BLOCK 13 WEEK 1 Flashcards
TB Microorganisms
- Acid fast bacilli -
- Special staining is required, using the Zeihl-Neelsen stain, which turns them bright red against a blue background
- TB can be stained with Ziehl Nielsen (stains red), or auramine (fluorescent).
TB Pathophysiology
The macrophages often migrate to regional lymph nodes, the lung lesion plus affected lymph nodes is referred to as a Ghon complex.
This leads to the formation of a granuloma which is a collection of epithelioid histiocytes.
There is the presence of caseous necrosis in the centre.
The inflammatory response is mediated by a TYPE 4 HYPERSENSITIVITY REACTION.
In healthy individuals the disease may be contained, in the immunocompromised disseminated (miliary TB) may occur.
Multiple small calcifications in the lung can be due to miliary TB, which is associated with extrapulmonary TB.
Can TB be transmitted via breastmilk and harm the baby?
Yes TB can be transmitted via breastmilk and harm the baby
Disease Progressision
Tuberculosis is mostly spread by inhaling saliva droplets from infected people. Once in the body, there are several possible outcomes:
-Immediate clearance of the bacteria (in most cases)
-Primary active tuberculosis (active infection after exposure)
-Latent tuberculosis (presence of the bacteria without being symptomatic or contagious)
-Secondary tuberculosis (reactivation of latent tuberculosis to active infection)
LATENT TUBERCULOSIS
Latent tuberculosis is present when the immune system encapsulates the bacteria and stops the progression of the disease.
Patients with latent tuberculosis have no symptoms and cannot spread the bacteria.
Most otherwise healthy patients with latent tuberculosis never develop an active infection.
When latent tuberculosis reactivates, and an infection develops, usually due to immunosuppression, this is called secondary tuberculosis.
Where do you get TB
The most common site for TB infection is in the lungs, where it gets plenty of oxygen. Extrapulmonary tuberculosis refers to disease in other areas:
-Lymph nodes
-Pleura
-Central nervous system
-Pericardium
-Gastrointestinal system
-Genitourinary system
-Bones and joints
-Skin (cutaneous tuberculosis)
BCG VACCINE
The Bacillus Calmette–Guérin (BCG) vaccine involves an intradermal injection of live attenuated (weakened) Mycobacterium bovis bacteria (a close relative of M. tuberculosis that does not cause disease in humans).
This creates an immune response, providing lasting immunity against M. tuberculosis without causing infection.
The vaccine protects against severe and complicated TB but less against pulmonary TB.
Before being given TB vaccine
MANTOUX TEST: Before vaccination, patients are tested with the Mantoux test and only given the vaccine if this test is negative. They are also assessed for the possibility of immunosuppression and HIV due to the risks related to a live vaccine.
The BCG vaccine is not part of the routine vaccination schedule. It is offered to patients at increased risk of TB, such as those from areas of high TB prevalence, with close contact with TB (e.g., family members) and healthcare workers
SYMPTOMS
Cough
Haemoptysis (coughing up blood)
Lethargy
Fever or night sweats
Weight loss
Lymphadenopathy
Erythema nodosum (tender, red nodules on the shins caused by inflammation of the subcutaneous fat)
Spinal pain in spinal tuberculosis (also known as Pott’s disease of the spine)
INVESTIGATONS
Investigations
Tuberculosis can be challenging to diagnose. The bacteria grow very slowly in a culture, cannot be stained with traditional gram stains and require specialist stains (e.g., Ziehl-Neelsen stain).
There are two tests for an immune response to tuberculosis caused by previous infection, latent TB or active TB:
- Mantoux test
- Interferon‑gamma release assay (IGRA)
In patients where active disease is suspected, investigations to support the diagnosis include:
-Chest x-ray
-Cultures
MANTOUX TEST
The Mantoux test involves injecting tuberculin into the intradermal space on the forearm. Tuberculin is a collection of tuberculosis proteins isolated from the bacteria. It does not contain any live bacteria.
The infection creates a bleb under the skin. After 72 hours, the test is “read”. This involves measuring the induration of the skin at the injection site. An induration of 5mm or more is considered a positive result.
- To manage and diagnose active TB where we show symptoms we use the NAAT test
- To manage diagnose or manage potential latent TB we do the Mantoux test
Erythema Nodosum
Interferon Gamma Release Assays
IGRA involves mixing a blood sample with antigens from the M. tuberculosis bacteria. After previous contact with M. tuberculosis, white blood cells become sensitised to the bacteria antigens and will release interferon-gamma on further contact. A positive result is when interferon-gamma is released during the test.
CHEST X RAY TB
Primary tuberculosis may show patchy consolidation, pleural effusions and hilar lymphadenopathy.
Reactivated tuberculosis may show patchy or nodular consolidation with cavitation (gas-filled spaces), typically in the upper zones.
Disseminated miliary tuberculosis gives an appearance of millet seeds uniformly distributed across the lung fields.
TB culture
Culture samples are ideally collected before starting treatment. This allows testing for drug resistance. However, cultures can take several months. Treatment is usually started while waiting for the culture results.
There are several ways to collect cultures:
-Sputum cultures (3 separate sputum samples are collected)
-Mycobacterium blood cultures (require special blood culture bottle)
- Lymph node aspiration or biopsy
NAAT
Nucleic acid amplification tests (NAAT) assess for the genetic material of a pathogen. To detect tuberculosis DNA, NAAT is performed on a sample containing the bacteria (e.g., a sputum sample). It provides information about the bacteria faster than traditional culture, including drug resistance. NAAT is used for:
-Diagnosing tuberculosis in patients with HIV or aged under 16
-Risk factors for multidrug resistance (where the results would alter management)
TREATMENT
Latent tuberculosis is treated with either:
Isoniazid and rifampicin for 3 months
Isoniazid for 6 months
The treatment for active tuberculosis can be remembered with the RIPE mnemonic:
R – Rifampicin for 6 months
I – Isoniazid for 6 months
P – Pyrazinamide for 2 months
E – Ethambutol for 2 months
TOM TIP
Remember that isoniazid causes peripheral neuropathy, and pyridoxine (vitamin B6) is co-prescribed to help prevent this.
An exam question might say, “…are started on R, I, P and E. What else should be prescribed?”
The answer would be pyridoxine or vitamin B6.
HOW TO WE STOP SPREAD IN HOSPITALS
In hospitals, negative pressure rooms are used to prevent airborne spread. Negative pressure rooms have ventilation systems that actively remove air to prevent it from spreading onto the ward.
SIDE EFFECTS OF TREATMENT
Side Effects of Treatment
Rifampicin can cause red/orange discolouration of secretions, such as urine and tears. It is a potent inducer of the cytochrome P450 enzymes and reduces the effects of drugs metabolised by this system, such as the combined contraceptive pill.
Isoniazid can cause peripheral neuropathy. Pyridoxine (vitamin B6) is co-prescribed to reduce the risk.
Pyrazinamide can cause hyperuricaemia (high uric acid levels), resulting in gout and kidney stones.
Ethambutol can cause colour blindness and reduced visual acuity.
Rifampicin, isoniazid and pyrazinamide are all associated with hepatotoxicity.
TOM TIP: A common exam question asks “…has recently started treatment for tuberculosis. They notice _____. Which medication is most likely to be implicated?” Numbness or unusual sensations in their feet implicates isoniazide (“I’m-so-numb-azid”). Difficulty recognising colours implicates ethambutol (“eye-thambutol”). Urine or tears that are orange or red implicates rifampicin (“red-I’m-pissin’”).
LUNG CANCER
- Lung cancer is the third most common cancer in the UK behind breast and prostate cancer.
- Lung cancer has the highest mortality rate.
- Smoking is the biggest cause.
- Around 80% of lung cancers are thought to be preventable.
CARCINOGENS IN CIGARETTES
CARCINOMA OF THE LUNGS - OTHER CAUSES
Anatomy of the lungs
-The right lung has three lobes.
-The left lung has two lobes.
-The heart is on the left, leaving less room for an extra lobe.
-Both lungs have an oblique fissure separating the lobes. The right lung also has a horizontal fissure.
Pleura
There is a membrane that surrounds the lungs called the pleura. There are two layers of this membrane, with a small amount of fluid between them (less than 20mls). These layers separate the lungs from the chest wall.
Lubrication between the two layers allows the lungs to expand and move without creating friction with the chest wall.
Between the two layers, there is a potential space, called the pleural cavity.
The two layers are usually touching each other, which is why it is only a potential space.
There is negative pressure within the pleural cavity, pulling the two layers of the pleura together.
As the chest wall expands, the negative pressure within the pleural cavity pulls the lungs outwards with the chest wall, causing them to expand.
Pleural Effusion
- A pleural effusion is when the potential space of the pleural cavity fills with excess fluid.
- This creates an inward pressure on the lungs, reducing the lung volume
Symptoms
- Dyspnoea (SOB) ( usually not suddenly could have a one month history of SOB for example)
- Reduced exercise tolerance
- Pleuritic chest pain (sharp chest pain when you breathe in)
Causes of Pleural effusion
Causes of pleural effusions are mainly divided into:
Exudative (protein content >35 g/l)
Transudative (protein content <35 g/l)
The history and clinical examination of the patient will usually be able to identify the most likely cause.
It is important to differentiate whether there is a unilateral effusion or bilateral effusions.
Note: transudative pleural effusions are more likely to be bilateral; exudative pleural effusions are more likely to be unilateral
Investigations Pleural Effusion
Blood Tests:
FBC – may show a raised WCC suggestive of infection
U&E – may show a raised creatinine suggestive of renal impairment
LFTs – may show a low albumin and raised alanine aminotransferase (ALT)/aspartate aminotransferase (AST) suggestive of cirrhosis
Imaging:
Chest X-ray is the first-line imaging investigation in all patients with a suspected pleural effusion
will reveal blunting of the costophrenic angle or white-out of lung (if large)
Pleural Effusion Question
Pleural Effusion question
Rhesus disease go over
MEIGS SYNDROME
Pleural Effusion question
Pleural Effusion Management
- Oxygen therapy for breathlessness
- Deal with underlying cause (eg. diuretics for heart failure or antibiotics for chest infections)
- Ultrasound guided Pleural Aspiration
- Pleuritic chest drain insertion - An intercostal drain – for large pleural effusions or empyemas (pus in pleuritic cavity)
- Chemical pleurodesis - for recurrent or persistent pleural effusions
This is injection of an irritant through a chest drain (usually sterile Talcum powder), which will cause a fibrotic reaction in the pleura aiming to seal the potential pleural space - Tunnelled indwelling pleural catheter – can be inserted to allow regular drainage of recurrent fluid
This is especially helpful in palliative patients and reduces hospital stays
Pleural Aspiration
Pleural Aspiration (Needle Thoracocentesis)
is an invasive medical procedure to remove fluid or air from the pleural space for diagnostic or therapeutic purposes. A cannula, or hollow needle, is carefully introduced into the thorax, generally after administration of local anesthesia.
Pneumothorax
- A pneumothorax is when air gets into the pleural cavity.
- which can be spontaneous or traumatic in origin.
SYMPTOMs:
- sudden onset of shortness of breath
- pleuritic chest pain (sharp pain when your breathe in)
Signs:
- reduced chest expansion,
- reduced or absent breath sounds on the affected side
- hyper resonant on affected side
Causes of pneumothorax
Causes can be classified into spontaneous and traumatic.
Spontaneous causes can be further classified:
- primary causes (no underlying lung pathology - typically tall thin young men)
- secondary causes (underlying lung pathology).
Secondary causes include connective tissue disease (such as Marfan’s syndrome and Ehlers-Danlos syndrome),
obstructive lung disease (such as asthma and COPD), infective lung disease (such as TB and pneumonia),
fibrotic lung disease (such as cystic fibrosis and idiopathic pulmonary fibrosis), and neoplastic disease (such as bronchial carcinoma).
Traumatic causes can be further classified into iatrogenic causes (such as insertion of a central line or positive pressure ventilation) and non-iatrogenic causes (either a penetrating trauma or blunt trauma with rib fracture).
A large right sided pneumothorax.
On left hand side you can see grey haziness which is the lung
- On the right hand side you can see black (all air) with a collapse lung on the side
Another example
Tension Pneumothorax pathophysiology
When there’s damage to the pleura, either due to lung disease or trauma to the chest wall, air from the outside or from the lungs can flow freely into the pleural space, but cannot leave.
The accumulated air in the pleural space puts positive pressure on the lung and prevents it from expanding properly, which causes respiratory distress.
As the air continues to accumulate, the trachea and other structures of the chest can be pushed away from the pneumothorax, leading to increased difficulty breathing.
Additionally, the increased pressure inside the chest can compress the heart and lead to a collapse of the blood vessels that drain to the heart, in turn decreasing venous return and cardiac output.
If left untreated, tension pneumothorax can rapidly progress to cardiovascular collapse, which ultimately leads to cardiac arrest.
Left sided tension pneumothorax
- The heart is being pushed to the right hand side
Pneumothorax question
Pneumothorax question
Iatrogenic pneumothorax is a patient safety indicator (PSI) condition. It is a traumatic pneumothorax secondary to an invasive procedure or surgery.
Non - small lung cancer
Non-small cell lung cancer can be further divided into:
-Adenocarcinoma (around 40% of total lung cancers)
-Squamous cell carcinoma (around 20% of total lung cancers)
-Large-cell carcinoma (around 10% of total lung cancers)
-Other types (around 10% of total lung cancers)
Small cell lung cancer:
- Small cell lung cancer cells contain neurosecretory granules that can release neuroendocrine hormones. This makes SCLC responsible for multiple paraneoplastic syndromes.
PANEOPLASTIC SYNDROME
- Paraneoplastic syndromes are a group of rare disorders that occur when the immune system has a reaction to a cancerous tumor known as a “neoplasm.”
- The immune system is very important in keeping you healthy.
EXTRAPULOMARY MANIFESTATIONS
Lung cancer is associated with a lot of extrapulmonary manifestations and paraneoplastic syndromes. These are linked to different types and distributions of lung cancer. Exam questions commonly ask you to suggest the underlying cause of the paraneoplastic syndrome. Sometimes they can be the first evidence of lung cancer in an otherwise asymptomatic patient.
Recurrent laryngeal nerve palsy presents with a hoarse voice. It is caused by a tumour pressing on or affecting the recurrent laryngeal nerve as it passes through the mediastinum.
Phrenic nerve palsy, due to nerve compression, causes diaphragm weakness and presents with shortness of breath.
Superior vena cava obstruction is a complication of lung cancer. It is caused by direct compression of the tumour on the superior vena cava. It presents with facial swelling, difficulty breathing and distended veins in the neck and upper chest. “Pemberton’s sign” is where raising the hands over the head causes facial congestion and cyanosis. This is a medical emergency.
Horner’s syndrome is a triad of partial ptosis, anhidrosis and miosis. It can be caused by a Pancoast tumour (tumour in the pulmonary apex) pressing on the sympathetic ganglion.
Syndrome of inappropriate ADH (SIADH) can be caused by ectopic ADH secreted by a small cell lung cancer. It presents with hyponatraemia.
Cushing’s syndrome can be caused by ectopic ACTH secretion by a small cell lung cancer.
Hypercalcaemia can be caused by ectopic parathyroid hormone secreted by a squamous cell carcinoma.
Limbic encephalitis is a paraneoplastic syndrome where small cell lung cancer causes the immune system to make antibodies to tissues in the brain, specifically the limbic system, causing inflammation in these areas. This causes symptoms such as short term memory impairment, hallucinations, confusion and seizures. It is associated with anti-Hu antibodies.
Lambert-Eaton myasthenic syndrome can be caused by antibodies produced by the immune system against small cell lung cancer cells. These antibodies also target and damage voltage-gated calcium channels sited on the presynaptic terminals in motor neurones. This leads to weakness, particularly in the proximal muscles but can also affect intraocular muscles causing diplopia (double vision), levator muscles in the eyelid causing ptosis and pharyngeal muscles causing slurred speech and dysphagia (difficulty swallowing). Patients may also experience dry mouth, blurred vision, impotence and dizziness due to autonomic dysfunction.
TREATMENT for Non-small cell lung cancer
Surgery is offered first-line in non-small cell lung cancer to patients that have disease isolated to a single area. The intention is to remove the entire tumour and cure the cancer. See below for more detail on surgery.
Radiotherapy can also be curative in non-small cell lung cancer when diagnosed early enough.
Chemotherapy can be offered in addition to surgery or radiotherapy in certain patients to improve outcomes (“adjuvant chemotherapy”) or as palliative treatment to improve survival and quality of life in later stages of non-small cell lung cancer (“palliative chemotherapy“).
TREATMENT for Small cell lung cancer
Treatment for small cell lung cancer is usually chemotherapy and radiotherapy.
Prognosis is generally worse for small cell lung cancer compared with non-small cell lung cancer.
Mesothelioma
- Mesothelioma is a lung malignancy affecting the mesothelial cells of the pleura.
- It is strongly linked to asbestos inhalation.
- There is a huge latent period between exposure to asbestos and the development of mesothelioma of up to 45 years.
- The prognosis is very poor.
- Chemotherapy can improve survival, but it is essentially palliative.
Mesothelioma
Mesothelioma
BREATHLESSNESS
BREATHLESSNESS
BREATHLESSNESS
COUGH
SPUTUM
HAEMOPTYSIS
WHEEZE
CHEST PAIN
SIGNS
CLASSIFFCATION OF PNEUMONIA
Community-acquired pneumonia (CAP) develops in the community
Hospital-acquired pneumonia (HAP) develops after more than 48 hours in a hospital
Ventilator-acquired pneumonia (VAP) develops in intubated patients in the intensive care unit
Aspiration pneumonia is when the infection develops due to the aspiration of food or fluids, usually in patients with impaired swallowing
4 Stages of Lobar Pneumonia
COMMUNITY ACQUIRED PNEUMONIA CAUSES
BRONCHOPNEUMONIA
Legionella pneumophila
Legionella pneumophila (Legionnaires’ disease) is typically caused by inhaling infected water from infected water systems, such as air conditioning units.
It can cause a syndrome of inappropriate ADH (SIADH), resulting in hyponatraemia (low sodium).
The typical exam patient has recently had a cheap hotel holiday and presents with pneumonia symptoms and hyponatraemia. A urine antigen test can be used as an initial screening test.
MYCOPLASMA PNEUMONIA
Mycoplasma pneumoniae causes milder pneumonia and a rash called erythema multiforme, characterised by varying-sized “target lesions” formed by pink rings with pale centres.
It can cause neurological symptoms in young patients.
CURB-65 score
CURB-65 score
INVESTIGATIONS
Investigations
Patients in the community with CRB 0 or 1 pneumonia do not necessarily need investigations.
A point-of-care test for the CRP level can be used in primary care to help guide diagnosis and the use of antibiotics.
Investigations for patients admitted to hospital include:
-Chest x-ray
-Full blood count (raised white cell count)
-Renal profile (urea level for the CURB-65 score and acute kidney injury)
-C-reactive protein (raised in inflammation and infection)
Patients with moderate or severe infection will also have:
-Sputum cultures
-Blood cultures
-Pneumococcal and Legionella urinary antigen tests
White blood cells and CRP are raised roughly in proportion to the severity of the infection.
The trend can help monitor the progress of the patient towards recovery. CRP starts rising 6 hours behind the onset of inflammation and peaks after 24-48 hours.
It may initially be low before becoming very high a day or two later.
PREVENTING PNEUMONIA
COMMENSUALISM AND OPPORTUNISTIC INFECTION
