Chronic Inflammation

Question 1

Characteristics of chronic inflammation

Answer 1

• predominance of mononuclear cells (macrophages, lymphocytes, plasma cells)
• vascular changes are minimal
• increased CT (fibrosis)
• alteration in tissue architecture

Question 2

Why does chronic inflammation occur?

Answer 2

• neutrophils are short lived and they signal macrophages –> macrophages are longer lived and proliferate in tissues
• persistence of antigen
• some stimuli signal chronic inflammatory cells directly

Question 3

_____ occurs because acute inflammation fails to eliminate stimulus

Answer 3

Abscesses

• liquefaction due to neutrophil enzymes
• color of exudate depends on pigment produced by inciting stimulus
• fibroblasts produce collagen and form thin CT around exudate –> matures into a fibrous capsule (takes a week to form a wall

Question 4

Microabscesses

Answer 4

Seen histologically, do not have a true capsule, is just an accumulation of neutrophils

Question 5

The inner wall of an abscess is _____

Answer 5

Granulation tissue

• pyogenic membrane with increased collagen
• full of vessels that allow continual recruitment of neutrophils

Question 6

NAG

Answer 6

Neoplasia, abscess, granuloma

Question 7

Classically activated macrophage

Answer 7

• microbicidal actions
• phagocytosis
• inflammation

Question 8

Alternatively activated macrophage

Answer 8

• anti-inflammatory effects

- wound repair, fibrosis

Question 9

Granulomatous means ________

Answer 9

MACROPHAGES!

- dependent upon presence of indigestible organisms/particles or presence of cell mediated immunity to inciting agent

Question 10

Gross appearance of granulomatous inflammation

Answer 10

• diffusely thickened tissue

- firm nodules of various sizes

Question 11

Micro appearance of granulomatous inflammation

Answer 11

• numerous macrophages present

- accompanied by variable numbers of lymphocytes and plasma cells, and CT

Question 12

Effect of granulomatous inflammation

Answer 12

• chronic infection which the body cannot eliminate

- interfere with organ function

Question 13

What are 4 causes of granulomatous inflammation?

Answer 13

• bacteria (resistant to phagocytosis): mycobacteria, actinobacilli, archanobacterium
• fungi: hisoplasma, cryptococcus, blastomyces
• parasitic diseases: parasitic larvae that die during migration
• foreign bodies: wood, grass awns, suture material

Question 14

Eqithelioid macrophages

Answer 14

Abundant eosinophilic cytoplasm and large pale nuclei

- more secretory and less phagocytic than typical macrophages

Question 15

Giant cells

Answer 15

Large multinucleated cells

- arise from fusion of macrophages

Question 16

When macrophages are in aggregates they are referred to as ________

Answer 16

Granulomas

Question 17

Classic granulomas

Answer 17

• central core of caseous necrosis
• zone of epithelioid macrophages and giant cells
• zone of lymphocytes (predominantly T cells)
• outer layer of fibroblasts and fibrosis

Question 18

Diffuse vs nodular

Answer 18

Morphologic forms based on immunologic response

• TH2: diffuse granulomatous inflammation
• TH1: nodular granulomas

Question 19

TH1

Answer 19

• cell mediated immunity and inflammation
• intracellular pathogens
• autoimmunity
• inflammation

Question 20

TH2

Answer 20

• antibody mediated immunity
• extracellular parasites
• asthma, allergy

Question 21

Stage 1 granuloma

Answer 21

Days after infection

• lesion site is infiltrated by neutrophils, monocytes, macrophages, and lymphocytes
• epithelioid macrophages form

Question 22

Stage 2 granuloma

Answer 22

From 48 hrs to multiple days and weeks
- lesions contain macrophages, epithelioid macrophages, thin rims of fibrous CT, variable numbers of lymphocytes and MCGs can form

Question 23

Stage 3 granuloma

Answer 23

From weeks to 1 month

• central area can caseate or become dense with macrophages and mineralize
• lymphocytes, plasma cells, a zone of fibroblasts, and a fibrous CT capsule surround this core

Question 24

Stage 4 granuloma

Answer 24

From several weeks to months

• lesion can be walled off by a dense capsule
• regions within the lesion can become mineralized and overtake the surrounding tissue

Question 25

Rhodococcus equi

Answer 25

Pneumonia in foals due to failure of phagolysosomal fusion - decreased IFN-gamma which is a key signal for macrophage activation - granulomatous to pyogranulomatous pneumonia

Question 26

Diffuse granulomatous inflammation

Answer 26

No well defined nodules, diffuse accumulation of epithelioid macrophages - ex: Johne's disease in cattle due to M. paratuberculosis

Question 27

Gross appearance of lymphocytic inflammation

Answer 27

Difficult to determine, if infiltrates are extensive, tissue may have a tan/white color

Question 28

Micro appearance of lymphocytic inflammation

Answer 28

Lymphocytes present, can be mixed with plasma cells

Question 29

Causes of lymphocytic inflammation

Answer 29

- viral infection (esp. viruses that infect the brain) - bacterial infection (listeria) - parasitic infection (t. gondii)

Question 30

Effects of lymphocytic inflammation

Answer 30

Indicates immune response is occurring against an agent | - cases involving nervous system are fatal

Question 31

Lymphocytes

Answer 31

Small cells, with very little cytoplasm - lymphocytes enter area of unresolved acute inflammation within 24-48 hrs - some organs (brain) have a perivascular pattern

Question 32

B cells

Answer 32

- lymphocytes take up and present antigen | - differentiate into plasma cells, secrete immunoglobulins

Question 33

Eosinophilic granulomas

Answer 33

Recruited into and stimulated to proliferate (IL-5, eotaxin) | - dense infiltrate of eosinophils with macrophages, varying numbers of lymphocytes and plasma cells

Question 34

Fibroblasts

Answer 34

Contribute to structural integrity of tissue - synthesis of collagen and ECM proteins - produce cytokines and chemokines that regulate extracellular environment - fibroblastic growth factors signal proliferation, continued release of factor can lead to extensive fibrosis

Question 35

Fibrous CT

Answer 35

Dense accumulation of fibroblasts and collagen | - with time, CT becomes more dense and fewer inflammatory cells

Question 36

Is fibrosis cellular?

Answer 36

NO

Question 37

What are the 4 phases of wound healing?

Answer 37

- hemostasis - inflammation - proliferation - remodeling

Question 38

Hemostasis

Answer 38

Platelet plug, angiogenesis

Question 39

Inflammation

Answer 39

Cardinal signs of inflammation, clean up cell debris from tissue injury - excessive inflammation inhibits wound healing

Question 40

Proliferation

Answer 40

New endothelium, epithelium and CT to restore normal function

Question 41

Remodeling

Answer 41

Remodeling of granulation tissue and conversion to mature CT

Question 42

Wound repair requires ______

Answer 42

ECM and must be resynthesized

Question 43

______ and _____ proliferate to fill in tissue defects

Answer 43

Fibroblasts and endothelial cells | - fibroblasts grow parallel to wound surface and are perpendicular to proliferating capillaries

Question 44

Proud flesh

Answer 44

Excessive granulation tissue that leads to a hypertrophic scar - skin wounds of distal limbs of horses - looks granular on surface and often bleeds

Question 45

T/F: granulation tissue is the same as granulamatous inflammation

Answer 45

FALSE!!

Question 46

Repair

Answer 46

If BM is damaged, healing will take longer - if healing is delayed, altered healing occurs = extensive fibrosis - -> inflammation, large tissue defect with loss of BM

Question 47

1st intention

Answer 47

Primary intention healing - when edges are directly apposed (surgery) - heals rapidly with little tract of wound

Question 48

2nd intention

Answer 48

Gaping wound or infected wound | - CT disorganized

Question 49

Epithelialization

Answer 49

Epithelial cells at periphery proliferate - very rapid in 1st intention healing - must move along BM - -> without a BM cells do not have a clear path, remaining cells will spread out to cover defect until cells can divide and replace

Question 50

Bone healing

Answer 50

Hematoma --> fibroblast and mesenchymal proliferation, osteoblasts for bone is immature --> callus formed (primary) and will see cartilage --> secondary callus formed (stronger lamellar bone)

Question 51

Inhibition of bone repair

Answer 51

- malnutrition - infection - instability - necrotic bone fragments - movement at site - inadequate blood supply