3. Chronic Inflammation Flashcards
(83 cards)
1
Q
Duration of chronic inflammation
A
• Unlike acute inflammation, chronic inflammation is long-lived
– >3 weeks – May persist for many weeks, months, even years!
2
Q
Chronic inflammation - definition
A
—> “Chronic response to injury with associated fibrosis”
3
Q
Acute Inflammation - overview
A
- Acute insult e.g. papercut, low level bacterial infection
- Acute inflammation
- Small amounts of damage ??
- yes = resolution
- no (repair is inefficient) = chronic damage
- yes = resolution
4
Q
Chronic inflammation - overview
A
repair is inefficient and leads to scarring
1. Chronic insult e.g. large burn, trauma – not localized 2. Chronic damage 3. Repair and scarring – replace damage tissue with collagen etc.
5
Q
Aim of chronic inflammation
A
—> aim to repair something that is damaged
6
Q
3 ways chronic inflammation can arise
A
- ‘take over’ from acute inflammation
…if damage is too severe to be resolved within a few days - May arise de novo
– Some autoimmune conditions (e.g. RA)
– Some chronic infections (e.g. viral hepatitis – virus replicates faster than immune system can clear it)
– “chronic low-level irritation” (e.g. allergy to dust, repeated exposure of dust = continuous irritation) - May develop alongside acute inflammation
– In severe persistent or repeated irritation
7
Q
What does chronic inflammation look like
A
- Large number of cells involved
- Characterized by the microscopic appearances which are much more variable than acute inflammation. (acute inflammation = neutrophil laden tissue)
8
Q
Macrophage - what is it
A
—> phagocytes derived from blood monocytes (myeloid cells) - monocytes differentiate into mature macrophage only when they enter the tissue
• They are tissue resident – Sense infection within tissues
• Important in acute and chronic inflammation
9
Q
Macrophage - functions
A
• Initial identification of pathogens
• Some early clearance of pathogen
• Phagocytosis and destruction of debris & bacteria
• Processing and presentation of antigen to immune system
• Synthesis of not only cytokines, but also complement components, blood clotting factors and proteases – use cell signaling IL8, TNF alpha
• Control of other cells by cytokine release
• Resolution of inflammation
○ Clearance of dead neutrophils
○ Release of anti-inflammatory cytokines such as IL10 – tells neutrophils to stay away
10
Q
2 types of macrophages
A
- M1 – pro inflammatory = sense damage, kickstart process
* M2 – second stage = clearing up neutrophils
11
Q
Lymphocytes - what is it
A
- • Any cells present resident in lymph: T cells and B cells
• Sometimes called ‘chronic inflammatory cells’
• Produce things to maintain inflammatory response until damage is cleared up
○ e.g. opsonins, immunoglobin (bind to and activate neutrophil and complement)
– But are a normal component of many tissues
12
Q
Lymphocyte function
A
- Complex, mainly immunological. - immunological memory
- T lymphocytes involved in control & some cytotoxic functions.
- B lymphocytes differentiate to produce antibodies
13
Q
Plasma cells
A
– Differentiated antibody-producing B lymphocytes. Usually implies considerable chronicity.
14
Q
Eoisinophils
A
– Allergic reactions, parasite infestations, some tumours.
15
Q
Fibroblasts / Myofibroblasts:
A
– Recruited by macrophages; make collagen – act as a scaffold to make new tissue
○ This just fills in the gap with collagen but doesn’t serve the same function
16
Q
Damage + immune response
A
• Release of things in from the cell that neutrophil has never seen before
More damage, more activation of immune system, more inflammation
17
Q
Giant cells - definition
A
• Multinucleate cells made dervied by fusion of macrophages
○ Used to deal with large scale problems
○ Macrophages fuse together (giant body) to try and encapsulate something, surround the bad thing so it can’t spread
18
Q
3 giant cell types
A
Langhans
Foreign Body Type
Touton (Fat necrosis) -
19
Q
Langhans giant cells
A
(tuberculosis- forms biofilms, covering across large area and granuloma grows on top of it and tries to destroy it with ROS and enzymes but biofilms are hard to kill)
○ Langhans try to destroy and encapsulate bio film but it is difficult as bio film sits on the surface of tissue
20
Q
Foreign Body Type giant cell
A
e.g. splinter and metal
21
Q
Touton (Fat necrosis) - giant cell
A
encapsulate areas of necrotic tissue
22
Q
Cell types in chronic inflammation
A
Macrophages Lymphocytes Plasmacells Eiosinophils Fibroblasts/myofidroblasts Giant cells
23
Q
4 effects of chronic inflamonation
A
- Fibrosis
- e.g. gall bladder (chronic cholecystitis), chronic peptic ulcers, cirrhosis
- Impaired function – loss of function
- e.g. chronic inflammatory bowel disease
- Rarely increased function due to chronic inflammation e.g. mucus secretion, thyrotoxicosis
- Atrophy
- gastric mucosa, adrenal glands
- Loss of structures – e.g loss of vili and surface area
- Stimulation of immune response
- Macrophage - lymphocyte interactions
24
Q
Fibrosis – chronic cholecystitis
A
- Repeated obstruction by gall stones
- Repeated acute inflammation (constantly happening) leads to chronic inflammation –> abscess
- Fibrosis of gall bladder wall
25
Inflammatory bowel disease
* Lost definition of vili
* Idiopathic inflammatory disease affecting large and small bowel
* Patients present with diarrhoea, rectal bleeding and other symptoms
* Ulcerative colitis and Crohn’s disease (bulbous structures within gut lumen)
Prevent passage of things through gut, build up of things in gut ---> inflammation
26
Ulcerative colitis
superficial
• Diarrhoea, bleeding
• Ulcers can be caused by infection with H.pylori
27
Crohn’s disease
ransmural
| • Strictures, fistula (abnormal connection between two eputhelieum lined organs)
28
Common causes of cirronsis
* Alcohol
* Infection with HBV, HCV
* Immunological
* Fatty liver disease
* Drugs and toxins
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Liver cirrhosis - impaired function
* Nodules seen on the surface that actually pass through the liver seen on the scan below
* Nodules of heathy tissues surrounded by unhealthy fibrosis tissues – limiting distribution of things in and out of healthy tissues
* Irreversible
30
Fibrosis
* Chronic inflammation with fibrosis… (disorganisation of architecture, attempted regeneration) …leads to Cirrhosis
* No more neat structures – no more proper function
31
Thyroxicosis - increased function
* Enlarged thyroid – grave's disease
* More cells present
* Too much thyroxin
* Lump on neck can be seen where thyroid becomes enlarged
32
Atrophy
gastric mucosa
Normal
• Neat organsiation of mucosa layers
• Vili
Abnormal
• vilus processes with loss definition
33
Autoimmune disease
– constant activation of adaptive immune system to try and clear something that it can never clear
• Autoimmunity is almost always characterised by chronic inflammation
○ Treatment = immunocompromise patient – dampen down immune response
34
Granulomatous inflammation
---> = chronic inflammation with granulomas!
35
Granuloma - what is it
* Could have foreign body penetrate skin that stays there
* Characterisitc encapsulation of area by immune cells
* Lose structure and organisation of surrounding tisses
36
Cells involved in a granuloma
• T and b cells
• macrophages
• Neutrophils – clear it up
• Dendritic cells (antigen presenting cells)
• Giant cells can form part of the granuloma
○ See the immune system at work, as the cells would normally work
37
Why do granulomas arise
* Persistent, low-grade antigenic stimulation e.g. bio film
* Hypersensitivity – collection of conditions that are allergic reaction that cause an abhorrent not normal immune respsonse
38
3 main causes of granulomatous infection
• Mildly irritant ‘foreign’ material
• Infections
– Mycobacteria: Tuberculosis, leprosy
– Other infections e.g. some fungi
• Unknown causes
– Sarcoid
– Wegener’s granulomatosis
– Crohn’s disease
39
Foreign material from breakdown of artificial joint
| Cause of a granuloma
* Metal on metal hip implants – metal grind against each other the metal acetabulum and femurla head rub against each other
* But this causes metal to drop off = form granulomas in surrounding tissue (damage to surrounding tissue is bad as this is what supports the implant
40
Tuberculosis
| Infection cause of granuloma
• Caused by Mycobacteria
– Especially M.tuberculosis.
– Difficult & slow to culture.
* Nature of organism
* Wall lipids (Mycosides).
* Produces no toxins or lytic enzymes
* Causes disease by persistence and induction of cell-mediated immunity.
* Biofilm product
Necrosis in centre = loss of integrity of underlying tisue
41
Sarcoidosis
| Granuloma unknown cause
Variable clinical manifestations
- young adult women
- non caseating granulomas = don't cause necrosis
42
Crohn's disease
| Granuloma unknown cause
Regional enteritis
| Patchy full thickness inflammation throughout bowel
43
Granulomatosis with polyangitis .
| Granuloma unknown cause
Causes grandlomatious inflammation in the vasculature
44
Wound
- A wound is an injury to the skin with/without underlying tissues/organs
45
Causes of wounds
* surgery
* a blow, a cut
* heat/cold
* friction/ shear force, pressure
* chemicals
* disease, such as ulcers or carcinomas
46
Examples of wounds
* Skin cut
* Burn
* Ulcer caused by inflammation or diseases
* Very severe trauma injuries including skin, underlying structures even organs and bones
47
Timings of wound healing
• Seconds-minutes: haemostasis
○ A lot of red blood cells and clot
• Minutes-hours: acute inflammation
○ Inflammatory cells migrate into wound
• 1-2 days: chronic inflammation
• 3 days: regeneration or repair → unique granulation tissue and epithelial cell growth
○ Cells and other moleculre accumulate
* 7-10 days = early forming of scar
* Weeks – 2 years = scar maturation or scar disappears in successful regeneration
48
4 cell types in healing
1. Inflammatory cells
• neutrophils, macrophages, lymphocytes
2. Endothelial (+progenitor) cells proliferation
3. Fibroblasts and myofibroblasts
4. Parenchymal cells- epithelial cells (basal cells)
49
Function of inflammatory cells
| neutrophils, macrophages, lymphocytes
○ Phagocytosis of debris
| ○ Production of chemical mediators
50
Function of Endothelial (+progenitor) cells proliferation
• Angiogenesis = form new blood vessels
51
Function of Fibroblasts and myofibroblasts
• Produce collagen and contract to help close wound
1. Fibroblasts and myofibroblasts
2. Accumulate in granulation tissue
3. Secret collagen
4. Form framework for granulation tissue
52
Function of Parenchymal cells- epithelial cells (basal cells)
• Proliferate and restore skin structure
53
Aim of wound healing
> aims to restore damage structure
54
4 stages of wound healing
1. Haemostasis
• as vessels are open → clot/scab to seal wound
2. Inflammation
• as there has been tissue injury → cytokines and phagocytosis
3. Proliferation
• as structures have been injured/lost → regrowth by stem cells → regeneration and repair
4. Remodelling → functional regaining (scar disappearing and regeneration complete)
• Tissue restoration, recover function
55
haemostasis
• as vessels are open → clot/scab to seal wound
56
Granulation tissue - definition
= special tissues that form in the wound
- Proliferation of the repair tissue
- Has a granular appearance and texture (red)(rich angiogenesis)
57
Cells in granulation tissue
1. Endothelial cells form new capillaries
2. Fibroblasts and myofibroblasts – produce collagen and contract wound
3. Type I collagen
4. Chronic inflammatory cells
58
Functions of granulation tissue
1. Fills the gap
2. Angiogenesis (red) to supply oxygen, nutrients and cells
3. Contracts and closes the wound
4. Help lost tissue to restore – skin cell re growth
59
4 Diseases due to defects in collagen synthesis
* Scurvy
* Ehlers- danlos syndrome
* Osteogenesis imperfecta
* Alport syndrome
60
Scurvy
○ Vitamin C deficency – lysol oxidase
○ Bleeding, delayed wound healing
○ Collagen synthesis requires vitamin c
61
Fibrous repair
---> Fibrous repair is scar formed by fibrovascular connective tissue that replaces lost tissue after an injury
62
When does fibrous repair occur
* Occurs when extensive lost of tissue or/and local infection/persistent harmful agent
* Forming by overgrowth of granulation tissue into dense collagen fibres
* Associated with loss of function: flexibility, sweating, sensation…
63
Scar
• See bundles of collagen formed in granulation tissues
• If something goes even more wrong = leloid overgrowth of scar – scar overgrows above skin levels
○ Increased bundles of collagen
○ Definitley damaged function
64
6 complications of fibrosis repair
* Insufficient fibrosis
* Formation of adhesions
* Loss of function (in heart)
* Disruption of complex tissue relationships within an organ
* Overproduction of fibrous scar tissues
* Excessive scar contraction
65
Insufficient fibrosis
○ Insufficient repair, danger of wound being open = hernia and ulcers
66
Formation of adhesions
○ Occurs in abdominal surgery
○ Fibrosi repairs Compromising organ function or blocking tubes, e.g., intestinal obstruction following abdominal surgery
67
Loss of function in heart
○ Due to healed myocardial infarction with non-contracting area scar
○ Connective tissue may replace some muscle of the heart – loss fo function in blood pumping
68
Disruption of complex tissue relationships within an organ
○ Distortion of architecture interfering with normal function, e.g., liver cirrhosis, connective tissues form scar between liver unit, destroy normal liver function
69
Overproduction of fibrous scar tissues
Keloid scar
70
Excessive scar contraction
○ Can cause obstruction of tubes, disfiguring scars following burns or joint contractures (fixed flexures)
71
Regeneration (functional repair)
• is the growth of cells and tissues to replace lost structures, in which new growth completely restores portions of damaged tissue and recovers normal function (eventually no scar)
72
Repair (fibrous repair)
• a process when severely damaged or non-regenerable tissues are replaced by the connective tissue –scar, with loss of specialised function
73
2 Clinical classification of healing
* Primary intention
| * Secondary intention
74
Primary intention
• Wound surfaces have been closed, with very little tissue loss and no infection (clean).
• Intact connective tissue scaffold. (e.g skin sharp cut, surgical incision, sutured wound)
→Regeneration
75
Secondary intention
• A wound that is extensive and involves considerable tissue loss, and in which the edges cannot be brought together (e.g. ulcer, burn), infected wound
→Fibrous repair
76
Tertiary intention healing
* Delayed secondary intention
| * Try and solve this problem with rescuing method for better healing
77
Healing of bone fractures
1. Haematoma (process haemostasis) : fills gap and surrounds injury. Inflammation occurs.
2. Granulation tissue forms (regernation stage) : Capillaries develop, cytokines activate osteoprogenitor cells
3. Soft callus: at 1 week, fibrous tissue and cartilage
4. Hard callus: after several weeks, initial woven bone forms–weaker and less organised than lamellar bone but can form quickly
5. Lamellar bone: (normal bone structure) replaces woven bone,
6. Remodelling to mechanical stress, and bone not physically stressed is resorbed, bone structure is re-established, weeks -2 years
78
Peripheral nerve regernation and repair
* Axons are myelinated by schwann cells
* Injury to peripheral nevres = damage
* Schwann cells can efficiently regenerate
* Neuron is recovered – axons can regenerate (but not cell body)
79
If regeneration goes wrong – and nerves can't become reconnected
* Neuroma formation
* Lack of long distance regernation
* Lost innervation
80
Neuroma
• Traumatic neuroma is a benign growth (tumor) of nerve tissue (nerve fibers and myelin), that occurs in response to injury or surgery, when normal growth is interrupted.
81
Factors influencing regeneration and repair
Systemic factors
1. Age - stem cell aging
2. Disease/health
• Diabetes/Obesity, Genetic disorders
3. Oxygen delivery-anaemia, hypoxia
4. Drugs - steroids (cortisol, immunosuppressive and inhibit collagen synthesis), cytotoxics…
5. Malnutrition
• Protein loss or lack of essential
• Vitamin C deficiency
82
Factors influencing regeneration and repair
Local factors
1. Type, size, location of wound
2. Blood supply
3. Local infection
4. Necrotic tissue or denervation
5. Mechanical stress or Physical factors:
• Protection (dressings)
• Surgical techniques
83
Synovitis
Synovium of joint becomes inflamed (swollen)
