By O. Rasarus. Judson College, Marion AL. 2019.
In the early 20th century we saw the frst connection between genetic inheritance and susceptibility to disease buy himplasia 30caps without a prescription. It recognises that complex diseases should no longer be considered as a single entity cheap himplasia american express. One disease may have many different forms purchase 30caps himplasia free shipping, or subtypes, resulting from the complex interaction of our biological make-up and the diverse pathological and physiological processes in our bodies. These will not only vary between patients who have the same disease but also within an individual patient as they get older and their body changes. As we integrate and analyse genomic and other data, we can fnd common factors and causes of variation, resulting in the discovery of new pathways of disease, changing how diseases are thought of and treated. All patients with the same condition receive the same frst line treatment even though it may be only 30 to 60% effective. This can be used for a wide range of cancers such as melanoma (skin cancer), leukaemia, colon, brain and breast cancers. It may also mean that patients with different types of cancer may, on the basis of the genomic diagnosis, receive similar treatments. It will create the opportunity to fnd new purposes for, and better use of, existing medicines including generics and biosimilars. It will also help us to use other non-pharmacological treatments, and even, in some patients, simple dietary or lifestyle interventions. Within Specialised Services for example, personalised medicine will be a key aspect of the strategic approach to meeting the health and wellbeing challenge, bringing a more preventative approach to these vital, but often rare and expensive treatments. It is the integration and analysis of this information that forms the powerhouse for personalised medicine. Building an integrated informatics system across a healthcare system is diffcult: weve tried in the past and struggled, but the challenges are not insurmountable. The scale of the interdependency between integrated informatics and delivering personalised medicine cannot be overstated. The information that comes from a single human genome produces enough information to fll a stack of paperback books over 60 meters high, so the data storage requirements are vast. The foundations for this step change in health care are already being put in place. The Project is coordinated by Genomics England, who have procured whole genome sequencing services and analytical providers. They have created a unique database that enables approved researchers, clinicians, and industry to work on de-identifed data to enhance clinical interpretation and answer arising research questions. Knowledge from the Project will enable clinical teams to better characterise an individuals condition, learn from others with the same disease and connect seemingly different conditions with the same underlying genomic cause. Whole Genomes Sequencing returned a molecular diagnosis, setting them free to make decisions about the treatment options for their child. Now that we have this doagnosis there are things we can do differently straight away. A special diet means her medication can decrease and her epilepsy be more easily controlled. Earlier detection will open up the prospect of new treatment options and support people to make informed lifestyle choices. This will create the potential to reduce the growing burden of disease, particularly for long term conditions such as cardiovascular diseases, cancer, chronic respiratory diseases and diabetes. More precise diagnoses Currently a diagnosis is made based on tests and investigations of a patients symptoms. But whilst two patients might share the same symptoms, the cause of them could be different. Knowledge of each individuals complex molecular and cellular processes, informed by other clinical and diagnostic information, will enable us to fully understand the abnormal function and determine the true cause of the symptoms. This ability to diagnose more precisely can be optimised when coupled with new and improved technologies such as those that provide rapid and real time results and those that can be used at the point of care. Patients and health professionals can make shared decisions about medicines and adjust dosing in real time. Targeted and personalised interventions Personalised medicine offers the opportunity to move away from trial-and-error prescribing to optimal therapy frst time round. Currently key pharmaceutical interventions are effective in only 30-60% of patients due to differences in the way an individual responds to and metabolises medicines. Knowledge of the genetic variants responsible for individual drug response can be used to create an individuals pharmacogenomic profle, identifying optimal treatment. We are already beginning to see the development of simple point of care tests, based on genomic knowledge, which enable clinicians in a wide variety of settings to identify the best therapy. This marks the beginning of an end to the frustrating and costly practice of trial-and-error prescribing. The development and regulatory approval of so called companion diagnostics - a diagnostic test, device or imaging tool used as a companion to a therapeutic drug - is already making this a reality. Warfarin Warfarin is a common and effective treatment to prevent blood clots, but patients show a 40-fold difference in dose needed. The current trial and error approach to discover the right dose for an individual means some suffer signifcant problems as their treatment is worked out. Appropriate testing can be used so people get the right dose sooner cutting side- effects and improving outcomes. The ability to predict and prevent their occurrence has signifcant potential to reduce burden on accident and emergency units and to signifcantly improve a patients experience. However about 1 in 17 people have a bad reaction to the drug which, at worst, can be fatal due to a variation in their immune system. All patients now have a specifc genomic test before they start taking Abacavir, which identifes those who would have an allergic reaction. A more participatory role for patients The ability for a clinician to discuss with their patients information about individual genomic characteristics, lifestyle and environmental factors, and interpret personal data from wearable technology will drive a new type of conversation. It might also lead patients to consider preventative measures when there is high likelihood of a disease developing. This is a new era of medicine and it requires new knowledge amongst professionals, patients and the public to have confdence in using the information available to them. Diabetes when less can be more The standard approach to newly-diagnosed Type 1 diabetes is to treat it with regular insulin injections. However there are other forms of diabetes that can appear clinically like Type 1 diabetes, but have different underlying causes and can be treated much more simply.
On basal membrane organ og Corti with receptors hair cells Adequate stimulus for auditory receptors sound - sound is produced by waves of compression and decompression transmitted in air (or other media such as water) order 30caps himplasia with mastercard, propagation in the air 335 m/s - sound composed of many unrelated frequencies - noise - frequency (nm purchase 30 caps himplasia mastercard. The vibrations are transferred by the ossicular system through the oval window on the structures of inner ear (by the vawe movement of perilymph) - stimulation of the organ of Corti causes action potencials in nerve fibres function of mm discount 30caps himplasia free shipping. Axons penetrate the base of the skull through openings in the cribriform plate of the ethmoid bone as olfactory nerve filaments (fila olfactoria) to olfactory bulb. Stimulation of the olfactory cells - olfactory receptors telereceptors - they response to the odorant substance (gas) in inhaled air dissolved in the mucus 66 - chemical interaction with the membrane of the cilia + - they evoke receptor (generator) potencial by changing permeability of membrane for Na - fast adaptation - in humans ability to distinguish between 2 4000 different odors - the olfactory cells the highest degree of chemical discrimination Intensity of the stimulus depends on concentration of the odor substance (the number of stimulated receptors and the number of moleculs reaching the cell) Quality of perception depends on concentration: at low c. Function of the muscle spindle Receptors - active at rest stretching of the muscle activation of the anulospiral endings higher frequency of the impulses facilitation of the alfa motoneurons of the its own muscle. Pavlov) - originated during development = mechanisms for assurance of ability to survive and live classification: - apetitive - protective - orientation - sexual Innate mechanisms: 1. Drive: - processes which represent an immediate response to fundamental necessities of the body - they force the human to fill the needs - after filling the needs - antidrive 3. Storing of encoded information biochemical, biophysical and electrophysiological processes 3. Each receptor is highly specific for a single hormone Principal mechanisms: 1) Confirmational changes of the receptor alter the membrane permeability to ions. Properties of the hormone effects: 1) Target effect hormone acts on target cells organ (estrogen uterus, mammary gland etc. It lies in the sella turrica at the base of brain and is connected with hypothalamus by the pituitary (hypophyseal) stalk. Symptoms: Hyperglycemia (through) increased glucocorticoid activity), negative nitrogene balance, fat infiltration of the liver. Effects (three main): 1) Mammotrophic effect development of the breasts at puberty 2) Luteotrophic effect stimulation of the corpus luteum, stimulation of the progesteron secretion 3) Role in secretion of milk - producing effect. In mothers who do not nurse their baby a decrease in prolactin level to basal value in 2-3 weeks. Prolactin and estrogen synergize in producing breast growth, but estrogen antagonizes the milk-producing effect of prolactin on the breast. Effect: Lipolysis Control of anterior pituitary secretion 1) Feedback control hormone of the peripheral gland (adrenal cortex, thyroidea. Melanocytes synthesize melanins transfer to keratocytes in skin for pigmentation of hair and skin darkening in 24 hours. Transport - intraneural in the axons of neurons to their endings 85 - in the posterior lobe. Vasoconstriction in splanchnic, renal, coronary, cutaneous and uterine circulation. Single layer of cells filled with colloid Production of thyroid hormones: - thyroxine (T4), - triiodthyronine (T3) Biosynthesis: Processes: 1/Iodination, 2/ condensation of tyrosine molecules 3/ binding in peptide linkage in thyroglobulin 4/secretion 1/ Iodination Iodide trapping mechanism (iodide pump) active transport against a concentration and electrical gradient. Enzymes: 5 deiodinase (T3), 5 deiodinase (rT3), diiodothyronines In the liver T4 and T3 conjugation to sulfates, glucuronides the bile the intestine. Effects of thyroid hormones 1) Effects on growth and development: General and specific effects. Regulation increase in plasmatic Ca++ causes an immediate increase in the rate of calcitonin secretion. Feedback opposite effect increase the Ca++ concentration decreased activity of the parathyroid glands. Hypoparathyreoidism after parathyreoidectomy decrease in Ca++ plasma level signs of neuromuscular hyperexcitability: Hypocalcemic tetany: Chvosteks sign contraction of facial muscles elicited by tapping over the facial nerve. Calcium Metabolism Ca++ - in the human body about 1100 g 99 % in skeleton The plasma Ca++ - 2. D3 (cholecalciferol) is produced in the skin from 7- dehydrocholesterol by sunlight. Other Effects of Glucocorticoids 93 1) Antiinflammatory effect - stabilization of the intracellular lysosomal membranes and inhibition of lymphoid tissue. Adrenal virilism excess growth of facial hair, in women mens type of figure, muscles. The key metabolic role of insulin means that its absence causes distortion of homeostasis. Insulin deficiency diabetes mellitus Insulin excess hypoglycemia convulsion, coma. Application subcutaneous way intensified therapy simulated physiological secretion. Phases: 1) Follicular phase formation of an ovum growth of the follicles production of estrogens 2) 14th day distended dominant follicle ruptures ovum is extended ovulation 3) Luteal phase production of the estrogens and progesterone by corpus luteum. Abnormalities of the endocrine ovarian functions Fermale hypogonadism in - childhood sex characteristics undeveloped - late puberty pubertas tarda - sexual infantilism - adulthood - amenorrhea absence of the menstruation - regression of the female sex characteristics - osteoporosis Female hypergonadism in - childhood pubertas praecox - adulthood abnormalities in cycle, amenorrhea, menorrhagia, metrorrhagia. Exposition to a permanent light suppression of the melatonin production Activation of the synthesis during the dark period night Light information (dark/light) retina tr. Effects on immune processes immunomodulatory role: - Stimulatory effect on the processes and lymphoid cells, thymus, spleen - Antioxidative effect scavenger of some reactive forms of oxygene. Jet lag from moving to a different time zone (W-E shortens, E-W lengthens day. The coordination of the biological clock melatonin - sleep-disorders sleep promoting effect - some types of depression seasonal affective disorder - imunomodulans/prevention. Another stimuli: Cooling of the newborns body Tactile and pain stimuli Stimulation of proprioceptors Reflexes of airways and lungs Diving Hering-Breuer deflation reflex 107 Visual. The first breath - strong negative pressure up - 75 mmHg - to overcome the resistance of the airways and viscosity of the lung fluid. The first expirium - positive - a cry - pushes the fluid to alveolocapillary membrane - resorption. Heat generated by fetal metabolism is dissipated by the amniotic fluid or the placenta to maternal blood in the intervillous spaces. Because of the newborns larger surface area to body mass ratio, decreased insulating subcutaneous fat, increased skin permeability to water.
At the heart of assertion training is learning to recognize and express ones own feelings and needs himplasia 30caps lowest price. In many cultures quality 30 caps himplasia, this is especially a challenge for women given their socialization to place others needs always before their own cheap himplasia 30 caps on line. Good assertion skills articulate ones own needs in the context of recognition of others needs and a willingness to cooperate to meet both sets of needs. Key in this is the concept of appropriate escalation of self assertion, beginning with clear but nondemanding clarification of ones own needs and moving toward more forceful insistence on these only in response to others failure to cooperate. Fortunately this is usually quite convenient to arrange whether in individual counseling or group programs. Role playing of interactions and rehearsal of approaches until individuals have a firm hand on their skills is important. Several guidelines are helpful to minimize this and to make role playing most effective. One is to keep role plays very specific around a particular point in an interaction, not the whole interaction. This will help keep the focus on specific skills and, in a group program, will keep the attention of other participants from drifting. In group settings, it is helpful to enact a rule that feedback after each role play should focus on (a) what the individual did well and (b) what they could do more of. Mistakes generally do not need to be identified most of us entering this kind of training or counseling have already had quite enough of our mistakes pointed out to us! This is a classic in the field and does a fine job of teaching not only how to be assertive but how to adjust the level of assertion and self representation to the specifics of the situation. Patient communication skills training: a review with implications for cancer patients. Family characteristics of diabetic adolescents: relationship to metabolic control. Family stress and resources: potential areas of intervention in children recently diagnosed with diabetes. Internet support services have meet on a regular basis to address challenges several advantages over traditional face-to- related to living with that condition. Support face support groups in that they are available groups provide a forum for participants to 24 hours a day, are inexpensive, and can both give and receive emotional and practical involve a greater number of participants. Participants learn how to handle Support groups for diabetes have been reported challenges that arise, cope with changes, and since the 1970s, although emotional health maintain healthy behaviors. Initial reports on support groups and people together to address psychological their effects on emotional health had mixed problems. A study by Hanestad and Albreksten There is a great deal of variety in support comparing people with diabetes who attended a groups. Some are structured diabetes education as well as diabetes around a series of relevant topics; others are education combined with participation in a less structured and more responsive to the support group can lead to an improvement in immediate concerns of the group. Groups both objective and subjective improvements in vary in size; the goal is that they be small knowledge and emotional health among enough for everyone to contribute and feel people with diabetes as a result of comfortable sharing with one another. In one study, In addition to face-to-face support groups, older diabetic patients participated in either an people now have the opportunity give and educational program alone or an educational receive support virtually via online social program followed by 18 months attendance in networks. A 2-year follow-up revealed generally called forums and message boards, that participants who attended both the where people with similar interests or 30 diabetes educational program and the 18 specific support measure and a general support months of support group sessions showed a scale for Internet users who received a social better overall quality of life than those who support intervention as compared to those who 8 had education alone, including less depression received diabetes information only. Another and affective disturbances, and also study found that participants reported greater maintained the knowledge learned from the hopefulness and perception of ability to cope 5 educational program. A survey want to make about the purpose and format of conducted among adults with diabetes who the group. Additionally, fifty-five key team members their level of interest and percent of the members agreed with the support for establishing support groups. As with any new service of concerns, can reduce the notion that ones program activity, planning needs to be done 7 with full awareness of resource needs and issues are unique and therefore frightening. By recognizing that others experience similar availability of resources to support it. Thus, may be somewhat easier and may simply support groups may provide participants with involve developing a resource list of reputable an opportunity to treat emotional factors that on-line diabetes support groups that are coincide with chronic disease that might available and appropriate for the patient otherwise go unresolved. Although the notion of Internet support Whether or not diabetes programs add a services is relatively new, research indicates support group component, it is important to that the use of Internet support groups is recognize that other program services and beneficial as a means of decreasing isolation activities provide support for participants. However, the characteristics with some groups led by promotoras, others of the support groups varied markedly among led by mental health professionals, and still the project sites. Some met as frequently as others co-led by diabetes educators, health twice a week while others met only once a professionals and/or promotoras. Some support groups were run in community members were frequently invited conjunction with or as follow-up to diabetes to participate and share their support. At sites that did not host support sites fostered peer support and healthy coping groups, local diabetes support groups were through their diabetes self-management promoted and participants referred to them. A diabetes problem solving support group: issues, process and preliminary outcomes. The effects of participation in a support group on self-assessed quality of life in people with insulin-dependent diabetes mellitus. Effects of a social support group, as an adjunct to diabetes training, on metabolic control and psychosocial outcomes. Stress management usually entails a comprehensive approach to dealing with Evidence Base stressors that includes three core approaches: To determine if group-based stress 1) How to appraise stressful events management can improve glucose metabolism realistically. Stress management was associated management is that between stressor and with small but significant reduction in stress. Others have also reported situation that is upsetting or challenging to us, benefits of stress management in terms of such as a belligerent colleague, an 2 hemoglobin A1c. An important disease found reductions in blood pressure and component of stress management is 3 several other cardiovascular risk factors. This is expressed in numerous describe so many emotions and concerns, this observations of folk wisdom, such as the entire Guide really can be seen as providing Serenity Prayer: Grant me the serenity to strategies for coping with stress. Program accept the things I cannot change, the courage managers may elect to incorporate one or to change the things I can, and the wisdom to more of these into existing self-management know the difference. On the other hand, stressors and (b) for reducing our own stress repeated conflicts with the boss or an responses. Problem-solving strategies, individual who is unlikely to be responsive to described elsewhere in this Guide, provide a our efforts to change things may be wisely left 34 good overall approach for coping with Program materials for sessions on stress stressors.
Subgroup analysis of the trial showed that benefit from perindopril is mainly in patients with a history of myocardial infarction cheap himplasia 30caps with mastercard. There is an increased risk of mortality following both coronary bypass surgery and angioplasty purchase genuine himplasia on-line; and there is a substantially increased risk of re-stenosis following angioplasty in diabetic patients purchase himplasia overnight delivery, partly ameliorated by the use of coronary stents. Indications for coronary angiography in patients with diabetes with symptomatic coronary disease are similar to those in non-diabetics, recognising the increased risk associated with revascularisation procedures. Patients should be given information to help them recognise the following risk factors: smoking dyslipidaemia hypertension hyperglycaemia central obesity and a plan made to help them reduce those which affect them. The additional factor to be considered is to obtain and maintain good glycaemic control. Microalbuminuria is defined by a rise in urinary albumin loss to between 30 and 300 mg day. This is the earliest sign of diabetic kidney disease and predicts increased total mortality, cardiovascular mortality and morbidity, and end-stage renal failure. Diabetic nephropathy is defined by a raised urinary albumin excretion of >300 mg/day (indicating clinical proteinuria) in a patient with or without a raised serum creatinine level. This represents a more severe and established form of renal disease and is more predictive of total mortality, cardiovascular mortality and morbidity and end-stage renal failure than microalbuminuria. The presence of retinopathy has often been taken as a prerequisite for making a diagnosis of diabetic nephropathy, but nephropathy can occur in the absence of retinopathy. In a Danish study of 93 people with type 2 diabetes, persistent albuminuria and no retinopathy, 69% had diabetic nephropathy, 12% had glomerulonephritis and 18% had normal glomerular structure. In most individuals this diagnosis is made clinically, as biopsy may not alter management. Classic diabetic kidney disease is characterised by specific glomerular pathology. In many individuals, kidney disease will be due to a combination of one or more of these factors, and people with diabetes may develop kidney disease for other reasons not related to diabetes. Patients on dialysis are classified as stage 5D The suffix T indicates patients with a functioning renal transplant (can be stages 1-5). Estimates of prevalence from individual studies must be interpreted in the context of their patient population, such as levels of deprivation and the proportion of individuals from ethnic minorities. The proportions of individuals with microalbuminuria and proteinuria over 15 years of follow up, for participants in the conventional management arm of the study, are shown in Table 6. There are data to 2- suggest that there has been a decrease in the incidence of diabetic nephropathy in people with type 1 diabetes diagnosed more recently, with earlier aggressive blood pressure and glycaemic control. Conventional urine dipstick testing cannot reliably be used to diagnose the presence or absence of microalbuminuria. The literature is confusing in relation to the timing of commencing screening in young people with diabetes. Early microvascular abnormalities may occur before puberty, which then appears to accelerate these abnormalities. Detection of an increase in protein excretion is known 2++ to have both diagnostic and prognostic value in the initial detection and confirmation of renal disease. Annex 3 explains the relationship between urinary protein (and albumin) concentrations expressed as a ratio to creatinine and other common expressions of their concentration. This benefit was at the expense of significantly more severe hypoglycaemic events in the intensive group 2. There are limited data using the surrogate end point of reduction in proteinuria which suggests that thiazolidinediones may have an additive benefit over other hypoglycaemic agents in reducing proteinuria. This may indicate that the maximum benefit of intensive glycaemic control occurs when treatment is initiated at an earlier stage of the disease process. However, in pancreatic transplant recipients with evidence of diabetic kidney disease pre-transplant, histological improvements have been seen after 10 years of euglycaemia. A Reducing proteinuria should be a treatment target regardless of baseline urinary protein excretion. No difference in blood pressure was noted between the treatment groups to explain the reduction in albumin excretion rate. This study alone produced opposite findings to the others in the meta-analysis (ie favoured placebo/no treatment), but, because of its size, accounted for 29% of the weighting of the overall result. By virtue of their baseline characteristics, the subjects in this study will have been at high risk of renovascular disease, which predisposes to acute renal failure both on initiation of treatment and in the case of another insult, eg volume depletion. In general, the trials were small, of short duration and poor methodological quality. Most trials demonstrated that spironolactone - 1 therapy reduced proteinuria (weighted mean reduction approximately 0. However, in the subgroup 1++ analysis of patients with diabetes (n=122) no benefit of statins on rate of progression or proteinuria was seen, although the authors concluded that larger studies were required to address this issue. It is not possible to deduce an optimal protein level from the available evidence. High protein intakes are associated with high phosphate intakes as foods that contain protein also tend to contain phosphate. Weight reduction and exercise No evidence was identified that weight reduction or exercise affect the development or progression of diabetic kidney disease. The benefits of a multifactorial approach in the management of people with type 2 diabetes and microalbuminuria have been clearly demonstrated. Only one person in the multifactorial intervention group required renal replacement therapy compared to six in the conventional treatment group (p=0. B People with diabetes and microalbuminuria should be treated with a multifactorial intervention approach. The median achieved haemoglobin in the intervention group was 125 g/l and in the control group was 106 g/l. A Erythropoiesis stimulating agents should be considered in all patients with anaemia of chronic kidney disease, including those with diabetic kidney disease. People with diabetes who are receiving dialysis require ongoing review of their diabetes. There may be ongoing issues regarding glycaemic control, such as symptomatic hyperglycaemia and recurrent hypoglycaemia which are usually best managed by diabetes healthcare professionals. Regular screening of eyes and feet are also essential given the high prevalence of sight-threatening retinopathy and foot disease in this patient group.
Patients not strictly meeting this duration of pain may still be said to have functional abdominal pain order himplasia with a visa. Mechanisms and Causes Functional abdominal pain is regarded is as being related to dysfunction of the brain-gut axis: pain is perceived in the abdominal region in the absence of pathology order himplasia overnight delivery. The central nervous system and psychosocial stressors combine to lead to a heightened experience of pain buy himplasia 30caps with mastercard. The pain of peptic ulcer disease may be food related and may improve with antacid. Intermittent obstruction of the cystic duct by a gallstone is known as biliary colic. Cholecystitis refers to a more long lasting, continuous pain in the same area due to impaction of a stone in the cystic duct. Obstruction of the common bile duct with a stone (choledocholithiasis) results in pain and jaundice. The presence of fever in such a patient indicates infection due to stasis of material in the biliary tree (cholangitis). As mentioned, functional abdominal pain is unrelated to eating, defecation or menses. Irritable bowel syndrome, is an almost identical disorder but is distinguished by disordered defecation. Functional abdominal pain may be due to a normal perception of abnormal gut motility or an abnormal perception of normal gut motility. It may not be due to the gut at all in that patients frequently have accompanying psychosocial difficulties. Important Historical Points and Physical Examination Features When chronic abdominal pain relates to a bodily function (defecation, eating, micturition or menstruation) investigation should focus upon the involved system. Functional pain is more frequent in those who have had recent conflicts, have experienced a death in the family, or have become overly concerned with fatal illness. Patients with functional abdominal pain do not have alarm symptoms such as fever, weight loss, or rectal bleeding. Diagnosis and Management Diagnostic testing for chronic abdominal pain is similar to that for acute abdominal pain. Investigation involves a combination of bloodwork, urinalysis, diagnostic imaging and endoscopic testing. Management of organic causes of the chronic abdominal pain is directed at the underlying disease process. For patients with functional abdominal pain, the physicians responsibility is to reassure the patient that no serious disease exists. Where such a relationship does not exist, the patient may consult many doctors without satisfaction. It is important to investigate to a degree to reassure both patient and physician that the diagnosis is correct. However, it is also important not to continually repeat investigations in the belief something is being missed. Shaffer 22 benefit from low-dose antidepressants, as in other chronic pain syndromes. Description A state characterized by increased serum bilirubin levels (hyperbilirubinemia) and a yellow appearance due to deposition of bile pigment in the skin and mucus membranes. Interruption of the breakdown pathway at any of a number of steps, or a marked increase in load due to red blood cell destruction, results in an increase in serum bilirubin and if high enough, clinical jaundice. Under normal circumstances, senescent red blood cells are taken up and destroyed in the reticuloendothelial system. Through a number of steps the heme molecule of hemoglobin is converted to bilirubin which is, tightly bound to albumin, and transported in the plasma to the liver cells. Hepatocytes take up bilirubin, conjugate it to glucuronide and excrete the bilirubin diglucuronide in bile into the duodenum. In the bowel, bacteria break down bilirubin to urobilinogen, 80% of which is excreted in the feces, contributing to the normal stool colour. The remaining 20% of urobilinogen is reabsorbed and excreted in bile and urine (enterohepatic circulation of urobilinogen). Functional defects in bilirubin metabolism or anatomic obstruction to excretion into the biliary system will result in an increase in serum bilirubin and jaundice. If the problem lies after the uptake and conjugation step, the increase is in serum conjugated bilirubin. In adults, aside from hemolysis or the common benign unconjugated hyperbilirubinemia of Gilberts syndrome, most patients with jaundice have a conjugated hyperbilirubinemia. Causes of jaundice are usually classified as: (1) hemolysis; (2) genetic defects in bilirubin handling; (3) hepatocellular disease; and (4) obstruction or cholestasis. Clinical Presentation Clinical jaundice is detected when the serum bilirubin level reaches 24 mg/dL (4080 mol/L). Jaundice is usually preceded by a few days of pale stools (as excretion of bilirubin into the intestine is decreased) and dark urine (due to increased glomerular filtration of conjugated bilirubin). Jaundice is usually first detected in the sclera, although the bilirubin is actually deposited in the overlying conjunctival membranes. Yellow skin without scleral icterus should suggest carotenemia (excess intake of foods high in carotene) or the ingestion of such drugs as quinacrine. Patients with jaundice due to a cholestasis often experience pruritis, presumably from deposition of bile salts in the skin. Other historical points to ask include inquiring about viral hepatitis risk factors (e. Shaffer 23 of portal hypertension (ascites, splenomegaly, dilated periumbilical veins) and asterixis (flapping of the outstretched hands, a sign of hepatic encephalopathy). Serum bilirubin can be fractionated from total bilirubin into conjugated and unconjugated. The presence of bile in the urine determined by a test strip at the bedside confirms that the bilirubin rise is predominantly in the conjugated form. If the bilirubin is primarily unconjugated, hemolysis or genetic defects are implicated. In adults, Gilberts syndrome is an inherited genetic disorder of impaired bilirubin conjugation.