Thrombosis, embolism and infarction Flashcards Preview

MRCS A Pathology > Thrombosis, embolism and infarction > Flashcards

Flashcards in Thrombosis, embolism and infarction Deck (50):


A thrombus is defined as a solid mass formed in the living circulation from the components of the streaming blood. This serves to distinguish it from a clot which may form:

• outside the body
• in a dead body
• outside of the vasculature

Thrombosis (the formation of thrombus) is a well- ordered series of events involving the blood platelets and the clotting cascade. Platelets adhere to areas of endothelial damage and if the stimulus is strong enough will go on to platelet activation with shape change and release of a number of substances which enhance the process of thrombosis at the same time as aggregating together.


Stages in the development of thrombosis I

Thrombus may form in the heart, arteries, veins, or capillaries. The first stage involves platelets sticking to the damaged endothelium, and then a dense layer of fibrin and leucocytes adhere to the surface of the platelet. Blood clot (fibrin and red cells) develops on this layer of leucocytes and platelets, and then a secondary layer of platelets collects on the surface of the blood clot.

The gradual extension of thrombosis leads to a propagated or consecutive thrombus. Organization then begins with adherence to the wall of the vessel as mural thrombus. A second stage develops with a further batch of platelets laid down over the initial aggregate and then a further layer of blood clot. In this way alternate layers of platelets and blood clot form a laminar arrangement.

This causes a differential contraction
of platelets and fibrin and gives a rippled appearance reminiscent of rippling of the sand on a beach. This has also been described as having a coralline appearance.

The ridges on the surface of the thrombi are known as the lines of Zahn.


Causes of thrombosis

Several factors contribute to thrombus formation and these are usually grouped together under three headings (Virchows triad). The factors in Virchow’s triad are:

• damage to the vessel wall
• alterations in blood flow
• alterations in the constituents of the blood

Not all these factors need to be present at the same time; some will be dominant in one clinical situation whilst others will predominate in another. For example, venous thrombosis is commonly due to alterations in blood flow, while arterial thrombosis is more commonly due to vessel wall changes of atheroma, which does not occur in veins.


Virchows triad: Damage to the vessel wall

• Arteries – atherosclerotic plaques or synthetic grafts
• Heart – congenital abnormalities or artificial valves
• Veins – local injury caused by pressure on the calves from bed or operating table or by insertion of intravenous cannulae; or distortion of the femoral vein during hip replacement.


Virchows triad: Damage to the vessel wall: Arterial thrombosis

Atheroma of the arterial wall presents a good example of how vessel damage can lead to thrombosis and it is also a very common and important clinical situation.

Vascular endothelial cells have intrinsic fibrinolytic activity in which plasminogen, an inactive plasma protein synthesised in the liver, is converted to the active fibrinolytic enzyme plasmin. Whether thrombosis occurs or proceeds depends on the balance between the processes of thrombosis and fibrinolysis.

As fatty streaks progress they present more obstruction to normal flow, and endothelial cells may be lost. Fibrin and platelets may become deposited on the surface and protrude into the lumen, causing more turbulence, and a complicated atheromatous plaque develops. In addition to the risk of thrombosis on a complicated plaque there is also a risk from haemor- rhage within it, and when it occurs it causes the plaque to protrude even further into the lumen.


Virchows triad: Damage to the vessel wall: Venous thrombosis

Mechanical damage and vascular inflammation are the commonest causes of damage to venous walls, with subsequent thrombus formation. Inflammation of vessel walls, either arteries or veins, can cause thrombus formation, but the converse is also true. Thrombus initiates an inflammatory response, and in any given instance it can be difficult to say whether the process represents phlebothrombosis (thrombus due to inflammation) or thrombophlebitis (inflammation due to thrombosis). However, the commonest cause of venous thrombosis is alteration to blood flow.


Virchows triad: Alteration in blood flow

The normal laminar flow may change to a turbulent pattern. This may happen with:

• prolonged inactivity following surgery, trauma, or a myocardial infarction
• heart failure
• proximal occlusion of the venous drainage.

Alterations in blood flow are critical in the venous system since pressure is much lower and the normal rate of flow is much slower than in the arteries. As pressure is so much lower in the venous system and the vein walls are so much thinner than the walls of arteries of the same calibre, use is made of the pumping action of the surrounding muscle groups to aid return of blood to the heart.

Consequently any decrease in muscle activity deprives venous blood of this added action and relative stasis occurs. Thus venous thrombosis becomes more likely in the veins of immobile subjects. The elderly are particularly at risk since they often have a degree of venous impairment or relative cardiac failure. One of the commonest deficiencies of the elderly venous system is impairment of the function of venous valves, and thrombosis is often seen to begin at the site of valves where, even under normal circumstances, some degree of turbulence is to be expected.


Virchows triad: Alterations in the constituents of the blood

Alterations which may occur include:
• increased number and adhesiveness of platelets following surgery or injury;
• increased adhesiveness of young platelets produced at this time;
• fluid loss, which may increase viscosity; and
• thrombophilia – a variety of hypercoagulable states due to an abnormal balance of clotting factors and natural anticoagulants.

Factor V which plays a role in the conversion of prothrombin to thrombin is inhibited by Protein C, Protein S and antithrombin.


Congenital thrombophilia

• factor V Leiden – a variant of Factor V which is relatively resistant to Protein C (named after the town in Holland where the original research was done)
• protein C deficiency
• protein S deficiency
• antithrombin deficiency
• prothrombin 20210A – which results in increased
plasma levels of prothrombin.


Acquired thrombophilia:
Antiphospholipid (APL) syndrome

• Antiphospholipid (APL) syndrome, also known
as lupus ‘anticoagulant’ or Hughes’ syndrome,
an auto-antibody which may be associated with systemic lupus.

Platelet surface phospholipids play a part in the activation of the coagulation cascade. The production of these is affected in this condition.


Acquired thrombophilia:
myeloproliferative disorders

• myeloproliferative disorders: e.g. polycythaemia, thrombocythaemia and chronic myeloid leukaemia;


Acquired thrombophilia:
advanced malignancy

• advanced malignancy: increased coagulation due to substances produced by tumours as yet unidentified. The thrombosis tends to be particularly aggressive and cases of venous gangrene are almost always due to this cause;


Acquired thrombophilia: Hyperhomocysteinaemia

Hyperhomocysteinaemia: the formation of cysteine and methionine in the body, requires vitamin B12 and folic acid as cofactors. If there is any block in this process then homocysteine is formed. A raised homocysteine level is widely accepted as a risk factor for arterial disease and venous thrombosis. Adequate intake of folic acid and B vitamins reduce blood levels of homocysteine and studies are ongoing to see if this improves the outlook for vascular disease.


Indications for investigating for thrombophilia:

• positive family history of thrombosis;
• recurrent thrombosis;
• venous thrombosis before the age of 40–50;
• unprovoked thrombosis at any age;
• unusual sites such as cerebral, mesenteric, portal or hepatic veins;
• thrombosis during pregnancy, oral contraceptives
or hormone replacement therapy; and
• unexplained abnormal laboratory test such as
prolonged PTT.


Fate of a thrombus

Thrombi may:
• undergo complete resolution
• become organised as a scar
• recanalise
• embolise in whole or in part.

It is not clear what factors determine which of these fates a thrombus will suffer, although size may be a factor. Small thrombi are being formed and resolved constantly, and some degree of disturbance of blood flow is probably required to tip the scales and cause a thrombus to organise.
Certainly a larger thrombus will cause turbulence and/or inflammation and make it likely that further thrombosis will occur on its surface, causing the thrombus to lengthen, a process known as propagation.


Thrombus resolution

(See diagram)

Resolution means that the clot is completely dissolved by processes of thrombolysis. In the clinical setting this is achieved by the use of thrombolytic enzymes, e.g. plasminogen activator or urokinase, but these have to be delivered onto the clot more or less directly, otherwise they diffuse through the blood stream and may become so dilute that they are ineffectual.

Current therapies involve substances that act directly or indirectly on plasminogen activators. Compounds such as aspirin and heparin help prevent further thrombus formation but do not help in lysis of an established thrombus. If the thrombus is not completely removed then the residue undergoes organisation.


Thrombus organisation

Organisation is the process by which the thrombus is converted to a scar and eventually covered by endothelial cells. Intravascular scarring is essentially similar to those processes involved in the production of scars from thrombi in wound healing generally.

The main difference between intravascular granulation tissue and a thrombus is that with a thrombus the vascular phase of granulation tissue is prolonged and, if the thrombus does not resolve completely, the capillaries fuse together, resulting in one or several new vessels passing through the scar. This process is called recanalisation and in some cases may result in one or more functional vascular channels.



Thromboembolism is embolisation of a thrombus and should be distinguished from emboli of other materials since the clinical setting is different, as is the treatment. The effects of thromboemboli depend upon where the embolus settles, which in turn depends upon where the thrombus forms and what size the embolus is.

Emboli arising from thrombi in veins will all go to the lungs (unless there is an abnormal connection between right and left heart). They will generally not arrest early in the circulation since the veins increase in diameter with the direction of blood flow as they approach the lungs, and only then do they start to turn into progressively smaller vessels of the lung bed. Arterial emboli will arrest in the artery with the smallest calibre which they can enter, and this will always be more peripheral than their origin because arterial size decreases in the direction of blood flow.



An embolus is an abnormal mass of undissolved material which passes in the blood stream from one part of the circulation to another, impacting in vessels too small to allow it to pass. The actual material which passes along the blood stream is termed an embolus. When it impacts and obstructs the flow of blood, this is known as an embolism. Thus when a thrombus in the leg breaks off, this is an embolus, and when it impacts in the pulmonary artery it is a pulmonary embolism. Emboli may consist of:

• thrombus
• gas (air and nitrogen)
• fat
• tumour
• amniotic fluid
• foreign body
• therapeutic emboli, e.g. gelfoam, muscle, steel coils.


Venous thromboembolism

The overwhelming majority of emboli arise from thrombus in the veins of the lower limbs. They then travel up through the inferior vena cava to the right side of the heart and finally impact in the pulmonary artery or one of its major branches, depending on the size of the embolus. The process of venous thrombosis and embolism is extremely common, and it has been estimated that approximately 30% of hospital inpatients have deep venous thrombosis (DVT) and in approximately 10% of postmortem examinations there is evidence of pulmonary embolism.

This is potentially such a common problem that most hospital in-patients should be on some form of prophylaxis against DVT. While mechanical methods such as elastic stockings and inflatable leggings used during operation are helpful, prophylactic subcutaneous heparin is probably the most reliable. Many hospitals now have a policy of giving heparin to all patients unless there is a specific contraindication.


Venous thromboembolism treatment

Traditionally unfractionated heparin was used but it has the disadvantage that for prophylaxis it needs to be given twice a day (or even three times for high risk patients) and if used therapeutically is ideally given by the i.v. route. Also it needs careful monitoring to ensure the correct dose is given.

Low molecular weight heparin (LMWH) is more expensive but has the advantage that it only needs to be given once a day, for prophylaxis or therapy, via the subcutaneous route and the dose required is predictably governed by the weight of the patient. There is therefore no need to check the dose with blood tests.


Heparin-induced thrombocytopenia

A serious but uncommon side-effect of heparin is heparin-induced thrombocytopenia (HITS syn- drome). HITS is caused by an immunological reaction that makes platelets aggregate within the blood vessels. Formation of platelet clots can lead to thrombosis. It has a lower incidence with LMWH than with the unfractionated variety and if it is going to occur, normally does so within 5–10 days of treatment. Thus anyone requiring a prolonged course of heparin should have a platelet count performed after a week’s treatment.


Embolism complications

Pulmonary emboli may be small and clinically ‘silent’ and often multiple. These are frequently dissolved by endogenous thrombolysis or they may become incorporated into the vessel wall with an overlying new endothelium accompanied by proliferation of smooth muscle cells. If multiple small emboli occur over a period of time and become organised in this way, diffuse narrowing of small vessels can result in pulmonary hypertension.

If the embolus is large, as from an iliofemoral venous thrombosis, then a massive pulmonary embolism may occur. If both main pulmonary arteries are blocked then sudden death will ensue. If only one side is blocked, severe shortness of breath and circulatory collapse may occur. It is not known precisely why this happens, since ligation of the main pulmonary artery, as in pneumonectomy, does not cause this problem. A vagal reflex inducing spasm of the coronary and pulmonary arteries, perhaps associated with peripheral vasodilatation, has been suggested.


Peripheral arterial embolism

Systemic emboli from the heart and proximal arteries deposit in arteries more distally along the arterial tree. Total occlusion of such arteries may produce relative ischaemia as a collateral supply may be available. If there is no collateral supply, infarction will occur.

Arterial thromboembolism may come from the following sites:
• heart, e.g. left atrial appendage in atrial fibrillation (accounts for 70%), mural thrombus following MI, valvular disease, including prosthetic valves
• proximal atherosclerotic plaques
• aneurysms
• paradoxical: from the venous system via a right to left shunt, e.g. patent interatrial septum (rare).

Thrombi affecting heart valves may be associated with infective endocarditis and in these circumstances the embolus may be infected (septic embolus). Septic emboli may subsequently cause infection of the artery in which they impact, resulting in a mycotic aneurysm. Platelet emboli may arise from the surface of atheromatous plaques. Where these occur on a stenosis of the internal carotid artery, they are responsible for classical transient ischaemic attacks.


Gas embolism

These occur in two main situations: The introduction of gas accidentally during trauma or surgery, particularly to the neck, and in decompression sickness. The relative negative venous pressure in the neck can cause air to be sucked into the blood stream if these vessels are open, particularly with the patient in an erect or sitting position.

The introduction of air via intravenous cannulae is possible with giving sets or syringes but is very uncommon, and volumes of air less than 100 mL very rarely cause serious problems. When air is introduced into the circulation it generally only causes a problem when it gets back to the heart and produces a frothy thrombus in the right ventricle and impedes output.


Nitrogen embolism

Nitrogen embolism may occur in decompression sickness when a diver ascends too rapidly. This results in nitrogen, which was in solution under high pressure, forming gas bubbles within the circulation as the pressure is rapidly reduced. Bubbles may also be formed in ligaments and joints, which can give severe pain, causing the patient to lie and bend himself up double in an attempt to relieve the pain – hence ‘the bends’.


Fat embolism

Following fractures, most commonly of long bones, globules of fat may enter the circulation. This is actually relatively common but significant clinical consequences are rare. Pulmonary fat embolism is a frequent post- mortem finding with fractures, although it is unlikely that this in itself was the cause of death, as the pulmonary vascular tree is so extensive.

Sometimes the emboli may pass through the pulmonary vessels and into the systemic circulation, where they may become impacted in the capillaries of the brain, kidneys, skin, and other organs. This tends to be more serious with fever, respiratory distress and cerebral symptoms. Occasionally the brain damage is sufficiently severe for coma and death to result. A haemorrhagic skin eruption can occur, as may subconjunctival and ret- inal haemorrhages.


Tumour embolism

All malignant tumours tend to invade blood vessels at an early stage, and isolated malignant cells are com- monly present in the circulation. A number of factors are responsible for survival of a metastatic tumour within the blood stream and for its ability to escape to surrounding tissue and to grow following impaction within a vessel bed of small enough calibre to impede its further progress.

These factors seem to be related to a genetic event in the development of the cancer, and various factors have been identified as being related to the different metastatic capabilities. It is likely that tumour emboli are coated by thrombus as a part of the defence mechanism of the body against tissue emboli, since they are rendered more attractive to phagocytic cells by this coating.


Amniotic fluid embolism

This occurs in labour when the placenta is detached from the uterine wall and amniotic fluid enters the maternal circulation. This eventually lodges in the lungs. The respiratory disturbance caused is often disproportionate to the volume of amniotic fluid, and the effects are likely to be chemical rather than simply mechanical.

Consequently the condition is often referred to as amniotic fluid infusion to distinguish it from those conditions in which the major effects are simple blockage of vasculature. The condition is rare, occurring in only 1:50 000 deliveries, which is fortunate since the mortality is about 85% and treatment is largely ineffectual. Onset is indicated by severe respiratory difficulty with shock and fits followed by disseminated intravascular coagulation in many cases.


Foreign body embolism

This usually arises due to some intravenous instrumentation where pieces of cannulae are broken off and can move through the blood stream until they are arrested in a vessel too small to permit their further progress. Intravenous injections with undissolved drugs or contaminants can also result in foreign material moving into the blood stream. Such materials will become coated with thrombus and will eventually impact, with clinical effects dependent upon the significance of the occluded vessel. Accidental intra-arterial injection, e.g. a misplaced injection by an intravenous drug abuser is becoming more common, resulting in arterial embolism and thrombosis.


Therapeutic embolism

Therapeutic emboli such as gelfoam, muscle, or steel coils may occasionally be used to stop haemorrhage, to thrombose aneurysms and small arteries, or to reduce the vascularity of a tumour prior to surgical removal.


Non-thromboembolic vascular insufficency

This occurs when the blood supply is interrupted by mechanisms not involving primary thrombosis. Such conditions include:

• atheroma
• torsion
• spontaneous vascular occlusion, e.g. spasm
• ‘steal’ syndrome, i.e. redirected blood supply
• external pressure occlusion, e.g. tumours,
tourniquets, fractures, tight plasters.



Atheroma tends to occlude the lumen of the arteries progressively, causing relative ischaemia and an increased risk of thrombosis occurring on an atheromatous plaque. Thus a typical history might include atheroma of the lower part of the aorta, extending into the femoral arteries, causing intermittent claudication and mild skin atrophy progressively for some years. With thrombus formation, total occlusion may supervene, with gangrene due to infarction of the tis- sues distal to the occlusion if correction of the condition is not rapidly undertaken.



Occlusion of vessels by external pressure causes the symptoms and signs of vascular insufficiency together with failure to drain the tissue via the veins. This is clearly seen in torsion of the testis.

As the testis rotates on its pedicle (the spermatic cord or the mesorchium) the tension in the twisted region first affects the lowest pressure vasculature, which is the venous return. At first the arterial supply is unaffected and continues to pump blood into the testis, which becomes engorged, painful and swollen. Fluid leaks from the vessels (mainly veins) into the tissue spaces and causes further swelling which eventually reaches a pressure sufficient to cause arterial occlusion, adding to the anoxia of the tissues.

The normal drainage system for tissue fluid is the lymphatic, but this is a low pressure system with no active pump mechanism and, therefore, also occluded early in the process. If the situation is not resolved spontaneously or surgically, infarction occurs. Torsion of the intestines (volvulus), ovarian lesions (cysts and
tumours) and strangulated hernias all demonstrate a similar sequence of vascular insufficiency.


Spontaneous vascular occlusion

Vascular spasm is also capable of causing symptoms and signs of vascular insufficiency, and a large number of myocardial events (heart attacks) seem to be due to this rather than a thrombotic event. Such spasm is directly induced by cigarette smoke and is particularly common in vessels with some degree of intimal damage such as atheroma.

Later, atheroma calcifies, and such vessels are protected from spasm to some extent by the calcification but are very prone to thrombus formation, usually secondary to plaque rupture. A milder degree of spasm is seen in Raynaud’s disease, generally affecting the hand and in the similar condition seen in people who have worked with vibrating tools (vibration- induced white finger (VWF)). The mechanism by which this spasm occurs is contraction of smooth muscle in the vascular wall. This is generally maintained in a relaxed state by nitric oxide (endothelium-derived relaxing factor) which is produced in response to vasoconstriction brought about by acetylcholine.


Steal syndrome

‘Steal’ syndromes are rare but are another theoretical cause of relative vascular insufficiency. They occur when blood is redirected preferentially along one branch of a vessel to the detriment of the end territory of the other branch. The classic example is ‘subclavian steal syndrome’ where the left subclavian artery is occluded proximal to the origin of the vertebral artery.

Muscular activity of the left arm may cause the flow in the vertebral artery to reverse so that blood goes preferentially down the arm, ‘stealing’ blood from the vertebral and causing symptoms such as dizziness. It may also be seen with arteriovenous fistulae in the proximal part of a limb, especially when these are created between the brachial artery and cephalic vein at the elbow.

The flow from the brachial artery goes preferentially through the cephalic vein if the anastomosis is large enough, very little blood going down the ulnar and radial arteries to supply the hand particularly if these are diseased, as may occur in diabetics.


External pressure occlusion

This may be caused by tumours, tourniquets, or a tight plaster of paris cast. It may also be caused by fractures of long bones, the classical examples being a supracondylar fracture of the humerus in which the distal fragment is drawn forwards, impinging on the brachial artery, or a supracondylar fracture of the femur if the distal fragment is drawn backwards, compressing and damaging the popliteal artery.


Infarction sequence of events I

This can be defined as a lack of blood supply (and oxygen) to an organ or tissue resulting in tissue death. It usually forms a well-defined area of coagulative necrosis which, with the passage of time, frequently becomes organised into scar tissue.

Sequence of events
Shortly after death of the tissue blood continues to seep into the ischaemic area through the damaged capillary walls. Bleeding may increase partly from venous reflux and partly because the obstruction is often incomplete at the beginning of the episode.

As a result the area may appear under the microscope to be ‘stuffed’ with blood (hence the name of the pathological process from the latin infarcire – to stuff). On cutting across an infarcted area in the initial stages, the blood may give a
red appearance (hence the term ‘red infarcts’).


Infarction sequence of events II

Over the next 24–36 hours swelling of the autolysing cells may squeeze out the blood and the area may become paler (hence the term ‘pale infarcts’). However, the term infarction adds little to the understanding of the pathological process, and the colour depends largely on the tissue involved. For example, cerebral infarcts are usually pale, while the spongy lung tissue remains red right up to the stage of repair.

The dead tissue undergoes progressive autolysis of parenchymal cells and haemolysis of red cells. The living tissues surrounding the infarction undergo an acute inflammatory response. There is a rise in poly- morph numbers and, after a few days, macrophage infiltration becomes prominent. This is known as the phase of demolition. Subsequently there is a gradual ingrowth of granulation tissue and the area is eventu- ally organised into a fibrous scar (repair phase). Some dystrophic calcification may take place.


CNS infarction

Because of the high metabolic rate, nerve cells undergo functional changes within a few seconds of total ischaemia, and cell death occurs within a few minutes. The infarct is usually caused by a thrombosis secondary to atheroma or embolism, although 20% of strokes are haemorrhagic. The necrosis is typically liquefactive, which may subsequently result in formation of a cavity. After an initial neutrophil response there is intense phagocytic activity by microglial cells.


Lung infarction

Pulmonary infarction is very rare in healthy young people, even if a main pulmonary artery is occluded, because of the additional bronchial arterial supply. However, in heart failure and especially mitral stenosis, infarction is more likely.

Pulmonary infarcts are caused by emboli of which 90% arise from the lower limb veins, and 10% from the right atrial appendage in patients with heart disease, especially mitral stenosis or atrial fibrillation from any cause. A pulmonary infarct tends to be wedge-shaped with the base being on the pleural surface of the lung. It is the inflammation of this lung surface rubbing against the parietal pleura that gives the typical pleuritic pain.

A transient pleural rub may be heard at the site of the pain, which disappears as a layer of fluid (effusion) develops over it and lubricates it. Tissue returns to normal because there is oedema and bleeding into the alveoli but no progression to necrosis, and thus subsequent resolution occurs. Strictly speaking this is not an infarct, as there is no necrosis.


Intestine infarction

Small bowel infarction is usually due to a mechanical cause such as strangulated hernia or twisting round an adhesive band, although it can occur from superior mesenteric artery thrombosis or embolism. Occasionally it is due to mesenteric venous thrombosis (MVT). When the ischaemia is not severe enough to cause massive infarctions, sometimes the mucosa may undergo necrosis while the outer part of the bowel survives.

This is the mechanism of ischaemic colitis, which can closely mimic ulcerative colitis with toxic dilatation, in fact ischaemia is often the final common path in a variety of colitic diseases. Repair may lead to an ischaemic stricture.

Transient ischaemic changes in the bowel can occur secondary to heart failure and shock. This has serious consequences, as the ischaemic bowel can allow bacterial translocation into the blood, causing a bacteraemia which may have a devasting effect in a patient who is already very ill.


Skeletal muscle infarction

Ischaemic necrosis of skeletal muscle due to arterial occlusion alone results in a moderate degree of fibrous replacement. However, when there is additional venous obstruction there is a tendency to haemorrhage into the muscle, resulting in a much more intense fibrosis. This constitutes the basis of Volkmann’s ischaemic contracture. This occurs most commonly in the fore- arm muscles following a supracondylar fracture of the humerus, but can occur at other sites.



Gangrene is necrosis with putrefaction of the tissues, sometimes as a result of the action of certain bacteria notably clostridia. The affected tissues appear black because of the deposition of iron sulphide from degraded haemoglobin.

True gangrene is particularly likely to occur in the gut, where putrefactive organisms abound.

In gradually progressive peripheral vascular disease, most commonly of the lower limb, the ischaemia may become severe enough to cause infarction of the toes and feet.

The area becomes dry, shrivelled and black due to altered haemoglobins secondary to desiccation. An inflammatory zone develops at the junction of the living and dead tissue, which is known as the ‘line of demarcation’. This version of necrosis is known as ‘mummification’ or ‘dry gangrene’.


Mummification or dry gangrene

Mummification occurs where the environmental humidity is low and the temperature high; dead tissue dries slowly, retaining its form. The description ‘dry gangrene’ is contradictory since there is no actual putrefaction. If no infection supervenes, the dead tissue gradually separates and ‘auto amputation’ can occur. This is particularly likely to occur with a digit such as a toe.


Wet gangrene

If saprophytic infection and putrefaction occurs, the condition is known as ‘wet gangrene’. Progressive infec- tion of a site of necrosis accentuates the ischaemia, causing spreading gangrene and necessitating more proximal amputation where the blood supply is better.


Gas gangrene

Gas gangrene is a dangerous form of spreading tissue necrosis which is likely to occur when the spores of clostridia gain access to a wound in which there is extensive soft tissue or muscle injury causing reduced oxygen supply to the tissues which allows the growth of anaerobic organisms. The most common causal organism is Clostridium perfringens.

Crepitus (a palpable crackling or bubbling) can often be detected under the skin due to the production of gas bubbles by the clostridia. Clostridia also produces powerful toxins which themselves cause tissue damage and thus enhance spread of the infection.


Meleney’s gangrene

This may occur at the site of abdominal surgery or at the site of an accidental abrasion of the skin. Meleney attributed the condition to synergy between a micro-aerophilic, non-haemolytic streptococcus and Staphylococcus aureus.

However, other bacteria were also
isolated and Entamoeba histolytica has also been implicated. It is probably best to look at the infection as being caused by a combination of anaerobic and aerobic bacteria which forms a cellulitis followed by gangrene.


Fournier’s gangrene

This is a spontaneous onset of rapidly progressive gangrene of the scrotum in otherwise healthy men and less commonly the perineum of women. Elderly diabetics are particularly prone. It is caused by synergism between faecal bacteria and anaerobes. Fournier’s gangrene and Meleney’s gangrene probably have similar aetiological factors, and only the site of infection distinguishes the two.


Necrotising fasciitis

This is a serious but rare infection of the deeper layers of skin and subcutaneous tissue which tends to spread along fascial planes. A few years back the popular press dubbed it the ‘flesh eating virus’. This is incorrect on two counts; firstly it is caused by bacterial infection, most commonly Group A Streptococcus and secondly the bacteria do not actually eat the tissues which are actually damaged by the release of toxins. This condition may follow minor abrasions or an otherwise simple and uncomplicated operation.

The initial external appearance of the skin remains normal while the necrotising process spreads along fascial plains causing extensive necrosis. Later the overlying skin, deprived of its blood supply, becomes painful, red and finally necrotic. The patient is severely ill with fever and toxaemia. The infection is more likely to affect immunocompromised patients or diabetics. Small vessels are occluded by microthrombi,
and the destruction of tissues occurs rapidly.

The progression of this disease is dramatic, and extensive surgical procedures involving wide excision and occasionally amputation, together with appropriate intravenous antibiotic therapy, offers the best hope of survival.