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
Outline the differences between bronchopneumonia, lobar pneumonia, and interstitial pneumonia.
- Bronchopneumonia: the acute inflammation of the walls of the bronchioles
- Lobar pneumonia: pneumonia affecting a whole lobe of the lung
- Interstitial pneumonia: inflammation of the squamous epithelium
What are the causative organisms of lobar pneumonia? Outline the pathogenesis.
Streptococcus pneumoniae (pneumococcus) and Klebseilla pneumoniae can cause lobar pneumoniae (pneumococcal pneumonia), more frequently following a viral infection such as influenza. Largely due to antibiotic therapy, the involvement of the lung tends to be incomplete.
Change in oropharyngeal flora in immunodepressed may lead to pneumonia. Conditions that predispose infection: cigarette smoking, chronic bronchitis, alcoholism, malnutrition, wasting disease, poorly controlled diabetes.
Bronchial secretions stimulated by viral infection provide a hospitable environment for S.pneumoniae proliferation. Thin, watery secretions carry it from the nasopharynx to the alveoli, initiating an inflammatory response.
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 symptoms of pneumococcal (lobar) pneumonia? What are the complications? [7]
- Symptoms: high fever, cough, shortness of breath, rapid breathing, chest pains.
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Complications include:
- Abscess formation
- Failure of resolution can lead to intra-alveolar fibrosis and loss of ventilatory function
- Pleuritis (inflamed lung pleura)
- Pleural effusion (abnormal amunt of fluid between lung and pleura due, due to inflammation in pneumonia)
- Pyothorax (infecion of pleural effusion)
- Empyema (collection of pus in cavity in pleura following from pyothorax)
- Bacteraemia (bacteria in blood)
What are the causative organisms of bronchopneumonia (staphyloccocal pneumonia)? Outline the pathology.
- Caused by Staphylococcus aureus, Haemophilus influenzae, Streptococcus, Klebsiella pneumoniae (hospital acquired)
- Staphylococcus infection is a common superinfection (following infection) after influenza and other viral RT infections.
- Staphylococcal pneumonia is characterised by the production of many small abscesses. More often in infants than adults these can lead to pneumatoceles (cystic spaces lined with respiratory tissue), which develop when an abscess breaks into an airway.
- Cavitation and pleural effusions are common complications, empyema is infrequent.
- Predisposing conditions: young/old age, viral infections, aspiration of food, bronchus obstruction, inhalation of irritant gas, major surgery, malnutrition.
What are common causes of viral pneumonia?
Approximately 1/3 of all pneumonia cases are caused by a virus. Some of these include:
- Influenza
- Parainfluenza
- Adenovirus
- Respiratory syncytial virus (RSV) (mostly in children)
- Cytomegalovirus in the immunocompromised.
Most commonly viruses cause interstitial pneumonia.
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.
How is smoking related to cancer?
Lung cancer is the leading cause of cancer deaths worldwide, with nearly 1 million new cases diagnosed each year. It is the third most common cause of death in the UK after heart disease and pneumonia.
Lung cancer is directly related to smoking, and the risk is directly related to the amount of cigarettes smoked. 25% of the US population smokes, and over 40 carcinogens are in cigarette smoke. Up to 40% of newly diagnosed lung cancers occur in former smokers.
List some of the causative agents of lung cancer.
- Cigarettes (90%)
- Asbestos
- Radon (radioactive gas from decay of uranium, thorium, radium in rocks in soil)
- Chemicals containing chromium and nickel, arsenic and coal tar.
- Radiation
- Passive smoking
- Prior lung disease (e.g. tuberculosis)
- Age (>65 years)
What are the two major divisions of lung cancer? What are further subdivisions?
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Primary lung cancer
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Non-small cell lung cancer (NSCLC) (80%)
- squamous cell carcinoma (35%)
- adenocarcinoma (35%)
- large cell lung cancer (10%)
- Small cell lung cancer (SCLC) (20%)
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Non-small cell lung cancer (NSCLC) (80%)
- Secondary lung cancer (spread from another primary site)
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
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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 adenocarcinoma.
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Primary lung cancer
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Non-small cell lung cancer (NSCLC) (80%)
- adenocarcinoma (~35%)
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Non-small cell lung cancer (NSCLC) (80%)
Smoking increases risk x3, occurs more often in non-smokers than quitters, males>females, survival 5 years 10-15%, arises from mucosal cells in bronchial epithelium.
Periperal location, commonly associated with asbestosis, metastases to brain, adrenal gland, and bone.
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%)
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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.
Outline large cell carcinoma.
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Primary lung cancer
-
Non-small cell lung cancer (NSCLC) (80%)
- large cell lung cancer (10%)
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Non-small cell lung cancer (NSCLC) (80%)
Peripheral lesion associated with early metastasis, survival 5 years 10-15%, cells less diffrentiated, tumours do not fit criteria of squamous cell, adeno-, or small cell carcinoma.
Outline small cell carcinoma (SCLC).
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Primary lung cancer
- Non-small cell lung cancer (NSCLC) (80%)
- Small cell lung cancer (SCLC) (20%)
Caused by smoking in 95% of patients, survival 5 years 1-5%, may secrete polypeptide hormones, more responsive to chemotherapy tha nradiation therapy or surgery.
What are the clinical symptoms of lung cancer? (symptom=experienced by patient)
Local symptoms:
- Cough
- Haemoptysis (blood in sputum) - due to ulceration of tumour
- Dyspnoea (difficulty breathing)
- Chest pain
- Wheezing
Non-specific systemic signs:
- Weight loss
- Anorexia
- Malaise
- Clubbing of fingers
What are the clinical signs of lung cancer? (sign=detected)
- Lobar collapse
- Pneumonia
- Pleural effusion
- Fixed inspiratory wheeze
- Tender ribs (secondary deposits of tumour in ribs)
- Mediastinal compression
- Superclavical/axillary lymphadenopathy
What are some paraneoplastic syndromes associated with lung cancer?
A paraneoplastic syndrome is asyndrome (a set of signs and symptoms) that is the consequence of cancer in the body but that, unlike mass effect, is not due to the local presence of cancer cells.
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Non Small Cell Lung Cancer
- Hypercalcaemia (due to parathyroid hormone related protein)
- skeletal-connective tissue syndromes
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Small Cell Lung Cancer
- ADH (antidiuretic hormone)
- ACTH (adrenocorticotropic hormone)
- neurologic/myopathic syndromes
What tests are done to diagnose lung cancer?
- History and physical exam
- Diagnostic: chest X-ray, biopsy
- Staging: CT of chest/abdomen, bone scan, bone marrow aspiration
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
What are the treatment options for SCLC?
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Limited Disease
- Chemotherapy
- Concomitant Radiation
- Prophylactic Cranial Irradiation (preventative brain irradiation to decrease the risk of brain metastases tumour development and to prolong survival)
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Extensive Disease
- Chemotherapy
- Palliative radiation (to reduce pain and improve patients’ quality of life).
What differences are observed histopathologically between lung carcinomas?
- Squamous cell carcinoma: nests of polygonal cells with pink cytoplasm and distinct borders. Nuclei hyperchromatic and angular. Well differentiated, occasionally anaplastic (loss of cell features), and may show keratin pearls.
- Adenocarcinoma: hyperchromatic nuclei, tubular, acinar, or papillary growth pattern.
- Bronchioalveolar carcinoma: columnar cells proliferated along alveolar septae, well differentiate.
- Large cell carcinoma: gross nuclear pleomorphism (variable size, shape nucleus), bizarre mitosis.
- Small cell carcinoma: ‘oat cells’ small dark blue cells with minimal cytoplasm.
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)
