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G protein-coupled receptors (GPCRs). Large family of transmembrane receptors that bind a wide variety of ligands, including neurotransmitters and hormones. The target receptors of many drugs, including adrenergic, dopamine, opioid, 5-HT and histamine agents. The receptor consists of seven membrane-spanning helices bound on the inner surface of the membrane to a G protein, so called because they bind guanine diphosphate (GDP) and triphosphate (GTP). G proteins consist of three subunits: Gα, Gβ and Gγ. In the inactive state, Gα has GDP on its binding site (Fig. 75a). Activation of the GPCR by a ligand causes an allosteric change in the Gα subunit, resulting in the displacement of GDP and replacement by GTP; the Gβ and Gγ subunits dissociate from the complex (Fig. 75b). The activated Gα subunit in turn activates an effector molecule, e.g. adenylate cyclase (see Fig. 5; Adenylate cyclase). Activated Gα is a GTPase that rapidly reconverts GTP to GDP, thus restoring the G protein to its inactive state.

Fig. 75 G protein-coupled receptor in (a) inactive and (b) activated states (see text)

Many types of Gα subunit exist, including:

ent Gα_s: stimulates adenylate cyclase, increasing levels of cAMP in the cell, e.g. β-adrenergic agonists and glucagon are Gα_s-coupled.

ent Gα_i: inhibits adenylate cyclase, e.g. α₂-adrenergic receptor agonists are Gα_i-coupled.

ent Gα_q: activates phospholipase C, generating inositol triphosphate (IP₃), e.g. α₁-adrenergic receptor agonists are Gα_q-coupled.

In addition to their coupling to second messenger systems, G proteins can also be directly coupled to ion channels. They have been investigated as possible sites for interaction with anaesthetic agents.

Hollmann MW, Danja Strumper D, Herroeder S, Durieux ME (2005). Anesthesiology; 103: 1066–88

See also, Receptor theory

G proteins, see G protein-coupled receptors

G6PD deficiency, see Glucose 6-phosphate dehydrogenase deficiency

GABA, see γ-Aminobutyric acid

GABA receptors, see γ-Aminobutyric acid receptors

Gabapentin. Oral anticonvulsant drug, also used in chronic pain management. In epilepsy, used mainly as add-on therapy for partial seizures. Is also useful as an adjunct for reducing postoperative pain and PONV. Although structurally related to GABA, it is thought to act by blocking voltage-gated calcium channels in the CNS. Peak plasma levels occur within 2–3 h of administration, with half-life of 5–7 h. Excreted renally.

• Dosage: 300 mg orally on the first day; bd then tds on successive days, then titrated to response up to 800 mg tds. For perioperative use (though not currently licensed): 300–600 mg preoperatively plus 200–300 mg tds postoperatively.

• Side effects include sedation, dizziness, ataxia, nystagmus, tremor, diplopia, nausea, convulsions, cough.

Kong VKF, Irwin MG (2007). Br J Anaesth; 99: 775–86

Gabexate mesilate. Synthetic serine protease inhibitor; has been studied as a protective and therapeutic agent in pancreatitis, as a neuroprotective agent in spinal cord injury, and as a treatment for DIC. Not available in the UK.

Gag reflex. Elevation and constriction of the pharynx following stimulation of the posterior pharyngeal wall. The afferent pathway is via the glossopharyngeal nerve; the efferent is via the vagus. Elevation of the soft palate when it is touched relies on afferent fibres in the maxillary division of the trigeminal nerve; often the two reflexes are elicited together. The gag reflex is abolished following local anaesthesia and lesions of the pharynx, lesions involving the vagal nuclei in the medulla, and deep anaesthesia or coma. Absence of the gag reflex may indicate that the airway is at risk, e.g. from aspiration of vomit. The reflex is assessed as part of testing for brainstem death.

Gain, electrical. Ratio of output signal amplitude to input signal amplitude. Thus a measure of amplification of signal, e.g. in monitoring equipment. May be specified as voltage, current or power gain; expressed as a simple ratio, or for power gain, also expressed as logarithm (base 10) of the ratio (e.g. in bels or decibels).

See also, Amplifiers

[Alexander Bell (1847–1922), Scottish-born US inventor]

Gallamine triethiodide, see Neuromuscular blocking drugs

Galvanic skin response (Skin conductance response; Sympathogalvanic response). Measurement of the skin’s electrical conductivity, which varies with its moisture level. Test of sympathetic afferent, efferent and spinal interconnecting pathways, used to assess the effects of sympathetic nerve blocks. Has also been used to assess other regional blocks in which sympathetic blockade occurs, e.g. epidural anaesthesia, brachial plexus block.

Skin electrodes are placed on dorsal and ventral surfaces of the hand/foot, with a reference electrode elsewhere. Opposite sides of the body are normally compared. The output is displayed on an oscilloscope (e.g. ECG machine); a steady line results. With intact sympathetic pathways, pinching the skin causes altered skin conductance via changes in sweat gland secretion, displayed as a deflection lasting under 5 s. Deflection is abolished by successful blockade. The response may be diminished by use of atropine, repeated testing and in the elderly.

Preblockade size of deflection has also been used to assess suitability for subsequent sympathetic block.

Changes in skin potential may also be measured.

Ganciclovir. Antiviral drug, related to aciclovir but more active against cytomegalovirus and more toxic, thus reserved for severe infections and to prevent infection during immunosuppression following organ transplantation. Valganciclovir, a prodrug, is available for oral use.

• Dosage: 5 mg/kg iv bd for 2–3 weeks (treatment) or 1–2 weeks (prophylaxis), followed by 5 mg/kg daily.

• Side effects: many, including blood dyscrasias, rash, hepatorenal impairment, GIT upset, arrhythmias, coma. Contraindicated in pregnancy. May cause severe myelosuppression in combination with zidovudine.

Ganglion blocking drugs. Nicotinic acetylcholine receptor antagonists acting at autonomic ganglia. The first antihypertensive drugs, now rarely used because of widespread side effects caused by sympathetic blockade (postural and exertional hypotension, decreased sweating) and parasympathetic blockade (constipation, urinary retention, impotence, dry mouth, blurring of vision). May first stimulate then block receptors (e.g. nicotine) or exhibit competitive antagonism (e.g. hexamethonium, pentolinium, trimetaphan). None is generally available in the UK.

Because of the similarity between neuromuscular and ganglionic nicotinic receptors, ganglion blockers (e.g. hexamethonium) may cause neuromuscular blockade, and neuromuscular blocking drugs (e.g. tubocurarine) may cause ganglion blockade.

Gangrene. Death and decay of body tissues; usually a consequence of ischaemia ± bacterial decomposition but may be caused by micro-organisms in well-perfused tissue (e.g. gas gangrene). Traditionally a clinical diagnosis, thus described according to the causative insult and clinical appearances, even though some of the terms are now obsolete: traumatic gangrene (resulting from direct injury); gas gangrene (associated with gas formation within the tissues); Fournier’s gangrene (affecting the perineum); wet gangrene (associated with venous congestion and oedema); dry gangrene (affected tissue is blackened and shrunken). Many terms have been superseded by more specific ones, e.g. necrotising fasciitis.

[Jean A Fournier (1832–1914), Paris dermatologist]

Gas. Form of matter whose constituent molecules or atoms are constantly moving, and whose mean positions are far apart. Tends to expand in all directions, and diffuse and mix with other gases. Governed by the gas laws under specified conditions. Formed when a liquid exceeds its critical temperature. The constituent particles are sufficiently far apart for the forces (e.g. Van der Waals forces) between them to be almost negligible, unless the gas is compressed. Pressure exerted by a gas is proportional to the number of collisions of atoms/molecules against the container’s walls (which is proportional to the number of gas molecules in the container).

Gas analysis. Possible methods:

ent chemical:

– gas reacts chemically with other substances to form non-gaseous compounds, with reduction of overall volume (e.g. Haldane apparatus) or pressure (e.g. van Slyke apparatus). Alternatively, the reaction results in emission of light that is measured by a photodetector, e.g. chemiluminescence nitric oxide analysis (NO + ozone producing O₂ + NO₂ + light).

– electrochemical: gas reacts with other substances, the number of electrons transferred during the reaction being proportional to the concentration of gas in the sample. Used in nitric oxide analysers (NO being converted to NO₂).

ent physical:

– spectroscopy (e.g. infrared).

– adsorption of vapours on to surfaces:

– rubber strips, e.g. in the Dräger Narkotest. Tension of the strips is reduced by volatile agents; the extent is proportional to their concentration. Temperature compensated using a bimetallic strip. Adjustable for use with different agents and in the presence of N₂O, to which it is also sensitive. Has a slow response; now rarely used.

– silicone polymer coating a vibrating quartz crystal, e.g. in the Engström Emma. Passing alternating current through a crystal can cause it to vibrate at its resonant frequency (the piezoelectric effect); change in resonant frequency is proportional to the concentration of volatile agent dissolved in the polymer coating.

– interferometer: a light beam is split and passed through two chambers, one for reference and the other for samples. The beams are delayed to different extents; thus the emergent beams are out of phase. The resultant interference pattern is visualised through a telescope, and is displaced when gas is drawn into the sample chamber. Degree of change is related to the sample concentration. Used for calibration, e.g. of vaporisers, not for perioperative monitoring.

– mass spectrometry.

– gas chromatography and detectors, e.g. katharometer, flame ionisation detector, electron capture detector.

– fuel cell, and paramagnetic and polarographic analysers, used for O₂ measurement.

– other methods (e.g. depending on different viscosities of gases or velocity of sound through gases) are rarely used now.

[Heinrich Dräger (1847–1917), German engineer; Carl-Gunnar Engström (1912–1987), Swedish physician]

Gas chromatography. Technique used for gas analysis. The sample mixture is injected into a stream of inert carrier gas (the mobile phase) that passes through a column of silica–alumina particles coated in oil or wax (the stationary phase). Separation of the sample component gases occurs along the column’s length, depending on their relative solubilities in the two phases. Temperature of the column is carefully controlled. Liquids may also be analysed. Suitable detectors (e.g. katharometer, flame ionisation detector or electron capture detector) are required.

Gas flow. Principles of flow are as for any fluid. Clinical applications:

ent flow is turbulent in the upper airway, trachea and bronchi, especially during forceful breathing; i.e. gas density is more important than viscosity. Thus in upper airway obstruction, flow is increased if low-density gas is used, e.g. helium–oxygen mixture.

ent flow is laminar in small bronchioles; i.e. viscosity is more important; although tube radius is very small, velocity is also very low. Helium has traditionally been considered of no use in improving gas flow in asthma, primarily a disease of small airways, but some evidence suggests that helium–oxygen may be useful in severe asthma, suggesting an element of turbulent flow.

ent flow may be mostly laminar during quiet breathing, with turbulence at branches in the trachea and bronchi. Turbulence is more likely at mid-inspiration/expiration, when flow rate is highest (e.g. up to 50 l/min).

ent Turbulence usually occurs in anaesthetic breathing systems during peak flow, especially if sharp-angled bends are present, e.g. at connections between components. Turbulence is more likely with narrow tubing and tubes.

ent other applications include the Venturi principle, fluidics, flow–volume loops and flowmeters.

See also, Airway resistance

Gas gangrene. Infection due to clostridium species, usually C. perfringens, a spore-forming Gram-positive anaerobic bacillus found in soil and faeces. Classically associated with deep war wounds, especially those contaminated with dirt or foreign bodies, but may follow any trauma, e.g. surgery. The incubation period is under 4 days, usually under 1 day.

The organism produces gas within tissues, often detectable clinically as subcutaneous emphysema. Local spread is rapid, with oedema, pain and tissue necrosis; endotoxin production often results in sepsis with MODS.

Prevented and treated by wound debridement and cleaning. Penicillin is an effective adjunct. Hyperbaric O₂ therapy has been used to increase local tissue O₂ content; antitoxin therapy is more controversial.

Gas laws, see Avogadro’s hypothesis; Boyle’s law; Charles’ law; Dalton’s law; Henry’s law; Ideal gas law

Gas transport, see Carbon dioxide transport; Oxygen transport

Gasp reflex. Production of a deep slow breath following a large positive pressure inflation of the lungs. Originally described in cats and dogs, but may be seen in newborn babies; during neonatal resuscitation, it may occur within primary apnoea. A similar response may also be seen after opioid administration in anaesthetised patients.

Head’s paradoxical reflex, although similar, is produced under different experimental circumstances.

Gasserian ganglion block. Block of the trigeminal ganglion which lies medially in the middle cranial fossa within a dural reflection (Meckel’s cave), lateral to the internal carotid artery and cavernous sinus. Results in anaesthesia of the face, forehead and anterior scalp (Fig. 76). Used mainly for treatment of trigeminal neuralgia, but also for surgery to the face. Performed using X-ray imaging to guide needle positioning.

Fig. 76 Innervation of the face

• Technique:

ent with the patient supine and looking straight ahead, a 22 G 10-cm needle is introduced 3 cm lateral to the angle of the mouth, level with the second upper molar. Aiming at the pupil from the front, and the midpoint of the zygoma from the side, it is inserted until it contacts bone (greater wing of sphenoid, anterior to the foramen ovale). It is redirected posteriorly 1–1.5 cm deeper, passing through the foramen. Correct positioning is confirmed by electrical stimulation of the needle, which elicits paraesthesia in the distribution of the appropriate branch of the trigeminal nerve.

ent after careful aspiration, 1–2 ml solution, e.g. 1% lidocaine, is injected. Alcohol injection or thermocoagulation may follow if ablative therapy is required. Accidental subarachnoid injection may occur.

Often painful; general anaesthesia or sedation may be employed, with waking up or reversal to confirm paraesthesia, followed by resedation for ablation. Propofol or a midazolam/flumazenil combination has been used. Complications include anaesthesia dolorosa.

[Johann Gasser (1723–1765), Austrian anatomist;

Johann Meckel (1714–1774), German anatomist]

Gastric contents. Anaesthetic importance:

ent absorption of orally administered drugs; e.g. related to gastric emptying, pH and drug interactions within the stomach.

ent aspiration of gastric contents; severity of aspiration pneumonitis is related to the pH and volume of aspirate, although the particulate nature of the aspirate is also important.

• Gastric secretion is increased by:

ent presence of food in the mouth (vagal reflex).

ent anger, stress.

ent presence of food in the stomach (local reflex).

ent protein meal, via duodenal gastrin secretion.

ent hypoglycaemia.

ent alcohol, caffeine.

• Gastric secretion and acidity are decreased by:

ent vagotomy.

ent H₂ receptor antagonists.

ent proton pump inhibitors.

ent drinking water.

Gastric acidity is decreased by antacids.

Gastric volume is related to gastric emptying and intake. Volume is reduced by H₂ antagonists and protein pump inhibitors, but increased by antacids.

Ng A, Smith G (2001). Anesth Analg; 93: 494–513

Gastric emptying. Normally results from peristaltic waves of contraction passing through the cardia, antrum, pylorus and duodenum, occurring up to three times/minute after a meal. Small amounts of liquid traverse the pylorus, which closes as the contraction wave reaches it, redirecting most of the propelled (solid) material back into the proximal stomach for further mixing. Thus liquids transit faster than solids. Carbohydrates leave faster than proteins and fats are slowest, due to inhibitory feedback mechanisms involving duodenal hormone secretion.

• Slowed by:

ent lying down.

ent increased sympathetic nervous system activity (e.g. anxiety, fear, pain).

ent mechanical obstruction and duodenal distension.

ent labour (little effect unless opioids given).

ent drugs, e.g. opioid analgesic drugs, anticholinergic drugs, alcohol, dopamine.

• Increased by:

ent gastric distension.

ent drugs, e.g. metoclopramide, domperidone (opioid-induced gastric stasis is not reversed; cf. cisapride).

Rate of emptying is important because of the risks of nausea, vomiting, regurgitation and aspiration of gastric contents. Emptying also affects absorption of orally administered drugs. A commonly used preoperative starvation guideline is 6 h for solid food/milk and 2 h for water in all but life-threatening emergencies; this is an estimate and gastric contents may be considerable even after fasting if gastric emptying is delayed. Small volumes of water (150 ml) given 2–3 h preoperatively have been shown to reduce the volume and acidity of gastric contents. Recent guidelines call for withholding of all solid food on the day of surgery, unrestricted clear fluids up to 3 h preoperatively and consideration of H₂ receptor antagonists for patients at risk.

• Measurement:

ent measurement of plasma levels of orally administered substance, e.g. paracetamol (absorbed from the small intestine, not from the stomach).

ent serial nasogastric aspiration, with measurement of orally administered marker substance.

ent measurement of impedance across the lower chest/upper abdomen; alters as composition of tissues, i.e. gastric contents, changes.

ent oral administration of radioisotope, with measurement of radioactivity over the stomach.

ent ultrasound imaging.

ent X-ray imaging following oral contrast medium.

Emptying can be aided by naso- or orogastric aspiration. The latter is more effective, using a wide-bore tube with multiple holes and lumina, but is unpleasant and rarely used except for emptying the stomach intraoperatively.

Emetic drugs are no longer used.

Ng A, Smith G (2001). Anesth Analg; 93: 494–513

Gastric intramucosal pH, see Gastric tonometry

Gastric lavage. Formerly performed following poisoning and overdose; now considered to have a very limited role, as evidence suggests risk of harm outweighs benefit in the majority of cases.

Previously performed up to 4 h after ingestion (longer if gastric emptying is delayed, e.g. by anticholinergic drugs, aspirin), or at any time if the patient is unconscious. Involves passage of a wide-bore orogastric tube, with aspiration to ensure the trachea has not been entered inadvertently. 300–600 ml warm water is introduced and allowed to drain under gravity; this is repeated until the aspirate is clear. Pulmonary aspiration may occur; the patient should be placed in the head-down lateral position with suction available. Tracheal intubation is required if laryngeal reflexes are absent. Lavage is contraindicated if petroleum derivatives have been ingested, since pulmonary aspiration is particularly harmful. Oesophageal/gastric perforation is also likely if caustic substances have been ingested.

Gastric tonometry. Indirect method of measuring gastric intramucosal pH, which in turn is used as an indicator of gastric (and therefore GIT) mucosal O₂ balance. Intramucosal acidosis may indicate impaired GIT O₂ delivery or impaired utilisation, and has been proposed as a useful indicator of poor splanchnic perfusion and mortality; may be used to guide vasoactive drug therapy in the ICU and during major surgery.

A tonometer incorporating a saline-filled balloon is placed via the oesophagus into the stomach, and luminal PCO₂ (which approximates to intramucosal PCO₂) determined by measuring PCO₂ in the saline. A gas-filled balloon has also been used, with recirculation of gas into and out of the balloon with continuous measurement of PCO₂ at the distal end of the system. H₂ receptor antagonists eliminate the effect of gastric acid, combining with pancreatic bicarbonate to produce CO₂. Direct measurement is also possible but involves mucosal trauma and is less reliable. Arterial bicarbonate concentration is measured simultaneously and approximates to mucosal concentration, allowing calculation of intramucosal pH (pH_i).