Week 3 - Leg Ulcers, Arterial, Venous & Lymphatic Disorders

Question 1

What are the differential diagnoses of chronic leg ulcers?

Answer 1

• Venous: varicose veins, thrombophlebitis.
• Arterial: atherosclerosis, diabetes.
• Neuropathic: diabetes.
• Malignancy: BCC, SCC, MM.
• Infections: leprosy, TB, Treponemal (Yaws).
• Others: dermatitis, vasculitis, lymphedema.

Question 2

Outline leg ulcers.

Answer 2

• Can be divided up into venous and non-venous.
• Venous ulcers are commonly found in the gaiter region whereas non-venous ulcers are more common on the foot.
• Leg ulcers are common because the lower part of the leg has ischaemia - blood pools in lower leg due to inactivity/abnormalities (constant ischaemia).
• Can be simple (infection) or serious (malignancy).
• Venous ulcers are the commonest clinically (80%). Arterial ulcers (10%), all other causes (10%).
• Diabetes can cause many different types of leg ulcers (arterial, neuropathic, infectious) but does not typically cause venous ulcers.

Question 3

Outline the aetiology of venous ulcers.

Answer 3

• Due to varicose veins (most common - obstruction to venous outflow) or thrombophlebitis (venous inflammation with thrombus formation).
• Ulcer results from stasis and infection.
• Loss of skin surface in drainage area of varicose vein, usually in lower leg.

Question 4

Explain the pathogenesis of venous ulcers.

Answer 4

1. Presence of varicose veins results in venous stasis.
2. Venous drainage of the skin becomes too poor to maintain metabolism & promote healing.
3. Epidermis dies and is sloughed off leaving a venous ulcer (also be triggered by minor trauma).

• Due to lack of venous drainage - obstruction to outflow.
• Blood enters the tissue but does not exit - block in vein results in accumulation of fluid → tissue will become more wet (more hydrostatic pressure then oncotic pressure - filtration is more).
• Ulcers will be wet - accumulation of fluid and stasis of blood → generalised ischaemia and accumulation of excretory products → area becomes ulcerated, red and oozy.
• Wet, bleeding, dermatitis.

Question 5

Describe the morphology of venous ulcers.

Answer 5

• Location: gaiter region (lower 1/3 of leg - above medial/lateral malleoli).
• Large, irregular, shallow.
• Wet, oedematous, oozing.
• Moist granulating base - bleeds on touch (arterial supply still intact).
• Surrounding eczematous stasis dermatitis (accumulation of waste material - tissue fluid → inflammation).
• Mild pain, relieved by elevation.
• Compression bandage helps (if veins still patent).
• Additional symptoms: skin is warm and oedema often present, possible infection.

Question 6

Identify the investigations and management of venous ulcers.

Answer 6

Investigations:
• Ankle pressure brachial index (APBI) using Doppler to exclude an arterial ulcer.
• Microbiology (if an infection is suspected).
• Patch testing (if associated dermatitis).

Management: compression bandage*
• Exudate & slough should be removed with normal saline.
• Antibiotics if signs of infection (as ulcers frequently colonised by bacteria).
• Surrounding eczema treated by corticosteroid.
• Local grafting of patients own healthy epidermis into ulcer with leg elevation.
• Vein surgery may help younger patients.

Question 7

Outline the aetiology, risk factors and pathogenesis of arterial ulcers.

Answer 7

Aetiology:
• Atherosclerosis (PVD - due to block in artery, no fluid enters → ulcer is dry).
• Diabetes.

Risk factors:
• Smoking.
• Hypertension.
• Diabetes.
• Hyperlipidaemia.

Pathogenesis:
• Decreased arterial supply to region of skin → poor metabolism/healing of skin.
• Dry, dark, painful.

Question 8

Describe the morphology of arterial ulcers.

Answer 8

• Location: distal and dorsal foot or toes (tips of toes). Thin part of skin over toe joints, under heel, over malleoli and anterior shin.
• Cold, pale feet, absent or weak pulses (signs of arterial disease).
• Dry, irregular clear border, grey black necrotic.
• Pale granulation, does not bleed on touch (arteries blocked).
• Painful (nocturnal), partly relieved by dependency - putting legs down.
• Skin: shiny, loss of hairs - suggests atrophy due to chronic ischaemia.
• Angiogram, no compression bandage.
• Complication: infection.

• Death of tissue is due to gangrene. Tips of toes → diabetic gangrene. Blood flow to the leg will be affected. Treatment - extensive amputation.

Question 9

Identify the investigations and management of arterial ulcers.

Answer 9

Investigations:
• APBI using Doppler, microbiology (<8 indicates arterial insufficiency).
• Angiogram.

Management:
• Do not use a compression bandage as this is dangerous (will further reduce arterial supply and cause larger areas of skin to become necrotic).

Question 10

Outline the aetiology of neuropathic ulcers.

Answer 10

• Due to nerve damage. Most common cause is diabetes.
• Ulcers due to lack of sensation, nerve fibre damage.
• Clean, caving, callus.

Question 11

Explain the pathogenesis of neuropathic ulcers.

Answer 11

• Multifactorial. Final common pathway is pressure leading to ischaemia & necrosis.

• Diabetes → damage to vessels (microangiopathy) → reduced blood supply to lower limbs.
• Diabetes → damage to nerves (neuropathy) → patient doesn’t feel damage to skin.
• Bed sores → compression vascular supply → ischaemia → ulcer.
• Usually clean, painless, surrounded by a rim of hard skin. This happens because of constant pressure e.g. footwear, bottom of foot (walking).
• Constant damage for a long time (months-years) due to footwear/walking → gradually causes ulceration because of lack of sensation, protection not there → pain not felt by patient.
• In response to constant damage, the skin becomes harder → corneal layer thickens around ulcer.

Question 12

Describe the morphology of neuropathic ulcers.

Answer 12

• Location: distal leg, pressure points.
• Clean punched-out ulcers, deep caving.
• Frequently painless, absent or weak pulses.
• Often with surrounding calluses (hyperkeratosis).
• Probing or debriding leads to brisk bleeding (arteries still intact - bleeding but no pain).
• May also have impaired sensation and diminished positional sense or 2-point discrimination in surrounding skin (extensive neural damage, diabetes).
• Complication: infection.

Question 13

Identify the investigations and management of neuropathic ulcers.

Answer 13

Investigations:
• Glucose tolerance (for diabetes).
• APBI using Doppler to exclude an arterial ulcer.
• Microbiology (if infection suspected).

Management:
• Prevention: Effective management of diabetes and care of feet (e.g. wearing shoes etc.)
• Prevention: For bedridden patients, should roll them or use pressure-relieving mattresses.

Question 14

Outline malignant ulcers.

Answer 14

• Growth, tumour.
• Cause: UV rays, idiopathic.
• Location: sun exposed.

Features:
• ABCDE*
• Irregular, punched-out, deep, caving with tumour.
• Swelling, extensive ulceration.
• Frequently painless (can be painful).
• Lymph nodes, spreading, metastases, cancer cachexia - weight loss etc.

*EXAM HINT - SCC, BCC, melanoma.

Question 15

Outline infectious ulcers.

Answer 15

• Multiple - many different types of infection can cause ulcers in the lower leg.
• Common in tropical area, islanders. Respond to penicillin.
• Cause: TB, Treponema (Yaws, Pinta) etc.
• Location: Not particular, usually multiple. Can occur anywhere but more common in legs.

Features:
• Irregular, non-specific.
• Associated with lymphadenitis.

Question 16

What are the 3 types of arteries?

Answer 16

Arteries (high pressure) are divided into 3 types based on their size and structure:
• Large - e.g. aorta and pulmonary arteries - classified by many elastic fibres which alternate with smooth muscle cells throughout the media (all elastic lamina in between smooth muscles).
• Medium (muscular) - any artery that has a name e.g. coronary, renal - only smooth muscle bundles in media. The media is composed primarily of smooth muscle cells, with elastin limited to the internal and external elastic lamina.
• Small/arterioles - capacitance vessels - hold a major amount of blood. Function - maintenance of BP. The media in these vessels is mostly composed of smooth muscle cells. No elastic lamina.

Question 17

Identify the diseases of arteries.

Answer 17

Arteriosclerosis: hardening of the arteries (age, diabetes, hypertension). Generic term reflecting arterial wall thickening and loss of elasticity. 3 distinct types:
• Atherosclerosis - large and medium arteries (macroangiopathy).
• Monkeberg medial sclerosis - medium arteries.
• Arteriolosclerosis - small arteries/arterioles (microangiopathy).

Arteritis: vasculitis - inflammation of blood vessels (arteries). 2 groups:
• Immune - ANCA +ve (anti-neutrophil cytoplasmic Ab) - formation of Ab’s that react with cytoplasm of neutrophils. Activated neutrophils cause damage to blood vessels.
- Giant cell arteritis.
- Polyarteritis nodosa.
- Wegener’s granulomatosis.
- Buerger disease.
• Infection - bacteria, virus, fungi, mycotic aneurysm, septicaemia.

Congenital disorders:
• Aneurysms, ectasia, AV malformations.
• Tumours (nevi - excess proliferation of BV), ectasia (birthmark - dilation of BV).

Tumours:
• Haemangioma (benign), angiosarcoma (malignant).
• Tumour like - pyogenic granuloma (complications of wound healing).

Question 18

Describe Monkeberg medial sclerosis.

Answer 18

• AKA medial calcific sclerosis.
• Characterised by the presence of calcific deposits in muscular arteries, typically in persons older than 50. The lesions do not encroach on the vessel lumen and usually are not clinically significant.
• Intima and media fibrosis and calcification - no obstruction* → not many clinical symptoms (except for calcification of arteries on X-ray).
• Fibrosis and calcification of blood vessels. Usually age associated - older age group.
• Dilation, hardening of large artery.
• Dilation and unfolding of aortic arch.

Question 19

Outline arteriolosclerosis (microangiopathy).

Answer 19

• Hardening and thickening of arterioles and capillaries.
• Common cause of organ failure, organ ischaemia and infarction in all lifestyle disorders - diabetes, hypertension, hypercholesterolaemia, obesity.
• 2 major types - hyaline and hyperplastic.

Question 20

Describe the 2 types of arteriolosclerosis.

Answer 20

Hyaline:
• Typically in diabetes.
• Deposition of proteins in the wall. Leakage of proteins, proteinuria.
• Is marked by homogenous, pink hyaline thickening of the arteriolar walls, with loss of underlying structural detail and luminal narrowing.
• The lesions stem from leakage of plasma components across injured endothelial cells, into vessel walls and increased ECM production by SMCs in response to chronic haemodynamic stress.
• In diabetes the underlying aetiology is hyperglycaemia-associated endothelial cell dysfunction.

Hyperplastic:
• Typically in hypertension.
• Proliferation of smooth muscle fibres.
• Vessels exhibit concentric, laminated thickening of arteriolar walls and luminal narrowing.
• The laminations consist of SMCs and thickened, reduplicated basement membrane.

• Mixture of both in either condition because diabetes usually associated with hypertension.

Question 21

Outline vasculitis.

Answer 21

• General term for vessel wall inflammation.
• Besides findings referable to the involved tissue(s), there are usually also signs and symptoms of systemic inflammation such as fever, myalgia, arthralgia and malaise.
• Although several forms of vasculitis have a predilection for relative large vessels (e.g. large or medium arteries), most affect small vessels (arterioles, capillaries and venules).
• 2 types:
- Immune mediated inflammation.
- Direct vascular invasion by infections pathogens. (Infections can also indirectly precipitate immune-mediated vasculitis e.g. by generating immune complexes or triggering cross-reactivity).
• It is critical to distinguish between infectious and immunologic mechanisms because immunosuppressive therapy is appropriate for immune mediated vasculitis but could exacerbate infectious vasculitis.
• Physical and chemical injury including that due to radiation, mechanical trauma and toxins can also cause vasculitis.

Question 22

Identify the main immunologic mechanisms underlying non-infectious vasculitis.

Answer 22

• Immune complex deposition.
• Anti-neutrophil cytoplasmic antibodies.
• Anti-endothelial cell antibodies.
• Autoreactive T cells.

Question 23

What are anti-neutrophil cytoplasmic antibodies?

Answer 23

• ANCAs are a heterogeneous group of autoantibodies directed against constituents (mainly enzymes) of neutrophils primary granules, monocyte lysosomes, and endothelial cells.
• Very useful diagnostic markers - their titers generally mirror clinical severity and a rise in titers after periods of quiescence is predictive of disease recurrence.
• ANCAs can directly activate neutrophils, stimulating the release of reactive oxygen species and proteolytic enzymes; in vascular beds, this may lead to endothelial cell injury.
• The ANCA autoantibodies are directed against cellular constituents and do not form circulating immune complexes.

Question 24

Outline giant cell (temporal) arteritis.

Answer 24

• Typically affects the temporal artery but can effect them all e.g. large aorta and all the medium sized arteries.
• Granulomatous (T cell) inflammation of large and medium arteries leading to fragmentation of internal elastic lamina, giant cells, thrombosis.
• Is associated with polymyalgia rheumatica (pain/stiffness in hip/shoulder).
• Frequently involves the temporal artery (ophthalmic artery - blindness). Ocular symptoms abruptly appear in 50% of patients and range from diplopia to complete vision loss.
• Usually occurs in older patients (>50 yo).
• Associated with HLA - autoimmune?
• Plenty of inflammatory cells - T lymphocytes and giant cells destroying the tunica media and elastic fibres → results in thrombosis of blood vessel.
• Clinically presents as painful, thickened, nodular temporal arteries.
• Segmental/patchy involvement - does not involve whole thickness. Therefore, a biopsy of the artery may be normal but show inflammation elsewhere (negative biopsy does not exclude the diagnosis).
• Aetiology/Pathogenesis: predominantly unknown but thought to involve immune factors.
• Clinical features: painful nodules on skull, headache, fever, fatigue, sudden blindness.
• Histology: inflammation in tunica media and interna with breaks in elastic tissue + presence of giant cells.
• Treatment: corticosteroids or anti-TNF therapy.

Question 25

What is Takayasu arteritis?

Answer 25

• Similar granulomatous vasculitis (T cell mediated immune reaction) but in younger patients (<50 yo).
• Severe obstruction of major vessels (e.g. aortic arch and arch vessels) → pulseless disease (lack of arterial pulse, weakening in upper extremities).

Question 26

Outline polyarteritis nodosa.

Answer 26

• Belongs to a group of diseases characterised by necrotising inflammation of the walls of blood vessels most likely caused by the deposition of immune complexes.
• In up to 30% of patients, the vasculitis is attributable to immune complexes composed of hepatitis B surface antigen (HBsAg) and anti-HBsAg antibody.
• Rare, immune, HBsAg. No association with ANCAs.
• Systemic necrotising vasculitis (renal, heart, liver and GIT but not lungs).
• Typically disease of medium/small arteries. Usually involves kidney vessels (can be systemic but does not involve lungs).

• Aetiology/Pathogenesis: is unknown but thought to be immune related. Hepatitis B infection is a risk factor (and conditions associated with HBs antigens).
• Clinical features:
- Nodules over arteries.
- Acute fever, muscle/joint pain, asymmetric polyarthritis.
- Malaise, rash, weight loss.
- Neuropathy, kidney failure.
- Produces necrotic ulcers (DDx for leg ulcers).
• Investigations: high ESR, CRP & WBC (suggestive of inflammation).
• Histology: infiltration of inflammatory cells, fibrinoid necrosis and luminal thrombosis.
• Treatment: immunosuppression.

Question 27

Outline Wegener’s granulomatosis.

Answer 27

• Necrotising vasculitis characterised by a specific triad of findings:

• Granulomas of the lung and/or upper respiratory tract (ear, nose, sinuses, throat).
• Vasculitis of small to medium arteries (capillaries, venues, arterioles and arteries), most prominently in the lungs and upper respiratory tract.
• Glomerulonephritis.

• Aetiology: cell mediated hypersensitivity reaction directed against inhaled infectious or environmental antigens.
• Pathogenesis: ANCA → activate neutrophils → endothelial cell injury and inflammation → thrombosis.
Antiproteinase-3 (PR3-ANCA) +ve.
• Clinical features: classic presentations include bilateral pneumonitis with nodule and cavitary lesions, chronic sinusitis, mucosal ulcerations of the nasopharynx and renal disease. Rash, myalgia, articular involvement, neuritis and fever can also occur.
• Morphology:
- Gross - lungs show cavitating grey-white lesions (similar to TB but no caseation).
- Microscopy - granulomatous inflammation around small vessels with epitheloid and giant cells.
• Complications: if untreated, 80% patients die within a year.
• Treatment: steroids, cyclophosphamide, TNF inhibitors and anti-B cell antibodies (rituximab).

• Granulomatous inflammation around small vessels.
• Vasculitis of small vessels, typically affects lungs. Begins with neutrophils and later goes to chronic granulomatous inflammation.

Question 28

Outline Buerger disease.

Answer 28

• AKA Thromboangiitis obliterans.
• Segmental inflammation (focal acute and chronic inflammation) with thrombosis of medium and small blood vessels (especially tibial and radial arteries).
• Occurs almost exclusively in heavy tobacco smokers and usually develops before age 35.
• Artery thrombosis - present with painful, peripheral gangrene → results in amputation.
• Also involves surrounding veins and lymphatics (but starts in arteries) - secondary extension.

• Aetiology/Pathogenesis: unknown. Strongly associated with tobacco and smoking (smoke antigen may produce antibodies that affect blood vessels/direct endothelial cell toxicity). Genetic predisposition - common in males, Jews, Indians.
• Clinical features:
- Peripheral gangrene develops in fingers and toes.
- Cold sensitivity in the hands (cold-induced Raynaud phenomenon).
- Chronic ulceration in toes, feet or fingers.
• Histology:
- Presence of acute and chronic inflammation.
- Thrombosis and fibrosis of small arteries in the arms and lower legs.
- Also involves veins and surrounding tissues.
• Treatment: smoking abstinence in the early stages of the disease can ameliorate further attacks.

Question 29

What is a pyogenic granuloma?

Answer 29

• Moist growth over a wound - excess inflammatory granulation tissue and new blood vessel.
• Wound complication producing excess granulation tissue.
• Commonly occurs in gingiva, fingers (palmar surfaces).

Question 30

Outline Kaposi sarcoma.

Answer 30

• Common in HIV patients - AIDS.
• Malignant - angiosarcoma (malignant tumour of blood vessels - can be seen without HIV too).
• Caused by infection with HHV-8 virus.
• Many types:
1. Classic KS: HIV negative - Jews* (typically seen in Mediterranean people and Jews).
2. Endemic African KS: HIV negative.
3. Transplant associated.
4. Common HIV associated.

Question 31

Outline Raynaud’s phenomenon.

Answer 31

• Vasoconstriction of digital arteries.
• Results from exaggerated vasoconstriction of arteries and arterioles in the extremities, particularly the fingers and toes but also sometimes the nose, earlobes or lips.
• The restricted blood flow induces paroxysmal pallor or cyanosis (alternating areas of pallor and cyanosis in the digits).
• 2 types:
- Primary (Raynaud’s disease).
- Secondary (Raynaud’s phenomenon).

• Primary: caused by exaggerated central and local vasomotor responses to cold or emotion (hyperactive blood vessel, cold/emotional trigger). Genetic, affects 3-5% of population, has a predilection for young women. Normal microscopy. Primary disease, no other associated disorders.
• Secondary: secondary to other blood vessel disorders. Vascular insufficiency due to arterial disease caused by other entities such as SLE, scleroderma, Buerger disease or even atherosclerosis.
• Cardiac Raynaud’s disease: myocardial vasospasm.

Question 32

What are the main venous disorders?

Answer 32

• Varicose veins and phlebothrombosis/thrombophlebitis account for at least 90% of cases of clinically relevant venous disease (varicose veins and venous thrombosis).

Question 33

Outline varicose veins.

Answer 33

• Dilated tortuous superficial veins produced by chronically increased intraluminal pressure and weakened vessel wall support (reversal of flow into superficial veins).
• Congenital (valve defect in deep veins of lower limb) or acquired (most common - obesity, pregnancy, prolonged standing etc.)
• Stasis dermatitis and ulcers - gaiter region (more common in lower legs - chronic ischaemia, ulceration).
• Lower extremity stasis, congestion, oedema, pain and thrombosis. Chronic varicose ulcers due to poor wound healing and superimposed infections.
• Note: embolism is very rare (PE) - blood clot does not go back against reversed flow.
• Compression stockings & surgery are options but treatment is not necessary.

Question 34

Explain the pathogenesis of varicose veins.

Answer 34

1. Normally blood returns from lower limbs to heart by muscle pump, aided by valves, which pumps blood from superficial venous system to deep venous system to heart.
2. Incompetent valves cause blood to reflux back from deep to the superficial veins, causing blood to pool → increased pressure in superficial system (venous hypertension).
3. Venous hypertension causes superficial veins to become dilated & tortuous (varicose veins.)
4. As the blood pools, this results in venous stasis.

• Normally, blood from superficial veins goes through muscle into deep veins - the valves prevent backflow. Walking/exercise causes contraction of calf muscles → squeezes the central deep veins to push blood back up into heart.
• When the legs are not used (immobilization - long flight, sitting) → not enough sufficient pressure in the legs to push blood back → results in accumulation of blood due to lack of activity of muscle pumps.
• Lack of activity of muscle pumps/abnormal valves (congential) → results in blood falling back. High pressure blood goes back into the superficial vessels. These vessels develop tortuous dilation as they have no muscle/fascia support (reversal of flow results in tortuous dilation → varicose vein).
• The deep veins are protected by muscle → do not dilate even though abnormality is present. Because there is reversal of flow, it is rare for a thrombus to go back from the superficial veins.
• Many types of varicose veins. Most common clinically is in the lower legs. Others include oesophageal varices and haemorrhoids.

Question 35

Outline the aetiology of deep vein thrombosis (DVT).

Answer 35

• Thrombosis of deep veins.
• Lower leg (but also occurs in pelvic, peritoneal, cerebral, SVC and IVC syndromes - due to infection/malignancy).
• Aetiology: Virchow’s triad (vein-blood-flow) - BV injury, hypercoagulability and stasis.

• Vessel damage (vein):
- Surgery.
- Trauma.
- MI.
- Stroke.
- Malignancy.
- Phlebitis - infections and inflammation of veins (thrombophlebitis vs. phlebothrombosis).
Thrombophlebitis - thrombi formation in a vein with inflammation.
Phlebothrombosis - thrombi formation in a vein without inflammation (i.e. DVT).

• Hypercoagulability (blood):

• Congenital - ATIII, protein C/S deficiency, factor V leiden, antithrombin deficiency, prothrombin mutation.
• Acquired - lupus anticoagulant, surgery, trauma, malignancy.
• Drugs - OCP, HRT, medications.
• Hyperviscosity - polycythemia, paraproteins.
• Hyperhomocysteinemia.

• Stasis (flow):

• Immobilisation.
• Paralysis.
• Long flight.
• In-patients/post surgical ward (immobilisation and coagulation).
• Pregnancy.
• Obesity.
• Heart failure.

Question 36

Describe the pathogenesis and clinical features of deep vein thrombosis.

Answer 36

Pathogenesis:
• Thrombosis (Virchow’s triad) → obstruction → stasis (acute)* - unlike varicose veins (no ulcers in DVT).

Clinical:
• Thrombi in the legs tend to produce few, if any reliable signs or symptoms. When present, local manifestations include:
- Oedema
- Heat
- Tenderness
- Redness
- Swelling
- Cyanosis
- Pain
- Superficial vein dilation
- Homan's sign - pain can be elicited by pressure over affected veins, squeezing the calf muscles or forced dorsiflexion of the foot.
• Symptoms are often absent, especially in bedridden patients. Absence of finding does not exclude DVT.

Question 37

Outline the complications and management of deep vein thrombosis.

Answer 37

Complications:
• Pulmonary embolism (PE) - sudden severe chest pain, DDx for MI → thrombus can break off and travels to the heart and then into pulmonary circulation and blocks one of the major vessels → infarction (blocking of pulmonary arteries).
• Paradoxical thrombus - left to right shunt (ASD, VSD, PDA) - thrombus gets into systemic circulation.

Management:
• Anticoagulant therapy.
• Prevention includes exercising calf muscles & maintaining hydration while flying, calf compression stockings for patients immobilised.
• DVT can be diagnosed by duplex ultrasound.

Question 38

Outline pulmonary embolism.

Answer 38

• Blood clot (emboli) that occlude pulmonary arteries.
• Most pulmonary embolisms arise from propagation of lower limb DVT.
• Part of a venous thrombi (from legs) breaks off and becomes an emboli.
• The emboli travels via the veins to IVC to pulmonary arteries to lungs.
• Emboli may become stuck in pulmonary arteries → the physiological response and clinical effects depend on extent to which the pulmonary artery blood flow is obstructed:
- Pulmonary haemorrhages due to small emboli → transient chest pain + cough.
- Pulmonary infarct → dyspnoea, tachypnoea, fever, chest pain, cough, haemoptysis, shock.
- Instantaneous death (due to large emboli).

Diagnosis:
• Well's Criteria.
• FBC, U+Es, clotting, D dimer (only in patients without high probability of PE - high sensitivity, low specificity).
• ECG.
• CXR - wedge shaped infarct.
• ABG.
• CTPa - sensitive and specific.
• Ventilation perfusion scan - rarely used.