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Complications of treatments for complicated diverticular disease Management Peritonitis Sigmoid colectomy is needed sildalist 120mg otc. When the colon is Anastomotic leak separated from the bladder it may not be possible Paralytic ileus to demonstrate the hole in the bladder safe 120mg sildalist. The dis- Multi-organ failure secondary to sepsis eased colon must be removed and bowel continuity Left ureter and bladder damage during dissection restored with an end-to-end anastomosis buy sildalist once a day. A vesicocolic fistula caused by an infiltrating cancer of the colon or bladder is usually a compli- mortality rises to more than 5 per cent if sigmoid cation of advanced disease and difficult to manage. Occasionally the orifice of the fis- to develop after an episode of diverticulitis because tula is visible. For obvi- Crohn’s disease is a chronic full thickness granulo- ous reasons, males notice this more readily. This may block the internal urinary monly affected is the terminal ileum immediately meatus and cause urinary retention. Endoscopy Colonic Crohn’s disease is becoming more fre- Cystoscopy (fibre or rigid) may show a reddened quent. Crohn’s disease is characterized by multiple area in the dome of the bladder, occasionally emit- ‘skip lesions’ – short diseased segments separated ting bubbles. Bleeding is usu- disease and may show barium in the fistula entering ally chronic rather than life-threatening. Patients with Crohn’s disease throughout the Blood tests colon may require panproctocolectomy and per- It is important to assess the degree of any anaemia manent ileostomy (Fig 19. Stool culture Complications It is important to remember that exacerbation of inflammatory bowel disease, both Crohn’s disease The complications specific to large bowel resections and ulcerative colitis, may be due to concomitant for Crohn’s disease are infection, and to send stool samples for culture. The inflammation extends from the rectum proximally Management and may affect any length from a few centimetres The medical management of ulcerative colitis is to the entire colon. The indications for severe and extensive ulcerative colitis have a higher surgical management are given in Table 19. This is major surgery and leaves the patient Investigation with a permanent stoma – an ileostomy. The ter- Clinical diagnostic indicators minal ileum is brought out through the abdomi- Ulcerative colitis presents in the second or third nal wall at an appropriate point. The main diagnostic clinical feature skin by the effluent from the ileum is prevented is incessant diarrhoea, which may contain blood. Panproctocolectomy has been performed safely for over 50 years and usually rapidly restores the patient to general good health. In the emergency situation or if the diagnosis is in doubt a subtotal colectomy with ileostomy is the operation of choice. This allows a more accu- rate histological assessment and reduces immediate postoperative complications. Should the patient be found to have Crohn’s colitis the continuity of the bowel can be restored later by an anastomosis of the ileum to the rectum. If ulcerative colitis is confirmed, it leaves the option of fashioning an ileo-anal pouch (see below). A stoma may be avoided for those who wish by means of a restorative proctocolectomy, in which an artificial pouch is constructed from ileal loops and joined to the anal canal (Fig 19. This surgery is complex and if there is leakage into the pelvis from the various anastomoses the subsequent pelvic sepsis is difficult to eradicate. To avoid this dreaded complication many surgeons fashion a proximal temporary loop ileostomy after constructing the pouch. Patients who have had pouch surgery or pan- usually precede perforation and the signs of gener- proctocolectomy are liable to suffer small bowel alized peritonitis. Patients with extensive ulcerative colitis and occasionally Crohn’s disease can develop a ful- Imaging minating condition in which the whole colon Plain chest and abdominal radiographs may show rapidly dilates and if left untreated may perforate. A carefully performed tion, abdominal distention and localized tenderness flexible sigmoidoscopy is preferable. Ischaemia of the colon 481 Management to ischaemia, fibrosis and fistula formation. These complications present in many ways and may be Patients should be given intravenous fluids and difficult to distinguish from cancer recurrence. They should be care- fully re-examined to see if abdominal signs of peri- Investigation tonitis are developing. Plain radiographs should be repeated daily to Radiation damage should be considered in any discover if the dilatation is developing or subsiding. The Systemic steroids in large doses should be given investigations should be appropriate to the present- to patients suspected of having early acute toxic ing symptoms. Laparotomy is indicated if the patient’s condi- In making the diagnosis and planning treatment tion deteriorates, especially if a perforation or a full it is important to exclude metastatic disease and thickness bowel infarct is suspected. The abdomen should be carefully washed out if there is evidence of faecal contamination. Results Late disease symptoms tend to wax and wane, and Emergency colonic surgery carries a high mortality surgery can usually be avoided. Surgery for stric- (5–10 per cent) when performed for complications tures and fistulae can be difficult and require stoma in patients who are often malnourished, toxic and formation. The mainstay of the splenic flexure and left colon, where the arterial treatment is oral or parenteral rehydration therapy. Campylobacter is the Clinical diagnostic indicators most common bacterial cause followed by Salmonella. Soon after undergoing pelvic radiotherapy Endoscopy patients may suffer from diarrhoea because of the The diagnosis is made by colonoscopy and biopsy. The diarrhoea may be severe and dis- tressing but generally settles spontaneously. Small Colonic ischaemia without signs of peritonitis is vessel thrombosis caused by the radiation can lead treated expectantly and usually resolves, presumably 482 The colon, rectum and anus because the ischaemia is mucosal rather than full been immobilized. It is unexpected that an ischaemic condi- large bowel obstruction caused by carcinoma. Many elderly patients who have a colonic bleed which set- Investigation of megacolon tles without treatment and have subsequent normal An abdominal X-ray gives the diagnosis of mega- investigation probably have had transient colonic colon. Patient’s with Hirschsprung’s disease have an A few patients develop colonic strictures which absent anorectal inhibitory reflex and a full thick- need resection and a few require urgent resection ness rectal biopsy is needed to confirm the diagnosis. Antibodies to The toxic megacolon associated with ulcerative Treponema cruzi can be identified. Hirschsprung’s disease Management This is caused by a lack or shortage of ganglia in the Hirschsprung’s disease is treated by resection of the myenteric plexuses in the wall of the colon or rec- affected segment of bowel with very low anastomo- tum. It usually presents in neonates with intestinal sis, often achieved by bringing normal colon down obstruction or in infants with constipation and fail- to the anal canal. The colon proximal to the contracted idiopathic megacolon and rectum by conservative aganglionic segment becomes grossly distended.

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Nausea and vomiting are common from N2O it is associated with malignant depth of anesthesia sildalist 120 mg otc. It is a matter of regret that none of the Ether Convulsion inhalational anesthetic agents fulfll the prop- Occurs in children and in disease states like Enflurane erties of an ideal agent best sildalist 120 mg. It is a halogenated ether and a volatile liquid • It is treated by administration of O2 anesthetic discount sildalist 120mgmg online. It was introduced in clinical prac- Classification thiopentone or diazepam and artifcial tice by Dobkin and associates in 1968. It may cause hepatotoxicity and hypothermia Halothane but less commonly than halothane. Diethyl Ether • It was frst prepared by Suckling in 1951 It produces moderate muscular relaxation This is probably the most extensively used and frst used clinically by Johnston of and excreted unchanged through the lungs. The reason for this is its wide safety • Physical properties have been described excreted through the kidney. It produces dose dependent depres- in 1965 and introduced in clinical anesthe- aldehyde in presence of light. It is typically produced by sux- threshold leading to the block of neuromus- the body. Sevoflurane • Teir action is opposed by increasing the A low blood/gas solubility coefcient facili- Suxamethonium local concentration of acetylcholine, e. It is well-suited for outpatient line molecules and acts in the same way at • Teir action is potentiated by certain surgery. Its action there- efect on the cardiovascular and respiratory fore, cannot be reversed. Because it acts on Characteristics of Nondepolarizing systems are similar to isofurane. Myocardium the acetylcholine receptor there is an initial Block is not sensitized to catecholamines. Tere is unsustained response to tetanic stimulation also called the ‘fade’ Nitrous Oxide Clinical Use response. Commonly used nondepolarizing agents (Entonox) is used for analgesia especially Dose: 1 to 1. Prolonged apnea-Some people have • Pancuronium late in the cavities of the body, e. Hyperkalemia-Occurs if it is given in Neuromuscular Blocking Agents patients with burn, tetanus and spinal Clinical Uses cord injury. The addition of muscle relaxants afords the dicated in patients with penetrating eye 2. For maintenance of paralysis during opportunity to deliver only sufcient inhala- injury. Relaxants good recovery of muscle power to maintain Depolarizing and nondepolarizing muscle Tey compete with acetylcholine for the end airway and respiration. Once a signifcant carinic action may induce a profound, brady- Tey act by causing depolarization block and number of receptors are blocked the end plate cardia, bronchoconstriction, etc. Tis technique combines Management of General Inhalation of nitrous oxide, oxygen plus a the advantages of both the intravenous and Anesthesia potent volatile anesthetic, e. Afer thetic drug dosage can be titrated according General anesthesia can be induced by giving induction, a depolarizing or nondepolarizing to the patient requirements. If there is some question about the General anesthesia reduces the tone of the Rapid Sequence Induction difculty of intubation, it can be attempted muscles that preserve the airway patency and Anesthesia is most commonly induced by while the patient is breathing spontaneously, hence there is a requirement for methods the method of rapid sequence induction in without giving a muscle relaxant. Tiopentone) is fol- children or ‘Needle – phobic’ adults and may or endotracheal tube to preserve the airway. Sir lowed by a depolarizing muscle relaxant, also be used for patients at risk of developing Ivan Magill developed the endotracheal tube e. Oxygen is usually given by mask Induction Intubation before hand (Preoxygenation) to allow maxi- Short­acting anesthetic drugs such as thio- 1. To provide positive pressure ventilation, mum time for intubation while the patient is pental, propofol or midazolam are ofen e. Urine output position of the patient is other than supine lution and is usually conducted by infusing 9. Accurate monitoring of vital functions is with the means of resuscitation and with • Accidental intubation of a main bronchus. Even for procedures under sedation, ously ill patient a high dependency unit or • Aspiration of vomitus during intubation. The com- laryngitis and laryngeal or subglottic Clinical Monitoring mon causes of failure to breathe afer general edema. Careful observation of physical signs and of anesthesia decreases, pupils-size, iii. Circulatory failure leading to respiratory capnography of the expiratory gases, inspira- • Nailbeds-Color, capillary refll. Alveolar hypoventilation from opioid ventilator disconnection alarms, are manda- drugs, or anesthetic agents. Following the induction of anesthesia, inha- Spinal, epidural and caudal blocks are lational or intravenous anesthetic agents are Auscultation commonly referred to as regional or administered to maintain an adequate depth • Chest-Ventilation and cardiac sounds. Blood pressure Locoregional anesthesia using local anes- required for maintenance. Skeletal muscle relaxation is excellent, the world, ether has generally been replaced 5. Desfurane and sevofurane are the most Common but not in routine Regional anesthesia is used most ofen recently introduced agents, conferring the 7. Tropical anesthesia Tey are preferred to esters because of disad- • Maximum safe dose is 2 mg/kg with or 3. Local anesthetic agents are used for local • Recently introduced, the levobupivacaine infltration, peripheral nerve blocks, obstetric isomer is claimed to have an improved Local Infiltration analgesia, acute and chronic pain relief, spi- cardiovascular safety profle. Ideal Local Anesthetic Agent Structurally, the propyl group of bupivacaine It is used during wound debridement, Should have a quick onset of action, long is replaced with a butyl group to produce central venous catheter placement or repair duration of action, should not cause motor ropivacaine. The agent of choice is blockade, and should be free from cardiac lidocaine 1 to 2 percent due to its quick onset toxicity. Maximum safe dose-3 mg/kg without adren- Epinephrine should not be used in areas Mechanism of Action aline and 8 mg/kg with it. A higher dose can be at risk of vascular compromise from arterial Local anesthetics act by blocking the recep- used because of lack of cardiotoxicity. Tus any injection given at a level • Spine of scapula – T 3 Tropical anesthetic agents are used on the below L is likely to touch the nerve roots, 2 • Inferior Angle of scapula – T7 skin, the urethral mucosa, nasal mucosa and but unlikely to damage them. Brachial plexus block-Tis is done for ticulate ligament, trabecula and the nerve Physiology of Neural Blockade surgery on the arm or hand. Tis creates a possibility Tere is a zone of diferential blockade for the local anesthetic solution is given into the of uneven distribution and may account motor and the sensory nerves. Motor Block for carotid endarterectomy and is the In spinal anesthesia, there is a diference in anesthetic method of choice. Vertebral Column motor and the sensory block by two seg- It comprises of the vertebrae with the inter- ments.

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This long refractory state precludes summated or tetanic contractions from occurring in normal cardiac muscle discount sildalist 120 mg without a prescription. Immediately after the action potential purchase sildalist 120 mg with mastercard, the membrane is transiently hyperexcitable and is said to be in a "vulnerable" or "supranormal" period 120 mg sildalist. Similar alterations in membrane excitability occur during slow action potentials but are not well characterized at present. Recall that the membrane potential of any cell at any given instant depends on the relative permeability of the cell membrane to specifc ions. As in all excitable cells, cardiac cell action potentials are the result of transient changes in the ionic permeability of the cell membrane that are triggered by an initial depolarization. Terefore, the membrane potentials are close to the potassium equilib­ rium potential (of -90 mV) during this period. In pacemaker-type cells, at least three mechanisms are thought to con­ tribute to the slow depolarization of the membrane observed during the diastolic interval. Tis gradual increase in the Na+fK+ permeability ratio will cause the membrane potential to move slowly away from the K+ equilibrium potential (-90 mV) in the direction of the Na+ equilibrium potential. For example, the resting membrane is quite permeable to K+ but there is little net K+ movement because the resting membrane potential is very close to the potas­ sium equilibrium potential. These permeability changes result in a specific current that occurs during diastole called the i-funny (if) current. When the membrane potential depolarizes to a certain threshold potential in either type of cell, major rapid alterations in the permeability of the membrane to specifc ions are triggered. Once initiated, these permeability changes cannot be stopped and they proceed to completion. The characteristic rapid rising phase of the fast-response action potential is a result of a sudden increase inNa+ permeability. This produces what is referred to as thefat inward current ofNa+ and causes the membrane potential to move rap­ idly toward the sodium equilibrium potential. As indicated in Figure 2-2C, this period of very high sodium permeability {phase 0) is short-lived.? In addition, under certain conditions, the electrogenic action of aNa+-Ca2+ exchanger {in which 3Na+ ions move into the cell in exchange for a single Ca2+ ion moving out of the cell) may contribute to the maintenance of the plateau phase of the cardiac action potential. The initial fast inward current is small (or even absent) in cells that have slow­ response action potentials (Figure 2-2D). Therefore, the initial depolarization phase of these action potentials is somewhat slower than that of the fast-response action potentials and is primarily a result of an inward movement of Ca2+ ions. In both types of cells, the membrane is repolarized (during phase 3) to its original resting potential as the K+ permeability increases to its high resting value and the Ca2+ andNa+ permeabilities return to their low resting values. These late perme­ ability changes produce what is referred to as the delyed outward current. The overall smoothly graded permeability changes that produce action potentials are the net result of alterations in each of the many individual ion channels within the plasma membrane of a single cell. These loops form a hollow conduction channel between the intracellular and extracellular fuids that are structurally quite spe­ cifc for a particular ion. The open/closed status of the channels can be altered by configurational changes in certain subunits of the molecules within the channel (referred to as "gates" or plugs) so that when open, ions move down their electro­ chemical gradient either into or out of the cell {high permeability). The patch clamp data indicate that a single channel is either open or closed at any instant in time; there are no graded states of partial opening. What igraded is the percentage of time that a given channel spends in the open state, and the total number of channels that are currently in an open state. Certain types of channels are called voltage-gated channel (or voltage-operated channels) because their probability of being open varies with membrane potential. Other types of channels, called ligand­ gated channel (or receptor-operated channels), are activated by certain neuro­ transmitters or other specifc signal molecules. Table 2-1 lists some of the major important currents and channel types involved in cardiac cell electrical activity. However, changes in membrane potential of slower onset, but the same magnitude, may fail to activate these channels at all. To explain such behavior, it is postulated that these channels have 2 independently operating "gates"-an activation gate and an inactivation gate-both of which must be open for the channel as a whole to be open. Both these gates respond to changes in membrane potential but do so with different voltage sensitivities and time courses. With a rapid depolarization of the membrane to threshold, the Na+ channels will be activated strongly to allow an inrush of positive sodium ions that further depolarizes the membrane and thus accounts for the rising phase of a "fast" response action potential, as illustrated in Figure 2-3B. This occurs because the activation gate responds to membrane depo­ larization by opening more quickly than the inactivation gate responds by closing. Tus, a small initial rapid depolarization to threshold is followed by a brief but strong, period of Na+ channel activation wherein the activaton gate is open but the inactivaton gate is yet to close. Within a few milliseconds, however, the inac­ tivation gates of the fast sodium channels close and shut of the inward movement ofNa+. After a brief delay, the large membrane depolarization of the rising phase of the fast action potential causes the activation (or d) gate of the Ca2+ channel to open. This permits the slow inward movement of Ca2+ ions, which helps maintain the depolarization through the plateau phase of the action potential (Figure 2-3C). Ultimately, repolarization occurs because of both a delayed inactivation of the Ca2+ channel (by closure of the inactivation (orf) gates) and a delayed opening of K+ channels (which are not shown in Figure 2-3). For example, high intracellular Ca2+ concentration during systole contributes to activation of cer­ tain K+ channels and increases the rate of repolarization. The inactivation gates of sodium channels remain closed during the remainder of the action potential, effectively inactivating the Na+ channel. This sustained sodium channel inacti­ vation, combined with activation of calcium channels and the delay in opening of potassium channels, accounts for the long plateau phase and the long cardiac refractory period, which lasts until the end of phase 3. With repolarization, both gates of the sodium channel return to their original position and the channel is now ready to be reactivated by a subsequent depolarization. The slow-response action potential shown in the right half of Figure 2-3 differs from the fast-response action potential primarily because of the lack of a strong activation of the fastNa+ channel at its onset. A conceptual model of cardiac membrane fast sodium and slow calcium ion channels: at rest (A), during the initial phases of the fast-response (Band C), and the slow-response action potentials (D and E). These channels are activated at the end of the repolarization phase and promote a slow sodium and calcium influx that gradually depolarizes the cells during diastole. This slow diastolic depolarization gives the inactivating h gates of many of the fast sodium channels time to close before threshold is even reached (Figure 2-3D). The depolarization beyond threshold during the rising phase of the action potential in these "pacemaker" cells is slow and caused primar­ ily by the influx of Ca2+ through slow channels (Figure 2-3E). Although cells in certain areas of the heart typically have fast-type action potentials and cells in other areas normally have slow-type action potentials, it is important to recognize that all cardiac cells are potentially capable of having either type of action potential, depending on their maximum resting membrane potential and how fast they depolarize to the threshold potential. As we shall see, rapid depolarization to the threshold potential is usually an event forced on a cell by the occurrence of an action potential in an adjacent cell. A chronic moderate depolarization of the resting membrane (caused, eg, by mod­ erately high extracellular K+ concentrations of 5-7 mM) can inactivate the fast channels (by closing the h gates) without inactivating the slow Ca2+ channels.

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Other causes sis and management of pancreatitis is still a results in infammation and predisposes An episode of acute pancreatitis may be mystery generic sildalist 120mg visa. The reason why necrosis precipitated by several other factors like trauma buy sildalist 120 mg on line, tumors generic 120 mg sildalist with visa, surgery, drugs, infections table 38. Metabolic – Hyperlipidemia trauma probably cause damage to the aci- – Hypercalcemia. Traumatic secretion and formation of calcifed stones – Blunt and penetrating abdominal trauma. One of the most important step of such activation is forma- tion of trypsin from trypsinogen which is the initiating or trigger mechanism in causing acute pancreatitis as described in Figure 38. Pathology In acute pancreatitis the pancreas is damaged by the digestive action of its own juices. Macroscopically, in the mildest form the main objective feature is edema of the pan- creas and the condition is called acute inter- stitial or edematous pancreatitis. At the other extreme, there is extensive necrosis of the pancreas with hemorrhagic extravasations in its vicinity and multiple points of fat saponifcation scattered through the abdomen or even more widely. In typical case, the peritoneal cavity contains blood stained ascetic fuid and white fecks of fat necrosis in the omentum, mesentery and peripancreatic tissue. Necrosis of arterioles and arteries with Diagnosis • Activation of kallikrein through chymo- areas of hemorrhages. Tere is no pathognomonic test for acute pan- trypsin leads to bradykinin formation d. The diagnosis rests on the interpre- which causes increased capillary perme- morphs, around the areas of necrosis and tation of clinical and laboratory informations. Serum Amylase • Phospholipase A activation leads to pro- Clinical Features • A serum amylase level four times above 2 duction of prostaglandins which will cause • Sudden onset of upper abdominal pain normal is indicative of the disease. Pain may be amylase > 1000units/liter may suggest pan- • Activation of thrombin may cause dis- relieved or reduced by leaning forward. However, there is no correlation seminated intravascular coagulation • Features of shock and dehydration. In these has a predictive performance similar to the mild or moderate infammation resulting cases the prognosis is bad. Differential Diagnosis Chronic pancreatitis leads to both exo- The less severe episode of acute pancreati- Conservative Treatment crine (steatorrhea) and endocrine (diabetes tis simulates acute cholecystitis, the more 1. The etiology of chronic pancreatitis has not nal obstruction or other causes of severe 2. Aspiration with Ryles tube to give rest to yet been demonstrated, with the exception of peritonitis. Antibiotics should only be used when The probable etiological factors are Acute pancreatitis is a disease with wide spec- pancreatitis is associated with biliary tract described in Table 38. Somatostatin or octreotide is ofen used to pancreatitis disease, which is associated with signifcant reduce pancreatic secretion. Excessive alcohol intake or chronic pancreatitis may need respiratory support alcoholism Assessment of Severity in the form oxygen supplementation or 2. Operative Treatment – Hypercalcemia Patients that present with two or fewer It is indicated in the following circumstances: – Hyperlipidemia criteria have no mortality, with three to four 1. Hereditary pancreatitis prognostic signs, have a mortality of 15 per- atory laparotomy. Obstruction of the pancreatic duct cent and with fve to six,they have mortality 2. Progressive deterioration in spite of con- – Gallstones of 50 percent and above, servative measures. In severe cases, surgical treatment is 90 percent cases of chronic pancreatitis and protease to well less than 10 percent of advocated. Endocrine dysfunction Diabetes mel- • In India, the disease is known as tropical litus occurs late in the disease, usually 10 • Obstructive jaundice. Most patients are non- to 15 years after the first symptom of the • Persistent pain. Puestow’s operation (Pancreatojejuno- of acute pancreatitis, rarely lead to chronic • Chronic pancreatitis is usually suspected stomy) – As the duct is dilated more than pancreatitis. Afer this the duct Pathology of pancreatic calcifcation or calculi is is anastomosed to the frst loop of jejunum Macroscopically, pancreas in usually hard about 95 percent specifc for chronic side to side as Roux –en – Yanastomosis. True (20%) late cells of the pancreas which are converted Differential Diagnosis • Congenital polycystic disease of the to myofbroblast like cells following an insult • Peptic ulcer disease. The role of proinfammatory macro- Complications • Retention cyst phages, cytokines and stellate cells in models • Pseudocyst of pancreas. Rarely perforation of a posterior gastric Pain is ofen exacerbated15 to 30 minutes • Removal of associated factors, e. Initially 251 Section 9  Hepatobiliary, Pancreas and Spleen anterior cyst wall and the posterior gastric The malignancy most commonly arises wall around the stoma. Laparoscopic cystogastrostomy is becom- Etiology ing popular, efective and less invasive • It is one of the commonest malignant nowadays. Malignant two layers, e–below transverse mesocolon, • Adenocarcinoma Pathology f–between layers of mesentery • Cystadenocarcinoma Macroscopically, the growth is infltrating, Secondly metastasis from carcinoma of hard and irregular. Microscopically – Adenocarcinoma is the the cyst is resonant because of loops of gas- B. Tumors of endocrine pancreas predominant lesion, accompanied by fbrous flled bowel in front of it, but as it increases in 1. Gastrinoma – (Zollinger – Ellison syn- The tumors may be: becomes dull to percussion (Fig. Excision of the cyst is impracticable because carcinoma of the Pancreas Gastric, hepatic, mesenteric and omental of intimate relationship of the cyst wall to the About 70 percent of pancreatic cancers arise nodes are also involved. The posterior wall of the stomach and the anterior wall of the cyst which are closely adherent to each other are now incised together for about 5cm. The contents of the cyst are sucked out, several inter- rupted stitches are applied between the 252 Chapter 38  Pancreas • Transcelomic implantation with perito- due to ulceration of the tumor and relief of 2. The ultrasound structures and viscera like duodenum, denal infltration will have occult blood in the examination may be obscured by gas in bile duct, portal vein, inferior vena cava, stools and ofen melena. Barium meal study shows widened Carcinoma of the Body and Tail duodenal “C” loop – pad sign in carci- Clinical Features The patient usually presents with pain, noma head of the pancreas. Reverse 3 Carcinoma of the Head of the weight loss and ofen a mass in the upper sign is seen in carcinoma of periampul- Pancreas abdomen. Pain radiating to the The pain is usually boring into the back back may result from posterior infltration between L and L vertebrae and relieved by Treatment 1 2 of the tumor and is relieved on bending stooping forward. Investigations • Jaundice is relieved by placing a stent • Palpable gallbladder - In jaundice due A. Laboratory tests through the tumor either transhepati- to carcinoma of the head of the pancreas, 1. Tumor markers - Pancreatic adeno- • Duodenal obstruction is relieved by • Chills and fever are not uncommon due to carcinomas are associated with ele- gastrojejunostomy. Palpable gallbladder Present Present Absent present early, have a reasonably good prognosis 6.

The reddish color of the skin during exercise in a warm environment reflects the large blood flow and dilation of skin arterioles and venules brought into play for dissipation of excess body heat (see Table 16 buy generic sildalist on-line. The increase in the skin’s blood flow when the body is exposed to heat probably occurs through two main mechanisms 120mg sildalist sale. First buy generic sildalist 120 mg online, an increase in body core temperature causes a reflex increase in the activity of sympathetic cholinergic nerves, which release acetylcholine. Second, simply increasing skin temperature will cause the blood vessels to dilate. This can result from heat applied to the skin from the external environment, heat from underlying active skeletal muscle, or increased blood temperature as it enters the skin. Total skin blood flows of 5 to 8 L/min have been estimated in humans during vigorous exercise in a hot environment. During mild-to-moderate exercise in a warm environment, skin blood flow can equal or exceed blood flow to the skeletal muscles. Exercise tolerance can, therefore, be lower in a warm environment because the vascular resistance of the skin, combined with very low vascular resistance in muscle, is too low to maintain an appropriate arterial blood pressure, even at maximum cardiac output. One of the adaptations to exercise is an ability to increase blood flow in skin and dissipate more heat. In addition, aerobically trained humans are capable of higher sweat production rates than normal, which accelerates heat loss from the surface of the skin (see Chapter 28). Most humans live in cool-to-cold regions, where body heat conservation is imperative. The sensation of cool or cold skin or a lowered body core temperature elicits a reflex increase in sympathetic nerve activity, which causes vasoconstriction of blood vessels in the skin, especially the arteriovenous anastamoses. Heat loss is minimized because the skin becomes a poorly perfused insulator, rather than a heat dissipater. As long as the skin temperature is higher than about 10°C to 13°C (50°F to 55°F), the neurally induced vasoconstriction is sustained. However, at lower tissue temperatures, the vascular smooth muscle cells progressively lose their contractile ability, and the vessels passively dilate to various extents. The reddish color of the hands, face, and ears on a cold day demonstrates increased blood flow and vasodilation as a result of low skin temperatures. To some extent, this cold-mediated vasodilation is useful because it lessens the chance of cold injury to exposed skin. However, if this process included most of the body surface, such as occurs when the body is submerged in cold water or inadequate clothing is worn hypothermia can result (see Chapters 28 and 29 for more detail). The human fetal placenta is supplied by two umbilical arteries, which branch from the internal iliac arteries of the fetus. The umbilical vein of the fetus returns oxygen and nutrients from the mother’s body to the fetal cardiovascular system, and the umbilical arteries bring in blood laden with carbon dioxide and waste products from the fetus to be transferred to the mother’s blood. Although many liters of oxygen and carbon dioxide, together with hundreds of grams of nutrients and wastes, are exchanged between the mother and fetus each day, the exchange of red blood cells or white blood cells is a rare event. This large chemical exchange without cellular exchange is possible because the fetal and maternal bloods are kept almost completely separate. The left and right sides of the fetal heart are separated solely for the purpose of illustration to emphasize the right-to-left shunt of blood through the open foramen ovale in the atrial septum and the right-to-left shunt through the ductus arteriosus. The numbers represent the percent saturation of blood hemoglobin with oxygen in the fetal circulation. Closure of the ductus venosus, foramen ovale, ductus arteriosus, and placental vessels at birth and the dilation of the pulmonary vasculature establish the adult circulation pattern. The insert is a cross-sectional view of a fetal placental villus, one of the branches of the treelike fetal vascular system in the placenta. The fetal capillaries provide incoming blood, and the sinusoidal capillaries act as the venous drainage. The villus is completely surrounded by the maternal blood, and the exchange of nutrients and wastes occurs across the fetal syncytiotrophoblast. The fundamental anatomic and physiologic structure for fetal/maternal exchange is the placental villus. As the umbilical arteries enter the fetal placenta, they divide into many branches that penetrate the placenta toward the maternal system. These small arteries divide in a pattern similar to a fir tree, the placental villi being the small branches. The fetal capillaries bring in the fetal blood from the umbilical arteries, and then, blood leaves through sinusoidal capillaries to the umbilical venous system. Exchange occurs in the fetal capillaries and probably to some extent in the sinusoidal capillaries. The mother’s vascular system forms a reservoir around the treelike structure such that her blood envelops the placental villi. The underlying cytotrophoblast is composed of less differentiated cells, which can form additional syncytiotrophoblast cells as required. As cells of the syncytiotrophoblast die, they form syncytial knots, and eventually, these break off into the mother’s blood system surrounding the fetal placental villi. The placental vasculatures of both the fetus and the mother adapt to the size of the fetus as well as to the oxygen available within the maternal blood. For example, a minimal placental vascular anatomy will provide for a small fetus, but as the fetus develops and grows, a complex tree of placental vessels is essential to provide the surface area needed for the fetal–maternal exchange of gases, nutrients, and wastes. If the mother moves to a higher altitude, where less oxygen is available, the complexity of the placental vascular tree increases, compensating with additional areas for exchange. If this type of adaptation does not take place, the fetus may be underdeveloped or may die from a lack of oxygen. During fetal development, the fetal tissues invade and cause partial degeneration of the maternal endometrial lining of the uterus. The result, after about 10 to 16 weeks of gestation, is an intervillous space between fetal placental villi that is filled with maternal blood. The intervillous space is supplied by 100 to 200 spiral arteries of the maternal endometrium and is drained by the endometrial veins. During gestation, the spiral arteries enlarge in diameter and simultaneously lose their vascular smooth muscle layer. It is the arteries preceding them that actually regulate blood flow through the placenta. At the end of gestation, the total maternal blood flow to the intervillous space is ~600 to 1,000 mL/min, which represents about 15% to 25% of the resting cardiac output. In comparison, the fetal placenta has a blood flow of about 600 mL/min, which represents about 50% of the fetal cardiac output. The exchange of materials across the syncytiotrophoblast layer follows the typical pattern for all cells. Gases, primarily oxygen and carbon dioxide, and nutrient lipids move by simple diffusion from the site of highest concentration to the site of lowest concentration. Large molecular weight peptides and proteins and many large, charged, water-soluble molecules used in pharmacologic treatments do not readily cross the placenta. Part of the transfer of large molecules probably occurs between the cells of the syncytiotrophoblast layer and by pinocytosis and exocytosis.

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In the past order sildalist 120mg mastercard, medical scientists have been seeing human health and survival from the level of the gene alone order sildalist 120mg on-line. Epigenetic-induced physiologic changes are making it clear that individuals are no longer doomed by their genes buy 120 mg sildalist with mastercard. In practical terms, research indicates that about 20% of an individual’s health, diseases, and how he or she ages is due to genetics, and the remaining 80% is dependent on epigenetic-induced alterations in human function via changes in lifestyle and environment. For example, many of the diseases that cause early death (high blood pressure, obesity, diabetes, heart attacks, strokes, cancer) are classified as 80/20: 20% due to genetics and 80% related to lifestyle. In summary, physiology has provided remarkable insight into how cells, tissues, and organs interact and how they are regulated. The interaction between physiology and the new science of epigenetics is showing that human health and survival are no longer determined by the limits set by our genes. Moreover, recent medical advances show the extraordinary influence individuals have over the control of their health, quality of life, and how they age. Lastly, the paradigm shift in epigenetic-induced functional changes is providing new directions for the future treatment of human diseases. Explain the difference between steady state and equilibrium, including the role of energy expenditure in these concepts. List the types of molecules that constitute the plasma membrane and explain how they are assembled to form a selectively permeable barrier. Describe how the plasma membrane maintains an internal environment that differs significantly from the extracellular fluid. Describe primary active transport and explain how secondary active transport is different. Describe the properties of epithelial cells that are necessary to produce directional movement of solutes and water. Outline the mechanisms that many cells use to regulate their volume when exposed to osmotic stress. List the key components of the Goldman equation and explain why this equation gives the value of the membrane potential. Compare and contrast autocrine, paracrine, and endocrine signaling in the control of cell function. Explain the major differences between intracellular signal transduction by G-protein–coupled receptors and tyrosine kinase receptors. Describe how intracellular calcium concentration is regulated and used in intracellular signal transduction. The scope of physiology ranges from the functions of individual molecules and cells to the interaction of our bodies with the external world. Understanding how the different cell types that constitute tissues are controlled, how they interact both within and with other tissues, and how they adapt to changing conditions is central to the study of physiology. To maintain health, conditions in the body must be optimized through closely regulated processes that require efficient communication between cells and tissues. The plasma membrane keeps ions, metabolites, and cell proteins needed for normal cell function from leaking out, allows specific ions and molecules to enter, and blocks entry of factors not needed by the cell. To function in coordination with the rest of the organism, cells send and receive information that is first processed by specific plasma membrane proteins. This chapter discusses topics related to regulation of cellular homeostasis and communication between cells and tissues. Specific topics include the internal environment, types of membrane transport mechanisms for ions and other solutes, steady state and equilibrium, intercellular and intracellular communication, negative and positive feedback, feedforward control, and intracellular signal transduction cascades. It is clear that conditions and processes in the body must be closely controlled and regulated-that is, kept within appropriate values. The 19th-century French physiologist Claude Bernard was the first to formulate the concept of the internal environment (milieu intérieur). Cells are not directly exposed to the external world but, rather, interact with it through their surrounding environment, which is continuously renewed by the circulating blood. For optimal cell, tissue, and organ function in animals, several facets of the internal environment must be maintained within narrow limits. These include but are not limited to (1) oxygen and carbon dioxide tensions; (2) concentrations of glucose and other metabolites; (3) osmotic pressure; (4) concentrations of hydrogen, potassium, calcium, and magnesium ions; and (5) temperature. Bernard stated, “Stability of the internal environment is the primary condition for a free and independent existence. A good example is the ability of warm-blooded animals to live in different climates. Over a wide range of external temperatures, core temperature in mammals is maintained constant by both physiologic and behavioral mechanisms. Homeostasis is the maintenance of steady states in the body by coordinated physiologic mechanisms. The key to maintaining the stability of the body’s internal environment is the masterful coordination of important regulatory mechanisms in the body. Cannon captured the spirit of the body’s capacity for self-regulation by defining the term homeostasis as the maintenance of steady states in the body by coordinated physiologic mechanisms. Understanding the concept of homeostasis is important for understanding and analyzing normal and pathologic conditions in the body. To function optimally under a variety of conditions, the body must sense departures from normal and then be able to activate mechanisms for restoring physiologic conditions to normal. Deviations from normal conditions may vary between too high and too low, so mechanisms exist for opposing changes in either direction. Homeostatic regulation of a physiologic variable often involves several cooperating mechanisms activated at the same time or in succession. The more important a variable, the more numerous and complicated are the mechanisms that operate to keep it at the desired value. When the body is unable to restore physiologic variables, then disease or death can result. The ability to maintain homeostatic mechanisms varies over a person’s lifetime, with some homeostatic mechanisms not being fully developed at birth and others declining with age. For example, a newborn infant cannot concentrate urine as well as an adult and is, therefore, less able to tolerate water deprivation. Older adults are less able to tolerate stresses, such as exercise or changing weather, than are younger adults. In fact, the ultimate goal of maintaining a constant internal environment is to promote intracellular homeostasis, and toward this end, conditions in the cytosol of cells are closely regulated. The components of a simple negative-feedback control system include a regulated variable, sensor, controller, and effector (Fig. Various disturbances may arise within or outside the system and cause undesired changes in the regulated variable. With negative feedback, a regulated variable is sensed, information is fed back to the controller, and the effector acts to oppose change (hence the term negative). The regulated variable is sensed, and information about its level is provided to a feedback controller, which compares it with a desired value (set point). If there is a difference, an error signal is generated, which drives the effector to bring the regulated variable closer to the desired value.

So discount sildalist 120mgmg with visa, normally all females will be having both isoforms of the syndrome purchase sildalist online from canada, just remember the enzymes whereas malignant transformation results in a single marker being expressed buy sildalist with a visa. Immunoglobulin receptor and T-cell receptor Hereditarily Like Familiar Females gene rearrangements serve as markers of clonality in B- and T-cell lymphomas, respectively. Autosomal dominant cancer syndrome – Inheritance of a single mutant gene increases the risk of development of cancer. Familial cancers – These are cancers occurring at high frequency in families without a clear defned pattern of transmission. These usually show early age of onset and are present is 2 or more close relatives of the index case. The seven fundamental changes in cell physiology that together determine the malignant phenotype are: 1. Evasion of apoptosis: Presence of resistance to apoptosis doubling of the nuclear material. Limitless replicative potential: Presence of unrestricted proliferative capacity due to It is a point of no return in the cell cycle telomerase activity 5. It is the shifting of glucose metabolism by the cancer cells from the effcient mitochondria to glycolysis. Activated E2F results in transcription of target genes essential for progression through the S phase. G2/M transition, such as the decrease in microtubule stability, the separation of centrosomes, and chromosome condensation. Transcriptional point has both p53 dependent as activation of p21 is under the control of p53 well independent mechanisms. The checkpoint effector molecules differ, depending on the cell-cycle stage at which they act. In the G1/S checkpoint, cell-cycle arrest is mostly mediated through p53, which induces the cell- cycle inhibitor p21. Arrest of the cell cycle by the G2/M checkpoint involves both p53-dependent (via cyclin A/cdK-2) and independent (via cdc 25) mechanisms. Proto-Oncogenes Proto-oncogenes (Normal genes required for cell proliferation and differentiation) Oncogenes (Genes promoting autonomous cell growth in cancer cells) Oncoproteins (Proteins lacking regulatory control and responsible for promoting Proto-oncogeneswere discovered cell growth) by Harold Varmus and Michael Selected Oncogenes, their mode of activation and associated human tumors Bishop. The fusion gene possesses uncontrolled tyrosine kinase activity responsible for causing cancer development. Tumor Suppressor Genes These genes normally regulate cell growth (they do not prevent tumor formation, so the name is actually a misnomer). Knudson’s Two Hit Hypothesis • In familial case of retinoblastoma, children are born with one normal and one defective copy of the Rb gene. So, till the time there is heterozygosity for the Rb gene, the cell behavior is not affected (no chances of cancer development). It means that the cell loses heterozygosity for the normal Rb gene (called as loss of heterozygosity). Knudson’s Two Hit Hypothesis According to this hypothesis, both the normal alleles should be inactivated for the development of retinoblastoma. Inherited/Familial Retinoblastoma (40%) In hereditary cases of Retinoblastoma one genetic change (frst hit) is inherited from the affected parent therefore it is present in all the somatic cells of the body. The second mutation (second hit) is required Familial Retinoblastoma is also to produce cancer. Sporadic Retinoblastoma (60%) In sporadic cases both mutations (hits) occur somatically within a single retinal cell whose progeny then form the tumor. The non-mutated p53 gene is also called as the ‘wild mutated gene in human cancers. However, sometimes individual may inherit one mutant p53 allele and the second acquired ‘hit’ may inactivate the normal p53 allele. This later condition is called Li-Fraumeni syndrome associated with development of sarcoma, breast cancer, leukemia and brain tumors. Cancers carrying p53 mutations are relatively resistant to chemotherapy and radiotherapy. Then it can either cause target Note: p73 (big brother of p53) and p63 are other members of the family of p53 gene. So, any mutation affecting any of these genes increases the chances and anti-apoptotic genes like bcl2. Genes Regulating Apoptosis is able to repress the function of Apoptosis (or programmed cell death) is promoted by the genes bax, bad, bcl- Xs and other genes. Understandably, any increase in bcl-2 would cause inhibition of apoptosis and development of cancer. Normally chromosome 14 has immunoglobulin heavy chain gene whereas chromosome 18 has bcl-2 gene. Detachment of tumor cells – Due to ↓ E-cadherin and ab- normal catenin Genes promoting metastasis 2. Degradation of extracellular cancer) and Ki55 [malignant matrix by serine, cysteine and melanoma] matrix metalloproteinases 4. Metastatic deposit Cancer causing agents Sir Percival Pott demonstrated the increased incidence of scrotal skin cancer in chimney Chemical carcinogenesis Radiation exposure Microbial carcinogenesis workers exposed to chemical soot. Chemical Carcinogens Chemical carcinogenesis has two steps called initiation and proliferation. Indirect acting agents (also called as procarcinogens) – These require metabolic Concept conversion to form active carcinogens. The proliferation of the tumor cells is done by Initiators cause irreversible promoters (chemicals causing multiplication of already mutated cells). The carcinogenic potential of a chemical is tested by Ames test of the tumor cells is done by promoters (chemicals causing Chemical Carcinogens multiplication of already mutated cells). Androgens Prostate cancer Aromatic amines (dyes) Bladder cancer Arsenic Cancer of the lung, skin Asbestos Cancer of the lung, pleura, peritoneum Concept Benzene Acute myelocytic leukemia Chromium Lung cancer In Ames test, a modifed bacte- Diethylstilbestrol (prenatal) Vaginal cancer (clear cell) rium Salmonella typhimurium Epstein-Barr virus Burkitt’s lymphoma, nasal T cell lymphoma is used, which is unable to pro- duce histidine due to absence Estrogens Cancer of the endometrium, liver, breast of histidine synthetase enzyme Ethyl alcohol Cancer of the liver, esophagus, head and neck in it. Immunosuppressive agents (azathioprine, Non-Hodgkin’s lymphoma The modifed bacteria are frst cyclosporine, glucocorticoids) put on a histidine free medium Nitrogen mustard gas Cancer of the lung, head and neck, nasal sinuses where it cannot grow. Nickel dust Cancer of the lung, nasal sinuses Then it is put on the same me- dium but now having additionally Oral contraceptives Bladder and cervical cancer the presence of the suspected Phenacetin Cancer of the renal pelvis and bladder mutagen. In the second case, the bacteria grow if the chemical Polycyclic hydrocarbons Cancer of the lung, skin (especially squamous cell has mutagenic potential. This is associated with its ability to cause chronic liver cell injury and infammation that is accompanied by liver regeneration. Mitotically active hepatocytes, surrounded by an altered environment, are presumably prone to genetic instability and cancer development. Since both p53 and Rb are tumor suppressor genes, so, their inactivation increases the chances of cancer development. Hypoglycemia Fibrosarcoma Insulin or insulin-like Other mesenchymal sarcomas substance Hepatocellular carcinoma Carcinoid syndrome Bronchial adenoma (carcinoid) Serotonin, bradykinin Pancreatic carcinoma Gastric carcinoma Polycythemia Renal carcinoma Erythropoietin Hypercalcemia is probably the Cerebellar hemangioma most common paraneoplastic syndrome. Hepatocellular carcinoma Nerve and Muscle Syndromes Myasthenia Bronchogenic carcinoma Immunologic Disorders of the central and Breast carcinoma peripheral nervous systems Dermatologic Disorders Trousseau phenomenon (Migra- Acanthosis nigricans Gastric carcinoma Immunologic; secretion of tory thrombophlebitis) is seen Lung carcinoma epidermal growth factor with pancreatic and broncho- Uterine carcinoma genic carcinoma Dermatomyositis Bronchogenic, breast carcinoma Immunologic Osseous, Articular, and Soft Tissue Changes Hypertrophic osteoarthropathy Bronchogenic carcinoma Unknown and clubbing of the fngers contd... Categorization of undifferentiated malignant tumor: Sometimes, many tumors lesion, its extent of spread to like anaplastic carcinoma, lymphoma, melanoma and sarcoma are diffcult to regional lymph nodes, and the distinguish with routine H and E staining because of poor differentiation. So, presence or absence of distant immunohistochemical stains can help in diagnosis e.