Path_1.txt

• 1. Etiology or cause- genetic or acquired
• 2. Pathogenesis- sequence of events in the response of cells or tissues to the etiologic event
• 3. Morphologic change - structural alteration in cells or tissues that are either characteristic of the disease or diagnostic of the etiologic event.
• 4. Clinical manifestation - The nature of the morphologic changes and their distribution in different organs or tissues influence normal function and determine the clinical features, course, and prognosis of the disease.

Hyperplasia

Hypertrophy

Atrophy

During times of stress and increased demand the cell adapts, if there is an inability to adapt the cell will die. If the stimulus is injurious the cell will die. Cell injury is reversible up to a certain point but if the stimulus persists the cell reaches the point of no return and suffers irreversible cell injury and death.

• 1. Necrosis - Response to abnormal stresses such as ischemia and chemical injury. Always pathologic.
• 2. Apoptosis - Cell dies through activation of an internally controlled suicide program. Eliminates unwanted cells in embryogenisis and also occurs in some pathologic events.

Calcium

The intercellular accumulation of a number of substances.

Hyperplasia, hypertrophy

Atrophy

Metaplasia

Acute reversible injury

Irreversible injury leading to cell death- necrosis or apoptosis

Subcellular alterations in various organelles

• factors produced by the cell or surrounding cells
• activation of cell surface receptors and downstream signaling molecules

Capable of DNA synthesis and cell division

• hormonal - increase of the female breast at puberty and uterus during pregnancy
• compensatory - increase tissue mass after damage or resection. The liver can regenerate. After nephrectomy the other kidney enlarges and makes up for the lose.

• Increase in local production of growth factors, increase in the number of growth factor receptors, or activation of intercellular signaling pathways.
• -All lead to in increase production of transcription factors leading to cellular proliferation.

excessive hormonal stimulation or growth factors acting on a target.

Synthesis of more structural components.

Increase do to the arrest of the cell cycle without undergoing mitosis

Increased functional demand or by specific hormonal stimulation.

• Induction of embryonic genes - Beta myosin in place of alpha myosin.
• Transcription factors -
• Growth factors - TGF-B, IGF-1, FGF
• Vasoactive agents- alpha adrenergic agonists, endothelin-1, angiotensin II.

• Secreted by the fetal atrium and ventricle and then by the adult atrium, response to pressure and volume change by regulating salt excretion to regulate volume and pressure.
• ex. increased atrial pressure due to excess venous return leads to higher levels of ANF excretion and an increase in urine production by the kidneys.

• 1. mechanical - stretch
• 2. trophic- growth factors and vasoactive agents secreted by non myocytes.

when the muscle reaches it limit for enlargement and is no longer able to compensate.

• 1. Decreased workload
• 2. Loss of innervation
• 3. Diminished blood supply
• 4. Inadequate nutrition- use of muscle for energy after fat stores are used up.
• 5. Loss of endocrine stimulation- loss of estrogen after menopause results in atrophy of the endometrium, breast, and vaginal epithelium.
• 6. aging
• 7. pressure - enlarged benign tumor can compress and cause atrophy of surrounding tissue.

can die if blood supply is inadequate for even the atrophied cell.

• degradation of cytosolic and nuclear proteins.
• Proteins are first conjugated to ubiquin then degraded within protease's.
• Stimulated by glucocorticoids and thyroid hormones
• Inhibited by insulin.
• Cytokines such ad TNF are capable of increasing muscle proteolysis in this way.

• reversible change from one cell type to another. May represent an adaptive substitution where one cell type is better suited to withstand an adverse environment.
• -most common is columnar to squamous, in the respiratory tract in response to chronic irritation. The new cells can survive but the special feature of mucus secretion is lost.

Esophageal squamous cells are changed to columnar under the influence of refluxed gastric acid.

Bone formation in muscle after bone fracture

• Not a change in the phenotype but reprogramming of the stem cells in the tissue or of undifferentiated mesenchymal cells in connective tissue.
• BMP's induce chondrogenic or osteogenic expression of stem cells while repressing differentiation to muscle of fat.

• activates phospholipases that degrade membrane phospholipids
• activates proteases that breakdown the membrane and cytoskeleton
• activates ATPase
• Activates endonucleases

Once induced free radicals cause an autocatalytic chain reaction producing more free radicals

• Absorption of radiation
• Enymatic metabolism of chemicals or drugs, CCL4
• Normal reduction oxidation reactions
• Transition metals

• Vit E
• Ascorbic acid
• Glutathione

• catalase
• glutathiione
• peroxidase
• superoxide dismutase

Irreverible cell injury

More Pink

Small dense nucleus

faint, dissolved nucleus

fragmented nucleus

• pyknosis
• karyorrhexis
• kayyolysis

• protein denaturation
• preservation of cell and framework
• hypoxic death except brain
• undergo heterolysis or autolysis

• when heterolysis or autolysis predominates over protein denaturation
• soft and fluid filled
• frequently seen in bacterial infection (abscess) and in the brain

appears soft, friable, and cheesy

• lipase activation in adipose tissue
• released fatty acids react with calcium to create soaps
• white chalky areas

• hypoxia still delivers nutrients for glycolysis
• ischemia injures faster

• Loss of Na/K pump, influx of Ca water and Na, cell swells
• Increased glycolysis, decreased pH and glycogen, clumping of chromatin, intracellular release of lysosomal enzymes
• detachment of ribosomes, loss of protein synthesis

• Pore formation in mitochondrial membrane and diffusion out of calcium and cytochrome C
• Cytochrome c drives apoptosis
• increases calcium activates enzymes and proteasses
• free fatty acids and lysophosphilipids accumulate in the ischemic cell, toxic to membranes

• increased generation of free radicals , incomplete reduction of oxygen by damaged mitochondria or normal anti-oxidase activity is disrupted
• Blood flow increases local inflammation
• activation of compliment, bind to IgM in the tissue

• membrane is not damaged
• smaller number of cells
• does not cause inflammation

• programmed cell death
• hormone dependent, endometrium
• maintain a constant cell number
• harmful self reactive lymphocyte
• eliminate virus

• Damaged DNA, cell kills itself rather then risk mutation
• viral infection, hepititis
• duct abstruction , pancrease
• Tumor cell death

it shrinks, and chromatin condenses

caspases

phosphatidylserine

extrinsic and intrinsic

• TNF receptor family
• TNF-1 or FAS ligand
• enzymtically cleave caspase 8 which starts a caspase cascade

• mitochondrial permeability is increased
• death receptors are not involved
• BCL-2 and BCL-x are anti-apoptotic
• When cells are deprived of survival signal bcl2 is lost and replaced by back, bax, and bim; pro-apoptotic
• cytochrom c is released into the cytoplasm and binds to Apaf-1 and trigers caspase 9.

• caspase 6 and 3
• cleave all types of protein

• c= cysteine for the active site
• aspase = cleaves after aspartic acid

• growth factor deprivation, intrinsic path
• DNA damage, radiation or chemo, p53 accumulates, arrests cell in G1 phase, p53 will act as a transcription factor for bax and bak and Apaf-1, p53 can be mutated in some cancers
• TNF; Fas(cd95)
• cytotoxic T lymphocyte; recognize forign material in host cell and secrete perforin, allows entrance to ganzyme B, activates caspase, can also ecpless FasL

undigested product

chronic ingestion of some drugs, leads to increased tolerance

megamitochondria

benign tumor consisting of cells with large mitochondria

• antitrypsin accumulates in the hepatocytes that produce it
• mutations slow folding , partly folded enzymes accumulate in the ER

• excessive entry of free fatty acids; starvation, corticosteroid therapy
• enhanced fatty acid synthesis
• increases esterfication of fatty acids to triglycerides
• decreased apoprotein synthesis; starvation
• impaired lipoprotein secretion; alcohol

Niemann-pick type C

accumulation of protein in the extracellular spaces

mallory bodies

Russell bodies

exogenous pigment in pulmonary macrophages

• increased dietary iron intake; primary hemochromotosis
• impaired utilization; thalassemia
• chronic transfusions

• increased secretion of parathyroid hormone; parathyroid tumor or ectopic parathyroid hormone secreting tumor
• Destruction of bone tissue; cancer, immobilization
• Vit D disorder; intoxication
• Renal failure; causes secondary hyperparathyroidism due to phosphate retention.

• reduced ATP generation
• diminished protein synthesis
• decreased capacity for nutrient uptake
• increased DNA damage, reduced repair
• accumulation of oxidative damage
• accumulation of glyation end products causing cross linking

• replicative senescence; limited number of replications, telomere shortening-lose a little piece with every replication. telemerease activation in cancer causes cell to keep dividing ( inactivates internal clock)
• genes that influence aging; decreased IGF-1 signaling can lead to prolonged life span
• progressive accumulation of metabolic and genetic damage from exogenous influence,

Werner syndrom, defect in DNA helicase causes rapid accumulation of DNA damage