Immunity, inflammation and infection
Inflammation
Introduction: Acute inflammation is the principal mechanism by which living tissues respond to injury. The purpose is to neutralise the injurious agent, to remove damaged or necrotic tissue and to restore the tissue to useful function. The central feature is formation of an inflammatory exudate with three principal components: serum, leucocytes (predominantly neutrophils) and fibrinogen.
Formation of inflammatory exudate involves local vascular changes collectively responsible for the four ‘cardinal signs of Celsus’—rubor (redness), tumor (swelling), calor (heat) and dolor (pain)—as well as loss of function. These vascular phenomena are described in Figure 3.1. The outcomes of acute inflammation are summarised in Figure 3.2.
Resolution: If tissue damage is minimal and there is no actual tissue necrosis, the acute inflammatory response eventually settles and tissues return virtually to normal without evidence of scarring. A good example is the resolution of mild sunburn.
Abscess formation (Fig. 3.3): An abscess is a collection of pus (dead and dying neutrophils plus proteinaceous exudate) walled off by a zone of acute inflammation. Acute abscess formation particularly occurs in response to certain pyogenic microorganisms that attract neutrophils but are resistant to phagocytosis and lysosomal destruction. Abscesses also form in response to localised tissue necrosis and to some organic foreign bodies (e.g. wood splinters, linen suture material). The main pyogenic organisms of surgical importance are Staphylococcus aureus, some streptococci (particularly Strep. pyogenes), Escherichia coli and related Gram-negative bacilli (‘coliforms’), and Bacteroides species (spp.).
Even with small, well-localised abscesses, showers of bacteria may enter the general circulation (bacteraemia) but are mopped up by hepatic and splenic phagocytic cells before they can proliferate. This is responsible for the swinging pyrexia characteristic of an abscess. The abscess site may not be clinically evident if deep-seated (e.g. subphrenic or pelvic abscess) and the patient may be otherwise well. In the presence of an abscess, circulating neutrophils rise dramatically as they are released from the bone marrow; thus, a marked neutrophil leucocytosis (i.e. WBC greater than 15 × 109/L with more than 80% neutrophils) usually indicates a pyogenic infection. Severe infection causing excessive cytokine responses spilling over into the systemic circulation causes systemic sepsis and rapid clinical deterioration (see p. 51).
Antibiotics and abscesses: If appropriate antibiotics are given early enough, organisms can be eliminated before abscess formation. In surgical operations with a particular risk of infection, therefore, prophylactic antibiotics dramatically reduce abscess formation and other infective complications. However, once an abscess has fully formed, antibiotics seldom effect a cure because pus and necrotic material remain and the drug cannot gain access to the bacteria within. Nevertheless, antibiotics may halt expansion or even sterilise the pus; the residual sterile abscess is known as an antibioma.
Organisation and repair: The most common sequel to acute inflammation is organisation, in which dead tissue is removed by phagocytosis and the defect filled by vascular connective tissue known as granulation tissue. This tissue is gradually ‘repaired’ to form a fibrous scar. Sometimes the original tissue regenerates, i.e. rebuilds its specialised cells and structure.
Wound healing
Healing by primary intention: The simplest example of organisation and repair is healing of an uncomplicated skin incision (see Fig. 3.4). There is no necrotic tissue and the wound margins are brought into apposition with sutures. An acute inflammatory response develops in the vicinity of the incision, and by the third day granulation tissue bridges the dermal defect. In the meantime, epithelium proliferating rapidly from the wound edges restores the epidermis. Fibroblasts invade the granulation tissue, laying down collagen so the repair is strong enough for suture removal after 5–10 days. The scar is still red but blood vessels gradually regress and it becomes a pale linear scar within a few months. This is known as healing by primary intention.
Healing by secondary intention: If tissue loss prevents the wound edges from coming together, healing has to bridge the defect, which is initially filled with blood clot. This later becomes infiltrated by vascular granulation tissue from the healthy wound base. Inflammatory exudate solidifies, forming a protective scab. Fibroblasts invade and lay down collagen in the extracellular spaces; after about a week, some fibroblasts differentiate into myofibroblasts and contraction of their myofibrils eventually shrinks the wound defect by 40–80%, beginning about 2 weeks after the injury. Over the weeks and months, blood vessels regress and more collagen is formed, leaving a relatively avascular scar; gradual contraction of the mature collagen (cicatrisation), combined with wound contraction, ensures the final scar is much smaller than the original defect. The epidermal defect is gradually bridged by epithelial proliferation from the wound margins. Epithelial cells slide over each other beneath the edges of the scab on the granulation tissue surface and the scab is eventually shed. This whole process is known as healing by secondary intention (see Fig. 3.4).
Chronic inflammation
Causes of chronic abscesses include:
• Infected foreign bodies are probably the most common cause in modern surgical practice. Foreign bodies implanted deliberately may become infected (e.g. synthetic mesh for inguinal hernia repair, prosthetic hip joint); others become embedded during trauma (e.g. glass fragments)
• Dead (necrotic) tissue can act as a foreign body, forming a nidus for infection. For example, diabetes may be complicated by deep foot infections with necrosis of tendon and bone leading to chronic abscesses and ulcers. Hairs deeply implanted in the natal cleft skin may cause a pilonidal sinus or abscess. An infected dead tooth or root fragment may intermittently discharge via an associated ‘gum boil’ (see Fig. 3.6). Chronic osteomyelitis is associated with remnants of dead bone known as sequestra
Fig. 3.6 ‘Gum boil’ as an example of a chronic abscess
Grossly neglected mouth showing widespread dental caries. There is an inflammatory swelling on the buccal (cheek) aspect of the alveolus G caused by a chronic apical dental abscess on the upper right incisor. Note the left central incisor 1 is missing and the left lateral incisor 2 has fractured at gum level because of caries. Sagittal section through gum boil of upper incisor tooth. The gum boil is in fact a sinus on the gum which discharges either chronically or intermittently. Exposed to infection, the tooth pulp has become necrotic while the apical abscess is slowly expanding due to the continued presence of infected necrotic tissue (i.e. the tooth pulp). The tooth root is all that remains after the crown has fractured due to dental caries
• Deep abscesses. A chronic abscess can arise without a foreign body if the acute abscess is so deep as to prevent spontaneous drainage. The best example is a subphrenic abscess
Specific granulomatous infections and inflammations
A tuberculous cold abscess, now rare in developed countries, is a pus-like accumulation of liquefied caseous material containing the occasional mycobacterium. In contrast to a pyogenic abscess, the lesion is cold to the touch since there is no acute inflammatory vascular response. Cervical lymph node tuberculosis (‘scrofula’) often produced a ‘collar-stud’ abscess, i.e. a superficial fluctuant abscess communicating with a deep (and often larger) lymph node abscess via a small fascial defect. Tuberculosis of the thoracolumbar spine causes local destruction and deformity and may track down beneath the inguinal ligament within the psoas sheath, presenting as a ‘psoas abscess’ in the groin. A tuberculous ulcer overlying tuberculous inguinal nodes is shown in Figure 3.7.
Case History
Fig. 3.7 Tuberculous ulcer
(a) This patient had lived in South Africa and had developed this painless and slowly enlarging ulcer about 3 months earlier. It originates from nearby infected lymph nodes and shows the typical appearances of a ‘wash leather’ base and an undercut edge. Diagnosis was based on a biopsy and treatment involved draining the involved lymph nodes visible above the ulcer and a course of antituberculous chemotherapy. (b) The healed lesion 2 months later
Infection
It is important to distinguish between colonisation, infection and sepsis:
• Colonisation is when bacteria are present in or on a host but do not cause an immune response or signs of disease
• Infection occurs when microorganisms provoke a sustained immune response and signs of disease, for example, when normal commensal bacteria in the colon such as E. coli contaminate the peritoneal cavity
• Sepsis (systemic sepsis) is the result of an excessive and inappropriate production of cytokines in response to severe infection or tissue necrosis (e.g. a gangrenous limb) that causes organ dysfunction and progressive organ failure
Clinically significant infection arises when the size of an inoculum or the virulence of a microorganism is sufficient to overcome the innate and adaptive immune responses and lead to symptoms. The virulence of an organism depends on its qualities of adherence and invasiveness and its ability to produce toxins. Tissue invasion of microorganisms may be enhanced by their secretion of enzymes (e.g. hyaluronidase and streptokinase), by mechanisms to avoid phagocytosis (e.g. encapsulation or spore formation), by inherent resistance to lysosomal destruction or by their ability to kill phagocytes. Toxins may be secreted by the organism (exotoxins) or released upon the death of the organism (endotoxins). In either case the toxin may produce local tissue damage (e.g. gas gangrene), cause distant toxic effects (e.g. tetanus), or activate cytokine systems to cause systemic sepsis, sometimes including disseminated intravascular coagulopathy.
Methods of control of nosocomial infection
Environment: Patient areas in hospitals must be clean and free from contaminating bacteria, including MRSA, especially where invasive procedures occur such as operating theatres and high-dependency units. Special precautions are taken in theatres (see Ch. 10, p. 124).
Staff: Staff must be vaccinated against hepatitis B. HIV-positive individuals should not undertake invasive procedures. Open wounds must be securely covered and staff with infective skin lesions should avoid patient contact. Universal blood and body fluid precautions should be taken to prevent viral transmission (see below) and guidelines followed for dealing with needle-stick injuries. Risk of MRSA and other infections can be drastically reduced by the simple measures such as washing hands with alcohol-based gel between every patient contact.
Patients: Bacterial swabs should be taken for MRSA from patients before admitting them to hospital and MRSA-positive patients should receive topical eradication therapy and have follow-up bacterial screening cultures to assess MRSA status before major surgery, e.g. hip replacements, arterial grafts. Patients known to have transmissible infections or to be carriers, e.g. of MRSA, should be nursed in isolation. Surgery should ideally be deferred on patients with acute respiratory or urinary tract infections.
