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Mechanisms of Disease > Session 3 -> Chronic inflammation > Flashcards

Session 3 -> Chronic inflammation Flashcards

1
Q

What is chronic inflammation?

A

-The chronic response to injury and process of healing with the production of granulation tissue and fibrosis

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2
Q

What is the predominant cell type in chronic inflammation?

A

-Macrophage

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3
Q

Give an example of a persisting injurous agent which can cause chronic inflammation

A
  • Foreign body
  • Necrotic tissue
  • Bacteria
  • Autoimmune antigen
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4
Q

When does chronic inflammation occur?

A
  • Alongside acute inflammation
  • After acute inflammation
  • Begins without any preceeding inflammation
  • Autoimmune conditions
  • Prolonged exposure to toxic agents
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5
Q

When would chronic inflammation occur alongside acute inflammation?

A

-During a severe or persistent irritation eg cholecystitis

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6
Q

Give an example of when chronic inflammation would occur without any preceeding acute inflammation

A

-In some chronic infections such as tuberculosis

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7
Q

Give an example of an autoimmune condition where chronic inflammation occurs

A

-Rheumatoid arthritis

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8
Q

Name a toxic agen which can cause chronic inflammation after prolonged exposure

A

-Silica

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9
Q

When do macrophages become activated in tissues?

A

-Can live and be dormant for many months until they are activated by a local challenge

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10
Q

Which cell type are the best at destroying persistent bacteria such as TB, neutrophils of macrophages?

A

-Macrophages

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11
Q

What are the functions of macrophages?

A
  • Phagocytosis
  • Present antigens to adaptive immune system
  • Secrete substances which summon and activate other cellls
  • Stimulate angiogenesis (important in wound healing)
  • Induce fever, acute phase reaction and fibrosis
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12
Q

What does lymphocyte presence in normally absent tissues indicate?

A

-Antigenic material is or has been present

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13
Q

Where are lymphocytes normally present?

A
  • Lymph nodes
  • Spleen
  • Liver
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14
Q

What are the functions of lymphocytes?

A
  • Secrete antibodies (plasma B cells)
  • Process antigens
  • Secrete cytokines
  • Kill cells
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15
Q

How do plamsa cells differ phenotypically from other lymphocytes?

A

-They have peri-nuclear hof -> pale cytoplasm due to abundance of ER and golgi producing antibody

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16
Q

What is the main function of eosinophils?

A

-Attack large parasites, eg worms

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17
Q

In what immune responses are eosinophils present in high numbers?

A
  • Asthma (in bronchi)
  • Tumours such as hodgkin’s lymphoma
  • Allergic reactions
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18
Q

What cell types are principally involved in chronic inflammation?

A
  • Macrophages
  • Lymphocytes
  • Eosinophils
  • Fibroblasts and myofibroblasts
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19
Q

What is the function of fibroblasts?

A
  • Produce connective tissue substances such as collagen, elastin and GAGs
  • Differentiate into myofibroblasts
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20
Q

What is a giant cell?

A

-A single giant multinucleate cell formed by the fusion of many macrophages

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21
Q

In what type of inflammation are giant cells often seen?

A

-Granulomatous inflammation

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22
Q

What do giant cells do?

A

-Perform frustrated phagocytosis

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23
Q

Describe Langhan giant cells

When are they often seen?

A
  • Cell nuclei arranged around the periphery in a horse-shoe
  • Foamy cytoplasm
  • Often, but not exclusively, seen in tuberculosis
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24
Q

Describe foreign-body giant cells

When are they seen?

A
  • Nuclei arranges randomly within the cell

- Often but bot exclusively seen when a hard to digest foreign body is present

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25
Q

How do foreign-body giant cells eradicate foreign bodies?

A
  • Small foreign bodies are phagocytosed

- Giant cells stick to the surface of large foreign bodies

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26
Q

Describe a touton giant cell

When are they often seen?

A
  • Nuclei are arranged in a ring towards the centre of the cell
  • Lipid is around the outside
  • Often formed in lesions where there is a high lipid content such as fat necrosis and xanthomas
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27
Q

Is there a typical composition of cells within chronic inflammation?

A

-No, the response is not sterotyped and thus the proportion of cells will vary depending on the cause
eg Rheumatoid arthritis = plasma cells
Chronic gastritic = lymphocytes
Leishmanaisis (protazoal infection)= macrophages

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28
Q

What is the cause of scarring?

A

-Excessive fibrous tissue deposition

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29
Q

List the possible complications of chronic inflammation

A
  • Fibrosis
  • Impaired function
  • Atrophy
  • Stimulation of immune response
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30
Q

When does excess fibrosis occur?

A

-When fibroblasts are stimulated by cytokines to produce excess collagen

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31
Q

How is collagen production important in chronic inflammation?

A
  • Walls off infected areas

- Production of a fibrous scar to replace damaged tissue

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32
Q

When does collagen deposition become problematic?

A

-when it is excessive or inappropriate and replaces normal parenchymal tissue and impairs the function of the organ

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33
Q

Provide an example of when collagen deposition occurs and impairs function?

A

-Interstitial fibrosis of the lung

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34
Q

How can myofibroblasts be problematic?

A

-When an area contains excess myofibroblasts there can be excessive contraction of the wound leading to contractures

35
Q

Provide an example of when myofibroblasts can impair function

A

-Contraction in the cirrhotic liver will impair the flow of portal blood resulting in ascites

36
Q

Chronic cholecystitis is an example of fibrosis, describe this process of inflammation

A
  • Gallstones blocking the cystic duct
  • Bile is not secreted and accumulates causing multiple repeated episodes of acute inflammation as it is toxic
  • Chronic inflammation ensues and the gall bladder becomes increasingly fibrous and thickens over time
37
Q

Why does the muscular component of the gallbladder thicken in cholecystitis?

A

-Repeated attempts at extruding gall stones

38
Q

What is gastric ulceration?

A

-Necrosis of epithelia on gastric mucosal surface

39
Q

What is another name for gastric ulceration?

A

-Peptic ulcer

40
Q

Why is gastric ulceration seen in chronic gastritis?

A
  • There is a focal imbalance of acid production and mucosal defence leading to erosion of the mucosal surface
  • The submucosa becomes washed with HCl
41
Q

What is often seen at the base of an ulcer?

A

-White slough

42
Q

What is inflammatory bowel disease?

A

-A group of diseases characterised by relapsing and remitting inflammation of the gastrointestinal tract

43
Q

What are the most common types of inflammatory bowel disease?

A
  • Crohn’s

- Ulcerative colitis

44
Q

Why are inflammatory bowel diseases described as episodic?

A

-Repeated episodes of acute inflammation which can be treated occur in addition to the underlying chronic inflammation

45
Q

What is the most common cause of inflammatory bowel diseases?

A

-It is most commonly idiopathic

46
Q

What are the main differences between ulcerative colitis and Crohn’s?

A
  • Ulcerative colitis is inflammation and ulceration of the superficial mucosa, usually effecting the rectum but can involve part of the colon or retreat and effect the whole colon
  • Crohn’s disease is transmural inflammation and ulceration which is usually segmental from the mouth to the anus (skip lesions)
47
Q

What is liver cirrhosis?

A

-A condition where the liver responds to injury by producing interlacing strands of fibrous tissue between which are nodules of regenerating cells

48
Q

How do patients with inflammatory bowel disease usually present?

A

-Diarrhoea, rectal bleeding and varied symptoms

49
Q

What is a stricture?

A

-Narrowing of a tube

50
Q

Do strictures and fistulas form in ulcerative colitis or crohn’s?

A

-Crohn’s

51
Q

What is a fistula?

A

-Abnormal connection between two epithelial lined organs

52
Q

How does a cirrhotic liver look characteristically?

A

-Shruken and nobbly

53
Q

How does cirrhosis occur?

A
  • Chronic inflammation leads to excess collagen deposition and fibrosis
  • This causes disorganisation of the architecture, whilst regeneration is attempted inbetween the bands of fibrosis
  • This leads to the multinodular liver with impaired function ie cirrhosis
54
Q

What are the common causes of liver cirrhosis?

A
  • Alcohol
  • Infection with HBV/HCV
  • Fatty liver disease
  • Immunological causes
  • Drugs/toxins
55
Q

What is atrophic gastritis?

A

-Atrophy of the gastric mucosa, possibly suceeding chronic gastritis but often occurs spontaneously as an autoimmune disease in association with pernicious anaemia

56
Q

Can the immune response induce inflammation?

A

-Yes, it uses inflammation as a non-specific weapon

57
Q

What is rheumatoid arthritis?

A

-An autoimmune disease where there is chronic inflammation in the synovial membrane of joints due to autoimmune antibodies

58
Q

What does the localised chronic inflammation in rheumatoid arthritis cause?

A

-Destruction of joints

59
Q

What are the systemic effects of chronic inflammation in rheumatoid arthritis?

A
  • Can cause amyloidosis (mis-folding of fibbres into b-sheets which become insoluble and deposit as amyloid fibres)
  • Can effect other organs such as skin, liver and lung
60
Q

What is the overlap between chronic inflammation and immune response?

A
  • Immune diseases cause pathology by chronic inflammation

- Chronic inflammatory processes can stimulate immune responses

61
Q

What is granulomatous inflammation?

A

-Chronic inflammation with granulomas

62
Q

What is a granuloma?

A

-A localised collection of cells characterised by the presence of epitheloid histiocytes, giant cells and monocytes/lymphocytes

63
Q

What are epitheliod histiocytes?

A

-Immobile macrophages which represent epithelial cells as they are elongated, have eosinophilic cytoplasm and are tightly packed

64
Q

When does granulomatous inflammation occur?

A
  • Persistant, on-going low-grade antigenic stimulation

- Hypersensitivity

65
Q

How do granulomas form in relation to the target material?

A

-They form around the particle which can be free or phagocytosed in the centre

66
Q

What immune cells are often found in the centre of granulomas and why?

A

-Monocytes as they try to wall the particle off from the environment

67
Q

How big are granulomas?

A

-Usually 0.5-1mm

68
Q

What are the two types of granuloma?

A
  • Foreign body granuloma

- Hypersensitivity/immune-type granuloma

69
Q

When do foreign-body granulomas occur?

A

-When there is persistent, ongoing low-grade stimulation

70
Q

Describe a foreign body granuloma

A

-Contains macrophages, foreign body giant cells, epitheloid cells and some fibroblasts at periphery. There are very few lymphocytes as the stimulus is non-antigenic

71
Q

Describe hypersensitivity/immune-type granulomas

A
  • Contain macrophages, giant cell (possible langhans), epitheloid cells, fibroblasts and lymphocytes
  • Can undergo central caseous necrosis and develop around insoluble but antigenic particles
72
Q

What is a granuloma, which has central caseous necrosis, associated with?

A

-TB

73
Q

What are the main causes of granulomatous inflammation?

A
  • Mildly irritant foreign material (artificial joint break down, surgical thread etc)
  • Persistant Infections (TB, leprosy, syphyllis, cat-scratch disease)
  • Unknown causes
74
Q

What is leprosy?

A

-Chronic disease caused by mycobacterium leprae that effects skin, mucous membranes and nerves

75
Q

What is cat-scratch disease?

A

-An infectious disease which is transmitted to humans by a cat scratch
which can become chronic

76
Q

What is sarcoidosis?

A

-A chronic disorder of unknown cause in which the lymph nodes are enlarged and granulomas form in the lungs, liver and spleen, however many other sites can be effected

77
Q

What is wegener’s granulomatosis?

A

-An autoimmune disease predominantly effecting the nasal passages, lungs and kidneys, characterised by the formation of necrotising granulomas in addition to pulmonary vasculitis

78
Q

Do granulomas appear in ulcerative colitis or crohn’s disease?

A

-Crohn’s disease

79
Q

How does tuberculosis cause disease?

A

-Through persistance and induction of cell-mediated immunity

80
Q

What giant cells are associated with tuberculosis?

A

-Langhan cells

81
Q

Describe a granuloma associated with TB

A

-Granuloma contains langhan cells and has central caseous necrosis (histiologically appears pink)

82
Q

What are the 4 possible outcomes of TB?

A
  • Arrest, fibrosis and scarring
  • Erosion into bronchus leading to bronchopneumonia or TB in the GIT through coughing and then swallowing
  • Tuberculosis empyema -> chronic active infection of the pleural space with calcification of the pleura
  • Erosion into the bloodstream which can result in focal tb(localised in one organ) or miliary TB (effects everywhere)
83
Q

Who is sarcoidosis most commonly seen in?

A

-Young women

84
Q

What macroscopic features of acute inflammation remain in chronic inflammation?

A

-Tumor and Dolor (swelling and pain)

Mechanisms of Disease (11 decks)

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