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TMS > Lung Fibrosis > Flashcards

Lung Fibrosis Flashcards

1
Q

what are the 5 type of cells present in the bronchial epithelium?

A
  1. ciliated
  2. goblet
  3. basal
  4. intermediate
  5. Clara
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2
Q

what are the two types of cell present in alveolus?

A
  1. Type I cell

2. Type II cell

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3
Q

what is the mechanism of breathing in/inspiration?

A

Inspiration

  1. External Intercostals - contract
  2. Internal Intercostals - relax
  3. Ribs and Sternum move upwards and outwards
  4. Diaphragm contracts and lowersIncrease in chest depth & volume
  5. As Lungs expand the pressure inside the lungs decreases
    - Therefore air rushes in, to balance pressure difference
  6. External intercostal contract and ribs lift up and out
  7. Diaphragm flattens + increases thoracic volume
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4
Q

what is the mechanism of expiration/breathing out?

A

Expiration

  1. relaxing the inspiratory muscles
  2. Gravity lowers ribs + sternum
  3. Lungs recall as diaphragm relaxes + returns to dome shape
  4. Reduced space in thorax increases air pressure
  5. Air in lungs is forced out
  6. Intercostals relax + ribs return to resting position
  7. Diaphragm re-domes + decreases thoracic volume
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5
Q

what happens to the following in breathing in and out?

  1. chest
  2. diaphragm
A 
breathing in 
1. chest - expands 
2. diaphragm- contracts 
breathing out 
1. chest - contracts 
2. diaphragm - relaxes
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6
Q

what is pulmonary fibrosis?

A

it is the end stage of a heterogenous group of interstitial lung disease

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7
Q

what is survival rate for IPF?

A

mean survival is 2-3 years

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8
Q

what is fibrosis?

A

accumulation of extracellular matrix

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9
Q

how is an IPF lung different from normal lung?

A
  1. scarred tissue- pale looking
  2. healthy tissues replaced by excessive matrix
  3. distorted airways - vulnerable to infection
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10
Q

what are the symptoms of IPF?

A
  1. dyspnoea - shortness of breath
  2. coughing (dry)
  3. fever
  4. weight loss
  5. clubbing (thickening of finger tips)
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11
Q

what does the physical examination consists of in IPF?

A

lung sounds -

  1. velcro sounds
  2. pleural rub
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12
Q

what are the management techniques for a patient with IPF?

A

Key management decisions

  1. administration of pharmacological agents
  2. monitoring of the disease (how)?
  3. decision of whether a patient should be refried for lung transplant
  4. state of the disease for e.g. whether it is the end stage and unlikely to respond to therapies then providing plaintive care is best approach
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13
Q

how is IPF monitored?

A
  1. pulmonary function tests

2. thoracic imaging - HRCT to measure the severity of disease

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14
Q

what does pulmonary function test include?

A
  1. FVC
  2. oxyhemoglobin saturation
  3. 6-minute test
  4. DLCO - lung diffusion capacity for CO
  5. FEV1/FVC ratio
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15
Q

briefly outline the pathomechanism for IPF

A
  1. epithelial cell injury |
  2. inflammation coagulation cascade activation (TF/FVIIa/FXa-> thrombin)
  3. establishment of chemokine networks, leukocyte infiltration and AEC proliferation (chemokine, ROS, TGFbeta, PDGF)
  4. fibroblast recruitment, proliferation and differentiation
  5. loss of organ function
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16
Q

what are the characters of ideal IPF model?

A
  1. mimics the key pathological features of IPF (like hyperplasia, fibroblastic foci,AECII)
  2. is progressive and fatal
  3. relative paucity of granulocytic inflammation?
  4. prone to acute exacerbations
  5. ideal for drug discovery
17
Q

what are the features in IPF model for drug discovery?

A
  1. large therapeutic window
  2. high throughput, reproducible
  3. low resource intensity
  4. can be established across multiple species
18
Q

which the most commonly used model for PF?

19
Q

what are the characteristics and fibrotic response of bleomycin?

A 
Characterics 
1. drug administered intratracheally
2. multiple species - mice, rats, rabbits etc 
Fibrotic response 
1. time frame: a few weeks 
2. doubling in lung collagen
20
Q

what are the two types pf CT used for imaging the lints in IPF?

A
  1. HRCT - commonly used in hospitals

2. mciroCT - commonly used in research to study detailed pathogy for better resoltuion

21
Q

what does acute exacerbation of IPF result in?

A
  1. major driver of IPF mortality
  2. diffused alveolar damage on background of UIP
  3. alveolar haemorrhage
22
Q

what is the incidence and mortality rate of IPF?

A

incidence - 5-19% patient/year

mortality - >80% (majority of patients die within a month)

23
Q

which viruses have b?een detected in IPF lungs?

A

Using PCR on lung tissue
1. herpes simplex virus
2. epstein-barr virus
3. human herpes virus 7 and 8 (HHV-7 and HHV-8)
4. cytomegalovirus
using immunohistochemcistry
1. EBV and HHV-8 antigen localised in airway epithelial cells

24
Q

what are the features of herpes virus?

A
  1. 8 members in herpes virus family
  2. ubiquitous (found everywhere)
  3. complex structure - consists of
    a. ds DNA
    b. toroidal shape
    c. icosahedral nucleocaspid
    d. tegument (covering)
25
what is the immune response to a viral infection?
1. presentation of viral antigen by the infected cells to pre-cytotoxic CD8+ via MHCI -> activation of effector CTL 2. release of perforins _ granzymes by the activated cell (effector CTL) to induce apoptosis of infected cell 3. phagocytosis of viral antigens by APC + APC presents viral antigens to CD4+ via MHCII 4. These CD4+ cells differentiate into Th1+ cells and release cytokines (IL-2,IL-12, IFN-gamma, TNF-alpha) which enhances the proliferation of CD8+ cells 5. these CD4+ can activated by APC can also differentiate into Th2 cells which produce cytokines (IL-4,IL-5, IL-6, IL-10 and TGF-beta) to facilitate the differentiation of B cells 6. viral antigens can be detected b y B cells also which present the antigens to Th2 cells via MHCII and co-receptor CD28 7. these activated B cells also differentiate into plasma cells for ab production and memory B- cell for immune memory
26
which human virus is used for exacerbation of IPF in bleomycin? on which day is it administered?
the virus gammaHV68 is used exacerbation and it is administered on Day 14
27
what are the non-pharmaceutical treatments for IPF?
1. self care - stop smoking - pneumococcal and seasonal influenza vaccinations 2. oxygen therapy - nasal tube or mask and oxygen concentrator 3. pulmonary rehabilitation - supervised programme that includes - health education - physical exercise - breathing exercises - advice on nutrition - psychological support, social support network 4. Lung transplant - 50%with five year survival rate following transplantation
28
define tissue repair in reference to IPF?
the regeneration of damaged tissue by parenchymal cells of same type or replacement by connective tissue - however, this goes wrong in fibrosis
29
what are the causes of tissue damage?
1. trauma 2. infection 3. physical and chemical agents (e.g. heat and acid) 4. tissue necrosis 5. foreign bodies 6. immune reactions (hypersensitivity reactions)
30
what is order of events in tissue repair/wound healing?
1. haemostats 2. inflammation 3. proliferation 4. re-modelling
31
``` During aberrant wound healing (lung fibrosis), which cells types are important? A.Epithelium B.Macrophages C.Fibroblasts D.Myofibroblasts E.Endothelial cells F.All of the above ```
F. All of the above
32
what are the features of extracellular matrix?
1. provides structural support 2. regulated the movement and growth of cells 3. consists of a. collagen - tensile strength (resistance of material to break under tension) b. elastin - elastic stretch and recoil c. proteoglycans - regulate ECM structure and permeability, modulate cell growth and bind GFs d. adhesive glycoproteins - fibronectin, laminin e. integrins - major cell surface receptor family, mediating cell adhesion to ECM
33
what are the pharmaceutical treatments available for IPF?
1. tyrosine kinase inhibitors 2. antifibrotic inhibitors 3. anti viral therapy
34
which drug is used as tyrosine kinase inhibitors and its mechanism?
- nintedanib | - inhibits PDGF receptors alpha and beta, VEGF1,2,3 and FGFR 1,2,3
35
which drug is used as anti fibrotic agent and its mechanism?
- pirfenidone - novel compound with combined anti-ifnlmmatory and antioxidant properties - mechanism is not fully understood yet
36
which drug is used as anti viral therapy and its mechanism?
- ganciclovir | - 2 week therapy might temporarily attenuate disease progression
37
what are the two life eyes of herpes virus?
1. latent (inactive) | 2. lytic (active for lysis)
38
what is bleomycin and how does it work? what are its advantaged and disadvantages?
it is an IPF model where antibiotic induces lung injury and fibrosis Advantages - best charactered model, clinically relevant, multiple delivery route Disadvantages - fibrosis does not develop in all animals, long timeframe, disease may be self limiting

TMS (10 decks)

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