronic stress

metaplasia