Pathology Flashcards
1
Q
What is an obstructive lung disease?
A
Restricted airflow especially on expiration
2
Q
What is a shunt?
A
When blood passes through the lungs without participating in gas exchange.
3
Q
What is dead space?
A
Air in the respiratory system that is not participating in gas exchange
4
Q
Name the types of dead space
A
Anatomical, alveolar and physiologic (total) dead space
5
Q
What are the differences between asthma and COPD
A
COPD is almost all smokers, this is not significant in asthma.
COPD is rare in <35 yo but asthma is very common in <35yo.
COPD has a productive cough which is very uncommon in asthma.
COPD breathlessness is persistent and progressive while breathlessness is asthma is variable.
COPD rarely wakes patents up with breathlessness/wheeze and variability in symptoms in uncommon however these are both very common in asthma.
6
Q
What is COPD?
A
The combination of chronic bronchitis and emphysema.
7
Q
Is COPD obstructive or restrictive ?
A
Obstructive
8
Q
Risk factors for COPD
A
Smoking, pollution, dust,
9
Q
Do chronic bronchitis and emphysema always occur together?
A
No not in the case of Alpha 1-antiprotease deficiency which causes emphysema alone.
10
Q
What is chronic bronchitis ?
A
Chronic bronchitis is a cough which produces sputum most days for three consecutive months for two or more consecutive years
11
Q
What does chronic bronchitis sometimes look like?
A
chronic bronchial asthma
12
Q
What is emphysema?
A
Loss of alveolar tissue causing dilation in distal airways.
13
Q
Types of emphysema
A
Centriacinar emphysema starts with bronchiolar dilation and then alveolar tissue is lost. It is found at the top of the lobes.
Panacinar emphysema infects all the alveoli in a whole area of lung.
Scar emphysema is no clinical effects and is just the formation of emphysema next to scars.
Periacinar empyema causes tissue loss at the edge of acini and if it leaks air into the pleural cavity then it causes a pneumothorax to develop.
14
Q
What causes emphysema
A
Build up of elastase enzymes.
15
Q
What deficiency causes a lack of anti-elastase enzymes?
A
alpha 1 antitrypsin deficiency
16
Q
What are the main effects of emphysema?
A
Hypoxia throughout the body.
High blood pressure - Blood is diverted from the damaged areas, which creates more resistance in the lungs, which means your heart has to pump harder.
Cor-pulmonale (failure of the right side of the lung) which leads to hypertrophy and oedema.
Fibrosis - Forms from long term vasoconstriction makes the constriction even worse.
Secondary polycythaemia - Increase in erythropoietin makes blood thicker and makes heart pump even harder.
17
Q
Symptoms of COPD
A
COPD presents with a cough, breathlessness, production of sputum, chest infections, wheezing, weight loss, loss of muscle mass, fatigue, swollen ankles, continued worsening of symptoms, cyanosis, raised JVP, cachexia, pursed lip breathing, hyperinflated chest (seen on X-ray), use of accessory muscles, peripheral oedema and acute exacerbations.
18
Q
How is COPD diagnosed ?
A
COPD is diagnosed with a combination of symptoms, history and spirometry. A FEV1/FVC ratio of <0.7 is key to diagnosis. Chest X-rays, and mMRC breathlessness scale results, lung volume or transfer factors tests (Low results may indict COPD) and CT scans can all also be used to help diagnose it. Many people with COPD are not diagnosed.
19
Q
What is a COPD acute exacerbation?
A
Worsening symptoms, chest tightening, temperature, fatigue, systematic upset (eating etc). Sometimes it can be fatal if the patient goes into respiratory failure.
20
Q
A COPD acute exacerbation can be caused by a … or …. infection?
A
Viral or bacterial.
21
Q
How is COPD managed?
A
Non-pharmacological (Most effective) = Smoking cessation, pulmonary rehabilitation, vaccination.
Pharmacological = SABA, LAMA, ICS and LABA.
22
Q
How are COPD acute exacerbations managed?
A
Short acting bronchodilators, Steroids (Prednisolone 40mg per day for 5-7 days) and Antibiotics.
23
Q
Is Asthma obstructive or restrictive ?
A
Obstructive
24
Q
What causes/triggers asthma?
A
Asthma is a type I hypersensitivity reaction. Exacerbations are triggered by a large range of things i.e. perfume, pollen, dust, exercise etc
25
Risk factors for asthma
Genetics - Atopic gene, where hay fever, eczema, asthma and allergic rhinitis are all common.
Maternal or grandmaternal Smoking - Causes smaller lungs in offspring giving a higher chance of lung conditions.
Occupation - i.e. bakers or painters.
26
What is Asthma?
Difficulty breathing as a result of airway narrowing. Narrowing is caused by smooth muscle contraction, increased mucus, inflamed and thickened wall.
27
How do you diagnose asthma?
There is no clear test. However asthma will respond to treatment.
28
Symptoms of asthma
Wheeze (in all children and most adults), variability of symptoms through the day, cough (especially in the mornings or at night), chest tightness, shortness of breath.
29
What to look for in the history of a potential asthmatic?
Atopic conditions, triggers (i.e. pets, occupations)
30
Investigations for asthma
Spirometry. May be normal in an asthmatic (because they are not currently having an exacerbation),
FeNO
Bronchodilator reversibility test.
Peak flow monitoring - variability suggests Asthma.
CXR - May show hyperinflation or hyperlucent
31
How to diagnose a child with asthma
Spirometry (before and after medication), bronchodilator response test, then a responsive spirometry test.
32
Asthma differential diagnosis
COPD
Bronchiectasis
Cystic fibrosis
Tumour or foreign body (indicated by stridor)
Cardiac cause
Lung cancer (Indicted by finger clubbing or cervical lymphadenopathy)
Collapsed lung (Asymmetrical expansion or dull percussion)
Bronchiectasis (Crackles)
33
Management of asthma
Action plan
Inhalers. Metered dose inhalers (pMDI) are used with spacers and medicine is released in combination with inhalation. Dry / Powder inhalers (DPI) relies on sucking. There are Short acting B2 agonists (SABA) which are relievers i.e. salbutamol (MDI and DPI) and terbutaline (DPI).
Oral therapy i.e. leukotriene receptor antagonists, theophylline, prednisolone
Specialist treatment include omalizumab and mepolizumab and bronchial thermoplastic. These can only be delivered by very high specialists.
34
Treating children with suspected asthma
As a rule of thumb in children especially if quality of life is effected then give a trial of treatment and see if it relieves symptoms and if quality of life is not effected then watch and see.
In children ICS course is given for 2 months. The over the Easter (While coughs and colds are less) a holiday from the inhaler is given to check that the symptoms do come back. Treatment in children may cause the child's total height to be 0.5-1cm less than would be otherwise.
35
Step up/step down approach in children
```
Step 1 - very low dose ICS
Step 2 - very low dose ICS + SABA
Step 3 - very low dose ICS + SABA + LABA
Step 4 - low dose ICS + SABA or Low dose ICS + SABA + LABA or very low dose ICS + SABA + LTRA
Step 5 -Refer to specialist care
```
36
Considerations before stepping up or down asthma treatment
Is the medication effective? If not is it because they don't have asthma? or they aren't taking the medication? or they aren't taking the medication properly
37
What does a mild asthma exacerbation look like?
Use inhalers, oral steroids, treatment of trigger, establish early follow up plana and a back up plan with these patients. Management is done using SABA via spacer or SABA via spacer + pred
38
What does a moderate asthma exacerbation look like?
Increased symptoms but able to speak and complete sentences, heart rate is less than 110. Respiratory rate is less than 25. Here patients should be brought into hospital and any patients admitted to hospital should have a blood gas test done. Management is done using SABA via neb +pred or SABA + ipra via neb + pred.
39
What does a severe asthma exacerbation look like?
The inability to complete sentences in one breath, HR ≥110 and respiratory rate ≥25. Here Nebulizers (Salbutamol/Ipratropium), Oral/IV Steroid, Magnesium, Aminophylline, Triggers – infection/allergen, CXR, possibly Level 2/3 care. Management is done using IV salbutamol, IV aminophylline, IV magnesium (neb), IV hydrocortisone, finally Intubate and ventilation in last case resort.
40
What does a life threatening asthma exacerbation look like?
Is one of any of the following Grunting, Impaired consciousness, confusion, exhaustion, Bradycardia/ arrhythmia/ hypotension, PEF < 33% predicted or best, Cyanosis, Silent chest, Poor respiratory effort, SaO2 < 92%, PaO2 < 8kPa, PaCO2 normal (4.6 - 6.0kPa because you should have blown off a lot of CO2 and therefore have a low PaCo2)
41
What is cystic fibrosis ?
A single gene autosomal recessive disorder of the CFTR gene which is found on chromosome 7 and codes for a chlorine ion channel protein. There are a high number of mutations occur on this gene causing CF.
42
What is the technical names of the most common cystic fibrosis mutation ?
delta F508
43
Describe the cellular changes that occur in a cell as a result of cystic fibrosis
Cl- increases in the cell
| This causes sodium and water to also move into the cell.
44
What is the effect of cystic fibrosis on the airways ?
Movement of water into the cells causes dehydration of the airways, thick mucous build up and stick to the walls, this mucus then rubs against the walls shearing the walls, the mucous collects bacteria and infections develop.
45
Describe the classifications of Cystic fibrosis mutations
Class 1 -3 cause severe disease and have no functioning proteins. (Most common)
Class 4-6 cause more mild disease and have some functioning proteins.
46
Describe the tests that can be used to diagnose cystic fibrosis.
Antenatal testing if there is a known high chance.
Neonatal Guthrie test.
Sweat test - Cells have high levels of chloride and so the sweat they produce contains a lot of chloride.
Faecal elastase.
47
How does cystic fibrosis present in the lungs?
Recurrently chest infections such as pneumonia etc. which cause damage to the airways and make it easier for the next infection to arise, Dehydrated thick mucus, sheering which causes inflammation.
CF will also present with clubbing.
48
As well as the lungs cystic fibrosis also effects the ...
Pancreas, prevents the production of certain enzymes that help in the digestion of food.
49
How is cystic fibrosis managed ?
Mucus obstruction is treated with airway clearance methods i.e. Physiotherapy, mucolytics, bronchodilators.
Chronic infections are treated with antibiotic.
Inflammation is treated with azithromycin.
Pancreatic insuffiencies are treated with taking replacing enzymes, boosting nutrition and eating a high calorie high fat diet.
Lung transplant.
50
What are some requirements and contra-indictions to having a lung transplant ?
```
Organ failure
Cancer in the last 5 years
Poor vascular health
Drug, nicotine or alcohol dependency.
Infections.
```
51
If a cystic fibrosis patient has diabetes what will be different?
They will still need to eat a high calorie diet and will almost always have Type II.
52
What can be some end stage complications of cystic fibrosis?
- Osteoporosis. CF causes gradual weakening of the bones
- Pneumothorax.
- Haemoptysis (may actually occur at any point)
53
What is pathogenicity ?
An microorganism ability to infect a patient
54
Based on there pathology micro-organisms can be classified into what categories ?
- Primary pathogens (Very infectious)
- Facultative pathogens (Infectious but require a bit of help such as an a open wound)
- Opportunistic pathogens (not very infectious and will only infect sick people)
55
Describe the defence mechanism in the respiratory system
- Macrophage-Mucociliary escalator system (where macrophages in the alveoli phagocytose pathogens and then join the mucus moving up out of the lungs by the cilia - This stops working in influenzas)
56
What is bronchiectasis ?
Permanent dilation of the bronchi and production of extra mucus causing a productive cough. Happens as a result of pneumonia or TB. It is often associated with poor respiratory health. It can cause parenchymal destruction which appears like signet rings on CXR.
57
What is pneumonia ?
Infection of the alveoli where there is a build up in fluid and a decrease in gas exchange.
58
What are the different types of pneumonia?
```
Bronchopneumonia
Segmental
Lobar
Obstructive
Aspiration
Retention
Hydrostatic
Endogenous lipid
```
59
What are risk factors to having pneumonia?
```
Old or young age
Smoking
Alcohol excess
Viral or lung disease/infection
Chronic illness
Immunocompromised
Hospitalization
```
60
What are the main symptoms and signs of pneumonia?
```
Productive cough
Fever
dyspnoea
haemoptysis
tachypnoea
tachycardic
reduced lung expansion
dull percussion
bronchial breathing
crepitations
```
61
What is CURB 65?
Used to assess the severity of pneumonia.
C = confusion,
U = blood urea > 7mmol/L.
R = respiratory rate ≥ 30/min.
B = systolic BP < 90 mmHg, diastolic blood pressure < 60mmHg.
65 = age ≥ 65.
A score of 0-1 mean you have low risk and could be treated in community.
A score of 2 means you have moderate risk and hospital treatment is usually required.
A score of 3-5 mean you have a high risk of death and need for ITU.
62
Treatment of Pneumonia
If mild there is sometimes no treatment given.
If CURB 0-1 Amoxicillin for 5 days (or clarithromycin or doxycycline is penicillin allergy).
CURB 2 Amoxicillin and clarithromycin for 5-7 days (levofloxacin is penicillin allergy).
CURB 3-5 Co-amoxiclav + clarithromycin for 7 – 10 days(Levofloxacin or
co-trimoxazole if penicillin allergy)
63
What is TB caused by ?
Mycobacterium infection (M.Tuberculosis, M.Africanum or M.Bovis) which can infect any part of the body but most commonly infects the lungs
64
How do you test for mycobacterium ?
Mycobacteria are tested for via AAFB test however a positive AAFB test does not mean you have TB it may be another mycobacterium disease such as leprosy.
65
Explain the transmission and infection of TB
Transmission of the infection occurs when someone with TB in there lungs or larynx coughs and releases TB aerosol droplets into the environment. These droplets can survive for hours in the air. Another person then breathes in these particles and the TB bacteria move into there lungs. NOTE UV destroys the bacteria so its unusual to transmit the infection outside. This causes an immune response (T cells move from the lymph nodes to release cytokines that activate the macrophages) which creates a granuloma (ball of immune cells) with a caseating necrosis (‘cheese’) centre where there are dead cells. This region is called the Ghon focus. In some healthy people the bacteria are destroyed and the granuloma reduces to leave a small calcified mass. In some other people there immune system isn’t good enough to destroy the bacteria but it keeps the bacteria in a latent period held within this granuloma. This latent period can last months, years or even an entire lifetime. However if this patient then becomes immunocompromised then the infection can become active and infect the lungs, this is called post primary or secondary infection. In some patients there immune system cannot keep the bacteria under control and an active infection occurs immediately after the primary infection. Note M.Bovis spreads through consumption of unpasteurized milk. The inflamed lymph nodes and alveolar damage is called the Ghon complex.
66
What are the risk factors of TB ?
Being non-UK born, between the age of 15 and 44, HIV positive, diabetes and being Immunosuppressed.
67
What are the symptoms of TB?
Cough, fever, sweats and weight loss
68
How is TB diagnosed?
```
CXR. In post-primary TB cavitation will appear in 10-30% of the lung and the apices will appear soft ‘fluffy’ and there will be a nodular upper zone. Lymphadenopathy can also be present. In primary infection there will be mediastinal lymphadenopathy, pleural effusion, miliary pneumonic lesion with enlarged hilar nodes.
Sputum samples (take 3 samples with a 3-24 hour gap and at least 1 early morning sample), bronchoscopy with BAL, endobronchial ultrasound with biopsy, lumber puncture, urine or aspirate/biopsy of tissue can also be used to diagnose TB.
```
69
How is TB treated?
Combination of drugs for 6-9 months. A HIV and hepatitis B and C test should also be carried out. There are a number of different drugs that can be used to treat TB; Isoniazid (H), Pyrazinamide (Z), Rifampicin (R), and Ethambutol (E). The standard treatment is two months of R, H, Z, E and then 4 mouths of E and H.
70
What are the side effects of Rifampicin ?
Cause orange ‘Irn Bru’ urine induced by liver enzymes, prednisolone, anticonvulsants and makes all hormonal contraceptive methods ineffective, Hepatitis
71
What are the side effects of Isoniazid ?
Hepatitis, Peripheral neuropathy (pyridoxine B6).
72
What are the side effects of pyrazinamide ?
Hepatitis and Gout
73
What are the side effects of Ethambutol?
Optic neuropathy (check visual acuity).
74
What is tuberculous bronchopneumonia?
Where the primary focus enlarges forming a cavity, the hilar lymph nodes enlarge so much that they compress the bronchi causing lobar collapse in the lung, and sometimes enlarged lymph nodes discharge into bronchus which has a poor diagnosis
75
What is miliary TB ?
Spread in the blood and develops in multiple organs.
76
Who should be screening for TB?
Over 65s, Those entering the country from a high TB area, and those who have been in contact with active TB
77
Why is lung cancer often detected so late?
Because symptoms doing start unto the cancer is every developed.
78
What are the main risks of lung cancer?
- Smoking (85% of lung cancer patients) because tobacco smoke mutates epithelial stem cells. Where a combination of mutations causes lung cancer.
- Asbestos and other occupational exposures.
- Radon
- Air pollution
- Deiseal exhaust etc
- Genetics, genetically you can be more addicted to nicotine and so have a higher change of cancer.
79
What therapy is available to non-smokers but not smokers for lung cancer?
Often the cancer is a due to a single mutation which allows it to be targeted by KRAS or EGFR drugs.
80
Signs and symptoms of lung cancer
```
Haemoptysis
Cough
SOB
Chest pain
Clubbing (Hands and feet)
```
81
How is lung cancer diagnosed?
CXR
CT scan
PET scan
Biopsy
82
If a tumour is found on a chest X-ray what might it be?
- Benign
- Carcinoid tumour (Low malignancy)
- Bronchial gland tumour
- Lymphomas
- Sarcomas
- Metastases from other parts of the body.
83
What do biopsies tell you ?
- Class of the tumour
| - If the tumour is cancer
84
Give examples of ways in which to take a biopsy.
- Bronchoscopy
- EBUS
- Ultrasound or CT guided
- Biopsies of other parts of the body i.e. lymph nodes (mediastinoscopy) or liver.
85
How is cancer staged?
TNM
T = Size of the tumour. Tx = tumour cannot be assessed. T1 ≤ 3cm it includes T1a T1b ad T1c. T2 is between 3-5cm of it there is involvement of the bronchus or visceral pleura. T3 is 5-7cm or if there is involvement of the chest wall. T4<7cm or any tumour that has invaded other structures.
N which is the nodal status (has it spread to the lymph nodes? This is done using a PET-CT, CT, mediastinoscopy and EBUS/EUS. N0 is no lymph node metastases, N1 is ipsilateral peribranchial, hilar or intrapulmonary nodes including by directed extension. N2 Ipsilateral mediastinal, subcarinal. N3 Contralateral mediastinal, contralateral hilar, scalene or supraclavicular. Nodes which are larger than 1cm are considered to be involved in disease.
M which is the metastasis. This is done using a PET-CT, CT or bone scan. M0 is no distant metastasis, M1 is distant metastasis, M1a is metastasis to another part of the lung, M1b is a single distant metastases. M1c is multiple distant metastases.
86
When considering treatment what considerations should be taken? (Lung cancer)
- Performance status
- Patient wishes
- Stage and classification
- MDT
- Aims of treatment
87
What are the different types of lung cancer?
- Squamous cells
- Adenocarcinoma
- Small cells carcinoma
- Large cell carcinoma
88
What is squamous cells lung cancer?
Cancer which shows evidence of squamous differentiation of characterization
89
What is adenocarcinoma lung cancer?
Cancer which shows glandular differentiation in the tumour
90
What is small and large cell carcinoma?
cancer which appears morphologically undifferentiated down a microscope however it will have differentiation at a molecular level towards newer endocrine type cells
91
Development of cancer in the periphery of the lung
Undergo atypical adenomatous hyperplasia, which develops adenocarcinomas in situ and then goes on to develop invasive adenocarcinomas (if patients have never smoked then it will be this type and molecularly be more simple).
92
Development of cancer in the central lung airways
Where bronchial basal cells undergo hyperplasia, developing into squamous dysplasia and carcinoma in situ, these then go on to becomes invasive squamous cells of the carcinoma. This is almost always caused by tobacco
93
Describe the features of non-small cell lung cancer
This is a cancer that has a cell diving time (doubling time) of 129 days. It is staged using TNM where stage four is where there is distant metastasis. Here surgery is sometimes used and after surgery chemo (to reduce chance of recurrence) and radiotherapy is sometimes offered. 1 in 5 patients who receive radiotherapy are curved from NSCLC.
94
Describe the features of small cell lung cancer
15% of patients, and have a cell diving time (doubling time) of 29 days. Surgery generally isn’t often unless it is found very early on. CRT curative treatment is often offered followed by prophylactic cranial radiation (PCI). There is often a combination of drugs used i.e. cisplatin and etoposide. There is very little advantage of many chemo reschemes. In very advanced disease you can give 4 cycles of combination chemotherapy. Small cell lung cancer tends to have a faster response to treatment than non-small-cell lung cancer. Radiotherapy to the brain is given prophylactically (“prophylactic” treatment is anything that is given to prevent something) as it is known that SCLC frequently spreads to the brain.
95
What are considerations that are looked at before decided if a lung cancer patient is fit for surgery ?
- Staging
- ECOG performance status
- FEV1. Must be more than 1 for a lobectomy and more than 2 for a pneumonectomy.
- CVS health
- Respiratory health
96
What is the ECOG performance status ?
Used to assess the performance status of a cancer patient.
0 is asymptomatic,
1 is symptomatic but able to do light work,
2 is a patent who has to rest but for less than half the day,
3 is a patient who has to rest for more than half a day,
4 is a patient who is bedbound and
5 is a patient who is dead
97
What are the different types of lung cancer surgery ?
- Lobectomy (One lobe removed)
- Pneumonectomy (Lung removed)
- Wedge resection (Tumour removed)
- Open and close thoracotomy (When surgery goes to be performed but then the damage is greater than expected and so nothing is removed)
98
Describe immunotherapy as a treatment for lung cancer
Revolutionising the treatment of lung cancer. Only available for stage III NSCLC after chemotherapy. In theory the mutated epithelial cells which produce of weird proteins (antigenicity) should be detected as ‘foreign’ by the immune system a cause a cellular and immune response removing these proteins before they form a tumour. However tumours do form and therefore this does not work in our bodies. Immunotherapy aims to stop these weird proteins from escaping the notice of the immune system. One of these pathways is the PD1/PD-L1 which is where a ligand molecule on the tumour switches off immune cells around them. Immunotherapy drugs therefore aim to interrupt relationships like this and so stop tumour formation.
99
Describe radiotherapy as a treatment for lung cancer
There are a number of regimes the most common of which is 55Gy in 20 fractions so patients are treated daily Monday to Friday for four weeks. Side effects my include lethargy, oesophagitis, SOB and long term cardiac, pulmonary fibrosis.
100
Describe SABR as a treatment for lung cancer
Stereotactic ablative radiotherapy is very high does for a very short period of time. Standard dose is 54Gy in 3 fractions. This can have similar outcomes to surgery.
101
Describe Chemotherapy as a treatment for lung cancer
Survival is better than RT. There are no standard chemo regimes, most centres use a doublet regime. You can give a patient sequential chemotherapy and then radiotherapy. Side effects include marrow suppression, nausea, neuropathy, and hair loss. Neutropaenic sepsis is the most common complication of chemotherapy.
102
Describe palliative treatment as a treatment for lung cancer
Palliative chemotherapy, palliative immunotherapy, TKI, Palliative radiotherapy,
