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
Cell Death - Necrosis
– unprogrammed cellular destruction resulting in lysis and spillage of reactive enzymes from lysosomes/organelles; contributes to tissues damage; elicits immune response; leads to chronic inflammation; interrupts new cell growth
Propagated by family of proteases called cathepsin – does NOT regulate
Ca+ enters cells activates calpain lysosome rupture cathepsin release cell death
Mechanism: small blebs form; the nucleus structure changes blebs fuse and become larger; no organelles are located in the blebs cell membrane ruptures and releases the cell’s contents; the organelles are not functional
Gangrene
– accumulation of necrotic tissue (wet/dry has nothing to do with wet/dry skin)
o Dry gangrene – interference with arterial blood supply in extremities
Common result of diabetes and frostbite
Mechanism: blockage of arteries ischemia cellular swelling cell dies
Symptoms: blackened skin – due to chronic hemostasis in necrotic tissue; heme interacts with bacteria (bacterial H2S reacts with heme to produce FeS (gives black color)
Treatment: amputation
o Wet gangrene – interference with venous blood supply in extremity
Results in accumulation of blood in the tissue
Common result of chronic pressure (bedsores) or infection (especially burn patients)
Symptoms: slight blackened skin and edema; clammy appearance from fluid buildup
• Bacterial growth as a result of hemostasis; lesser appearance of blackened skin
Treatment: O2 therapy, antibiotics, debridement, sterile-bred maggots
HBsAg
– DNA hepadnavirus
o Transmitted via infected blood or sexual contact (present in saliva/semen/vaginal secretions)
o Incidence: 1.25 million people in US; 400 million worldwide
o Highest Risk: patients on dialysis, previous STD treatment, tattoos, healthcare workers
HBV Mechanism
o Direct cellular injury by virus (immune tolerant phase)
Virus reside in hepatocytes; HBsAg is now present on hepatocytes virus replicates without damaging cell
o Induction of the immune response (presentation of symptoms) – begins as soon as virion replication in previous phase causes cell lysis and enters circulation and infects other hepatocytes eliciting an immune response where cytotoxic T cells destroy infected hepatocytes liver enzymes and contents (ex: bilirubin) enter circulation
Clinical Signs of Hepatitis
– fatigue, hepatomegaly, athralgias (joint pain), polyarteritis nodosa (large red patches on skin as result of ruptured medium sized arteries), membranoproliferative glomerulonephritis, jaundice
RBC Degradation
• RBC degradation reticuloendothelial system in liver and spleen RBC breakdown globin (made of amino acids) & heme heme broken down to biliverdin via heme oxidase bilirubin via biliverdin reductase binds to albumin and enters liver
o Damaged hepatocytes cannot move bilirubin efficiently into the GI tract for clearance
3 Possible Immune Outcomes to Hepatitis Infection
o HBsAG totally cleared = immune stage
o Inactive carrier stage = no injury or inflammation of hepatocytes but patient can suffer from acute flares
o If virus cannot be cleared and replication continues for >6 months = chronic hepatitis
Chronic Hepatitis
o Commonly due to poor T cell response in immunocompromised host (HIV, neonates)
o Continual destruction and regeneration of liver parenchyma
Increases risk of cirrhosis and carcinoma
o Superinfection with hepatitis D – there’s risk of chronic liver disease and fulminant hepatitis
Liver Failure
o Reduced liver protein synthesis
o Impaired glycogenolysis and gluconeogenesis
o Reduced production of bile salts
o Impaired processing of endogenous steroid hormones
Acute Inflammation
– caused by Infection, trauma, exposure to physical/chemical agents, tissue necrosis, foreign bodies, hypersensitivity reactions, endothelial injury
o Vascular reaction deliver plasma proteins and immune cells to site of inflammation
Histamine/NO release increased vascular permeability
Kinin system & angiogenes increased vascular permeability
o Cellular reaction leukocyte rolling, adhesion, extravasation, and activation; leukocytes ultimately responsible for tissue injury
Chronic Inflammation
– gateway to many disease states
o Continuous T-cell activation resulting in increased TNF-alpha;
o TNF-alpha is responsible for proliferation of fibroblasts excess causes fibrosis less functioning tissue
