Respiratory System Pathology Flashcards
1
Q
Define infectivity.
A
The proportion of persons exposed to an infectious agent who become infected.
2
Q
Define incubation period.
A
The time elapsed between exposure to a pathogen and when symptoms start to occur. People are usually non-infectious during the incubation period.
3
Q
Define virulence.
A
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.
4
Q
Define attenuation.
A
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.
5
Q
List some myxoviruses
(muxo→myxo:mucous, reacts with mucin on erythrocytes)
A
- 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
6
Q
What are the types of upper respiratory inflammatory diseases?
A
- 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)
7
Q
List some upper respiratory neoplastic diseases.
A
- Nasopharyngeal carcinoma (Epstein-Bar virus)
- Laryngeal papilloma
- Squamous cell carinoma of larynx (most common larynx tumour, associated with smoking)
8
Q
Outline influenza.
A
- 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.
9
Q
Outline the influenza virus.
A
- 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)
10
Q
How are the viral proteins on the surface of influenza involved in pathogenesis?
A
- 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.
11
Q
What is the difference between antigenic drift and antigenic shift? How do these play parts in the influenza virus?
A
- 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)
12
Q
What are the criteria for establishing a new pandemic of influenza virus in humans? [4]
A
- A novel virus, with a new haemagglutanin subtype (antigenic shift)
- Association with disease
- Susceptible population
- Ability of virus to transmit from person to person
13
Q
What are the risk factors for the acquisition of zoonotic avian or non-human influenza A?
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
14
Q
What does the seasonal flu vaccine contain?
A
- one A (H3N2) virus
- one A (H1N1) virus
- one B virus
15
Q
What drugs are available to treat the flu?
A
- Zanamivir: neuraminidase inhibitor (effective against A and B)
- Oseltamivir: neuraminidase inhibitor (treat and prevent A and B)
- Amantadine: inhibitors of viral M2 protein
16
Q
List some lower respiratory diseases.
A
-
Pneumonia
- Bronchopneumonia
- Lobar pneumonia
- Interstitial pneomonia
- Bronchitis
-
Lung cancer
- Non-small cell lung cancer (NSCLC)
- Small cell lung cancer (SCLC)
17
Q
What are the signs and symptoms of a lower respiratory disease?
A
- Cough
- Sputum
- Haemoptysis (blood in sputum)
- Wheezing
- Breathlessness
- Chest pain
- Cyanosis (<5g/dl deoxygentated heamoglobin)
- Clubbing of fingers (Lung abscess, bronchogenic carcinoma)
18
Q
What are the different classifications of pneumonia?
A
- Aetiology: Bacterial, viral, fungal
- Morphology: Bronchopneumonia vs. lobar pneumonia
- Community acquired vs. hospital acquired
- Opportunistic pneumonia infections
19
Q
Outline the differences between bronchopneumonia, lobar pneumonia, and interstitial pneumonia.
A
- 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
20
Q
What are the causative organisms of lobar pneumonia? Outline the pathogenesis.
A
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.
21
Q
What are the pathological stages in lobar pneumonia? What causes them and how are they characterised?
A
- 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.
22
Q
What are the symptoms of pneumococcal (lobar) pneumonia? What are the complications? [7]
A
- Symptoms: high fever, cough, shortness of breath, rapid breathing, chest pains.
-
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)
23
Q
What are the causative organisms of bronchopneumonia (staphyloccocal pneumonia)? Outline the pathology.
A
- 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.
24
Q
What are common causes of viral pneumonia?
A
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.
25
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**.
26
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.
27
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**.
28
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)
29
What are the **two major divisions** of **lung cancer**? What are further **subdivisions**?
* **Primary lung cancer**
* **Non-small cell lung cancer (NSCLC)** (80%)
* ****squamous cell carcinoma (35%)
* adenocarcinoma (35%)
* large cell lung cancer (10%)
* **Small cell lung cancer (SCLC)** (20%)
* **Secondary lung cancer** (spread from another primary site)
30
What are some of the **genetic alterations** in the **pathogenesis** of **lung cancer**? What **changes** are observed in **tissues**?
1. ***K-ras oncogene***: adenocarcinomas, large cell tumours, less commonly squamous cell carcinoma. Correlates with smoking and poor prognosis.
2. ***Myc oncogene***: overexpression in 10-40% of SCCs, rare in other types.
3. ***Bcl-2***: antiapoptotic protooncogene expressed in 25% of squamous cell carcinomas, 10% adenocarcinomas.
4. ***Rb*** and ***p53***: in both in 80% SCCs, less frequent in NSCCs.
31
Outline **squamous cell carcinoma**.
* **Primary lung cancer**
* **Non-small cell lung cancer (NSCLC) (80%)**
* **squamous cell carcinoma (~35%)**
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.
32
Outline **adenocarcinoma**.
* **Primary lung cancer**
* **Non-small cell lung cancer (NSCLC) (80%)**
* **adenocarcinoma (~35%)**
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.
33
Outline **bronchioalveolar carcinoma.**
* **Primary lung cancer**
* **Non-small cell lung cancer (NSCLC) (80%)**
* **Adenocarcinoma (~35%)**
* **Bronchioalveolar carcinoma (2%)**
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.
34
Outline **large cell carcinoma.**
* **Primary lung cancer**
* **Non-small cell lung cancer (NSCLC) (80%)**
* **large cell lung cancer (10%)**
**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.
35
Outline **small cell carcinoma (SCLC).**
* **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.
36
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
37
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
38
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.
* **Non Small Cell Lung Cancer**
* Hypercalcaemia (due to parathyroid hormone related protein)
* skeletal-connective tissue syndromes
* **Small Cell Lung Cancer**
* ADH (antidiuretic hormone)
* ACTH (adrenocorticotropic hormone)
* neurologic/myopathic syndromes
39
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**
40
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**
1. Primary tumour \> 3cm or
2. Tumour invades visceral pleura or
3. Partial collapse of lung
**T3**
1. Tumour of any size invading chest wall, diaphragm, mediastinal pleura or parietal pericardium
2. 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
41
What are the **treatment** options for **SCLC**?
* **Limited Disease**
* Chemotherapy
* Concomitant Radiation
* Prophylactic Cranial Irradiation (preventative brain irradiation to decrease the risk of brain metastases tumour development and to prolong survival)
* **Extensive Disease**
* Chemotherapy
* Palliative radiation (to reduce pain and improve patients' quality of life).
42
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.
43
Diagnose:
**Adenocarcinoma**
Peripheral location, arises from bronchial epithelium, tubular growth pattern, hyperchromatic.
44
Diagnose:
**Bronchoalveolar Carcinoma**
Tumour nodules, columnar cells proliferated along alveolar septae.
45
Diagnose:
**Small cell carcinoma**
'oat-cells', small dark blue cells with minimal cytoplasm packed together
46
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)
