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Formation of isocitrate via cis aconitate The enzyme aconitase catalyzes the reversible transformation of citrate to isocitrate 35 mg alendronate otc menstruation every 2 weeks, through the intermediary formation of cis aconitate cheap 70mg alendronate free shipping breast cancer 60 mile 3 day walk. Conversion of succinyl CoA to succinate The product of the preceding step, succinyl CoA is converted to succinate to continue the cycle. Hydration of fumarate to malate The reversible hydration of fumarate to malate is catalyzed by fumarase. As one molecule of glucose gives rise to two molecules of pyruvate by glycolysis, intermediates of citric acid cycle also result as two molecules. The frst reaction of the pentose phosphate pathway is the dehydrogenation of glucose 6-phosphate by glucose 6-phosphate dehydrogenase to form 6-phosphoglucono d-lactone. Glycogenesis is a very essential process since the excess of glucose is converted and stored up as glycogen which could be utilised at the time of requirement. In the absence of this process the tissues are exposed to excess of glucose immediately after a meal and they are starved of it at other times. Step 1 The frst step in the breakdown of glycogen is catalyzed by two enzymes which act independently. The frst enzyme, namely glycogen phosphorylase with inorganic phosphate catalyses the cleavage of a terminal a 1-4 bond of glycogen to produce glycogen with one molecule less and a molecule of glucose 1-phosphate. This is carried out by another enzyme called the debranching enzyme (a 1-6 glucosidase) which hydrolyses these bonds and thus make more a 1-4 linkage accessible to the action of glycogen phosphorylase. The combined action of glycogen phosphorylase and the debranching enzyme converts glycogen to glucose 1-phosphate. Glucose 6-phosphatase removes phosphate group from glucose 6-phosphate enabling the free glucose to diffuse from the cell into the extra cellular spaces including blood. It usually occurs when the carbohydrate in the diet is insuffcient to meet the demand in the body, with the intake of protein rich diet and at the time of starvation, when tissue proteins are broken down to amino acids. In glycolysis, glucose is converted to pyruvate and in gluconeogenesis pyruvate is converted to glucose. Fructose 6-phosphate is formed from fructose 1,6-diphosphate by hydrolysis and the enzyme fructose 1,6-diphosphatase catalyses this reaction. Most of the glucogenic amino acids are converted to the intermediates of citric acid cycle either by transamination or deamination. Further metabolism of glycerol does not take place in the adipose tissue because of the lack of glycerol kinase necessary to phosphorylate it. Instead, glycerol passes to the liver where it is phosphorylated to glycerol 3-phosphate by the enzyme glycerol kinase. Hence, glycogen stored up in the muscle is converted into lactic acid by glycogenolysis followed by anaerobic glycolysis and thus lactate gets accumulated in the muscle. Muscle tissue lacks the enzyme glucose 6-phosphatase hence it is incapable of synthesizing glucose from lactic acid and the conversion take place only in the liver. In the liver lactate is oxidised to pyruvate which undergoes the process of gluconeogenesis resulting in the resynthesis of glucose. The glycogen may be once again converted to glucose (glycogenolysis) and may be recycled to the muscle through the blood. The process of gluconeogenesis completes the cycle by converting glucose once again to muscle glycogen. So the word diabetes milletus refers to chronic excretion of large volume of urine containing glucose. Diabetes mellitus, caused by a defciency in the secretion or action of insulin, is a relatively common disease. Diabetes mellitus is really a group of diseases in which the regulatory activity of insulin is defective. Type one requires insulin therapy and careful, life long control of the balance between glucose intake and insulin dose. Decreased permeability of the cell membrane for glucose resulting in the accumulation of glucose in the blood. The diabetic has voracious appetite, but inspite of over eating, they lose weight and become lean and emaciated.

By slowing the transit of chyme order 35mg alendronate amex menopause dry skin, segmentation and a reduced rate of peristalsis allow time for these processes to occur buy alendronate 35 mg low cost research on women's health issues. In contrast, sublingual gland saliva has a lot of mucus with the least amount of amylase of all the salivary glands. When the bolus nears the stomach, the lower esophageal sphincter relaxes, allowing the bolus to pass into the stomach. Chapter 24 1 C 3 A 5 C 7 C 9 A 11 D 13 C 15 C 17 A 19 D 21 C 23 D 25 C 27 A 29 B 30 An increase or decrease in lean muscle mass will result in an increase or decrease in metabolism. When excess acetyl CoA is produced that cannot be processed through the Krebs cycle, the acetyl CoA is converted into triglycerides and fatty acids to be stored in the liver and adipose tissue. The individual amino acids are broken down into pyruvate, acetyl CoA, or intermediates of the Krebs cycle, and used for energy or for lipogenesis reactions to be stored as fats. In diabetes, the insulin does not function properly; therefore, the blood glucose is unable to be transported across the cell membrane for processing. If the disease is not controlled properly, this inability to process the glucose can lead to starvation states even though the patient is eating. Vasoconstriction helps increase the core body temperature by preventing the flow of blood to the outer layer of the skin and outer parts of the extremities. Chapter 25 1 B 3 D 5 B 7 D 9 A 11 C 13 B 15 B 17 A 19 B 21 C 23 D 25 D 27 B 29 C 31 The presence of white blood cells found in the urine suggests urinary tract infection. This greatly increases the passage of water from the renal filtrate through the wall of the collecting tubule as well as the reabsorption of water into the bloodstream. It is transformed into carbonic acid and then into bicarbonate in order to mix in plasma for transportation to the lungs, where it reverts back to its gaseous form. The gas diffuses2 into the renal cells where carbonic anhydrase catalyzes its conversion back into a bicarbonate ion, which enters the blood. Without these stimuli, the Müllerian duct will develop and the Wolffian duct will degrade, resulting in a female embryo. Because these organs are only semifunctional in the fetus, it is more efficient to bypass them and divert oxygen and nutrients to the organs that need it more. These are mild contractions that do not promote cervical dilation and are not associated with impending birth. In response to this pressure change, the flow of blood temporarily reverses direction through the foramen ovale, moving from the left to the right atrium, and blocking the shunt with two flaps of tissue. The increased oxygen concentration also constricts the ductus arteriosus, ensuring that these shunts no longer prevent blood from reaching the lungs to be oxygenated. Getting blood pressure under control: high blood pressure is out of control for too many Americans [Internet]. It may be reproduced in whole or in part for study or training purposes subject to the inclusion of an acknowledgement of the source. P6 Section 3: Patient management The curriculum is underpinned by the principles P8 Section 4: Common problems and of adult learning. It is outcomes based, providing conditions a strong foundation for workplace learning and P11 Section 5: Safe patient care assessment, and facilitating doctors to refect on their current practice and take responsibility P12 Section 6: Communication for their own learning. A holistic approach is P12 Section 7: Professionalism adopted, focusing on integrated learning and P15 References assessment, identifying commonalities between different activities and delineating meaningful P16 Appendix 1: Patient Safety Framework key clinical and professional activities. Introduction to the Addiction Medicine module The Hospital Skills Program Addiction Medicine Doctors working within designated alcohol module identifes capabilities required to provide and other drug services have an extended role safe care to patients with alcohol and other drug requiring additional capabilities that are shaded problems. Central to the module is the professional development and training (see need for doctors to educate colleagues in order References). There is a large degree of does not extend beyond substance abuse to overlap between the two groups with a common other addictions such as gambling and eating base of knowledge, skills and attitudes. Has a good case-specific nuances and linking understanding of working knowledge their relational significance, a situation to appropriate of the management of thus reliably identifying key action. Fluent in most Has a comprehensive clinical decision making procedures and clinical understanding of the rural and clinical proficiency in management tasks. Responsibility (R) Uses and applies Autonomously able to Works autonomously, integrated management manage simple and consults as required for approach for all cases; common presentations and expert advice and refers consults prior to disposition consults prior to disposition to relevant teams about or definitive management or definitive management for patients who require and arranges senior review more complex cases.

Erythrocyte enzyme deficiencies Hereditary hemolytic anemia has been associated with 284 Hematology at least ten red cell enzyme deficiencies trusted alendronate 35mg menopause young age. Rather than producing acute hemolysis in association with drug ingestion alendronate 70 mg free shipping womens health 3 week workout plan, it causes a chronic congenital nonspherocytic hemolytic anemia. Pyrimidine-5’-nucleotidase deficiency A chronic hemolytic anemia inherited as an autosomal recessive and characterized by large numbers of erythrocytes with basophilic stippling is due to deficiency in an enzyme, Pyrimidine-5’-nucleotidase, which dephosphorylates the ribonucleotides of cytidine and uridine. Generally the term hemoglobinopathy is used to signify a structurally abnormal hemoglobin with at least one amino acid substitution. Structural abnormalities may cause premature red cell destruction; easily denatured hemoglobins; hemoglobins with abnormal oxygen affinity; altered hemoglobin solubility; and, in a few instances, reduced globin synthesis. Hemoglobin S By far the most important hemoglobinopathies are those related to the presence of sickle hemoglobin (HbS). Sickle hemoglobin results form replacement 287 Hematology of the sixth amino acid form the N-terminal end of the β- chain, glutamic acid, by valine. Hemoglobin C syndromes Hemoglobin C (HbC) is probably the second most common hemoglobinopathy (2-3% gene frequency in black populations). HbC is caused by substitution of lysine for glutamic acid in the sixth position form the N- terminal end of the β-hemoglobin chain (same location as the substitution in HbS). A variety of acquired clinical conditions result in shortened survival of previously normal red cells. These include immune-mediated destruction, red cell fragmentation disorders, acquired membrane defects, splenic effects, and the results of infections and environmental toxins. Immunohemolytic anemia 288 Hematology Immunohemolytic anemias are the result of the binding of antibody, complement, or antibody plus complement to red cells. Antibodies formed against erythrocyte antigens may be either warm (active at 37oC) or cold (active at room temperature and below). In some cases, these antibodies activate a series of proteins, referred to collectively as complement; in others, the red cells are coated with antibody alone. As a result of complement activation by hemolytic antibodies, intravascular red cell lysis and release of hemoglobin may occur. Immunohemolytic anemias fall into one of three major categories: autoimmune, in which the patient makes an autoantibody against his or her own red cells; alloimmune, where the patient’s antibody is directed against foreign red cells; and drug-induced, where a drug-dependent or related antibody is responsible for hemolysis (Table 17. The red cells are usually coated with IgG alone, IgG and complement or complement alone, but a minority of cases show IgA or IgM coating alone or combined with IgG antibody. Part of the coated membrane is lost so the cell becomes 290 Hematology progressively more spherical to maintain the same volume and is ultimately prematurely destroyed, usually predominantly in the spleen. The disease may occur at any age in either sex and presents as a hemolytic anemia of varying severity. Laboratory findings The hematological and biochemical finding are typical of a hemolytic anemia with spherocytosis prominent in the peripheral blood. The hallmark of autoimmune hemolytic anemia is the presence of antibody or complement, or both, on the patient’s own red cells. In these syndromes the autoantibody, whether monoclonal (as in the idiopathic cold hemeagglutinin syndrome or associated with 291 Hematology lymphoprolifertative disorders) or polyclonal (as following infection, e. Hemolytic syndromes of varying severity may occur depending on the titer of the antibody in the serum, its affinity for red cells, its ability to bind complement, and its thermal amplitude (whether or not it bids to red cells at 37oC). Intravascular hemolysis occurs in some of the syndromes, in which the complement sequence is completed on the red cell surface. Low serum levels of complement in other case may help to protect the patient from a more sever clinical disease. Paroxysmal cold hemoglobinuria This rare disease, characterized by hemoglobinuria following cold exposure, is caused by an IgG autoantibody to the red cell antigen P. This Donath- Landsteiner autoantibody is unique in that it binds to red cells at cold temperatures, in contrast to other IgG antibodies. Furthermore, it binds complement well, and brisk hemolysis results when the cells are warmed and the complement sequence proceeds to completion. Drug induced immune hemolytic anemias Four pathophysiologic mechanisms account for most cases of drug-induced red cell sensitization and positive 293 Hematology direct Coombs test. The drug-induced problem may result in serious hemolytic anemia on the one hand, or a laboratory abnormality without clinical sequelae on the other.

The active transport of Ca++ ions back in to the sarcoplasmic reticulum buy 35 mg alendronate free shipping women's health journal primary care, is energy dependent order 35mg alendronate with mastercard menstrual jelly. Smooth muscle The majority of these muscles are present in the walls of hollow organs, blood vessels and tubular structures in the body. Their contraction exerts pressure on the contents and regulates the forward movement of contents of these structures. Smooth muscles are spindle-shaped, have 1 nucleus and are much smaller in size (2-10 μm in diameter 92 and 50-100 μm in length). Three types of filaments present in smooth muscles are • Thin actin filaments, which have tropomyosin but lack troponin • Thick myosin filaments, longer than those found in skeletal muscles. Smooth muscles do not form myofibril and are not arranged in sarcomere pattern of skeletal muscle. Smooth muscle myosin interacts with actin only when the myosin is ++ phosphorylated. During excitation, cytosolic Ca increases, that acts as an intracellular messenger, initiating a series of biochemical events that result in phosphorylation of myosin. In Smooth muscles Ca++ binds with calmodulin and intracellular protein similar to troponin in structure. This calcium- calmodulin complex binds to and activates another protein, myosin kinase, which in turn phosphorylats myosin. Phosphorylated myosin then binds with actin thin filament starting cross bridge cycle. Single- unit smooth muscle (visceral smooth muscles) • Found in the walls of hollow organs/viscera - digestive, reproductive, urinary tract and small blood vessels. Slow wave potential Slow contractile response of smooth muscle A smooth muscle contractile response is slower than of muscle twitch. A single smooth muscle contraction may last as long as 3 sec (3000 msec) compared to the maximum of 100 msec for a single contraction response skeletal muscle. Describe the generation of action potential, its phases, ionic basis and mode of propagation 4. Describe the transmission of neural signals at the neuromuscular junction of skeletal muscle. It transports substances from place to place, buffers pH changes, carries excess heat to the body surface for loss, plays a very crucial role in the body’s defense against microbes and minimizes blood loss by evoking homeostatic responses when a blood vessel is injured. Cells need a constant supply of oxygen to execute energy-producing chemical reactions that produce carbon dioxide that must be eliminated continuously. Blood is about 8% of total body weight and has an average volume of 5 liters in women and 5. A very tiny portion of the cardiac output passes through each capillary, bringing oxygen, nutrients, and hormones to each cell and removing carbon dioxide and metabolic end products (waste products). Blood composition Blood consists of erythrocytes, leukocytes, and platelets suspended in liquid called plasma. The white cells and platelet after centrifugation are packed in a thin, cream colored layer because they are colorless, the “buffy coat”, on top of the packed red cell column. The hematocrit averages 42% for women, 45% for men, with average volume occupied by plasma being 58% for women and 55% for men. They are biconcave disks, manufactured in the red bone marrow, losing their nuclei before entering the peripheral circulation. Red cells having nuclei seen on the peripheral smear suggest an underlying disease state. Their biconcave shape gives them enough 104 flexibility so they can easily pass through small capillaries to deliver oxygen to the tissues. The other 2 bonds (besides 4 nitrogen) are formed on either side of the planar porphyrin ring. The affinity of hemoglobin for oxygen is affected by pH, temperature, and 2, 3-diphosphoglycerate concentration. These factors facilitate oxygen uptake in the lungs and its release in the tissues. Structure of a hemoglobin molecule Globin is a tetramer, consisting of two pairs of polypeptide chains. Changes in the polypeptide subunits of globin can also affect the affinity of hemoglobin for oxygen. The major normal variants of hemoglobin, depending on its variation of globin chain is as follows: Table 10.