Bryan R. Cullen, PhD
https://medicine.duke.edu/faculty/bryan-r-cullen-phd
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Constriction of arterioles (vasoconstriction) increases systemic vascular resistance pregnancy symptoms at 4 weeks order serophene 50 mg online, whereas constriction of veins (venoconstriction), especially splanchnic veins, increases the relative intravascular volume, and hence venous return to the heart. Systemic vascular resistance does not change significantly with venoconstriction when compared with vasoconstriction. Autonomic reflexes mediate neurological control of the peripheral vascular system. In these reflexes peripheral vasoconstriction, increased heart rate and increased myocardial contractility. There is continuous tonic activity in sympathetic noradrenergic but not cholinergic neurones. The carotid sinus is an enlargement of the internal carotid artery just above its origin. They respond to the degree of stretch in the vessel or heart wall, and hence to the pressure (or more strictly the transmural pressure) in the vessel or heart. When intraluminal pressure increases, wall stretch increases and the frequency of impulses discharged by baroreceptors increases. The baroreceptor impulses exert an inhibitory influence on the pressor centre, and baroreceptor control thus represents a negative feedback control system to maintain cardiovascular stability. Baroreceptors respond not only to pressure magnitude but also to rate of change of pressure. At low pressures there are few discharges during the upstroke of arterial pressure. At higher mean arterial pressures, discharges are present throughout more of the cycle. The effect of this is that baroreceptors respond not only to changes in pressure but also to changes in pulse pressure and heart rate. Influence of higher centres on vasomotor tone the vasomotor centres also respond to higher centres in the brain. The hypothalamus also controls cutaneous vasodilatation and vasoconstriction in response to environmental or body temperature changes. Type A receptors discharge predominantly during atrial systole, while type B discharge during atrial filling, particularly over the later part of diastole. When intravascular volume expands, atrial filling is increased, and both A and B receptors are stimulated. The impulses from these receptors are relayed to the medulla by the vagus nerves, which causes inhibition of the pressor centre and stimulation of the sinus node. This results in vasodilatation, a fall in blood pressure, increased renal blood flow, increased urine output, and a rise in heart rate. During chronic hypertension, the baroreceptors adapt to higher pressures and the response curve is shifted to the right. Carotid and aortic baroreceptor reflex Baroreceptors in the carotid sinus and the arch of the aorta monitor arterial pressure, arterial pulse pressure and heart rate.
Somatic (voluntary) control is present only during the initial stages of swallowing and in external anal sphincter control of defecation menopause water retention serophene 50 mg purchase without prescription. Oesophageal stage Swallowing Swallowing moves food from the mouth to the stomach without aspiration into the trachea. It is a reflex with voluntary and involuntary components which cannot be interrupted once initiated. If primary peristalsis fails, secondary peristalsis is initiated by the continued stimulation of oesophageal stretch receptors. Modality Parasympathetic Nerves/ganglia Vagus and sacral fibres; preganglionic Sensory afferents Pain, distention, toxins Secretomotor efferents " gastrin " salivary production " pancreatic and bile secretion " salivary production Motor efferents " motility " tone " force of contraction " gastric emptying # motility # gastric emptying vasoconstriction Sympathetic Coeliac, mesenteric and pelvic ganglia; postganglionic Pain, distention Chapter 20: Gastrointestinal physiology 457 Oesophagus the oesophagus is 30 cm long in the adult and has upper and lower sphincters. The upper oesophageal sphincter consists of the cricopharyngeal and pharyngeal constrictor muscles. It is innervated by the vagus and is usually in a state of tonic contraction to prevent entrainment of air during respiration. Gastric emptying the pylorus does not close completely during antral systole, and small amounts of liquid chyme are squirted into the duodenum with each contraction. This emptying is regulated to optimise small bowel performance via complex control mechanisms. Gastric emptying is reduced with pain, anxiety and stress mediated by activation of the sympathetic nervous system. Distension of the stomach leads to the stimulation of vagal and local enteric reflexes and the release of gastrin. As a result there is increased secretion of acid and antral peristaltic activity, thereby increasing gastric emptying and the production of chyme. The composition of the chyme reaching the duodenum also regulates gastric emptying. If the stomach empties too quickly, duodenal receptors may be activated by stretch, increasing acidity, osmolarity or concentration of fatty or amino acids. As a result, carbohydrate-rich meals leave the stomach within a few hours, protein more slowly, and fatty food the slowest. The acute angle where the oesophagus joins the stomach and the encircling diaphragmatic muscle results in a flutter-valve action below the diaphragm that helps to prevent reflux when intragastric pressure is raised. As food enters the stomach the proximal stomach relaxes, minimising any further increase in intragastric pressure (receptive relaxation). Secondly there are rhythmic synchronised contractions in the lower part of the stomach (antral systole) which mix food with acid, mucus and pepsin, grinding it down to a fine paste called chyme.
Fosaprepitant is a prodrug of aprepitant and provides an intravenous alternative with rapid conversion in hepatic microsomes (97% conversion within 15 minutes) by dephosphorylation pregnancy no symptoms purchase 25 mg serophene fast delivery. Haloperidol and benperidol are primarily used as antipsychotic agents, but haloperidol possesses substantial anticonvulsant activity. Side effects include extrapyramidal phenomena, neuroleptic malignant syndrome and hyperprolactinaemia with gynaecomastia. There are a number of chemically different agents that are antagonists at histaminergic receptors. These are particularly effective in the treatment and prevention of motion sickness. The antiemetic action is centrally mediated, but H1 antagonism may not be the sole mechanism of antiemesis. Ethanolamines (such as diphenhydramine) are potent antihistamines with some anticholinergic activity, which are thought to work at the labyrinth and the neural interface between the labyrinth and the vomiting centre. It has anticholinergic activity, resulting in dry mouth, and can cause tachycardia if given intravenously. Buclizine has a long duration of action but is only available in combined formulation with other drugs. It also contains sodium and phosphate such that it combines two forms of dexamethasone. Miscellaneous antiemetics r Sedatives and anxiolytics often have an antiemetic effect by reducing the psychological component of the nausea. Metoclopramide hydrochloride is a white crystalline salt that is chemically related to procaine. It has antidopaminergic (D2) activity in the chemoreceptor trigger zone and also inhibits the emetic effects of gastric irritants. Extrapyramidal effects (such as oculogyric crisis) are the major potential side effects. Domperidone is a benzimidazole derivative that has both centrally and peripherally mediated effects. Peripherally, domperidone promotes gastric emptying and increases lower oesophageal sphincter tone.
In a child the carotid or femoral pulse should be used for assessment fsh 80 menopause order serophene 100 mg, and in infants the brachial or femoral pulse. If there are no signs of circulation or the pulse rate is less Chapter 8: Principles of resuscitation 189 than 60 bpm with poor perfusion, rescue breathing should be combined with cardiac compressions. Cardiac compressions should compress the chest by at least one-third of its depth at a rate of 100 compressions per minute. The correct ratio of cardiac compressions to rescue breaths is 15:2 for two rescuers, but if alone use the adult ratio of 30:2, which will allow a single rescuer to perform the recommended 100 compressions per minute. The advice is to push hard, push fast, minimise interruptions and allow for full chest recoil. It is important that the pressure is applied over the lower third of the sternum and not the ribs. In infants either two fingertips may be used to apply cardiac compressions or, when two or more rescuers are present, the two-thumb encircling technique. The twothumb encircling technique has been shown to produce higher coronary perfusion pressures, as the correct depth and force of compressions are more consistently achieved. However, for the single rescuer it is difficult to swap from cardiac compressions to rescue breathing, so the twofinger technique is preferable. Once spontaneous circulation and ventilation is established the child must be placed in the recovery position. Foreign-body airway obstruction the majority of choking episodes in children and infants are witnessed and occur during play or eating. The child or infant is usually conscious in the initial stages, but if the obstruction is not rapidly cleared, cardiac arrest secondary to hypoxia will ensue. Choking, which occurs suddenly, must be differentiated from other causes of upper airway obstruction in children and infants, such as laryngitis, epiglottitis and croup, in which they are systemically ill and require different management. If there is an inadequate cough, and the child remains conscious, then back blows followed by abdominal thrusts should be used to attempt to dislodge the foreign body. These are similar to chest compressions, but sharper in nature and delivered at a slower rate. Abdominal thrusts should not be used to treat choking in infants, because the more horizontal position of their ribs leaves the upper abdominal viscera more exposed to trauma. Obviously the position used will depend on the size of both the child and the rescuer. The increasing use of capnography during resuscitation attempts not only provides a monitor of the effectiveness of chest compressions but may also give an early indication of return of spontaneous circulation.
Normally the extraction ratio is about 25% breast cancer 8 years later buy serophene 25 mg on line, but it can double to 50% if tissue demand increases Both of the above indices are dependent on mixed venous saturation and cardiac output. Increased tissue demand due to exercise or disease is normally compensated for by increased oxygen delivery. This has to be mediated by increasing cardiac output, since the ability to increase SaO2 and Hb is limited. Not all stored oxygen is available for use, since severe hypoxaemia occurs before even half of the oxygen stored in combination with Hb and myoglobin is released. The cardiac output from the right ventricle passes through the lungs into the left atrium. The cardiac output from the right ventricle is almost the same as that from the left ventricle. The distributions of blood flow and ventilation throughout the lungs are generally very well matched, but this may vary markedly during anaesthesia or disease. The pulmonary artery is a thin-walled structure which arises from the right ventricle and divides immediately into left and right branches and then divides successively, following a similar pattern to the conducting airways down to the terminal bronchioles. The oxygenated blood is collected by venules that run between the lobules and then unite to form the four pulmonary veins that drain into the left atrium. The pulmonary vascular system is a low-pressure, low-resistance system in series with the right ventricle. Pressures in the pulmonary circulation are about 20% of those in the systemic circulation. The innervation of the pulmonary vasculature is supplied by the sympathetic nervous system, with -adrenergic fibres producing vasoconstriction and -adrenergic fibres vasodilatation. Bronchial arteries from the thoracic aorta supply oxygenated blood to the supporting tissue of the lung, including connective tissue, septa and bronchi, and drain into the pulmonary veins, contributing to the anatomical shunt. Normal pulmonary arterial pressure has a systolic value of 25 mmHg, a diastolic value of 8 mmHg, and a mean of 15 mmHg. The mean pulmonary capillary pressure is 10 mmHg, with a pulmonary venous pressure of 4 mmHg at heart level. Pulmonary arterial and right ventricular pressures are not greatly influenced by increases in cardiac output in normal subjects, demonstrating the distensibility of the pulmonary vasculature.
The aim is to restore cellular oxygenation before the onset of irreversible shock pregnancy vaccines serophene 50 mg purchase mastercard. Physiological responses to haemorrhage Trauma compromises tissue oxygenation because haemorrhage reduces oxygen delivery while at the same time tissue injury and inflammation increase oxygen consumption. Compensatory responses to haemorrhage are categorised into immediate, early and late. The loss of blood volume is detected by low-pressure stretch receptors in the atria and arterial baroreceptors in the aorta and carotid artery. Efferents from the vasomotor centre trigger an increase in catecholamines, which causes arteriolar constriction, venoconstriction and tachycardia. Long-term compensation to haemorrhage is by several mechanisms: reduced glomerular filtration rate, salt and water reabsorption (aldosterone and vasopressin), thirst, and increased erythropoiesis. A decrease in systolic pressure suggests a loss of > 30% Pathophysiology of trauma and hypovolaemia Several mechanisms are involved in the development of cellular injury after severe trauma. The commonest is haemorrhage, causing circulatory failure with poor tissue perfusion and generalised hypoxia (hypovolaemic shock). Myocardial trauma may cause cardiogenic shock, while spinal cord trauma may cause neurogenic shock. Pure haemorrhage without the presence of significant tissue injury may not cause this typical pattern of a stepwise increase in heart rate. Occasionally, the heart rate may remain relatively low until the onset of cardiovascular collapse. Resuscitation must restore oxygen delivery rapidly if irreversible haemorrhagic shock and death is to be prevented. Up to 50% of the patients developing organ failure early after trauma do so in the absence of bacterial infection. Paramedics are trained to minimise on-scene time; a prolonged time to definitive care will increase mortality. Unless the patient is trapped, on-scene interventions should be restricted to Chapter 9: Major trauma 197 control of the airway and ventilation, and stabilisation of the spine. The receiving hospital should be given advanced warning of the impending admission of a severely injured patient. Ambulance personnel should be able to communicate directly with emergency department staff via a talkthrough link. This will include running through drip sets, turning on fluid warmers, and drawing up anaesthetic drugs. Members of the resuscitation team put on protective clothing comprising gloves, plastic aprons and eye protection.
The mechanism for this is not well understood menstruation in children quality serophene 50 mg, but during Chapter 23: Physiology of pregnancy 529 Protein binding the diffusibility of a protein-bound drug is negligible compared with that of free drug. Acidosis reduces the protein binding of local anaesthetic, and low serum albumin in pre-eclampsia will cause a higher proportion of unbound drug and therefore promote transfer of drugs across the placenta. Molecular weight of drug Drugs with molecular weight of 600 daltons or less readily diffuse across the placenta. Most drugs used in anaesthetic practice have molecular weights < 600, and therefore diffuse readily. Maternal levels fall rapidly because of the greater capacity for maternal metabolism. Morphine is poorly lipid-soluble and weakly plasma protein-bound, but readily crosses the placenta. Fentanyl is highly lipid-soluble, crossing the placental membrane rapidly, but is largely albumin-bound (74%). Alfentanil is less lipophilic than fentanyl but is more highly bound to plasma protein. Administration of remifentanil has been associated with rapid placental transfer and has potential to produce respiratory depression in the newborn. Fetal blood concentrations of remifentanil are generally about half of that of the mother just before delivery. Placental blood flow With poorly diffusible drugs, the concentration in maternal and fetal blood changes little during placental transit, and hence blood flow has little impact on transplacental gradient. With highly diffusible drugs, concentration gradient falls significantly as a result of transfer, and hence blood flow has a marked effect on gradient. Placental transfer of individual drugs Opioids All opioids cross the placenta in significant amounts. It is about Local anaesthetic agents Local anaesthetic agents cross the placenta by simple diffusion. Commonly used local anaesthetics have molecular weights ranging from 234 daltons (lidocaine) to 288 (bupivacaine). They are weak bases and have relatively low degrees of ionisation and high lipid solubility at normal pH. This occurs when reduced pH in the fetus produces increased ionisation of the local anaesthetic and resultant lower diffusibility. Transfer to the fetus is also affected by other factors, which include dose, site of administration and effects of adjuvants such as adrenaline. The vascularity of the site of injection will determine the rate of absorption of the drug.
Local anaesthetic toxicity Local anaesthetic toxicity may be local breast cancer on ultrasound serophene 25 mg order with mastercard, systemic or related to hypersensitivity reactions. Allergy to amides is extremely rare, and the reaction can range from local hypersensitivity to anaphylaxis. The development of toxicity depends on the build-up of harmful plasma levels either by direct intravascular injection or by absorption from the injection site. This in turn is dependent on the physicochemical properties of the agent used (lipid solubility, intrinsic vasoactivity), site of injection (vascularity) and cumulative dose. Thus toxicity may develop immediately or be delayed, especially in the case of catheter placement. The anaesthetist must maintain a high level of vigilance and assess risk on a case-by-case basis. At a neuronal level, initial suppression of inhibitory pathways results in early excitatory phenomena, superseded by later depressant effects. This may be due to direct spread from subarachnoid injection or by excessive systemic absorption. Toxicity results from the presence of ionised drug within the cell blocking the ion channel. Acidosis effectively reduces the proportion of diffusible drug within the cells, and slows clearance. Chapter 7: Regional anaesthesia 141 Cardiovascular system Most local anaesthetic agents (except cocaine) relax vascular smooth muscle, causing vasodilatation. In addition, centrally administered drugs cause vasodilatation by sympathetic blockade. Direct cardiovascular toxicity is caused by the membrane-stabilising activity of the drugs on myocardial muscle, which is a feature of blockade of voltage-gated fast sodium channels. This reduces the maximum rate of rise of the cardiac action potential and reduces the duration of the action potential. Bupivacaine blocks transient outward potassium flux, decreasing baseline cardiac membrane potential and interfering with myocardial repolarisation. Bupivacaine may bind to the enzyme protein carnitine-acylcarnitine translocase of the mitochondria, preventing entry of the fatty acids which serve as energy substrates to power myocardial contraction. A direct antiplatelet effect (probably due to membrane stabilisation) reduces platelet aggregation and blood viscosity. Anaphylactoid reactions Anaphylactoid reactions are very rare with amide local anaesthetics, and some of those reported have been due to preservatives (such as metabisulphite and methylparaben). Effects range from local erythema and swelling to systemic hypotension and bronchospasm.
Lukar, 41 years: It has been superseded by the plastic cannula over needle pattern, which is associated with a much lower incidence of extravasation. Inspiration of cool unhumidified gases by a patient can potentially lead to a loss of more than 10% (> 10 W) of basal metabolic energy requirements. It has the advantage of being mechanically simple, small in size (and dead space) and cheap to produce. There are five structural heavy chain variants to produce IgG, IgM, IgA, IgD and IgE.
Kirk, 38 years: The dorsal horn Nociceptors terminate almost exclusively in the dorsal horn of the spinal cord. Information is processed in the hippocampus as a short-term memory, and then stored as a long-term memory, which lasts for years. It can withstand bending moments of up to 10 Nm (equivalent approximately to 4050 kg weight hanging from the outlet). Afferent thermal sensing comes from hypothalamus, spinal cord, deep thoracic and abdominal viscera and skin.
Derek, 22 years: Intravenous induction Intravenous induction agents are drugs that induce loss of consciousness in one armbrain circulation time when given in an appropriate dosage. In the lung, gravity gives rise to an intravascular hydrostatic pressure gradient that increases from the top of the lung to the base. Anaesthetic risk relates mainly to regional anaesthetic techniques and the possibility of vertebral canal haematoma following epidural or spinal anaesthesia. Depending on gestational age, prophylactic steroid injection should be considered to optimize fetal lung maturation in case preterm birth takes place.
Hassan, 34 years: High lipid solubility also increases the rate of onset and duration of action of local anaesthetic agents. The demand dose should be large enough to provide an analgesic effect but small enough to prevent unwanted side effects, and may have to be altered depending on the clinical effect. The result is massive heat production and a rapid uncontrolled rise in body temperature with metabolic acidosis and myoglobinuria. Auditory and sensory evoked potential data support an anatomical site of action for volatile anaesthetic agents somewhere between brainstem and cortex, with the thalamus the most likely primary target.
Gambal, 50 years: In blood, commonly occurring strong ions (measurable ions) include Na+, K+, Ca2+ and Mg2+. Triamterene and amiloride interfere with the sodium channels through which the effects of aldosterone are mediated. The explanation should detail the possible benefits and side effects and/or complications. A special case of immunity and renal failure is the acute humoral-mediated rejection of a transplanted kidney, as described below.
Tangach, 49 years: Postoperative analgesia for fractures and soft tissue injuries is best provided by regional anaesthesia, although there remains a debate about the development of compartment syndrome being masked if there are forearm or lower leg fractures. Conjugated bilirubinaemia suggests obstructive jaundice whereas unconjugated bilirubinaemia suggests a prehepatic or hepatic cause. Dental surgery Inferior alveolar nerve, infiltration If ambulant patients are discharged with paralysed, insensate limbs specific printed advice regarding care of the limb should be given. Such twisted chains can form more complex molecules by assuming a tertiary structure, resulting in sheets or fibres.
Cronos, 53 years: When activated, they decrease neuronal excitability by inhibiting voltage-dependent sodium channels and activating potassium and calcium channels. There is a risk that laparoscopic procedures may be converted to open procedures if the anatomy is difficult or if bleeding becomes a problem. There is also movement intracellularly of chloride following sodium into the cell along the electrical gradient. Complications of surgery are a common reason for admission, as is prolonged surgery with consequent slow postoperative recovery, usually because the criteria for day surgery have been breached, either by unsuitable surgery or by an unsuitable surgeon.
Zapotek, 28 years: The high prevalence of this debilitating disease is a result of balanced polymorphism driven by the relative resistance of heterozygotes to malaria. It is supplied as an aqueous solution in several concentrations, formulated as a weak acid with a pH between 3. Desflurane in particular appears to maintain contractility initially, perhaps as a result of increased sympathetic stimulation. In this model, the height of the water determines the pressure and is analogous to the agent partial pressure.
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