Basic Pathologic Process Part II

Question 1

What is the difference between reversible and irreversible cellular injury?

Answer 1

Reversible injury is when damaged cells can return to normal if stimulus is removed.
Irreversible injury is when damaged cells cannot return to normal.

Question 2

Common causes of cellular injury.

Answer 2

1. Hypoxia, ischemia
2. Toxins
3. Infectious disease
4. Immunologic agents
5. Genetic abnormalities
6. Nutritional imbalance
7. Physical agents
8. Aging

Question 3

What are the two main morphologic correlates of reversible cellular injury?

Answer 3

1. Cellular swelling - increased permeability of plasma membrane
2. Fatty change - appearance of triglyceride-containing lipid vacuoles.

Question 4

What are the 3 characteristics of irreversible cellular injury?

Answer 4

1. Inability to restore mitochondrial function.
2. Loss of structure/functions of plasma membrane.
3. Loss of DNA/chromatin integrity.

Question 5

Necrosis v. Apoptosis

Answer 5

1. Necrosis - accidental cell death due to severe damage
2. Apoptosis - programmed cell death when cell is deprived of growth factors (no host response)
3. Necroptosis - necrosis morphology and apoptosis mechanically

Question 6

What are the morphological changes of necrosis?

Answer 6

• 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

Question 7

What are the gross appearance of each type of necrosis?

Answer 7

1. Coagulative
2. Liquefactive
3. Gangrenous
4. Caseous
5. Fat
6. Fibrinoid

Question 8

What are the mechanisms of serum lab test to detect cellular necrosis?

Answer 8

• intracellular proteins in general circulation; detection of tissue-specific necrosis

Question 9

What is similar and different between physiologic and pathologic apoptosis?

Answer 9

Physiologic - during development, some cells die and are replaced, no inflammation response
Pathologic - elminiates damaged cells beyond repair

Question 10

What are the general principles that determine the cellular response and consequences of an injurious stimulus?

Answer 10

Principle - type of injury, duration, severity

Consequences depends on the above.

Question 11

What are the principle biochemical mechanisms of cellular injury?

Answer 11

1. Hypoxia, ischemia - failure of many energy-dependent pathways (necrosis)
2. Multiple injurious stimuli - oxidative stress (necrosis)
3. Mutations, cell stress, infection (apoptosis)
4. Radiation - (necrosis/apoptosis)
5. Infection, immunologic disorder (necrosis/apoptosis)

Question 12

What are the four main cellular adaptations to stress?

Distinguish between physiologic and pathologic adaptation.

Answer 12

1. Hypertrophy
2. Hyperplasia
3. Atrophy
4. Metaplasia

Physiologic - response to hormone/endogenous chemical mediators/stress

Pathologic - cell modulates structure/functions to allow cell escape at expense of normal function

Question 13

What are the main categories of intracellular accumulations?

Answer 13

1. Fatty change - triglyceride accumulation (fatty liver)
2. Cholesterol, cholesteryl esters - lipid-filled phagocytic cells (atherosclerosis)
3. Proteins - too much proteins presented or too much production in cell (immunoglobins/protein defects)
4. Glycogen - glycogen deposits (diabetes)
5. Pigments - endogenous v. exogenous (lack of enzymes v indigested materials)

Question 14

What are the differences between dystrophic and metastatic calcification?

Answer 14

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

Question 15

Describe a typical inflammation reaction.

Answer 15

1. Recognition - host cells recognizes stimulus
2. Recruitment - of leukocytes and plasma cells
3. Vasodilation - increases vascular permeability
4. Activation - of leukocytes and plasma cells
5. Regulation - reaction is controlled
6. Healing - damage tissue is repaired

Question 16

Distinguish between acute and chronic inflammation.

Answer 16

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.

Question 17

Describe the reaction of blood vessels in acute inflammation.

Answer 17

Vasodilation (increase diameter arterioles --> capillary) slows down blood flow for leukocyte adhesion
Increased permeability (retraction of endothelial cells) allows exudate to enters ECF

Question 18

Describe leukocyte recruitment (from margination to chemotaxis)

Answer 18

1. Margination - leukocytes rolls along the periphery of endothelial vessel walls around site of inflammation. (selectins)
2. Integrins activated by chemokines at the site of inflammation
3. Stable adhesion of leukocytes
4. Migration through endothelium - leukocytes squeeze through intercellular junctions into extravascular tissues
5. Chemotaxis - movement of leukocytes by chemical gradient (chemoattractants) toward the stimulus of inflammation

Question 19

Describe the roles of the dominant molecules during leukocyte recruitment.

Answer 19

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

Question 20

Describe steps of phagocytosis.

Answer 20

1. Recognition and attachment of the particle to be ingested by the leukocyte
2. Engulfment, with subsequent formation of a phagocytic vacuole (phagosomes)
3. Killing or degradation of the ingested material

Question 21

List the mediators of inflammation (source and action).

Answer 21

1. Histamine
   Source: Mast cells, basophils and platelets.
   Action: Vasodilation, increased vascular permeability, endothelial activation.
2. Prostaglandins
   Source: Mast cells, Leukocytes
   Action: Vasodilation, pain and fever.
3. Leukotrienes
   Source: Mast cells, leukocytes
   Action: Increased vascular permeability, chemotaxis, leukocyte adhesion and activation.
4. 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).
5. Chemokines-
   Source: Leukocytes, activated macrophages
   Action: Chemotaxis, leukocyte activation.
6. Platelet-activating factor-
   Source: Leukocytes, mast cells
   Action: Vasodilation, increased vascular permeability, leukocyte adhesion,
   Chemotaxis, degranulation, oxidative burst.
7. Complement-
   Source: Plasma (produced in liver)
   Action: Leukocyte chemotaxis and activation, direct target killing, (membrane attack complex), vasodilation (mast cell stimulation)
8. Kinins
   Source: Plasma (produced in liver)
   Action: increased vascular permeability, smooth muscle contraction, Vasodilation and pain.

Question 22

What are the 3 main functions of the complement system?

Answer 22

1. Inflammation
2. Opsonization/Phagocytosis
3. Cell Lysis

Question 23

What is the critical step in activating the complement system?

Answer 23

Splitting of inactive C3 into activated C3a and C3b.

Question 24

What are the pathways that leads to activation of the complement system?

Answer 24

1. Classical pathway
2. Alternative pathway
3. Lectin pathway

Question 25

What are the four (4) main morphologic patterns of acute inflammation?

Answer 25

1. Serous 2. Fibrinous 3. Purulent, abscess 4. Ulcers

Question 26

What is the cause, result and example of serous inflammation?

Answer 26

Exudation of cell-poor fluid, effusion, skin blisters

Question 27

What is the cause, result and example of fibrinous inflammation?

Answer 27

Large vascular leaks or procoagulant stimulus, fibrin forms in extracellular space, scar

Question 28

What is the cause, result and example of purulent inflammation?

Answer 28

By pus-producing bacteria, pus-containing abscess, appendicitis

Question 29

What is the cause, result and example of ulcers?

Answer 29

Shedding of inflamed necrotic tissue near surface of tissue, margins and based becomes scarred, diabetic ulcers

Question 30

Describe the 3 usual outcomes of acute inflammation.

Answer 30

1. Complete resolution - Elimination of offending agent, restoration of site to normal 2. Healing by connective tissue replacement (scarring or fibrosis) - tissue incapable of regeneration, abundant fibrin exudation that cannot be cleared 3. Progression to chronic inflammation response - persistence of injurious agent or interference with normal process of healing

Question 31

What is chronic inflammation and some common settings in which it may arise?

Answer 31

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

Question 32

What are the morphologic changes of chronic inflammation?

Answer 32

Cellular infiltrate (WBC's), fibrosis (severe or progressive

Question 33

What are the characteristic features of granulomatous inflammation?

Answer 33

Chronic inflammation with collection of activate macrophages sometimes with associated central necrosis. Immune v. Foreign body

Question 34

What are the differences between the two main types of granulomas?

Answer 34

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

Question 35

Compare and contrast the two main types of reactions that lead to tissue repair.

Answer 35

Regeneration - proliferation of cells that survive injury; in only some tissues Connective deposition - scar formation, when regeneration is not possible, framework is damaged, fibrosis.

Question 36

Describe common systemic effects of inflammation.

Answer 36

1. Fever (eleveation by 1-4 degree C) 2. Acute-phase proteins (C-reactive protein, serum amyloid, fibrinogen, hepcidin) Leukocytosis (elevated, 15-20K) Increased HR, BP, decreased sweating.

Question 37

Define etiology.

Answer 37

Underlying causes responsible for disease initiation and progression.

Question 38

Define pathogenesis.

Answer 38

Cellular and molecular changes that produce structural/functional abnormalities specific to a disease

Question 39

Define homeostasis.

Answer 39

maintenance and regulation of stable, constant internal environment

Question 40

Define adaptation.

Answer 40

New steady state while still preserving viability and function.

Question 41

Define necrosis.

Answer 41

form of cell death where cellular membranes deteriorate causing cellular enzymes to leak out and digest cell

Question 42

Define apoptosis.

Answer 42

Regulated, programmed cell death via enzymatic degradation of cells DNA, nuclear and cytoplasmic proteins

Question 43

Define hemotoxylin.

Answer 43

Blue dye --> basophilia

Question 44

Define eosin.

Answer 44

Red dye --> eosinophilia

Question 45

Define pyknosis.

Answer 45

Nuclear shrinkage and increased basophilia; DNA = dark, shrunken mass

Question 46

Define karyorrhexis.

Answer 46

Shrunken nuclear mass undergoes fragmentation.

Question 47

Define: Karyolysis

Answer 47

Basophilia fades because DNAase digests DNA

Question 48

Define autophagy.

Answer 48

"Self eating" as survival mechanism when nutrient deprived, lysosomal digestion of cell's own component

Question 49

Define hypoxia

Answer 49

Oxygen deficiency in tissues

Question 50

Define ischemia

Answer 50

Reduced blood supply; lead to deficiency in nutrients and build up of toxic metabolites

Question 51

Define hypertrophy

Answer 51

An increase in the SIZE of cells resulting in increased size of the organ

Question 52

Define hyperplasia

Answer 52

An increase in the NUMBER of cells in an organ that stems from increased proliferation

Question 53

Define atrophy

Answer 53

Shrinkage in the size of cells by the loss of cell substance

Question 54

Define metaplasia

Answer 54

A change in which one adult cell type is replaced by another cell type

Question 55

Define exudate

Answer 55

Escape of fluid, proteins and blood cells from vascular system into interstitial tissue or cavities due to inflammation

Question 56

Define transduate

Answer 56

Extravascular fluid with low protein content, little or no cellular material pushed out of capillaries due to high blood pressure

Question 57

Define edema

Answer 57

Accumulation of extravascular fluid; known as swelling at site of injury

Question 58

Define lymphangitis

Answer 58

Red streaking, swelling near a skin wound as a telltale sign of infection

Question 59

Define lymphadenitis

Answer 59

Inflammation of the lymph node.

Question 60

Define effusion.

Answer 60

Accumulation of fluid into a space or cavity created by injury

Question 61

Define purulent (suppurative)

Answer 61

Pus, inflammatory exudate consisting of neutrophils, liquefied debris of necrotic cells

Question 62

Define abscess

Answer 62

Localized collection of pus

Question 63

Define ulcer

Answer 63

Local defect of surface of an organ or tissue that is produced by shedding of inflamed necrotic tissue.