Oxford Handbook of Clinical Surgery (4 edn)
Annotate
Cite
Cellular injury 142
Inflammation 144
Wound healing 146
Ulcers 148
Cysts, sinuses, and fistulas 150
Atherosclerosis 152
Thromboembolic disease 154
Gangrene and capillary ischaemia 158
Tumours 160
Carcinogenesis 162
Screening 164
Grading and staging 168
Tumour markers 170
Surgical microbiology 172
Surgically important organisms 174
Soft tissue infections 176
Blood-borne viruses and surgery 178
Bleeding and coagulation 180
Anaemia and polycythaemia 182
Cellular injury
Causative agents
Cellular injury is caused by:
Trauma.
Thermal injury.
Chemicals, including drugs.
Infectious organisms.
Ionizing radiation.
Mechanisms of injury
These causative agents cause cell damage via a number of mechanisms.
Mechanical disruption. Trauma, freezing, osmotic imbalance.
Failure of membrane integrity. Failure of ion pumps, cytolysis, trauma.
Blockage of metabolic pathways. Cellular respiration (e.g. cyanide), protein synthesis (e.g. streptomycin), DNA damage or loss (e.g. X-rays).
Deficiency of essential metabolites. Oxygen (ischaemia), glucose (diabetic ketoacidosis), hormones (↓ trophic hormones results in apoptosis).
Free radicals. Toxins (e.g. carbon tetrachloride), ischaemia-reperfusion injury, intracellular killing of bacteria.
Necrosis
Necrosis is death of tissue or cells.
Coagulative necrosis
This is the most common form of necrosis and occurs in all organs. Cells retain their shape as cell proteins coagulate and metabolic activity stops. Digestion by macrophages may cause the tissue to become soft. Histologically, there is progressive loss of staining. The presence of necrotic material normally provokes an inflammatory response.
Colliquative necrosis
This occurs in the brain because of the lack of tissue architecture provided by substantial surrounding stroma.
Caseous necrosis
Dead tissue lacks any structure and is characterized by a white, soft, or liquid ‘cheesy’ appearance. This is common in TB.
Gangrene
Necrosis with dessication or putrefaction (see 
p. 158).
Fibrinoid necrosis
In malignant hypertension, necrosis of smooth muscle vessel walls allows seepage of plasma into the media and deposition of fibrin.
Fat necrosis
Direct trauma. Release of extracellular fat produces an inflammatory response, fibrosis and eventually, in some cases, a palpable mass.
Acute pancreatitis. Fat is digested by pancreatic lipase to produce fatty acids which precipitate with calcium in the process of saponification.
Apoptosis
Apoptosis (programmed cell death) is the cell-mediated, controlled elimination of individual cells.
Apoptosis is a physiological process requiring energy. It is the normal means of maintaining the size of an organ in the face of continuing cell turnover or a reduction in size during atrophy. It is mediated by endogenous endonucleases. The cell shrinks and fragments into apoptotic bodies. Examples include:
Physiological. Epithelium of GI tract, bone marrow, clonal selection in immune system, targets of cytotoxic T cells.
Pathological. After exposure to ionizing radiation, chemotherapy, smooth muscle cells around atherosclerotic plaque, viral hepatitis.
Inflammation
Inflammation is the local physiological response to tissue injury. It can be acute or chronic.
Acute inflammation
This is the initial tissue reaction to a wide range of agents: accumulation of neutrophil polymorphs in the extracellular space is diagnostic. It lasts hours to days and is usually described with the suffix ‘-itis’.
Causes
Physical and chemical, e.g. mechanical trauma, X-rays, acid, alkali.
Infection: bacteria, viruses, parasites, fungi, or protozoa.
Ischaemia.
Hypersensitivity.
Macroscopic appearance
Calor, rubor, tumor, dolor, and functio laesa (heat, redness, swelling, pain, and impaired function). Special macroscopic appearances include:
Serous. Inflammation + abundant fluid-rich exudates, e.g. peritonitis.
Catarrhal. Inflammation + mucus hypersecretion, e.g. common cold.
Haemorrhagic. Inflammation + vascular injury, e.g. pancreatitis.
Suppurative. Inflammation + pus produced to form abscess or empyema.
Fibrinous. Exudates contain fibrin which forms coating, e.g. pericarditis.
Membranous. Coating of fibrin and epithelial cells, e.g. laryngitis.
Pseudomembranous. Superficial mucosal ulceration with slough, e.g. pseudomembranous colitis secondary to C. difficile (see p. 396).
Necrotizing (gangrenous). Inflammation + tissue necrosis (see p. 158).
Microscopic changes
Mediated by endogenous chemicals released by cells (histamine, prostaglandins, leukotrienes, serotonin, and lymphokines) and plasma factors (complement, kinin, coagulation, and fibrinolytic cascades). Changes are:
Changes in vessel calibre and flow.
Immediate and transient smooth muscle vasoconstriction.
Vasodilation (active hyperaemia) lasting 15min to hours.
Capillaries, then arterioles dilate to increase blood flow.
Increased vascular permeability and fluid exudates.
Capillary hydrostatic pressure is increased.
Endothelial cells contract, creating gaps.
Plasma proteins escape into extracellular space.
Increase in colloid osmotic pressure draws more fluid.
Formation of cellular exudates.
Accumulation of neutrophil polymorphs in extracellular space.
Begins with margination of neutrophils (flow next to vessel walls).
Neutrophils then adhere to vessel walls: mechanism unknown.
Migrate by amoeboid movement through gaps between cells.
Neutrophil polymorphs phagocytose debris and kill microbes intracellularly using oxygen-dependent (hydrogen peroxide and hydroxyl radicals) and -independent (lysosymes) means.
Sequelae of acute inflammation
Resolution. Restoration of tissue to normal; likely if minimal tissue damage, rapid destruction of causal agent, rapid removal of exudates by good vascular drainage, and organ with restorative capacity, e.g. liver.
Suppuration. Formation of pus (see p. 144).
Organization. Replacement by granulation tissue.
Chronic inflammation.
Chronic inflammation
This is an inflammation where lymphocytes, plasma cells, and macrophages predominate, granulation tissue often accompanies.
Causes
Resistance of infective agent to phagocytosis (TB, viral infections).
Foreign body (endogenous, e.g. urate or exogenous, e.g. asbestos).
Autoimmune (e.g. contact hypersensitivity, RA, organ-specific).
Primary granulomatous disease (e.g. Crohn's, sarcoidosis).
Unkown aetiology (e.g. ulcerative colitis).
Macroscopic appearances
The commonest appearances are:
Chronic ulcer, e.g. peptic ulcer;
Chronic abscess cavity, e.g. empyema;
Thickening of wall of hollow viscus, e.g. Crohn's disease;
Granulomatous inflammation, e.g. TB;
Fibrosis, e.g. chronic cholecystitis.
Microscopic changes
Lymphocytes, plasma cells, and macrophages (see p. 145) predominate; neutrophil polymorphs are scarce, eosinophil polymorphs are present. Fluid exudate is not prominent.
Granuloma
This is different to granulation tissue (see p. 147).
A granuloma is an aggregate of epithelioid histiocytes.
Causes
Specific infections.
Endogenous. necrotic bone or fat, keratin, urate.
Exogenous. Talc, silicone, asbestos, sutures.
Drugs. Sulphonamides, allopurinol.
Unknown. Crohn's, sarcoidosis, Wegener's granulomatosis.
Wound healing
Clean. Non-traumatic wounds with no break in surgical technique, no septic focus, and no viscus opened (e.g. hernia repair).
Clean contaminated. Non-traumatic wounds with contaminated entry into a viscus, but with minimal spillage (e.g. elective cholecystectomy).
Contaminated. Clean, traumatic wounds or significant spillage from a viscus or acute inflammation (e.g. emergency appendectomy).
Dirty. Includes traumatic wounds from a dirty source or when significant bacterial contamination or release of pus is encountered.
General principles of healing
Tissue healing in any organ follows some basic principles:
Cells may be labile (good capacity to regenerate, e.g. surface epithelial cells), stable (capacity to regenerate slowly, e.g. hepatocytes), or permanent (no capacity to regenerate, e.g. nerve and striated muscle cells).
Tissue architecture is important: complex arrangements cannot be reconstructed if destroyed, e.g. renal glomeruli.
Complete restitution occurs when part of a labile population of cells is damaged, e.g. a minor skin abrasion.
Key revision points—the four stages of wound healing
When specialized tissue is destroyed, it cannot be replaced and a stereotyped response called repair then follows in four stages:
Haemostasis (immediate). In response to exposed collagen, platelets aggregate at the wound and degranulate, releasing inflammatory mediators. Clotting and complement cascades activated. Thrombus formation and reactive vasospasm achieve haemostasis.
Inflammation (0–3 days). Vasodilation and increased capillary permeability allow inflammatory cells to enter wound and cause swelling. Neutrophils amplify inflammatory response by release of cytokines, reduce infection by bacterial killing, and debride damaged tissue. Macrophages follow and secrete cytokines, growth factors, and collagenases. They phagocytose bacteria and dead tissue and orchestrate fibroblast migration, proliferation, and collagen production.
Proliferation (3 days–3 weeks). Fibroblasts migrate into the wound and synthesize collagen. Specialized myofibroblasts containing actin cause wound contraction. Angiogenesis is stimulated by hypoxia and cytokines and granulation tissue forms.
Remodelling (3 weeks–1y). Reorientation and maturation of collagen fibres increases wound strength.
Granulation tissue is the combination of capillary loops and myofibroblasts. This is unrelated to a granuloma (see p. 145).
Organization is the process where specialized tissues are repaired by formation of mature connective tissue, e.g. pneumonia or infarcts.
Wound contraction mediated by myofibroblasts; can reduce the tissue defect by up to 80%, but can lead to problems, e.g. burns contractures.
Collagen is secreted at the same time to form a scar.
Factors affecting wound healing
Impaired arterial supply or venous drainage (global or local).
Excessive movement, local distension, or distal obstruction.
Infection, malignancy, foreign body, necrotic tissue, smoking.
Malnutrition. Obesity, recent weight loss, nutrient deficiency.
Immunosuppressive. Cancer, steroids, immunosuppressants, HIV.
Anticancer therapies. Radiotherapy and chemotherapy.
Metabolic. Diabetes, jaundice, uraemia, musculoskeletal diseases, age.
Wound healing in specific tissues
Skin: first intention healing
This takes place where there is close apposition of clean wound edges.
Thrombosis in cut blood vessels prevents haematoma formation.
Coagulated blood forms a surface scab which keeps the wound clean.
Fibrin precipitates to form a weak framework between the two edges.
Capillaries proliferate to bridge the gap.
Fibroblasts secrete collagen into the fibrin network.
Basal epidermal cells bridge the gap and are eventually resorbed.
The elastic network in the dermis cannot be replaced.
Skin: second intention healing
This takes place in wounds where skin edges cannot be cleanly apposed.
There is phagocytosis to remove debris.
Granulation tissue to fill in defects.
Epithelial regeneration covers the surface.
Gastrointestinal tract
Erosion is loss of part of the thickness of the mucosa.
Adjacent epithelial cells proliferate to regenerate the mucosa.
Healing may take place this way in a matter of hours.
Ulceration is loss of the full thickness of the mucosa.
Mucosa is replaced from the margins.
The muscularis propria cannot be regenerated: it is replaced by scar.
Damaged blood vessels bleed, fibrin covers the raw surfaces.
Macrophages migrate in and phagocytose dead tissue.
Granulation tissue is produced in the base.
If the cause persists, the ulcer becomes chronic.
Fibrous scar tissue may result in contractions.
Ulcers
An ulcer is a breach in an epithelial surface.
Classification
Venous, arterial, diabetic, neuropathic, malignant, traumatic.
Features to note on examination
Site. Neck, groin, and axilla (TB); legs and feet (vascular); anywhere (malignant).
Surface. Usually depressed. Elevated in malignancy, vascular granulations.
Size. Measure the ulcer. Is it large by comparison to the length of history?
Shape. Oval, circular, serpiginous, straight edges.
Edge. Eroded (actively spreading), shelved (healing), punched out (syphilitic), rolled or everted (malignant).
Base. Fixed to underlying structures? Mobile? Indurated? Penetrating?
Discharge. Purulent (infection), watery (TB), bleeding (granulation or malignancy).
Pain. Usually occurs during the extension phase of non-specific ulcers. In diabetic patients, ulcers are relatively painless.
Number. Widespread locally (local infection such as cellulitis), widespread generally (constitutional upset).
Progress. Short history (pyogenic), chronic (vascular or trophic, e.g. post-phlebitic syndrome, decubitus ulceration of paraplegia).
Lymph nodes. In the region of an ulcer may indicate secondary infection or malignant change.
Natural history
Extension. There is discharge, thickened base, inflamed margin. Slough and exudates cover the surface.
Transition. Slough separates and the base becomes clean. The discharge becomes scanty, the margins less inflamed.
Repair. Granulation becomes fibrous tissue and forms a scar after re-epithelialization.
Investigations
History, biopsy and histology, serology, as indicated by presentation.
Chronic leg ulcers
Their aetiology is diverse, but can usually be diagnosed clinically.
Venous ulcers
Part of post-phlebitic limb syndrome where there may be a history of past DVT. The ulcer is associated with oedema, lipodermatosclerosis (woody thickening of soft tissues around the calf), and venous congestion with secondary calf perforators and varicose veins. The ulcer is usually over the medial malleolus, but can be large, involving the whole of the gaiter region.
If pulses are absent in the foot, there may be an arterial element which can be excluded by measurement of the ankle to brachial pressure index (ABPI).
If any doubt persists, a vascular referral for arterial reconstruction should be considered, but four-layer bandaging must be avoided when there is arterial insufficiency.
Arterial ulcers
These are often multiple and occur distally over and between the toes or at pressure points such as heels or malleoli. They may occur elsewhere on the leg, usually when there is an associated diabetic or venous element. There is usually a history of arterial disease, particularly peripheral vascular disease with claudication.
Unlike venous ulcers where bacterial colonization is common, the presence of organisms suggests infection, particularly when there is moisture around the ulcers: wet gangrene (caused by staphylococci and streptococci, not clostridia, see later) may ensue with cellulitis.
If the leg is kept dry, infection is minimized and a line of demarcation may aid in decision-making for the level of amputation.
Arterial reconstruction should be considered before this stage.
Diabetic ulcers
These commonly occur in conjunction with arterial disease. They represent large- and small-vessel disease with an impaired ability to heal and increased susceptibility to infection. Ulcers may occur in the arterial distribution, particularly at pressure points, and involve deep tissue infections (such as plantar abscesses) and osteomyelitis. The associated diabetic neuropathy with Charcot's joints presents with deformed feet and joints, which are susceptible to ulceration.
Management involves good diabetic and ulcer care, which includes orthotist help with shoes and gait.
Surgery aims to avoid major amputation, but requires debridement of necrotic tissue, drainage of abscesses, and excision of dead tissue, often involving bone as ‘ray’ excisions of toes.
Other causes
Include pressure, vasculitic, lymphatic, infective, and artefactual causes. Leg ulcer clinics have emphasized the value of a team approach.
Cysts, sinuses, and fistulas
A cyst is a collection of fluid in a sac lined by endothelium or epithelium which usually secretes the fluid.
True cysts are lined by endo- or epithelium.
False cysts are the result of exudation or degeneration, e.g. pseudocyst of pancreas, cystic degeneration in a tumour.
Cysts
Classification
Congenital
Sequestration dermoid. Due to displacement of epithelium along embryonic fissures during closure, e.g. skin. Sites include outer and inner borders of orbit, midline of the body, anterior triangle of neck (brachial cyst), (cf. implantation dermoid due to skin implantation from injury).
Tubulo-dermoid/tubulo-embryonic. Abnormal budding of tubular structures, e.g. enteric cysts, post-anal dermoid, thyroglossal cyst.
Dilatation of vestigial remnants. For example, urachal, vitellointestinal, paradental and branchial cleft cysts, hydatid of Morgagni, Rathke's pouch.
Acquired
Retention cysts. Due to the blocking of a glandular or excretory duct, e.g. sebaceous cyst (sweat gland); ranula (salivary gland); and cysts of the pancreas, gall bladder, parotid, breast, epididymis, Bartholin's glands, hydronephrosis, hydrosalpinx.
Distension cysts. Due to the distension of closed cavities as a result of exudation or secretion, e.g. thyroid or ovarian cysts; hygroma (lymphatic cysts), hydrocoele, ganglia, bursas (false cysts).
Cystic tumours. For example, cystadenoma, cystadenocarcinoma of ovary.
Parasitic cysts. For example, hydatid cysts (Taenia echinococcus).
Pseudocysts. Due to necrosis of haemorrhage with liquefaction and encapsulation, e.g. necrotic tumours, cerebral softening, or coalescence of inflammatory fluid collections, e.g. pseudocyst of pancreas.
Clinical features
Subcutaneous/superficial
Smooth, spherical, soft, and fluctuant when palpated in two planes with the fingers at right angles to each other. If tense contents, may produce pain in the cyst or surrounding tissue. If the fluid is clear, the swelling will transilluminate. Ultrasound and aspiration of contents are methods of determining whether a given swelling is cystic and may differentiate a cyst from a lipoma. May compress surrounding tissues. May produce pain if complications supervene. They are also subject to infection, torsion if on a pedicle, haemorrhage, and calcification.
Treatment
Excision. Only if symptomatic, cosmetic, or concern over diagnosis.
Marsupialization (deroofing and suture of the lining to skin). If chronic or infected.
Drainage (deep site). If symptomatic or complicated. Not if concern over malignancy.
Sinuses/fistulas
A sinus is a blind epithelial track, lined by granulation tissue which extends from a free surface into the tissues, e.g. pilonidal sinus.
A fistula is an abnormal communication between two epithelial surfaces. It is lined by granulation tissue and colonized by bacteria, e.g. fistula-in-ano, pancreaticocutaneous, colovesical, vesicovaginal.
Causes
Specific disease, e.g. Crohn's.
Abscess formation and spontaneous drainage, e.g. diverticular abscess discharging into vagina with fistula formation.
Penetrating wounds.
Iatrogenic (e.g. anastomotic leak discharging via wound).
Neoplastic.
Persistence of a fistula is due to the following
Presence of foreign material, e.g. suture/bone in a sinus.
Distal obstruction of the viscus of origin.
Continuing active sepsis, e.g. TB, actinomycosis.
Epithelialization of the track.
Chronic inflammation, e.g. Crohn's.
Malignancy in the track.
Investigation
Establish the extent by sinography/fistulogram. MRI scan is often helpful.
Treatment
Principles of sinus treatment:
Ensure adequate drainage, laying it open and remove granulations.
Remove septic material, foreign bodies.
Biopsy sinus wall if concern over underlying diagnosis.
Loose packs may be used to help drainage.
Principles of fistula treatment:
Treat any sepsis, fluid imbalances, and poor nutrition if associated.
Ensure good drainage to prevent fistula extension.
Identify the anatomy, use examination under anaesthetic (EUA) or imaging if required.
Biopsy the fistula if concern over underlying diagnosis.
Definitive treatment requires:
Excision of the organ of origin or closure of the site of origin.
Removal of chronic fistula track and surrounding inflamed tissue.
Closure of ‘recipient’ organ if internal or drainage of external site if to skin.
Atherosclerosis
Atherosclerosis is a degenerative disease of large and medium-sized arteries characterized by lipid deposition and fibrosis.
Aetiology
Reversible risk factors include smoking, hypercholesterolaemia, obesity, and hypertension. Irreversible risk factors include diabetes, male sex, age, and family history.
Pathological features
There are three stages of atheromatous lesion; fatty streaks are linear lesions on the artery lumen, composed of lipid-filled macrophages, and which progress to fibrolipid plaques and finally, complex lesions .
In sites predisposed to atherosclerosis (sites of vessel bifurcation, turbulent flow, post-stenotic areas, areas denuded of endothelial cells), lipid-laden macrophages enter the vessel wall via gaps between endothelial cells.
A fibrolipid plaque contains a mixture of macrophages and smooth muscle cells which migrate into the plaque, capped by a layer of fibrous tissue.
Growth factors, particularly platelet-derived growth factor (PDGF), stimulate the proliferation of intimal smooth muscle cells and the synthesis of collagen, elastin, and mucopolysaccharide.
Lipid accumulates within the plaque extracellularly and in the myocytes, ultimately producing foam cells.
Cell death eventually ensues with the release of intracellular lipids, calcification, and a chronic inflammatory reaction.
High levels of circulating LDL-cholesterol are thought to lead to atherosclerosis by damaging endothelium, both directly by increasing membrane viscosity and indirectly through free radical formation, and by inducing secretion of PDGF.
In larger vessels such as the aorta, atherosclerotic plaques may release atheroemboli and mural thrombus or impinge on the vessel media, causing tissue atrophy resulting in aneurysm formation or dissection.
Acute MI is caused by three processes in coronary vessels: progressive atherosclerosis, disruption of unstable plaque with acute thrombosis, and acute haemorrhage into the intima around the plaque.
Thromboembolic disease
Thrombus
A thrombus is a solid mass of blood constituents formed within the vascular system.
The formation, structure, and appearance of thrombus and clot are completely different. Clinical features of thrombus—see p. 120.
Aetiology
Described by Virchow, the three types of risk factors for thrombus are called Virchow's triad (see Box 3.1). Not all three are needed: any one of them may result in thrombus formation in arteries or veins. Arterial thrombus is most commonly associated with atheroma, venous thrombus with stasis.
Disruption in the blood vessel endothelium.
Atheromatous plaque, e.g. acute MI.
Thrombophlebitis, e.g. DVT.
Trauma, e.g. from pressure, surgery, fractures, previous thrombus.
Disruption in the pattern of blood flow.
Stasis, e.g. immobilization, surgery, low CO states.
Turbulence, e.g. post-stenotic, atherosclerotic plaques.
Changes in blood constituents.
Age.
Smoking.
Malignancy.
DIC, HITT.
Pregnancy, oral contraceptive pill.
Thrombus formation
Wherever thrombus forms, the principal mechanisms are similar.
Initial trigger is one or more of Virchow's triad.
Fibrin deposition on vessel wall and formation of platelet layer.
Red cells trapped in fibrin meshwork on top of platelet layer.
Mass projects into lumen, causing turbulent blood flow.
Thrombus grows in direction of blood flow: propagation.
In veins, alternating patterns of white platelets and red blood cells may be seen: lines of Zahn.
Thrombophlebitis is inflammation of veins secondary to thrombus.
Phlebothrombosis is thrombus formation secondary to phlebitis.
Phlegmasia alba dolens (white painful leg) occurs after slow thrombosis formation in the ileofemoral veins and is a chronic condition.
Phlegmasia cerulean dolens (blue painful leg) is due to acute massive ileofemoral venous thrombosis and can result in shock and gangrene.
Thrombophlebitis migrans are transient thromboses in previously healthy veins anywhere in the body, suggesting visceral cancer.
Embolism
An embolism is a mobile mass of material in the vascular system capable of blocking its lumen.
Types of embolism
The aetiology is very different, depending on the cause of embolism. The clinical effects depend on the territory supplied by the vessel that is blocked. Emboli can be divided into:
Both types of embolism can be further classified by the substance involved:
Thrombus. Most emboli are derived from thrombi.
Gas. Injection or entraining of air, decompression sickness.
Fat. Long bone fractures, severe burns, extensive soft tissue trauma.
Amniotic fluid. ↑ Intrauterine pressure forces fluid into uterine veins and into systemic circulation.
Septic emboli. Vegetations from heart valves.
Atheromatous plaque. Peripheral vascular disease, iatrogenic.
Tumour. Common route of metastasis.
Foreign bodies. IV drug users, medically inserted catheters.
Clot
A clot is a solid collection of blood cells within a fibrin network.
Clot forms in vessels after death or outside the body as part of the response to trauma. Activation of the clotting cascade (see p. 119) results in formation of fibrin from fibrinogen, resulting in the formation of fibrin meshwork that enmeshes cells in a solid, elastic clot.
Ischaemia and infarction
Ischaemia is tissue effect due to insufficient oxygen delivery.
Infarction is tissue death due to insufficient oxygen delivery.
Oxygen supply-demand mismatch is caused by:
Vascular narrowing (atherosclerosis, thrombus, embolus, spasm).
Global hypoperfusion (shock, cardiopulmonary bypass).
Hypoxaemia (anaemia, hypoxia).
Vascular compression (ventricular distension, venous occlusion).
Increased oxygen demand (exercise, pregnancy, hyperthyroidism).
Pathological features
The shape of the infarct depends on the territory and perfusion of the occluded vessel.
Seconds. Change from aerobic to anaerobic metabolism.
Minutes. ↓ Contractility of muscle, cell and mitochondria swell.
Hours. Myocyte death, coagulation necrosis, muscle pale, oedematous.
Days. Inflammatory exudates with polymorphonuclear leucocytes, then fibroblast infiltration beginning scar formation; macroscopically, the infarcted area appears yellow and rubbery with haemorrhagic border.
Weeks. Neovascularization and margins.
Months. Scar maturation—tough, white, contracted area.
Gangrene and capillary ischaemia
Gangrene is ischaemic tissue necrosis with dessication (dry gangrene) or putrefaction (wet gangrene).
Gangrene
Aetiology
Thrombosis, e.g. appendiceal artery secondary to inflammation.
Embolus, e.g. atherosclerotic emboli in peripheral vascular disease.
Extrinsic compression, e.g. fracture, organ torsion, tourniquet.
Clinical appearances
Dry gangrene
The affected limb, digit, or organ is black because of breakdown of haemoglobin, dry, and shrivelled. Dry gangrene shows little or no tendency to spread. A zone of demarcation appears between the dead and viable tissue and separation begins to take place by aseptic ulceration in a few days.
Wet gangrene
Veins as well as arteries are blocked. Pain is initially severe, but lessens as the patient becomes more septic. There is always infection (putrefaction). The skin and superficial tissues become blistered. There is a broad zone of ulceration which separates it from normal tissue. Proximal spread is a feature, leading to septicaemia and death.
Gas gangrene
Gangrene complicated by infection with gas-producing anaerobic bacteria, e.g. Clostridium perfringens. Gases elaborated from putrefaction lead to surgical emphysema and crepitus (see p. 175).
Principles of treatment
Systemic treatment.
Aggressive fluid resuscitation is often necessary.
Pain relief (IV morphine 5–10mg).
IV antibiotics—broad-spectrum (e.g. benzylpenicillin, metronidazole, piperacillin/tazobactam, or according to microbiological advice).
Conservative treatment. Only possible for non-vital organs affected by dry gangrene (e.g. toes/forefoot). Aim is to let the affected areas mummify and spontaneously separate.
Surgical salvage procedures. Conservative excision possibly combined with reconstruction or restoration of blood supply (e.g. foot amputation and bypass surgery for distal lower limb gangrene).
Radical surgical excision. Only possible where affected organ is completely resectable (e.g. limbs, perineal tissues)—excision must be radical in spreading or gas gangrene. Ensure all pus is released, all affected tissue (not just the necrosed area) is excised back to bleeding healthy tissue. Often requires ‘relook’ surgery to ensure adequate excision of infected tissue.
Palliative care. Consider for unresectable gangrene (e.g. retroperitoneal gangrene, very extensive intestinal gangrene) or for elderly sick patients where surgery is inappropriate.
Capillary ischaemia
This is ischaemia mediated by injury to capillaries.
Frostbite. Exposure to cold with freezing results in fixed capillary contraction, ischaemia, and infarction.
Trenchfoot. Exposure to cold without freezing results in capillary contraction followed by fixed dilation.
DIC (see p. 116).
Cryoglobulinaemia, sickle cell, parasites.
Tumours
Metaplasia. Reversible transformation of one type of terminally differentiated cell into another fully differentiated cell type.
Dysplasia. Potentially premalignant condition characterized by increased cell growth, atypical morphology, and altered differentiation.
Neoplasia. Autonomous abnormal growth of cells which persists after the initiating stimulus has been removed.
A neoplasm is a lesion resulting from neoplasia.
Metaplasia
This represents an adaptive response of a tissue to environmental stress. It is mediated by changes in expression of genes involved in cellular differentiation. It does not progress to malignancy: if the environmental changes persist, dysplasia may result and progress to malignancy. For example:
Change from ciliated to squamous cells in the respiratory epithelium of the trachea and bronchi in smokers;
Change from squamous to columnar cells in the oesophageal epithelium of patients with gastro-oesophageal reflux disease (Barrett's) (see p. 280).
Dysplasia
Potentially premalignant condition. May be a response to chronic inflammation or exposure to carcinogens. Early forms may be reversible: severe dysplasia has a high risk of progression to malignancy, for example:
Dysplasia arising in colonic epithelium due to chronic ulcerative colitis.
Squamous dysplasia in the bronchi of smokers (sputum cytology).
Classification of tumours
Use this classification to give a differential diagnosis for any neoplasm.
Tissue of origin. Organ and tissue type (see Table 3.1).
Behaviour. Benign or malignant.
Primary or secondary.
| Tissue of origin | Tumour type |
|---|---|
Epithelium | Benign: papilloma, adenoma (glandular epithelium) |
Malignant: carcinoma (adenocarcinoma, squamous cell carcinoma indicate cell types) | |
Connective tissue | Benign: fibroma (fibrous tissue), lipoma (fat), chondroma (cartilage), osteoma (bone), leiomyoma (smooth muscle), rhabdomyoma (striated muscle) |
Malignant: sarcoma, e.g. fibrosarcoma, osteosarcoma, etc. (if well differentiated); spindle cell sarcoma, etc. (if poorly differentiated) | |
Neural tissue | These arise from nerve cells, nerve sheaths, and supporting tissues, e.g. astrocytoma, medulloblastoma, neurilemmoma, neuroma, etc. |
Haemopoietic | The leukaemias, Hodgkin's disease, multiple myeloma, lymphosarcoma, reticulosarcoma |
Melanocytes | Melanoma |
Mixed origins | E.g. fibroadenoma, nephroblastoma, teratoma (all three germ layers), choriocarcinoma |
Developmental blastomas | E.g. neuroblastoma (adrenal medulla), nephroblastoma (kidney), retinoblastoma (eye) |
| Tissue of origin | Tumour type |
|---|---|
Epithelium | Benign: papilloma, adenoma (glandular epithelium) |
Malignant: carcinoma (adenocarcinoma, squamous cell carcinoma indicate cell types) | |
Connective tissue | Benign: fibroma (fibrous tissue), lipoma (fat), chondroma (cartilage), osteoma (bone), leiomyoma (smooth muscle), rhabdomyoma (striated muscle) |
Malignant: sarcoma, e.g. fibrosarcoma, osteosarcoma, etc. (if well differentiated); spindle cell sarcoma, etc. (if poorly differentiated) | |
Neural tissue | These arise from nerve cells, nerve sheaths, and supporting tissues, e.g. astrocytoma, medulloblastoma, neurilemmoma, neuroma, etc. |
Haemopoietic | The leukaemias, Hodgkin's disease, multiple myeloma, lymphosarcoma, reticulosarcoma |
Melanocytes | Melanoma |
Mixed origins | E.g. fibroadenoma, nephroblastoma, teratoma (all three germ layers), choriocarcinoma |
Developmental blastomas | E.g. neuroblastoma (adrenal medulla), nephroblastoma (kidney), retinoblastoma (eye) |
Benign tumours
Slow growing, usually encapsulated, do not metastasize, do not recur if completely excised, rarely endanger life. Effects are due to size and site.
Histology: well differentiated, low mitotic rate, resemble tissue of origin.
Malignant tumours
These expand and infiltrate locally, encapsulation is rare, metastasize to other organs via blood, lymphatics or body spaces, endanger life if untreated.
Histology: varying degrees of differentiation from tissue of origin, pleomorphic (variable cell shapes), high mitotic rate.
Invasion
Invasion is the most important single criterion for malignancy and is also responsible for clinical signs and prognosis as well as dictating surgical management. Factors that enable tumours to invade tissues include:
Increased cellular motility.
Loss of contact inhibition of migration and growth.
Secretion of proteolytic enzymes, such as collagenase, which weakens normal connective tissue bonds.
Decreased cellular adhesion.
Metastasis
Metastasis is a consequence of these invasive properties: it is the process by which malignant tumours spread from their site of origin (primary tumour) to form secondary tumours at distant sites. Carcinomatosis denotes extensive metastatic disease. The routes of metastasis are:
Haematogenous. Via the bloodstream.
Five tumours—breast, bronchus, kidney, thyroid, prostate—classically metastasize via haematogenous spread to bone.
Lung, liver, and brain are common sites for secondaries.
Lymphatic. To local, regional, and systemic nodes.
Transcoelomic. Across pleural, pericardial, and peritoneal cavities.
Implantation. During surgery or along biopsy tracks.
Carcinogenesis
Carcinogenesis is the process that results in malignant neoplasm formation. Usually more than one carcinogen is necessary to produce a tumour, a process which may occur in several steps—multistep hypothesis.
Initiators produce a permanent change in the cells, but do not themselves cause cancer, e.g. ionizing radiation: this change may be in the form of gene mutation.
Promoters stimulate clonal proliferation of initiated cells, e.g. dietary factors and hormones: they are not mutagenic.
Latency is the time between exposure to carcinogen and clinical recognition of tumour due to:
Time taken for clonal proliferation to produce a significant cell mass.
Time taken for exposure to multiple necessary carcinogens.
Persistence is when clonal proliferation no longer requires the presence of initiators or promoters and the tumour cells exhibit autonomous growth.
See Table 3.2 for a list of common risk factors for cancer.
| Known carcinogen | Type of cancer |
|---|---|
Chemicals | |
Polyaromatic hydrocarbons | Lung cancer (smoking), skin cancers |
Aromatic amines | Bladder cancer (rubber and dye workers) |
Alkylating agents | Leukaemia |
Viruses | |
HIV | Kaposi's sarcoma, lymphoma |
Epstein–Barr virus | Burkitt's lymphoma, nasopharyngeal cancer |
Human papillomavirus | Squamous papilloma (wart), cervical cancer |
Hepatitis B virus | Liver cell carcinoma |
Radiation | |
UV light (UVB>UVA) | Malignant melanoma, basal cell carcinoma |
Ionizing radiation | Particularly breast, bone, thyroid, marrow |
Biological agents | |
Hormones, e.g. oestrogens | Breast and endometrial cancer |
Mycotoxins, e.g. aflatoxins | Liver cell carcinoma |
Parasites, e.g. schistosoma | Bladder cancer |
Miscellaneous | |
Asbestos | Mesothelioma and lung cancer |
Nickel | Nasal and lung cancer |
Host factors | Type of cancer |
Race | |
Caucasians | Malignant melanoma, stomach cancer |
Diet | |
High dietary fat | Breast, colorectal cancer |
Alcohol | Breast cancer |
Gender, inherited risks | |
Female sex | Breast cancer |
Familial polyposis coli | Colorectal cancer |
Multiple endocrine neoplasia | Phaeo, parathyroid, medullary cancer thyroid |
BRCA1–17q21 | Breast, ovarian and prostate cancer |
Premalignant lesions and conditions | |
Adenomatous rectal polyp | Colorectal adenocarcinoma |
Mammary ductal hyperplasia | Breast carcinoma |
Ulcerative colitis | Colorectal adenocarcinoma |
Transplacental exposure | |
Diethylstiboesterol | Vaginal adenocarcinoma |
| Known carcinogen | Type of cancer |
|---|---|
Chemicals | |
Polyaromatic hydrocarbons | Lung cancer (smoking), skin cancers |
Aromatic amines | Bladder cancer (rubber and dye workers) |
Alkylating agents | Leukaemia |
Viruses | |
HIV | Kaposi's sarcoma, lymphoma |
Epstein–Barr virus | Burkitt's lymphoma, nasopharyngeal cancer |
Human papillomavirus | Squamous papilloma (wart), cervical cancer |
Hepatitis B virus | Liver cell carcinoma |
Radiation | |
UV light (UVB>UVA) | Malignant melanoma, basal cell carcinoma |
Ionizing radiation | Particularly breast, bone, thyroid, marrow |
Biological agents | |
Hormones, e.g. oestrogens | Breast and endometrial cancer |
Mycotoxins, e.g. aflatoxins | Liver cell carcinoma |
Parasites, e.g. schistosoma | Bladder cancer |
Miscellaneous | |
Asbestos | Mesothelioma and lung cancer |
Nickel | Nasal and lung cancer |
Host factors | Type of cancer |
Race | |
Caucasians | Malignant melanoma, stomach cancer |
Diet | |
High dietary fat | Breast, colorectal cancer |
Alcohol | Breast cancer |
Gender, inherited risks | |
Female sex | Breast cancer |
Familial polyposis coli | Colorectal cancer |
Multiple endocrine neoplasia | Phaeo, parathyroid, medullary cancer thyroid |
BRCA1–17q21 | Breast, ovarian and prostate cancer |
Premalignant lesions and conditions | |
Adenomatous rectal polyp | Colorectal adenocarcinoma |
Mammary ductal hyperplasia | Breast carcinoma |
Ulcerative colitis | Colorectal adenocarcinoma |
Transplacental exposure | |
Diethylstiboesterol | Vaginal adenocarcinoma |
Tumour growth
Tumour doubling time depends on cell cycle time, growth function, and cell loss fraction. In tumours such as leukaemias, the doubling time remains remarkably constant: the cell mass increases proportionally with time. This is exponential growth. In solid tumours, doubling time slows as size increases. This is referred to as Gompertzian growth.
Genetic abnormalities in tumours
Two genetic mechanisms of carcinogenesis are proposed:
Oncogenes. Enhanced expression of stimulatory dominant genes.
Tumour suppressor genes. Inactivation of recessive inhibitory genes.
Oncogenes
At least 60 oncogenes have been identified. They can be classified according to the function of the gene product (e.g. growth factors, cell signalling agents). The proteins produced (oncoproteins) can be produced in abnormal quantities or be abnormally active forms and cause:
Independence from extrinsic growth factors.
Production of tumours in immunotolerant animals.
Production of proteases to assist in invasion of normal tissues.
Reduced cell cohesiveness assisting metastasis.
Growth to higher cell densities and abnormal cellular orientation.
Examples include BRCA1, p53, k-ras, APC, DCC.
Screening
Screening is testing any population for a disease.
The aim is reduction in morbidity and mortality from screened diseases.
Requirements for successful screening
The population screened must be:
Easily identified and contactable.
Compliant.
The disease screened must be:
Detectable in a treatable, premalignant form or earlier stage.
Preventable or more amenable to successful or curative treatment.
A sufficient burden on the population to justify cost of screening.
Chronic or of suitable evolution for sporadic testing to detect it.
Disadvantages of screening
Cost (time and resources).
The benefit may be small.
False positive tests may be physically or psychologically detrimental.
Examples of screening programmes
Abdominal aortic aneurysm (4000 deaths/y)
The UK multicentre aneurysm screening study of 68 000 men showed screening halves aneurysm-related deaths by reducing risk of rupture. The conclusion was that aneurysm screening should be offered in the UK. The MASS study showed a benefit where other studies failed because:
It was adequately powered (see p. 8).
Screening compliance was higher:
GP-based ultrasound had a better compliance than specialist clinics.
Participants unlikely to attend were excluded from the study.
Breast cancer (14 000 deaths/y)
A meta-analysis of thirteen breast cancer screening trials concluded that screening mammography significantly reduced breast cancer mortality in women aged 50–74. A BMJ analysis concluded that:
For every 1000 women screened over 10y, around 200 (depending on age) are recalled because of an abnormal result and of these:
Around 60 will have at least one biopsy.
About 15 will have invasive cancer and 5 will have ductal carcinoma in situ (DCIS).
About 0.5, 2, 3, and 2 fewer deaths from breast cancer occur over 10y per 1000 women aged 40, 50, 60, and 70y, respectively, who choose to be screened.
Ten per cent of invasive carcinoma is not radiologically detectable.
Risk of a false positive screen is approximately 25% over 10y.
Studies suggest up to a 30% reduction in mortality from screen-detected early breast cancer.
Features looked for on screening mammography include: spiculated calcification, microcalcification.
What is offered?
Since 1988, population-based screening offered.
Starts age 50 and continues to age 70 (covers peak ages of incidence of new diagnoses and excludes low risk younger women—prevents ‘psychological morbidity of screening the well’).
Seventy per cent of women offered it accept screening (lowest take-up in lower socio-economic groups and those difficult to contact, e.g. rapidly changing addresses or no fixed address).
Two-view (lateral and oblique) mammography of both breasts.
Suspicious or malignant-looking lesions invited for clinical assessment by standard triple assessment.
Cervical cancer (1500 deaths/y)
Since the mid-1980s, incidence of and mortality from cervical cancer in women under 70 in England and Wales has fallen. Screening is thought to be the most likely explanation. A BMJ analysis concluded that:
In the NHS cervical screening programme, 1000 women need to be screened for 35 years to prevent one death:
150 have an abnormal result and 75 need repeat for inadequate test.
80 undergo biopsy.
55 have an abnormal biopsy result.
2 have carcinoma, the rest have dysplasia.
At least one woman dies within the 35y despite being screened.
Prostate cancer (9000 deaths/y)
A third of men over 50y have evidence of prostate cancer at post-mortem, but less than 1% of these have clinically active disease. Screening is controversial because:
Prostate-specific antigen (PSA), rectal examination, and transrectal ultrasound have low specificity and sensitivity alone or in combination.
Treatment of prostate cancer is controversial (see p. 374).
No randomized trial has shown a survival benefit in screened populations: screening may cause more harm than good.
Screening can be carried out on request despite the evidence above.
Colorectal cancer (16 000 deaths/y)
The lifetime risk of colorectal cancer is about 1 in 20. A nationwide screening programme is likely, following current pilot centres:
Several possible screening tests exist:
Faecal occult blood (low sensitivity, 90% specificity)—requires colonoscopy for positive results (false positives common).
Colonoscopy (sensitivity and specificity near 100%).
Flexible sigmoidoscopy (sensitivity 80%, specificity near 100%).
Colorectal cancer is suited to screening:
It has a detectable premalignant phase.
It is detectable at an earlier and potentially highly treatable stage.
Screening has been shown to be cost-effective and acceptable.
Grading and staging
Staging is the process of assessing the extent of local and systemic spread of a malignant tumour or the identification of features which are risk factors for spread.
Grading is the process of assessing the degree of differentiation of a malignant tumour.
Key facts
The objectives of staging and grading a tumour are:
To plan appropriate (treatment) for the individual patient.
To give an estimate of the prognosis.
To compare similar cases when assessing outcomes or designing clinical trials.
Staging and grading methods
Staging
The commonest system is the internationally agreed TNM classification (see Table 3.3). It is not appropriate for leukaemia, lymphomas, or myeloma. A four-stage classification (I. II, III, IV) is also often used and is compatible with TNM. Specific staging systems also exist for some tumour sites (e.g. Duke's stage in colorectal cancer, see p. 400).
| Classification | Interpretation |
|---|---|
Primary tumour (T) | |
TX | Primary tumour cannot be evaluated |
T0 | No evidence of primary tumour |
Tis | Tumour in situ |
T1, T2, T3, T4 | Size and extent of primary tumour |
Regional lymph nodes (N) | |
NX | Regional lymph nodes cannot be evaluated |
N0 | No regional lymph node involvement |
N1, N2, N3 | Number and location of involved lymph nodes |
Distant metastasis (M) | |
MX | Distant metastasis cannot be evaluated |
M0 | No distant metastasis |
M1 | Distant metastasis |
| Classification | Interpretation |
|---|---|
Primary tumour (T) | |
TX | Primary tumour cannot be evaluated |
T0 | No evidence of primary tumour |
Tis | Tumour in situ |
T1, T2, T3, T4 | Size and extent of primary tumour |
Regional lymph nodes (N) | |
NX | Regional lymph nodes cannot be evaluated |
N0 | No regional lymph node involvement |
N1, N2, N3 | Number and location of involved lymph nodes |
Distant metastasis (M) | |
MX | Distant metastasis cannot be evaluated |
M0 | No distant metastasis |
M1 | Distant metastasis |
Additional codes used with the TNM: pul, pulmonary; hep, hepatic; V, vascular; Ly, lymphatic vessels; R, radial margin. Prefixes used with the TNM: u, ultrasound; r, radiological; p, pathological.
Staging may be:
Radiological (often performed preoperatively): indicated by the prefix ‘r’ before the letter (e.g. rT3, rM1). If different radiological modalities are used, separate prefixes can be used, e.g. ‘u’ for ultrasound (uT2). Radiological staging is used to plan treatment (e.g. neoadjuvant therapy, selection for surgery, planning of surgery).
Pathological (performed on surgical specimens): indicated by the prefix ‘p’ before the letter (e.g. pT3, pN2, pM1). If there has preoperative radiotherapy used, the prefix ‘y’ is used to denoted that the pathological stage may have been modified by this (e.g. ypT2). Pathological staging is used to plan adjuvant treatment (chemotherapy or radiotherapy) and for informing prognosis.
An example of lung cancer staging is:
Stage I (T1N0, T2N0), 85% 5y survival with surgery.
Stage II (T1N1, T2N1, T3N0), 60% 5y survival with surgery.
Stage IIIa (T3N1 or any N2), 20% 5y survival with surgery.
Stage IIIb (any T4, any N3), <20% 5y survival, no benefit with surgery.
Stage IV (M1), <10% 5y survival, no benefit with surgery.
Other pathological features may be included with the TNM system for some tumours, for example:
Presence of extratumoural vascular invasion V0 or V1.
Presence of extratumoural lymphatic invasion Ly0 or Ly1.
Presence of viable tumour cells at or within 1mm of the surgical margin of excision R0, R1 (microscopic), R2 (macroscopic).
Histological grading
Gives a guide to the behaviour of a cancer by describing the degree of differentiation of the tumour (e.g. breast cancer).
Grade 1, represents the least malignant tumours.
Grade 2, 25–50% of the cells are undifferentiated.
Grade 3, 50–75% of the cells are undifferentiated.
Grade 4, >75% of the cells are undifferentiated.
Other methods of describing tumours
Depth of invasion (e.g. Breslow thickness in malignant melanoma).
Tumour type (e.g. small cell versus non-small cell lung cancer).
Tumour markers
Key facts
Tumour markers (see Table 3.4) are complex molecules, often proteins that can be detected by a variety of techniques, including chemical, immunological, or bioactivity testing.
Most are molecules normally produced by normal cells in small amounts, but which may be produced in increased amounts by tumour cells due to changes in cellular function (e.g. increased production, increased gene expression, decreased degradation, increased release).
| Marker | Useful in | Notes/use |
|---|---|---|
AFP | Hepatoma; teratoma (75% of cases); pancreatic carcinoma some patients) | Elevated in liver disease, e.g. hepatitis, cirrhosis, and pregnancy |
β-HCG | Choriocarcinoma (almost all cases); testicular tumours/teratoma (75%); other germ cell tumours | Measured both in blood and urine |
PAP | Seminoma; ovarian adenocarcinoma | |
CEA | Colonic adenocarcinoma; ovarian adenocarcinoma; advanced breast cancer; pancreatic cancer | Not useful for diagnosis or screening. Used to monitor response to treatment and identify relapse in tumours showing raised CEA at diagnosis. May be elevated in pancreatitis, ulcerative colitis, gastritis, and heavy smokers |
CA 19–9 | Pancreatic cancer (80%); advanced colorectal cancer (75%) | A polysialated antigen (Lewis blood group antigen). Ratio of CA 19–9:CEA most sensitive for pancreatic cancer diagnosis |
LDH | Lymphoma | |
Thyroglobulin | Thyroid cancer | Used to monitor and identify relapse after treatment |
Calcitonin | Medullary carcinoma of the thyroid | Used to monitor and identify relapse after treatment |
PSA | Prostate cancer | May be measured in serum and tissue by immunohistochemistry. Serum level closely relates to disease status |
Alkaline phosphatase | Osteosarcoma | Also raised in bony metastases, osteitis, Paget's disease |
| Marker | Useful in | Notes/use |
|---|---|---|
AFP | Hepatoma; teratoma (75% of cases); pancreatic carcinoma some patients) | Elevated in liver disease, e.g. hepatitis, cirrhosis, and pregnancy |
β-HCG | Choriocarcinoma (almost all cases); testicular tumours/teratoma (75%); other germ cell tumours | Measured both in blood and urine |
PAP | Seminoma; ovarian adenocarcinoma | |
CEA | Colonic adenocarcinoma; ovarian adenocarcinoma; advanced breast cancer; pancreatic cancer | Not useful for diagnosis or screening. Used to monitor response to treatment and identify relapse in tumours showing raised CEA at diagnosis. May be elevated in pancreatitis, ulcerative colitis, gastritis, and heavy smokers |
CA 19–9 | Pancreatic cancer (80%); advanced colorectal cancer (75%) | A polysialated antigen (Lewis blood group antigen). Ratio of CA 19–9:CEA most sensitive for pancreatic cancer diagnosis |
LDH | Lymphoma | |
Thyroglobulin | Thyroid cancer | Used to monitor and identify relapse after treatment |
Calcitonin | Medullary carcinoma of the thyroid | Used to monitor and identify relapse after treatment |
PSA | Prostate cancer | May be measured in serum and tissue by immunohistochemistry. Serum level closely relates to disease status |
Alkaline phosphatase | Osteosarcoma | Also raised in bony metastases, osteitis, Paget's disease |
Testing
Testing is most commonly in vitro via serum measurements or testing tissue specimens. Common uses include:
Screening (detection of subclinical disease).
Diagnosis (including differentiation of tumour origin in metastatic disease).
Monitoring response to treatment.
Monitoring for development of recurrence.
Non-tumour related elevations in tumour marker levels (reducing the specificity of these tests for tumours) may occur due to:
Increased production/release due to inflammation, infection, trauma, or surgery.
Decreased removal/destruction due to renal or liver disease.
AFP (alpha-fetoprotein).
β-HCG (beta-human chorionic gonadotrophin).
PAP (placental alkaline phosphatase).
CEA (carcinoembryonic antigen).
LDH (lactic dehydrogenase).
PSA (prostate-specific antigen).
Surgical microbiology
Key facts
Three-quarters of nosocomial infection occur in surgical patients who account for 40% of hospital inpatients.
Risk factors for wound infection include the type of surgery, patient age, malnutrition, immunosuppression, obesity, lack of appropriate antibiotic prophylaxis, foreign bodies, and residual malignancy or necrotic tissue.
Nosocomial infections are acquired in hospital.
Community acquired infections are acquired outside hospital.
Sources of surgical infection
Three-quarters of nosocomial infections occur in surgical patients (see Table 3.5) who account for 40% of hospital inpatients. Sources of infection include:
Patient's own body flora:
Failure of correct aseptic technique.
Contaminated surgery (see p. 146).
Indirect contact:
Contact from hands of doctors, nursing staff, patients, visitors.
Contaminated surfaces, e.g. door handles, cups.
Direct inoculation:
Surgeon or environmental flora through failure of aseptic technique.
Contaminated instruments or dressings.
Colonization of indwelling drains, catheters, intravenous lines.
Airborne contamination:
Skin and clothing of staff, patients, and visitors.
Air flow in operating theatre or ward.
Haematogenous spread:
Intravenous and intra-arterial lines.
Contaminated infusions.
Sepsis at other anatomical sites.
Food and waterborne.
Faecal-oral.
Insect borne.
| Type of surgery | Rate of post-operative infection (%) |
|---|---|
Clean (no viscus opened), e.g. hernia repair | <2 |
Clean contaminated (viscus opened minimal spillage), e.g. cholecystectomy | <10 |
Contaminated (open viscus with spillage or inflammatory disease), e.g. simple appendicectomy | 15–20 |
Dirty (pus or perforation or incision through abscess), e.g. perforated appendicectomy | >40 |
| Type of surgery | Rate of post-operative infection (%) |
|---|---|
Clean (no viscus opened), e.g. hernia repair | <2 |
Clean contaminated (viscus opened minimal spillage), e.g. cholecystectomy | <10 |
Contaminated (open viscus with spillage or inflammatory disease), e.g. simple appendicectomy | 15–20 |
Dirty (pus or perforation or incision through abscess), e.g. perforated appendicectomy | >40 |
Risk factors for wound infection
General:
Age.
Malnutrition, obesity, malnutrition.
Immunosuppression, including steroid therapy, chemotherapy.
Endocrine and metabolic disorders, e.g. diabetes, jaundice, uraemia.
Hypoxia and anaemia.
Local:
Type of surgery (see Table 3.5), lengthy procedures.
Necrotic tissue.
Residual local malignancy.
Foreign bodies, including prosthetic implants.
Ischaemia, haematoma.
Microbiology:
Lack of antibiotic prophylaxis.
Type and virulence of organism, size of inoculate.
Modes of occupational infections of health workers
Direct percutaneous inoculation of infected blood (e.g. needle-stick injury, scalpel wounds).
Entry of infection through minute skin abrasions after contact with spilled infectious bodily fluids (e.g. blood, saliva, semen, urine, faeces).
Entry of infection via mucosal surfaces after exposure to contaminated infectious bodily fluids (e.g. eye splashes in theatre, faecal-oral route).
Transfer of infection by fomites (e.g. via contaminated equipment—prions transferred by neurosurgical equipment).
Procedures designed to minimize transmission
See also p. 174 for HIV and hepatitis.
Identify infected (infectious) patients by serology.
Identify potentially infected (infectious) patients by risk factors (e.g. IV drug users at risk from hepatitis B carriage).
Specific procedures for the care of infected (infectious) patients (e.g. barrier nursing for C. difficile diarrhoea).
Careful disposal of disposable items related to patient care.
Specific treatment and sterilization of non-disposable equipment.
Additional/specific precautions for theatre staff:
Make all procedures ‘safe’ procedures by having the highest standards of safety and care using instruments and sharps: remember ALL patients may be infected/infectious.
Wearing of plastic aprons in procedures with expected soiling with urine/faeces/ascites.
Wearing of two pairs of gloves to reduce the risk of skin exposure when gloves tear.
Wearing of re-enforced gloves for procedures with a high risk of penetrating injury (e.g. fragmented fractures).
Wearing of glasses, goggles, or visors for eye protection.
Handle all sharps using a transfer container: never pass them hand to hand.
Don't allow unnecessary blood or fluid spillage.
Surgically important organisms
Normal body flora
These are usually involved in infections in surgical patients and include:
Staphylococci
Normal flora of skin, oropharynx, and nasopharynx.
S. aureus is an important pathogen in many surgical infections.
S. aureus is the only staphylococcus that can coagulate plasma.
‘Coagulase negative’ effectively means non S. aureus staph, e.g. S. epidermis: they are usually dismissed as contaminants, but they are an increasingly common cause of line and prosthesis infections, particularly in immunocompromised patients.
Antibiotic sensitivities: cephalosporins especially cefuroxime, gentamicin, fusidic acid, vancomycin, rifampicin, teicoplanin.
Antiseptic sensitivities: chlorhexidine, povidone-iodine.
Methicillin-resistant S. aureus (MRSA) is resistant to all cephalosporins; vancomycin, teicoplanin, fusidic acid should be reserved to treat this.
Streptococci
Normal flora of skin, oropharynx, and nasopharynx.
‘ α -haemolytic’ streptococci haemolyse blood agar, e.g. S. pyogenes.
‘ β -haemolytic’ streptococci also haemolyse erythrocytes, e.g. S. viridens.
Pneumococci and enterococci (below) are subtypes of streptococci.
S. pyogenes has been called ‘the most important human pathogen’: it causes ‘strep throat’, a range of skin infections, septicaemia, necrotizing fasciitis, toxic shock syndrome, and valvular disease in rheumatic fever.
Antibiotic sensitivities: penicillin, erythromycin, cephalosporins, clindamycin, fusidic acid, mupirocin.
Antiseptic sensitivities: chlorhexidine, povidone-iodine.
Enterococci
Normal flora of large intestine.
These are an increasingly important cause of nosocomial infections.
Involved in wound infections, intra-abdominal sepsis, urinary tract infections, intravascular line infections, and dialysis-related infections.
Antibiotic sensitivities: enterococci are intrinsically resistant to many antibiotics, including all cephalosporins, and must usually be treated by a combination drug regime, e.g. ampicillin plus glycoside.
Vancomycin-resistant enterococcus (VRE) is resistant to all cephalosporins and vancomycin, and sometimes teicoplanin.
‘The Gram-negative rods’
Normal flora of large intestine.
Gram-negative bacilli (also known as coliforms) include Escherichia coli, Salmonella, Klebsiella, Enterobacter, and Proteus.
Pseudomonas and Actinobacter are non-coliform Gram-negatives.
Antibiotic sensitivities: most are intrinsically resistant to penicillin and there is increasing resistance to amoxicillin and ampicillin; cephalosporins are the commonest first-line treatment for non-resistant forms or ‘extended range’ penicillins (e.g. piperacillin/tazobactam), aminoglycosides (e.g. gentamicin, streptomycin, amikacin, tobramycin), alone or in combination with cephalosporins, offer good bactericidal action.
Anaerobes
Normal flora of skin, oropharynx, large bowel, terminal ileum, and genitourinary tract.
Include Bacteroides and clostridia (bowel).
C. difficile causes pseudomembranous colitis (see p. 396).
Cause anaerobic infections, including cellulitis, gas gangrene, empyemas, and colonize diabetic foot ulcers.
Act usually with aerobes to produce ‘synergistic’ necrotizing infections of skin, fascia, and muscle spontaneously or after trauma or surgery.
Antibiotic sensitivities: metronidazole is only active against anaerobes and resistance is rare; most anaerobes are also sensitive to penicillins, cephalosporins, clindamycin, erythromycin, and co-trimoxazole.
Specific infections
Gas gangrene
Gas gangrene is caused by Clostridium perfringens, a Gram-positive bacillus, found in soil or faeces. Injury may be trivial. More common in immunocompromised patients. There is exudate and gas in the tissues; skeletal muscle is affected. Oedema, spreading gangrene, and systemic signs follow. Aggressive debridement and fasciotomies are required, with resuscitation, organ support, and penicillin (2g 4-hourly IV) and metronidazole.
Synergistic spreading gangrene (Meleney's or Fournier's gangrene)
Also known as necrotizing fasciitis . The organisms involved are not clostridial, but rather aerobes and synergistic microaerophilic/anaerobes. Patients may be immunocompromised. The initial wound might have been minor or an uneventful operation. Severe wound pain and gas in the tissues (crepitus) may be seen: the extent of subdermal gangrene may not be apparent. Systemic support and antibiotics are required, with excision of involved tissues.
Tetanus
This is a rare infection in the UK, but is common in many parts of the world, with a mortality rate of about 60%. The causal organism, Clostridium tetani, produces a powerful exotoxin which is neurotoxic. It enters the spinal cord via peripheral nerves where it blocks inhibitory spinal reflexes. It is found widely: infection often follows a trivial puncture wound. Treatment is benzylpenicillin, 1g every 6h IV, metronidazole, and human anti-tetanus immunoglobulin 30U/kg IM. If a wound is present, it is excised and left open to heal by secondary intention. Immunization with 10-yearly boosters is protective.
Soft tissue infections
Cellulitis is the presence of actively dividing infectious bacteria within the skin tissues.
Abscess is a liquid collection of pus lined by granulation tissue and fibrosis (if chronic).
Lymphangitis is the presence of actively dividing infectious bacteria in the lymphatic vessels of an area of the body.
Fasciitis is inflammation of connective tissue that may be infective.
Myositis is infection or inflammation of muscle tissue.
Cellulitis
Pathological features
Skin entry by pathogenic bacteria (scratch, ulcer, hair follicle).
Usually Gram +ve cocci (e.g. Streptococcus pyogenes, S. aureus).
Usually heals by resolution if treated promptly.
Spread may result in lymphangitis, suppuration results in a furuncle (skin gland), carbuncle (upper dermis), or an abscess (deep skin tissue).
Clinical features
Skin widely involved: warm, red (usually blanches with pressure), swollen (often pitting), and exquisitely painful.
Crepitus indicates the development of gas-forming tissue necrosis which may be an emergency (see p. 175).
Treatment
IV antibiotics: benzylpenicillin (1g qds) and flucloxacillin (500mg qds).
Always assess with microscopy and culture, if possible.
Abscess
Pathological features
Contain polymorphonuclear neutrophils (PMNs)/macrophages, lymphocytes (live and dead), bacteria (dead and viable), and liquefied tissue products.
May rupture (‘pointing’), discharge into another organ (forming a fistula eventually), or open onto another epithelial surface (sinus) (see p. 151).
Incomplete treatment due to resistant organisms (mycobacteria) or poor treatment may lead to chronic abscesses.
Complete elimination of the organisms in a chronic abscess without drainage can lead to a ‘sterile abscess’ (‘anti-bioma’).
Typical causes
Suppuration of tissue infection (e.g. renal abscess from pyelonephritis).
Contained infected collections (e.g. subphrenic abscesses).
Haematogenous spread during bacteraemias (e.g. cerebral abscesses).
Diagnosis
Deep abscesses are characterized by swing fever, rigors, high WCC, and high CRP. Untreated, they lead to catabolism, weight loss, and a falling serum albumin. Ultrasound, CT, MRI, or isotope studies may be necessary to confirm the diagnosis.
Treatment
Drain the pus, e.g. incision and drainage (perianal abscess), CT-guided drain (renal abscess), closed surgical drainage (chest empyema), or surgical drainage and debridement (intra-abdominal abscess).
IV antibiotics (may require course of several weeks, indicating PICC line insertion).
Fasciitis
Suspect when pain, oedema, and skin necrosis appear within 24–48h of injury or operation.
Signs
The skin may be normal, oedematous, or mottled. There may be spiking fever, hypotension, mental confusion.
Treatment
IV fluids; extensive excision may be indicated.
Antibiotics on the basis of Gram stain.
Dress incisions with moist gauze impregnated with dilute aqueous antiseptics. Change these frequently under general anaesthetic.
Myositis
The bacterial infection has penetrated and destroyed muscle bundles.
Cause
Usually Clostridium perfringens, a Gram-positive, anaerobic, spore-forming rod.
Management
Recognize the condition: there is oedema and serosanguinous exudate; exposed muscle is swollen and ranges from salmon pink to
deep green/black in appearance. Crepitation may be present. There is a ‘sickly sweet’ smell.
Excise dead tissue until healthy, contractile, bleeding muscle is encountered.
Carry out Gram staining immediately. Streptococcal myositis rarely needs amputation, clostridial may.
Replace extracellular fluid (ECF) deficit. Transfuse if needed.
High-dose penicillin (IM or IV, 0.6–1.2g every 2h). May need antianaerobic therapy.
Excision of all infected tissue may necessitate full thickness excision of abdominal wall with prosthetic mesh replacement. Amputations are performed by guillotine technique and the wounds packed open.
There is no proven advantage to hydrogen peroxide dressings or the use of hyperbaric oxygen, but passive immunization in proven clostridial gangrene has been suggested, using a variety of bacterially derived products.
Osteomyelitis
Blood-borne viruses and surgery
Viral hepatitis
Commonest liver disease in the world.
May cause acute liver failure or chronic active hepatitis.
Hepatitis A
Formerly known as infectious hepatitis. This is the most common form of jaundice in children and young adults.
Spread is by the faecal-oral route; the incubation period is 1 month.
The antibody to the virus is anti-HAV.
There is no vaccine and health care workers do not have to be tested.
Hepatitis B
Double-shelled DNA virus: 565 new cases in UK in 2000. Ten per cent of adults fail to clear the virus after infection. Up to 5% people worldwide are carriers.
Infection is largely blood-borne and is transmitted by blood transfusion, inoculation, sharing syringes (drug addicts), sexual intercourse during menstruation (with an infected partner), and anal intercourse.
Transmission from a contaminated sharps injury is 30%.
Antigens appear in the serum: HBsAg, the surface antigen; HBcAg, the hepatitis core antigen; HBeAg, the ‘e’ antigen; the Dane particle; double-stranded DNA; and DNA polymerase activity.
Antibodies formed against these antigens (anti-HBs, anti-HBe) can be detected in the peripheral blood:
HBsAg +ve. Failure to clear infection, residual infectivity.
HBsAb +ve. Protection marker from immunization or infection.
HBeAg +ve. Close correlation of infectivity.
Hospital staff are routinely offered vaccination for hepatitis B:
Infectious carriers may not perform exposure-prone procedures.
Vaccination against hepatitis B is not compulsory. The alternatives are frequent testing to check infectivity or limited clinical practice.
The NHS Injury Benefits Scheme provides some benefits where hepatitis B has been occupationally acquired.
Treatment. Any health care worker who remains HBeAg +ve may undergo antiviral therapy under supervision by a hepatologist including:
Immunomodulation with interferon.
Viral suppression with nucleoside analogues.
Hepatitis C
RNA virus which causes cirrhosis of the liver and primary liver cancer. There is no vaccination. Detected in 1 in 150 screened blood donations: 0.4% of the UK population are chronically infected. Transmission from a contaminated sharps injury is 2–3%. Surgeons must be tested for hepatitis C and may not carry out exposure-prone procedures if hepatitis C +ve.
Human immunodeficiency virus (HIV)
Double-stranded RNA retrovirus transmitted by passage of infected body fluids from one person to another by several methods: anal and vaginal sexual intercourse, peripartum, sharps, and infected blood products.
HIV infection results in widespread immunological dysfunction, manifested by a fall in CD4 +ve lymphocytes, monocytes, and antigen-presenting cells (APCs).
There is usually a 3-month asymptomatic, but infective viraemia.
During this period, ELISA tests for HIV antibodies are negative.
At seroconversion, an acute illness can occur.
This is followed by generalized lymphadenopathy.
Acquired immunodeficiency syndrome (AIDS) develops in 5–10y.
Median survival with untreated AIDS is 2y, treated is >20y.
High risk populations (2004 WHO statistics)
Prevalence in adult population of southern Africa is 15–30%.
Prevalence in adult population of sub-Saharan Africa is 5–15%.
Prevalence in homosexual men at London genitourinary clinics is 10%.
Prevalence of HIV in injecting drug users in UK is about 1%.
High risk procedures
The UK General Medical Council (GMC) has made it clear that surgeons are obliged, if required, to operate on patients with AIDS or HIV infection. Always use universal precautions. High risk procedures include:
Any invasive procedure in HIV +ve patients.
Invasive procedures in at-risk populations (see above).
Biopsies for the diagnosis of opportunistic infection or suspected HIV.
Procedures to deal with malignancies, e.g. Kaposi's sarcoma, B-cell and non-Hodgkin's lymphoma, squamous oral carcinoma.
The HIV risk from an HIV contaminated hollow needle is 0.3%.
The risk from splashes on broken skin or mucous membranes is 0.1%.
PEP 
Go to occupational health or A&E out of hours. PEP reduces the risk of seroconversion by over 80% if started within 1h of exposure; PEP is continued for 4 weeks. Side effects include diarrhoea and vomiting.
These are designed to protect workers from exposure to diseases spread by blood and body fluids. All patients are assumed to be infectious for blood-borne diseases, including HIV.
They apply to blood; amniotic, synovial, pleural, peritoneal and pericardial fluid; semen, vaginal secretions; and CSF.
They do not apply to faeces, sputum, urine, vomit, or saliva.
Universal precautions include:
Use of protective clothing, e.g. gloves, gowns, masks, eye-guards.
Removing hazards from work place, e.g. sharps bins, ventilation.
Work practice, e.g. hand washing, handling of sharps, transport of soiled goods, reducing unnecessary procedures.
Single use disposable injection equipment.
Hospital policy for all sharps injuries: squeeze, wash, and report.
Bleeding and coagulation
Haemostasis
This is the physiological process by which bleeding is controlled. It has four components:
Vessel wall response, primarily vasoconstriction due to smooth muscle contraction, is the first response.
Platelet activity results in formation of a platelet plug.
Platelets adhere to exposed endothelial collagen, a process which required von Willebrand factor (VWF) (factor VIII).
Release of adenosine diphosphate (ADP), arachidonic acid, prostaglandin, and thromboxane A2 promotes platelet aggregation .
Aggregated platelets react with thrombin and fibrin, forming a plug.
Aspirin irreversibly inhibits the cyclooxygenase-mediated formation of prostaglandin, lasting for the life of the platelet (7–10 days); clopidogrel irreversibly inhibits ADP-mediated aggregation (7–10 days).
The coagulation cascade converts prothrombin to thrombin to produce a fibrin clot: two interacting pathways are involved.
The intrinsic pathway involves only normal blood components and starts when factor XII (Hageman factor) is activated by binding to a damaged vessel, resulting in the sequential activation of factors XI, IX, VIII, and X.
The extrinsic pathway requires thromboplastin (a tissue phospholipid) which forms a complex with calcium and factor VII, which activates factor X.
Both these pathways converge at the activation of factor X, which converts prothrombin to thrombin: thrombin converts soluble fibrinogen to fibrin to produce a stable clot.
All of the soluble factors are manufactured by the liver except factor VIII (made by endothelium).
Warfarin inhibits the manufacture of vitamin K-dependent clotting factors (prothrombin, VII, IX, and X): taking 3–4 days to have effect.
The fibrinolytic system terminates thrombus propagation to maintain circulating blood in a fluid state; it depends on four proteins.
Plasmin, a serine protease which is produced by the action of thrombin on plasminogen and attacks unstable bonds between fibrin molecules to generate fibrin degradation products.
Antithrombin III which deactivates thrombin, XIIa, IXa, and Xa.
Proteins C and S which prevent thrombin generation by binding factors Va and VIIIa. Tissue factor pathway inhibitor, produced by platelets, inhibits factors Xa and VIIa.
Heparin potentiates antithrombin III with immediate effect; protamine binds heparin, reversing its effect almost immediately.
Disorders of haemostasis
These can be thought of in terms of the four components below:
Vessel wall abnormalities, e.g. Henoch–Schonlein purpura, Cushing's syndrome, steroid use, vitamin C deficiency (scurvy).
Platelet abnormalities.
Thrombocytopaenia (<100 x 109/L3) caused by reduced production (bone marrow failure, radiotherapy, chemotherapy, infiltrative disease, e.g. neoplasia, leukaemia); faulty maturation (e.g. folate and B12 deficiency); abnormal distribution (splenomegaly); increased destruction (autoimmune disorders, drugs, DIC, haemorrhage); dilutional thrombocytopaenia in massive banked blood transfusion.
Abnormal function, e.g. von Willebrand's disease, uraemia, idiopathic causes, drug effects, especially aspirin and clopidogrel.
Coagulation abnormalities.
Congenital, e.g. haemophilia A (↓ factor VIII), haemophilia B or Christmas disease (↓ factor IX), von Willebrand's disease (↓ VWF).
Acquired, e.g. DIC (see p. 118); ↓ vitamin K (which is produced by gut flora) secondary to poor nutrition, antibiotic therapy, obstructive jaundice; liver disease; exogenous anticoagulants.
Preoperative evaluation of haemostasis
NICE guidelines
Routine testing not recommended unless patient is ASA 3 as a result of renal disease.
For at-risk patients undergoing ‘major +’ cardiac or neurosurgery, testing may be considered.
History and examination
Ask about bleeding problems, e.g. menorrhagia, bruising, family history of bleeding, and medication (specifically aspirin, clopidogrel, and warfarin which should all be stopped 5 days before elective surgery) (see p. 72).
Look for petechiae and purpura, jaundice, and hepatosplenomegaly.
Laboratory investigation
Platelet count. Normally 200–400 x 109/L; 70 x 109/L is needed for surgical haemostasis, <20 x 109/L results in spontaneous bleeding.
Blood film. Estimate of platelet count and indicates morphology.
Bleeding time. Useful as normal bleeding time indicates normal platelets, normal function, and normal vascular response to injury, but uncommonly used as a screening test.
Prothrombin time (PT). Reflects the extrinsic pathway (I, II, V, VII, X).
Partial thromboplastin time (PTT). Reflects the intrinsic pathway (all factors except VII).
Individual clotting factor assays.
Thrombin time (TT). Rate of conversion from fibrin to fibrinogen.
Fibrin degradation products. These are released by the action of plasmin and are raised in DIC.
Principles of management
Indications for FFP, platelets, and anti-fibrinolytics are listed on p. 96.
IV heparin may be reversed with protamine and/or FFP.
Warfarin may be reversed over 12–24h with 1mg vitamin K SC or acutely with FFP.
Anaemia and polycythaemia
Anaemia
This is a reduction in haemoglobin concentration below normal (approximately 13–16g/dL in men, 11.5–15g/dL in females). It is classified as follows:
Decreased red cell production.
Haematinic deficiency (↓ Fe, B12, folic acid).
Bone marrow failure (congenital, chemotherapy, radiotherapy, infiltrative disease).
Abnormal red cell maturation.
Myelodysplasia.
Sideroblastic anaemia.
Increased red cell destruction (haemolytic anaemias).
Inherited (e.g. sickle cell, thalassaemia).
Acquired (e.g. autoimmune, DIC—see p. 118).
Chronic disease (common cause of anaemia in surgical patients).
Renal failure (↓ production of erythropoietin).
Endocrine, liver disease.
Iron deficiency anaemia
Commonest cause of anaemia in surgical patients. Causes include:
Menstruation (in 15% of females).
GI losses (peptic ulcer, oesophagitis, gastric carcinoma, colorectal carcinoma).
Reduced iron uptake (poor diet, coeliac disease, malabsorption).
Sickle cell anaemia
Single base substitution gene defect causing an amino acid substitution in haemoglobin, making HbS instead of HbA. Deoxygenated HbS polymerizes and causes red blood cells to sickle, resulting in occlusion of small blood vessels and infarction. Common in black Africans. Homozygotes have high levels of HbS and are prone to crises. Heterozygotes (‘sickle trait’) are only symptomatic in hypoxic conditions, e.g. unpressurized aircraft, limb ischaemia.
Most patients are diagnosed: screening for sickle cell is widespread.
The patient typically has an Hb of 6–8g/dL, reticulocytes 10–20%.
There are three types of sickle cell ‘crisis’:
Thrombotic crises. Precipitate by cold, dehydration, infection, ischaemia, may mimic acute abdomen or pneumonia, priapism;
Aplastic crises. Due to parvoviruses and require urgent transfusion;
Sequestration crises. Spleen and liver enlarge rapidly from trapped erythrocytes, resulting in right upper quadrant (RUQ) pain, ↑ INR, ↑ LFT, ↓↓ Hb.
Treatment involves removing causes and decreasing percentage of HbS.
Keep warm and well hydrated, if necessary with IV fluids.
Give O2.
Give opiate analgesia.
Empirical antibiotics if any evidence of sepsis.
If Hb <6g/L, give blood; if Hb >9g/dL, exchange transfusion.
Exchange transfusion to maintain HbA >60% before cardiac surgery.
Thalassaemia
Thalassaemias are genetic diseases of Hb synthesis, resulting in underproduction of one chain which results in destruction of red cells while they are still in the bone marrow. ⍺-thalassaemia leads to ↓ ⍺ chain production with unbalanced 𝛃 chain production and 𝛃-thalassaemia leads to ↓ 𝛃 chain production. Common in the Mediterranean to Far East.
Severity correlates with the genetic deficit.
Death may result by 1y of age without transfusion.
Symptoms of iron overload after 10y: endocrine failure, liver disease, and cardiac toxicity.
Death at 20–30y due to cardiac siderosis.
Preoperative screening of anaemia: NICE guidelines
FBC ‘should be considered’ for all surgery in adults >60y of age.
FBC is recommended for ‘intermediate’ surgery (e.g. primary repair of inguinal hernia, varicose vein surgery) in adults >60y of age.
FBC is recommended in any adult undergoing major surgery.
Sickle cell screening is recommended in any patient of African descent undergoing a general anaesthetic: consent should be obtained.
Preoperative evaluation of anaemia
↓ Mean cell volume (MCV) or microcytic anaemia
Iron deficiency (blood loss, dietary): ↓ serum ferritin and iron, ↑ total iron binding capacity (TIBC).
Thalassaemia (↑ serum iron and ferritin, ↓ TIBC).
Hyperthyroidism.
↑ MCV or macrocytic anaemia
B12 or folate deficiency (dietary, pernicious anaemia, anti-folate drugs).
Alcohol.
Liver disease.
Myelodysplasia and bone marrow infiltration.
Hypothyroidism.
Normal MCV or normocytic anaemia
Anaemia of chronic disease, renal failure, bone marrow failure, haemolysis, pregnancy, dilutional.
Management of anaemia
Elective patients should be investigated and treated appropriately.
Blood transfusion (see p. 96) is indicated in patients with Hb <8g/dL undergoing emergency or elective surgery.
Evidence suggests that maintaining Hb 7–9g/dL has a better outcome than maintaining Hb 10–12g/dL, except in patients with unstable angina.
Polycythaemia
Relative (↓ plasma volume). Dehydration from alcohol or diuretics).
Absolute (↑ red cell mass).
Primary (polycythaemia rubra vera).
Secondary (altitude, smoking, COPD, tumours, e.g. fibroids).
Treat underlying cause; consider venesection.
