Respiratory - Pulmonary vascular disease & eosinophilia Flashcards
What is a PE?
PE, or pulmonary embolism, is an obstruction of part or whole of the pulmonary arterial tree by thrombus that has become detached from its site of formation - usually in the peripheral venous system and carried to the lung via the right heart.
What factors predispose to PE?
These are summarized in Virchow’s triad:
1) Venous stasis (e.g. CCF)
2) Increased blood coagulability
3) Damage to vessel endothelium (e.g. peripheral vascular disease)
Conditions producing these include immobility, surgical or accidental trauma, heart disease, pregnancy, oral contraceptives, obesity and intravascular catheters.
What are the morphological features of venous thrombi?
These thrombi are formed in areas of less active blood flow most often in veins of the lower extremities (and in the periprostatic or other pelvic veins).
They are dark red with a higher concentration of RBCs than arterial thrombi. Lines of Zahn are not prominent or may be absent altogether.
They are often associated with concurrent venous inflammatory changes. Inflammation of veins from thrombus formation is referred to as thrombophlebitis.
How does the size of the thrombus affect where it lodges in the lung? What is a saddle embolus?
Large emboli impact in major pulmonary arteries or sit at the bifurcation of both the right and left main trunks - “saddle embolus”.
Small emboli lodge in more peripheral segmental arteries.
What type of infarct do PE’s cause?
Infarction is necrosis resulting from ischaemia caused by obstruction of blood flow. The necrotic tissue is referred to as an infarct.
Infarcts can either be anaemic of hemorrhagic.
Hemorrhagic infarcts are red infarcts, in which red cells ooze into the necrotic area. They occur characteristically in the lung and gastrointestinal tract as the result of arterial occlusion. These sites are loose, well vascularised tissues with redundant arterial blood supplies (in the lung from the pulmonary and bronchial systems; in the GIT from multiple anastomoses between branches of mesenteric artery) and a haemorrhage into the infarct occurs from the non-obstructed portion of the vasculature.
What diseases predispose to increased coagulation?
Thrombotic disorders are classified as either anti-thrombotic (haemorrhagic) leading to pathologic bleeding states such as haemophilia and vWD. They can also be prothrombotic leading to hypercoagulability with pathologic thrombus.
These can be summarised as:
1) Hereditary thrombophilias (factor V liden, protein C and S deficiency, prothrombin 20210A transition etc)
2) Antiphospholipid syndrome
3) DIC
4) Heparin induced thrombocytopaenia (HIT) syndrome
How is the heart affected by a PE?
The heart can undergo structural changes following a PE which leads to impaired function. Acute right ventricular dilatation can occur with massive obstruction of the pulmonary artery. This leads to acute RVF. Systemic shock is due to decreased pulmonary blood flow leading to decreased left ventricular filling and output. There is an additional effect of hypoxia on heart muscle function.
Right ventricular hypertrophy tends to occur in cases of recurrent pulmonary thromboembolism causing pulmonary hypertension.
What are the results of a PE?
These are highly dependent on the size of the embolus and the status of the cardiopulmonary system:
1) Silent: up to 80% of emboli are clinically silent because they are small and are often lysed by fibrinolysins. Infarction does NOT occur in these circumstances, and in the absence of significant myocardial disease (e.g. HF) because of adequate collateral bronchial circulation
2) Infarction
3) Recurrent emboli
4) Sudden death: massive embolism with obstruction of a large artery can result in death or acute right sided heart failure followed by death
5) Circulatory shock: with massive emboli
6) Chronic pulmonary hypertension: an uncommon but important cause which may be difficult to diagnose
7) Abscess: some infarcts become secondarily infected and form abscesses. Alternatively an embolus may be septic
What is the most common cause of pulmonary infarction?
Infarction is usually associated with an embolism but may rarely occur due to a primary vascular thrombosis associated with an abnormal circulation - e.g. in pulmonary hypertension
What is the macroscopic appearance of pulmonary infarction?
The lower lobes are involved in 75% of cases. The infarcts are pyramidal in shape and haemorrhagic with their base on the pleural surface, over which there is a fibrinous reaction.
What are the results of pulmonary infarction?
These vary with the size and multiplicity of the infarcts:
1) Pulmonary dysfunction: due to loss of lung tissue
2) Pulmonary vascular obstruction
3) Pleurisy and pleural effusion: often haemorrhagic
4) Healing: resulting in a fibrous scar
5) Septic infarction: primary septic embolism or secondary infection leading to abscess formation
What is a fat embolism?
This is an example of a non-thrombotic emobolism. Fat emboli tend to occur following fracture of long bones and are sometimes fatal. Clinically they present with cerebral signs (e.g. confusion, dysphasia), dyspnoea, and petechial rash. This is called the fat embolism syndrome.
What are the features of an amniotic fluid embolus?
This is an incredibly rare event but release of amniotic fluid into the circulation in labour can result in sudden cardiovascular collapse or ARDS. Foetal squamous cells are seen in the pulmonary vessels.
How does an air embolism occur?
Air can enter the circulation after trauma or surgery to the great veins or by faulty apparatus or techniques with intravascular therapy. If quantities of air are large enough, sudden cardiovascular collapse occurs due to functional obstruction to the pulmonary circulation and acute right heart failure.
What is Caisson disease?
This is decompression sickness. Rapid decompress releases bubbles of nitrogen as well as oxygen and carbon dioxide into the blood. Nitrogen bubbles cause problems in the CNS and bones particularly, and in pulmonary vessels can produce obstruction.
What are the clinical features of a PE?
The clinical features of pulmonary embolism depend on the size and severity of embolism. Broadly speaking important features in at risk patients to watch out for include: dyspnoea, pleuritic chest pain, haemoptysis, syncope, fever.
Signs: pyrexia, cyanosis, tachypnoea, tachycardia, hypotension, raised JVP, pleural rub, pleural effusion, calf swelling (look for cause).
If an acute minor PE is associated with infarction it tends to produce pleuritic chest pain, haemoptysis and fever.
How should suspected PE be investigated? What are the ECG features of PE?
Consider the diagnosis of PE in all patients with unexplained breathlessness, pleuritic pain, haemoptysis or sudden collapse.
Chest x ray, ECG and arterial blood gases are essential first line investigations:
- CXr: may be normal; can show dilated pulmonary artery small effusion, wedge shaped opacities or cavitation (rare)
- ECG: may be normal or show tacchycardia, RBBB, RV strain (inverted T in V1 to V4) or classic S1Q3T3 pattern
- ABG: hypoxia and hypocapnia (due to hyperventilation)
FBC, U&E and baseline clotting important
What is the role of the D-dimer in diagnosing PE?
D-dimer is useful in excluding a PE but not in confirming it - i.e. only perform in those patients WITHOUT a high probability of a PE. A negative D-dimer test effectively excludes a PE in those with low or intermediate clinical probability and imaging is NOT required. However a positive test does not prove a diagnosis of a PE and imaging is required.
(Wells score suggests that score of >3 carries a high probability of a PE)
What is the gold standard investigation for PE?
CTPA is the recommended first line imaging modality which can show a clot down to the 5th order pulmonary arteries.
V/Q scanning is now rarely performed except on young patients (e.g. females) because the dose of radiation may be too high.
What is the management of a PE?
1) Anticoagulate with LMWH
2) Start warfarin
3) Stop heparin* when INR is >2 and continue warfarin for a minimum of 3 months, aim for an INR of 2-3
Warfarin has a prothrombotic effect for the first 72 hours so heparin cover is required.
For a massive PE:
1) Thrombolysis with alteplase 10mg IV over 1 min then 90mg IV over 2h
2) Consider placement of a vena caval filter in patients who develop emboli despite adequate anticoagulation
What is the mechanism of action of Heparin?
Heparin is a mucopolysaccharide that binds to and activates a circulating natural anticoagulant protein called antithrombin. The heparin anti-thrombin complex inhibits the action of a number of activated clotting factors in the coagulation cascade (IXa, Xa, XIa and XIIa). It also binds directly to thrombin and inhibits its ability to convert fibrinogen to fibrin.
What are the 2 forms of heparin?
Heparin can be used as an unfractionated molecule or as low molecular mass molecules.
Unfractionated heparin has a very short half life, which depends on the dosage and route of administration. LMWHs have a much longer duration of action and half life because they do not bind to plasma proteins or to endothelial cells (like unfractionated forms do). LMHW is the drug of choice in pregnant women requiring anticoagulation.
Examples of low molecular weight heparin include ENOXPARIN (clexane) and TINZAPARIN
