Basis of Disease

Question 1

Pathophysiology

Answer 1

– not only cellular and organ changes that occur with disease, but with the effects that these changes have on total body function

Question 2

Cell Responses

Answer 2

– 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

Question 3

Atrophy

Answer 3

– 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

Question 4

Hypertrophy

Answer 4

– 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

Question 5

Hyperplasia

Answer 5

– 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

Question 6

Metaplasia

Answer 6

– 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

Question 7

Dysplasia

Answer 7

– 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

Question 8

Hypoxia and Ischemia

Answer 8

• 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

Question 9

Extremes of Temperature

Answer 9

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

Question 10

Chemical agents

Answer 10

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

Question 11

Mechanisms of Cell Injury

Answer 11

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

Question 12

Depletion of ATP

Answer 12

– 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

Question 13

Ischemia-Reperfusion Injury

Answer 13

– 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

Question 14

Free Radical Injury

Answer 14

– 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

Question 15

Cell Death - Apoptosis

Answer 15

– 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

Question 16

Cell Death - Necrosis

Answer 16

– 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

Question 17

Gangrene

Answer 17

– 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

Question 18

HBsAg

Answer 18

– 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

Question 19

HBV Mechanism

Answer 19

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

Question 20

Clinical Signs of Hepatitis

Answer 20

– fatigue, hepatomegaly, athralgias (joint pain), polyarteritis nodosa (large red patches on skin as result of ruptured medium sized arteries), membranoproliferative glomerulonephritis, jaundice

Question 21

RBC Degradation

Answer 21

• 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

Question 22

3 Possible Immune Outcomes to Hepatitis Infection

Answer 22

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

Question 23

Chronic Hepatitis

Answer 23

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

Question 24

Liver Failure

Answer 24

o Reduced liver protein synthesis
o Impaired glycogenolysis and gluconeogenesis
o Reduced production of bile salts
o Impaired processing of endogenous steroid hormones

Question 25

Acute Inflammation

Answer 25

– 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

Question 26

Chronic Inflammation

Answer 26

– 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