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In older patients who demonstrate re- advanced age and accounts for substantial functional im- duced initiative and attention purchase betoptic 5ml with mastercard medicine dispenser, these medications may be pairment (Reynolds et al order betoptic 5 ml otc treatment zone lasik. Greater dependence on others for cognitive and 5ml betoptic free shipping medications information, at times buy betoptic 5ml online medications mexico, physical tasks may engender feelings of loss The elderly represent a rapidly growing population with a and helplessness. The thoughtful application of principles of ge- ing and titration should be adjusted based on the time- riatric medicine will improve the assessment and manage- honored philosophy of “start low, go slow” in recognition ment of this complex patient group. Nevertheless, timely of heightened sensitivity to medication side effects and po- and appropriate rehabilitative and neuropsychiatric inter- tential drug-drug interactions with other nonpsychotropic ventions may provide older patients with substantial func- medications. Neurobiol Aging 18:431–435, 1997 in older adults: epidemiology, outcomes, and future implica- Friedman G, Froom P, Sazbon L, et al: Apolipoprotein E-epsilon4 tions. J Am Geriatr Soc 54:1590–1595, 2006 genotype predicts a poor outcome in survivors of traumatic brain injury. Brain Inj 10:145–148, 1996 outcome and mortality in elderly patients with head injuries. Biol Psy- functional recovery from brain injury following postacute re- chol 54:35–54, 2000 habilitation. Semin and time to onset of Alzheimer’s disease: a population-based Nucl Med 37:69–87, 2007 study. The prevention can include many aspects, but both disorders (Substance Abuse Task Force 1988). Moreover, of disorders as independent and interactive enhances the 58% of all surgical admissions and 72% of all hospital total treatment of the patient (Kreutzer et al. Those who are actively involved in mented because often specific testing and history taking the treatment must be skilled in the intervention, referral, for drugs are not part of either routine clinical practice or and, in some cases, the actual long-term management of research studies. Although a specialist may be em- the implications of drug histories when clear evidence ex- ployed for either category of disorder, he or she must know ists. The reasons for poor documentation are complex and the ramifications of both disorders. For instance, the ad- include poor skills in assessing the importance of drugs diction specialist must know and work with the limita- and alcohol as well as ignorance that effective treatment 461 462 Textbook of Traumatic Brain Injury for alcohol and drug disorders exists. Fifty percent of all fatal acci- do not often include measurement of urine or blood for il- dents in the United States are motor vehicle accidents. The common occurrence these fatal motor vehicle accidents, 50% are associated of multiple drug and alcohol use or addiction in high-risk with alcohol and drugs. The prevalence rate for alcoholism in the United States The high degree of association of alcohol/drug use and is approximately 15%. Studies of prog- 22 years in men and 25 in women, according to the Epide- nosis and outcome after brain injury frequently exclude miologic Catchment Area study (Miller 1991b). The re- individuals who are addicted to drugs, alcohol, or both be- ported prevalence rate for drug addiction in the general fore accidents, even though this practice produces signif- population ranges from 9% to 20%. The majority of drug- icant and relevant distortions of data (Sparadeo and Gill addicted individuals are addicted to alcohol, and substan- 1989; Substance Abuse Task Force 1988). In one evaluation of primary care physicians studies suggest that ethanol may have a neuroprotective (Miller 2002), 94% were unable to identify a substance effect, though these results are conflicting and warrant disorder as one of five diagnostic possibilities in case stud- more prospective studies (O’Phalen et al. When case studies described early signs of a drug disorder in teenagers, 41% of pediatricians failed to provide sub- stance disorder as one of five diagnostic possibilities. Also, Intervention in the Acute State nearly three-fourths of patients seeking treatment for a drug disorder did not receive guidance from their primary The first clinical caveat is that if alcohol or drug addiction, care physician. Frequent complications include tions is 50%–75% and 25%–50% in medical populations. Other average age for men in treatment is 30–35 years, and the possible complications include behavioral dyscontrol, average age for women is 25–30 years. One hundred thousand peo- tory depression after acute intoxication and overdose are ple die annually in accidents in the United States. Importantly, some vehicle accidents are the leading cause of death for teens in intoxicated patients are discharged from the emergency the United States, accounting for more than one-third of department when in fact they have undiagnosed brain in- the deaths in this age group. In a study of 167 patients (Gallagher and Browder between the ages of 15 and 19 were killed and almost 1968), alcohol obscured changes in consciousness, lead- 400,000 were treated in emergency rooms for injuries sus- ing to misdiagnosis or delayed diagnosis of complications tained in motor vehicle accidents (Centers for Disease Con- of brain trauma. Criteria for substance dependence Drug-drug interactions A maladaptive pattern of substance use, leading to clinically Drug overdose significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12- Increased sensitivity to medication effects month period: Seizures from either drug intoxication or drug or alcohol (1) tolerance, as defined by either of the following: withdrawal (a) a need for markedly increased amounts of the Hallucinations substance to achieve intoxication or desired effect Delusions (b) markedly diminished effect with continued use of the Anxiety same amount of the substance Depression induced by intoxication and withdrawal from drugs (2) withdrawal, as manifested by either of the following: Alcohol and drug seeking from the presence of an addictive (a) the characteristic withdrawal syndrome for the disorder substance (refer to Criteria A and B of the criteria sets for withdrawal from the specific substances) diagnosed only at postmortem (Galbraith 1976), and oth- (b) the same (or a closely related) substance is taken to ers have reported similar results (Rumbaugh and Fang relieve or avoid withdrawal symptoms 1980). Two of the seven criteria reflect With physiological dependence: evidence of tolerance or development of tolerance and dependence on alcohol and withdrawal (i. Any three of the seven criteria are required to make the Without physiological dependence: no evidence of tolerance or diagnosis of alcohol or drug dependence, or both. The manifest loss of control often is reflected by the circum- Early partial remission stances surrounding and including the actual trauma that Sustained full remission culminates in the brain injury. Sustained partial remission It has been well documented that the most effective On agonist therapy clinical approach to both diagnosis and treatment of an al- In a controlled environment cohol or drug disorder involves the acknowledgment of Source. Reprinted from Diagnostic and Statistical Manual of Mental substance dependence as a disease state rather than as a Disorders, 4th Edition, Text Revision, pp. Copy- provide adequate support for the powerful role of inherit- right © 2000 American Psychiatric Association. A parallel may be drawn between substance disor- ders and other inherited diseases such as hypertension, in dence, accept responsibility for treatment, and adopt a which a person has little control over the development of commitment to long-term recovery. The use of medica- the disorder but is solely responsible for treatment of the tions for the treatment of withdrawal from alcohol or drugs disorder. By using this approach in a clinical setting, pa- and to assist patients with achieving abstinence may aid in tients often are able to overcome the common feelings of the belief that alcohol or drug dependence is, in fact, a dis- shame and blame associated with alcohol or drug depen- ease (Miller 2001). The partnership of these assessment tools characteristic course and predictable consequences. Although patients with alcoholism and Identification of the neural basis of pathological crav- those with drug addictions report drinking and using drugs ing for alcohol and drugs may also serve as a vital tool for because of anxiety and depression, objective and con- diagnosing patients with a substance dependency (Dackis trolled studies fail to confirm the hypothesis that alcohol and Miller 2003). Neuroimaging studies have identified and drugs are used to improve mood and thinking. The limbic system pathways that are responsible for both nor- conclusions from many studies are that continued alcohol mal and pathological cravings in human and animal stud- and drug use results in the appearance and worsening of ies. Changes in limbic system pathways have been identi- psychiatric symptoms in proportion to the amount and du- fied in studies in which human and animal subjects have ration of alcohol and drug use (Mayfield and Allen 1967; had chronic exposure to alcohol or drugs. A new set Family history is the best predictor for the onset of al- point, or alleostasis, may be responsible for intense crav- coholism and drug addiction in a given individual. After a period of abstinence, the degree of atro- that require diagnosis, intervention, and treatment. Un- phy in these regions tends to diminish, especially when treated family members with an addiction can have an ad- abstinence occurs at a younger age. Screening tests are available for alcohol disorders that can be modified for drugs by inserting drug for the word alcohol. During agnosis of alcoholism (positive response to one question this initial abstinence, the influence of alcohol and drugs means probable alcohol dependence). If this is used as a self-administered written instrument, the scoring system should not be shown on the form. In general, benzodiazepines are used to treat alcohol only drug or alcohol addiction, or both.

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In most cases order discount betoptic online treatment 5th disease, the descending pathways act through synaptic connections on interneurons order cheapest betoptic medications 44 175. The magnocellular portion of the red nucleus is the origin of the rubrospinal tract purchase cheap betoptic line symptoms electrolyte imbalance. The reticular formation is the source of two tracts: one from the pontine portion and one from the medulla cheap betoptic 5ml free shipping medications that cause tinnitus. Rubrospinal tract The red nucleus of the mesencephalon receives major input from both the cerebellum and the cerebral cortical motor areas. Output via the rubrospinal tract is directed predominantly to contralateral spinal motor neurons that are involved with movements of the upper limbs. The axons of the rubrospinal tract are located in the lateral spinal white matter. Rubrospinal action enhances the function of motor neurons innervating upper limb flexor muscles while inhibiting extensors. In higher mammals like humans, the corticospinal tract supersedes most of the function of the rubrospinal tract. However, when lesions of corticospinal tract occur, the rubrospinal tract can partially compensate for the loss of corticospinal tract inputs to upper limb motor neurons. Vestibulospinal tract The principal functions of the vestibular system are to activate neck, trunk, and limb muscles to maintain posture in response to movements of the head and to maintain visual fixation of the eyes on a target as the head moves through space. Both of these functions are controlled by pathways that originate from the vestibular complex located in the pons and medulla. The vestibular complex contains four nuclei (superior, lateral, medial, and inferior vestibular nuclei) that receive information about the position of the head in space from the vestibular apparatus of the inner ear and proprioceptive information from the spinal cord (see Chapter 4). The vestibular nuclei also are reciprocally connected to the cerebellum and adjacent reticular formation from which it receives sensory- and motor-related inputs. The vestibular nuclei modify both muscle tone and initiate automatic adjustments in posture through two descending pathways, the lateral and medial vestibulospinal tracts. The lateral vestibulospinal tract originates primarily from cells in the lateral vestibular nucleus. The axons from these cells travel in the ipsilateral ventrolateral spinal cord white matter to terminate at all levels of the spinal cord where they excite interneurons and α and γ extensor motor neurons that innervate truncal and proximal limb muscles. These extensor motor neurons and their musculature are important for maintaining posture and modulating posture-related reflexes that help stabilize the body’s position against the forces of gravity. As these axons descend, they give off collateral branches at multiple spinal cord levels, which ensure proper coordination of postural reflexes across multiple levels. Lesions in the brainstem secondary to stroke or trauma may abnormally enhance the influence of the vestibulospinal tract and produce dramatic clinical manifestations. The medial vestibulospinal tract arises primarily from the medial vestibulospinal nucleus and descends bilaterally to terminate on motor neuron in the cervical spinal cord that controls neck extensor and flexor muscles. The function of this pathway is to reflexively activate neck muscles in response to changes in head position. Reticulospinal tracts The reticular formation is a complicated network of neurons located in the central gray matter core of the brainstem. Within this network are also discrete circuits that control a diverse set of functions such as sleep, autonomic functions, and eye movements. Within the medial regions of the caudal reticular formation are groups of large neurons that are involved in somatic motor control of both cranial nerve and spinal cord motor neurons. Two descending tracts important in the control of spinal lower motor neurons arise from medial reticular formation cells. These pathways mostly influence motor neurons that innervate truncal and limb extensor muscles. Through their influence on gamma motor neurons, these pathways modulate muscle tone and help make anticipatory adjustments in posture during movement. The medial (pontine) reticulospinal tract arises from pontine reticular nuclei and descends bilaterally with an ipsilateral preponderance in the anterior spinal cord white matter. This pathway relays excitatory action potentials to interneurons that influence α and γ motor neuron pools. The medullary reticulospinal tract arises from the reticular formation in the medulla and descends ipsilateral in the spinal cord white matter adjacent to the anterior horn. This pathway has an inhibitory influence on interneurons that modulate extensor motor neurons. The rubrospinal tract terminates mostly on interneurons in the lateral spinal intermediate zone, but it also has some monosynaptic connections directly on motor neurons to muscles of the extremities. This tract supplements the corticospinal tract for independent movements of the upper extremities. The vestibulospinal and reticulospinal tracts terminate in the ventromedial part of the intermediate zone, an area in the gray matter containing propriospinal interneurons (Fig. There are also some direct connections with motor neurons of the neck and back muscles and the proximal limb muscles. The vestibulospinal and reticulospinal tracts influence motor neurons that control axial and proximal limb muscles. In accordance with their medial or lateral distributions to spinal motor neurons, the reticulospinal and vestibulospinal tracts are thought to be most important for the control of axial and proximal limb muscles, whereas the rubrospinal (and corticospinal) tracts are most important for the control of distal limb muscles, particularly the flexors Sensory and motor systems work together to control posture. The maintenance of an upright posture in humans requires active muscular resistance against gravity. For movement to occur, the initial posture must be altered by flexing some body parts against gravity. Balance must be maintained during movement, which is achieved by postural reflexes initiated by several key sensory systems. Vision, the vestibular system, and the somatosensory system are important for postural reflexes. Somatosensory input provides information about the position and movement of one part of the body with respect to others. The vestibular system provides information about the position and movement of the head and neck with respect to the external world. Vision provides both types of information as well as information about objects in the external world. Visual and vestibular reflexes interact to produce coordinated head and eye movements associated with a shift in gaze. Vestibular reflexes and somatosensory neck reflexes interact to produce reflex changes in limb muscle activity. The quickest of these compensations occurs at about twice the latency of the monosynaptic myotatic reflex. The extra time reflects the action of other neurons at different anatomic levels of the nervous system. The cortex modifies sensory-evoked involuntary movements like brainstem- and spinal cord–related postural adjustments by continuous modulation of brainstem descending motor pathways and spinal cord reflex pathways. The role of this modulation is readily apparent when it is damaged (see Clinical Focus 5. Cortical control of skilled voluntary movements, most of which involve the distal extremities, is accomplished through connections with cranial nerve motor nuclei and spinal cord interneurons and motor neurons that control skilled movement.

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The scrotal temperature is believed to be due to dilatation of the usually higher in the presence of varicocele tubules of the epididymis (inferior aberrant Acute Epididymo-orchitis and this may impair spermatogenesis purchase betoptic without prescription medications that cause dry mouth. The condition commonly occurs in associa- Tey are brilliantly transilluminate because tion with infection of the urinary tract such Treatment they contain crystal clear fuid order 5 ml betoptic mastercard illness and treatment. Asymptomatic varicocele-No treatment like a bunch of tiny grapes order betoptic visa medications ending in zine, located behind the follow instrumentation of the urinary tract discount betoptic amex symptoms 37 weeks pregnant. Tese are cysts in connection with the epidi- following embryonic remnants around the Severe pain in the testes and groin along dymis divided into the following types: epididymis. The paradidymis or organ of Geraldes Culture of urethral discharge and urine can degeneration of the appendages of epidi- which represents the mesonephric reveal the ofending organism. Tis is the common- • Strict bed rest and scrotal support is of the mesonephric tubules and the duct. Elephantiasis is due to obstruction of the • Tere may be vesicular eruptions over the pelvic lymphatics by W. Secondary hydrocele or chylocele in In the tropics, the commonest cause is Causes of Lymphangitis the tunica vaginalis. Eosinophilia 5 to 15 percent in early cases, ofen due to a hematogenous spread than products from dead worms, undergo- no such fnding in late cases. Local dressing with povidone iodine • In every case, urine must be examined for rent attacks of lymphangitis. Excision of the hypertrophied and edema- tive, a culture may be positive and should lymph nodes. The performed to rule out urinary and pulmo- • Lymphatic obstruction brought about raw shaf of the penis is covered with either nary tuberculosis respectively. In long-standing cases the The epididymitis will usually resolve on scrotum becomes so much enlarged that antitubercular therapy. Excess blood loss-Blood transfusion to Gangrene sets in as the toxin induced be dealt within two ways: be arranged during operation. If there is lack of scrotal or perineal in the scrotum with fever and a bad smell. Locally, wide excision of the necrotic tis- Patients are almost always immunocompro- sue and laying open of the afected areas Difficulties mised with conditions such as diabetes mellitus. Injury to the urethra-It can be avoided The wound initiating the infection may The debridement may be extensive by passing a dilator or catheter during have been minor but severely contaminated and patients may need large areas of skin operation. Active strategy-Wearing helmets become a leading cause of death in developed their success or failure. The spectrum of injury control consists of cational such as antidrunk eforts or leg- a. Care at the site of accident or prehospital surveillance, prevention and treatment. Breathing support is given by: • Signs at the site of accident ambulance crew or relatives. Each is administered to provide circulatory • Secondary survey area of the body should be completely exam- support. The following things are done in second- word triage = to sort) which is a dynamic • A-Airway management ary survey. Intravenous line is secured with a wide Triage involves grouping the casualties • C-Circulation with hemorrhage control bore cannula (16 Fr), preferably in the into three priorities and diferent color faps • D-Disability (neurologic status) upper limb if not already secured. The three priorities are: genation and ventilation are reassessed and • Blood sugar, urea and electrolytes (Na, • Immediate priority, e. P is bles the clinician to investigate the pos- The Golden Hour roughly equal to a score of 8 on Glasgow sibility of intraperitoneal bleeding. X-rays of skull, cervical spine, chest, many critical trauma patients during this Secondary Survey: The secondary survey pelvis and the limbs are commonly period. Other general measures which should the polytrauma case and in patients with of good medical practice. Definitive Care Phase assessment of a trauma patient, one should • Vital parameters are recorded every 15 During this phase, the comprehensive care remember to reevaluate the fndings. Impaired consciousness is the most dine are efective drugs; nowadays doubtful diagnosis or visceral injury in case common cause of a diagnosis being missed. Tey do not produce sedation transfer of the patient to a referral trauma Rehabilitation and quite efective in relieving moderate center, e. Intracranial lesions-It may be of two parenchyma but without any surface lacera- of their life and are of composite nature as the types viz. Tere may be associated cerebral edema injury to the skull bones, intracranial vessels • Focal injury-When the injury is and defects in blood brain barrier. Intracranial hematoma Cerebral Laceration Which may be a intracerebral or Tis is a severe degree of brain injury asso- extracerebral hematoma. By mechanism brain area and can be a concussion be due to skull fracture or shearing forces. In Tere is tearing of pia and arachnoidmater communication between the intradural difuse axonal injury there is acute and may be a associated with intracerebral contents and the environment. It may be due to The pathological changes due to trauma to compression of healthy brain. Moderate when Glasgow coma scale is Primary brain injury is the injury caused at subdural, 9 to 12. Skull fractures-May be a vault frac- Tis is a severe degree of brain injury mani- • The most important aspect of the manage- ture or a basilar fracture. An ipsilateral dilated pupil is a sign of Aim of treatment is to prevent secondary resuscitation extradural hemorrhage. X-ray skull and cervical spine if injury • Sedation, analgesia and paralysis to of bleeding. Indications of skull X-ray in recent head • Nursing the patient with 30° head up e. Five percent Dextrose is best investigations it is difcult to localize the site avoided as it increases cerebral edema. A vascularized fap of bone is raised and • Strict glycemic control between 70 – the clot is evacuated under vision. Following this the fap is • Prompt surgery to drain the intrac- hematoma replaced and the scalp incision is closed. If it is from the bony canal in dural space resulting in a greater tendency to • Regular monitoring of vital parameters. If the bleeding is from the dural sur- Clinical features include drowsiness, con- • Treatment of associated fractures of face, the bleeding point is secured either by fusion, headache and hemiplegia. Tere is progressive site is exposed and a burr-hole is made hematoma via a trephine hole or burr – hole neurologic deterioration.

Pancreatic secretion is under neural and hormonal control and consists of three phases: cephalic order 5ml betoptic free shipping treatment hyponatremia, gastric purchase betoptic toronto medications breastfeeding, and intestinal purchase betoptic australia medications used for migraines. Proteins are digested to form amino acids buy betoptic with a visa medicine to calm nerves, dipeptides, and tripeptides before being taken up by enterocytes and transported in the blood. The gastrointestinal tract absorbs water-soluble vitamins and ions by different mechanisms. Most of the salt and water entering the intestinal tract, whether in the diet or in gastrointestinal secretions, is absorbed in the small intestine. Lipids absorbed by enterocytes are packaged and secreted as chylomicrons into the lymph. Carbohydrates, when digested, form maltose, maltotriose, and α-limit dextrins, which are cleaved to brush border enzymes to monosaccharides and taken up by enterocytes. Heme and nonheme iron are absorbed in the small intestine by different mechanisms. Parasympathetic stimulation induces salivary acinar cells to release the protease: A. Parasympathetic stimulation induces the release of kallikrein by the salivary acinar cells, which then converts kininogen to form lysyl-bradykinin (a potent vasodilator). Kinins are peptides that are related in amino acid sequence and physiological activity to bradykinin. Aminopeptidase releases amino acids from the amino end of peptides and is found in the brush border membrane and cytoplasm of enterocytes. Which of the following best describes enterokinase, an enzyme necessary for protein digestion? It is produced by the pancreas and directly converts ribonuclease into its active form. It is produced by the pancreas and prevents autodigestion of the pancreas by pancreatic enzymes. Enterokinase is an enzyme produced by the cells of the duodenum (crypt of Lieberkühn) that converts trypsinogen to its active form, trypsin. Hartnup disease is an inherited autosomal recessive disorder involving the malabsorption of amino acids, particularly tryptophan by the small intestine. Feeding di- and tripeptides containing tryptophan to patients with this disease improves their clinical condition because: A. Amino acids as well as di- and tripeptides use different brush border transporters for their uptake. Pancreatic lipase hydrolyzes triglyceride to form 2-monoglyceride and fatty acids. Only hydrolysis of phosphatidylcholine results in the formation of lysophosphatidylcholine, so the hydrolysis of triglyceride does not result in the formation of lysophosphatidylcholine. Although diglyceride is an intermediate in the hydrolysis of triglyceride by pancreatic lipase, the hydrolysis continues until 2-monoglyceride and fatty acids are formed. Pancreatic lipase does not hydrolyze triglyceride totally to form glycerol and fatty acids. A gastroenterologist administers 50 g of lactose by mouth to the child and measures an increase in the boy’s expired hydrogen gas. From a physician’s standpoint, what recommendations and advice can be given to this patient to address his problem with lactose intolerance? Lactose is hydrolyzed by a brush border enzyme called lactase to glucose and galactose. The monosaccharides are then absorbed by sodium-dependent secondary active transport. If the lactase enzyme is deficient, lactose will not be broken down and will remain in the intestinal lumen. The osmotic activity of the lactose draws water into the intestinal lumen and results in a watery diarrhea. In the colon, bacteria metabolize the lactose to lactic acid, carbon dioxide, and hydrogen gas. The extra fluid and gas in the intestine result in distention and increased motility (cramps). Avoiding foods that contain lactose (milk, dairy products) is recommended for lactose-intolerant people, but calcium and caloric intake should not be compromised. Milk can be pretreated with an enzyme obtained from bacteria or yeasts that digests lactose, or lactase pills can be taken with meals. Describe how the architectural arrangement of the hepatocytes allows for the rapid exchange of molecules. Explain how vitamin A is stored in the liver and transported to other parts of the body when needed. It is composed of several distinct cell types including Kupffer cells, sinusoidal epithelial cells, cholangiocytes, and hepatocytes, but the vast majority, 70% to 80%, is hepatocytes. Given its wide range of functions, the liver is an extremely vital organ for maintaining whole-body homeostasis. A healthy liver also contributes to both the innate and adaptive immunological defense mechanisms of the body. The liver is a unique organ because it has a dual blood supply and it is the only internal human organ capable of regenerating lost tissue. With as little as 25% of the liver remaining, it can regenerate into an entire organ, which is possible because hepatocytes are capable of reentering the cell cycle and undergoing mitosis. This chapter summarizes the liver’s many functions including (1) detoxification of hormones, drugs, and waste products; (2) metabolism of carbohydrates, proteins, and fats; (3) storage of iron and vitamins; (4) hormone production; and (5) innate and adaptive immunity. Given the liver’s wide range of functions, there is surprisingly little specialization among liver cells. The hexagonally shaped lobule is the functional unit of the liver and is built around a central vein (Fig. Individual lobules are made up of many cellular plates radiating from the central vein like spokes in a bicycle wheel. Each plate consists of specialized hepatocytes that contain discrete granules and perform a wide variety of metabolic functions and secretory tasks including the manufacture of specific proteins, detoxification of xenobiotics, and the production and secretion of bile. The lobule is arranged in a hexagonal fashion and is delineated by vascular and bile channels. The lobule contains specialized cells, such as hepatocytes, sinusoidal cells, and Kupffer cells. Architectural arrangement of hepatocytes in the liver lobule enhances the rapid exchange of material. The bile canaliculus is formed by the intercellular space located between neighboring hepatocytes. Impermeable tight junctions separate the canaliculus from the pericellular space and prevent the mixing of contents between the two regions (see Fig. Bile originating in the bile canaliculus drains into a series of ducts that eventually join the pancreatic duct near where it enters the duodenum. The sphincter of Oddi, located at the duodenal connection between the bile duct and the pancreatic duct, regulates drainage of bile and pancreatic juice into the duodenum. The pericellular space between two hepatocytes is continuous with the perisinusoidal space (see Fig.