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Secretion by centroacinar cells and by cells of the extralobular ducts of the pancreas buy 120mg starlix with amex. Chloride concentrations (right) were determined on fluid collected by micropuncture discount starlix 120mg mastercard, and the bicarbonate concentrations were inferred from the fact that the fluid is isotonic order starlix 120mg otc. The first pattern is basal secretion discount starlix 120mg visa, which is punctuated every 1 or 2 hours by bursts of increased bicar- bonate and enzyme secretion that last 10 to 15 minutes. The second pattern is the postprandial stage, which results from a complex interaction of neural and hormonal mechanisms. The cephalic phase occurs in response to the sight, smell and taste of food and is mediated by the vagus cholinergic nerves. The gastric phase occurs in 3 response to distention of the stomach, which affects vagova- gal neural reflexes and stimulates the release of gastrin. Both vagal reflexes and gastrin stimulate pancreatic enzyme secretion and gastric parietal cell acid secretion. The intestinal phase, which is initiated in the duodenum, accounts for the major stimulation of both enzyme and bicarbonate secretion. As the chyme reaches further into the small intestine, a number of hor- mones are released which are capable of inhibiting both basal and stimulated pancreatic secretion, and therefore serve as feedback inhibitory mechanisms on enzyme and bicarbonate secretion. Pancreatic Function Test The diagnosis of pancreatic insufficiency is quite evident in the presence of thestrongly suggested by the clinical triad of pancreatic calcification, steatorrhea and, less commonly, diabetes. These radiological tests demonstrating characteristic structural abnormalities of the pancreas, coupled with steatorrhea and or diabetes, are largelyso strongly suggestive of pancreatic insufficiency that often a clinican will not proceed to functional testing of the gland itself for diagnosis. Steatorrhea resulting from fat malabsorption has typical clinical features (foul-smelling floating stools, oil droplets). It ) and appears earlier than protein malabsorption (azotorrhea) in pancreatic exocrine insufficiency, because of the low survival of lipase. Nonetheless, development of steatorrhea and azotorrhea requires the destruction of at least 90% of the pancreas. Diabetes is less common in pancreatic diseases, since the islets are remarkably resistant to damage during the inflammatory process. However, when diabetes is present, it follows a more brittle course, since the nonbeta cells producing the counter-regulatory hormones glucagon and somatostatin are also affected. OverPancreatic function tests were initially divised for diagnosis of pancreatic dysfunction. They the years, pancreatic function tests have been devised not only as a diagnostic tool, but more frequently as research tools. These pancreatic function tests may can be divided into two main groups: direct or indirect tests requiring (duodenal intubation,) and indirectnon-invasive, indirect tests. Of the pancreatic function tests, the direct invasive tests are the gold standard. Sleisenger & Fordtrans Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management 2006; page 1197-1199; and 2010, page 928. These tests are based on the principle that as pancreatic flow increases with stimulation, there is a progressive increase in bicarbonate con- centration (> 80 mEq/L) and a corresponding decrease in chloride concentra- tion. However, the accuracy of the Lundh test is affected by small bowel mucosal disease, rate of gastric emptying and surgical interruption of the gastroduodenal anatomy. Neither test is frequently used because of their disadvantages, including the prolonged (23 hours) and unpleasant intubation, and the difficulty of accurate tube positioning. This technique allows the measurement of pure pancreatic juice secretion uncontaminated by biliary or intestinal secretion. Here, tThe patient is placed on a 100 g/day fat diet and the stool is collected daily for three days. Individuals with normal pancreatic function excrete less than 7% of the total amount of fat ingested, whereas those with pancreatic exocrine insufficiency excrete more than 20%. Only a few other conditions, such as extensive small bowel mucosal disease and short bowel syndrome, could cause such a degree of fat malabsorption, such as very extensive small bowel mucosal disease and short bowel syndrome. The major drawbacks ofto stool fat estimations are the lack of specificity and the inconvenience of collecting and analyzing the specimens. Measurements of stool nitrogen and stool chymotrypsin have not proved superior to fecal fat determinations. Attempts to screen for steatorrhea with less offensive tests (such as urine oxalate levels, C- triolein/3H-oleic acid assimilation test, and tripalmitate or palmitic acid breath tests) are promising but not generally accepted. The bentiromide test is a urinary test that directly determines pancreatic chymotrypsin secretion. Intestinal mucosal, liver and kidney diseases under- standably adversely affect the accuracy of the bentiromide test; m. The pancreolauryl test, using fluorescein dilaurate, has been extensively evaluated in Europe. However, it can detect only severe pancreatic insuffi- ciency and is therefore rarely used. Chronic pancreatitis may give rise to an abnormal Schilling test, but rarely causes clinical B12 deficiency. Vitamin B12 is initially bound to an R factor present in saliva, which stabilizes B12 in acidic gastric pH. Pancreatic enzymes release the R factor from B12 to allow B12 to bind to the intrinsic factor secreted by the stomach, which is required for B12 absorption at the terminal ileum. It is elevated during an attack of pancreatitis and in renal failure, and is decreased in severe pancreatic insufficiency, cystic fibrosis and insulin-dependent diabetes without exocrine insufficiency. The levels of trypsinogen in cystic fibrosis decrease with age if the pancreas is involved. Patients with pan- creatic insufficiency who have ongoing inflammation may have normal or raised levels. This fact, in addition to low levels in noninsulin-dependent diabetes, casts some doubt on the usefulness of this test in diagnosing pancreatic insufficiency. It may be useful in patients with steatorrhea that is due to nonpancreatic causes. Amylase is produced and released from a variety of tissues, including the salivary glands, intestine and genitourinary tract. Normal serum contains three types of isoamylases as identified by isoelectric focusing. Electrophoresis on polyacrylamide gel can separate five isoamylases on the basis of electrode mobility. Amylases originating in the fallopian tubes, tears, mucus and sweat have the same mobility as salivary amylase. All amylases have similar molecular weight and amino acid composition, but vary in terms of their glycosylation or deamination. Amylase is filtered through the glomerular membrane and is reabsorbed in the proximal tubule. During acute pancreatitis, there is an increase in amylase clearance as opposed to creatinine clearance. Although this ratio was once thought to be specific to acute pancreatitis, other conditions that produce hyperamylasemia (such as diabetic ketoacidosis, burns, renal failure and per- forated duodenal ulcer) may demonstrate a similar elevation. Occasionally, the serum amylase may be markedly increased in the absence of pancreatic or salivary diseases, whereas the urinary amylase is normal. In the latter condition normal serum amylase is bound by an immunoglobulin A (IgA), forming a complex that is too large to be filtered by the glomerulus. Affected individu- als have an elevated serum amylase and a low to normal urinary excretion rate. Frequently physicians are faced with a patient who has no overt salivary gland disease but has hyperamylasemia and no specific abdominal findings. As a rule, the level of amylase in pancreatitis usually is elevated to greater than 3 times the upper limit of normal and returns to normal within 2 to 10 days. If the amylase continues to be elevated in the absence of pancreatic complications, other causes (such as malignancy and macroamylasemia) should be investigated. A rapid rise and fall in serum amylase in a patient with abdominal pain suggests the passage of a stone through the ampulla of Vater. When the serum amylase remains elevated for several days, the gallstone disease is usually complicated by pancreatitis.

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In the feet discount starlix 120mg line, 130 cm below the heart cheap 120 mg starlix free shipping, the arterial pressure is 200 torr (see Exercise 8-4b) order starlix 120mg on line. Thus purchase 120mg starlix otc, a person may feel momentarily dizzy as he/she jumps up from a prone position. This is due to the sudden decrease in the blood pressure of the brain arteries, which results in a temporary decrease of blood ow to the brain. The same hydrostatic factors operate also in the veins, and here their eect may be more severe than in the arteries. When a person stands motionless, the blood pressure is barely adequate to force the blood from the feet back to the heart. Thus when a person sits or stands without muscular movement, blood gathers in the veins of the legs. This increases the pressure in the capillaries and may cause temporary swelling of the legs. Hormones are molecules, often proteins, that are produced by organs and tissues in dierent parts of the body. They are secreted into the blood stream and carry messages from one part of the body to another. Hormones aecting the heart are produced in response to stimuli such as need for more oxygen, changes in body tempera- ture, and various types of emotional stress. These small vessels that receive blood from the arteries have an average diameter of about 0. The walls of the arterioles contain smooth muscle bers that contract when stimulated by nerve impulses and hormones. The con- traction of the arterioles in one part of the body reduces the blood ow to that region and diverts it to another. Since the radius of the arterioles is small, con- striction is an eective method for controlling blood ow. Poiseuilles equation shows that if the pressure drop remains constant, a 20% decrease in the radius reduces the blood ow by more than a factor of 2 (see Exercise 8-5). A stress-induced heart condition called stress cardiomyopathy (broken heart syndrome) has only recently been clearly identied by Western medicine. The syndrome occurs most frequently after a sudden intense emotional trauma such as death in the family, an experience of violence, or extreme anger. The symptoms are similar to an acute heart attack, but the coronary arteries are found to be normal and the heart tissue is not damaged. It has suggested that the condition is triggered by an excessive release of stress-related hormones called chatecholamines. During the period of ow, the velocity of the blood is about three times as high as the overall average value calculated in Exercise 8-6. For example, when the total ow rate is 5 liter/min, the blood velocity in the capillaries is only about 0. The kinetic energy of the blood becomes more signicant as the rate of blood ow increases. This energy is no longer neg- ligible compared to the blood pressure measured at rest. In healthy arteries, the increased velocity of blood ow during physical activity does not present a problem. During intense activity, the blood pressure rises to compensate for the pressure drop. Assuming a Reynolds number of 2000, the critical velocity for the onset of turbulence in the 2-cm-diameter aorta is, from Eq. But as the level of physical activity increases, the ow in the aorta may exceed the critical rate and become turbulent. In the other parts of the body, however, the ow remains laminar unless the passages are abnormally constricted. Laminar ow is quiet, but turbulent ow produces noises due to vibrations of the various surrounding tissues, which indicate abnormalities in the circu- latory system. These noises, called bruit, can be detected by a stethoscope and can help in the diagnosis of circulatory disorders. In the United States, an estimated 200,000 people die annually as a consequence of this disease. In arteriosclerosis, the arterial wall becomes thickened, and the artery is narrowed by deposits called plaque. Sixty to seventy percent is considered severe, and a narrowing above 80% is deemed critical. The increased kinetic energy is at the expense of the blood pressure; that is, in order to maintain the ow rate at the higher velocity, the potential energy due to pressure is converted to kinetic energy. Because of the low pressure inside the artery, the external pressure may actually close o the artery and block the ow of blood. When such a blockage occurs in the coronary artery, which supplies blood to the heart muscle, the heart stops functioning. Stenosis above 80% is considered critical because at this point the blood ow usually becomes turbulent with inherently larger energy dissipation than is associated with laminar ow. As a result, the pressure drop in the situa- tion presented earlier is even larger than calculated using Bernoullis equation. The blood impinging on the arterial wall may dislodge some of the plaque deposit which downstream may clog a narrower part of the artery. If such clogging occurs in a cervical artery, blood ow to some part of the brain is interrupted causing an ischemic stroke. The artery has a specic elasticity; therefore, it exhibits certain springlike prop- erties. Specically, in analogy with a spring, the artery has a natural fre- quency at which it can be readily set into vibrational motion. Deposits of plaque cause an increase in the mass of the arterial wall and a decrease in its elasticity. As a result, the natural frequency of the artery is signicantly decreased, often down to a few hundred hertz. The plaque- coated artery with its lowered natural frequency may now be set into resonant vibrational motion, which may dislodge plaque deposits or cause further dam- age to the arterial wall. We will now compute the power generated by the heart to keep the blood owing in the circulatory system. Therefore, as shown in Exercise 8-10, the power output of the right ventricle is 0. While in fact the systolic blood pressure rises with increa- sed blood ow, in these calculations we have assumed that it remains at 120 torr. Both abnormally high and abnormally low blood pressures indicate some disorders in the body that require medical attention. High blood pres- sure, which may be caused by constrictions in the circulatory system, certainly implies that the heart is working harder than usual and that it may be endan- gered by the excess load. Blood pressure can be measured most directly by inserting a vertical glass tube into an artery and observing the height to which the blood rises (see Fig. This was, in fact, the way blood pressure was rst measured in 1733 by Reverend Stephen Hales, who connected a long ver- tical glass tube to an artery of a horse. Although sophisticated modications of this technique are still used in special cases, this method is obviously not satisfactory for routine clinical examinations. Routine measurements of blood pressure are now most commonly performed by the cut-o method. Although this method is not as accurate as direct measurements, it is simple and in most cases adequate. In this technique, a cu containing an inatable balloon is placed tightly around the upper arm. The balloon is inated with a bulb, and the pressure in the balloon is monitored by a pressure gauge. The initial pres- sure in the balloon is greater than the systolic pressure, and the ow of blood through the artery is therefore cut o. The observer then allows the pressure in the balloon to fall slowly by releasing some of the air. As the pressure drops, she listens with a stethoscope placed over the artery downstream from the cu. No sound is heard until the pressure in the balloon decreases to the systolic pressure. Just below this point the blood begins to ow through the artery; however, since the artery is still partially constricted, the ow is turbulent and is accompanied by a characteristic sound.

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When prescribing certain drugs purchase 120 mg starlix fast delivery, as blood levels of liver enzymes buy 120mg starlix amex, can help predict doctors must take into account these added effects proven 120mg starlix. Because they are following drug termed bioavailability trusted 120mg starlix, is a critical feature that actions in the body, researchers who specialize in chemists and pharmaceutical scientists keep in pharmacokinetics must also pay attention to an mind when designing and packaging medicines. No matter how well a drug works in a laboratory Pharmacokinetics research uses the tools of simulation, the drug is not useful if it cant make mathematics. Bernard discovered that curare causes While it may seem obvious now, scientists did not paralysis by blocking chemical signals between always know that drugs have specic molecular nerve and muscle cells. In the mid-1880s, the French that chemicals can carry messages between nerve physiologist Claude Bernard made a crucial cells and other types of cells. By guring out how a researchers have discovered many nervous system chemical called curare works, Bernard pointed messengers, now called neurotransmitters. These to the nervous system as a new focus for pharma- chemical messengers are called agonists, a generic cology. Curarea plant extract that paralyzes term pharmacologists use to indicate that a molecule muscleshad been used for centuries by Native triggers some sort of response when encountering a Americans in South America to poison the tips cell (such as muscle contraction or hormone release). Curare (half circles) paralyzes muscles by blocking acetylcholine from attaching to its muscle cell receptors. Effect Effect side effect, in the body Scientists care a lot about dose-response data (Y-axis). Dose Sometimes, it takes years to gure out exactly 1 10 100 which molecules are working together, but when Amount of Drug testing a potential medicine, researchers must X-axis rst show that three things are true in an experi ment. Second, adding more of the plot data from dose-response experiments on a drug (up to a certain point) causes an incremental graph. A typical dose-response curve demon change in effect (lower blood pressure with more strates the effects of what happens (the vertical drug). Third, taking the drug away (or masking Y-axis) when more and more drug is added to its action with a molecule that blocks the drug) the experiment (the horizontal X-axis). One of the rst neurotransmitters identied in a communication between the outside of the was acetylcholine, which causes muscle contrac cell and the inside, which contains all the mini- tion. Because receptors but nevertheless ttinginto receiving molecules have a critical role in controlling the activity of cells, called receptors on a muscle cell, curare prevents they are common targets for researchers designing acetylcholine from attaching and delivering its new medicines. No acetylcholine means no contraction, Curare is one example of a molecule called and muscles become paralyzed. Drugs that act as antagonists Most medicines exert their effects by making compete with natural agonists for receptors but physical contact with receptors on the surface of act only as decoys, freezing up the receptor and a cell. Inserting a key into want to block cell responses, such as a rise in a door lock permits the doorknob to be turned blood pressure or an increase in heart rate. Agonists open that reason, many drugs are antagonists, designed cellular locks (receptors), and this is the rst step to blunt overactive cellular responses. Researchers who study how developing drugs that attach only to receptors drugs and other chemicals exert their effects in on the target cells. While kidneys, and so onare very interested in the agonists may t nearly perfectly into a receptors shapes of molecules. Some drugs have very broad shape, other molecules may also brush up to effects because they t into receptors on many receptors and sometimes set them off. Some side effects, such as types of unintended, nonspecic interactions dry mouth or a drop in blood pressure, can result can cause side effects. They can also affect how from a drug encountering receptors in places other much drug is available in the body. Various just a chemical name for any substance that has steroids have important roles in the bodys repro a characteristic chemical structure consisting of ductive system and the structure and function of multiple rings of connected atoms. Researchers have also discovered that steroids can be active in the brain, where they affect the nervous system. R multiple rings (hexagons Douglas Covey of Washington University in and pentagon, below). Louis, Missouri, has uncovered new roles for several of these neurosteroids, which alter electrical activity in the brain. The main job of this neurotransmitter is to dampen electrical activity throughout the brain. Covey is also investigating the potential of neuroprotective steroids in preventing the nerve-wasting effects of certain neurodegenerative disorders. Usually, this Clinical Pharmacology important analysis involves mathematical equa Prescribing drugs is a tricky science, requiring tions, which take into account many different physicians to carefully consider many factors. Some of the variables include the physi Your doctor can measure or otherwise determine cal and chemical properties of the drug, the total many of these factors, such as weight and diet. You uals age and body mass, the health of the persons already know that every time you go to the doctor, liver and kidneys, and what other medicines the he or she will ask whether you are taking any other person is taking. Clinical pharmacologists also drugs and whether you have any drug allergies or measure drug metabolites to gauge how much unusual reactions to any medicines. Sometimes, doctors Interactions between different drugs in the give patients a loading dose (a large amount) body, and between drugs and foods or dietary rst, followed by smaller doses at later times. This supplements, can have a signicant inuence, approach works by getting enough drug into the sometimes fooling your body into thinking body before it is metabolized (broken down) into you have taken more or less of a drug than you inactive parts, giving the drug the best chance to actually have taken. By measuring the amounts of a drug in blood or urine, clinical pharmacologists can calculate Natures Drugs Feverfew for migraines, garlic for heart disease, small studies have St. These are just a conrmed the useful few of the many natural substances ingested by ness of certain herbs, millions of Americans to treat a variety of health like feverfew, other conditions. The use of so-called alternative medi herbal products have cines is widespread, but you may be surprised to proved ineffective or learn that researchers do not know in most cases harmful. For example, how herbs workor if they work at allinside recent studies suggest the human body. Johns wort is of no benet in treating Herbs are not regulated by the Food and Drug major depression. Whats more, because herbs are Administration, and scientists have not performed complicated concoctions containing many active careful studies to evaluate their safety and effec components, they can interfere with the bodys tiveness. While some 14 National Institute of General Medical Sciences Pump It Up Bacteria have an uncanny ability to defend the bacteria themselves. The pumps are used One reason, says Kim Lewis of Northeastern to monitor incoming chemicals and to spit out University in Boston, Massachusetts, may be the ones that might endanger the bacteria. Many body molecules and drugs (yellow balls) encounter multidrug-resistance pumps (blue) after passing through a cell membrane. These machine, or set of machines, powered by a control early studies led to descriptions of the circulatory, system called metabolism. The conversion of food digestive, respiratory, nervous, and excretory into energy integrates chemical reactions taking systems. In time, scientists came to think of the place simultaneously throughout the body to body as a kind of machine that uses a series of assure that each organ has enough nutrients and chemical reactions to convert food into energy. An important prin ciple central to metabolism is that the bodys basic unit is the cell. In turn, each cell contains tiny organs, called organelles, that perform specic metabolic tasks. Discovery By Accident The work of a scientist is often likened to locking together the pieces of a jigsaw puzzle. Slowly and methodically, one by one, the pieces t together to make a pretty picture. The truth is, scientists dont have a puzzle box to know what the nished picture is supposed to look like. If you know the result of an experiment ahead of time, its not really an experiment. Being a scientist is hard work, but most researchers love the freedom to explore their curiosities. They test ideas methodically, nding answers to new problems, and every day brings a new challenge. Medicines By Design I Body, Heal Thyself 17 The cell is directed by a command center, the One important type of metabolism that occurs nucleus, where the genes you inherited from your constantly in our bodies is the reading and inter parents reside. These proteins personalized instruction manualare kept safe underlie the millions of chemical reactions that in packages called chromosomes. Proteins perform structural roles, cells has an identical set of 46 chromosomes, keeping cells shaped properly.

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Miscellaneous skin Skin biopsy for histopathology (to conrm subepi- dermal blister/bulla) buy generic starlix 120 mg. Circulating IgG against antigen in the basement Skin pigmentation membrane is detectable in the serum of approxi- mately two-thirds of patients with bullous Abnormalities of skin pigmentation are seen in a var- pemphigoid order starlix 120 mg on-line. Long-term low dose maintenance therapy is often then disappear spontaneously in a matter of hours order 120 mg starlix with mastercard. Often itching is the rst symptom order 120mg starlix otc, followed shortly afterwards by the Dermatitis herpetiformis development of pink weals over a variable-sized area, e. A chronic relapsing erythematous papules and vesicles, which are com- form, in which attacks last for weeks, months or mon on the elbows and other extensor surfaces. Blisters/bullae may be burst by scratching, with If possible, triggers should be identied and marked excoriation. Most types of T a b le 1 S kin tum ur T um ur idem i l gy/ clin ica lfea tur es T ea tm en t B S eborrh oeic k eratoses ( basal cel l om m on especial l yin th e el derl y I frequired, treatm en toption sran gefrom cryoth erapy papil l om as; seborrh oeic w arts) S ol itaryorm ul tipl e forsm al l erl esion stocurettage an d surgical excision. R aised, at- topped l esion s, ran gin g in col ourfrom l igh t brow to deepl ypigm en ted. R ou d w ith raised edges an d ch aracteristic cen tral sh oul d becon sidered for al l l esion sth atcan otbe k eratin pl ug redden ed/ in am ed base rel iabl ydifferen tiated cl in ical l yfrom a squam ouscel l. S l igh tl yraised, sk in - col oured orpigm en ted P yogen ic gran ul om a ( ben ign ol ypoidal l esion w h ich m aybl eed profusel yfol l ow in g urettage orsurgical excision w ith h istol ogical prol iferation ofbl ood vessel s/ m in ortraum a exam in ation brobl asts) D A ctin ic ( sol ar eratoses reasofdyspl astic squam ousepith el ium, w h ich typical l y opical appl ication of5 - uorouracil, im iquim od ora ( P l ate 1 devel op in U V radiation exposed areas( e. V aried appearan ce: ul cer eratotic n odul e, rapidl y expan din g pol ypoidal m ass L en tigo m al ign a ( utch in son s atch ofm al ign an tm el an ocytesth ath aven otyetbecom e iopsyto con rm diagn osis fol l ow ed bysurgical m al ign an tfreck l e ) l ate 1 in vasive excision. Congenital: albinism, phenylketonuria These generally fall into one or more of three Hyperpigmentation categories:. Angioedema/anaphyl- body (alopecia universalis)) and trichotillomania axis are medical emergencies (p. Excessive hair growth and development of hair in of the wrist and forearms, lower back, mouth and abnormal sites hirsutism describes male-pattern genitalia. The papules a virilising tumour; hypertrichosis is excessive hair may be widespread or conned to one or two sites. Thecauseisunknown,butseveraldrugs Nail abnormalities can produce an identical eruption, e. The epidermis Nail disorders may occur in isolation or may be a sign is inltrated with T cells. An increase (reticulocytosis) suggests conrmed on the basis of laboratory ndings. The serum cell membrane) renal failure, carcinoma transferrinisnormalorlowbut,unlikeirondeciency,. HowellJolly bodies (remnants of nuclear material) tion may show malignant disease (leukaemia, myclo- splenectomy (or non-functioning spleen) ma, metastasis) or myelobrosis. Reticulocytes are pre- factor, anti-nuclear antibodies and if positive spe- mature red cells in which traces of nucleoprotein cic tests for antibodies against nuclear antigens remain as ne, reticular strands. Erythropoietin can alsoreverseanaemiaassociatedwithcancer,although concerns have been raised that erythropoietin may contribute to tumour progression. Pernicious anaemia is now usually diagnosed by nd- Iron deciency is caused by poor intake, poor ing low serum vitamin B12 with parietal cell and absorption, poor iron use by the marrow or intrinsic factor antibodies, rather than with the Haematology 323 Schilling test (B12absorptionbefore and after intrinsic stick together. Check the haemoglobin, and reticulocyte re- indicator of inammation or infection. The serum iron is characteristically reduced, and so is the transferrin (iron-binding capacity), unlike the Anaemia ndings in iron-deciency anaemia. The marrow iron stores are increased, but the iron is not incorporated There are three major types of anaemia, classied by fully into red cell precursors. The symptoms are tiredness, physical fatigue and dyspnoea, with angina, heart failure and confusion in older people. Pancytopenia Anaemia can be caused by a deciency in: Thisis ararecombinationofanaemia,leucopeniaand. Slow gas- trointestinal loss is a common cause, with peptic ulceration, gastric carcinoma and carcinoma of the descending colon most common. Carcinoma of the Marrow suppression ascending colon or caecum frequently produces no symptoms and its presence must be considered in Secondary bone marrow failure may affect one or all all cases of iron-deciency anaemia. In the elderly, of the formed elements of the blood red cells, dietary deciencies remain an important cause, and white cells or platelets. This includes assessment of pallor (very imprecise), glossitis, angular stomatitis, koilonychia and rectal examination. Investigate the gastrointestinal tract if Erythrocyte sedimentation no other cause is identied. A signicant difference between one phages but reduced amounts in developing erythro- blasts. See if the cells are normal (normocytic), Management small (microcytic) or large (macrocytic) In the absence of active bleeding, ferrous sulphate 200mg b. Transferrin 23g/l (iron-binding Raised in iron deciency (and Hazards of blood transfusion plasma protein) pregnancy) Reduced in anaemia of. Transfusion reaction minimise risk by cross- chronic disease, acute matching patients serum with donor blood. It is associated with other organ-specic and the transferrin raised, with a low saturation. Serum ferritin re- tiply using up B12), a vegan diet, Crohns disease ects the state of the iron stores and is therefore low. Exhaustion fall because of reduced numbers of both lymphocytes and lethargy are the most common presenting com- and neutrophils (Table 20. Some neutrophils may plaints, although pallor may be noticed incidentally, show hypersegmentation of the nuclei (>5lobes). The tongue may be tender, locytes and megaloblasts present evidence that an- smooth and red because of atrophy of the mucosa. Later, features of subacute combined degen- inactive nucleus (maturation arrest) in a relatively eration of the cord may develop. There is an increased incidence presence denotes vitamin B12 or folate deciency, of gastric carcinoma. Vasculitis and drug hypersensitivity Causes of lymphopenia (low lymphocyte count). Parasitic infestation of gut or other tissues (muscles, subcutaneous tissues, liver, urinary tract). Uro- bilinogen is present in the urine as a result of reduced red cell survival and ineffective erythropoiesis. Anti- bodiestoparietalcellsarepresentin>90%ofpatients and to intrinsic factor in approximately 55%. Patients with pernicious anaemia treated with vitamin B12usually have normal peripheral blood and a normal marrow within 24h. Treatment Vitamin B12 as hydroxocobalamin 1mg is given ve times at 2-day intervals and then every 3 months for life. The response of the marrow to therapy is very rapid with an early reticulocyte response maximal on the fourth to sixth day. The rapid pro- duction of cells with therapy may reveal an associated deciencyof,and demandfor,iron,potassiumor folic acid and supplements should be given where necessary. Neurological features of B12 deciency usually im- prove to some degree; sensory abnormalities more completely than motor, and peripheral neuropathy morethanmyelopathy. Blood transfusion contains enough B12 to correct the marrow and to make interpretation of serum B12 levels difcult. It may precipitate heart failure and deathsomeauthoritiesbelievethattransfusionmust never be given to patients with pernicious anaemia. In the tropics it is often seen in association with multiple deciencies and with gut infection and infestation. If sufciently severe, vitamin B12 and folate Haemolysis results in increased red cell formation, deciencies produce depression of all the marrow which requires folate more than B12. Phenytoin therapy interferes isusuallysomehaemolysiswitharaisedunconjugated with folate metabolism. Haematology 327 Hereditary haemolytic anaemias Haemolytic anaemia These are caused by defects in the red cell membrane or specic red cell enzyme deciencies. Haemolysis Hereditary spherocytosis is characterised by jaundice with a raised unconjugat- ed serum bilirubin, increased urobilinogen in urine An autosomal dominant disorder that causes in- and stools, increased haptoglobins and reticulocyto- creased osmotic fragility and produces spherocytes sis. There is no bile pigment in intermittent jaundice, which may be confused with the urine (the jaundice is acholuric).

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