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29 Cards in this Set

  • Front
  • Back
Cell Injury & Adaptation
- kinds of adaptations
Hypertrophy / atrophy –Of entire cell –Of specific organelle
•Hyperplasia

•Metaplasia
•Dysplasia
These are a response to direct cellular injury or stress, or to changing hormonal or chemical signals.
what is and what causes hypertrophy
-physiologicas vs. pathological
-describe cardiac hypertrophy
is cellular or organelle enlargement in response to a stimulus. This stimulus can be stress or hormonal or chemical signaling. Genetic interactions can occur.
-Hypertrophy can be either physiologic or pathologic. Examples of physiologic hypertrophy include cardiac or skeletal muscle hypertrophy in an athlete and the enlargement of the uterine wall during pregnancy. An example of pathologic cardiac hypertrophy would be in the setting of hypertension, cardiac valve problems, or adjacent to an infarct (dead area of myocardium). Unlike physiologic hypertrophy, pathologic cardiac hypertrophy often results in heart failure. Cardiac hypertrophy has several causal mechanisms - it is induced by mechanical stretching as well as by several growth factors as shown
Atrophy
-what is it
-caused by
Cell shrinkage or loss
•Caused by: –Lack of hormonal signals (atrophic breasts after menopause) –Loss of innervation ( –Lack of use –Loss of blood supply –Starvation – disuse- Individual cell death
what is and what causes cachexia
Generalized wasting, called cachexia, occurs with starvation, disseminated tumors, and chronic inflammatory diseases such as advanced tuberculosis or AIDS. It is an extremely common proximal cause of death - death occurs when the body reaches about 68% of ideal body weight regardless of whether the patient, for example, is starving, has a large metastatic tumor burden, or has AIDS
protein and lipid degradation
-hypertropy and atropy reversibel?
-what is lipofuscin
Proteins are usually completely degraded, generally by the ubiquitin-proteasome pathway - they are conjugated to ubiquitin, then degraded in a cytoplasmic vacuole called the proteasome. Lipids and lipid bound structures (like mitochondria) are degraded in lysosomes. Some oxidized lipids cannot be completely degraded and remain in cytoplasmic vacuoles. This lipid, lipofuscin, is more abundant with aging and, since the cells are smaller, it is more prominent in atrophic cells. Hypertrophy and atrophy are reversible; if conditions change, the cells can revert to normal.
what is Hyperplasia what are causes
Increase in number of cells
•Causes are similar to hypertrophy (stress, hormones, etc.)
•Can occur with hypertrophy
•Examples: –BPH –liver, kidney –breast, endometrium
pathological hyperplasia vs. phisiological
Examples of physiologic hyperplasia are after a liver resection or resection of one kidney, the remaining portion of the liver or the other kidney undergoes hyperplasia to recover needed function. Fibroblasts and epidermal cells undergo hyperplasia as a skin wound heals. Examples of pathologic hyperplasia are the very common benign prostatic hyperplasia of the prostate (an extremely common cause of urinary obstruction in older men), ductal hyperplasia of the breast, and endometrial hyperplasia. In some cases (particularly endometrial hyperplasia and atypical ductal hyperplasia of the breast, but not prostatic hyperplasia) the hyperplasia connotes an increased risk for developing cancer. Depending on the site, the new cells in hyperplasia arise from either the remaining mature cells or from stem cells - precursor cells that proliferate in response to appropriate signals.
Metaplasia

reversible
Replacement of one cell type by another
•Examples: –Smoker's (Squamous metaplasia of smoker's small bronchusairways) –Cervix –Barrett's esophagus (columnnar cells with reflux)

-Metaplasia can be reversible; in some situations it is preneoplastic. Metaplasia can be caused by chronic injury (gastroesophageal reflux, smoking), by lack of vitamins (Vitamin A suppresses squamous metaplasia), or by growth factors or cytokines
Dysplasia causes

what does it look like
Disordered hyperplasia without maturation
•Preneoplastic
•Examples: –Uterine cervix –Bowel in IBD –Esophagus with Barrett's

-It is recognized by disorderly maturation that varies from cell to cell, and, in many examples, nuclear anisocytosis (meaning that not all of the nuclei look the same - some probably have too many chromosomes). This is often a cancer precursor. A typical example is HPV-infected (human papilloma virus) squamous epithelium in the uterine
Causes of cell injury & death
Trauma - force, heat, cold •Ischemia - inadequate circulation •Toxins & radiation •Infection •Inflammation •Genetic diseases •Nutritional problems (too much or little, vitamin deficiency) •Tumors (replaycing normal tissue or interupting blood flow
Cells Most Prone to Injury
High metabolic activity –Cardiac myocytes –Renal tubular cells –Hepatocytes •Rapidly proliferating –Testicular germ cells –Intestinal epithelium –Hematopoietic cells
what are Free Radicals
what causes them
what propagates them
what stops them
Unpaired electron in outer orbital (such as •OH) •Major cause of cellular damage •Causes: –radiation –ischemia (and reperfusion) –toxins –inflammatory mediators (NO, HOCl in neutrophil respiratory burst via myeloperoxidase) –Iron can propagate free radicals •Degraded by glutathione, catalase, vitamins A, C, & E
what is ischemia - reperfusion injury
Reperfusion after an hypoxic event brings oxygen into an area with free radicals, producing more free radicals, thus propagating the injury. This is called ischemia - reperfusion injury.
Degrees of cell injury

reversibel vs. irreversible

when is more likely reversible
examples of reverible
Reversible •Damage not enough to kill cellthe cell must maintain its integrity - the cell membrane, mitochondria, basic biosynthetic pathways, and DNA must remain intact)Injury is more likely to be reversible if the time of injury is limited (a few minutes), and the extent of injury is limited. It helps if the cells were in relatively good condition to begin with
-
( •Examples: –ATN (Severacute tubular injury in the kidney (often some of the tubular cells die, but others remain and, over a period of days, replace those that are lost
–Toxic liver injury –)e exercise
-Irreversible - Cell Death •More severe damage –Holes in cell membrane –Long Ca++ influx –Mitochondrial loss
two kinds of cell death

nuclear pyknosis
•Two types: –Necrosis (uncontrolled) –Apoptosis (programmed cell death)

-samll, dark blue, nonfunctional nuculei
what is seen in Reversible Injury

what two things are often both seen
Hypoxia - loss of ATP. Anaerobic glycolysis with acidosis. Cell swelling - loss of Na pump.

-Often, there is both a temporary loss of function (loss of proper control of the extent of fluid and electrolyte excretion by the kidney) and morphologic changes (cell swelling from loss of sodium pumping), and intracellular accumulation of lipid in hepatocytes (fatty liver) or other storage products. Cell membrane blebs and clumped nuclear chromatin are often seen with cell injury, whether reversible or not.
Apoptosis basic features
Orderly, energy-requiring cell death •Often a normal phenomenon •No inflammation, One cell at a time •Happens in: –Normal embryology –Normal cell turnover (intestine, skin, menses) –Viral infection –Damaged cells (DNA, other) –Immunologically mediated •Fas or TNF signals
what caspase is a key marker

explain the detaisl of apoptosis
caspase 3

). A cascade of intracellular signals happen, largely orchestrated by specific cytoplasmic proteins called caspases (cleaved (and thus activated) caspase 3 is a key marker) and by mitochondrial signaling proteins such as Bcl-2 and its relatives (Bax, Bad, and a dozen others) that send antiapoptotic (Bcl-2) or proapoptotic (Bax and Bad) signals. Early in apoptosis, phosphatidylserine (PS, a cell membrane phospholipid normally present only on the inner side of the cell membrane) appears on the outer surface. External PS gives an "eat me" signal to macrophages, which engulf the dying cell or its fragments. DNA clumping and degradation and clustering of nuclear pores occurs early in apoptosis. Histologically, the nuclear chromatin becomes clumped, the nucleus fragments, and the cytoplasm shrinks early in apoptosis. Despite the presence of nuclear debris, inflammation is absent. Often, via p53, Bcl-2, or other signaling molecules, neoplasms develop a mechanism to inhibit their apoptosis, enhancing tumor cell survival.
Nuclear changes in cell death
Nuclear pyknosis -
Karyolysis
Karyorrhexis
Nucleus is shriveled and dark
-Digested, pale nucleus
-Nuclear fragmentation
Necrosis
Uncoordinated cell death
•Cell membrane disruption, Ca++ signal influx, & energy loss (ATP depletion) are EARLY events
•Often happens to cell clusters rather than individual cells
•Incites acute inflammation from leakage of cell contents (lysosome digest cytoplasmic contents and leak into adjacent tissue)
•Cells often swollen (loss of ion pumps early in process)
-nucleaus reamins intact longer but eventulayy undergoes same 3 things as in apoptosis
--apoptosis
Causes
Mechanisms
Early processes
Late processes
Normal process
Cytosol
Single cells
apoptosis
normal development & turnover, viral infection, immune reactions, DNA damage

-intracellular signals,
caspase cascade
-nuclear degradation & fragmentation,
PS externalized
-fragmentation, phagocytosis,
no acute inflammation
-often
-shrunken
-usually
--necrosis
Causes
Mechanisms
Early processes
Late processes
Normal process
Cytosol
Single cells
trauma, ischemia, neutrophil infiltrate (abscess), some toxins
-holes in cell membrane,
lack of ATP, Ca++ influx
-lysosomal degradation,
cell contents leak from cell
-acute inflammation,
nuclear degradation
-never - always pathologic
-swollen (ion pumps lost early)
-Rarely
Patterns of Necrosis
Coagulative - with ischemia - see infarct (gross area of necrosis)
•Liquefactive - loss of substance - in brain or abscess (soft area of complete destruction resulting in hole or cystic space)
•Fat necrosis - necrosis in fat (calcium soaps form/chalk-like appearance; microscopically; (foamy macrophages, then fibrosis)
seen in fat with trauma (breast and in pancreatitis)
•Caseous necrosis - necrotizing granulomas - combination of liquefactive & coagulative (cheese like appearance that calcifies
- Fungal or TB infection
•Gangrenous necrosis
-dry; ischemic coagulative necrosis
-wet; also extensive infection
Organelle Changes
•Example: liver
-Injured organelles:
Organelles, like cells, can undergo hypertrophy or atrophy
- Liver - increased smooth ER with barbiturate use. Increased cytochrome p450 2C can metabolize other drugs or toxins more quickly
• Mallory body in liver from alcohol or other injury - eiosinophilic cytoplasmic clump of intermediate filaments
•Injured organelles:
-Neurofibrillary tangles in brain in Alzheimer's patient
Abnormal Storage Products
•Fatty change of liver –Common & nonspecific –See with: alcoholism, obesity, starvation, toxins
•Glycogen accumulation –In liver in diabetes –In glycogen storage disease (store glycogen in different tissue; liver and muscle –In certain tumors
•Lipid storage –Lipid storage disease -xanthomas (lipid filled macrophages- Fabry's - Gaucher's –In vessels in atherosclerosis
Brown Storage Products

3
•Lipofuscin - brown, degraded, indigestable lipid in lysosomes –increases with age, free radical damage
•Bilirubin - hemoglobin breakdown product –normally present in bile –increased with biliary obstruction & hepatocyte disorders –too much causes jaundice / icterus
•Hemosiderin - iron containing pigment –Increased with excessive iron absorption, bleeding into tissues
Protein Storage
intracellular

3
impaired secretion or excessove production
–α-1-antitrypsin deficiency (in hepatocytes
–Russell bodies in plasma cells (large deposits of immunoglobulin)
protein storage
extracellular

3
Amyloid
•Beta pleated sheet protein accumulations
•Can be more than a dozen different protein types (often immunoglobulin light chains)
•Occurs in a variety of diseases
•Seen in vessels, brain, heart (arrythmias), glomeruli (making fragile and leaky), tumors, and other sites
Misc. Storage Products•
•Anthracosis

-Calcification; 2 types
-
- carbon pigment
–Harmless, but other harmful materials can be deposited with it (silica, asbestos) –Mostly in lungs

-–Dystrophic Calcification - into damaged tissue (granuloma, artheroscloric plaque)
–Metastatic Calcification - into normal tissue
•Disorder of calcium metabolism (hypercalciumia) (renal failure, hyperparathyroidism, malignancy)
-both turn in to hydroxyapatite (bone)