Mechanisms of Cell Injury and Adaptation Flashcards Preview

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Flashcards in Mechanisms of Cell Injury and Adaptation Deck (46):
1

Cell response to injury

-adapt to change or be damaged and respond in injured way

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Cellular adaptation

-adapt to increased work demands
-size (atrophy and hypertrophy)
-number (hyperplasia)
-form (metaplasia)
-potentially reversible

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Metaplasia

-replacement of adult cells
-not a normal physiologic process and may be the first step toward neoplasia
-this is the one we worry about --> this is the type of cell change that we regard as the first step in neoplasia or cancer

4

Dysplasia

-abnormal proliferation of cells that is characterized by changes in cell size, shape, and loss of cellular organization
-still potentially reversible
-birth defect or congenital abnormality
-usually a developmental process

5

Actinic Keratosis

-change in the skin --> you see keratinocytes that are atypical
-you see actinic elastosis
in epidermis you see presence of unusual cell forms

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cerebral atrophy in pt with Alzheimers

-gyri are narrowed, sulci widened, particularly toward frontal portion

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causes of atrophy

-atrophy
-denervation
-loss of stimulation (endocrine)
-malnutrition
-ischemia

-decrease in cell size and activity reduces energy requirements and makes cells more efficient

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hypertrophy

-muscle unable to adapt with mitotic division
-hypertrophy may be physiologic, pathologic, or compensatory
-marked thickening of the left ventricle in pt with systemic hypertension

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hyperplasia

-increased cell number
-tissue cells must be capable of mitosis (i.e. nerve and muscle cells CANNOT DO THIS)
-activation of genes for cell division
-prostatic hyperplasia (nodular)

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metaplasia

-reversible process when irritant is removed
-RESPECTS TISSUE BOUNDARIES
-loss of one cell function type for another - replace one cell type with a completely different cell type
-ex) constant irritation from smoking, Barrett's esophagus (from gastric reflux - precursor of malignant transformation)

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dysplasia

-this is farther down the road toward neoplasia
-most of the time this is congenital
-HPV can cause this on cervix

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types of accumulation

-endogenous
-abnormal products
-exogenous

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endogenous accumulation

-fatty acids in liver in DM
-genetic enzyme deficiencies
-tao protein in Alzheimers or amyloid

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abnormal product accumulation

-tay sachs - abnormal lipids accumulate in tissues

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exogenous

-lead, coal dust, tar and ash in cigarette smokers, etc.

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MCC of cellular injury

-hypoxia (MCC) - usually related to hypoxia or lack of perfusion

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effects of hypoxia

-lack of O2 --> reduced ATP --> lactic acid buildup --> protein degradation --> pump failure --> swelling --> lysosomal enzyme leakage to EC

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major causes of hypoxia

-ischemia (MCC)
-cardiopulm failure
-decreased O2 capacity in blood (anemia)

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mechanisms of cell injury

-peroxidation caused by O2 derived free radicals
-mitochondrial dysfunction
-increased cell membrane permeability

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effect of Ca on cell injury

-its a second messenger so it can activate a lot of enzymes
-Protease
-ATPase
-Phospholipase
-Endonuclease

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protective factors against free radicals

-Antioxidants: vitamins A, E, C
-Superoxide dismutase: superoxide → hydrogen peroxide (H2O2)
Glutathione peroxide: hydoxyl radical or hydrogen peroxide → water
Catalase: hydrogen peroxide → oxygen and water

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reversible cell injury types

-Cellular swelling: impairment of the energy-dependent Na+/K+ pump, usually as the result of hypoxic cell injury (Sometimes due to lack of ATP or lack of perfusion)
-Fatty change: linked to intracellular accumulation of fat. Indicates severe injury (Telling you that the cell is tipping over to irreversible changes)

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causes of reversible cell injury

-Decreased synthesis of ATP by oxidative phosphorylation
-Decreased function of Na/K ATPase pumps → cellular swelling
-Switch to glycolysis: decrease intracellular pH
-Detachment of ribosomes from the RER → decreased protein synthesis

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irreversible cell injury

-Severe membrane injury
-Marked mitochondrial dysfunction
-Rupture of the lysosomes
-Nuclear changes
-Cytoplasmic enzyme leaks
-Influx of Ca

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Pyknosis

degeneration and condensation of nucleus (shrunken and dark)

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karyorrhexis

nuclear fragmentation

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karyolysis

dissolution of the nucleus

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markers of myocardial injury

-Creatine phophokinase (CPK) – MB izoenzyme (CPKMB)
-Lactate dehydrogenase (LDH)
-Troponin

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markers of cellular injury

The loss of cell membrane integrity (=cell death) allows intracellular enzymes to leak out, which can then be measured in the blood

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markers of hepatitis

transaminases (AST/ALT)

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markers of pancreatitis

amylase and lipase

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markers of biliary tract obstruction and bone

alkaline phosphate

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reversible cell injury

-decrease Na/K pump (influx of Na and efflux of K)
-increase glycolysis (decrease glycogen, increase lactic acid)
-ribosomal detachment (decrease protein synthesis)

34

necrosis vs apoptosis

Necrosis:
-many cells undergo necrosis at once, then definable patterns of necrosis are produced. Unregulated enzymatic destruction of cellular components, loss of cell integrity, release of substances, initiation of inflammatory response.
Involves uncontrolled enzymatic destruction of tissue
Initiations a potent inflammatory response

Apoptosis
-A more orderly process of cell death in which there is individual cell necrosis, not necrosis of large numbers of cells.
Individual cells die instead of mass amounts of cells

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Morphological types of necrosis

Coagulative necrosis
Liquefaction necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
Gangrenous necrosis

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coagulative necrosis

-MOST COMMON FORM OF NECROSIS
-Due to coagulation and denaturing of proteins within the cytoplasm
-Common in most organs including the heart, liver, adrenal gland, spleen and kidney
-etiology of coagulative necrosis is usually vascular with loss of blood supply --> infarcts are often wedge-shaped

37

liquefaction necrosis

-There is a liquid center in an area of tissue injury
-release of proteolytic enzymes destroys the surrounding tissues
-Occurs in abscesses, brain infarct, lung, liver and pancreatic necrosis (pancreatic enzymes turn on themselves and kill the pancreas)
-common in the brain with infarct

38

caseous necrosis

-Combination of coagulation + liquefaction necrosis that is most characteristic of granulomatous inflammation
-This is what you see when you talk about a granuloma
-Characteristic of tuberculosis
-The hilar node he showed has a cheesy tan to white appearance.

39

fat necrosis

-Caused by the action of lipase on fatty tissue
-In breast, pancreas, omentum
-When fat cell dies, TG released.
-Lipase breaks TG to fatty acids: negatively charged.
-They attract Ca with positive charge to the area = saponification --> creation of SOAP!!
-Infiltration of the tissue with calcium
-Soaps break down fats

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fibrinoid necrosis

-Can be seen in the walls of small or medium-sized muscular blood vessels (it does not involve arterioles, capillaries, or venules).
-It is associated with immune-complex vasculitis and hypertension.
-Fibrin deposition occurs in damaged necrotic vessel walls.
-Malignant hypertension and polyarteritis nodosa are common causes.

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gangrenous necrosis

-Gangrene occurs when a considerable mass of tissue undergoes necrosis.
-caused by thrombosis or lack of blood flow and subsequent contamination with bacteria
-Common sites: lower limbs, gallbladder, GI tract, and testes
-best tx = revascularization, but by the time it is gangrenous, its often too late
-Microscopic pattern of dry gangrene: is coagulative necrosis (i.e. frostbite)
-Microscopic pattern of wet gangrene: is liquefactive necrosis

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apoptosis

-Is a specialized form of programmed cell death, often affect only single cell or small group of cells. Involves controlled autodigestion of intracellular components.
-Apoptosis is controlled by many mechanisms.
-It can be an active process regulated by genes.
-It can be due to injury caused by viral infection like hepatitis.

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genes involved in apoptosis

-bcl-2 gene = inhibit apoptosis (youth gene!) therefore, during apoptosis bcl-2 are turned off
-p53 gene is a suppressor gene; temporarily arrest the cell cycle to repair DNA damage (abort apoptosis) or promote apoptosis if DNA damage is too great by activating the Bax gene.
-Bax genes are turned on, stimulate apoptosis
(Bax gene overrides p53 and causes apoptosis)
-c-myc genes (When associated with p53 leads to apoptosis, When associated with bcl-2 inhibits apoptosis)

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stimulus for apoptosis

-Cell injury and DNA injury
-Lack of hormones, cytokines, or growth factors
-Receptor-ligand signals (Ligand like: Fas or TNF)
-Worn out cells
-Cells have been produced in excess
-Cells have developed improperly
-Cells have been infected by viruses

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execution of apoptosis

-Mediated by a cascade of proteolytic enzymes called caspases (killing enzyme)
-Caspases digest nuclear and cytoplasmic proteins
-Caspases also activate endonucleases
-Note that during apoptosis, there is a lack of an inflammatory response!!
-Apoptosis tends to happen without any inflammation
-As opposed to necrosis, apoptosis has a pretty intact membrane to begin with

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physiologic examples of apoptosis

-Embryogenesis: organogenesis and development, webbing of fingers, formation of heart
-Menstrual cycle: a hormone dependent apoptosis (the cells in the lining of the endometrium undergo apoptosis when the progesterone drops)
-Thymus selective death of lymphocytes
-Bone marrow and blood cell components
-Possibly neurodegenerative diseases