Basic Pathologic Process Part II Flashcards
What is the difference between reversible and irreversible cellular injury?
Reversible injury is when damaged cells can return to normal if stimulus is removed.
Irreversible injury is when damaged cells cannot return to normal.
Common causes of cellular injury.
- Hypoxia, ischemia
- Toxins
- Infectious disease
- Immunologic agents
- Genetic abnormalities
- Nutritional imbalance
- Physical agents
- Aging
What are the two main morphologic correlates of reversible cellular injury?
- Cellular swelling - increased permeability of plasma membrane
- Fatty change - appearance of triglyceride-containing lipid vacuoles.
What are the 3 characteristics of irreversible cellular injury?
- Inability to restore mitochondrial function.
- Loss of structure/functions of plasma membrane.
- Loss of DNA/chromatin integrity.
Necrosis v. Apoptosis
- Necrosis - accidental cell death due to severe damage
- Apoptosis - programmed cell death when cell is deprived of growth factors (no host response)
- Necroptosis - necrosis morphology and apoptosis mechanically
What are the morphological changes of necrosis?
- discontinuities in plasma and organelles
- increase in eosinophils
- breakdown of DNA/chromatin (pyknosis, karyorrhexis, karyolysis)
- calcification due to degradation into fatty acids binding calcium salts
What are the gross appearance of each type of necrosis?
- Coagulative
- Liquefactive
- Gangrenous
- Caseous
- Fat
- Fibrinoid
What are the mechanisms of serum lab test to detect cellular necrosis?
- intracellular proteins in general circulation; detection of tissue-specific necrosis
What is similar and different between physiologic and pathologic apoptosis?
Physiologic - during development, some cells die and are replaced, no inflammation response
Pathologic - elminiates damaged cells beyond repair
What are the general principles that determine the cellular response and consequences of an injurious stimulus?
Principle - type of injury, duration, severity
Consequences depends on the above.
What are the principle biochemical mechanisms of cellular injury?
- Hypoxia, ischemia - failure of many energy-dependent pathways (necrosis)
- Multiple injurious stimuli - oxidative stress (necrosis)
- Mutations, cell stress, infection (apoptosis)
- Radiation - (necrosis/apoptosis)
- Infection, immunologic disorder (necrosis/apoptosis)
What are the four main cellular adaptations to stress?
Distinguish between physiologic and pathologic adaptation.
- Hypertrophy
- Hyperplasia
- Atrophy
- Metaplasia
Physiologic - response to hormone/endogenous chemical mediators/stress
Pathologic - cell modulates structure/functions to allow cell escape at expense of normal function
What are the main categories of intracellular accumulations?
- Fatty change - triglyceride accumulation (fatty liver)
- Cholesterol, cholesteryl esters - lipid-filled phagocytic cells (atherosclerosis)
- Proteins - too much proteins presented or too much production in cell (immunoglobins/protein defects)
- Glycogen - glycogen deposits (diabetes)
- Pigments - endogenous v. exogenous (lack of enzymes v indigested materials)
What are the differences between dystrophic and metastatic calcification?
Dystrophic - normal Ca2+ metabolism, Ca+ deposits into injured cells causing atherosclerotic lesions (aortic stenosis).
Metastatic - Ca2+ deposits into healthy tissues due to hypercalcemia due to tumors/disease
Describe a typical inflammation reaction.
- Recognition - host cells recognizes stimulus
- Recruitment - of leukocytes and plasma cells
- Vasodilation - increases vascular permeability
- Activation - of leukocytes and plasma cells
- Regulation - reaction is controlled
- Healing - damage tissue is repaired
Distinguish between acute and chronic inflammation.
Acute - initial, rapid response, short duration; accumulation of fluid and plasma proteins (edema) and the emigration of neutrophils
Chronic - reaction progresses to protracted type of inflammation, longer duration, more tissue destruction, the presence of lymphocytes and macrophages, the proliferation of blood vessels and fibrosis.
Describe the reaction of blood vessels in acute inflammation.
Vasodilation (increase diameter arterioles --> capillary) slows down blood flow for leukocyte adhesion Increased permeability (retraction of endothelial cells) allows exudate to enters ECF
Describe leukocyte recruitment (from margination to chemotaxis)
- Margination - leukocytes rolls along the periphery of endothelial vessel walls around site of inflammation. (selectins)
- Integrins activated by chemokines at the site of inflammation
- Stable adhesion of leukocytes
- Migration through endothelium - leukocytes squeeze through intercellular junctions into extravascular tissues
- Chemotaxis - movement of leukocytes by chemical gradient (chemoattractants) toward the stimulus of inflammation
Describe the roles of the dominant molecules during leukocyte recruitment.
Selectins: receptors on endothelium that mediate weak interactions between leukocytes and endothelium
Integrins: receptors on leukocytes that allow firm interactions between leukocytes and endothelium
Chemokines: activates integrins from low-affinity to high-affinity
Chemoattactants - chemical gradient attacting leukocytes toward the stimulus of inflammation
Describe steps of phagocytosis.
- Recognition and attachment of the particle to be ingested by the leukocyte
- Engulfment, with subsequent formation of a phagocytic vacuole (phagosomes)
- Killing or degradation of the ingested material
List the mediators of inflammation (source and action).
- Histamine
Source: Mast cells, basophils and platelets.
Action: Vasodilation, increased vascular permeability, endothelial activation. - Prostaglandins
Source: Mast cells, Leukocytes
Action: Vasodilation, pain and fever. - Leukotrienes
Source: Mast cells, leukocytes
Action: Increased vascular permeability, chemotaxis, leukocyte adhesion and activation. - Cytokines (TNF, IL-1, IL-6)
Source: Macrophages, endothelial cells, and mast cells
Action: Local: endothelial activation (expression adhesion molecules).
Systemic: fever, metabolic abnormalities, hypotension (shock). - Chemokines-
Source: Leukocytes, activated macrophages
Action: Chemotaxis, leukocyte activation. - Platelet-activating factor-
Source: Leukocytes, mast cells
Action: Vasodilation, increased vascular permeability, leukocyte adhesion,
Chemotaxis, degranulation, oxidative burst. - Complement-
Source: Plasma (produced in liver)
Action: Leukocyte chemotaxis and activation, direct target killing, (membrane attack complex), vasodilation (mast cell stimulation) - Kinins
Source: Plasma (produced in liver)
Action: increased vascular permeability, smooth muscle contraction, Vasodilation and pain.
What are the 3 main functions of the complement system?
- Inflammation
- Opsonization/Phagocytosis
- Cell Lysis
What is the critical step in activating the complement system?
Splitting of inactive C3 into activated C3a and C3b.
What are the pathways that leads to activation of the complement system?
- Classical pathway
- Alternative pathway
- Lectin pathway
What are the four (4) main morphologic patterns of acute inflammation?
- Serous
- Fibrinous
- Purulent, abscess
- Ulcers
What is the cause, result and example of serous inflammation?
Exudation of cell-poor fluid, effusion, skin blisters
What is the cause, result and example of fibrinous inflammation?
Large vascular leaks or procoagulant stimulus, fibrin forms in extracellular space, scar
What is the cause, result and example of purulent inflammation?
By pus-producing bacteria, pus-containing abscess, appendicitis
What is the cause, result and example of ulcers?
Shedding of inflamed necrotic tissue near surface of tissue, margins and based becomes scarred, diabetic ulcers
Describe the 3 usual outcomes of acute inflammation.
- Complete resolution - Elimination of offending agent, restoration of site to normal
- Healing by connective tissue replacement (scarring or fibrosis) - tissue incapable of regeneration, abundant fibrin exudation that cannot be cleared
- Progression to chronic inflammation response - persistence of injurious agent or interference with normal process of healing
What is chronic inflammation and some common settings in which it may arise?
Response of prolonged duration
(weeks/months) in which inflammation, tissue
injury, and attempts at repair coexist, in varying combinations.
Settings: persistent infections, prolonged exposure to toxic agents, autoimmunity, some cancers
What are the morphologic changes of chronic inflammation?
Cellular infiltrate (WBC’s), fibrosis (severe or progressive
What are the characteristic features of granulomatous inflammation?
Chronic inflammation with collection of activate macrophages sometimes with associated central necrosis.
Immune v. Foreign body
What are the differences between the two main types of granulomas?
Immune - persistent T-cell mediated response when inciting agent cannot be eliminated
Foreign body - response to immobile foreign body, forms around talc, sutures, other fibers
Compare and contrast the two main types of reactions that lead to tissue repair.
Regeneration - proliferation of cells that survive injury; in only some tissues
Connective deposition - scar formation, when regeneration is not possible, framework is damaged, fibrosis.
Describe common systemic effects of inflammation.
- Fever (eleveation by 1-4 degree C)
- Acute-phase proteins (C-reactive protein, serum amyloid, fibrinogen, hepcidin)
Leukocytosis (elevated, 15-20K)
Increased HR, BP, decreased sweating.
Define etiology.
Underlying causes responsible for disease initiation and progression.
Define pathogenesis.
Cellular and molecular changes that produce structural/functional abnormalities specific to a disease
Define homeostasis.
maintenance and regulation of stable, constant internal environment
Define adaptation.
New steady state while still preserving viability and function.
Define necrosis.
form of cell death where cellular membranes deteriorate causing cellular enzymes to leak out and digest cell
Define apoptosis.
Regulated, programmed cell death via enzymatic degradation of cells DNA, nuclear and cytoplasmic proteins
Define hemotoxylin.
Blue dye –> basophilia
Define eosin.
Red dye –> eosinophilia
Define pyknosis.
Nuclear shrinkage and increased basophilia; DNA = dark, shrunken mass
Define karyorrhexis.
Shrunken nuclear mass undergoes fragmentation.
Define: Karyolysis
Basophilia fades because DNAase digests DNA
Define autophagy.
“Self eating” as survival mechanism when nutrient deprived, lysosomal digestion of cell’s own component
Define hypoxia
Oxygen deficiency in tissues
Define ischemia
Reduced blood supply; lead to deficiency in nutrients and build up of toxic metabolites
Define hypertrophy
An increase in the SIZE of cells resulting in increased size of the organ
Define hyperplasia
An increase in the NUMBER of cells in an organ that stems from increased proliferation
Define atrophy
Shrinkage in the size of cells by the loss of cell substance
Define metaplasia
A change in which one adult cell type is replaced by another cell type
Define exudate
Escape of fluid, proteins and blood cells from vascular system into interstitial tissue or cavities due to inflammation
Define transduate
Extravascular fluid with low protein content, little or no cellular material pushed out of capillaries due to high blood pressure
Define edema
Accumulation of extravascular fluid; known as swelling at site of injury
Define lymphangitis
Red streaking, swelling near a skin wound as a telltale sign of infection
Define lymphadenitis
Inflammation of the lymph node.
Define effusion.
Accumulation of fluid into a space or cavity created by injury
Define purulent (suppurative)
Pus, inflammatory exudate consisting of neutrophils, liquefied debris of necrotic cells
Define abscess
Localized collection of pus
Define ulcer
Local defect of surface of an organ or tissue that is produced by shedding of inflamed necrotic tissue.
