MCB Lecture 62 & 63 Tissue Injury, Chronic Inflammation Flashcards Preview

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Flashcards in MCB Lecture 62 & 63 Tissue Injury, Chronic Inflammation Deck (85)
0

What are the two outcomes of tissue injury?

Regeneration of tissue

Scarring, replacement by connective tissue

1

When can normal function be regained?
When is function not regained?

Normal function is regained when the tissue is regenerated, or if the scar is small

Function is lost when there is extensive fibrosis

2

What are the requirements for regeneration?

- The tissue must be made up of labile or stable cells
- Underlying structure of the organ must not be lost

3

When does scarring occur?

Scarring occur when the underlying tissue is lost, or when the cells are not capable of proliferation

4

Which compound regulates cell cycle?

Cyclins

5

When will a cell enter G0?

When growth factors are removed

6

What does FACS analysis tell us about the effect of removing growth factors from cells?

Normal: most cells in S phase, DNA content more than 1
Remove GF: cells enter Go, DNA content = 1
Apoptotic stumulus: cells die, DNA content less than 1

7

What are the three different classifications of cells based on proliferative capacity?

Labile
Stable
Permanent

8

What is labile tissue?
Eg. ?

These cells never enter Go and are always replicating
These tissues are capable of regeneration

For example: epithelium of skin and GIT, hematopoetic cells

9

What is stable tissue?
Eg. ?

This tissue leaves the cell cycle, but can re-enter if required to do so.

For example: parenchyma of most solid organs (liver, kidney), endothelium, smooth muscle

10

What is permanent tissue?
Eg. ?

These cells enter Go and cannot exit
These tissue can never be regenerated
These cells are do terminally differentiated

For example: neurons, cardiac and skeletal muscle

11

What changes occur in cells during proliferation?

Increase in cell size
Increase in mitosis
Protection against apoptosis

12

What are the triggers of proliferation? (3)

- Growth factors
- Hormones
- Cytokines

13

What is the mechanism of growth factors causing proliferation?

Growth factors initiate a signal transduction pathway, leading to the transcription of genes such as cyclins that push the cell into the cell cycle.
- prevent apoptosis
- increase protein synthesis

14

What are the outcomes of growth factor signalling?

Migration
Angiogenesis
Proliferation
Differentiation

15

Which cytokine results in proliferation?

IL-2

16

What are the two basic classes of cells in an organ?

Parenchyma and stroma

17

What is parenchyma?
Give some examples

These are the function cells of an organ

Eg. Hepatocytes, myocytes, neurons

18

What is stroma?
What is it made up of?

The stroma is the support structure for the parenchyma

It is made up of connective tissue

19

What are the two forms of stroma?

Basement membrane
Interstitial matrix

20

Describe the possibility of tissue regeneration in the kidney

There is limited capacity for regeneration, and the underlying structure must be intact

The proximal ducts undergo hypertrophy and hyperplasia when the other kidney is removed

21

Describe tissue regeneration in the liver

The liver has good regenerative capacity if the underlying structure is maintained.

5-10% of the tissue may be regenerated in 4-6 weeks

22

What is steatosis?

This is when there are some fibrous hepatic nodules due to moderate alcohol intake. The nodules can be regenerated

23

What are the steps in repair by connective tissue?

1. Angiogenesis
2. Migration and proliferation of fibroblasts
3. ECM deposition by fibroblasts
4. Remodeling

24

When does repair by connective tissue occur?

If the tissue can not be regenerated, or if the underlying structure is lost

25

What is the aim of angiogenesis?

To bring the blood supply back to the damaged tissue

26

Describe the mechanism of angiogenesis

1. Vasodilation and increased permeability of the existing vasculature
2. Migration of endothelial cells
3. Proliferation of endothelium
4. Inhibition of proliferation and remodelling
5. Recruitment of peri endothelial cells

27

What are the features of the new vasculature produced in angiogenesis

Leaky, as the tight junctions haven't properly formed yet

28

Describe the migration and proliferation of fibroblasts during tissue regeneration

1. Macrophages and endothelium produce growth factors: PDGF and FGF-2
2. The growth factors stimulate recruitment and proliferation of fibroblasts

29

What is the function of fibroblasts in tissue regenerative by connective tissue?

To synthesise and secrete ECM, especially collagen

30

What are the stages of tissue repair?

Granulation tissue -> scar formation

31

Compare granulation tissue with scar tissue

Granulation:
Proliferating fibroblasts
Vascularised
Loose ECM

Scar tissue:
Inactive fibroblasts
A vascular
Dense collagen and connective tissue

32

What is occurring during remodelling?
What does this result in?

- Switch from type III collagen to type I
- Collagen is no longer degraded

This results in increased tensile strength of the wound

33

What are the two types of cutaneous wound healing?

Healing by first intention
Haling by second intention

34

Describe what happens in healing by first intention in the first 24 hours

1. Scab formation
2. Inflammation

35

What sort of wounds result in healing by first intention?
What are the features of these wounds?

Surgical wounds
Paper cuts

They are very clean, small wounds

There is no necrotic tissue or inflammation

36

What are the features of healing by second intention?

Everything is larger: the wound, the clot, inflammation and granulation tissue

37

Describe wound contraction

When does it occur?

This is when the some of the cells in gap the specialised granulation tissue contract like smooth muscle cells (myofibroblasts)

This occurs in healing by the second intention

Wound size reduced by 5-10% in 4-6 weeks

38

What are the aims of successful healing?

To regain function
Rapidly resolve the injury
Transient scar

39

What factors affect successful healing?

Nutrition
Location of the scar
Effect of contraction
Persistence of foreign bodies
Infection

40

What are some complications of healing that can occur?

Wound dehiscence
Contraction
Keloid formation

41

Describe wound dehiscence

This is when the wound opens us due to poor suturing, nutrition, mechanical forces or infection

42

What is keloid formation?

This is hypertrophy of the scar tissue, causing a raised mass of scar tissue due to excess collagen

43

What problems can occur with contractions of myofibroblasts ?

The limb contracts

44

What are the features of chronic inflammation? (Give histology cal features too)

Inflammation lasts weeks, to months to years
Injury, inflammation and healing all occur at the same time
- mononuclear cells
- tissue damage
- repair by fibroblasts
- fibrosis

45

What are the two broad categories of cause of chronic inflammation?

Primary chronic inflammation

Unresolved acute inflammation

46

How can acute inflammation lead to chronic inflammation?

Excessive cellular exudate
Excessive necrosis
Persistent causal agent

47

What are peptic ulcers?
What is it an example of ?

This is when there is damage to the epithelium of the stomach (infection or anti-inflammatory drug) that can't be resolved

It is an example of acute infections persisting and causing chronic inflammation

48

Describe the histology of peptic ulcers

Epithelial interruption
Necrotic debris (acellular)
Non specific acute inflammation
Granulation tissue
Fibrosis

49

What is osteomyelitis?
What is it an example of?

This is when there is an unresolved infection in the bone (because the blood supply is poor)

It is an example of unresolved acute infection turning into chronic infection

50

What is chronic choleystitis?

This is gall stones of the liver causing inflammation and thickening of the wall and chronic infection

51

What is primary chronic inflammation?

This is when the injury leads directly to chronic infection

52

What are the causes of primary chronic inflammation? (4)

1. Persistent infection
2. Immune mediated
3. Toxic agent
4. Primary granuloma

53

Which cells are involved in the chronic inflammatory response?

Macrophages
Lymphocytes

Other leukocytes

54

Describe the two types of macrophages and how each is activated

M1: classical activation: IFN-gamma and microbicidal products
M2: alternate activation: cytokines: IL-4 and IL-13

55

What are the functions of macrophages in chronic inflammation?

M1: inflammation and killing
M2: inhibition of inflammation and tissue repair

56

What is the role of lymphocytes in chronic inflammation?

They make antibody and kill infected cells

57

Describe the vicious circle of T cell and macrophage activation

M1 activates lymphocytes by presenting antigen and releasing stimulatory cytokines

T cells stimulate macrophages by releasing IFN-gamma and IL-4 and IL-13

58

What are the macroscopic morphologies of chronic inflammation?

Chronic ulcers - peptic ulcer
Chronic abscess cavities - bacterial abscesses in the lung
Thickened wall - chronic choleystitis
Granulomatous - sarcoidosis
Fibrosis - Asbestosis of lung

59

What are the two classes of morphology of chronic inflammation?

Diffuse
Granulomatous

60

Describe the structure of diffuse chronic inflammation

Give an example

No granuloma

Eg. Asbestosis

61

Describe the Pathogenesis of asbestosis

1. Asbestos fibres are inhaled and penetrate deep into the lung
2. Diffuse pulmonary interstitial fibrosis forms
3. Contraction of the walls leads to enlarged air spaced and honey combed effect
4. Walls of visceral pleura are thick and fibrous

62

What are other types of diffuse chronic inflammation?

Chronic bronchitis
Bronchiectisis
Ulcerative colitis
Rheumatoid arthritic
Atherosclerosis
Peptic ulcers

63

What is the structure of granulomatous chronic inflammation?

Give the structure of this feature

Possible zone of necrosis (caseating or non caseating)
Epithelioid cells
Lymphocytes
Macrophages
Multi nucleates giant cells
Collagen and fibroblasts around the outside

64

What are the different types of granulomatous lesions?

Immune mediated (caseating, non-caseating)

Foreign body

65

What causes the immune mediated granulomas?

Describe the structure of the granuloma

Caused by a nonfiction such as tuberculosis

The granuloma has caseous necrotic tissue in the centre

66

What is an example of something causing non-caseating granuloma?

What is the structure of the granuloma?

Sarcoidosis

Cause unknown

No necrotic tissue in the granuloma

Non horseshoe arrangement of nuclei in the giant cells

67

Where do non-caseating granulomas occur?

They occur in many different organs throughout the body, but cause the most harm in the lungs

68

Describe the steps leading to foreign body mediated granuloma

1. Inert, foreign material enters (talc, silica, splinter, prosthesis)
2. Too large to be phagocytosed
3. Granuloma forms to barricade it off to prevent further damage

69

What are the sequelae of chronic inflammation? (4)
Give example of diseases for each

Contraction of fibrous tissue
- chronic rheumatic fever
Loss of parenchyma and thus function
- cirrhosis of the liver
Metaplasia
- smoking
Neoplasia
- hepatocellular carcinoma (in the liver)

70

Describe what happens in healing by the first intention over the next 3 days

1. Mitoses under the scab
2. Neutrophils are replaced by macrophages, which clear the debris
3. Granulation tissue forms: fibroblasts make ECM , angiogenesis

71

Describe what happens over the next few weeks in healing by first intention

1. Scarring
- fibroblasts inactive
- vasculature decreases
- type 1 -> type 3 collagen ( strong wound)
- oedema drains
- epithelium has been regenerated

72

What type of morphology of chronic inflammation is chronic bronchitis?

What causes it?

Diffuse

Cigarette smoke and pollutants - exogenous toxins

73

What type of morphology of chronic inflammation are peptic ulcers?

What causes it?

Diffuse, chronic ulcers

Caused by persistent infection of helicobacter pylori

74

What type of morphology of chronic inflammation is ulcerative colitis?

What causes it?

Diffuse

Autoimmune, inappropriate immune response

75

What type of morphology of chronic inflammation is rheumatoid arthritis?

Diffuse, immune complexes in joints

Type III hypersensitivity

76

What type of morphology of chronic inflammation is sarcoidosis?

Granulomatous (non-caseating)

77

What type of morphology of chronic inflammation is asbestosis?

Diffuse, fibrous thickening of visceral pleura

78

What type of morphology of chronic inflammation is tuberculosis?

What causes it?

Granulomatous; caseating granuloma in lungs

Persistent infection of mycobacterium tuberculosis in. Alveolar macrophages

79

What type of morphology of chronic inflammation is foreign body?

Granulomatous, non necrotic

80

What type of morphology of chronic inflammation is atherosclerosis?

What causes it?

Diffuse

Caused by an endogenous toxin

81

What type of morphology of chronic inflammation is chronic choleystitis?

Diffuse, thickening of wall of gall bladder

82

Which different CD4+ t lymphocytes have a role in chronic inflammation? Differentiate between their different roles

Th1: classically activate macrophages by secreting IFN-gamma

Th2: secrete IL-4 IL-5 IL-13 for alternate macrophage activation
Allergic inflammation, protection against helminthic parasites

Th17: secrete IL-17 for leukocyte recruitment

83

What is a tubercle?

It is the lesion in mycobacterium tuberculosis chronic inflammation

84

What is chronic rheumatic fever?

This happens after a strep infection --> type II hypersensitivity.

This causes fibrosis of the mitral valves. The thick fibrous tissue contracts --> stenosis

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