Importance of these proteins can be appreciated in disorders like hereditary spherocytosis buy discount tadalafil 2.5 mg erectile dysfunction acupuncture. Anemia is defned as any reduction below normal limits of the total circulating red cell mass which is characterized by the clinical features of pallor of skin and nails purchase cheap tadalafil on-line impotence specialists, dizziness buy discount tadalafil 2.5 mg on-line erectile dysfunction medscape, palpitations, lethargy and fatigue. However, the earliest change in the peripheral blood is leucocytosis (caused by increased mobilization from the marginal pools) followed by reticulocytosis and thrombocytosis. The blood loss is leucocytosis chief fndings are a hypercellular bone marrow with megaloblasts in the bone marrow along followed by reticulocytosis and thrombocytosis. There is characteristically presence of large and hypersegmented neutrophils (neutrophils having > 5 lobes). The earliest manifestation of megaloblastic anemia is presence of hypersegmented neutrophils. Diagnosis is made if even a single neutrophil with ≥ 6 lobes is seen or > 5% neutrophils with 5 lobes are seen. Note: • Triad of megaloblastic anemia includes oval macrocytes, Howell Jolly bodies and hyperseg- mented neutrophils. The vitamin B12 (or cobalamin) is present in the bound form (bound with dietary proteins) in the diet. It is freed by the action of pepsin in stomach and then binds with salivary proteins called R-binders (also known as cobalaphilins). In the duodenum, this cobalamin-cobalaphilin complex is broken by the action of pancreatic proteases. Free cobalamin now binds with the intrinsic factor (Castle’s factor) secreted from the parietal cells of the stomach. Biochemical functions of vitamin B12 • It is required for the conversion of homocysteine to methionine • It is also involved in the conversion of methylmalonyl CoA to succinyl CoA which is required for the formation of normal neuronal lipids. Also, there are increased levels of methylmalonic acid in the serum and urine of the patient with defciency of this vitamin. Vitamin B12-intrinsic factor Pernicious anemia com plex is taken by the ileal enterocytes. It is an autoimmune disorder against parietal cells of the stomach by auto-reactive T cells resulting in chronic atrophic gastritis and parietal cells loss (responsible for decreased intrinsic factor production). CoA to succinyl CoA which is required for the formation Morphology of normal neuronal lipids. Bone marrow Megaloblasts, hypersegmented neutrophils and precursors of granulocytes along with megakaryocytes are seen. The combined The combined involvement of involvement of the axons in the ascending tracts of posterior column and the descending pyramidal the axons in the ascending tract is a characteristic feature of vitamin B12 defciency giving the term as subacute combined tracts of posterior column degeneration of the spinal cord. Laboratory tests Schilling test: It is performed • Serum antibodies against intrinsic factor are present. Due to Defective Hemoglobin Synthesis associated with megaloblastic anemiaQ (i) Iron defciency It is the commonest cause of anemia worldwide. Normal iron metabolism The metabolism of iron can be divided in the following headings: Absorption Ankylostoma duodenale is Iron is present in two forms in the food: heme and nonheme iron. Most chances of atherosclerosis of the iron absorbed from the gut is lost because of mucosal lining shedding whereas in and throm bosis (because of increased requirements it is absorbed in a greater percentage. In case of iron depletion the level of this negative regulatory protein is decreased thereby increasing the absorption of iron and vice versa. Mutation of the gene coding for hepcidin Iron is absorbed primarily from is implicated in the causation of hemochromatosis. Transport and storage of iron From the enterocytes, the absorbed iron is transferred to a plasma protein called transferrin that delivers it to different cells of the body expressing high levels of transferrin receptors on their surface. These cells include hepatocytes and the developing erythroblasts in the bone marrow. Absorbed iron is transferred Normally, transferrin is 33% saturated (one-third saturation) with iron. Since, the serum to a plasma protein called transferrin concentration is nearly 300-350 μg/dl (also called as total iron binding capacity transferrin. The iron which is not immediately required by the cells is stored in the form of ferritin which is a protein iron complex present in all the tissues especially liver, spleen and bone marrow. A small amount of ferritin is also present in the plasma which is derived from the storage pools of the body iron; so, serum ferritin is an indicator Each molecule of transferrin of body iron stores. Intracellular iron is converted into hemosiderin which stains positively can transport two molecules of with potassium ferrocyanide giving a positive Prussian blue stain. The causes of iron defciency anemia include the following: Dietary lack Impaired Increased Chronic blood loss Iron is stored in ferritin in the absorption requirement ferric form. Features of Iron Defciency Anemia It is characterized by the following stages: Serum ferritin is an indicator of Stage I or stage of negative iron balance body iron stores. This is a stage characterized by decreased amount of storage iron manifesting as decreased serum ferritin concentration and reduced amount of bone marrow iron staining with Prussian blue stain. Clinical features include fatigue, impaired growth and development, pica (eating noedible substances like mud, etc. Poikilocytosis is seen in form of small and The normal requirement of iron in the diet is nearly 1 mg/d. Bone marrow Hypercellular bone marrow (having increased erythroid progenitors) with depleted bone marrow iron stores. The treatment of anemia is with the help of either oral or parenteral iron therapy the response of which is clinically assessed with the reticulocyte count on about 8th - 9th day which demonstrates reticulocytosis. Differential diagnosis of microcytic hypochromic anemia In iron defciency anemia, microcytosis is seen before Tests Iron Infammation Thalassemia Sideroblastic appearance of hypochromia. Anemia of chronic disease is differentiated from iron defciency (ii) Anemia due to marrow infltration anemia morphologically by the This type of anemia is caused due to infltration of the bone marrow resulting in fact that microcytosis follows myelophthisic anemia. It is characterized by presence of immature erythroid and hypochromia (microcytosis myeloid precursors in the blood (this is called as leukoerythroblastosis). These are Sideroblastic anemia is char- normoblasts having pin point iron granules (easily demonstrable with the help of acterized by the presence of ringed sideroblasts. The pathogenesis of the diseases involves defective heme synthesis resulting in ineffective erythropoiesis which thereby contributes to There is increase in serum iron overload. Note: Abnormal sideroblasts are also seen in thalassemia, megaloblastic anemia and hemolytic ane- mias. Aplastic anemia This is a disorder characterized by marrow failure associated with pancytopenia (anemia, thrombocytopenia and leukopenia). Bone marrow aspiration in The bone marrow biopsy shows it is characteristically hypocellular being replaced by fat cells (in aplastic anemia reveals “dry contrast to aleukemic leukemia and myelodysplastic syndrome in which we have pancytopenia as- tap”. It is treated with either bone marrow transplantation (in young patients) or antithymocyte globulin (in old patients).
Iatrogenic vagotomy results in a rapid emptying of liquids and a delayed emptying of solids order 5mg tadalafil amex erectile dysfunction needle injection. Truncal vagotomy impairs adaptive relaxation and results in increased contractile tone in the gastric reservoir (see Fig generic 20 mg tadalafil visa erectile dysfunction drugs available in india. Elevated contractile tone increases pressure in the gastric reservoir buy tadalafil 5mg without prescription young person erectile dysfunction, which ejects liquids more forcefully through the antral pump into the duodenum. Paralysis with a loss of propulsive motility and, consequently, the trituration of solids by the antral pump occur in diabetic autonomic neuropathy and after a vagotomy. The result is gastroparesis, which can account for the delayed emptying of solids after a vagotomy. Up to 80% of patients with anorexia nervosa have delayed gastric emptying of solids. Another such condition is idiopathic gastric stasis, in which no evidence of an underlying condition can be found. These kinds of disorders for which no physiologic or biochemical explanation for the patient’s symptoms can be found are called functional gastrointestinal motility disorders. The absence of inhibitory motor neurons and achalasia of the circular muscle in the pyloric canal are factors that account for the obstructive stenosis. Rapid Gastric Emptying Resection of the distal stomach might be done as a treatment for cancer or peptic ulcer disease. Surgical pyloroplasty used to be done together with vagotomy for the treatment of peptic ulcer disease and might still be done at times in patients with idiopathic gastroparesis. Both resection and pyloroplasty compromise mixing and renders the stomach incontinent for solids. Premature and rapid gastric emptying (“dumping”) of solids and liquids into the duodenum in these cases causes hyperglycemia. Vagotomy, done at the same time as pyloroplasty, impairs receptive relaxation and accommodation in the gastric reservoir and exacerbates the dumping symptoms of anxiety, sweating, strong hunger, dizziness, weakness, and palpitations. The dumping syndrome is managed by restricting the patient to small meals of complex carbohydrates ingested together with small volumes of liquids. The rate of gastric emptying decreases as the acidity of the gastric contents increases. Meals with a low caloric content empty faster than those with a high caloric content. The neurophysiologic control mechanisms for gastric emptying keep the caloric delivery rate to the small intestine within a narrow range, regardless of the source (i. Fat is emptied at the slowest rate and is the most potent inhibitor of gastric emptying. This inhibition involves the enteroendocrine release of cholecystokinin in the upper small intestine. For digestible particles a lag phase is required for the grinding action of the antral pump to reduce the particle size to a sufficiently small size for emptying. However, not all particles are released from the stomach at the same time and the smaller particles are selectively released first (sieving action of the stomach). The emptying of a solid or semisolid meal is preceded by a lag phase, which is the time required for particles to be reduced to a sufficiently small size for emptying. Contractions of the duodenum and hormonal signals arising from there significantly influence gastric emptying. Transit of material through the small intestine is influenced by three fundamental patterns of motility: (1) the interdigestive pattern, (2) the digestive pattern, and (3) power propulsion. The segmentation appearance is the result of peristaltic contractions, which propagate for only short distances and occur simultaneously at multiple sites along the bowel. Receiving segments with an expanded lumen separate circular muscle contractions that form short propulsive segments on either end of the receiving segment (Fig. Each propulsive segment jets the contents in both directions into the opened receiving segments, where stirring and mixing occur. This happens continuously at closely spaced sites along the entire length of the small intestine. Propulsive segments separated by receiving segments occur randomly at multiple sites along the small intestine. Receiving segments convert to propulsive segments, whereas propulsive segments become receiving segments. Digestion of food no longer occurs in the large intestine, but absorption of H O, minerals, and vitamins and fecal compaction do occur. Contractile2 activity occurs continuously in the normally functioning large intestine. Whereas the contents of the small intestine move through sequentially with no mixing of individual meals, the large bowel contains a mixture of the remnants of several meals ingested over 3 to 4 days. The arrival of undigested residue from the ileum does not predict the time of its elimination. The hepatic flexure is the boundary between ascending and transverse colon; the splenic flexure between transverse and descending colon. The longitudinal smooth muscle layer in humans is restricted to bundles of fibers called taeniae coli. Power propulsion occurs in the transverse and descending colon and fits the general pattern of neurally coordinated peristaltic propulsion. Increased delivery of ileal contents into the ascending colon, as occurs following a meal, often triggers mass movements into the colon. The increased incidence of mass movements and generalized increase in segmental movements following a meal is called the gastrocolic reflex. Power propulsion in the healthy bowel usually starts in the middle of the transverse colon and is preceded by relaxation of the circular muscle and the downstream disappearance of haustral contractions. Chemoreceptors and mechanoreceptors in the cecum and ascending colon provide feedback for controlled delivery of the ileum contents into the ascending colon, analogous to gastric emptying into the small intestine. Neuromuscular mechanisms, analogous to adaptive relaxation in the gastric reservoir, permit filling of the ascending colon to occur without large increases in intraluminal pressure. Dwell time in the ascending colon is long when compared to the small intestine but short when compared to the transverse colon. This suggests that the ascending colon is not the primary site for the storage, mixing, and removal of H O from the feces. The significance of retrograde propulsion in this region is uncertain; it may be a mechanism for temporary retention of the contents in the ascending colon. Forward propulsion is probably controlled by feedback signals related to the fullness of the transverse colon. Motility of the transverse colon is specialized for storage and removal of water from the feces. The contents of the transverse colon are retained for about 24 hours, suggesting that this is the primary location for the removal of H O and electrolytes and the storage of solid feces.
The intensity of the dye can be densitometrically quantified buy generic tadalafil 2.5mg online impotence of organic origin icd 9, and changes to the normal pattern are clinically relevant order tadalafil 10 mg overnight delivery impotence quoad hoc. A wide variety of serum immunoassays are available in which a precipitation reaction occurs as a result of antibodies combining with a specific antigen cheap tadalafil 10mg on-line erectile dysfunction treatment perth. The detection and quantification of either antibodies or antigens are diagnostically valuable. For example, elevation of smooth muscle cell antibodies and antinuclear antibodies points toward autoimmune hepatitis. Elevation of gluten or antigliadin antibodies can be used to diagnose celiac disease. Abnormal antigens found on microorganisms can be detected by immunoassay and can often identify infected people before symptoms appear; alternatively, the presence of circulating antibodies to particular antigens can be used to determine if a recovered patient was infected with a particular microorganism. In most cases, however, the antigen–antibody complexes must be labeled for detection (e. The blood tests that are cited are meant to be neither an exclusive nor an exhaustive list. However, it is useful to remember that the blood is the conduit for moving both nutrients and waste products and is, therefore, where many of the aberrations of homeostasis will be expressed. This figure shows the size and appearance of cells and cell fragments (thrombocytes) found in the circulation. Blood viscosity increases or decreases as the total number2 of formed elements or plasma proteins changes. Pumping high-viscosity blood puts strain on the heart because a higher pressure is required to achieve tissue perfusion. In healthy people, a slight increase in the relative blood cell concentration and, hence, blood viscosity can occur (for instance, due to dehydration), but this is easily tolerated. Decreased blood viscosity is usually indicative of other serious health problems that cause a decrease in plasma proteins or formed elements. Hct can be determined by centrifugation of anticoagulated blood within small capillary tubes to separate blood cells from the plasma. Hct values have a relatively large normal range and vary somewhat between men and women (Table 9. Immediately after hemorrhage, the Hct does not change because cells and plasma are lost in equal proportions. Dehydration, which decreases the H O content and thus the volume of plasma, also2 results in an increased Hct. The Hct can only be used to determine anemia when fluid status is taken into account. People with red blood cells that are covered with A or B molecules are said to have type A blood or type B blood, respectively. Inappropriate combinations between the blood groups of the recipient and the donor can lead to potentially fatal agglutination, because the recipient’s immune system will have antibodies against the donor’s red blood cells. Agglutination of red blood cells may lead to improper blood circulation, release of hemoglobin (Hgb) that crystallizes, and eventually, kidney failure. People have antibodies of the immunoglobulin (Ig) M class directed against the antigens that are not on their red blood cells. Therefore, someone with an A blood type will have anti-B antibodies; someone with B blood type will have anti-A antibodies and someone with O blood type will have antibodies to both A and B. Type O persons can receive blood from a type O person only but can donate to all groups and are, thus, called universal donors. Blood type can further be useful for a person’s identification, such as in forensic medicine and for the identification of family relationships in disputed parentage. The latter is possible because the blood type of the child is related to that of the parents. For instance, if the mother and the child have type O blood, the father’s blood type must be A, B, or O. Most likely, these differences will gradually disappear because of increased mobility and a greater societal acceptance of interracial marriages. In the United States, whites are currently characterized by a higher frequency of type A and a lower frequency of type B in comparison with African and Asian Americans, whereas Indians have a low frequency of both A and B types. The blood type of a person is unrelated to his or her Hgb type because blood antigens are membrane factors, whereas Hgb is dissolved within the cell cytoplasm. The Rh system is complex, involving three genes producing Rh antigens C, D, and E. Rh D, the most important, is found in the blood of 85% of people, + − who are classified as Rh (Rhesus positive). Knowing about the Rh factor is important in pregnant women because a baby’s life can be + − endangered if it inherits Rh blood from its father but the mother is Rh. Late in pregnancy, or at parturition, the baby’s blood may cross to the mother’s system, where the erythrocytes are recognized as foreign and antibodies are formed against them. These antibodies pose a serious threat to any future + Rh babies of hers in following pregnancies. To prevent this, the mother receives anti-Rhesus D + immunoglobulin around the 28th week of pregnancy and right after delivery. The Ig attaches to Rh cells from the baby in the mother’s bloodstream and destroys them, preventing the triggers for the mother’s immune system to produce its own anti-D antibody. The actual measured value will vary with the total Hgb, which is why anemia can lead to severe hypoxemia. This information provides invaluable clues to the type of illness but also requires careful analysis. Therefore, changes in blood concentrations indicate changes in the storage pool equilibrium. Decreased PltsC may be the result of bone marrow failure or of peripheral platelet destruction. A visual analysis of the blood cells in a blood smear can validate any cellular abnormalities or determine the presence of certain microorganisms. Blood smears are commonly stained with a polychrome stain such as Wright-Giemsa after fixing the cells with methanol. The cell’s cytoplasm is rich in Hgb, an iron-containing biomolecule that readily binds with O. Erythrocytes consist mainly of hemoglobin, a unique pigment containing heme groups in which iron atoms bind to oxygen. Erythrocytes have the shape of biconcave disks, with a diameter of about 7 μm and a maximum thickness of 2. They contain several hundreds of hemoglobin molecules, each consisting of four polypeptide chains (two α and two β), with each chain containing iron bound to its heme group. These polypeptide chains contain two α- globin molecules and two molecules of another type of globin chain (β, γ, δ, or ε). The production of each type of globin chain is controlled by individual structural genes with five different loci. Mutations can occur anywhere in the five gene loci resulting in the production of abnormal Hgb molecules leading to hemoglobinopathies. The most common of this spectrum of diseases is sickle cell anemia, which is caused by a point mutation (single amino acid substitution) in the β-globin chain.
Glomerulonephritis can be acute (a sudden inflammatory attack) or chronic that comes on gradually cheap tadalafil amex erectile dysfunction and smoking. Nearly all forms of acute glomerulonephritis tend to progress to the chronic stage purchase tadalafil online erectile dysfunction drugs with the least side effects. The condition is characterized by irreversible and progressive glomerular and tubulointerstitial fibrosis 5 mg tadalafil otc erectile dysfunction drugs wiki. The condition is triggered by an immunologic reaction causing inflammation and proliferation of glomerular tissue that damages the base membrane and capillary endothelium. If the progression of the disease is not halted, it leads to chronic kidney disease with severe cardiovascular complications. The cause of glomerulonephritis is due either to an infection or to an immune disorder. The types of infection include poststreptococcal, bacterial endocarditis, or viral infection. Glomerulonephritis can occur a week or two after recovery from strep throat infection. To fight the streptococcal infection, the body produces extra antibodies that often settle in the glomeruli. If glomerulonephritis occurs on its own, it is known as primary glomerulonephritis. If another disease, such as lupus or diabetes, is the cause, it is called secondary glomerulonephritis. Bacterial endocarditis is the result of a bacterial infection that spreads through the bloodstream and lodging in the heart, causing infection in one or more of the heart valves. Although there is a connection between endocarditis and glomerular dysfunction, the exact mechanism is not clear. Immunological diseases such as lupus and Goodpasture syndrome can trigger glomerulonephritis. Lupus is a chronic inflammatory disease that affects many organs, such as the skin, joints, kidneys, heart, lungs, and blood. Goodpasture syndrome is a rare immunological lung disorder that can mimic pneumonia and causes bleeding in the lungs and glomeruli. Kidney blood flow is autoregulated; it is also profoundly influenced by nerves and hormones. Glomerular filtration rate is determined by the glomerular ultrafiltration coefficient, glomerular capillary hydrostatic pressure, hydrostatic pressure in the space of the Bowman capsule, and glomerular capillary colloid osmotic pressure. The transport of water and most solutes across tubular epithelia is dependent on active + reabsorption of Na. The kidneys save water for the body by producing urine with a total solute concentration (i. The loops of Henle are countercurrent multipliers; they set up an osmotic gradient in the kidney medulla. Vasa recta are countercurrent exchangers; they passively help maintain the medullary gradient. Collecting ducts are osmotic equilibrating devices; they have a low water permeability, which is increased by arginine vasopressin. The renal clearance of a substance is equal to its rate of excretion divided by its plasma concentration. Inulin clearance provides the most accurate measure of glomerular filtration rate. The rate of net tubular reabsorption of a substance is equal to its filtered load minus its excretion rate. The rate of net tubular secretion of a substance is equal to its excretion rate minus its filtered load. An elderly, diabetic woman arrives at the hospital in a severely dehydrated condition and is breathing rapidly. Blood plasma (glucose) is 500 mg/dL (normal is ~100 mg/dL) and the urine (glucose) is zero (dipstick test). As a consequence, the proximal tubules may be able to reabsorb all of the filtered glucose (because the filtered load is reduced), even though the plasma (glucose) is elevated. If splay is increased, glucose Tm is low, or threshold is low, then glucose should be present (not absent) from the urine. An abnormally high glucose Tm would reduce glucose excretion, but in the scenario presented, this is not a likely cause of the absence of glucose in the urine. This substance is a weak, lipid-soluble organic acid that is reabsorbed by nonionic diffusion in the kidneys. Which of the following would be the best way to promote urinary excretion of this substance? Excretion of phenobarbital is promoted by increasing urine output and by making the urine more alkaline. The latter would keep phenobarbital in its anionic form, which is not reabsorbed by the kidney tubules. A few weeks before, he had an upper respiratory tract infection, probably caused by a virus. Puffiness around the eyes, abdominal swelling, and pitting edema in the legs are observed. The child is treated with the corticosteroid prednisone, and the edema and proteinuria disappear in 2 weeks. Glomeruli are normal by light microscopy, but effacement (obliteration) of podocyte foot processes and loss of filtration slits are seen with the electron microscope. What features in this case would lead you to suspect the presence of nephrotic syndrome? Why does the abnormally high rate of urinary protein excretion underestimate the rate of renal protein loss? Proteinuria is a consequence of an abnormally high permeability of the glomerular filtration barrier to the plasma proteins. This condition might be due to an increased physical size of “holes” or pores in the basement membrane and filtration slit diaphragms or a loss of fixed negative charges from the glomerular filtration barrier. Proteins that have leaked across the glomerular filtration barrier are not only excreted in the urine but are reabsorbed by proximal tubules. The endocytosed proteins are digested in lysosomes to amino acids, which are returned to the circulation. Both increased renal catabolism by tubule cells and increased excretion of serum albumin in the urine contribute to the hypoalbuminemia. Note that the permeability of the glomerular filtration barrier to macromolecules (plasma proteins) was abnormally high, but permeability to fluid was not increased. The edema is due to altered capillary Starling forces and renal retention of salt and water.