Basis of Disease Flashcards
Pathophysiology
– not only cellular and organ changes that occur with disease, but with the effects that these changes have on total body function
Cell Responses
– either cellular adaptation or cellular injury
o Cell adaptation – intentional, reversible response to a stress; resolves once the stress is removed
atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia
o Cell injury – unintentional response to a stress; initially reversible but after a certain amount of damage, the injury reaches “point of no return” and becomes irreversible, resulting in cell death
Mechanical forces, electrical injuries (burnt cells or altered electrical impulses), nutritional imbalances, biological agents, and poisons
Atrophy
– decrease in size of tissue organs resulting from a decrease in cell size or in number of cells
o Causes: disuse, loss of trophic stimuli, insufficient nutrients, decreased blood flow, persistent cell injury, aging
Hypertrophy
– increase in cell size (NOT #) and thus increase in the amount of functioning tissue mass
o Involves an increase in functional components of the cell that allows it to achieve equilibrium between demand and functional capacity
o Causes: increased workload (physiologic or pathologic) imposed on an organ or body part
Hyperplasia
– increase in number of cells in an organ or tissue
o Only occurs in tissues that are capable of mitotic division
o Controlled process (uncontrolled = tumor) that occurs in response to an appropriate stimulus and ceases after the stimulus has been removed
o More dangerous than hypertrophy
Metaplasia
– reversible change in which one adult cell type is replaced by another adult cell type
o Replacing cells must be the same cell family as the cells that are being replaced
Ex: epithelial cells can only be replaced by another type of epithelial cell
o Thought to involve the reprogramming of undifferentiated stem cells that are present in tissue
o Usually occurs in response to chronic irritation and inflammation which allows for substitution of cells that are better able to survive
Dysplasia
– characterized by unorganized cell growth of a specific tissue that results in cells that vary in size/shape/appearance; replacement of mature cells with immature cells
o Involves sequential mutations in proliferating cell populations
o The pattern is most frequently encountered in metaplastic squamous epithelium of the respiratory tract and uterine cervix
o Strongly implicated as a precursor of cancer
Hypoxia and Ischemia
- Hypoxia – low O2 and low glucose low ATP shift from aerobic to anaerobic metabolism increase in lactic acid and depolarization leading to increase neurotransmitters firing auto-oxidation free radicals, proteolysis, glial injury main IRREVERSIBLE cell injury
- Ischemia – lack of blood flow; can result in hypoxia
Extremes of Temperature
o Heat – accelerates cell metabolism by increasing enzyme kinetics; inactivates temperature sensitive enzymes; disrupts the cell membrane; coagulation of blood vessels; coagulation of tissue proteins
o Cold – increases blood viscosity; induces vasoconstriction (SNS); ice crystal formation; capillary stasis; arteriolar and capillary thrombosis
Chemical agents
o Lead poisoning – NO amount of lead is safe for the body no matter how little or how much; cells recognize it as calcium and is brought into cells and stored as if it were calcium
Causes an increase in Reactive Oxygen Species and a decrease in antioxidant systems; glomerular fibrosis and proximal tubule mitochondrial damage; crosses and damages the blood brain barrier because the tight junctions are regulated by calcium channels;
High levels – mental retardation, convulsions, death
Low levels – reduced IQ and attention span, impaired growth, hearing loss
Mechanisms of Cell Injury
o Some agents (like heat, electricity, and poison) produce direct cell injury
o Some agents (like genetic derangement) produce their effects indirectly through metabolic disturbances and altered immune responses
o Most involve: ATP depletion, free radical formation, disruption of intracellular Ca+ homeostasis
Depletion of ATP
– cell lacks either nutrients or oxygen
o Failure of Na/K pump membrane depolarization increase in intracellular Ca cellular swelling lysis
o Switch to anaerobic metabolism increase in lactic acid decrease in cellular pH lysing of lysosomes lysis via protease degradation of cell membrane
Ischemia-Reperfusion Injury
– reintroduction of oxygen after a period of hypoxia
o Causes MORE cell injury than the hypoxia itself
o During ischemia – tissues release cytokines, chemokines, ROS
o During reperfusion – above factors initiate an excessive inflammatory response
Upregulation of leukocyte adhesion membrane receptors + above factors cause massive amounts of platelet aggregation and leukocyte adhesion fibrosis and tissue damage
o Kidney used to study this phenomenon because of single artery and vein entry/exit
Free Radical Injury
– any molecule with unpaired electron
o Normally found in cells and phagocytic cells but cause injury when in excess amounts
o Caused by: ionizing radiation, UV light, metabolism, inflammation, air pollution, smoking
o 3 major effects: main cause of cell death in chronic disease states
Lipid peroxidation – alters the membrane’s flow and movement
Oxidative modification of proteins – inhibits proper protein function
DNA mutation
Cell Death - Apoptosis
– programmed cell death that allows cell to die without lysing; highly regulated; prevents an immune response; preserves surrounding tissue
Propagated by a family of cysteine proteases called capsases
Mechanism: small blebs form (bulging on cell membrane) nucleus begins to break apart and DNA breaks into small pieces; organelles also located in the blebs cell breaks into several apoptotic bodies; the organelles are still functional
Intrinsic Pathway – something inside cell initiates apoptosis and begins at mitochondria
Extrinsic Pathway – external factor recognizes that the cell needs to die; requires apoptotic cellular receptor
