Extracellular Health Dictionary

The appropriate balance of ?uid input and output (along with dissolved salts essential for life) over 24 hours. During this period, about 2,500 millilitres (ml) of ?uid should be taken in by a 70-kg man and the same amount excreted; of this, 1,500 ml will be drunk, 800 ml will be in the food eaten, and 200 ml produced by food metabolism. Excreted water is made up of 1,500 ml of urine, 800 ml insensible loss and 200 ml in the faeces. A 70-kg man’s total body ?uid is 42 litres – 60 per cent of body weight. Intracellular ?uid comprises 28 litres, extracellular, 14 litres and blood, 5 litres. Water is controlled mainly by the sodium concentration in the body ?uids via the release of antidiuretic hormone (ADH – see VASOPRESSIN) from the posterior part of the PITUITARY GLAND. In seriously ill people, close monitoring of ?uid intake and output, along with measurements of PLASMA sodium and calcium concentrations, is an essential factor in treatment.... fluid balance

The body’s defence against foreign substances such as bacteria, viruses and parasites. Immunity also protects against drugs, toxins and cancer cells. It is partly non-speci?c – that is, it does not depend on previous exposure to the foreign substance. For example, micro-organisms are engulfed and inactivated by polymorphonuclear LEUCOCYTES as a ?rst line of defence before speci?c immunity has developed.

Acquired immunity depends upon the immune system recognising a substance as foreign the ?rst time it is encountered, storing this information so that it can mount a reaction the next time the substance enters the body. This is the usual outcome of natural infection or prophylactic IMMUNISATION. What happens is that memory of the initiating ANTIGEN persists in selected lymphocytes (see LYMPHOCYTE). Further challenge with the same antigen stimulates an accelerated, more vigorous secondary response by both T- and B-lymphocytes (see below). Priming the immune system in this manner forms the physiological basis for immunisation programmes.

Foreign substances which can provoke an immune response are termed ‘antigens’. They are usually proteins but smaller molecules such as drugs and chemicals can also induce an immune response. Proteins are taken up and processed by specialised cells called ‘antigenpresenting cells’, strategically sited where microbial infection may enter the body. The complex protein molecules are broken down into short amino-acid chains (peptides – see PEPTIDE) and transported to the cell surface where they are presented by structures called HLA antigens (see HLA SYSTEM).

Foreign peptides presented by human leucocyte antigen (HLA) molecules are recognised by cells called T-lymphocytes. These originate in the bone marrow and migrate to the THYMUS GLAND where they are educated to distinguish between foreign peptides, which elicit a primary immune response, and self-antigens (that is, constituents of the person themselves) which do not. Non-responsiveness to self-antigens is termed ‘tolerance’ (see AUTOIMMUNITY). Each population or clone of T-cells is uniquely responsive to a single peptide sequence because it expresses a surface molecule (‘receptor’) which ?ts only that peptide. The responsive T-cell clone induces a speci?c response in other T-and B-lymphocyte populations. For example, CYTOTOXIC T-cells penetrate infected tissues and kill cells which express peptides derived from invading micro-organisms, thereby helping to eliminate the infection.

B-lymphocytes secrete ANTIBODIES which are collectively termed IMMUNOGLOBULINS (Ig)

– see also GAMMA-GLOBULIN. Each B-cell population (clone) secretes antibody uniquely speci?c for antigens encountered in the blood, extracellular space, and the LUMEN of organs such as the respiratory passages and gastrointestinal tract.

Antibodies belong to di?erent Ig classes; IgM antibodies are synthesised initially, followed by smaller and therefore more penetrative IgG molecules. IgA antibodies are adapted to cross the surfaces of mucosal tissues so that they can adhere to organisms in the gut, upper and lower respiratory passages, thereby preventing their attachment to the mucosal surface. IgE antibodies also contribute to mucosal defence but are implicated in many allergic reactions (see ALLERGY).

Antibodies are composed of constant portions, which distinguish antibodies of di?erent class; and variable portions, which confer unique antigen-binding properties on the product of each B-cell clone. In order to match the vast range of antigens that the immune system has to combat, the variable portions are synthesised under the instructions of a large number of encoding GENES whose products are assembled to make the ?nal antibody. The antibody produced by a single B-cell clone is called a monoclonal antibody; these are now synthesised and used for diagnostic tests and in treating certain diseases.

Populations of lymphocytes with di?erent functions, and other cells engaged in immune responses, carry distinctive protein markers. By convention these are classi?ed and enumerated by their ‘CD’ markers, using monoclonal antibodies speci?c for each marker.

Immune responses are in?uenced by cytokines which function as HORMONES acting over a short range to accelerate the activation and proliferation of other cell populations contributing to the immune response. Speci?c immune responses collaborate with nonspeci?c defence mechanisms. These include the COMPLEMENT SYSTEM, a protein-cascade reaction designed to eliminate antigens neutralised by antibodies and to recruit cell populations which kill micro-organisms.... immunity

n. a solution whose hydrogen ion concentration (pH) remains virtually unchanged by dilution or by the addition of acid or alkali. The chief buffer of the blood and extracellular body fluids is the bicarbonate (H2CO3/HCO3?) system. See also acid-base balance.... buffer

n. an enzyme that catalyses the cleavage of DNA. A genetically engineered form, recombinant human DNAse (dornase alfa), is used in the treatment of *cystic fibrosis to reduce the viscosity of the sticky secretions in the lungs. Administered by inhalation via a jet nebulizer, it appears to hydrolyse extracellular DNA that accumulates with other neutrophil debris in the airways. Trade name: Pulmozyme.... dnase

n. 1. (in histology) the substance of a tissue or organ in which more specialized structures are embedded; for example, the ground substance (extracellular matrix) of connective tissue. 2. (in radiology) the division of an image into rows and columns with equally sized elements (*pixels). The final image is completed by assigning a density to each of these elements. Increasing the number of pixels in the matrix improves the resolution of the final image. A typical value could be 256 rows × 256 columns.... matrix

This is the pressure that is maintained by the brain tissue, intracellular and extracellular ?uid, cerebrospinal ?uid and blood. An increase in intracranial pressure may occur as a result of in?ammation, injury, haemorrhage, or tumour in the brain tissue as well as of some congenital conditions. The pressure is measured by lumbar puncture in which a syringe attached to a mamometer (pressure-measuring device) is inserted into the cerebrospinal ?uid surrounding the lower part of the spinal cord. Where continuous pressure monitoring is necessary, an in-dwelling device can be implanted into a cerebral ventricle. Normal pressure is around 10 mm of mercury (Hg), with the acceptable upper limit being 25 mm Hg.... intracranial pressure

A particle that carries an electrical charge; positive ions are called cations and negative ions are called anions. Many vital body processes, such as the transmission of nerve impulses, depend on the movement of ions across cell membranes. Sodium is the principal cation in the fluid that bathes all cells (extracellular fluid). It affects the flow of water into and out of cells (see osmosis), thereby influencing the concentration of body fluids.

The acidity of blood and other body fluids depends on the level of hydrogen cations, which are produced by metabolic processes. To prevent the fluids from becoming too acidic, hydrogen cations are neutralized by bicarbonate

anions in the extracellular fluid and blood, and by phosphate anions inside cells (see acid–base balance).... ion

A simple compound that is essential for all life. Its molecular structure is H2O (2 atoms of hydrogen bonded to 1 of oxygen). Water is the most common substance in the body, accounting for about 99 per cent of all molecules, but a smaller percentage of total body weight. Approximately 2 thirds of the body’s water content is contained within the body cells, and the remaining third is extracellular (found, for example, in the blood plasma, lymph, and cerebrospinal and tissue fluid).

Water provides the medium in which all metabolic reactions take place (see metabolism), and transports substances around the body. The blood plasma carries water to all body tissues, and excess water from tissues for elimination via the liver, kidneys, lungs, and skin. The passage of water in the tissue fluid into and out of cells takes place by osmosis.

Water is taken into the body in food and drink and is lost in urine and faeces, as exhaled water vapour, and by sweating (see dehydration). The amount of water excreted in urine is regulated by the kidneys (see also ADH). Extra water is needed to excrete excess amounts of substances, such as sugar or salt, in the blood, and high water intake is essential in hot climates where a large amount of water is lost in sweat.

In some disorders, such as kidney failure or heart failure, insufficient water is excreted in the urine, resulting in oedema.... water

n. a large glycoprotein that acts as a host defence mechanism. In the plasma it induces phagocytosis and on the cell surface it induces protein linkage which is important in the formation of new epithelium in wound healing. It is also involved in platelet aggregation. It is concentrated in connective tissue and the endothelium of the capillaries and is a component of the extracellular matrix. In pregnancy, fetal fibronectin (fFN) is found in high concentrations in secretions from the cervix and vagina before fusion of the membranes occurs at around 21 weeks of gestation. Inflammation or trauma to the fetal–maternal surface after then causes secretion of fFN into the cervix and vagina. Vaginal swabs that detect fFN can be used to predict preterm birth between 22 and 34 weeks gestation.... fibronectin

n. a mineral element and an important constituent of the human body (average sodium content of the adult body is 4000 mmol). Sodium controls the volume of extracellular fluid in the body and maintains the acid-base balance. It also helps maintain electrical potentials in the nervous system and is thus necessary for the functioning of nerves and muscles. Sodium is contained in most foods and is well absorbed, the average daily intake in the UK being 8.1 g/day. The amount of sodium in the body is controlled by the kidneys. An excess of sodium leads to the condition of hypernatraemia, which often results in *oedema. This can be fatal in newborns, and is more likely to occur in formula-fed infants, particularly if the formula is made up at too high a concentration. Infants are at higher risk as they are less able to remove sodium from the body than adults. Sodium is also implicated in hypertension: a high-sodium diet is thought to increase the risk of hypertension in later life. The UK government target is for adults to consume less than 6 g/day. Symbol: Na.... sodium

n. spaces around the kidney tubules containing cells and extracellular components. The tubulointerstitium is believed to influence many aspects of the development and functioning of the tubules and blood vessels of the kidney. —tubulointerstitial adj.... tubulointerstitium

The study of all aspects of micro-organisms (microbes) – that is, organisms which individually are generally too small to be visible other than by microscopy. The term is applicable to viruses (see VIRUS), BACTERIA, and microscopic forms of fungi, algae, and PROTOZOA.

Among the smallest and simplest microorganisms are the viruses. First described as ?lterable agents, and ranging in size from 20–30 nm to 300 nm, they may be directly visualised only by electron microscopy. They consist of a core of deoxyribonucleic or ribonucleic acid (DNA or RNA) within a protective protein coat, or capsid, whose subunits confer a geometric symmetry. Thus viruses are usually cubical (icosahedral) or helical; the larger viruses (pox-, herpes-, myxo-viruses) may also have an outer envelope. Their minimal structure dictates that viruses are all obligate parasites, relying on living cells to provide essential components for their replication. Apart from animal and plant cells, viruses may infect and replicate in bacteria (bacteriophages) or fungi (mycophages), which are damaged in the process.

Bacteria are larger (0·01–5,000 µm) and more complex. They have a subcellular organisation which generally includes DNA and RNA, a cell membrane, organelles such as ribosomes, and a complex and chemically variable cell envelope – but, unlike EUKARYOTES, no nucleus. Rickettsiae, chlamydia, and mycoplasmas, once thought of as viruses because of their small size and absence of a cell wall (mycoplasma) or major wall component (chlamydia), are now acknowledged as bacteria; rickettsiae and chlamydia are intracellular parasites of medical importance. Bacteria may also possess additional surface structures, such as capsules and organs of locomotion (?agella) and attachment (?mbriae and stalks). Individual bacterial cells may be spheres (cocci); straight (bacilli), curved (vibrio), or ?exuous (spirilla) rods; or oval cells (coccobacilli). On examination by light microscopy, bacteria may be visible in characteristic con?gurations (as pairs of cocci [diplococci], or chains [streptococci], or clusters); actinomycete bacteria grow as ?laments with externally produced spores. Bacteria grow essentially by increasing in cell size and dividing by ?ssion, a process which in ideal laboratory conditions some bacteria may achieve about once every 20 minutes. Under natural conditions, growth is usually much slower.

Eukaryotic micro-organisms comprise fungi, algae, and protozoa. These organisms are larger, and they have in common a well-developed internal compartmentation into subcellular organelles; they also have a nucleus. Algae additionally have chloroplasts, which contain photosynthetic pigments; fungi lack chloroplasts; and protozoa lack both a cell wall and chloroplasts but may have a contractile vacuole to regulate water uptake and, in some, structures for capturing and ingesting food. Fungi grow either as discrete cells (yeasts), multiplying by budding, ?ssion, or conjugation, or as thin ?laments (hyphae) which bear spores, although some may show both morphological forms during their life-cycle. Algae and protozoa generally grow as individual cells or colonies of individuals and multiply by ?ssion.

Micro-organisms of medical importance include representatives of the ?ve major microbial groups that obtain their essential nutrients at the expense of their hosts. Many bacteria and most fungi, however, are saprophytes (see SAPROPHYTE), being major contributors to the natural cycling of carbon in the environment and to biodeterioration; others are of ecological and economic importance because of the diseases they cause in agricultural or horticultural crops or because of their bene?cial relationships with higher organisms. Additionally, they may be of industrial or biotechnological importance. Fungal diseases of humans tend to be most important in tropical environments and in immuno-compromised subjects.

Pathogenic (that is, disease-causing) microorganisms have special characteristics, or virulence factors, that enable them to colonise their hosts and overcome or evade physical, biochemical, and immunological host defences. For example, the presence of capsules, as in the bacteria that cause anthrax (Bacillus anthracis), one form of pneumonia (Streptococcus pneumoniae), scarlet fever (S. pyogenes), bacterial meningitis (Neisseria meningitidis, Haemophilus in?uenzae) is directly related to the ability to cause disease because of their antiphagocytic properties. Fimbriae are related to virulence, enabling tissue attachment – for example, in gonorrhoea (N. gonorrhoeae) and cholera (Vibrio cholerae). Many bacteria excrete extracellular virulence factors; these include enzymes and other agents that impair the host’s physiological and immunological functions. Some bacteria produce powerful toxins (excreted exotoxins or endogenous endotoxins), which may cause local tissue destruction and allow colonisation by the pathogen or whose speci?c action may explain the disease mechanism. In Staphylococcus aureus, exfoliative toxin produces the staphylococcal scalded-skin syndrome, TSS toxin-1 toxic-shock syndrome, and enterotoxin food poisoning. The pertussis exotoxin of Bordetella pertussis, the cause of whooping cough, blocks immunological defences and mediates attachment to tracheal cells, and the exotoxin produced by Corynebacterium diphtheriae causes local damage resulting in a pronounced exudate in the trachea.

Viruses cause disease by cellular destruction arising from their intracellular parasitic existence. Attachment to particular cells is often mediated by speci?c viral surface proteins; mechanisms for evading immunological defences include latency, change in viral antigenic structure, or incapacitation of the immune system – for example, destruction of CD 4 lymphocytes by the human immunode?ciency virus.... microbiology

(MMP) any one of a group of zinc-containing proteases capable of digesting the extracellular tissue matrix. These enzymes play an important role in cell division, cell migration, inflammation, neoplastic invasion (*metastasis), and *angiogenesis.... matrix metalloproteinase

any one of a class of drugs that interfere with cell growth in a variety of different ways by inhibiting the action of tyrosine kinases. This family of enzymes, which occur both within cells and as components of cell-membrane receptor sites, have an important role in cell division and cell growth. Many tumour cells have been shown to have both intracellular enzymes and extracellular receptor sites, and a variety of anticancer agents have been developed to inhibit enzyme activity at these sites. Among these drugs are *imatinib, dasatinib, and nilotinib, used for treating chronic myeloid leukaemia; *sunitinib, for treating renal cell carcinoma; and erlotinib, for treating pancreatic cancer and non-small-cell lung cancer. See also epidermal growth factor receptor.... tyrosine kinase inhibitor