Respiratory System Pathology Flashcards
Define infectivity.
The proportion of persons exposed to an infectious agent who become infected.
Define incubation period.
The time elapsed between exposure to a pathogen and when symptoms start to occur. People are usually non-infectious during the incubation period.
Define virulence.
The ability of any agent of infection to produce disease. It depends upon the ability of the pathogen to adhere, colonise, invade, escape from the immune response, and produce toxins.
Define attenuation.
The alteration of virulence of a pathogen by passage through another species, or serial passage in vitro. This decreases the virulence of the pathogen for the host, e.g. BCG, MVA, live polio vaccine.
List some myxoviruses
(muxo→myxo:mucous, reacts with mucin on erythrocytes)
- Influenza (A,B,C)
- Parainfluenza (1,2,3,4)
- Respiratory Syncytial Virus
- Coronavirus
- Rhinoviruses (>100 types)
- Coxsackie Virus A
- Coxsackie Virus B
- Echoviruses
- Adenoviruses (1,2,3,5,7,14,21 responsible for respiratory illnesses
- Mycoplasma pneumoniae
What are the types of upper respiratory inflammatory diseases?
- Acute rhinitis (common cold, allergic rhinitis, bacterial infection)
- Sinusitis (inflammation of paranasal sinuses)
- Laryngitis (inflammation of larynx)
- Pharyngitis (inflammation of pharynx)
- Acute epiglottits (caused by Haemophillus influenzae)
List some upper respiratory neoplastic diseases.
- Nasopharyngeal carcinoma (Epstein-Bar virus)
- Laryngeal papilloma
- Squamous cell carinoma of larynx (most common larynx tumour, associated with smoking)
Outline influenza.
- Caused by influenaza viruses (A,B,C)
- Targets the upper and lower respiratory epithelium, causing the airway to become red, reflecting acute inflammation and cngestion of the mucosa.
- 5-10% annual attack rate in adults and 20-30% in children.
- Symptoms: sudden onset high fever, dry cough, headache, muscle pain, severe malaise, sore throat and runny nose.
- Young and old people, people with weakened immune systems, and pregnant women are most at risk.
- Transmitted through cough droplets that can be breathed in.
Outline the influenza virus.
- Family: orthomyxoviridae
- -ve RNA virus, enveloped, segmented genome (8).
- Type A (humans, birds, pigs, horses), Type B (humans), Type C (humans). Type A and B are much more common than C, hence there only being seasonal vaccines for A and B.
- Viral subtypes are distinguished by their surface proteins haemagglutanin (HA) and neuraminidase (NA). 16 HA subtypes, 9 NA subtypes (HA1,2,3 and N1,2,8 in humans)
How are the viral proteins on the surface of influenza involved in pathogenesis?
- Haemagglutanin and neuraminidase are present on the surface of influenza viruses.
- HA agglutinates certain species of erythrocyte and binds to sialic acid sugars on the surface of epithelial cells. The HA protein contains two parts: HA<strong>1</strong> globular head, and HA<strong>2</strong> polypeptide linked by a single basic amino acid.
- Neuraminidase allows the virus to be released from the host cell. Catalyses the cleavage of sialic acid and an adjacent sugar residue from glycoproteins in the mucous; allows the virus to permeate through the mucin overlying epithelial surfaces.
What is the difference between antigenic drift and antigenic shift? How do these play parts in the influenza virus?
- Associated with influenza type A
- Antigenic drifts are small changes in the viruses genetic material that happen as the virus replicates, whereas antigenic shift is an abrupt change in the virus which may result in new HA/N proteins in influenza from acquisition of a complete new RNA segment 4 and/or 6.
- Every time the influenza virus replicates there may be small changes to the genome; this is why annual vaccines are needed. Any epidemics are short-term.
- Antigenic shifts in influenza lead to pandemics as people usually have little or no protection against the new combination of viral protein. The pandemics are usually prolonged, e.g. Swine flu (H1N1, 2009), Asian flu (H2N2, 1957), Hong Kong flu (H3N2, 1968)
What are the criteria for establishing a new pandemic of influenza virus in humans? [4]
- A novel virus, with a new haemagglutanin subtype (antigenic shift)
- Association with disease
- Susceptible population
- Ability of virus to transmit from person to person
What are the risk factors for the acquisition of zoonotic avian or non-human influenza A?
- Close/direct contact with diseased poultry/domestic fowl
- Close/direct contact with diseased mammalian species with unusual influenza A viruses (swine, seals)
- Inhalation, ingestion or mucosal contact with infectious material
What does the seasonal flu vaccine contain?
- one A (H3N2) virus
- one A (H1N1) virus
- one B virus
What drugs are available to treat the flu?
- Zanamivir: neuraminidase inhibitor (effective against A and B)
- Oseltamivir: neuraminidase inhibitor (treat and prevent A and B)
- Amantadine: inhibitors of viral M2 protein
List some lower respiratory diseases.
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Pneumonia
- Bronchopneumonia
- Lobar pneumonia
- Interstitial pneomonia
- Bronchitis
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Lung cancer
- Non-small cell lung cancer (NSCLC)
- Small cell lung cancer (SCLC)
What are the signs and symptoms of a lower respiratory disease?
- Cough
- Sputum
- Haemoptysis (blood in sputum)
- Wheezing
- Breathlessness
- Chest pain
- Cyanosis (<5g/dl deoxygentated heamoglobin)
- Clubbing of fingers (Lung abscess, bronchogenic carcinoma)
What are the different classifications of pneumonia?
- Aetiology: Bacterial, viral, fungal
- Morphology: Bronchopneumonia vs. lobar pneumonia
- Community acquired vs. hospital acquired
- Opportunistic pneumonia infections
What are the pathological stages in lobar pneumonia? What causes them and how are they characterised?
- Red hepatisation: earliest stage of pneumococcal pneumonia where protein-rich oedema containing numerous organisms fills the alveoli. Capillary congestion causes outpouring of polymorphonuclear leukocytes (PMNs) and intra-alveolar haemorrhage. The lung becomes firm and red, reminiscent of the liver.
- Grey hepatisation: occurs after 2 or more days and involves the lysis of the PMNs and appearance of macrophages that phagocytise fragmented neutrophils and other inflammatory debris. At this stage congestion has diminished, but the lung is still firm.
- Resolution: Enzymatic lysis and removal of fibrin via sputum that begins 8-9 days without antibiotics. The condition suddenly improves.
What are the causative organisms of interstitial pneumonia? [6] Outline its pathogenesis.
Interstitial pneumonia is most commonly caused by viruses, although other organisms may also cause significant interstitial inflammation. These include Cytomegalovirus, measles infection, varicella infection, herpes simplex, adenovirus pneumonia, influenza virus.
Type I cells (squamous) are the most sensitive to damage, and their loss of integrity leads to intra-alveolar oedema. The proteinaceous exudate and cell debris form hyaline (pink-staining tissue) membranes, and type II cells (produce surfactant) multiply to line the alveoli. Interstitial inflammation is characterised mainly by mononuclear cells, it generally resolves, but occasionally progresses to interstitial fibrosis.
Outline the pathology and pathogenesis of lung abscesses.
A lug abscess is a localised accumulation of pus accompanied by the destruction of pulmonary parenchyma (functional tissue), including alveoli, airways and blood vessels.
Pathology: Range from 2-6 cm, 10-20% have multiple cavities. They have a high level of PMNs and variable number of macrophages (depending on lesion age). Surrounded by haemorrhage, fibrin and inflammatory cells, a fibrous wall forms around it as it ages.
Pathogenesis: two conditions needed- large number of anaerobic bacteria in oral flora, and cough reflex/tracheobronchial clearance impaired. Alcoholism is the most common predisposing factor, also drug overdose, epileptics at increased risk. Other causes include necrotising pneumonias, bronchial obstruction, infected pulmonary emboli, penetrating trauma, extension of infection from adjacent lung.
What are some of the genetic alterations in the pathogenesis of lung cancer? What changes are observed in tissues?
- K-ras oncogene: adenocarcinomas, large cell tumours, less commonly squamous cell carcinoma. Correlates with smoking and poor prognosis.
- Myc oncogene: overexpression in 10-40% of SCCs, rare in other types.
- Bcl-2: antiapoptotic protooncogene expressed in 25% of squamous cell carcinomas, 10% adenocarcinomas.
- Rb and p53: in both in 80% SCCs, less frequent in NSCCs.
Outline squamous cell carcinoma.
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Primary lung cancer
-
Non-small cell lung cancer (NSCLC) (80%)
- squamous cell carcinoma (~35%)
-
Non-small cell lung cancer (NSCLC) (80%)
Smoking increases risk by 25%, males>females, survival 5 years 15-20%, arises in bronchial squamous metaplasia.
Centrally located, may cavitate (10%), local spread common, metastatic spread late.
Outline bronchioalveolar carcinoma.
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Primary lung cancer
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Non-small cell lung cancer (NSCLC) (80%)
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Adenocarcinoma (~35%)
- Bronchioalveolar carcinoma (2%)
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Adenocarcinoma (~35%)
-
Non-small cell lung cancer (NSCLC) (80%)
Arises from smoking, males=females, survival 5 years 25-40%.
Single/multiple tumour nodules, miliary ( accompanied by a rash with lesions resembling millet seed) tumour, pneumonic form.
Explain how TNM staging works.
A system for stage grouping of non-small cell lung cancer by primary tumor, regional lymph node, and distant metastasis (TNM) was developed by the International System for Staging Lung Cancer in 1986.
T0 No evidence of tumour
Tis Carcinoma in situ
T1 Primary Tumour ≤ 3cm
T2
- Primary tumour > 3cm or
- Tumour invades visceral pleura or
- Partial collapse of lung
T3
- Tumour of any size invading chest wall, diaphragm, mediastinal pleura or parietal pericardium
- Tumour in the main bronchus not involving carina but extending within 2cm of it or associated with collapse of entire lung
T4 Tumour invading mediastinum, heart, great vessels, trachea, oesophagus, vertebrae
No lymph node not involved
N1 Metastatic tumour in same side intrapulmonary or hilar lymph nodes
N2 Metastatic tumour in same side mediastinal or subcarinal nodes
N3 Metastatic tumour in contralateral side mediastinal or hilar nodes or supraclavicular nodes
M0 No distant metastasis; M1 Distant metastasis
Diagnose:
Adenocarcinoma
Peripheral location, arises from bronchial epithelium, tubular growth pattern, hyperchromatic.
Diagnose:
Bronchoalveolar Carcinoma
Tumour nodules, columnar cells proliferated along alveolar septae.
Diagnose:
Small cell carcinoma
‘oat-cells’, small dark blue cells with minimal cytoplasm packed together
Diagnose:
Squamous cell carcinoma
Locally spread, centrally located, nests of polygonal cells with pink cytoplasm and distinct borders, nuclei hyperchromatic and angular, ‘kreatin pearls’ (arrow)
