Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y1 - Pathology > 7_Inflammation and Repair > Flashcards

7_Inflammation and Repair Flashcards

1
Q

inflammation:

define, cells involved, mechanism

A
  • def: protective complex host response to injury
  • cells involved:
    • host cells, blood vessels, and proteins, and other mediators
    • required to eliminate the initial cause of cell injury, necrotic cells and tissues resulting from the original insult
  • mech:
    • caused by diluting, destroying or neutralizing the harmful agent and injured tissue –>
    • to permit injured tissue to permit healing/repair
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

inflammation:

histo/clinical features, w/o inflammation, etc

A
  • histo/clinical features: can vary considerably, depending upon extent of injury and nature and injurious agent
  • w/o inflammation, infections would go unchecked and wounds would never heal
  • pathological:
    • inflammatory rxn and repair process can be harmful as also capable of injuring normal tissues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the process of inflammation/damage/and repair

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

acute and chronic inflammation

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the most important cell in:

  • acute
  • chronic
A
  • acute phase: key/most important cell is the neutrophil
  • chronic phase: key/most important cell is chronic inflammatory cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

acute inflammation:

define

A
  • the immediate response; neutrophil is most important cell
  • rapid response (min to hours) to injurious agents/stimuli
    • infxns,
    • trauma (physical/chem agents),
    • tissue necrosis,
    • foreign bodies (splinters, dirt sutures, etc),
    • immune reactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

acute inflammatory response:

function, mech

A
  • exudate carries plasma proteins, fluid, and cells from local blood vessels into the damaged area to mediate local defenses
  • mech:
    • infective or causative agent (e.g. bacteria) present in the damaged area
    • can be destroyed or diluted and eliminated by components of the exudate
    • the damaged tissue can be broken down and partially liquefied and the debris removed or digested from the site of damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the two major components in the acute inflammatory response?

A
  • vascular changes: smooth muscle vasodilation, increased permeability of endothelium
  • cellular events: emigration of neutrophils, their metabolic activation and chemotactice migration to site of injury, phagocytosis of microbes/damaged tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

when are there cells in the extracellular matrix?

A

there aren’t many cells in ECM unless you’re fighting infection

(normally they’re in the blood vessel)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the 3 key effects on the inflammatory site during acute inflammation

A
  1. increased blood flow
  2. leakage of plasma proteins –> edema
  3. neutophil emigration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are the various stimuli for acute inflammation?

A
  • microbial infections
  • hypersensitivity reactions/ immune reactions –> excessive immune rxn
  • physical agents
    • trauma, UV, ionizing radiation, burns, cooling
  • irritant and corrosive chemicals
  • tissue necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

list some examples of acute inflammation

A
  • laryngitis, pharyngitis, –itis
  • skin rxn to burn/or scratch
  • acute hepatitis, pericarditis
  • pneumonia, inflammation of lung
  • pleurisy, inflammation of the pleura
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

which mechanisms do necrotic cells use to recognize microbes?

A
  1. Pattern recognition receptors - recognize molecular patterns common to microbes
    • e.g. phagocytes, dendritic cells, epithlial cells can detect molecular components from dead cells
  2. Toll like receptors - recognize bacterial DNA, endotoxin, viral dsRNA;
    • providing defense against all classes of infectious pathogens –> activates TFs causing synthesis of mediators of inflammation, interferons, that activate acute inflammation
  3. Inflammasomes - cytoplasmic complex that recognizes ingested products of dead cells, extracellular ATP, microbial products, cholesterol crystals and free fatty acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

inflammasome:

mechanism, and effects

A
  • mech:
    • triggering inflammasome –> activates caspase-1 –> cleaves pro-IL-1b into biologically active IL-1b –> secreted and is an important cytokine recruiting leukocytes
  • effects:
    • cholesterol and fatty acids accumulate in atherosclerosis –> contributes to low-grade chronic inflammation of that disease
    • cholesterol crystals are present in significant number of endodontic periapical lesions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

describe the vascular changes in inflammation

(and clinical symptoms)

A
  1. transient vasoCONSTRICTION (seconds)
  2. prolonged vasoDILATION of arterioles
    • hyperemia: inc BF in capillary beds
    • inc. intravascular hydrostatic pressure –> pushes fluid through vessel wall (transudate) –> excess extravascular fluid (edema)
    • inc. vascular permeability

clinically: the area is warm (calor) and red (rubor/ erythema)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

difference between transudate and exudate?

A
  • Transudate: (less protein, few cells)
    • fluid pushed through the capillary due to high pressure within the capillary;
    • can occur w/ normal vessel permeability
  • Exudate (more protein, may have some RBCs/WBCs)
    • is fluid that leaks around the cells of the capillaries caused by inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the hallmark of acute inflammation w/ regards to vasculature?

(and resulting sxs)

A

INC. VASCULAR PERMEABILITY;

  • inc in permeability –> leakage of fluid rich in protein/lrg molecules/ & eventually cells –> into surrounding tissue (exudate)
  • inc extravascular proteins –> contribute to inflamm respose & draw fluid via osmosis
  • inc hydrostatic pressure (pushing fluids out of vessel) + THE OSMOTIC PULL OF FLUIDS –> results in inc. in extravascular fluid (edema)

Sxs: swelling (tumor), and pain (dolor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what effect does the increased vascular permeability have on the blood flow? –> downstream effects?

A
  • inc. vasc perm –> outpouring of protein-rich fluid into extravascular tissues –>
  • RBCs in flowing blood becomes more concentrated –> inc viscosity –> stasis (slowing circulation) –> neutrophils marginate (accumulate) –> neutrophils adhere to endothelium –> emigrate into ECM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the 7 key mechanisms of increased vascular permeability?

A
  1. endothelial cell CONTRACTION
  2. endothelial RETRACTION
  3. direct endothelial INJURY
  4. delayed prolonged LEAKAGE
  5. leukocyte-mediated endothelial injury
  6. increased TRANSCYTOSIS
  7. leakage from REGENERATING CAPILLARIES
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

endothelial contraction:

mechanism of inc. permeability

A
  • Aka “Immediate Transient Response”
    • Most common mechanism
    • Response is rapid, short-lived (15-30 mins) and reversible
  • Leads to widened intercellular gaps in post-capillary venules
  • Elicited by histamine, bradykinin, leukotrienes, etc binding to specific receptors on endothelium that lines post-capillary venules.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

endothelial retraction:

mechanism of inc. permeability

A
  • Reversible; Slower and more prolonged retraction of endothelial cells –> leads to widened intercellular gaps in post-capillary venules
  • Occurs via reorganization of cytoskeleton, which is a more complex change
    • taking 4-6 hours to compete and lasting for 24+ hours.
    • Induced by cytokines IL-1 and TNF.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

direct endothelial injury:

mechanism of inc. permeability

A
  • Leakage is “immediate and sustained” until vessel thromboses or is repaired with new endothelium.
  • Increased permeability due to endothelial cell necrosis and detachment (severe mechanical injuries, burns, bacterial lytic infections).
    • Affects any or all levels of the microvasculature (arterioles, capillaries and/or venules) depending on type/extent of the injury.
23
Q

delayed prolonged leakage:

mechanism of inc. permeability

A
  • Another type of direct injury that involves venules and capillaries only because the injury is less severe (bacterial toxins, sunburns, after X-irradiation).
    • Leakage begins in 2-12 hours and lasts for hours or days.
    • Mechanism unclear, but delayed cell damage occurs.
24
Q

leukocyte-mediated endothelial injury:

mechanism of inc. permeability

A
  • Consequence of leukocytes accumulating in vessels at sites of injury, becoming “activated” and releasing toxic substances (enzymes, free radicals) that can damage adjacent endothelial cells.
  • Largely restricted to sites where leukocytes adhere to the endothelium (venules at sites of inflammation, pulmonary capillaries).
25
Q

increased transcytosis:

mechanism of inc. permeability

A
  • There are “channels” present in normal endothelium formed by a vesiculovacuolar organelle system that extends across endothelial cells near cellular junctions.
    • ^^ This transport system is increased in inflammation
    • Induced by VEGF.
26
Q

leakage from regenerating capillaries:

mechanism of inc. permeability

A
  • Newly forming capillaries are an important part of angiogenesis and repair of tissues following injury.
  • Regenerating capillaries are patent but not tightly adherent to each other, so leakage occurs.
  • Tissues in early stages of repair are still edematous.
27
Q

describe the process of leukocyte extravasation from the blood vessel

A
  • stasis allows leukocytes to leave central column of blood –> MARGINATE along BV wall –> come in contact w/ ACTIVATED ENDOTHELIUM (*site of injury)
    1. ROLLING: tumble over the endothelium, transiently sticking to cell surface adhesion molecules expressed by the “activated” endothelium.
    2. INTEGRIN ACTIVATION BY CHEMOKINES: transient adhesions are mediated by selectins expressed on surface of endothelium (CD62E and CD62P) and leukocytes (CD62L). Selectins bind to sialylated oligosaccharides attached to mucin-like glycoproteins on the other cell.
    3. ADHESION: slowed leukocytes –> firm adhesion by inegrins (ICAM-1, VCAM-1) on “Activated” endothlial cells
    4. DIAPEDESIS: Transmigration of leukocytes (diapedesis) occurs mainly at endothelial intercellular junctions in post-capillary venules.
28
Q

which integrins and chemokines and CDs are involved in leukocyte recruitment

A
  • •Once leukocytes have sufficiently slowed, firm adhesion to endothelium is mediated by high affinity leukocyte cell surface integrins binding to ligands (ICAM-1, VCAM-1) on “activated” endothelial cells.
  • Endothelial cells express CD31 at cell junctions and neutrophil CD31 binds to it forming a dimer, signaling where to transmigrate.
    *
29
Q

Function of collagenase and chemokines during leukocyte recruitment?

A
  • Collagenase aids in piercing the vascular basement membrane
  • Chemokines aid in firm adhesion and induce leukocytes to transmigrate.
30
Q

when/where do neutrophils accumulate, and when do monocytes become involved?

A
  • Neutrophils accumulate at sites of acute inflammation first:
    • more numerous in the blood,
    • they respond more rapidly to chemotactic factors, and
    • attach more firmly to adhesion molecules initially expressed by endothelium.
  • Transmigration of monocytes become more numerous 24-48 hrs later. T
    • They become macrophages and live longer.
    • Very important phagocytic cell in inflammation that removes necrotic tissue, dead neutrophils, etc.
31
Q

which curve corresponds with:

  • monocytes
  • edema
  • neutrophils

and why?

A
  • edema - is extravascular fluid; and leakage
  • neutrophils are more numerous and respond to chemotactic factors
  • monocytes become macrophages and live longer; but take longer to transmigrate
32
Q

in a patient w/ fever/cough and yellowish sputum x 2 days –>

which type of inflammatory cell would be most likely present in GREATLY INCREASED NUMBERS in the sputum?

A

NEUTROPHILS;

accumulate; found in sputum

33
Q

what are the key steps of leukocyte transmigration?

A
34
Q

(slide 35)

A
35
Q

how is leukocyte activation process induced?

A

A number of chemical factors (chemical mediators, products of necrotic tissue, bacterial components) bind cell surface receptors (e.g. TLRs) and induce this process

36
Q

what metabolic changes are involved in leukocyte activation?

A
  • Enhanced phagocytosis and intracellular destruction of microbes
  • Increased secretion of lysosomal enzymes, free radicals to destroy extracellular microbes, breakdown necrotic tissue.
  • Increased production of mediators that recruit more cells, expand the inflammatory response.
37
Q

when can leukocyte activation be harmful?

A

•can be potentially harmful if occurs away from site of injury (e.g. in the blood vessel causing endothelial damage).

38
Q

leukocyte phagocytsis:

definition, and mechanism

A
  • def: Engulfment of cell debris, microbes, foreign material. Principal phagocytes are neutrophils, monocyte/macrophages
  • mech:
    • 1) recognition and attachment occurs via opsonins
    • 2) engulfment - binding of opsonized particles to leukocyte cell surface tiggers engulfment
    • 3) killing/degradation - phagosome and lysosome fuse –> lysosomal contents spill into phagolysosome –> resulting in enzymic degradation adn degranulation of the granulocyte
39
Q

what are the mechanisms of microbial killing and degradation?

A
  • Bacterial killing occurs via reactive oxygen species formed in phagolysosome.
  • Phagocytosis leads to a burst in O2 consumption:
    • as NADPH oxidase oxidises NADPH( reduced nicotinamide adenine dinucleotide phosphate) and in the process converts O2 to superoxide free radical.
    • Superoxide then converted to H2O2
    • Lysosomal myeloperoxidase then uses Cl- + H2O2 to create HOCl free radical. Most efficient bacteriocidal system, killing bacteria by halogenation or protein/lipid peroxidation.
  • •Dead bacteria are then further degraded by lysosomal acid hydrolases.
40
Q

how do the following affect microbial killing and degradation?

  1. inherited deficiency in MPO, or an
  2. inherited deficiency in NADPH reductase
A
  1. inherited deficiency in myeloperoxidase (MPO)–> can still kill microbes via superoxide, hydroxyl free radical, OONO radical.
  2. Inherited deficiency in NADPH oxidase –> results in chronic granulomatous disease, recurrent infections.
41
Q

what are the non-oxygen dependent mechanisms in microbial killing and degradation?

A

“BLAM!” are non-oxygen dependent

  • Bacterial permeability-increasing protein (activates phospholipase and membrane phospholipid degradation)
  • Lysozyme degrades bacterial coat oligosaccharides
  • Arginine-rich cationic peptides (defensins) that kill microbes by creating holes in membranes
  • Major basic protein produced by eosinophils that is cytotoxic to parasites.
42
Q

function of granule components secreted by leukocytes? (re:microbial killing/degradation)

mechanisms of secretion?

A
  • fxn: to destroy extracellular microbes (enzymes like elastase, antimicrobial peptides)
  • mech:
    • phagolysosome remains transiently open as it forms, releasing enzymes into surrounding tissue (regurgitation during feeding)
    • Inability to phagocytose particles (microbes, immune complexes) on a surface leads to activation of leukocyte and secretion of enzymes (frustrated phagocytosis)
    • Leukocyte death may release active or ruptured phagolysosomes
43
Q

neutrophil extracellular traps (NETs):

define, structure

A
  • def: Extracellular fibrillar networks produced by neutrophils in response to microbial pathogens, inflammatory mediators
  • structure:
    • framework of nuclear chromatin with embedded granule proteins (antimicrobial peptides, enzymes).
    • high conc of antimicrobial substances at sites of infection & traps the microbes preventing their spread
    • chromatin is supplied by the neutrophils, resulting in cell death.
44
Q

what is postulated to be the source of nuclear antigens in systemic autoimmune diseases (e.g. lupus)?

A

exposed nuclear chromatin (includes histones, DNA, etc) of NETs

(NETs contain a framework of nuclear chromatin with embedded granule proteins (antimicrobial peptides, enzymes)

45
Q

describe the processed by which leukocytes can induce tissue injury?

A
  1. The products produced and potentially released from leukocytes can contribute to tissue injury.
  2. Bystander tissues can be damaged –>Certain infections difficult to eradicate (TB, some viral diseases) the host response contributes more to the pathologic process than does the microbe.
  3. Autoimmune response – normal tissues can be damaged inappropriately
  4. Excessive reaction to non-toxic environmental substances (asthma, pneumoconioses)
  5. Prolonged inflammation –> inflammatory reaction can be responsible for much of the tissue injury. (Immune-mediated vasculitis, arthritis, atherosclerosis, glomerulonephritis, septic shock, etc)
46
Q

what are the possible consequences of leukocyte dysfunction?

A
  • increased susceptibility to infection
  • can causes of defective inflammation
    • bone marrow suppression caused by tumors or tx (chemo, radiation)
    • metabolic disease such as diabetes (causes abnormal leukocyte fxn)
      *
47
Q

list some examples of inherited disorders of leykocyte dysfunction

A
  • Leukocyte adhesion deficiency type-1: defective leukocyte integrins
  • LAD-2: absence of sialylated glycoprotein on leukocytes for E-selectin
  • Chronic granulomatous disease-defect in microbicidal activity
  • Chediak-Higashi syndrome: A.R. impaired fusion of lysosomes and phagosomes, impaired secretion of lytic granules by cytotoxic T cells.
48
Q

draw out the process map of ACUTE vs CHRONIC inflammation

A
49
Q

serous inflammation:

define, location

A

when exudate is protein-poor resulting –> in watery fluid that accumulates:

  • in area of injury (e.g. a skin blister) or
  • in body cavities by mesothelial secretion (effusion).
50
Q

when considering histological slides, what are we evaluating for?

A
  • nature of the injurious agent
  • severity of the tissue injury
  • type of tissue injured –> all influence the histological picture (morphology)
51
Q

fibrinous inflammation:

define, mech, pathology

A
  • def: consequence of severe injuries, resulting in greater vascular permeability that allows fibrin to pass the endothelial barrier, greater outflow of protein into extravascular spaces.
  • mech:
    • Fibrinogen into the body cavities –> clotting/sticky fibrin mass that coats surfaces of the cavity, fills the space causing organs to adhere to body wall.
      • (e.g. Pleural, pericardial, peritoneal cavities lined by mesothelium
    • With fibrinolysis and phagocytosis of debris, body cavity structure and function restored (resolution).
  • PATHOLOGICAL: if fibrinolysis is not timely, fibroblasts and new blood vessels migrate into the fibrin mesh forming granulation tissue (organization) leading ultimately to fibrosis/scarring –> Results in permanent fibrous adhesions of organ, restricting movement.
52
Q

suppurative (purulent) inflammation:

define, cause, clinical

A
  • def: dominated by large numbers of neutrophils, edema and necrotic debris (pus).
  • cause: Typically due to pyogenic bacterial infections such as Staphylococci, actinomyces.
  • clinical signs:
    • Abscesses: localized foci of suppurative inflammation in a tissue, organ, or confined space.
      • May persist for months, walled off by fibrous tissue.
      • Due to central tissue destruction, usual outcome is fibrous scar.
53
Q

ulcers:

define, location, cause

A
  • define: Local defect in surface of organ or tissue produced by sloughing of inflamed, necrotic tissue
  • location: most common in the GI tract, mouth and on skin of lower extremities in elderly with poor circulation. Involves focal loss of epithelium.
  • cause:
    • Underlying acute and chronic inflammation;
    • ulcers from chronic inflammation can become extensive when healing is slow or there is repeated insult (peptic ulcer, large aphthous ulcers).

Y1 - Pathology (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions