Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

*Medicine: Cellular Pathology > Principles of inflammation > Flashcards

Principles of inflammation Flashcards

1
Q

What is inflammation?

A
  • Body’s response to any form of cellular injury (infection, heat, trauma, hypoxia, radiation etc)
  • Aims to remove injurious agents, clear dead tissue + trigger healing
  • Intended to be a protective response
  • However, harmful when inappropriately activated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two main types of inflammation?

A
  • Acute: rapid, transient, vascular changes + neutrophil accumulation
  • Chronic: persistent, on-going tissue destruction + attempted repair
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Acute inflammation is orchestrated by cytokines released by injured cells, examples?

A
  • Histamine
  • Serotonin
  • Prostaglandins
  • Leukotrienes
  • Platelet-activating factor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 2 major events in acute inflammation?

A
  1. Vascular changes
  2. Neutrophil leukocytosis and accumulation in area of damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe vascular changes that occur

A
  • Dilatation of blood vessels resulting in inc blood flow to area of injury
  • Endothelial cell activation -> inc permeability of capillaries -> leaking of fluid + small proteins (eg fibrinogen) into area of damage
  • Activation of coagulation cascade -> production of thrombin, converts fibrinogen into fibrin at area of damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe neutrophil leukocytosis and accumulation

A
  • Inc neutrophil production in bone marrow
  • Neutrophil leukocytosis (above normal range)
  • Endothelial cell activation -> up-regulation of adhesion molecules on endothelial cells (ICAM-1, VCAM-1)
  • Neutrophils migrate to area of damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The end result of these two events of acute inflammation is the formation of acute inflammatory exudate in area of damage. What does it consist of and why is it important?

A
  • Fluid, fibrin, neutrophils
  • Fibrin acts as scaffold which neutrophils can use to move around area of inflammation
  • Neutrophils phagocytose and kill microorganisms + release enzymes to break down damaged tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the local effects of acute inflammation?

A
  • warmth (calor) - due to inc BF
  • redness (rubor) - due to inc BF
  • swelling (tumor) - due to inc perm + leakage of fluid
  • pain (dolor) - due to infl mediators activating pain nerves
  • loss of function - due to pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

When the injury is severe, there are also systemic effects - what are these and what causes them?

A
  • Caused by inflammatory mediators eg. IL-1, IL-6, TNF-a
  • fever
  • liver secretes acute phase proteins eg. CRP
  • hormone production eg. ADH, cortisol, adrenaline
    • -> malaise, weakness, appetite loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is C-reactive protein (CRP)?

A
  • acute phase protein produced by liver
  • in response to IL-6 secreted by macrophages
  • CRP is an opsonin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is opsonisation?

A

Process of coating a particle, such as a microbe, to target it for phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does CRP act as an opsonin?

A
  • CRP binds to bacterial cell walls (phosphocholine)
  • Phagocytes such as macrophages have receptors that recognise the CRP and initiate phagocytosis
  • Thus, CRP facilitates phagocytosis of bacteria
  • And represents an important part of body’s inflammatory response to bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does a significantly elevated CRP suggest?

A
  • Consider bacterial infection as they are potent stimulators of CRP production, but raised CRP not specific for bacterial infection + cannot rely on CRP for this purpose
  • High CRP may be associated with other inflammatory conditions: burns, trauma, polymyalgia, rheymatica, giant cell arthritis etc.
  • Patients with severe bacterial infection may only have a mildly raised (or even normal) CRP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

A raised CRP has been found to be an independent risk factor for what?

A
  • Atherosclerosis (an inflammatory condition)
  • However, CRP is not recommended as a CVD screening test for average-risk adults without symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the possible outcomes of acute inflammation?

A
  • Regeneration (resolution) - damaged cells replaced with exactly same cell type -> normal tissue, best outcome
  • Repair - with scarring
  • Progession to chronic inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The particular outcome of acute inflammation which occurs in any particular case depends on what factors?

A
  • Severity of injury
    • more severe the damage, less likely regen is poss
      ​
  • Type of cell damaged
    • continuously dividing or quiescent tissues are able to regenerate (eg epithelia, fibroblasts, sm muscle)
    • non-dividing tissue are not able to regenerate (eg neurons, skeletal + cardiac muscle)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is regeneration?

A
  • complete restoration of normal structure + fxn
  • more likely when there is limited tissue destruction without significant damage to connective tissue framework
  • more likely when damaged cells able to regenerate (eg epithelia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

A good example of regeneration is healing of the donor site of a split thickness skin graft. When is this used and what does it contain?

A
  • skin grafting used in many situations
    • extensive trauma, burns, areas of extensive skin loss due to infection eg. necrotising fasciitis, cancer surgery where there is a large defect
  • a split thickness graft contains all the epidermis and a variable amount of dermis. Part of the dermis including appendages are left behind at the donor site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is the skin graft harvested?

A
  • A dermatome is used to harvest skin graft
  • Zimmer powered dermatome (rapidly oscillating blade) used
  • Donor site regenerates spontaneously by proliferation of epithelial cells from the remaining appendages, a few months later the donor site will look normal again
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is repair and when is it more likely?

A
  • results in fibrous scar formation
  • more likely when there is substantial tissue destruction leading to significant damage to connective tissue framework
  • more likely when the damaged cells are unable to regenerate (eg. nerve, muscle)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the two steps of the repair process?

A
  • organisation
  • scar formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the ‘organisation’ step in repair following acute inflammation

A
  • replacement of inflammatory exudate by granulation tissue
  • granulation tissue is a fragile complex
  • consisting of proliferating capillaries, macrophages + fibroblasts
  • macrophages phagocytose the debris
  • capillaries give granulation tissue its distinctive red colour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the ‘scar formation’ step in repair following acute inflammation

A
  • granulation tissue is replaced by a scar
  • scar is laid down by fibroblasts
  • scar is composed mainly of fibrous tissue
  • collagen fibres are main component of fibrous tissue
  • scar is mechanically strong but lacks specialised fxn of original tissue leading to loss of specialised fxn
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Give a brief example of repair

A
  • Scarring of myocardium following an MI
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is an abscess?

A
  • localised collection of pus
  • within a newly-formed cavity in a tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe abscess formation

A
  • initiated by certain bacterial infections (pyogenic organisms eg. staph a.)
  • cause damage to tissues -> body mounts inflammatory response
  • inflammatory response characterised by massive emigration of neutrophils which die after phagocytosis of organisms
  • and release large amounts of lysosomal enzymes
  • this + bacteria-derived substances (endotoxins) that also damage tissues -> formation of cavity
  • cavity contains pus - thick, opaque yellow-green fluid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

An abscess has clearly defined zones. It’s a cavity which contains pus. What does pus contain?

A
  • liequfied dead (necrotic) tissues
  • with dead and dying neutrophils
  • fibrin
  • oedema fluid
  • at periphery of pus there is a layer of living neutrophils + fibrin (main components of acute inflammatory exudate)
28
Q

An abscess also has a wall (membrane) composed of which two distinct zones?

A
  • inner layer of granulation tissue containing new capillaries
  • outer layer of fibroblastic tissue laying down scar tissue

these two layers of the wall represent the body’s attempt to repair the area of damage

29
Q

What else does the abscess wall do apart from repairing existing damage?

A
  • Acts as a barrier to prevent further spread of infection
  • Localises the infection
  • Abscess formation is protective
30
Q

Why can’t healing occur with the abscess enclosed? What needs to be done?

A
  • Abscess wall prevents release of abscess contents
  • Prevents healing occurring
  • Therefore, incision + drainage required to enable healing to occur
31
Q

Where do abscesses form?

A
  • Most common site = the skin and in association with a tooth (‘dental abscess’)
  • In theory, an abscess can form within any solid tissue
32
Q

What is the difference between empyema and abscess?

A
  • Empyemas are accumulations of pus in pre-existing rather than newly formed anatomical cavity
33
Q

What is chronic inflammation?

A
  • When inflammation persists for weeks, months or longer
  • It may arise from unresolved acute inflammation or occur from outset
  • It is important as it’s much more likely to cause tissue destruction and heal with irreversible scarring rather than regeneration
34
Q

What are examples of chronic inflammation?

A
  • Persistent infection eg. H. Pylori, M. Tuberculosis, Hep C
  • Autoimmune diseases
  • Non-living material eg. asbestos -> asbestosis; coal dust -> pneumoconiosis
  • Chronic gastric ulcer
35
Q

List and explain some consequences of chronic inflammation

A
  • Scarring (=fibrosis): healing by scarring may lead to problems eg. chronic gastric ulcer -> gastric outlet obstruction
  • Tissue destruction: eg. gastric ulcer -> perforation or haemorrhage
  • Development of cancer: eg. H. Pylori gastritis -> gastric carcinoma
  • Diversion of nutrients: huge demand to maintain inflammatory response -> weight loss, anaemia of chronic disease, decreased host resistance
  • Amyloidosis: reactive systemic amyloid (AA amyloid)
36
Q

Granulomatous inflammation is a specific type of chronic inflammation. What is a granuloma?

A
  • granuloma = aggregate of activated (epithelioid) macrophages
37
Q

What are causes of granulomatous inflammation?

A
  • infections eg. mycobacteria
  • sarcoidosis
  • Crohn’s disease

Granulomas in mycobacterial infections are protective. Role of granulomas in sarcoidosis and Crohn’s disease unknown.

38
Q

Tuberculosis is an example of granulomatous inflammation. It is caused by Mycobacterium Tuberculosis. What are characteristics of this bacterium species?

A
  • small rod-shaped bacillus w/ thick lipid-rich cell wall
  • remarkably slow at growing
  • able to persist in latent form within cells for many years
  • allows reactivation of disease many years after infection first acquired
39
Q

What happens following spread of TB?

A
  • spread via respiratory route
  • infections begins in terminal air spaces right at periphery of lungs, beneath pleural surface
  • bacilli inhaled into terminal airways engulfed by alveolar macrophages
  • alveolar macrophages unable to destroy mycobacteria bc their thick cell wall resists attack
  • survival of organism allows it to multiply within macrophages
  • leads to cell death + release of more microorganisms
  • over weeks, mycobacteria spread in macrophages via blood to apices of lungs + multiple other organs such as kidneys, adrenals, bones + meninges
40
Q

Does the dissemination of tuberculosis described show in patients as they begin to be infected?

A

No - in majority (95%) of infected individuals this dissemination remains entirely asymptomatic

41
Q

What happens after a few weeks following TB infection?

A
  • T cell mediated immunity established
  • macrophages (APCs) activate mycobacteria-specific CD4+ T helper cells via MHC class II
  • the Th1 helper cells produce interferon-g
  • this cytokine is powerful activator of macrophages
  • promoting increased levels of intracellular killing
42
Q

TB: what happens following activation of macrophages?

A
  • activated macrophages aggregate around mycobacteria
  • to form granulomas
  • granulomas wall off viable organisms in an anoxic + acidic environment
  • which does not favour mycobacteria survival
  • granulomas that form in TB infection are protective
  • centre of the lesion becomes necrotic w/ an appearance like soft cheese + most bacteria die
  • lesion eventually becomes quiescent + sealed off by fibrous scar tissue (may calcify)
  • few bacilli however survive in dormant form + cause reactivation of TB months/years later
43
Q

What is the Ghon complex?

A
  • In over 95% of cases, development of specific cell-mediated immunity is protective and holds the organism in check
  • The ultimate result is a calcified scar in the lung parenchyma and the hilar lymph node
44
Q

What is active TB?

A

Where mycobacteria are growing and causing symptoms/signs of disease

45
Q

In which two main circumstances may active TB occur?

A
  • a small minority of people are unable to contain the initial infection due to an inadequate T cell immune response -> progress immediately to active TB
  • recativation of latent disease - often the underlying cause for reactivation is clear (eg. immunosuppression). However, in many cases, there is no obvious immunodeficiency + underlying reason for reactivation is unclear
46
Q

Which people are at risk of active TB?

A
  • immunocompromised individuals, particularly HIV
  • immigrants from countries w/ high rates of TB
  • elderly
  • alcoholics
  • diabetes mellitus
47
Q

Why are those with HIV particularly at risk of active TB?

A
  • HIV infects CD4 T helper cells
  • consequently CD4 count is reduced
  • impairs cell-medated immunity
  • may be reactivation of latent TB as cell-mediated immunity becomes impaired by HIV
48
Q

How is active TB related to an inappropriate T helper cell response?

A
  • a strong Th1 response is associated w/ protective immunity resulting in granuloma formation which contains infection
  • if, however, T helper cell response is more Th2 driven, an inappropriate repertoire of immune cells are recruited -> intense but ineffective immune response to organism -> extensive tissue destruction + survival of organisms
49
Q

What is the difference between active tuberculosis disease and latent infection?

A
  • Active tuberculosis disease - infection w M. tuberculosis where mycobacteria are growing + causing symptoms + signs of disease
  • Latent infection - infection w M. tuberculosis where mycobacteria are alive but not currently causing active disease
50
Q

TB can be classified into pulmonary and extrapulmonary. How does active pulmonary TB present?

A
  • presents as chronic pneumonia
  • feeling unwell for weeks/months, persistent cough
  • constitutional symptoms - fever, night sweats, app/weight loss
51
Q

How does ‘open’ tuberculosis develop?

A
  • if an enlarging focus erodes into airway
  • bacilli enter sputum
  • if major airway involved, necrotic material drains away
  • focus transforms into a cavity containing enormous numbers of organisms in cavity wall
  • patients w/ cavitating TB are particularly infectious bc their sputum contains large numbers of mycobacteria + they cough frequently
52
Q

How do you diagnose active pulmonary TB?

A
  • compatible history
  • radiological findings - CXR, CT
  • lab features
    • 3 resp samples (spontaneous, deep cough sputum)
    • sputum smear stained w/ Ziehl-Neelsen stain
    • culture remains gold standard to confirm diagnosis

problem with culture is that it takes 3-6 weeks due to slow-growing nature of organism. If clinical features are consistent w/ diagnosis of TB then treatment is started without waiting for culture results

53
Q

How is the nucleic acid amplification test beneficial in diagnosis of active pulmonary TB?

A
  • NAAT - test used to detect fragments of nucleic acid
  • allowing rapid + specific diagnosis of M. tuberculosis directly from clinical samples
  • may be indicated for a variety of reasons incl
    • if there is a clinical suspicion of TB disease
    • the person has HIV infection
    • or rapid info about mycobacterial species would alter patient’s care
54
Q

What is extrapulmonary TB?

A
  • ~ 15% cases of active TB involve other organs than lungs, most commonly in children + immunocompromised adults
  • during initital infection, haematogenous dissemination of bacilli to a number of organs can occur
  • these localised infections usually become walled off in small granulomas where mycobacteria remain dormant
  • if they reactivate at a later time -> extrapulm TB
55
Q

What are the most common sites of involvement of extra-pulmonary TB?

A
  • lymph nodes (mainly cervical + supraclavicular)
  • kidneys
56
Q

What is miliary TB?

A

patients w severely impaired immunity may develop rapidly progressive disease with wide dissemination resulting in numerous small foci of infection developing in many organs - miliary TB

57
Q

What are a few important mangement issued to take away for tuberculosis?

A
  • Antituberculous therapy should be commenced - often quadruple therapy (rifampicin, isoniazid, pyrazinamide, ethambutol - RIPE), compliance to be monitored
  • TB is a notifiable disease, so diagnosis must be notified
  • Contract tracing should be undertaken for those with active pulmonary disease
58
Q

What is atherosclerosis?

A
  • chronic inflammatory process
  • affecting intima of arteries
  • characterised by formation of lipid-rich plaques in vessel wall
59
Q

What are the important modifiable risk factors for developing atherosclerosis?

A
  • smoking
  • hypertension
  • diabetes mellitus
  • dyslipidaemia (abnormal liporotein levels)
  • obesity
  • diet
  • exercise

The top 4 risk factors damage the endothelium!

60
Q

What are the most important non-modifiable risk factors for developing atherosclerosis?

A
  • family history
  • male gender
61
Q

What results from a damaged endothelium?

A
  • becomes dysfunctional
  • there is increased permeability
  • endothelial cells produce adhesion molecules + cytokines
  • attract inflammatory cells + prothrombotic molecules
  • eg. VCAM-1 (vascular cell adhesion molecule-1) binds monocytes + T-cells
  • -> recruitment of infl cells to site of injury: monocytes + T-cells adhere to endothelium + migrate to intima
  • monocytes differentiate into macrophages
62
Q

At the site of injury, what effects do the macrophages have?

A
  • produce free radicals that drive LDL oxidation -> form oxidised LDL (which is highly atherogenic)
  • they engulf oxidised LDL and cholesterol crystals, becoming foam cells (foam cell is a macrophage containing abundant lipid in its cytoplasm)
  • foam cells produce growth factors that stimulate migration of smooth muscle cells from media to intima - this is also driven by factors released by activated platelets + endothelial cells
63
Q

How are fatty streaks formed and what is their clinical significance?

A
  • oxidised LDL accumulates within macrophages + sm muscle cells just underneath the endothelial cells
  • collections of lipid-laden macrophages sitting in the intimal layer may be visible as yellow elevations called fatty streaks
  • the fatty streak has no clinical significance
  • but is important bc it may progress -> atherosclerotic plaque
64
Q

How is the atherosclerotic plaque formed?

A
  • core of lipid debris forms as foamy macrophages die + lipid in cytoplasm released
  • smooth muscle cells proliferate + change their behaviour
  • they secrete collagen + other ECM proteins
  • resulting in formation of fibrous cap over core
  • the core is composed of oxidised lipid + infl cells
  • the cap represents the body’s attempt to repair by scarring
65
Q

How does atherosclerosis exhibit the three hallmarks of a chronic inflammatory process?

A
  • persistent injury (endothelial damage due to prev desc risk factors)
  • on-going inflammation (macrophages + lymphocytes)
  • repair with scarring (fibrous cap of plaque)

*Medicine: Cellular Pathology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions