Medical Instructor, University of Washington School of Medicine
However medications dialyzed out purchase prometrium 200mg free shipping, bicarbonate can also be generated intracellularly via the activity of the enzyme carbonic anhydrase treatment keloid scars buy prometrium without prescription. Solidarrowsrepresentstimulatory effects symptoms inner ear infection purchase prometrium with visa, whereas dashed arrows indicate inhibition symptoms of a stranger buy prometrium 100 mg visa. The second releasing factor, monitor peptide, is released by pancreatic acinar cells into pancreatic juice. Because the releasing factors are peptides, they will be subject to proteolytic degradation by enzymes such as pancreatic trypsin in exactly the same way as dietary protein. However, when dietary protein is ingested, it is present in much greater amounts in the lumen than the releasing factors and thus "competes" with the releasing factors for proteolytic degradation. The secretory products of pancreatic acinar cells are largely presynthesized and stored in granules that cluster toward the apical pole of acinar cells. Stimulation of acinar cells results in phosphorylation of a series of regulatory and structural proteins within the cell cytosol that move the granules closer to the apical membrane, where the granules fuse with the plasma membrane. The contents of the granule are then discharged into the acinar lumen and washed out by an exudate of plasma crossing the tight junctions, linking the acinar cells together, and subsequently by ductular secretions. In the period between meals the granule constituents are resynthesized by the acinar cells and then stored until needed to digest the next meal. Resynthesis may be stimulated by the same agonists that evoke the initial secretory response. Biliary Secretion Another important digestive juice that is mixed with the meal in the small intestinal lumen is bile. Bile is produced by the liver, and the mechanisms that are involved, as well as the specific constituents, will be discussed in greater detail in Chapter 32 when we address the transport and metabolic functions of the liver. However, for purposes of the current discussion, bile is a secretion that serves to aid in digestion and absorption of lipids. Bile flowing out of the liver is stored and concentrated in the gallbladder until it is released in response to ingestion of a meal. When considering the small intestinal phase of meal assimilation, the bile constituents we are most concerned with are the bile acids. These form structures known as micelles that serve to shield the hydrophobic products of lipid digestion from the aqueous environment of the lumen. Bile acids are in essence biological detergents, and large quantities are needed on a daily basis for optimal lipid absorption-as much as 1 to 2 g/day. The majority of the bile acid pool is recycled from the intestine back to the liver after each meal via the enterohepatic circulation. We will consider the processes involved in assimilation of each of these nutrients in turn, beginning with carbohydrates. Carbohydrate digestion occurs in two phases: in the lumen of the intestine and then on the surface of enterocytes in a process known as brush border digestion. The latter is important in generating simple absorbable sugars only at the point where they can be absorbed. This may therefore limit their exposure to the small number of bacteria present in the small intestinal lumen that might otherwise use these sugars as nutrients. Passive Terminal Ileum Portal vein asbt Active Digestion of Carbohydrates Dietary carbohydrates are composed of several different molecular classes. Starch, the first of these, is a mixture of both straight- and branched-chain polymers of glucose. The straight-chain polymers are called amylose and the branched-chain molecules are called amylopectin. Starch is a particularly important source of calories, especially in developing countries, and is found predominantly in cereal products. Disaccharides are a second class of carbohydrate nutrients that includes sucrose (consisting of glucose and fructose) and lactose (consisting of glucose and galactose), the latter being an important caloric source in infants. It is, however, a key principle that the intestine can absorb only monosaccharides and not larger carbohydrates. Finally, many food items of vegetable origin contain dietary fiber, which consists of carbohydrate polymers that cannot be digested by human enzymes. These polymers are instead digested by bacteria present largely in the colonic lumen (see Chapter 31), thereby allowing salvage of their caloric value. Dietary disaccharides are hydrolyzed to their component monomers directly on the surface of small intestinal epithelial cells by brush border digestion, mediated by a family of membrane-bound, heavily glycosylated hydrolytic enzymes synthesized by small intestinal epithelial cells. Brush border hydrolases critical to the digestion of dietary carbohydrates include sucrase, isomaltase, glucoamylase, and lactase (Table 30. Glycosylation of these hydrolases is believed to protect them to some extent from degradation by luminal pancreatic proteases. However, between meals the hydrolases are degraded and must therefore be resynthesized by the enterocyte to participate in digesting the next carbohydrate meal. Sucrase/isomaltase and glucoamylase are synthesized in quantities that are in excess of requirements, and assimilation of their products into the body is limited by the availability of specific membrane transporters for these monosaccharides (see Uptake of Carbohydrates). The relative paucity of lactase means that digestion of lactose, rather than uptake of the resulting products, is rate limiting for assimilation. If lactase levels fall below a certain threshold, the disease of lactose intolerance results. Active uptake of conjugated bile acids occurs via the apical sodium-dependent bile acidtransporter(asbt). However, when the meal contents reach the terminal ileum, after lipid absorption has been completed, the conjugated bile acids are reabsorbed by a symporter, the apical Na+-dependent bile acid transporter (asbt), that specifically takes up conjugated bile acids in association with sodium ions. Only a minor portion of the bile acid pool is left to spill over into the colon in health, and here bile acids become deconjugated and subject to passive reabsorption.
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The bile acid secretion rate normally averages 30g/24h medications help dog sleep night order 200mg prometrium amex, whereas the synthesis rate averages 0 administering medications 7th edition ebook buy prometrium with visa. The pairs of vertical and horizontal dotted lines depict the normal range for bile acid secretion and synthesis medicine januvia cheap 100 mg prometrium visa, respectively medicine plus order 200 mg prometrium with mastercard. Increased secretion (simulated by bile acid feeding) increases the rate of return of bile acids to the liverviaportalblood,whichexertsanegativefeedbackonsynthesis. Conversely,interruptionoftheenterohepaticcirculation,suchasafter ileal resection, can increase synthesis to values more than 10-fold higherthannormal. Thusthefigureillustratesthatthemajorityof the bile acid pool circulatesbetweenthe liver, gallbladder, and small intestine,ratherthanbeinginthesystemiccirculation. Finally, conjugated bilirubin, which is water soluble, and a variety of additional organic anions and cations formed from endogenous metabolites and xenobiotics are secreted into bile across the apical membrane of the hepatocyte. Bile Modification in Ductules the cholangiocytes lining the biliary ductules are specifically designed to modify the composition of bile. Flow of bile is thereby increased during the postprandial period when bile acids are needed to aid in assimilation of lipid. However, in the period between meals, outflow is blocked by constriction of the sphincter of Oddi, and thus bile is redirected to the gallbladder. During gallbladder storage, bile becomes concentrated because sodium ions are actively absorbed in exchange for protons, and bile acids, as the major anions, are too large to exit across the gallbladder epithelial tight junctions. Any additional bile acid monomers that become available as a result of concentration are thus immediately incorporated into existing mixed micelles. This also reduces to some extent the risk that cholesterol will precipitate from bile. However, cholesterol is supersaturated in the bile of many adults, with precipitation normally being inhibited by the presence of 576 S E C T I O N 6 Berne & Levy Physiology antinucleating proteins. Prolonged storage of bile increases the chance that nucleation can occur, thus making a good case for never skipping breakfast and perhaps explaining why gallstone disease is relatively prevalent in humans. Bile is secreted from the gallbladder in response to signals that simultaneously relax the sphincter of Oddi and contract the smooth muscle that encircles the gallbladder epithelium. In addition, intrinsic neural reflexes and vagal pathways, some of which themselves are stimulated by the ability of cholecystokinin to bind to vagal afferents, also contribute to gallbladder contractility. The net result is ejection of a concentrated bolus of bile into the duodenal lumen, where the constituent mixed micelles can aid in lipid uptake. Then, when no longer needed, the bile acids are reclaimed and reenter the enterohepatic circulation to begin the cycle again. However, the other components of bile are largely lost in stool, thus providing for their excretion from the body. Bilirubin Formation and Excretion by the Liver the liver is also important for excretion of bilirubin, which is a metabolite of heme that is potentially toxic to the body. Bilirubin is an antioxidant and also serves as a way to eliminate the excess heme released from the hemoglobin of senescent red blood cells. Indeed, red blood cells account for 80% of bilirubin production, with the remainder coming from additional heme-containing proteins in other tissues such as skeletal muscle and the liver. Bilirubin can cross the blood-brain barrier and, if present in excessive levels, results in brain dysfunction secondary to neuronal cell death and the activation of astrocytes and microglia; it can be fatal if left untreated. Bilirubin and its metabolites are also notable for the fact that they provide color to bile, feces, and to a lesser extent urine. By the same token, when bilirubin accumulates in the circulation as a result of liver disease, it is responsible for the common symptom of jaundice, or yellowing of the skin and conjunctiva. Bilirubin is synthesized from heme by a two-stage reaction that takes place in phagocytic cells of the reticuloendothelial system, including Kupffer cells and cells in the spleen. The enzyme heme oxygenase that is present in these cells liberates iron from the heme molecule and produces the green pigment biliverdin. Because bilirubin is essentially insoluble in aqueous solutions at neutral pH, it is transported through the bloodstream bound to albumin. In the microsomal compartment, bilirubin is then conjugated with one or two molecules of glucuronic acid to enhance its aqueous solubility. In both cases, bilirubin conjugates are formed in the liver, but with no means of exit they regurgitate back into plasma for urinary excretion. Notably the conjugated forms of bilirubin cannot be reabsorbed from the intestine, thereby ensuring they can be excreted. However, transport of bilirubin across the hepatocyte (and indeed its initial uptake from the bloodstream) is relatively inefficient, so some conjugated and unconjugated bilirubin is present in plasma even under normal conditions. Both circulate bound to albumin, but the conjugated form is bound more loosely and thus can enter the urine. In the colon, bilirubin conjugates are deconjugated by bacterial enzymes, whereupon the bilirubin liberated is metabolized by bacteria to yield urobilinogen, which is reabsorbed, and urobilins and stercobilins, which are excreted. Absorbed urobilinogen in turn can be taken up by hepatocytes and reconjugated, thus giving the molecule yet another chance to be excreted. Measurement of bilirubin in plasma, as well as assessment of whether it is unconjugated or conjugated, is an important tool in the evaluation of liver disease.
Neuroimaging abnor malities are nonspecific and include enhancement of the meninges postcontrast administration treatment centers for drug addiction buy genuine prometrium online, communicat ing and/or obstructive hydrocephalus medicines360 purchase prometrium 200mg online, and infarctions typically in the basal ganglia symptoms tuberculosis discount 200mg prometrium overnight delivery. Treatment of tuberculous meningitis includes a combination of isoniazid medicine 5513 cheap 100mg prometrium with mastercard, rifampin, pyrazin amide, ethambutol, and pyridoxine. This complication may also require a ventriculostomy or a ventriculoperitoneal shunt. The treatment of tubercu lomas includes a three or fourdrug regimen similar to the treatment of tuberculous meningitis. Superficial tuberculomas can be surgically excised if they do not respond to antituberculous chemotherapy. Two or more adjacent vertebral bodies are often involved, and infection can spread to the disk and/or the epidural space. The thoracic and lumbar spine are the most commonly affected areas, and thus the clinical presentation is with back pain in the thoracic or lumbar area and fever. When the epi dural space is involved, signs and symptoms of progres sive spinal cord compression can develop. Treatment includes antituberculous chemotherapy and surgical decompression if spinal cord compression is present. Deep, infected punctures are most susceptible, because organisms thrive best anaerobically. Clostridium tetani: grampositive, spore-bearing rods tetanus the bacterium Clostridium tetani produces a neurotoxin tetanospasmin (tetanus toxin) in wounds it contami nates. Tetanus toxin enters the central nervous system by retrograde axonal transport in motor neurons from its site of formation in a wound to its site of action- the motor neuron cell bodies in the ventral gray of the spinal cord and brainstem. With the loss of inhib itory input, the uninhibited lower motor neuron increases resting muscle tone, producing rigidity. Tetanus is divided into four clinical forms: localized, generalized, cephalic, and neonatal. The incubation period is followed by the period of onset of tetanus, which is defined as the interval from the first symptom to the first reflex spasm. Localized tetanus is limited to the extremity in which there is a contami nated wound, blister, or burn. This is followed by the develop ment of a continuous spasm or rigidity in the group of muscles in close proximity to the wound. In generalized tetanus, the usual manifesting sign is trismus (lockjaw), which is a rigidity of the mas seter muscles, causing an inability to open the mouth to speak or to chew. Another early sign is risus sardoni cus due to increased tone in the orbicularis oris, causing a sneering grin. The generalized spasm consists of opis thotonic posturing with flexion and adduction of the arms, clenching of the fists, and extension of the lower extremities. Sudden spasms of the muscles of respiration may stop respiration for 10 to 20 seconds, and laryngeal or pharyngeal spasms may obstruct the airway, compromising respiration. Cephalic tetanus involves the muscles supplied by one or more cranial nerves and almost always follows a head wound. Neonatal tetanus typically develops as a result of infection of the umbilical stump, and the usual manifesting symptom is poor feeding. The infant cannot suck, and when a finger is put into its mouth its jaw clamps tightly. This is fol lowed by involvement of the muscles of facial expres sion, risus sardonicus, and then opisthotonos. Toxin produced locally passes via bloodstream or along nerves to central nervous system Motor neurons of spinal cord (anterior horn) and brainstem become hyperactive because toxin specifically attacks inhibitory (Renshaw) cells Spasm of jaw, facial, and neck muscles (trismus [lockjaw], risus sardonicus), and dysphagia are often early symptoms after variable incubation period Complete tetanic spasm in advanced disease. When tetanus is suspected, a careful immunization history should be obtained because tetanus is unlikely if the patient has received a complete primary series of toxoid injections with booster doses every 10 years. Diagnosis is depen dent on ruling out the diseases that have an appearance similar to tetanus, including strychnine poisoning, a dystonic reaction secondary to a neuroleptic agent or a dopamineblocking agent, and rabies. Dystonic reactions are quickly reversed with intravenous benz tropine or diphenhydramine. In many instances, the cause is a viral; less often, mycobacterial, spirochetal, parasitic, or fungal infection is responsible. A similar syndrome can arise with sarcoidosis, various connective tissue diseases, neoplastic leptomeningeal involvement, or as a drug induced complication. Louis encephalitis virus is transmitted mainly in North America during late summer or early autumn and typically causes mild nonspecific symptoms but occasionally an encephalitic illness. Eastern equine encephalitis virus, found in the Carib bean and eastern United States, infects humans, horses, and some bird species. Other variants of the virus occur in Central and South America, where they cause equine disease. When symptoms do occur, they may consists solely of a mild nonspecific flulike systemic illness, with head ache, fever, malaise, aching pains, and vomiting, from which complete recovery occurs with 7 to 10 days in the absence of cerebral involvement. In uncommon instances, however, a fulminating encephalitic illness occurs after an incubation period of 3 to 10 days and is characterized by confusion, delirium, irritability, rest lessness, seizures, and, eventually, loss of consciousness. The encephalitic illness is associated with a 33% mor tality rate, and about Half of the survivors have residual cognitive or other neurologic deficits. No vaccine is available, and prevention therefore depends on reducing exposure to mosquitoes. The West Nile virus, a flavivirus usually found in Africa, West Asia, and the Middle East, was not docu mented in the Western Hemisphere until 1999.
They can be converted to active androgens peripherally and provide about 50% of circulating androgens in women medications not to be taken with grapefruit buy cheap prometrium 100 mg on-line. Excessive adrenal androgens in women can lead to various degrees of virilization and ovarian dysfunction treatment definition prometrium 100mg without prescription. It promotes Na+ and water reabsorption by the distal tubule and collecting duct while promoting renal K+ and H+ secretion treatment 7th feb discount prometrium 100mg with mastercard. It also has a proinflammatory medications with codeine order cheap prometrium, profibrotic effect on the cardiovascular system and causes left ventricular hypertrophy and remodeling. Common symptoms include hypotension, hyperpigmentation, muscle weakness, anorexia, hypoglycemia, and hyperkalemic acidosis. Congenital adrenal hyperplasia is caused by a congenital enzyme deficiency that blocks production of cortisol. Functional chromaffin cell plasticity in response to stress: focus on nicotinic, gap junction, and voltage-gated Ca2+ channels. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes. Selective glucocorticoid receptor modulation: new directions with non-steroidal scaffolds. Describe the general anatomical components of the male and female reproductive system. Map out the organization of the testis, with the Sertoli cells and developing sperm cells within the intralobular compartment, and the Leydig cells and capillary plexus within the interlobular/interstitial compartment. Diagram the process of testosterone synthesis within the Leydig cells, and the peripheral conversion of testosterone to estradiol or dihydrotestosterone. Diagram the male hypothalamus/pituitary/testis axis, including all cell types and hormones involved. Map out the organization of the ovary, and describe the various stages of follicular development, ovulation and corpus luteum formation. Map out the steroidogenic pathways in the corresponding cell types that lead to androgen, estrogen and progesterone synthesis. Diagram the female hypothalamus/pituitary/ovarian axis during the menstrual cycle, including all cell types and hormones involved. Explain changes in the female tract, with emphasis on the uterine endometrium, during the menstrual cycle. Describe the development and function of the mammary glands fertilization, implantation, and gestation. Normal gametogenesis in the gonads and development and physiology of the reproductive tract are absolutely dependent on the endocrine function of the gonads. The clinical ramifications of this hormonal dependence include infertility in the face of low sex hormone production, ambiguous genitalia in dysregulated hormone or receptor expression, and hormoneresponsive cancers, especially uterine and breast cancer in women and prostate cancer in men. In adult men the basic roles of gonadal hormones are (1) support of gametogenesis (spermatogenesis), (2) maintenance of the male reproductive tract and production of semen, and (3) maintenance of secondary sex characteristics and libido. The Testis Histophysiology Unlike the ovaries, the testes reside outside the abdominal cavity in the scrotum. The human testis is covered by a connective tissue capsule and divided into about 300 lobules by fibrous septa. The rete testis is continuous with small ducts, the efferent ductules, that lead the sperm out of the testis into the head of the epididymis on the superior pole of the testis. Once in the epididymis, the sperm pass from the head, to the body, to the tail of the epididymis and then to the vas (ductus) deferens. Viable sperm can be stored in the tail of the epididymis and vas deferens for several months. The gonads (testes and ovaries) perform an endocrine function that is regulated within a hypothalamicpituitary-gonadal axis. The gonads are distinct from other endocrine glands in that they also perform gametogenesis. Intratubular Compartment the seminiferous tubule is lined by a complex seminiferous epithelium composed of two cell types: sperm cells in various stages of spermatogenesis and the Sertoli cell, which is a "nurse cell" in intimate contact with all sperm cells. Developing Sperm Cells Spermatogenesis involves the processes of mitosis and meiosis. Stem cells called spermatogonia reside at the basal level of the seminiferous epithelium. Spermatogonia divide mitotically to generate daughter spermatogonia (spermatocytogenesis). One or more spermatogonia remain within the stem cell population, firmly adherent to the basal lamina. However, the majority of these daughter spermatogonia enter meiotic division, which results in haploid spermatozoa on completion of meiosis. These divisions are accompanied by incomplete cytokinesis such that all daughter cells remain interconnected by a cytoplasmic bridge. This configuration contributes to the synchrony of development of a clonal population of sperm cells.
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