Inflammation acute

Question 1

Inflammation general

Answer 1

occurs in living vascularised tissue
Cause acne be exogenous or endogenous
Response purpose = diluting/inactivating bio or chemical toxins, killing microbes, foreign material, necrotic tissue and neoplastic cells, degrading forming materials, providing wound healing factors.
Brings leukocytes _ plasma proteins circulating around the blood to the site of tissue damage.

Question 2

Typical inflammatory reaction (5) steps

Answer 2

Host cells and molecules recognise offending agent
Leukocytes and plasma proteins arrive at the location
Leukocytes and proteins are activated and working together destroy and eliminate the offending substance
The reaction is controlled an terminated
Damaged tissue is repaired

Question 3

List some issues with the inflammatory reaction when it is misdirected (4)

Answer 3

1. Autoimmune disease
2. Neuro degenerative disorders
3. Allergies
4. Neoplastic processes (cancer promoting as the inflammation factors/components can cause DNA damage in specific genes and cell proliferation )

Question 4

Cardinal signs of inflammation

Answer 4

Rubor
Calor
Tumour
Dolor
functio leasa

Signs are typically more prominent in acute inflammation than in chronic inflammation and many of these are consequences of the local vascular changes initiated by inflammation

Redness (rubor) and heat (calor) due to increased blood flow to inflamed site with vasodilation
Swelling (tumour) is caused by the accumulation of fluid in extravascular
Pain (dolar) is due to release of chemicals that stimulate nerve endings
Loss of fx (functio leasa) things that destroy foreign invaders and other causes of inflammation have an intrinsic ability to injure normal tissues with secondary loss of fx

Question 5

Pattern of inflammation: acute vs chronic

Answer 5

Acute - main features are exuding of fluid and plasma proteins and leukocytic emigration, principally neutrophils followed by rapid repair and healing.

Chronic- longer duration and it is associated histologically with presence of lymphocytes and macrophages, the proliferation of blood vessels, fibrosis and tissue necrosis

Question 6

Cells involved in the acute ad chronic inflammatory response and why these are the cells are in this order

Answer 6

Acute
neutrophils predominate during first 6-24hrs
Monocytes 24-48hrs
Reasoning for the process above- more numerous in blood = neutrophils, respond more rapidly to chemokine and they may attach more firmly to adhesion molecules on endothelial cells,

But neutrophils are short lived and undergo apoptosis after 24-48hrs, whereas monocytes survive longer

Question 7

Explain variations with inflammation cellular patterns

Answer 7

Pseudomonas organism —> neutrophils predominate over 2-4 days.
Viral infections —> lymphocytes arrive first
Parasitic infections consists of eosinophils
Allergies —> mast cells and eosinophils maybe the main type

Question 8

Explain the initiators of the inflammation

Answer 8

Innate immune system has numerous PRRs (pattern recognition receptors)—> recognise = PAMPS (Pathogen-associated molecular patterns)

Sentinel cells - macrophages ( express PRRs)

When macrophages PRRs detect microbial product = cascade of reactions in the cell

Activated macrophage —> inside cell synthesise and release pro inflammatory cytokines —> these then signal other inflammatory ells and blood vessels in the area

Example of studied PRRs activated by PAMPs are the toll-like receptors (TLRs) a family that detects bacteria, viruses, fungi and protozoa

Question 9

Explain sterile inflammation

Answer 9

Instead of bacterial it is trauma, physical and chemical injury, foreign bodies or inappropriate products of adaptive immunity

DAMPSs or alarmins these activate the macrophages

Question 10

How do DAMPS work?

Answer 10

Derived from normal proteins and metabolites found in the cytoplasm or nucleus of host cells which are released after necrosis.

Therefore the extracellular presence of these molecules indicates cellular injury in the vicinity- Numerous PRRs specifically recognize DAMPs leading to the same activation and signalling cascade as that occurring with PAMPs

Question 11

Three major components of acute inflammation (3)

Answer 11

1. Dilation of small vessels= increased blood flow
2. Increased permeability of microvasculature enabling plasma proteins to leave the circulation
3. Emigration of leukocytes from the microcirculation to focus of injury + activation to eliminate the offending agent

Question 12

When an individual encounters an injurious agent, such as an infectious microbe or dead cells

Answer 12

phagocytes that reside in all tissues try to eliminate these agents
Cytokines + lipid messenger + mediators of inflammation —> release phagocytes and other sentinel cells to those areas
Some of the mediators act on small blood vessel in area promoting efflux of plasma and recruitment of circulating leukocyte

Question 13

Reactions of blood vessels in acute inflammation

Answer 13

Change blood flow + permeability to allow plasma proteins + leukocytes leave—> circulation into—> infection site

Question 14

Explain exudation

Answer 14

The escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities is known as exudation

Question 15

Explain an exudate

Answer 15

An exudate is an extravascular fluid that has a high protein concentration and contains cellular debris

Question 16

Most of the changes observed in the early stage of the vascular reaction are mediated by

Answer 16

histamine and other chemical compounds released by inflammatory cells, mainly mast cells, that are widely distributed in the normal connective tissue

Question 17

Explain the two steps of acute inflammation response to injury

Answer 17

1. Begins vasodilation (widening of blood vessels) = increase blood volume —> the increase diameter =. Slow velocity blood
   the slowing of blood means leukocytes principally neutrophils begin to accumulate along the vascular endothelial surface ( this the first step)
2. Increase in vascular permeability
   allowing fluid and plasma proteins into interstitial tissue (exudate process)

Question 18

What is margination

Answer 18

As stasis develops, leukocytes (principally neutrophils) begin to accumulate along the vascular endothelial surface—a process called margination 


Question 19

Explain the importance of plasma protein in exudate

Answer 19

not only important for diluting the inciting agent, but some of them have an active role in removing and immobilizing them

Question 20

Immunoglobulins are important?

Answer 20

for improving phagocytosis (opsonisation), activating the complement system and directly inactivating some organisms

Question 21

The complement system

Answer 21

The cascade to the MAC

Question 22

Fibrinogen is an important plasma protein in exudates

Answer 22

that polymerizes in extravascular spaces to form fibrin. Polymerized fibrin confines the stimulus to an isolated area, has chemotactic properties and induces blood clot formation, as well as forms a framework for fibroblast and endothelial cell migration during the initial stage of wound healing

Question 23

Mechanisms of increased vascular permeability (3)

Answer 23

In healthy tissue protein -rich flow stays in the vessel due to endothelial cells intercellular tight junctions

1. Endothelial gaps can occur
2. Direct injury to endothelial cells
3. Increased transcytosis induced by VEGF

Question 24

Explain how endothelial gaps occur

Answer 24

by contraction of endothelial cells or reorganisation of cytoskeletal microtubule and microfilament proteins within endothelial cells

occurs most the time in postacapullary venues
Transient (15-30mins)
Histamine part of chemical mediators

Question 25

Explain direct injury to endothelial cells (2) and lx

Answer 25

injury - detachment of the cell from the underlying basement membrane occurs quickly by thermal injury, radiation, bacterial cytotoxins . Neutrophils that adhere to the endothelium during inflammation may also injure the endothelial cells and thus amplify the reaction. It affects arterioles, capillaries and postacapillary venules

Question 26

Explain normal leukocyte movement

Answer 26

Flow rapidly in the blood

Question 27

Explain the recruitment of leukocytes (4 steps)

Answer 27

This processes purpose is to move leukocytes from the vascular lumen to extravascular space where issues usually are Step 1. Margination and rolling along the vessel wall 2. Firm adhesion to the endothelium 3. Transmigration between endothelial cells 4. Migration in interstitial tissues toward a chemotactic stimulus Cytokines influence these processes

Question 28

Explain leukocyte Rolling ( the selectins)

Answer 28

Traveling leukocytes are slowed down by brief binding of selectin to their ligands. L selectins on leukocytes P selectins on endothelial + platelets E selectins on endothelial cells

Question 29

Explain leukocyte stable adhesion

Answer 29

Leukocyte - B2 integrin molecules <-binds-> ICAM1 (inter cellular adhesion molecule) leukocyte had to be stimulated to express B2 integrin molecules 4 B2 interns with identical B subunit (CD18)

Question 30

Explain LAD

Answer 30

Leukocyte adhesion deficiency cattle, Dog (Irish setters) and humans No B2 integrin expression = normal fx neutrophils but impaired passage across vascular walls Therefore —> infections cannot be cleared Hallmark = lesion has no neutrophils but they are in the blood vessels

Question 31

Explain leukocyte Diapedesis

Answer 31

Diapedesis = the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation. Leukocytes going through the endothelial layer Mediated by Endothelial cell adhesion molecule 1 Junctional adhesion molecules JAMs

Question 32

L - selectin

Answer 32

Expressed by leukocytes for rolling

Question 33

P-selectin

Answer 33

Expressed by endothelial cells and platelets for rolling

Question 34

E-selectin

Answer 34

expressed by endothelial cells for rolling

Question 35

B2 integrin

Answer 35

Expressed by leukocytes for ‘stable adhesion’

Question 36

ICAM-1

Answer 36

expressed by endothelial cells for ‘stable adhesion’

Question 37

PECAM1

Answer 37

Expressed by endothelial cells/leukocytes for’ diapedesis

Question 38

JAMs

Answer 38

Expressed by endothelial cells/leukocytes for’ diapedesis

Question 39

Define chemotaxis

Answer 39

Locomotion along a chemical gradient

Question 40

Leukocytes chemotaxis steps

Answer 40

1. Chemoattractants on Plasma membrane extend pseudopods to region of greatest chemotactic 2. The pseudopoda then pulled the whole cell towards that direction These influence inflammatory cells Influenced by the complement system

Question 41

What stimulates leukocyte?

Answer 41

Exogenous or endogenous stimuli | This often occurs at a site of infection or tissue necrosis.

Question 42

Leukocytes’ defensive functions at the site of inflammation (3)

Answer 42

Phagocytosis Liberation of substances Production of mediators

Question 43

Explain leukocytes phagocytosis 3 steps

Answer 43

1. Recognition and attachment 2. Engulfment —> formation of phagocytic vacuole 3. Intracellular destruction by phagosomes ( ROS and nitrogen species and lysosomal enzymes)

Question 44

Explain liberation of substances that destroy extracellular microbes and dead tissues of leukocytes

Answer 44

Largely the same as the phagocytic vesicles, but contained within leukocytes granules

Question 45

List the three chemical mediators of acute inflammatory response

Answer 45

1. Histamine 2. The complement cascade 3. Arachidonic acid metabolites

Question 46

Explain histamine

Answer 46

Stored in mast cells, basophils + platelets ``` Stimulated to be released by IgE C3a C5a Heat Cold Substance P ATP Products from leukocytes ``` ``` Fx/effect (mediator of inflammattion) Vasodilation Increased vascular permeability Pain Itch Neural reflexes Bronchial contraction Eosinophilic chemotaxis ``` Duration and onset effect immediate = within minutes Lasting 30-90mins

Question 47

Explain the complement cascade

Answer 47

The molecules are produced by the liver cascade all form the AMC Classical = antigen-antibody Alternative pathway = LPS Gram -ve and polysaccharides from fungal cell wall Lectin pathway = mannose-binding lectins to microbial product C3a nd C5a - influence mast cells to release histamines and other mediators

Question 48

Arachidonic acid metabolites

Answer 48

Arachidonic acid = poly unsaturated fatty acid ltx = plasma membrane Inflammation occurs = cell membrane is injured = lipids in there are rapidly rearranged = arachidonic acid is released + several active lipid mediators are produced. Producing autacoids Three COX isoenzymes COX1 COX2 COX3

Question 49

What are autacoids

Answer 49

Metabolites acting as local hormones and short -lived and most important ones are prostaglandins and leukotrienes produced by the cycloxygenase and lypooxygenase enzyme pathways.

Question 50

Explain COX 1

Answer 50

Is constitutively expressed and present in almost all tissues

Question 51

Explain COX 2

Answer 51

Induced by exogenous and endogenous stimuli and occurs locally in sites of inflammation

Question 52

Explain COX 3

Answer 52

Recently discovered COX3 | Expressed in cereal cortex of dogs and humans

Question 53

Explain the general action of Aspirin, naproxen, ibuprofen etc

Answer 53

Inhibit arachonic acid metabolites produced by cox 1 and cox 2 pathways

Question 54

Morpholoigcal patterns of acute inflammation (4)

Answer 54

1. Serous inflammation 2. Catarrhal inflammation 3. Fibrinous inflammation 4. Suppurative inflammation

Question 55

Explain serous inflammation morphology

Answer 55

Ltx = hypersecretion of inflamed serous glands thermal injury to skin or acute allergic response Process = the watery fluid leaks from the small gaps between endothelial cells and from hypersecretion of inflamed serous glands Stx = watery fluid accumulation with low concentration of plasma proteins No to low numbers of leukocytes Grossly looks like 1. Excessive clear to slightly yellow watery fluid leaking from the tissue on cut section 2. Forms raised fluid-filled vesicles

Question 56

Explain Catarrhal inflammation morphology

Answer 56

Secretion or accumulation of a thick gelatinous fluid containing abundant mucus and muffins from mucous membrane Ltx Occurring in ltxs of tissue with abundant goblet cells and mucous glands Grossly —> surface or cut surface of affected tissue may be covered with or contain a slightly opaque thick fluid

Question 57

Explain fibrinous inflammation

Answer 57

Accumulation of fluid with high concretion of plasma proteins and low number of leukocytes Cause = servere endothelial cell injury Fibrinogen leaks from capillaries and postcapullary venues and polymerises outside of the vessels to fibrin ( homogenous and hypereosinophilic protein) Ltx most common —> infection microbes and in serous membranes of the body cavities. Grossly - the surface of affected tissues are red and covered with thick , stringy, elastic, white-grey to yellow exudate

Question 58

Explain Suppurative inflammation

Answer 58

fluid accumulation —> high concentration of plasma proteins and high number of leukocytes, predominantly neutrophils. Commonly known as pus Most commonly causes by bacteria

Question 59

Systemic effects of an acute inflammatory response (7)

Answer 59

``` Loss of appetite Leathery Muscular wasting (Cachexia) Haemodynamic changes (shock) Fever Leukocytosis Alterations to acute phase proteins ```

Question 60

Explain how fever is inducedWhat mediates systemic effects of acute inflammation

Answer 60

mediated by the systemic release of TNFα, IL1 and IL6 by activated leukocytes Others effects serve to conserve energy and mobilize resources to aid in the resource-expensive process of inflammation (anorexia, lethargy, cachexia)

Question 61

Explain how fever is induced

Answer 61

Exogenous —> LPS Endogenous —> IL1, and TNF (Tumour Necrosis Factor) Then Pyrogens stimulate prostaglandin synthesis in hypothalamus = increased production of neurotransmitters = reset the temperature set-point at a higher level

Question 62

Explain the hypothesis of the benefits of a fever (8)

Answer 62

May induce heat shock proteins = these then enhance lymphocyte response to microbial antigens Increased expression of some cytokines Enhanced phagocytosis Increased T cell proliferation Inhibition of growth of some microbes Induction or iron-sequestering proteins Enhanced interferon-stimulated responses Increased motility and activation of some leukocytes

Question 63

What is leucocytosis

Answer 63

Increased number of leukocytes circulating in the blood

Question 64

Explain the acute inflammation leukocytosis generally

Answer 64

Primary a neutrophillia reaction. This occurs because accelerate release of cells from the bone marrow post mitotic reserve pool (neutrophils with mature cells) Compared to prolonged infection there is depletion of bone marrow store of mature cells and proliferation of precursors in the bone marrow cause increased production of CSFs (colony-stimulating factors). It is one of the most important clues a veterinarian has in gauging whether the animal’s clinical signs stem from an inflammatory process, especially if the site of inflammation is not immediately evident.


Question 65

Acute phase proteins

Answer 65

-plasma proteins —> synthesised in liver ( plus = leukocytes, adipocytes, heart, GI tract, kidney) these increase during inflammation Concentration rises very quickly peak 24-48hrs 10-100 times normal serum concentrations The increased synthesis of these molecules is upregulated cytokines as IL16, IL1 or TNF Eg major in dogs, rabbits pigs and primates is C-reactive protein (CRP) fx = bind to certain components of surface of bacteria, parasites or damaged cells enhancing their clearance Other APPs are serum amyloid A, haptoglobin, fibrinogen, ceruloplasmin

Question 66

List possible outcomes of acute inflammation (3)

Answer 66

The following are based on severity of tissue damage Ability of cells to regenerate Physical or biologic features of the case of injury determine these outcomes 1 Resolution 2 Scarring occurs 3 Actor to chronic transition occurs

Question 67

Explain how a resolution can become the outcome of an acute inflammation.

Answer 67

Correct sequence Macrophage and lymphatic vessels remove the exudate Inciting agent is eliminated Connective tissue is intact and provides support fro regeneration of epithelial cells

Question 68

Explain how scarring can become the outcome of an acute inflammation.

Answer 68

Severe tissue destruction Inflammatory injury involves tissues that are incapable of regeneration Or Abundant fibrin exudate

Question 69

Explain how a transitioning to chronic can become the outcome of an acute inflammation.

Answer 69

Acute response cannot resolve, because of persistence of injurious agent or to some interference with normal process of healing