Acute episodes are often triggered by infection antibiotics for prevention of uti discount ampicillin 500mg online, pregnancy infection specialist order genuine ampicillin on-line, medications virus - zippy generic ampicillin 500mg line, or other endothelial injury bacteria photos cheap ampicillin on line. These small vessel thrombi result in microangiopathy and organ dysfunction due to ischemia ear infection 1 year old purchase ampicillin master card. In contrast to disseminated intravascular coagulation (discussed below) treatment for dogs eating chocolate purchase ampicillin paypal, there is no consumption of clotting factors chest infection discount 500mg ampicillin visa, and coagulation assays are usually normal antibiotic resistance in bacteria is an example of which of the following generic ampicillin 250mg with visa. This syndrome is classically associated with a prodrome of bloody diarrhea resulting from infection with enterohemorrhagic bacteria expressing Shiga-like toxin. Exposure to Shiga-like toxin appears to trigger endothelial injury, which has a predilection for the renal vasculature. Idiopathic forms of this disease (not associated with a diarrhea prodrome) also occur, frequently associated with mutations in certain complement regulatory proteins. Acquired Defects in Platelet Function Uremia: results in defective platelet function. Thrombocytosis: Causes Reactive usually associated with chronic underlying inflammation. Vitamin K deficiency Vitamin K is a lipid-soluble substance that is present in many foods (particularly green leafy vegetables), and synthesized by intestinal bacteria. Antagonism of vitamin K dependent post-translational modification of these factors is the mechanism for the antithrombotic effect of warfarin (see Chapter 11, part 2). Conditions associated with vitamin K deficiency include antibiotic therapy, nutritional deficiency, biliary obstruction (bile salts are necessary for proper absorption of the vitamin), malabsorption syndromes, and ingestion of warfarin or related compounds. Oral or parenteral vitamin K begins to replete coagulation factors within 12-24 hours, but 2-3 days are required for maximal effects. This is a consequence of poor transport of vitamin K by the placenta and lack of colonization of the newborn gut by bacteria. Bleeding in patients with liver disease represents a difficult therapeutic problem. Local sites of bleeding, including gastritis and esophageal varices may require specific treatment. In contrast to the normal localized coagulation response, thrombin and/or plasmin activity is present in the systemic circulation, and generation of fibrin and platelet activation occur in a disorganized manner. The consequences of this excessive, systemic generation of thrombin and plasmin include consumption of coagulation factors and platelets, depletion of inhibitors, bleeding, deposition of fibrin in small vessels with resulting microangiopathy, and varying degrees of organ dysfunction. Acquired coagulation inhibitors these are usually circulating immunoglobulins of the IgG class. These inhibitors can be alloantibodies that arise in the context of factor replacement therapy for patients with hemophilia, or autoantibodies that arise spontaneously without a pre-existing coagulation defect, usually in elderly patients. These inhibitors are most common in severe hemophiliacs, presumably because these patients are more likely to recognize the replaced factor as a foreign antigen. In hemophilia A or B, these inhibitors neutralize the clotting factor given to treat the disease, and can result in life threatening bleeding. Patients with spontaneous inhibitors are usually given immunosuppressive treatment as well. Increased transmural pressure can be either an acute (valsalva with coughing, vomiting), or chronic (venous stasis) etiology. Decreased mechanical strength of the microcirculation can result from an inherited (Ehlers Danlos syndrome) or acquired connective tissue or vessel defects (scurvy, infiltration by amyloid, glucocorticoids, aging). Endothelial damage may result from infection (Rickettsial, viral), trauma including factitious purpura (usually involving a suction devices applied to the skin), embolism (cholesterol, fat), and allergy or inflammation (serum sickness, vasculitis). List and compare the major clinical risk factors for arterial and venous thrombosis. Compare and contrast the approach to treatment for a patient with arterial thrombosis to a patient with venous thrombosis. List five hereditary disorders that increase the risk of venous thrombosis, and briefly describe how the genetic defect in each condition increases the risk of thrombosis. Describe the most important laboratory findings and clinical features associated with antiphospholipid syndrome. Describe the indications, mechanism of action, major complications, and suggested laboratory monitoring of therapy with unfractionated heparin and low molecular weight heparin. Definitions/Descriptions Thrombosis a term that describes the pathologic process in which intra-luminal (or intra-cardiac) thrombus interrupts the arterial supply or venous drainage of a limb or organ system. Thrombosis occurs through the same biochemical pathways as coagulation and platelet activation/aggregation, suggesting defective regulation of the response. Arterial thrombi are typically platelet rich (white clot), formed under conditions of high shear stress (rapid flow) with underlying endothelial abnormalities. Examples include myocardial infarction, thrombotic (occlusive) stroke, and mesenteric ischemia. Arterial thrombi can form emboli, portions of the clot that break off and travel into the distal circulation. The most common example is embolic stroke from an intracardiac thrombus caused by atrial fibrillation, valvular disease, or severe left ventricular dysfunction. Most commonly, venous thrombosis involves the deep venous system in the lower extremities or pelvis. Thrombus formation is generally cyclic, with layers enriched for fibrin and red blood cells. Pathophysiology of Arterial Thromboembolism Development of arterial thrombosis is closely linked to atherosclerotic vessel disease, making it difficult to discern risk factors for arterial thrombosis separately from factors that predispose to the underlying vessel disease. Underlying atherosclerosis is associated with increased age, smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus, family history of heart disease, and sedentary life style. The precise mechanisms by which the inflammatory and coagulation responses interact are active areas of investigation. Clinical presentation depends on the specific vascular bed involved and the acute vs. Formation of thrombus on an underlying atherosclerotic plaque is often the final event in clinical presentations such as myocardial infarction. Specific clinical syndromes are covered in your cardiovascular and neuroscience courses. Since the etiology is multigenic, we consider inheritance of defective alleles as genetic risk factors for development of thrombosis, not disease states per se. Clinical risk factors may be transient (pregnancy) and/or reversible (estrogen therapy), or represent chronic, ongoing conditions (age, obesity, malignancy). Endothelial/vessel injury o trauma o surgery/general anesthesia (especially hip and knee fracture/replacement) o pregnancy (especially post-partum) o smoking 3. These antibodies may be directed against a variety of epitopes, including cardiolipin and 2-glycoprotein I. The detection of these antibodies is common enough in the general population that their pathologic significance is unclear, unless present in high titers, in association with other autoantibodies, or in patients with other evidence of the antiphospholipid antibody syndrome. In contrast, heparin rarely causes a moderate to severe (greater than 50% reduction), late onset (5-7 days) thrombocytopenia due to development of a heparin-dependent antibody. The marked platelet activation results in moderate thrombocytopenia (due to consumption) and may trigger fulminant arterial and/or venous thrombosis. Myeloproliferative/bone marrow disorders (see chapter 8) Polycythemia vera is associated with increased incidence of venous thrombosis. Venous thrombosis and microvascular arterial events are most common, including digital ischemia. Must be differentiated from reactive thrombocytosis, which generally poses little to no risk. Each of these risk factors has a modest individual contribution to the overall risk of venous thromboembolism. Thus, even in patients with underlying genetic predisposition, thrombotic events are generally triggered by addition of one or more acquired factors (surgery, pregnancy, immobility). The relative risk for venous thrombosis compared to the general population is increased up to 20 fold in some families with hereditary antithrombin, protein C, or protein S deficiency. The relative risk in individuals with factor V Leiden or prothrombin mutation is increased ~2-5 fold. The homozygous state (complete absence of antithrombin in the blood) has never been described and is probably not compatible with life. Protein C deficiency more common (1/350 blood donors), autosomal dominant condition in which protein C activity is about 50% of normal. The homozygous state (complete or near-complete absence of protein C) results in a severe thrombotic disorder beginning in infancy (neonatal purpura fulminans). Protein S deficiency rare autosomal dominant condition, no good estimates of prevalence. The Factor V Leiden polymorphism is the most common (5% of Caucasian population) autosomal dominant condition that is associated with a 4-5 fold increase in the relative risk of venous thromboembolism. Homozygotes have substantially higher risk than heterozygotes (perhaps 50 times higher than general population). Unlike antithrombin, protein C and protein S deficiencies, which are associated with many different mutations, the molecular defect in factor V Leiden is a single base change in the factor V gene that eliminates a protein C cleavage site in factor Va, resulting in activated protein C resistance and defective termination of coagulation by activated protein C. Prothrombin G20210A polymorphism is a relatively common (2% of the general population), autosomal dominant condition that is associated with 15-30% higher levels of prothrombin antigen in the plasma. Severe elevations result from homozygous cystathionine synthetase deficiency (homocystinuria, a rare congenital disease). Mild elevations are much more common, and may result from other inherited or acquired defects in homocysteine metabolism. The mechanism is unclear, but may involve induction of endothelial procoagulant activity by homocysteine and related compounds. Lowering homocysteine levels (for example, by administration of folate and B12) has not lowered thrombotic risk, at least in the short term, in several clinical trials. Major complications include the post-phlebitic syndrome (chronic, sometimes disabling, leg swelling and pain due to venous stasis) and sudden 273 death from pulmonary embolism. Anticoagulant therapy given to prevent recurrent venous thromboembolism has significant clinical benefits, but is also associated with an increased risk of bleeding complications. The risk of recurrent venous thromboembolic disease varies significantly depending on the clinical and genetic risk factors present in a particular patient. Clinical risk factors may be transient or reversible (surgery, estrogens), or alternatively represent chronic conditions (congestive heart failure, venous insufficiency). The heterogeneity in thrombotic risk among families with single gene defects, and the lack of established risk factors in the majority of thrombophilic patients, suggests that additional unknown genetic factors are involved in the development of thrombosis in many cases. The ability to select patients with a high likelihood of recurrent venous thromboembolism for long-term anticoagulation would greatly improve the risk: benefit ratio of therapy. The multigenic etiology of venous thromboembolism and our incomplete knowledge of the risk-associated alleles significantly limit the ability to perform global genetic risk assessment. Thus, laboratory evaluation of hypercoagulable states does not contribute to the clinical management of most patients. Such testing may be helpful in selected patients presenting at a young age, and/or with a significant family history. The signs and symptoms of venous thromboembolism are sufficiently non-specific that objective testing to demonstrate the presence of thrombi is critical. Overview of therapeutic indications for Antithrombotic therapy See part 2 of this chapter for discussion of individual drugs. Oral thrombin and Xa inhibitors, discussed in chapter 11, are potential alternatives to warfarin. Often treated for 6-12 months, but optimal duration of therapy remains unclear and some patients may benefit from long-term anticoagulation. Used to prevent pulmonary embolism in patients with strong contraindications to anticoagulation, or for patients who have recurrent events while on therapeutic anticoagulation. Prophylaxis of Venous Thromboembolism Many hospitalized patients are at risk for venous thromboembolism. The most effective form of prophylaxis is anticoagulation, but the benefits of anticoagulant prophylaxis must be weighed against the risk of bleeding associated with such treatment. Mechanical methods are somewhat less effective than pharmacologic prophylaxis, but may be preferred in patients at high risk for bleeding. Anticoagulation for Atrial Fibrillation Chronic atrial fibrillation is associated with a significantly increased risk of thromboembolic stroke. Antiplatelet Agents for primary and secondary prevention of cardiovascular events 1. This imposes upon the medical garding the degree of disability such examiner the responsibility of fur doubt will be resolved in favor of the nishing, in addition to the etiological, claimant. Every element fortable at home or upon limited activ in any way affecting the probative ity. Both the use of ability, this disability shall be ratable manifestations not resulting from serv at 60 percent or more, and that, if there ice-connected disease or injury in es are two or more disabilities, there shall tablishing the service-connected eval be at least one disability ratable at 40 uation, and the evaluation of the same percent or more, and sufficient addi manifestation under different diag tional disability to bring the combined noses are to be avoided. Total disability will regarded where the percentages re be considered to exist when there is ferred to in this paragraph for the serv present any impairment of mind or ice-connected disability or disabilities body which is sufficient to render it are met and in the judgment of the rat impossible for the average person to ing agency such service-connected dis abilities render the veteran unemploy follow a substantially gainful occupa able. Marginal employment may both eyes, or becoming permanently also be held to exist, on a facts found helpless or permanently bedridden. In making such determinations, currence, or the date the condition the following guidelines will be used: reached the stabilized level, is a gen (a) Marginal employment, for exam eral requirement in order to establish ple, as a self-employed farmer or other the fact that present unemployability person, while employed in his or her is the result of the disability. The resulting dif advancing age or intercurrent dis ference will be recorded on the rating ability, may not be used as a basis for sheet. Fair ratings for conditions of doubtful diag ness and courtesy must at all times be nosis, or for those not fully supported shown to applicants by all employees by clinical and laboratory findings. Findings suffi ity or application to individual cases ciently characteristic to identify the involving unusual difficulties, will be disease and the disability therefrom, addressed to the Director, Compensa and above all, coordination of rating tion and Pension Service. Claims in regard to which the converted to the nearest degree divis schedule evaluations are considered in ible by 10, which is 50 percent. Thus, a are only three disabilities will be con person having a 60 percent disability is verted to the nearest degree divisible considered 40 percent efficient. Thus, ceeding from this 40 percent efficiency, if there are three disabilities ratable at the effect of a further 30 percent dis 60 percent, 40 percent, and 20 percent, ability is to leave only 70 percent of respectively, the combined value for the efficiency remaining after consid the first two will be found opposite 60 eration of the first disability, or 28 per and under 40 and is 76 percent. The indi will be combined with 20 and the com vidual is thus 72 percent disabled, as bined value for the three is 81 percent. Thus, with a 50 per cedure in determining the combined cent disability and a 30 percent dis degree of disability. This procedure will facilitate a the bilateral factor applies, and simi close check of new and unlisted condi larly whenever there are compensable tions, rated by analogy. Prestabilization ratings are for assign effective the first day of such author ment in the immediate postdischarge period. In each of hospital discharge effective the prestabilization rating an examination will ninth day of authorized absence. If service con release to non-bed care) or outpatient nection for the disability under treat release that entitlement is warranted ment is granted after hospital admis under paragraph (a) (1), (2) or (3) of this sion, the rating will be from the first section effective the date of hospital day of hospitalization if otherwise in admission or outpatient treatment and order. Particular at prior to the termination of a total rat tention, with a view to proper rating ing under this section. When complete ex the examination on which ratings are aminations are not conducted covering based adequately portray the anatom all systems of the body affected by dis ical damage, and the functional loss, ease or injury, it is impossible to vis with respect to all these elements. Insta should be considered as a continuously bility of station, disturbance of loco disabling process, whether or not an motion, interference with sitting, actively discharging sinus or other ob standing and weight-bearing are re vious evidence of infection is manifest lated considerations. For the purpose from time to time, and unless the focus of rating disability from arthritis, the is entirely removed by amputation will shoulder, elbow, wrist, hip, knee, and entitle to a permanent rating to be ankle are considered major joints; mul combined with other ratings for resid tiple involvements of the interphalan ual conditions, however, not exceeding geal, metacarpal and carpal joints of amputation ratings at the site of elec the upper extremities, the interphalan tion. Muscle atrophy must also be ac related to strain on the neighboring curately measured and reported. Simple wound of muscle with (2) In the case of an ankylosed shoul out debridement or infection. Service de long bones, scapula, pelvic bones, sac partment record or other evidence rum or vertebrae, with epithelial seal showing hospitalization for a prolonged ing over the bone rather than true skin period for treatment of wound. Record covering in an area where bone is nor of consistent complaint of cardinal mally protected by muscle. Indications on palpation of loss the trapezius and serratus in wounds of of deep fascia, muscle substance, or the shoulder girdle. Tests of tire muscle following simple piercing strength and endurance compared with by a projectile. Record quired condition, it is to be remem of consistent complaint of cardinal bered that depression of the longitu signs and symptoms of muscle dis dinal arch, or the degree of depression, ability as defined in paragraph (c) of is not the essential feature. The atten this section, worse than those shown tion should be given to anatomical for moderately severe muscle injuries, changes, as compared to normal, in the and, if present, evidence of inability to relationship of the foot and leg, par keep up with work requirements. Ragged, de superior portion of the os calcis, me pressed and adherent scars indicating dial deviation of the insertion of the wide damage to muscle groups in mis Achilles tendon, the medial tilting of sile track.
Iron tablets may resemble candy (M&Ms) virus upper respiratory discount ampicillin 250mg fast delivery, and as few as three tablets could cause major toxicity 90 bacteria 10 human order ampicillin in india. The gastrointestinal mucosa undergoes necrosis antibiotics for uti cause diarrhea 500 mg ampicillin with mastercard, leading to nausea virus with diarrhea discount ampicillin 500mg line, vomiting antimicrobial essential oil recipe order 500 mg ampicillin mastercard, and bloody diarrhea antibiotic guideline malaysia generic ampicillin 500mg on-line. Summary Iron is essential to life but paradoxically cannot be free in the body because of its toxicity antibiotic resistance spread vertically by buy ampicillin 500mg. Elegant methods are employed by the body to conserve iron and to shield it within transport and storage proteins z pack antibiotics for sinus infection order ampicillin canada. It is common in young children and in women in the child-bearing years as a result of an imbalance between supply and demand, whereas in older women and men it is commonly a result of gastrointestinal losses, of which cancer is the greatest concern. Describe, and be able to recognize under the microscope, the morphologic findings in the blood and bone marrow in megaloblastic anemia. Describe the pathophysiology and the clinical and laboratory features of vitamin B12 and folate deficiency, including the important similarities and differences between them. Red cell precursors with this abnormality are called megaloblasts rather than normoblasts. Circulating red cells in megaloblastic anemia are typically larger than normal and are therefore called macrocytes. Definitions Macrocytic anemia is a subset of anemia in which the non-nucleated erythrocytes are larger than 100 femtoliters (fl). It is found in association with liver disease, alcoholism, hypothyroidism, and several forms of marrow damage as well as in B12 and folic acid deficiency. Macrocytes are red cells released before they have divided enough times to be normal-sized. For example, because reticulocytes are considerably larger than mature red cells (some young ones may be 150 fl), hemolytic anemia with a high reticulocyte count may be macrocytic on that basis alone. Megaloblastosis is the visible change in nucleated cells that results from a lag in nuclear maturation relative to cytoplasmic maturation. Folic acid deficiency is probably the most common cause of megaloblastic anemia in the general population, but cobalamin deficiency may be a more common cause in parts of the world where intake of animal protein, the dietary source of vitamin B12, is low. Megaloblastic anemia due to vitamin deficiency is a manifestation of advanced deficiency. In a referral hospital with a large proportion of cancer patients, however, the most common cause of megaloblastic change is cancer chemotherapy. Marked macrocytosis and hypersegmentation of neutrophils occur in patients treated with hydroxyurea. In normal people, most neutrophils will have two, three or four lobes, and fewer than five percent will have five lobes. The peripheral blood expressions of megaloblastosis (macrocytosis and neutrophil hypersegmentation) may occur with minimal anemia. Deficiency of Folate or Vitamin B12 Vitamin deficiency is almost invariably the result of one or more of the following five processes: Inadequate intake of folic acid is common among alcoholics and institutionalized patients. Strict vegetarians ingest very little vitamin B12 and should take a vitamin pill containing B12. Other highly restricted diets lacking in meat and fresh vegetables may produce folic acid deficiency. Drugs may prevent removal of glutamic acid residues on folic acid and thereby impair its absorption. Pregnancy and hemolysis increase the need for folate by accelerating its rate of use and are also extremely rare causes of vitamin B12 deficiency. Nitrous oxide inactivates some of the cobalamin, and may be hazardous in subjects with marginal stores. Two centuries ago, a Scottish naval surgeon, James Lind, proved that fresh lemons and limes cured and prevented scurvy among sailors, but the next clear proof of a specific disease due to a specific nutritional deficiency was not recognized until the early 20th century, when thiamine deficiency was shown to cause beriberi among rice-eating peoples of Southeast Asia. Pernicious anemia was well described morphologically and clinically for at least half a century before it was shown to be caused by a nutritional deficiency, although the distinguished American physician, Austin Flint, wrote in 1860 that the disorder was probably due to a failure to assimilate some necessary nutrient from the diet. Flint also proposed to accept the credit for his idea as soon as someone could do the work necessary to prove its validity! Unfortunately, he did not live long enough to see the proof offered by Minot and Murphy in 1926. Their work was intended to determine the most efficacious diet for the regeneration of blood, and they found, of course, that refeeding the blood to the dog was most efficacious. George Minot, an investigative physician in Boston, knew of the work of Whipple and Robscheit-Robbins and was of the opinion that pernicious anemia might be a special kind of nutritional deficiency. Thus, it had been established as early as 1926 that some substance in liver was curative for patients with pernicious anemia. The injection of liver extract every two to four weeks prevented death and neurologic disease, and corrected anemia in patients with pernicious anemia. For several decades before the therapeutic triumph of Minot and Murphy, it was known that patients with pernicious anemia had severe atrophy of the gastric mucosa. Also, their gastric juices were known to be scanty and lacking in acid and peptic activity. William Castle postulated that the gastric pathology might be playing a causal role in pernicious anemia, and he proved his postulate with brilliantly conceived and controlled therapeutic trials. During the next ten days, however, he fed the patient the same quantity of hamburger with normal human gastric juice, and generated an impressive reticulocyte response, increase in hemoglobin and sense of well-being. We now know that the function of gastric "intrinsic factor-a phrase coined by Castle-is to bind dietary B12 (found in the hamburger in this experiment) and facilitate its absorption in the ileum. The identification of the anti-pernicious-anemia principle in liver had to wait until 1948. In that year, scientists at American and British pharmaceutical firms simultaneously and independently reported the isolation and crystallization of vitamin B12. Each of these groups had demonstrated that the crystallized vitamin was extremely effective in the treatment of pernicious anemia. The first reports showed that, on one occasion, the injection of as little as ten micrograms of vitamin B12 led to a significant hematologic improvement. It was soon demonstrated that the red vitamin (so named because of its deep red color) contained cobalt bound into a tetrapyrrole ring, somewhat analogous to the iron in heme. A second Nobel prize related to vitamin B12 was awarded to Dorothy Hodgkin for her X-ray crystallographic studies demonstrating the exact structure of the vitamin (molecular weight 1,350 daltons), as diagrammed in Figure 3. Commercial vitamin B12 is derived from microbial synthesis, an efficient and inexpensive process compared to chemical synthesis; a quantity sufficient to treat a pernicious anemia patient for a whole year costs no more than a few dollars. Physiology the typical daily Western diet contains five to thirty micrograms (g) of vitamin B12 in animal, bird and fish products, of which the liver and kidney are especially rich sources. Their function in the gut is unknown but it has been speculated that they help dispose of inactive cobalamin analogues. In the absence of intrinsic factor, only one to two percent of B12 is absorbed, but with intrinsic factor, 60-90% of a test dose of aqueous B12 will be absorbed. It is likely that megaloblastic anemia and neurologic disease due to vitamin B12 deficiency occur after body stores of the vitamin have decreased to less than 20% of normal. Biochemistry Cyanocobalamin, a stable form of vitamin B12 was the first cobalt-containing organic compound shown to have a biologic role. Students of animal husbandry knew that cobalt was an essential nutrient for sheep. After isolation, crystallization and partial characterization of cyanocobalamin from liver in 1948, the role of cobalt in the maintenance of life of all animals and many bacteria began to emerge. In mammals, only two reactions clearly requiring vitamin B12 have been identified. The reversible conversion of methylmalonyl CoA to succinyl CoA is catalyzed by methylmalonyl CoA mutase, which requires adenosylcobalamin as a cofactor. Deficient activity of methylmalonyl CoA mutase is thought by some investigators to be the cause of the neurologic disease in B12 deficiency. The methylation of homocysteine to form methionine requires enzyme-bound 5 methylcobalamin and N -methyltetrahydrofolate as a methyl donor. Methionine provides a methyl group for modification of myelin basic protein; a deficiency of methionine is believed by some to decrease synthesis of myelin, leading to demyelination of the posterior and lateral columns of the spinal cord. However, since homocysteine accumulation in serum is regularly seen in folate deficiency as well as in B12 deficiency, the failure of this enzyme reaction does not explain the extreme rarity of neurologic disease in folate deficiency and the frequency of neurologic disease in cobalamin deficiency. Linkage of folate and cobalamin in the methylation of homocysteine to form methionine. The interdependence of vitamin B12 and folate in this methyl transfer is shown schematically in Figure 3. There is evidence that the sera of vitamin B12-deficient patients contain higher than expected levels of methyltetrahydrofolate. Thus, it appears that B12 deficiency leads to a functional folate deficiency in dividing cells. If intracellular folate deficiency is the common lesion in B12 and folate deficiency, the morphologic identity of the megaloblastic abnormalities in these two conditions is understandable. Mechanisms of Vitamin B12 Deficiency the most common cause of B12 deficiency in the Western world is an acquired loss of intrinsic factor, also known as "pernicious anemia. Parietal cells may be lost by autoimmune destruction of the gastric mucosa, by physical or chemical injury, or by surgical removal. Autoimmune destruction of gastric parietal cells is far and away the most common cause of B12 deficiency. The risk of vitamin B12 deficiency from inadequate intake is greatest in strict vegans, who eat neither eggs nor milk products. There are few true vegans in the United States, so dietary insufficiency is rarely a cause of megaloblastic anemia. Because B12 is avidly taken up and biochemically altered by many microorganisms, one might expect some patients with small intestinal disease accompanied by massive bacterial overgrowth to suffer from B12 malabsorption and deficiency. This is the case in several anatomic and physiologic disorders of the gut, especially large diverticula of the small intestine or a surgically created blind loop (hence the term "blind loop syndrome"). Anaerobic organisms such as Bacteroides avidly bind vitamin B12, even when it is coupled to intrinsic factor, 55 rendering the vitamin unavailable for absorption. Fish tapeworm infestation is common in Finland, and B12 deficiency often follows because the worm is a successful competitor for B12. The pancreas also plays a role in B12 absorption; patients with extensive chronic pancreatitis or with cystic fibrosis often fail to absorb B12 when given an oral test dose. The malabsorption is corrected by the simultaneous oral administration of pancreatic extract or trypsin. At the ileum, B12 is transferred from its intrinsic factor complex into the circulation and cells of the body. Thus, structural injury to the gastrointestinal tract (destruction of the gastric mucosa, injury to the pancreas, blind loop or giant diverticulae of the small intestine, or destruction of the ileum) leads to B12 deficiency more commonly than dietary nutritional deficiency or genetic metabolic derangement. The use of nitrous oxide for anesthesia in unrecognized subclinical B12 deficiency has led to severe neuropathy. Recreational abuse of nitrous oxide has led to macrocytosis and neuropathy indistinguishable from B12 deficiency. Nitrous oxide reduces the activity of methionine synthetase probably by inactivating the B12 coenzyme portion of the molecule. Pernicious Anemia A formal definition of pernicious anemia is autoimmune or idiopathic gastric atrophy sufficient to cause vitamin B12 malabsorption due to lack of intrinsic factor. Serology Sera from most patients with pernicious anemia contain autoantibodies to gastric parietal cells, but these antibodies have low specificity. Anti-parietal cell antibodies are relatively common in patients with other autoimmune diseases such as myxedema, diabetes, and gastritis. Autoantibodies to intrinsic factor are present in only about 60% to 70% of sera from patients with pernicious anemia, but they have high specificity. The presence of intrinsic factor antibodies is almost diagnostic of "pernicious anemia. The failure to absorb vitamin B12 is permanent in patients with pernicious anemia, who must receive supplemental B12 for life. Clinical Manifestations Pernicious" anemia is now a misnomer, because the disease is simple to treat with an injection of vitamin B12. Vitamin B12 deficiency is a disease of the second half of life, the incidence being roughly one new case per year per 4,000 people over 40 years of age. There also is a hereditary form of lack of functional intrinsic factor, known as "juvenile pernicious anemia. In addition to the usual physical findings of anemia, the pernicious anemia patient may complain of a sore tongue, which is often smooth, red, and glistening due to lack of papillae. The tongue symptoms and appearance will improve promptly after the correction of the vitamin B12 deficiency. Patients may complain of paresthesias and difficulty walking in the dark, and may appear neurotic. Neurologic examination will often reveal absence of vibratory sensation and proprioception. Individuals with mild to moderate neurologic deficits can be expected to make a complete recovery following B12 therapy, though the time required to recover full function may be as much as twelve to sixteen months. Recovery from advanced neurologic damage (inability to walk, incontinence) is unlikely to be complete. Neurologic disease in a person with megaloblastic anemia is highly suggestive of B12 deficiency rather than folate deficiency. In some patients, the neurologic disease is prominent with little or no anemia, while others have prominent anemia with normal neurologic examinations. If a patient with B12 deficiency is mistakenly treated with folate, neurologic disease may progress to irreversible crippling. Degeneration of the posterior and lateral columns of the spinal cord in vitamin B12 deficiency. Pancytopenia (decreased red cell, platelet, and granulocyte production) may occur in severe deficiency. Macrocytosis and dissociation of maturation in nucleus and cytoplasm have also been described in cells from other rapidly growing tissues such as skin, tongue, testis, bronchus, stomach, and cervix. There are cases of infants who became B12 deficient while nursing from mothers who were strict vegans or who had gastric bypass for obesity. Red cell destruction is mainly in the marrow rather than in the blood (see chapter 2). The erythroid marrow is hypercellular with a 1:1 G:E ratio, and the total marrow mass is greatly increased. The Schilling Test the most common cause of B12 deficiency is malabsorption rather than dietary deficiency. There are several different mechanisms of B12 malabsorption, and a radioactive B12 absorption study is a procedure to sort them out. Though no longer used clinically, it elucidates the pathophysiology of B12 deficiency. The urine radioactivity test (Schilling Test) was developed to measure B12 absorption. Radioactivity appearing in the urine after an oral dose of radioactive B12 represents absorbed vitamin. Because absorbed B12 is normally bound to plasma transcobalamins, no radioactive vitamin is filtered at the glomerulus (molecular weight of B12 is 1,350 daltons). Serum B12 concentration should be measured in all patients with dementia and neuropathy, so that this treatable cause of serious neurologic disease is not overlooked. Measurements of serum homocysteine and methylmalonate are useful in defining metabolic evidence of cobalamin deficiency. One should bear in mind that as tests for clinically significant cobalamin deficiency, these measurements appear to have excellent sensitivity but poor specificity. Treatment of B-12 deficiency Vitamin B12 is used to treat or prevent deficiency, usually given parenterally. History Within a few years after the demonstration of the remarkable efficacy of liver in the treatment of pernicious anemia, it was realized that not all megaloblastic anemia was due to a deficiency of the factor present in injectable liver extract. She demonstrated in a convincing manner that injections of purified liver extract (so wonderfully efficacious in pernicious anemia in London) did not benefit the megaloblastic anemia of pregnancy in Bombay. She did find that eating generous amounts of "marmite" (a yeast extract) led to impressive hematologic and subjective improvement. From this observation came the term "Wills Factor" to identify that beneficial nutrient in yeast. In 1946 folic acid was identified and synthesized by scientists at Lederle Laboratories studying growth factors for certain bacteria. Yeast is the richest nonmedicinal source of folate, but many vegetables, dairy products, and seafoods are excellent dietary sources. Food folate found in spinach, beans, broccoli, and other green leafy vegetables is in the polyglutamate form. An intestinal brush border deconjugase cleaves all but the last glutamate and thus enhances absorption. The biologic half-life of folic acid is less than one month, in contrast to the 18 month half-life of vitamin B12. For example, the methylation of deoxyuridine monophosphate to deoxythymidine monophosphate is catalyzed by thymidylate synthetase in a reaction linked to dihydrofolate reductase.
The nurse realizes the patient may have the following complication virus island walkthrough buy ampicillin 500 mg with visa, which requires prompt intervention: (1) Fat embolism (2) Infection (3) Compartmental syndrome (4) Venous stasis Rationale: the correct answer is (3) infection risk factors purchase ampicillin 500mg free shipping. Compartmental syndrome is the increased pressure in a closed area resulting from edema virus 58 symptoms buy cheap ampicillin on-line. It causes pain and reduced circulation to the area as well as pressure on muscles that can result in permanent anesthesia and paralysis virus 10 states order ampicillin with american express. Infection would not cause these symptoms bundespolizei virus discount 250 mg ampicillin otc, venous stasis would likely cause thrombosis antibiotic bactrim purchase ampicillin visa, and a fat embolism is usually pulmonary and causes shortness of breath and shock antibiotic xidox order ampicillin 500 mg otc. The pulmonary circulation is often the site where fat emboli become obstructed antibiotic resistance quizlet buy cheap ampicillin 500 mg, causing dyspnea, chest pain, coughing, tachycardia, and restlessness. Rheumatoid arthritis is diagnosed in freely movable (synovial) joints in which the synovial membrane is in flamed. There is no minimum time to take the test, but you may have no more than 5 hours to finish. It is not true that the fewer the number of questions you answer the better (or worse) you did. The test questions are primarily application and analysis, which means that you must use the information you have learned to make decisions in real-life situations. Some examples of questions that utilize different parts of the nursing process are: Assessment Which of the following information given by the patient indicates that she is in danger of When assessing a client with disease, the nurse should expect which of the following symptoms To determine if she is likely to have, the nurse should ask which of the following questions After giving drug, the nurse should check the patient for which of the following side effects Ifthe patient has not been fully assessed, then the answer is likely to involve making an assessment such as taking the blood pressure, assessing respira tions, determining urine output, etc. After assessing, the nurse should plan, and questions about prioritizing care (which should the nurse do first Implementation and evaluation questions are less likely to be confusing in this way. Be sure not to give the patient false reassurance or give advice instead of trying to help the patient understand what her problem is or what her options are. It is best to ask a patient what they meant when they said something rather than suggesting what they should do. If a question involves broken equipment, remember it is necessary to check the patient first before looking at the equipment. This type of question is used to make sure the nurse knows what problems are more urgent than others. Now that there are more and more types of caregivers, nurses need to know what kinds of care are appropriate for each type. The signs and symptoms of serious complications, such as hypoglycemia as a result of poor glucose control, which could easily occur in a hospital or nursing care facility. Know the signs and symptoms of toxicity of common drugs that have serious side effects. Know the antidotes of common drugs such as magnesium sulfate (calcium gluconate), heparin (protamine sulfate), and Coumadin (vitamin K or aquamephyton). Know the implications of high or low values and what diseases they are associated with. Remember that addiction is not a concern when giving narcotics in almost all situations, and that pain is determined by the patient. When determining the readiness of a patient to be advanced to a regular diet, the nurse knows that the most significant indication of return of bowel function is (1) normal bowel sounds. The nurse will be administering an enteral feeding to the elderly patient who is unable to take foods orally. Aspirating to check for gastric residual not only determines if the previous feedings are being digested, but it confirms the correct placement of the tube. The nurse is preparing to insert a nasograstic tube in the patient being treated for paralytic ileus. Prior to insertion, the nurse measures the distance to insert the tube by using the tube to measure and mark the distance with tape from the (1) upper part of the nose to the left midclavicular line. The usual way of measuring the length to insert a nasogastric tube is to measure from the earlobe to the nose to the lower part of the sternum. Massaging will not help, and it is incorrect to tell the patient that this is a common side-effect that will pass. Weight loss, increased temperature, nervousness and irritability, as well as tachycardia are signs of hyperthyroid ism. The patient, who is 62-years-old, overweight, and has a family history of diabetes presents to the nurse for her first follow-up visit after her diet and exercise plan has been put in place. Without checking the chart, the nurse knows that this patient most likely has (1) Type I diabetes. In the glucose challenge test, which is used to screen for diabetes in pregnancy, a reading of 140 or over should be followed by the glucose tolerance test. A glucose level less than 105 is a good reading for a fasting blood glucose, and between 130 and 165 includes readings between 140 and 165, which are considered high. The blood sugar guidelines apply to all patients and are not different for each individual. The nurse is reinforcing the importance of proper foot care to the elderly diabetic. The nurse correctly replies: (1) Foot care as well as any other type of hygiene is always important. Proper foot care is one of the most important things to teach diabetics, since they often cannot feel injuries to their feet, and neglected infections can and frequently do cause loss of a leg or death. The diabetic client is demonstrating her knowledge of self care by discussing the diet that has been prescribed for her, the symptoms of hyper and hypoglycemia, as well as the role of exercise in her treatment. However, bowling once a week is exercise that is not of sufficient intensity nor is it frequent enough to help in diabetic management. The breakfast trays are delayed, and the diabetic, who received her insulin an hour ago, tells the nurse that she is feeling sweaty, shaky and that she feels a tingling sensation on her fingers and around her mouth. Coffee is not a source of glucose, and peanut butter would eventually provide glucose, but not quickly enough to help this patient. In teaching the newly diagnosed diabetic about the exchange system, the nurse explains that potatoes would be considered a (1) vegetable exchange. She explains that one of the most common health problems in this age group is osteoporosis. Decreasing the amount of saturated fat in the diet is not thought to affect osteoporosis, while weight-bearing exercise, calcium supplementation, and estrogen do help prevent osteoporosis. She is instructing him in diet, exercise, and the avoidance of high cholesterol foods. An African American adolescent came into the ambulatory clinic complain ing of fatigue and occasional shortness of breath when playing sports. In order to assess for skin pallor, which might be a symptom of anemia, the nurse examines the (1) nail beds. The buccal mucosa is considered to be the most accurate area of the body to assess skin pallor on those with dark skin. Caesar salad with spinach frittata would be a meal high in vitamin K, which is an antagonist to Coumadin. Mannitol is an osmotic diuretic to promote diuresis, which can decrease intracranial pressure. Dexamethasone is a glucocorticoid and anti-inflammatory drug that can decrease swelling; phenytoin is an anticonvulsant to prevent seizures. The nurse knows to position her (1) on her right side with the head of the bed slightly elevated. Cold hands are a symptom of peripheral vasoconstriction characteristic of a sympathetic nervous system response. Bradycardia, pinpoint pupils, and diarrhea are all symptoms of parasympathetic dominance. The nurse should (1) gently suction the nasal secretions to prevent coughing or sneezing. Cerebrospinal fluid will test positive for glucose, and this finding should be reported. Adequate fluids are necessary for surgical patients in the post-operative period in order to maintain (1) peristalsis and range of motion. Fluids lost due to blood loss of surgery, npo, diaphoresis or other insensible loss, and urine all contribute to potential dehydration or hypovolemia. Caitlin Block brings her grandmother to the clinic for her routine cardiac checkup. While you are interviewing the older woman, you notice Caitlin has exophthalmus, a slight goiter, and mild tremors. You ask her if she has any other symptoms related to this disease such as (1) thinning hair, weight loss, tachycardia, or oligomenorrhea. The increase in metabolic rate due to excessive thyroid hormone causes the symptoms in answer (1). Visual disturbances and de creased urinary output can also be indicative of this problem. Every effort must be made to keep the urinary bladder free from microorganisms so the last step before inserting the catheter will be when one sterile glove becomes contaminated. One of the most important functions to assess when caring for a patient with myasthenia gravis is (1) bowel activity. Patients with myasthenia gravis often have upper body muscle weakness including the respiratory muscles. Manifestations of the disorder progress so slowly that years may go by before the patient needs total physical care. The most important sign to watch a patient with head injury is for (1) a widening pulse pressure and change in the level of consciousness. After head injury the risk of intracra nial injury is possible without any visible signs. While talking to the nurse before her exam, Marie says that she and her husband have been having sex less frequently, because she has been experiencing discomfort when they had sex. The nurse explained that physiological changes of aging can affect certain aspects of sexual expres sion. One of the best interventions to assist these clients is for the nurse to (1) explain that decreasing interest in sex is normal, and that most elderly people do not miss it much. Age related changes in sexual functioning can often be alleviated by the use of lubricants. The nurse is talking with a middle-aged woman who has come to the clinic for an annual physical. She starts to discuss her 25-year-old son, who has recently become engaged and also has been promoted at his engineering company. Young adults are initiating intimate relationships, establishing stable employment, and beginning to accept responsibilities. The nurse is treating a 16-year-old patient who is in the hospital for a broken shoulder. When discussing his care, it is important for the nurse to remember that adolescents (1) can only understand information and examples that are concrete. Adolescents are seeking autonomy and want to make decisions for themselves as much as possible. The nurse replies that the assessment is completed at (1) 5 and 10 minutes after birth. The nurse is assessing a third day postpartum cesarean section patient who is to be discharged later in the day. The young woman comes to the clinic with amenorrhea, urinary frequency, and nausea. The nurse explains that these are referred to as (1) presumptive signs of pregnancy. The presumptive signs of pregnancy are: amenorrhea, nausea and vomiting, breast sensitivity, urinary frequency, fatigue, weight gain, and quickening. When providing teaching for the elderly home care patient, the nurse knows to emphasize which of the following to help prevent a major cause of disability in the elderly Susceptibility to accidents in the elderly is increased by a number of factors, including a decline in sensory acuity, increased reflex time, confusion, and medications that may cause drowsiness. The second time mother of a newborn and a 3-year-old daughter, Amanda, confides to the nurse that Amanda, who has been trained and cup feeding for some time, now wants to wear a diaper and drink from a bottle on occasion. Amanda is regressing because of the stress of a new family member and decreased amount of time with her mother. To help her adjust it is helpful to meet her needs for attention and recognition ((1) and (4)) as well as helping her to find an acceptable way of adjusting by identifying with her mother (2). Shaming her (3) is unlikely to be of any long-term benefit and may slow her adaptation by making her feel worse. In the case of Amanda and her baby sister, Amanda is using a defense mechanism to deal with the stress of a new family member. Regression is coping with a stressor through actions and behaviors associated with an earlier developmental period. The patient states that her last menstrual period was on May 15, 1999, and asks the nurse when she can expect to deliver. Prolonged rupture of membranes allows for greater likelihood of an ascending infection, which can affect both the mother and infant. Amnionitis (1) is an infection of the amniotic fluid, jaundice (2) is a newborn condition due to increased levels of bilirubin, and hypoglycemia (3) is low blood sugar. The nurse told Jack that the baby could see, and that the position Jack was holding him in was ideal for the baby to see most clearly. Abundant lanugo (1) is a character istic of preterm infants, as is a flat areola (2), and a scarf sign past mid line (4). The oncoming nurse is given the following facts about the postoperative patient during the 3 p. A patient who has not voided for seven hours requires prompt assessment and intervention. Before the procedure is started, the nurse must (1) explain the benefits and risks of the procedure. Insertion of a central line is a procedure that requires informed consent, and the nurse is responsible for verifying that a signed consent form has been obtained. She replies that this is primarily the responsibility of (1) hospital discharge planning. The individual or department that handles discharge planning is responsible for coordinating and implementing adequate arrangements for discharge from the acute care facility. Input from the physician and family are important, but the responsibility remains with the hospital. Since the daughter has signed a do not resuscitate order, resuscitation equipment, such as the ambu bag, should not be kept by the patient.
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