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Human Diseases > W5 24 respiratory tract pathology > Flashcards

W5 24 respiratory tract pathology Flashcards

1
Q

What is COPD?

A

Characterised by 2 disorders Co-existing:
Emphysema and chronic bronchitis

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2
Q

What is emphysema?

A

Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles

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3
Q

What is chronic bronchitis?

A

Persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Tends to affect more proximal, larger airways.

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4
Q

What are the aetiological causes of COPD?

A

Biggest factor = cigarette smoking
Less common - other inhaled toxins, inherited deficiency of alpha 1 antritrypsin

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5
Q

What is the pathogenesis of emphysema? (PG262 IMG)

A

(some genetics as not everyone who smokes will develop it)
Toxin-induced injury to epithelial and mesenchymal acinar cells induces inflammation
Inflammatory cells cause more cell injury in the lung and produce substances that degrade the extra-cellular matrix
Damaged mesenchymal cells are unable to repair the extra-cellular matrix, resulting in destruction and enlargement of the airspaces. (Healthy mesenchymal cells like fibroblasts would be able to produce collagen and other EVM components to repair the damage).

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6
Q

What are some mediators of emphesyma and what do they do?

A
  • elastases degrade surrounding tissues, oxidants do similarly, cytokines promote inflammation
  • counter-balancing these mediators are antioxidants and alpha1-antitrypsins, to work against degrading enzymes to prevent tissue damage. thus inherited alpha1antitryosin defect means they will be unable to prevent some of the damage that occurs due to these enzymes
  • TGF-b and matrix metalloproteinases are important mediators in the laying down of fibrosis and remodelling of collagen. If affected, alveolus is unable to repair from the damage.
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7
Q

What is the morphological difference between cigarette smoking emphysema and alpha1-antitrypsin deficiency?

A

Cigarette smoking causes centriacinar emphysema - affecting upper 2/3 of lungs - larger respiratory bronchioles and spares distal alveolar structures
Alpha1-antitrypsin deficiency causes panacinar emphysema, affecting the lower lungs

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8
Q

What is the pathogenesis of chronic bronchitis?

A

Toxins cause epithelial injury in bronchioles which stimulates inflammation by lymphocytes, macrophages and neutrophils, and damage to surrounding tissues
Inflammation induces mucous (squamous) metaplasia of respiratory epithelium, mucus hypersecretion and bronchiolar wall fibrosis

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9
Q

What happens in the trachea and larger bronchi compared with the smaller bronchi and bronchioles in chronic bronchitis?

A

Trachea and larger bronchi - enlargement of mucus secreting glands. Squamous metaplasia of respiratory epithelium.
Smaller bronchi and bronchioles - goblet cell metaplasia results in mucus plugging. Inflammation. Fibrosis.

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10
Q

What type of reaction is asthma?

A

Type I hypersensitivity reaction with excessive TH2 response

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11
Q

Briefly, what are the pathological stages of asthma?

A

Initiation/sensitisation
Re-exposure - immediate phase, late phase

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12
Q

What is the aetiological cause for asthma?

A

An abnormal response to an allergen (most commonly pollen, dust etc)

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13
Q

What happens when an allergen interacts with the mucosal lining of the respiratory tract?

A

The antigen from the allergen interacts with the mucosal lining of the respiratory tract. Components of that allergen are recognised by dendritic cells (APCs). These will internalise those antigens and represent them in MHC class II molecules, for presentation for CD4+ T cells.

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14
Q

What is the problem in asthma - initiation/sensitisation stage?

A

The response of the T helper cells is driven towards a TH2 response, which is mainly designed to deal with large extracellular pathogens. Under the influence of interleukins like IL4, a TH2 response is generated in asthma. This results in:
- B cells are stimulated to produce IgE which recognises the allergen present in the pollen. This binds to mast cells and sits there awaiting further binding of the allergen.
- activated mast cells will release some IL5, which recruits eosinophils, so there will be some inflammation present (but generally not significant)

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15
Q

What happens in re-exposure, the immediate phase?

A

(when the main disease begins to show)
Antigen-induced cross-linking of IgE bound to mast cells in the airways

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16
Q

What mediators do mast cells release and what is their action? (Pg265 image)

A

Histamine, platelet activating factor, leukotrienes, PGs - these increase vascular permeability, bronchospam (via vagus nerve activation) and mucus production (from goblet cells)
Chemokines, TNF, leukotriene B4 - leukocyte recruitment

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17
Q

What is the main driver of the disease asthma?

A

The release of the mast cell mediators is the main driver of the disease

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18
Q

How are mast cells activated?

A

Mast cells which already have the IgE antibody bound to them will bind the allergen as it is exposed to the mast cells which are present beneath the epithelium of the respiratory lining. The allergen binds to the antibodies and activates the mast cells.

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19
Q

When does the late phase of re-exposure occur?

A

Within hours of exposure

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20
Q

What happens in the late phase of re-exposure?

A

Recruited neutrophils, eosinophils, basophils, lymphocytes and monocytes cause further inflammation - a dense inflammatory response, traversing the vascular endothelium in the respiratory tissues.
Epithelial cells damaged by factors released from eosinophils.
Large amount of mucous produced by the goblet cells

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21
Q

The longer the process and the more severe the inflammation, the more marked the histological and morphological changes in asthma. What is the end result of the inflammatory processes?

A

Bronchial occlusion by mucous plugs in lumen of airways (airway obstruction)
Eosinophil rich inflammation
Airway remodelling

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22
Q

How is the airway remodelled in asthma? (PG266 COMPARISON)

A

Thickening of the airway wall - driven by healing and repair and fibrosis
Sub-basement membrane fibrosis
Increased vascularity - by ongoing inflammatory mediators release from activated mast cells
Goblet cell metaplasia - from damaged epithelium
Increased number of submucosal glands - mucosal hypersecretion
Hypertrophy and/or hyperplasia of bronchial smooth muscle cells (becomes chronic from bronchospams in early presentation)

23
Q

What is pneumonia?

A

Infection of the lung

24
Q

What is the brief pathogenesis of pneumonia?

A

Normal defence mechanisms become overwhelmed by infection

25
Q

What are the classifications of pneumonia?

A

Community acquired pneumonia (CAP)
Atypical pneumonia
Nosocomial pneumonia
Chronic pneumonia
Necrotising pneumonia and lung abscess
Pneumonia in the immunocompromised host

26
Q

What are the innate immune system lung defence mechanisms?

A

Mucociliary elevator - cilia on respiratory epithelial cells waft mucous upwards (with bacteria trapped)
Phagocytosis by alveolar macrophages - engulf bacteria and pathogens
Neutrophil recruitment - to areas of infection in lung to destroy pathogen
C3b opsonisation - part of complement cascade, can target bacteria for destruction
Antigen presentation - APCs can present bacterial antigens to lymph nodes to drive the adaptive immune response

27
Q

What are some adaptive immune system lung defence mechanisms?

A

Secreted IgA in the upper airways - to bind and degrade bacteria in the airways
C3b and IgG opsonisation (classical pathway) - can bind to bacteria and target them for destruction
T-cell recruitment - recruited to area of inflammation to cause further inflammation and degrade the pathogen

28
Q

What is the most common cause for community acquired pneumonia (CAP)?

A

Streptococcus pneumoniae

29
Q

What are the risk factors for CAP?

A

Underlying chronic disease (eg COPD, diabetes, heart disease)
Immunodeficiency
Reduced/absent function of spleen

30
Q

What are the 2 anatomic patterns of CAP?

A

Bronchopneumonia - results from infection of bronchi and bronchioles with extension into adjacent alveoli. Tends to be multifocal.
Lobar pneumonia - results from homogenous infection of contagious airspace
Underlying pathogenesis is the same.

31
Q

What are the 4 pathological stages of CAP and their macroscopical appearance?

A
  1. Congestion - heavy, red and baggy
  2. Red hepatisation - liver-like consistency, becomes more dense and firm
  3. Grey hepatisation - dry, grey and firm
  4. Resolution (in healthy tissue) - normalisation of lung appearance (maybe some scarring)
32
Q

What are the 4 stages of CAP and their microscopical appearance?

A
  1. Congestion - congestion, fluid, neutrophils, bacteria - early stages of acute inflammation causing vasodilation and oedema from increased BV permeability
  2. Red hepatisation - alveolar spaces packed with neutrophils, erythrocytes (from haemorrhage) and fibrin
  3. Grey hepatisation - persisted fibrin and neutrophils but lysis of erythrocytes
  4. Resolution (in healthy tissue) - digested granular debris, fibroblast proliferation
33
Q

What are the commonest aetiologies for atypical pneumonia?

A

Mycoplasma pneumonia (bacterium)
Viruses - influence, adenovirus, coronavirus

34
Q

What is the pathogenesis of atypical pneumonia?

A

Attachment of organisms to respiratory epithelium (overwhelming normal host defences causing infection)
Inflammation largely confined to the walls of the alveoli!

35
Q

What is the commonest aetiological agent for chronic pneumonia?

A

Mycobacterium tuberculosis (bacterium)

36
Q

What is chronic pneumonia?

A

Persistent (chronic) infection of the lung

37
Q

What are the risk factors for tuberculosis?

A

Poverty
Malnutrition
Chronic disease
Immunosuppression

38
Q

What is primary tuberculosis?

A

Develops in a previously unexposed host. Normally doesn’t result in clinically significant disease.

39
Q

What is secondary tuberculosis?

A

Develops in a minority of previously sensitised hosts, often years after primary infection. Usually occurs due to weakened host resistance.

40
Q

What is the pathogenesis of primary tuberculosis?

A

M. tuberculosis inhaled from airborne aerosols is engulfed by alveolar macrophages sitting in alveolar spaces. This TB bacteria is able to inhibit normal microbicidal responses by preventing phagolysosome formation. This results in unchecked bacillary proliferation in alveolar macrophages and airspace’s, leading to bacteraemia and seeding to other sites.

41
Q

What happens about 3 weeks after initial bacterium inhalation in TB?

A

Processed mycobacterial antigens are presented to CD4+ T cells in lymph nodes by dendritic cells and macrophages secreting IL-12 (takes long since bacteria are good at evading host mechanisms).
Induces TH1 phenotype and production of IFN-y, activating macrophages to produce NO and free radicals, having a bactericidal effect with TNF, leading to monocyte recruitment and granuloma formation.
(controlled, bacteria not eradicated)

42
Q

What are the consequences of primary tuberculosis?

A

Cell-mediated immunity and resistance
Potential for development of secondary TB if host defences are weakened.
Can occasionally lead to progressive primary tuberculosis if infection cannot be controlled

43
Q

What is the aetiology of secondary tuberculosis?

A

Direct progression of primary TB
Reactivation of dormant primary lesions
Exogenous reinfection

44
Q

What is the pathogenesis of secondary TB?

A

Elicits a prompt and florid tissue response that walls off the focus but also causes localised erosions (since the immune system is already familiar with the bacterium)
This can damage bronchi, blood vessels and lymphatics, allowing widespread dissemination of the infection

45
Q

What is the aetiology of lung cancer?

A

Mostly cigarette smoking
Other: asbestos exposure, heavy metals, coal, radiation, air pollution etc

46
Q

What is the pathogenesis of lung cancer?

A

Carcinogens in cigarette smoke cause a stepwise accumulation of genetic abnormalities. Eg lint mutations, amplifications, deletions, translocations, aneuploidy, epigenetic change

47
Q

What are some common gene alterations in lung cancer?

A

3p deletion, EGFR mutation, KRAS mutation, TP53 mutation, ALK translocation
Can cause loss of tumour suppressor genes or oncogenes.

48
Q

Why don’t all smokers get lung cancer?

A

Certain (favourable) P-450 polymorphisms give an increased capacity to metabolise pro-carcinogens from cigarette smoke. Protects heavy smokers.

49
Q

Describe how squamous metaplasia is a precursor lesion for lung cancer?

A

(3p deletion)
Under long term persistent irritation, normal ciliated columnar epithelium (respiratory epithelium) becomes metaplastic into squamous epithelium. This is better protected against the toxins of cigarette smoke however the metaplastic epithelium is not immune to the mutagenic features of the toxins. Metaplastic tissue is predisposed to develop mutations and cancer.

50
Q

What is dysplasia and how is it a precursor lesion to cancer?

A

Dysplasia is accumulation of further mutations. Cytological have features of malignancy: nuclear enlargement, hyperchromasia, loss of normal maturation. Atypical cells. Confined by the basement membrane, not invading the stroma, so pre-cancerous change. Theoretically if detected and remove could prevent cancer but not practically possible.

51
Q

What are the microscopic subtypes of lung cancer?

A

Small cell neuroendocrine carcinoma
Adenocarcinoma (non-small cell)
Squamous cell carcinoma

52
Q

Where are adenocarcinomas and squamous cell carcinomas located and characterised by?

A

Adenocarcinomas - often peripherally located and characterised by gland formation
Squamous cell carcinomas - often centrally located in major bronchi and characterised by keratin formation.

53
Q

What are the local effects of lung cancer and the mechanism how it causes this?

A

Pneumonia - tumour obstruction of airways
Pleural effusion - tumour spread to pleura
Hoarseness - recurrent laryngeal nerve invasion
Dysphagia - tumour invasion of oesophagus
Superior vena cava obstruction - direct tumour invasion/compression
Horners syndrome - direct invasion of sympathetic ganglia
Pericarditis - tumour invasion of pericardium

54
Q

Lung cancer can cause paraneoplastic hormone production. What are the hormones, the effect and the associated cancer with it?

A

ADH - hyponatremia (SIADH) - associated with small cell cancer
ACTH - Cushing syndrome - associated with small cell cancer
PTH-related peptide prostaglandin E - hypercalcaemia - associated with squamous cell cancer

Human Diseases (75 decks)

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