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Candidates with a residual defect diabetes mellitus definition emedicine purchase avapro with paypal, loose bodies or abnormal imaging are graded P8 blood sugar readings discount avapro on line. Candidates with a history of systemic lupus erythematosus treatment diabetes mellitus order discount avapro on-line, scleroderma diabetes insipidus in young adults buy online avapro, polyarteritis nodosa diabetic eating plan order cheap avapro on line, polymyositis and other connective tissue disorders are graded P8 blood glucose 90 buy avapro 300 mg without prescription. All cases of myopathy with muscle wasting are graded P8, but those with minimal post-traumatic wasting, causing no significant loss of function, may be graded P2 provided functional assessment is normal. General guidance about previous fractures of all appendicular skeletal bones is provided below. Specific guidance may also be found under conditions affecting the U and L assessment. For those with normal function and with no deformity, a period of at least 12 months must have elapsed since the fracture before selection due to remodelling following fracture which often takes up to 12 months. In cases of doubt consult the single-Service Occupational Physicians responsible for the selection of recruits. Candidates with fractures where union is confirmed without deformity, who are asymptomatic with activity comparable with military training and have full function of the joints above and below the injury may be graded P2. If there is mild deformity with no symptoms and full function, referral to the single-Service Occupational Physicians responsible for the selection of recruits should be considered. Fractures with union confirmed, no deformity, and asymptomatic with exercise comparable with military training, may only be accepted following referral to the single-Service Occupational Physicians responsible for the selection of recruits because function is often restricted and requires specialist assessment. Candidates with the following simple (non-fixed) fractures may be considered fit after 6 months. In cases of doubt consult the single-Service Occupational Physician responsible for the selection of recruits: a. A period of at least 12 months must have elapsed since the latest surgery in all cases before selection, as remodelling following a fracture often takes up to 12 months. Candidates with upper limb fractures whose union is confirmed, without deformity, with no tenderness over the area of metal work / fracture site who are asymptomatic with exercise comparable with military training over the last 3 months and have full function of the joints above and below the injury may be graded P2. If surgery has resulted in restitution of anatomy, the candidate may be acceptable provided they are symptom-free with activity comparable with military training for 3 months and have been referred for specialist assessment. Candidates who have received complex surgery involving joints or surgical fixation of major upper and lower limb joints are normally. Candidates recovered from uncomplicated, single stress fractures who are symptom free with proven activity comparable with military training for a minimum of 3 months and radiological confirmation of healing may be graded P2. Candidates with any femoral neck stress fracture or multiple or recurrent stress fractures at any site are graded P8. Candidates who have had joint prostheses (including articular resurfacing) are normally graded P8. Candidates with a current diagnosis of osteopaenia or osteoporosis due to any cause, are normally graded P8. J R Army Med Corps 2005; 151: 2-4) 149 Osteopaenia is defined as a T Score of between -1 and -2. Deformities of individual parts of the upper limbs, such as loss of any finger or parts of a finger or other parts of the hand are assessed according to functional capacity. Particular consideration must be given to weapon handling and formal competent assessment is recommended in all cases. The advice of the single-Service Occupational Physicians responsible for the selection of recruits should be obtained when there is any doubt regarding the grading under U. Candidates with loss of any finger of either hand may be graded U2, however, grading should be assessed according to residual functional capacity. Those with non-union of fractures of the carpal bones or painful wrist with limitation of movement are graded P8U8. Those with greater loss are usually graded P8U8 although referral may be indicated. Candidates who have lost more than 20 of either pronation or supination are graded P8U8. Varus or valgus angulation should not preclude entry provided that normal function can be demonstrated. The following guidance is provided for candidates who have suffered shoulder dislocation: a. Candidates with no more than two episodes of dislocation (in the same shoulder), who 151 have full shoulder function, are asymptomatic, and with negative apprehension test be graded U2 subject to referral for further assessment. Candidates with three or more dislocations (in the same shoulder), regardless of any subsequent stabilisation procedure, or who are symptomatic, have evidence of early arthritic change or have a positive apprehension test are to be graded P8U8. Candidates who have had a single shoulder stabilisation procedure who have full shoulder function, are asymptomatic, and with negative apprehension test (see b. Candidates who have had more than one shoulder stabilisation procedure in the same shoulder should be graded P8U8. Subluxation requiring acute medical intervention is to be treated as a shoulder dislocation. The interaction between load carriage equipment and mal-union or un-united fracture of the clavicle often results in pain. At least 12 months must have elapsed since the fracture/dislocation/surgery with the exception of a simple fracture of the clavicular shaft that may be considered for assessment after 6 months. Candidates with a deformity from a fractured clavicle that is asymptomatic, allows full shoulder movement and does not cause symptoms with load carriage during activity comparable with military training for 3 months may be graded U2. Candidates with deformity that is asymptomatic, allows full shoulder movement and does not cause symptoms with load 152 carriage during activity comparable with military training for 3 months may be graded U2. Candidates with deformity that causes symptoms, restriction of movement or interferes with load carriage are graded P8U8. Candidates with any history of pain related to overuse (eg para-tendonitis crepitans), or of upper limb disorders, such as carpal tunnel syndrome, bursitis and epicondylitis, are normally graded P8U8. Service life places great demands upon the lower limbs and even minor abnormalities and conditions can be exacerbated by, and may break down during training. Lower limb injuries (especially knee) are the main cause of medical discharge during training and of early invaliding. This should include particular reference to physical activity, (see paragraph 2) sports and symptoms arising in association with footwear of any kind. Candidates are to be judged on individual merit with their grading based on functional capacity and prognosis. Normal structure and function of the spine is an essential requirement for military service. Candidates with minimally abnormal scoliosis, kyphosis or lordosis with no associated back pain with full and free movement of all spinal segments (cervical, thoracic and lumbar) may be graded L2. Candidates with scoliosis or other curvature requiring treatment, that is associated with an on-going disease process/neuromuscular 155 or neurological dysfunction or back pain are to be graded P8U8 or P8L8 as appropriate. Candidates without symptoms who have achieved 3 months activity comparable with military training (especially load-carrying ability) are to be referred for specialist assessment. All candidates who have been diagnosed with these conditions (whatever the degree of slip for spondylolisthesis) but are now asymptomatic during activity comparable with military training for a minimum of 3 months are to be referred to single-Service Occupational Physician responsible for the selection of recruits. Candidates with an incidental finding, without history of symptoms and in the absence of other abnormality may be graded L2. Candidates with any history of spinal fracture (including wedge fractures of the vertebral body but excluding resolved spinous and transverse process fractures) are to be 156 graded P8L8. However, candidates who have had a single-level discectomy (eg for sequestered disc) may be graded L2 subject to referral to single-Service Occupational Physician responsible for the selection of recruits providing the candidate is at least 2 years post-operation, is asymptomatic when undertaking activity comparable with military service and has been doing so for at least 3 months and there is no evidence of osteo-arthritis on imaging. Candidates with previous non-bony neck injury (eg whiplash or muscular sporting injury) may be graded U2 provided they are asymptomatic for at least 12 months including exercise comparable with military training for 3 months. There is strong evidence that a history of back pain is the best predictor of future problems most notably, frequency and duration of symptoms, time since last episode, referred pain, surgery and time off work. Bending forward accentuates paraspinal and rib prominences, which is suggestive of scoliosis. This is the hallmark examination finding that leads to a suspicion of scoliosis during screening evaluation. The presence of an asymmetric scapular prominence may suggest an upper thoracic curve. The reason for this is not established but a change in the general shape of the spine affects its mechanical performance and such candidates are likely to suffer recurrent episodes of back pain. Occupational Health Guidelines for the Management of Low Back Pain 2000 Evidence Review and Recommendations. Predicting who develops chronic low back pain in primary care: a prospective study. Candidates with a single episode of simple acute back pain with no radiation which has responded to treatment, without structural cause in the previous 12 months and who are now asymptomatic with activity comparable with military training for a minimum of 6 months may be graded P2 provided the triggering event indicates that the individual is not at undue risk of recurrence. Candidates with a history of three or more episodes of back pain are to be graded P8L8. Candidates with any episode of chronic back pain (at least 12 weeks) are graded P8L8 d. Candidates with a history of sciatic pain with or without back pain are graded P8L8 Leg length discrepancy 38. However, those who are asymptomatic with no over-riding or callosity of the second toe; or who have had hallux valgus osteotomy, have normal function and are asymptomatic during activity comparable with military training are to be referred to the single-Service Occupational Physician responsible for the selection of recruits. Candidates with minor conditions that allow the usage of normal footwear (and simple off-the-shelf orthotics if necessary) and are asymptomatic during activity comparable with military training for 3 months may be graded L2. However, candidates who require custommade footwear and/or orthotics are to be graded P8L8. Candidates with evidence of abnormal pressure areas (eg red inflamed skin, soft or hard corns) are to be graded P8L8, as these findings indicate abnormalities of biomechanics/gait. Those with loss of terminal phalanx of great toe with no painful stump may be graded L2. Those with total or sub-total loss of other toes may be graded L2 subject to the outcome of functional testing. Those with mobile flat feet causing symptoms or with rigid flat feet are graded P8. Candidates with a deformity that has caused no trouble in the past with a foot that is mobile with no pressure areas or fixed clawing may be graded L2 if the condition is considered compatible with the demands associated with training and the wearing of boots, and provided that there is no associated neurological disorder (such as peroneal muscular dystrophy, etc). Candidates with a positive past history, or limitation of movements or evidence of pressure areas are graded P8L8. Candidates with previous ankle sprain or fracture may be graded L2 provided that they have made a full recovery, have no limitation of movement, and are asymptomatic during activity comparable with military training for 3 months. Candidates who have had a ligamentous repair (eg Brostrom-Gould Repair) or ligamentous replacement (eg Evans Tenodesis) are to be referred to the single-Service Occupational Physician responsible for the selection of recruits provided at least 12 months has elapsed post-surgery, normal function has been restored and there are no symptoms during activity comparable with military training for 3 months. Knee problems account for a large proportion of the medical discharges that occur during recruit training. Candidates who have been symptom-free for at least 12 months (at least 24 months for Osgood-Schlatter disease) during activity comparable with military training for 3 months may be graded L2. Candidates who have an arthroscopic partial or sub-total meniscectomy and who are asymptomatic during activity comparable with military training for 3 months may be graded L2. Those who have had complete 158 or open meniscectomy or meniscal transplantation (including autologous chondrocyte 159 transplantation) are graded P8L8. Candidates with any history of complete Anterior or Posterior Cruciate Ligament rupture whether managed conservatively or surgically are graded P8L8. Candidates with a history of partial tears of the Anterior or Posterior Cruciate Ligament are to be referred to the single-Service Occupational Physician responsible for the selection of recruits. Candidates with a history of partial of complete rupture of any other knee ligaments are to be referred to the single-Service Occupational Physician responsible for the selection of recruits. Candidates with any history of hip disease or fixation, regardless of apparent recovery, are to be referred to the single-Service Occupational Physician responsible for the selection of recruits. Candidates with a history of slipped femoral epiphysis where the hip has been remodelled to normality, have a full range of internal and external rotation and are asymptomatic during activity comparable with military training for 3 months may be graded L2 subject to referral to the single-Service Occupational Physician responsible for the selection of recruits. If imaging confirms normal anatomy and the candidate is asymptomatic with a full range of hip movement and a satisfactory functional assessment candidates are to be referred to the single-Service Occupational Physician responsible for the selection of recruits. Enquiry should be made as to exercise undertaken eg running, sport, hill-walking and this information should be included in the 160 referral. The M grading is a clinical quality distinguishing those whose mental capacity makes them suitable for normal training and posting, from those of limited intellectual capacity who necessitate rejection. The recruit selection test procedures will usually provide an objective assessment of mental ability to facilitate grading. All examining medical officers should have a good knowledge of mental health matters and having consulted the guidance in this section are encouraged to make a confident decision at the time of examination. However, it should not be assumed that a recorded or acknowledged history of a mental health problem is absolute evidence for it.

Preeclampsia superimposed on chronic hypertension and proteinuria diabetes symptoms you tube purchase avapro 300 mg online, both present before 20 weeks (severe exacerbation of blood pressure blood glucose iphone discount avapro 150mg overnight delivery, systolic>180 mmHg diabetes type 1 undiagnosed 300 mg avapro visa, diastolic>110 mmHg diabetes test wikipedia generic 150mg avapro amex, in last half of pregnancy) c diabetic diet webmd generic avapro 150mg with visa. Masked chronic hypertension (persists beyond 12 weeks postpartum) Key Objectives 2 Describe normal changes in blood pressure during pregnancy and define hypertension in pregnancy with these changes in mind diabetes symptoms blood pressure purchase avapro 150 mg line. Outline the changes in utero-placental circulation (impaired trophoblast invasion and placental ischemia) that occur in preeclampsia. Outline later changes resulting from placental ischemia such as altered capillary permeability, intravascular inflammatory response, abnormal prostaglandin metabolism, and activation of endothelial cells and the coagulation system. Regardless of underlying cause, certain general measures are usually indicated (investigations and therapeutic interventions) that can be life saving. Myxedema, Addison, liver failure Key Objectives 2 Elicit clinical and laboratory information necessary to diagnose the correct type of hypotension/shock. Outline the effect of cardiac output and systemic vascular resistance on blood pressure and tissue perfusion. Describe the effect of prolonged, severe hypotension on systemic tissue perfusion (results in decreased oxygen delivery, deprivation, and eventual cellular hypoxia). List some derangement of critical biochemical processes (cell membrane ion pump dysfunction, intracellular edema, leakage of intracellular contents, inadequate regulation of intracellular pH) that result from cellular hypoxia. Latex Key Objectives 2 Differentiate anaphylaxis from conditions which are similar such as shock from other causes, other flush syndromes, restaurant syndrome, increased endogenous histamine production, acute respiratory failure syndromes, or non-organic syndromes such as panic attacks or Munchausen syndrome. Invasive (invasive ductal/lobular carcinoma, tubular, medullary, papillary, mucinous) 2. An appropriate and prompt evaluation is important in order to relieve anxiety, even though breast cancer is not generally considered a medical emergency. It is the responsibility of the primary care physician to be an advocate for the patient throughout the entire process of evaluation of the breast lump. The physician should learn about the proficiency of local consultants in order to communicate these facts to the patient. The patient needs to be followed very carefully, maximizing exchange of ideas at every step of the process until suitable resolution is achieved. Abnormal breast discharge (usually Uni ductal, bloody or serosanguineous) breast neoplasm, benign or malignant Key Objectives 2 Differentiate between galactorrhea and breast discharge. Primary gonadal failure (Klinefelter, enzymatic defects in testosterone synthesis, testicular infections, trauma, malnutrition/starvation, renal failure) ii. Inhibitors of testosterone synthesis/action (aldactone, cimetidine, flutamide) iii. Idiopathic Key Objectives 2 Differentiate between gynecomastia and breast carcinoma. Contrast pathophysiological mechanisms for gynecomastia (absolute increase in free estrogens compared to decreased endogenous free androgens, versus relative increase in free estrogen/free androgen ratio, as opposed to androgen insensitivity). An understanding of the patho-physiology and treatment of burns and the metabolic and wound healing response will enable physicians to effectively assess and treat these injuries. Communicate with the burn patients or their legitimate delegates in order to obtain consent or refusal to investigate or treat. Explain the potential outcome of the burn and available options; determine whether the patient can provide the information back to you in a coherent manner. Consult hospital ethics committees about continuing care in patients with burns so extensive that mortality approaches 100%. In patients with severe burns, avoid marginally beneficial investigations or therapies. Describe the local (necrosis, inflammation) and systemic (fluids and electrolytes, hypermetabolism) manifestations of thermal injury. Discuss the unique features of electrical injury in relation to skeletal muscle injury and potential effect on cardiac and renal function. This differentiation by physicians is important for both diagnostic and management reasons. Miscellaneous Key Objectives 2 Although not common, hypercalcemia can cause severe anatomic injury to the kidneys, and if severe, patients may develop hypercalcemic crisis. Formulate a management plan for hypercalcemia consistent with its causal condition. Outline the metabolism of calcium including absorption, various forms of calcium in the blood, deposition, resorption and excretion. Hypomagnesemia Key Objectives 2 Calculate a corrected calcium concentration in the presence of hypoalbuminemia before initiating any other investigation (0. Include the various hormones (parathyroid, calcitonin), vitamin D and calcium receptors affecting these processes. Contrast the action of furosemide and thiazide diuretics on renal calcium handling. Serum phosphate concentration is primarily determined by the ability of the kidneys to excrete dietary phosphate. As a consequence, balance is maintained unless the load is acute and excessive (>130 mmol/day). In the community, cardiac arrest most commonly is caused by ventricular fibrillation. As a consequence, operational criteria for cardiac arrest do not rely on heart rhythm but focus on the presumed sudden pulse-less condition and the absence of evidence of a non-cardiac condition as the cause of the arrest. Acquired (associated with ischemic injury from coronary atherosclerosis, hypertension, diabetes mellitus) i. Chest wall trauma Key Objectives 2 this ultimate medical emergency requires immediate treatment. However, in other situations, most ethicists believe that autonomy takes precedence over beneficence. As a consequence, physicians generally request decisions about resuscitation from patients and their families. This does not mean that physicians should not provide patients and families with their expert opinion on the advisability of the procedure. This would be akin to abandoning responsibility to protect patients against inappropriate therapy in favor of complete autonomy. Rather than absolute autonomy, a more balanced approach of enhanced autonomy or fiduciary role is considered appropriate. Informed consent is a process that requires the involvement of both patient and physician. It is required that the physicians provide an opinion regarding what is considered the proper course of action. Informed consent requires explanations by physicians to patients and other decision-makers that facilitate reaching a decision. Consequently, it is important to determine whether the patient had expressed intention for such donation through advanced directives. This may lead to exclusion of patients who might benefit from evolving neurological therapies as well as lost opportunities for potential organ donation for those patients who may be neurologically dead but not yet diagnosed. The process of making such decisions should include a careful definition and full discussion with family about the goals of therapy. Consideration should be given to whether the goal is cure at the expense of short-term discomfort or to relieve pain and suffering or the possibility of organ donation. If prognostic information indicates that there is no hope of meaningful recovery, end-of-life care is advised and provided. Outline the interaction between factors such as anatomic and functional abnormalities. Explain the importance of determining the underlying heart rhythm on pathophysiological understanding as well as potential treatment strategies. Although coronary heart disease primarily occurs in patients over the age of 40, younger men and women can be affected (it is estimated that advanced lesions are present in 20% of men and 8% of women aged 30 to 34). Physicians must recognise the manifestations of coronary artery disease and assess coronary risk factors. Myocardial infarction -<2% in primary care (acute, evolving, recent, established) B. Compare some of the debated issues related to the genesis of heart sounds/murmurs and the mechanism of their production. Formulate the pathophysiology of myocardial ischemia in terms of myocardial oxygen demand and supply. With respect to demand, evaluate the role of heart rate, afterload, myocardial wall tension/stress (product of preload and myocardial muscle mass), and myocardial contractility. With respect to supply, evaluate the role of oxygen carrying capacity of blood (oxygen tension and hemoglobin level), degree of oxygen unloading from hemoglobin, and coronary flow. With respect to coronary flow, evaluate role of coronary artery diameter, collateral flow, perfusion pressure (gradient from aorta, to coronary artery, to left ventricular end diastolic pressure), and heart rate/diastolic period. In children or infants, suspicion of a bleeding disorder may be a family history of susceptibility to bleeding. If a coherent and consistent justification does not exist, identify a substitute decision-maker. However, if the patient refuses because of a lifelong widely shared religious belief that prohibits blood transfusions, the capacity to give consent is probably present, and the decision should be respected. Prenatal diagnosis of sickle cell disease and thalassemia has been feasible for over 15 years and raises ethical issues for physicians. The decision to receive prenatal diagnosis is influenced by many things (culture, religion, education, number of children, etc. Access to prenatal genetics services for all is important lest genetic screening become limited to the wealthy. In reproductive genetics, there may be ethical obligations to both mother and fetus. Prenatal counseling should be non-directive not restricted to those willing to have an abortion. Since the only pragmatic options for mothers are abortion or no children, it is vital that women not be pressured into prenatal diagnosis. At times it is possible that a child with extensive bruises represents not a bleeding diathesis but child abuse. There is a need to first make certain whether the problem is one of abuse or bleeding disorder. If the problem is suspected to be child abuse, there may be a requirement for reporting. Factor V Leiden mutation, antithrombin deficiency (>50% of inherited thrombophilias) b. Other (antiphospholipid antibody syndrome, nephrotic syndrome) Key Objectives 2 Identify patients at risk for venous thromboembolism. One definition is straining, incomplete evacuation, sense of blockade, manual maneuvers, and hard stools at least 25% of the time along with<3 stools/week for at least 12 weeks (need not be consecutive). Bowel obstruction Key Objectives 2 Since constipation is usually not due to serious disease, first exclude low fibre and lack of activity. It is important to differentiate functional from organic causes in order to develop appropriate management plans. Endocrine/Metabolic (hypothyroid, diabetes insipidus/mellitus, hypercalcemia, hypokalemia, medications) Key Objectives 2 Determine whether the constipated infant/child should be investigated for a serious cause or should be managed symptomatically. Counselling patients about which method to use, how, and when is a must for anyone involved in health care. Sterilization, female Key Objectives 2 Determine whether there are any absolute or relative contraindications to the use of hormonal contraceptives. Although different provinces specify different ages at which a patient is deemed capable of giving consent, minors may require contraceptive advice and prescriptions while at the same time desiring parental non-involvement. Physicians need to learn whether certain provinces make specific provisions for adolescents having the right to consent to contraceptives. The physician who for personal reasons does not wish to provide confidential contraceptive advice to an adolescent should provide names and phone numbers of other physicians or clinics where this type of advice and care is available.

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This anatomic arrangement facilitates limited segmental resections of the liver as is sometimes performed for partial hepatectomy diabetes in dogs vomiting order avapro 300mg overnight delivery. The initial right and left branches of the portal vein diabetes test amazon trusted 300mg avapro, hepatic artery diabetes type 1 diagnosis code order avapro line, and bile duct lie just outside the liver diabetes symptoms extreme fatigue buy generic avapro 150mg on line. The remaining branches travel in parallel within the liver in portal tracts diabetes prevention images buy avapro now, ramifying variably through 17 to 20 orders of branches diabetic diet breakfast buy cheap avapro 300mg. The vast expanse of hepatic parenchyma is serviced via approximately 450,000 terminal branches of the portal tract system. Portal vein blood enters the parenchyma via penetrating septal venules; hepatic arteriolar twigs supply the parenchyma, the major bile ducts, the vasa vasorum of the major portal veins and hepatic veins, and the hepatic capsule. Blood from all sources is collected into ramifications of the hepatic vein, which exits by the "back door" of the liver into the closely apposed inferior vena cava. Classically, the liver has been divided into 1to 2-mm diameter hexagonal lobules oriented around the terminal tributaries of the hepatic vein (terminal hepatic veins), with portal tracts at the periphery of the lobule. Accordingly, the hepatocytes in the vicinity of the terminal hepatic vein are called "centrilobular" (or centrolobular); those near the portal tract are "periportal. In the "acinus," the parenchyma is divided into three zones, zone 1 being closest to the vascular supply, zone 3 abutting the terminal hepatic venule, and zone 2 being intermediate. This zonation is of considerable metabolic consequence, since a lobular [2] gradient of activity exists for many hepatic enzymes. While acinar architecture is of greater physiologic significance, the anatomic terminology of the liver remains anchored in the older lobular terminology. The hepatic parenchyma is organized into cribiform, anastomosing sheets or "plates" of hepatocytes, seen in microscopic sections as cords of cells (Fig. Hepatocytes immediately abutting the portal tract are referred to as the limiting plate, forming a discontinuous rim around the mesenchyme of the portal tract. There is a radial orientation of the hepatocyte cords around the terminal hepatic vein. Hepatocytes exhibit minimal variation in overall size, but nuclei may vary in size, number, and ploidy, particularly with advancing age. Uninucleate, diploid cells tend to be the rule, but with increasing age, a significant fraction are binucleate, and the karyotype may range up to octaploidy. Blood traverses the sinusoids and exits into the terminal hepatic vein through innumerable orifices in the vein wall. Hepatocytes are thus bathed on two sides by well-mixed portal venous and hepatic arterial blood, placing hepatocytes among the most richly perfused cells in the body. The sinusoids are lined by fenestrated and discontinuous endothelial cells, which demarcate an extrasinusoidal space of Disse, into which protrude abundant microvilli of hepatocytes. Scattered Kupffer cells of the mononuclear phagocyte system are attached to the luminal face of endothelial cells, and scattered fat-containing perisinusoidal stellate cells are found in the space of Disse. These stellate cells play a role in the storage and metabolism of vitamin A and are transformed into collagen-producing myofibroblasts when there is inflammation of the liver. The portal tract carries branches of the portal vein, hepatic artery, and bile duct system. The portal vein gives rise to branching septal veins, which penetrate the hepatocellular parenchyma at regular intervals. Blood from the septal veins enters directly into the parenchymal sinusoids between hepatocytes. The hepatic artery gives off capillaries that supply the bile duct system; these capillaries usually dump into the portal vein but may deposit blood directly into sinusoids. The bile duct system gives off bile ductules, which traverse the mesenchyme of the portal tract to penetrate the parenchyma; at that point, they become hemicircular, abutting hepatocytes (not shown) to form the canals of Hering. Bile traveling through the bile canalicular system between hepatocytes enters into the biliary tree through these canals of Hering. Blood from the portal vein and hepatic artery travels through the sinusoids of the parenchyma toward the terminal hepatic vein, leaving the liver by this route. On the basis of blood flow, three zones can be defined, zone 1 being the closest to the blood supply and zone 3 being the farthest. Pathologists refer to the regions of the parenchyma as "periportal, midzonal, and centrilobular," the last term owing to the historical concept that the terminal hepatic vein was at the center of a "lobule. Note the blood-filled sinusoids and cords of hepatocytes; the delicate network of reticulin fibers in the subendothelial space of Disse stains light blue. The most obvious is necrosis of hepatocytes immediately around the terminal hepatic vein (so-called centrilobular necrosis, using the historical terminology), an injury that is characteristic of ischemic injury and a number of drug and toxic reactions. Pure midzonal and periportal necrosis are rare; the latter may be seen in eclampsia. With most other causes of hepatic injury, a variable mixture of hepatocellular death through the parenchyma is encountered. The hepatocyte necrosis may be limited to scattered cells within hepatic lobules (focal or spotty necrosis) or to the interface between the periportal parenchyma and inflamed portal tracts (interface hepatitis). With more severe inflammatory injury, necrosis of contiguous hepatocytes may span adjacent lobules in a portal-to-portal, portal-to-central, or central-to-central fashion (bridging necrosis). Necrosis of entire lobules (submassive necrosis) or of most of the liver (massive necrosis) is usually accompanied by hepatic failure. With disseminated candidal or bacterial infection, macroscopic abscesses may occur. Injury to the liver associated with an influx of acute or chronic inflammatory cells is termed hepatitis. Destruction of antigen-expressing liver cells by cytotoxic lymphocytes is a common mechanism of liver damage, especially during viral infection. In viral hepatitis, quiescent lymphocytes may collect in the portal tracts as a reflection of mild smoldering inflammation, spill over into the periportal parenchyma as activated lymphocytes (interface hepatitis) causing a moderately active hepatitis, or suffuse the entire parenchyma in severe hepatitis. However, scavenger macrophages (Kupffer cells and circulating monocytes recruited to the liver) engulf the apoptotic cell fragments within a few hours, generating clumps of inflammatory cells. Hence, identification of apoptotic hepatocytes is a sign of very recent hepatocyte destruction. Foreign bodies, organisms, and a variety of drugs may incite a granulomatous reaction. Hepatocytes have long life spans, and they proliferate in response to tissue resection or cell death (see Chapter 3). Hepatocellular proliferation is marked by mitoses, thickening of the hepatocyte cords, and some disorganization of the parenchymal structure. When hepatocellular necrosis occurs and 881 leaves the connective tissue framework intact, almost perfect restitution of liver structure can occur, even when the necrosis is submassive or massive. Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver. Unlike other responses, which are reversible, fibrosis points toward generally irreversible hepatic damage. However, there is now considerable debate about the irreversibility of liver fibrosis and even cirrhosis (see below). Deposition of collagen has lasting consequences on patterns of hepatic blood flow and perfusion of hepatocytes. In the initial stages, fibrosis may develop around portal tracts or the terminal hepatic vein or may be deposited directly within the space of Disse. With continuing fibrosis, the liver is subdivided into nodules of proliferating hepatocytes surrounded by scar tissue, termed "cirrhosis. The ebb and flow of hepatic injury may be imperceptible to the patient and detectable only by abnormal laboratory tests (Table 18-1). The major clinical consequences of liver disease are listed in Table 18-2 and are discussed next. This may be the result of sudden and massive hepatic destruction, with about 2500 new cases per year in the United States. Whatever the sequence, 80% to 90% of hepatic functional capacity must be eroded before hepatic failure ensues. In many cases, the balance is tipped toward decompensation by intercurrent diseases that place demands on the liver. These include gastrointestinal bleeding, systemic infection, electrolyte disturbances, and severe stress such as major surgery or heart failure. In most cases of severe hepatic dysfunction, liver transplantation is the only hope for survival. Overall, mortality from hepatic failure without liver transplantation is 70% to 95%. This is most often drugor toxin-induced, as from acetaminophen (38% of massive hepatic necrosis cases in the United States), halothane, antituberculosis drugs (rifampin, isoniazid), antidepressant monoamine oxidase inhibitors, industrial chemicals such as carbon tetrachloride, and mushroom poisoning (Amanita phalloides), collectively accounting for an additional 14% of cases. Hepatitis A infection accounts for 4% of cases, hepatitis B infection accounts for 8%, and other causes (including unknown) account for 37%. This is the most common route to hepatic failure and is the endpoint of relentless chronic hepatitis ending in cirrhosis. Hepatocytes may be viable but unable to perform normal metabolic function, as with Reye syndrome, tetracycline toxicity, and acute fatty liver of pregnancy. Hypoalbuminemia, which predisposes to peripheral edema, and hyperammonemia, which may play a role in cerebral dysfunction, are extremely worrisome developments. Fetor hepaticus is a characteristic body odor that is variously described as "musty" or "sweet and sour" and occurs occasionally. It is related to the formation of mercaptans by the action of gastrointestinal bacteria on the sulfur-containing amino acid methionine and shunting of splanchnic blood from the portal into the systemic circulation (portosystemic shunting). Impaired estrogen metabolism and consequent hyperestrogenemia are the putative causes of palmar erythema (a reflection of local vasodilatation) and spider angiomas of the skin. Each angioma is a central, pulsating, dilated arteriole from which small vessels radiate. Hepatic failure is life-threatening because with severely impaired liver function, patients are highly susceptible to failure of multiple organ systems. Thus, respiratory failure with pneumonia and sepsis combine with renal failure to claim the lives of many patients with hepatic failure. The resultant bleeding tendency can lead to massive gastrointestinal bleeding as well as petechial bleeding elsewhere. Intestinal absorption of blood places a metabolic load on the liver, which worsens the extent of hepatic failure. The outlook of full-blown hepatic failure is grave: A rapid downhill course is usual, death occurring within weeks to a few months in about 80% of cases. A fortunate few can endure an acute episode until hepatocellular regeneration restores adequate hepatic function. Two particular complications merit separate consideration, as they herald the most grave stages of hepatic failure. Hepatic encephalopathy is manifested by a spectrum of disturbances in consciousness, ranging from subtle behavioral abnormalities to marked confusion and stupor to deep coma and death. These changes may progress over hours or days in fulminant hepatic failure or more insidiously in a patient with marginal hepatic function from chronic liver disease. Associated fluctuating neurologic signs include rigidity, hyperreflexia, and particularly asterixis: nonrhythmic, rapid extension-flexion movements of the head and extremities, best seen when the [5] arms are held in extension with dorsiflexed wrists. Hepatic encephalopathy is regarded as a disorder of neurotransmission in the central nervous system and neuromuscular system and appears to be associated with elevated blood ammonia levels, which impair neuronal function and promote generalized brain edema. In the great majority of instances, there are only minor morphologic changes in the brain, such as edema and an astrocytic reaction, and the encephalopathy is reversible if the underlying hepatic condition can be corrected. Hepatorenal syndrome refers to the appearance of renal failure in patients with severe chronic liver disease, in whom there are no intrinsic morphologic or functional causes for the renal [6] failure. Sodium retention, impaired free-water excretion, and decreased renal perfusion and glomerular filtration rate are the main renal functional abnormalities. Several factors are involved in its development, including a decreased renal perfusion pressure due to systemic vasodilation, activation of the renal sympathetic nervous system with vasoconstriction of the afferent renal arteriolae, and increased synthesis of renal vasoactive mediators, which further decrease glomerular filtration. Onset of this syndrome is typically heralded by a drop in urine output, associated with rising blood urea nitrogen and creatinine. The ability to concentrate urine is retained, producing a hyperosmolar urine devoid of proteins and abnormal sediment, and surprisingly low in sodium (unlike renal tubular necrosis). Rapid development of renal failure is usually associated with a precipitating stress factor such as infection, gastrointestinal hemorrhage, or a major surgical procedure. Insidious development of renal failure is the result of progressive destabilization of circulatory physiology, frequently in the setting of severe refractory ascites. The prognosis is poor, with a median survival of only 2 weeks in the rapid-onset form and 6 months with the insidious-onset form. An example of the progression to cirrhosis is given under the subsequent discussion on alcohol. Focal injury with scarring does not constitute cirrhosis, nor does diffuse nodular transformation without fibrosis. It should be noted that rapid development of fibrosis, as in alcoholic hepatitis, may leave little time for the development of spherical nodules.

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Even tions will be taken through the surface and to if no tissue is visible diabetes type 2 lose weight fast avapro 300 mg line, the blood and mucus secure the specimen properly to ensure that small should still be submitted for histologic evaluapieces are not lost diabetes diet exercise cure order 300mg avapro otc. These tasks can be accomtion diabetes symptoms 7 days safe 150 mg avapro, as they may contain entrapped small epitheplished in several ways diabetes mellitus komplikasyonları buy avapro 300mg with mastercard. For endometrial be bisected perpendicular to the surface and specimens managing type 1 diabetes in pregnancy order cheap avapro online, if the tissue obtained is not repremarked with either mercurochrome or tattoo sentative of functioning endometrium diabet-x plus discount avapro 300mg amex. If the endocervix, lower uterine segment, or surface specimen is small, it can be secured between Gelendometrial epithelium only), this fact should foam sponges, within ne-mesh biopsy bags, or be specied. The gynecoloestimate the percentage of the specimen ingist may also submit the biopsy oriented mucosal volved by tumor. In this case, instruct your histotechnologist to embed and cut the biopsy specimen perpendicular to the mounting surface. All biopsy speciCervix mens should be entirely submitted, and it is often useful to routinely request that multiple levels be examined by the histology laboratory. Loop Electrocautery Excisions Endometrial biopsies should be handled similarly to curettage specimens. Their use is increasing in the treatment of squamous Endocervical and endometrial curettings consist intraepithelial lesions. Depending on the type of of multiple small fragments of epithelium, which loop used and on the depth of the excision, the are often admixed with blood and mucus. The specimen may be large enough to allow one to surgeon may put the curettings on Telfa pads or orient, open, and process it like a conventional 146 147 148 Surgical Pathology Dissection cone biopsy, as described later. However, many on the fact that most cervical lesions arise on of these specimens arrive in the surgical patholthe anterior and posterior surfaces, rather than ogy laboratory already xed in formalin and/or laterally. The endocervical margin will board with the epithelial surface upward, using sometimes be submitted separately, and an pins placed through the stroma on both sides. Examine the mucosal surface, and look for any If multiple fragments are submitted, identify lesions, especially along the squamocolumnar the mucosal surface, and try to distinguish the junction. Divide perpendicular to the mucosal surface in the plane the fragments into strips with sections perpenof the endocervical canal. For apex as a pivot, and angle the cuts to provide shallow, saucer-shaped specimens, divide the a continuous line from the endocervical mucosa specimen radially as illustrated. For small conical specimens that compass the squamocolumnar junction and will are already well xed, divide the specimen into demonstrate the extent of the transformation anterior and posterior halves, and section each zone. All ting the biopsy this way is similar to the handling sections should be submitted sequentially and of the perpendicular sections of the distal urethral designated as to their clock-face orientation. Although cautery artifact may make the limits of resection of these specimens difcult Important Issues to Address to evaluate, it is always best to ink the mucosal in Your Surgical Pathology margins and exposed stroma for histologic Report on the Cervix evaluation. If so, what is to the endocervical canal, the diameter at the the depth of invasion from the base of the epitheectocervical margin, and the diameter at the enlium, either surface or glandular, from which it docervical margin. What is the horizontal is described as a clock face with the most superior spread (in millimeters) Common indications for hysterectomy 149 150 Surgical Pathology Dissection include uterine prolapse, leiomyomas, endometrial Orient the uterus by identifying the stubs of hyperplasia, cervical cancer, and endometrial the round ligaments that insert anterior to the cancer. The ovaries should lie postericesses and the variation in the appearance of orly. Vaginal tive status when evaluating a hysterectomy and abdominal hysterectomies may be distinspecimen. The pericomponents: (1) the uterine corpus and (2) the toneum appears V-shaped in a vaginal and Uuterine cervix. Weigh the left cornual regions are located superolaterally, uterus, and record the following measurements: at the insertion of the fallopian tubes. The inferior fundus to ectocervix, cornu to cornu, and anterior 1 to 2 cm of the corpus is referred to as the isthmus to posterior. The cervix encomthe uterus can now be evaluated with a syspasses the lower portion of the uterus, beginning tematic examination of each of its main compoat the internal os. These may be seen more frequently on squamocolumnar junction moves in and out of the posterior aspect. This section provides an approach to the evalBeginning at the cervix, incise the uterus with a uation of hysterectomy specimens in four catelarge blade using the probe as a guide to divide gories: (1) hysterectomies for nonmalignant it into anterior and posterior halves. Another disease, (2) hysterectomies for endometrial canmethod for bivalving the uterus is to use a pair of cer, (3) radical hysterectomies for cervical cancer, scissors to cut along the lateral margins from the and (4) pelvic exenterations with vaginectomies ectocervix to the cornu. At this point, the uterus may be photographed and then pinned to Hysterectomy for a wax tablet for xation. Always include sections demonstratversely, a thick endometrium in a premenopausal ing the border between the leiomyoma and the woman may reect only the normal secretory surrounding myometrium or overlying endomephase. In these cases, the general corpus and lower uterine segment, and record rule of one section per 1 cm of tumor diameter the maximum myometrial thickness. Smooth muscle tumors less intramural leiomyomas or evidence of adenothan 5 cm do not need to be sampled, as they myosis. Adenomyosis is usually more extensive rarely metastasize, regardless of their microin the posterior wall and may be recognized by scopic appearance. If no lesions are identied, standard sections Important Issues to Address of the uterus include longitudinal sections of in Your Surgical Pathology the anterior and posterior cervix (including the Report on Hysterectomies for transformation zone) and full-thickness sections of the anterior and posterior walls of the Non-Malignant Disease uterus to include endometrium, myometrium, and serosa. If functional, In the case of endometrial hyperplasia, the enspecify whether it is in the proliferative or tire endometrium may need to be evaluated to secretory phase. Specify whether underlying myometrium can be submitted in the leiomyomas are submucosal, intramural, a limited number of tissue cassettes. For low-grade squamous intraepithelial lesions, a section from each quadrant may sufce. Hysterectomy the evaluation of a uterus with multiple leiofor Endometrial Cancer myomas deserves special mention. A leiomyomatous uterus is one of the most frequently encountered specimens, and the gross examthe approach to hysterectomies performed for ination of these specimens is the key to their endometrial cancer parallels the approach to proper handling. Record steps include inking the paracervical and parathe number of nodules present and their size. All nodules Orient, weigh, and measure the uterus as should be sectioned at 1to 2-cm intervals and described in the section on hysterectomies for examined grossly but not necessarily microscopibenign disease, and ink the soft tissue resection cally. Their border with parametrial tissue, which extends along the body the surrounding myometrium is smooth and of the uterus and into the broad ligament. If these criteria are met, fully examine the serosal surfaces for evidence of representative sampling of each leiomyoma is tumor extension. Ink these areas a different color 153 154 Surgical Pathology Dissection for orientation. If the adnexa are present, remove may be too thick to t in a standard-size tissue them at their lateral insertions along the uterus. In these situations, divide the section Make multiple transverse cuts through the ovary into endometrial and serosal halves. Be sure to and fallopian tube, looking for evidence of either designate their relationship clearly in your sumdirect tumor extension or metastatic spread. Submit at least one section from each side to Lymph nodes from the pelvic and para-aortic demonstrate the ovary and fallopian tube with regions may also be included as separate speciadjacent soft tissue. They can be handled in a routine manner Bivalve the uterus by using a long, sharp knife for evaluation of metastatic disease. Endometrial carcinomas can be shaggy, sessile Important Issues to Address tumors or polypoid masses arising from the surin Your Surgical Pathology face of the endometrium. The sounding depth of the uterus from the external cervical os to the superior limit of the for Endometrial Cancer endometrial cavity may be measured, but it is no longer used in the staging of endometrial cancers. Note whether or not the tumor grossly indeepest point of invasion (in millimeters) Give the distance front, an inltrating nger-like pattern, or is it of the tumor from closest margin (in centidiscontinuous In addition, measure the number of nodes examined at each specied total myometrial thickness at this point, and site. When selecting sections for histologic analysis, include Radical Hysterectomy the deepest point of tumor invasion as well as for Cervical Cancer the interface with grossly uninvolved endometrium. The best sections are those that show Radical hysterectomies are performed for early the full thickness from the endometrium to the stage invasive squamous carcinomas and adeserosa. In addition to the 155 156 Surgical Pathology Dissection uterus and cervix, the specimen has attached paraextent of the tumor is documented by taking metrial/paracervical soft tissue and a vaginal sections of the cervical tumor that include the cuff. Margins to be evaluated Begin by orienting, measuring, and weighing include the left and right parametrial/paracervithe uterus and cervix as described in the section cal tissues, submitted in their entirety, and the on hysterectomies for benign disease. The anterior and posterior cervical sure the size of the attached parametrial/paracersoft tissue margins should be submitted to devical tissue and the length of the attached vaginal lineate the extent of the tumor in relationship cuff. Ink the right and left Lymph nodes are usually submitted separately parametrial/paracervical tissues, the anterior/ by the surgeon from the right and left internal posterior soft tissue margins of the cervical canal, iliac, external iliac, obturator, pelvic, and paraand the vaginal cuff margin. They can be handled in a metrial/paracervical tissue by shaving each side routine manner for evaluation of metastatic close to its lateral attachment on the cervix. Important Issues to Address in Next, amputate the cervix at the level of the Your Surgical Pathology Report internal os, and open the canal with a longitudinal incision opposite the tumor. Measure the for Cervical Cancer maximum tumor width and length as well as the distance to the nearest vaginal margin. Examine the corpus with serial point of deepest tumor invasion (in millitransverse sections as you would in any hysterecmeters) If the tumor is not visible, Specify the extent of involvement and depth the cervix with attached vaginal cuff should be of invasion. The inferior is close to but does not involve a resection 157 158 Surgical Pathology Dissection margin, give the distance between the tumor the four main components. Record the numAppropriate examination of the central tumor ber of lymph nodes with metastases and the involves demonstrating its in situ relationship to number of lymph nodes identied by site. When a total pelvic exenteration specimen is received for recurrent cervical cancer, do not Pelvic Exenterations panic. Specically, look for Including Vaginectomies the ureters, urethra, bladder, uterus, fallopian tubes, ovaries, vagina, and rectum. Take shave Vaginectomies for vaginal cancer include a porsections of the vaginal, ureteral, and urethral tion of vagina attached to the uterus and cervix. Take perpendicular sections from the these specimens can be handled in the same proximal and distal rectal margins, providing manner as radical hysterectomies for cervical ink for margin orientation. Next, ink all the cancer, although the paracervical soft tissues may exposed soft tissue that surrounds the cervix not be present. Submerge the entire specimen in formaosis appears as a red, granular change on the lin, and x it overnight. This is best accomplished by using Important observations include the size of the probes in the urethra and uterine canal as midline tumor and the distance of the tumor to the vaginal guides. If the uterus has been previously rea diagram can facilitate the description of the moved,the resultingvaginal pouchcan beopened tumor, including its extension. Take sections of along one side and handled in the same manner the tumor to demonstrate invasion of the bladder, as a large skin excision. Docuso as to demonstrate the greatest depth of tumor ment the vaginal and paracervical soft tissue marinvasion, the tumor with adjacent normalgins with perpendicular or shave sections. Last, appearing mucosa, and the relationship of the dissect the soft tissue surrounding the cervix, and tumor to the cervix. If the bladder is included submit for histology a section of any lymph with the uterus the resection is termed an anterior nodes found. With these added structures, additional sections include documentation of the extent of tumor inImportant Issues to Address in volvement of the bladder or rectal wall, and an Your Surgical Pathology Report evaluation of their respective surgical margins. That is, does it reach the musResection margins are best handled if each of cular wall, submucosa, or mucosa

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