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Methods and Types of Secretion Exocrine glands can be classified by their mode of secretion and the nature of the substances released tadalafil 10 mg generic, as well as by the structure of the glands and shape of ducts (Figure 4 purchase tadalafil 10 mg visa. The secretions are enclosed in vesicles that move to the apical surface of the cell where the contents are released by exocytosis effective tadalafil 2.5mg. For example purchase tadalafil 10mg, watery mucous containing the glycoprotein mucin order 20mg tadalafil visa, a lubricant that offers some pathogen protection is a merocrine secretion. Apocrine sweat glands in the axillary and genital areas release fatty secretions that local bacteria break down; this causes body odor. Both merocrine and apocrine glands continue to produce and secrete their contents with little damage caused to the cell because the nucleus and golgi regions remain intact after secretion. In contrast, the process of holocrine secretion involves the rupture and destruction of the entire gland cell. New gland cells differentiate from cells in the surrounding tissue to replace those lost by secretion. The serous gland produces watery, blood-plasma-like secretions rich in enzymes such as alpha amylase, whereas the mucous gland releases watery to viscous products rich in the glycoprotein mucin. Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. The matrix usually includes a large amount of extracellular material produced by the connective tissue cells that are embedded within it. Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: cells, large amounts of amorphous ground substance, and protein fibers. The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialized cells; for example, a phagocytic cell that engulfs pathogens and also rids tissue of cellular debris. Functions of Connective Tissues Connective tissues perform many functions in the body, but most importantly, they support and connect other tissues; from the connective tissue sheath that surrounds muscle cells, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs and, of course, the skeletal system. Transport of fluid, nutrients, waste, and chemical messengers is ensured by specialized fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body. The first connective tissue to develop in the embryo is mesenchyme, the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton’s jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body. Classification of Connective Tissues The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Table 4. Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection. Supportive connective tissue—bone and cartilage—provide structure and strength to the body and protect soft tissues. In fluid connective tissue, in other words, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins. Connective Tissue Examples Connective tissue proper Supportive connective tissue Fluid connective tissue Loose connective tissue Cartilage Areolar Hyaline Adipose Fibrocartilage Blood Reticular Elastic Dense connective tissue Bones Regular elastic Compact bone Lymph Irregular elastic Cancellous bone Table 4. Fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Macrophages, mast cells, lymphocytes, plasma cells, and phagocytic cells are found in connective tissue proper but are actually part of the immune system protecting the body. Polysaccharides and proteins secreted by fibroblasts combine with extra-cellular fluids to produce a viscous ground substance that, with embedded fibrous proteins, forms the extra-cellular matrix. As you might expect, a fibrocyte, a less active form of fibroblast, is the second most common cell type in connective tissue proper.

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Prospective ran- domized controlled treatment trials were understandably lacking dur- ing the first epidemic of this novel disease discount tadalafil 5mg overnight delivery. Appropriate empirical antibiotics are thus necessary to cover against common respiratory pathogens as per na- tional or local treatment guidelines for community-acquired or noso- comial pneumonia (Niederman et al 2001) discount tadalafil 10 mg free shipping. In addition to their antibacterial effects order 20 mg tadalafil fast delivery, some antibiotics are known to have immunomodulatory properties discount 5mg tadalafil overnight delivery, notably the quinolones (Dalhoff & Shalit 2003) and macrolides (Labro & Abdelghaffar 2001) purchase tadalafil 5 mg amex. A minority of patients with a mild illness recover either without any specific form of treatment or on antibiotic therapy alone (Li G et al 2003; So et al 2003). Antiviral therapy Various antiviral agents were prescribed empirically from the outset of the epidemic and their use was continued despite lack of evidence about their effectiveness. The use of ribavirin has attracted a lot of criticism due to its unproven efficacy and undue side effects (Cyranoski 2003). However, lower doses of ribavirin did not result in clinically signifi- cant adverse effects (So et al 2003). Preliminary results suggest that the addition of lopinavir-ritonavir to the contemporary use of ribavirin and corticosteroids might reduce intubation and mortality rates, especially when administered early (Sung 2003). The Chinese experiences were mostly in combining the use of interferons with immunoglobulins or thymosin, from which the efficacy could not be ascertained. Faster recovery was observed anecdotally in the small ® Canadian series using interferon alfacon-1 (Infergen , InterMune Inc. Inter- feron β was found to be far more potent than interferon α or γ, and remained effective after viral infection. These in vitro results suggested that interferon β is promising and should be the interferon of choice in future treatment trials. Human immunoglobulins Human gamma immunoglobulins were used in some hospitals in China and Hong Kong (Wu et al 2003; Zhao Z et al 2003). Convalescent plasma, collected from recovered patients, was also an experimental treatment tried in Hong Kong. It is believed that the neutralizing immunoglobulins in convalescent plasma can curb in- creases in the viral load. Preliminary experience of its use in a small number of patients suggests some clinical benefits and requires further evaluation (Wong et al 2003). It has been postulated that the mechanisms are medi- ated through the nitrous oxide pathway (Cinatl et al 2003a). This hypothesis may be substanti- ated from the observation that clinical deterioration can paradoxically occur despite a fall in the viral load as IgG seroconversion takes place (Peiris et al 2003b), as well as from autopsy findings which demon- strate a prominent increase in alveolar macrophages with hemophago- cytosis (Nicholls et al 2003). A tri-phasic model of pathogenesis com- prising viral replicative, immune hyperactive and pulmonary destruc- tive phases was thereafter proposed (Peiris et al 2003b; Sung 2003). However, there is much scep- ticism and controversy about the use of corticosteroids, centering on their effectiveness, adverse immunosuppressive effects and impact on final patient outcomes. An early Singaporean report on five patients on mechanical ventila- tion indicated that corticosteroids showed no benefits (Hsu et al 2003). A retrospective series of over 320 patients from a regional hospital in Hong Kong concluded that two-thirds progressed after early use of ribavirin and corticosteroids, but only about half of these subsequently responded to pulsed doses of methylprednisolone (Tsui et al 2003). A cohort study also noted that about 80% of patients had recurrence of fever and radiological worsening (Peiris et al 2003b). This contrasted with another paper which described four patient stereotypes for pulsed methylprednisolone therapy, namely the good responder, good re- sponder with early relapse, fair responder and poor responder. The timing of initiating corticosteroids should coincide with the onset of a truly excessive immune response, which may be best represented by a combination of clinico-radiographic surrogate criteria. The dosage of corticosteroids should be chosen to sufficiently counterbalance the degree of hyper-immunity. Too short a course may result in a re- bound of cytokine storm with lung damage, whereas protracted usage will put the patient at risk of various corticosteroid compli- cations. The ultimate aim should theoretically be to strike an optimal immune balance so that the patient can mount a sufficient adaptive immune response to eradicate the virus, but without the sequelae of irreversible lung damage from immune over-reactivity. A published protocol (Ap- pendix 1) based on the above rationale was reported to have achieved satisfactory clinical outcomes (So et al 2003; Lau & So 2003). Profound immunosuppression, resulting from needlessly high doses or protracted usage of corticosteroids, not only facilitates coro- naviral replication in the absence of an effective antiviral agent, but also invites bacterial sepsis and opportunistic infections. The common phenomenon of “radiological lag” (radiological resolu- tion lagging behind clinical improvement) must be recognized.

Infants are considered premature if they are born before 38 weeks of gestation or weigh less than 2500 g at birth safe tadalafil 20mg. Anesthetic management: most infants are hypovolemic with a metabolic acidosis requiring fluid resuscitation order tadalafil 5mg amex; blood and blood products should be ordered order tadalafil 5 mg with mastercard; awake intubation is intubation of choice generic 2.5 mg tadalafil; anesthetic agents-opioids and ketamine discount tadalafil 2.5 mg amex; hypothermia is common problem. Pyloric stenosis – incidence is higher in males; common in first-born males of parents who had pyloric stenosis; presentation: persistent, bile-free vomiting; the infant is dehydrated and lethargic; vomiting may be projectile, causing loss of hydrogen, chloride, sodium, and potassium ions from stomach; this results in hypokalemic, hypochloremic metabolic alkalosis. Olive-sized mass may be palpated in the mid-epigastrium; noninvasive diagnostic tests include ultrasound; pyloric stenosis is a medical emergency not a surgical emergency. Anatomically pediatric airways are narrower, resulting in greater resistance to air flow, and the tongue is relatively larger; all patients can be divided into those who will be difficult to intubate but can be ventilated by mask and those who are difficult or impossible to ventilate by mask. The latter group poses a more difficult anesthetic challenge and may require emergency tracheostomy; if child can be ventilated by mask, then a number of options-fiberoptic intubation, blind nasal intubation or use of a retrograde transtracheal wire can be attempted. Hurler’s syndrome /mucopolysaccharidosis type 1H/-associated with severe mental retardation, deafness, stiff joints, dwarfism, pectus excavatum, hepatosplenomegaly and severe valvular and early coronary artery disease; upper airway obstruction and difficult intubation are common, getting worse with age. Crouzon’s syndrome – congenital craniofacial synostosis, wide, towering skull with proptosis, maxillary hypoplasia and a beaked nose; maxillary hypoplasia can make mask ventilation difficult. Cleft lip and palate – associated with more than 150 syndromes; risk for pulmonary aspiration; large defects can cause difficulty with intubation; postoperative airway problems are also common. Fluid management in infants-normal daily water consumption in the infant is 10% to 15% of body weight; estimated fluid requirements may be calculated using formula”4-2-1” for weight less than 10kg – 4 ml/kg/hr, 10-20kg - 2ml/kg/hr. Blood replacement: estimated blood volume ranges from 90 ml/kg in neonates to 65 ml/kg in teenagers; the decision to transfuse depends on preoperative hemoglobin level, estimated surgical loss, the patient cardiovascular response. Persistent pulmonary hypertension in the neonate – leads to respiratory failure and death unless treated. Croup versus epiglottitis – both present with evidence of airway obstruction; in 80% of all pediatric patients with acquired stridor, infection is the etiology. Other causes of respiratory distress-foreign body, subglottic stenosis, tracheitis, retropharyngeal abscess. The Infant airway - position: larynx is more cephalad, rima glottitis is opposite the interspace of the C3 and C4; larynx is more anterior in infants. Epiglottis: is longer and stiffer, it tends to be U- or V-shaped, where the adult epiglottis is flatter and more flexible. Laryngeal exposure: blade may have to be passed perpendicularly with the head in the neutral position; lifting an infants upper back and shoulder area is helpful in obtaining proper neck extension; gentleness in manipulation of the laryngeal tissues is important. Vocal cords: as the cartilaginous portion is angled down the trachea and inward, the infantile cords are concave, whereas concavity is minimal in the adult. Cricoid ring: the narrowest point of the infant larynx is at the level of the cricoid cartilage, whereas the rima glottides is the narrowest point of the adult upper respiratory tract. Factors that increase heat loss in infants: relatively larger body surface area, less keratin in skin/preemies/. There are three mechanisms by which heat can be produced: increased physical activity, shivering – ability to shiver not present until~3 m old, nonshivering thermogenesis – the only means of heat production in anesthetized neonate, a result of brown fat metabolism. Meconium staining is present in 12% to 13% of all live birth and 36% of postdate pregnancies have meconium-stained fluid. Conditions associated with meconium staining: uteroplacental 37 insufficiency/late decelerations/, post-term pregnancies, maternal hypertension, placenta previa, maternal pulmonary disease, placental abruptions, cord prolapse and cord compression. Meconium is the sterile breakdown product of swallowed amniotic fluid, gastrointestinal cells and intestinal secretions. Mechanical airway obstruction by particles of meconium plays the most important role in meconium aspiration syndrome. Current recommendations include the early suction of fetal mouth and pharynx before the delivery pf the shoulders. Intubation and tracheal suctioning are reserved only for depressed infants or exposed to thick particulate matter on emergence. Clinical presentation: shifted cardiac sounds, scaphoid abdomen, diminished breath sounds on the affected side. Contralateral pneumothorax should be suspected if sudden changes in heart rate, blood pressure, PaO2 happening.

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The addition of anaesthetic vapours The anaesthetic machine Vapour-specific devices are used to produce an Its main functions are to allow: accurate concentration of each inhalational • the accurate delivery of varying flows of gases to anaesthetic: an anaesthetic system cheap tadalafil 5mg with mastercard; •Vaporizers produce a saturated vapour from a • an accurate concentration of an anaesthetic reservoir of liquid anaesthetic cheap tadalafil 10mg without prescription. Sevotec) to account for the loss of latent heat that causes cooling and reduces Measurement of flow vaporization of the anaesthetic buy tadalafil 10 mg otc. This is achieved on most anaesthetic machines by The resultant mixture of gases and vapour is the use of flowmeters (‘rotameters’ buy tadalafil 20mg free shipping; Fig cheap tadalafil 5mg amex. From this point, specialized the patient’s peak inspiratory demands (30– breathing systems are used to transfer the gases 40L/min) to be met with a lower constant flow and vapours to the patient. It also acts as a further Checking the anaesthetic machine safety device, being easily distended at low pres- It is the responsibility of each anaesthetist to check sure if obstruction occurs. The main danger is that the anaesthetic spontaneous ventilation, resistance to opening is machine appears to perform normally, but in fact is minimal so as not to impede expiration. In the valve allows manual ventilation by squeezing order to minimize the risk of this, the Association the reservoir bag. Its main aim is to ensure that oxygen flows through the oxygen delivery system and is The circle system unaffected by the use of any additional gas or vapour. Most modern anaesthetic machines now The traditional breathing systems relied on the po- have built-in oxygen analysers that monitor the in- sitioning of the components and the gas flow from spired oxygen concentration to minimize this risk. Even the most efficient system is Anaesthetic breathing systems still wasteful; a gas flow of 4–6L/min is required The mixture of anaesthetic gas and vapour travels and the expired gas contains oxygen and anaes- from the anaesthetic machine to the patient via an thetic vapour in addition to carbon dioxide. Delivery to the patient is via a inefficiencies: facemask, laryngeal mask or tracheal tube (see pages • The expired gases, instead of being vented to the 18–25). There are a number of different breathing atmosphere, are passed through a container of systems (referred to as ‘Mapleson A’, B, C, D or E) soda lime (the absorber), a mixture of calcium, plus a circle system. The details of these systems are sodium and potassium hydroxide, to chemically beyond the scope of this book, but they all have a remove carbon dioxide. As • Supplementary oxygen and anaesthetic vapour several patients in succession may breathe through are added to maintain the desired concentrations, the same system, a low-resistance, disposable bacte- and the mixture rebreathed by the patient. Gas rial filter is placed at the patient end of the system, flows from the anaesthetic machine to achieve this and changed between each patient to reduce the can be as low as 0. Components of a breathing system There are several points to note when using a circle All systems consist of the following: system. The inspired oxygen 43 Chapter 2 Anaesthesia Connection to scavenging system Adjustable expiratory valve Fresh gas input Reservoir bag Figure 2. Note the port on the expiratory valve (white) to allow connection to the anaesthetic gas scavenging system. A wide variety of anaesthetic ventilators are avail- • The inspired anaesthetic concentration must be able, each of which functions in a slightly different monitored, particularly when a patient is being way. One of During spontaneous ventilation, gas moves into the commonly used preparations changes from the lungs by a negative intrathoracic pressure. A positive pressure is applied to the anaesthetic gases to overcome airway resistance and elastic 44 Anaesthesia Chapter 2 Fresh gas I input Soda E lime Expiratory valve Reservoir bag Figure 2. The internal arrangement of the pipe-work in the system al- lows most of the components in the diagram to be situated on the top of the absorber. In both sponta- requires a source of energy: gravity, gas pressure or neous and mechanical ventilation, expiration oc- electricity. Un- Gravity derventilation will lead to hypercapnia, causing a The Manley is a typical example of a ventilator respiratory acidosis. Gas from the anaes- globin dissociation curve are the opposite of above, thetic machine collects within a bellows that is along with stimulation of the sympathetic nervous compressed by a weight. At a predetermined time a system causing vasodilatation, hypertension, valve opens and the contents of the bellows are tachycardia and arrhythmias. In patients with pre-existing lung disease this may cause a pneumothorax, and, long Gas pressure term, a condition called ventilator-induced lung Gas from the anaesthetic machine collects in a bel- injury. Minimizing theatre pollution Unless special measures are taken, the atmosphere Electricity in the operating theatre will become polluted with Electrical power opens and closes valves to control anaesthetic gases. The breathing systems described the flow (and volume) of gas from a high-pressure and mechanical ventilators vent varying volumes source. Alternatively, an electric motor can power a of excess and expired gas into the atmosphere, the piston within a cylinder to deliver a volume of gas patient expires anaesthetic gas during recovery to the patient (Fig.

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