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The patient in this vignette has pancreatitis. Patients typically present with severe, colicky abdominal pain that gets worse with ingestion of food. Risk factors for pancreatitis include alcohol (35%), gallstones (45%), hypertriglycerideemia, obesity and family history.
Ranson's criteria is used for prognosis in pancreatitis. There are two sets of criteria that compose Ranson's criteria: criteria on admission and criteria at 48 hours.
Ranson's criteria on admission:
1. Glucose > 200 <br>
2. Age > 55 <br>
3. LDH> 350 <br>
4. AST > 250 <br>
5. WBC > 16,000 <br>
These criteria can be remembered with the mnemonic GA LAW.
The criteria at 48 hours are:
1. Calcium < 8 mg/dL <br>
2. Hematocrit drop > 10% (absolute % drop) <br>
3. O2 < 60 (PaO2) <br>
4. Base deficit > 4 <br>
5. BUN increase > 5 <br>
6. Sequestration > 6L <br>
These criteria can be remembered with the mnemonic C HOBBS (like Calvin and Hobbes).
Ranson's criteria predict mortality in acute pancreatitis as summarized in figure 1. Acute medical treatment for pancreatitis consists of aggressive fluid administration, and narcotics for pain. Once discharged, patients should be advised to avoid any alcohol consumption. Occasionally, patients may have recurrent unrelenting pain for which surgical treatment is indicated.
<img src="http://static.wikidoc.org/5/5f/Screen_Shot_2016-09-10_at_8.48.58_PM.png" alt="Figure 1" width="400">
Figure 1. Ranson's score vs mortality.<br/>
'''Educational Objective:''' Serum amylase is not part of Ranson's criteria.<br/>
'''References:''' Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974;139(1):69-81. +
This patient most likely suffered a posterior shoulder dislocation as a result of his seizure. Posterior shoulder dislocations are rare (<5%). In most shoulder dislocations, the humerus is displaced anteriorly (>95%). Seizure can cause posterior shoulder dislocation when tetanic contractions of the external shoulder rotators (teres major, subscapularis, latissimus dorsi, and pectoralis major) overpower the internal rotators (teres minor and infraspinatus). This causes the head of the humerus to be pulled posteriorly out of the glenoid fossa. If a bilateral posterior shoulder dislocation is encountered, this almost always indicates injury due to a seizure. Approximately 15% of posterior shoulder dislocations are bilateral.<br>
In most cases, posterior shoulder dislocation can be corrected by closed reduction using the Depalma method (not high yield for Shelf exam). However, when diagnosis is delayed closed reduction under general anesthesia may be necessary. The joint should be immobilized for 4 weeks following reduction.<br/>
'''Educational Objective:''' Posterior shoulder dislocation may be caused by seizures or electrocution. During these events, tetanic contraction of the external rotators of the shoulder can pull the humerus posteriorly out of the glenoid fossa.<br/>
'''References:''' Perron AD, Jones RL. Posterior shoulder dislocation: avoiding a missed diagnosis. Am J Emerg Med. 2000;18(2):189-91.<br>
Wallis LA, Greaves I. Injuries associated with airbag deployment. Emerg Med J. 2002;19(6):490-3.<br>
Betz ME, Traub SJ. Bilateral posterior shoulder dislocations following seizure. Intern Emerg Med. 2007;2(1):63-5. +
The patient in this vignette has cerebral toxoplasmosis. The differential for CNS lesions in HIV patients should include: toxoplasmosis, progressive multifocal leukoencephalopathy, and primary CNS lymphoma. The MRI in this patient shows multiple, contrast enhancing lesions. The most anterior of these lesions produces a small midline shift from mass effect. Typically primary CNS lymphoma would present with a solitary intracranial mass (the primary tumor), making this diagnosis unlikely. The presence of a mass effect in this scan makes progressive multifocal leukoencephalopathy, a demyelinating disease caused by JC virus, a less likely diagnosis. The imaging and symptoms in this patient are most consistent with cerebral toxoplasmosis.
Given the diagnosis of cerebral toxoplasmosis, the best definitive treatment is pyrimethamine, an antibiotic that inhibits dihydrofolate reductase, the bacterial enzyme responsible for folic acid synthesis. Because of its mechanism of action, patients are also treated with folic acid to protect against myelosuppression. Pytimethamine has been a controversial drug in the media lately, as its manufacturer (Turing Pharmaceuticals) raised its price by 5000%.
In reality, the approach to HIV patients with CNS lesions is complicated by the fact that they can sometimes have more than one active process occuring. In one study of HIV patients undergoing brain biopsy, 6% had histologic evidence for more than one diagnosis.<br/>
'''Educational Objective:''' Multiple ring enhancing lesions in the brain of an HIV infected patient is highly concerning for cerebral Toxoplasmosis. Pyrimethamine is the preferred therapy.<br/>
'''References:''' Blueprints Neurology 3E page 91. <br>
Gildenberg PL, Gathe JC, Kim JH. Stereotactic biopsy of cerebral lesions in AIDS. Clin Infect Dis. 2000;30(3):491-9. +
The patient in this vignette has transverse myelitis. She has symptoms of an upper motor neuron lesion (hyperreflexia) in both lower extremities. Her CNS insult is therefore either in the spine or the brain.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
The patient in this vignette has elevated intracranial pressure as a result of traumatic brain injury (TBI). Intracranial pressure can be due to pressure in three compartments: the blood, the CSF or the brain. In this case, there is no discrete component of blood in the brain, and we have no reason to believe there is any obstruction of CSF flow that would increase the CSF pressure. Instead, it appears that there is swelling of the brain parenchyma causing increased intracranial pressure. Several maneuvers can work to decrease intracranial pressure in this case, including:
- elevating the head of the bed
- positioning the patients head in a midline fashion to encourage venous outflow (otherwise jugular veins can be compressed)
- hyperosmolar agents
Dexamethasone would be unlikely to work in this case, as corticosteroids tend to work for cases of increased intracranial pressure due to tumors rather than trauma.<br/>
'''Educational Objective:''' Hyperosmolar therapy is the best treatment for patient with elevated intracranial pressure and kidney failure.<br/>
'''References:''' Stocchetti N, Maas AI. Traumatic intracranial hypertension. N Engl J Med. 2014;370(22):2121-30. +
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'''Educational Objective:''' sfghdyw89789<br/>
'''References:''' +
The most common sites for bedsores are the sites in direct contact with the bed when the patient is lying on his/her back, which are sacrum, hips and heels.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
The novel agent induces an acute vasoconstriction of the epicardial coronary arteries and may result in either near or complete arterial occlusions. Coronary artery spasm typically manifests in angina with ST-segment elevations (not depressions) on 12-lead ECG. Modulation of contraction and relaxation of vascular smooth muscles is mainly mediated by the phosphorylation and dephosphorylation of myosin light chain kinase (MLCK) and phosphatase (MLCP). In the classical muscle contraction pathway, stimuli (e.g. histamine) initially bind to Gq protein-coupled receptors located on the surface of vascular smooth muscle cells. The binding process activates phospholipase C, which mediates the synthesis of both 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 then binds to receptors on the sarcoplasmic reticulum to mediate the mobilization of stored calcium into the cytosol. As cytosolic calcium concentration increases, calcium/calmodulin complexes form and activate MLCK, which result in the phosphorylation of myosin light chain and smooth muscle contraction.<br/>
'''Educational Objective:''' In the classical muscle contraction pathway, stimuli (e.g. histamine) initially bind to Gq protein-coupled receptors located on the surface of vascular smooth muscle cells. The binding process activates phospholipase C, which mediates the synthesis of both 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 then binds to receptors on the sarcoplasmic reticulum to mediate the mobilization of stored calcium into the cytosol. As cytosolic calcium concentration increases, calcium/calmodulin complexes form and activate MLCK, which result in the phosphorylation of myosin light chain and smooth muscle contraction.<br/>
'''References:''' Lanza GA, Careri G, Crea F. Mechanisms of coronary artery spasm. Circulation. 2011;124:1774-82.<br>
Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science. 1996;273(5272):245-8.<br>
Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature. 1994; 372(6503):231-6.
Monday disease is a form of nitrate tolerance that occurs among individuals who are exposed to high concentrations of organic nitrates, such as those who work in the manufacture of explosives, fireworks, and fertilizers. While healthy individuals may report clinical manifestations related to either the mechanism of action of nitrates (venodilation), such as light-headedness and fatigue, some may experience adverse reactions related to nitro exposure, such as severe, violent headaches. In contrast, patients with angina pectoris often report improved symptoms during the weekdays and recurring chest pains during the weekends. Workers are often exposed to nitrates during the weekdays, developing tolerance to the effects of nitrates. However, the tolerance effect is lost over the weekend, and patients typically re-experience symptoms the next Monday. The discovery of nitroglycerin tolerance was originally attributed to the observations of Monday disease among workers with occupational exposure.<br/>
'''Educational Objective:''' Monday disease is a form of nitrate tolerance that occurs among individuals who are exposed to high concentrations of organic nitrates, such as those who work in the manufacture of explosives, fireworks, and fertilizers.<br/>
'''References:''' Ferreira JCB, Mochly-Rosen D. Nitroglycerin use in myocardial infarction patients: risks and benefits. Circ J. 2012;76(1):15-21.<br>
Mayer B, Beretta M. The enigma of nitroglycerin bioactivation and nitrate tolerance: news, views and troubles. Br J Pharmacol. 2008;155:170-84. +
Raynaud's phenomenon is characterized by transient digital ischemia due to excessive vasoconstriction triggered by either cold temperatures or stressful situations. Clinical manifestations of Raynaud's phenomenon often include vasoconstrictive changes (well-demarcated areas of pallor or bluish (cyanotic) discoloration of the digits) followed by vasodilatory changes and reactive hyperemia (red skin). Raynaud's phenomenon may either be an isolated phenomenon (primary) or a manifestation of more serious, systemic diseases (secondary), such as CREST syndrome. Raynaud's phenomenon is typically managed by avoiding triggers, such as keeping warm hands during winter seasons, and possibly vasodilators. The addition of pharmacologic agents may be reserved to patients to experience severe vasoconstrictive changes, such as those who develop digital ulcers. Dihydropyridine calcium channel blockers (CCBs), such as nifedipine, amlodipine, or felodipine, are the first-line pharmacologic agents for Raynaud's phenomenon. Other pharmacologic agents include nitroglycerin, hydralazine, papaverine, minoxidil, prostaglandins, or niacin, all of which have not been as extensively studied as CCBs for the management of Raynaud's phenomenon.
Triphasic discoloration of digits on exposure to cold environment is a typical presentation for Raynaud phenomenon. Among the drug classes that have been used are calcium channel blockers, vasodilators, sympatholytic agents, and prostaglandins<br/>
'''Educational Objective:''' Raynaud's phenomenon is typically managed by avoiding triggers, such as keeping warm hands during winter seasons, and possibly vasodilators. The addition of pharmacologic agents may be reserved to patients to experience severe vasoconstrictive changes, such as those who develop digital ulcers. Dihydropyridine calcium channel blockers (CCBs), such as nifedipine, amlodipine, or felodipine, are the first-line pharmacologic agents for Raynaud's phenomenon.<br/>
'''References:''' Wigley FM. Raynaud's phenomenon. N Engl J Med. 2002;347:1001-8.<br>
First Aid 2015 page 301.
Carcinoid syndrome is caused by a carcinoid tumor, which is a neuroendocrine tumor that is characterized by excessive production of serotonin and histamine. Carcinoid tumors are rare tumors that typically develop in the gastrointestinal tract. Carcinoid tumors are typically silent until hepatic metastasis occurs. Prior to metastasis, serotonin produced by the tumor undergoes first pass metabolism and is eliminated by the liver. Once hepatic metastasis occurs, the first pass metabolism is bypassed, the clinical manifestations develop. Clinical manifestations of carcinoid syndrome are multisystemic and include cardiac, pulmonary, GI, and cutaneous manifestations. Valvular involvement usually includes either tricuspid insufficiency or pulmonic stenosis (right-sided). Facial flushing observed in carcinoid syndrome is mediated primarily by vasodilatory actions of histamine, which is not affected by prostaglandin inhibition by aspirin. Pellagra (vitamin B3 deficiency) may occur when tryptophan is depleted by accelerated synthesis of serotonin, which is converted to 5-hydroxyindoleacetic acid (5-HIAA) and is excreted in the urine. Management of carcinoid syndrome is surgical resection, but pharmacologic therapy, such as octreotide, are usually administered to provide symptomatic relief.<br/>
'''Educational Objective:''' Carcinoid syndrome is a neuroendocrine tumor that is characterized by excessive production of serotonin and histamine. Accelerated synthesis of serotonin by the carcinoid tumor is converted to 5-hydroxyindoleacetic acid (5-HIAA) and is excreted in the urine.<br/>
'''References:''' Zuetenhorst JM, Taal BG. Metastatic carcinoid tumors: a clinical review. Oncologist. 2005;10(2):123-31.<br>
First Aid 2015 page 336. +
Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects the lungs, pancreas, liver, and intestine. It is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions.
CF is caused by mutation of the gene CFTR (cystic fibrosis transmembrane conductance regulator) which encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. The encoded protein functions as a chloride channel and controls the regulation of other transport pathways. ΔF508 is the most common type of mutation within the CFTR gene. The mutation is a deletion of the three nucleotides that comprise the codon for phenylalanine (F) at position 508. Individuals with the CFTRΔF508 mutation produce an abnormal CFTR protein that lacks this phenylalanine residue. This protein does not escape the endoplasmic reticulum for further processing and fails to be translocated to the epithelial surface, rendering epithelial membranes relatively impermeable to chloride ions. In sweat ducts, there is decreased absorption of chloride through CFTR with decreased absorption of sodium through epithelial sodium channel (ENaC) which results in production of hypertonic sweats. In the gastrointestinal tract, there is decreased secretion of chloride through CFTR with increased absorption of sodium through ENaC which leads to production of dehydrated mucus. In the airways, the absence of functional CFTR causes upregulation of the ENaC channel which further decreases salt and water secretion by reabsorbing sodium ions. As such, the respiratory complications in cystic fibrosis are not solely caused by the lack of chloride secretion, but instead by enhanced reabsorption of sodium and water.
Cystic fibrosis is a multisystem disease that affects epithelial cells of virtually all organs. It is characterized by excessive salt loss via sweat glands, meconium ileus, bilious vomiting, intestinal obstructionm, malabsorption, steatorrhea, chronic pulmonary infections that result in pulmonary fibrosis, cardiac arrhythmias, pancreatic insufficiency, and male infertility (bilateral congenital vas deferens). Clinical manifestations often occur early during the course of the disease, and patients may develop clinical features of CF as early as day 1 of birth (e.g. meconium ileus). The thickened secretions from the pancreas block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas. This causes atrophy of the exocrine glands and progressive fibrosis. The observed delay for pancreatic fibrosis to develop accounts for the delayed damage to the endocrine pancreas, whose manifestations often appear at an advanced stage of the disease. The median age at diagnosis of cystic fibrosis-related diabetes (CFRD) is 18-21 years.<br/>
'''Educational Objective:''' The thickened secretions from the pancreas block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas. This causes atrophy of the exocrine glands and progressive fibrosis. The observed delay for pancreatic fibrosis to develop accounts for the delayed damage to the endocrine pancreas, whose manifestations often appear at an advanced stage of the disease. The median age at diagnosis of cystic fibrosis-related diabetes (CFRD) is 21 years.<br/>
'''References:''' Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352:1992-1991.<br>
Ntimbane T, Comte B, Mailhot G, et al. Cystic fibrosis-related diabetes: From CFTR dysfunction to oxidative stress. Clin Biochem Rev. 2009;30(4):153-77.<br>
First Aid 2015 page 84.
When hamster ovary cells are incubated with the investigational agent, cell division arrests at metaphase. In the absence of an intact mitotic spindle, duplicated chromosomes cannot correctly align along the division plate and may result in apoptosis. Paclitaxel is a microtubule-stabilizing agent that differs from the vinca alkaloids and colchicine derivatives in that it binds to a different tubulin site and promotes, rather than inhibits, microtubule formation. Paclitaxel blocks cell in the G2-M phase of the cell cycle by binding to the beta-subsunit of tubulin. Remarkably also, it has the ability to polymerize tubulin with the absence of any cofactor. The taxanes have a central role in the treatment of ovarian, breast, lung, gastrointestinal, genitourinary, and head and neck cancers.<br/>
'''Educational Objective:''' Paclitaxel is a microtubule-stabilizing agent that differs from the vinca alkaloids and colchicine derivatives in that it binds to a different tubulin site and promotes, rather than inhibits, microtubule formation. Paclitaxel blocks cell in the G2-M phase of the cell cycle by binding to the beta-subsunit of tubulin. The epothilones resemble taxanes in that they bind to beta-tubulin and trigger microtubule nucleation and cell-cycle arrest at the G2-M interface.<br/>
'''References:''' Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Microtubules. Available from: http://www.ncbi.nlm.nih.gov/books/NBK9932/<br>
First Aid 2015 page 411. +
Meconium ileus is characterized by thickening meconium that is congested in the ileum. It is associated with abdominal distension and bilious vomiting that occur soon after birth. Failure of meconsium passage may be associated with either Hirschsprung's disease or cystic fibrosis. GIven that the two diseases may manifest similarly at birth, a rectal biopsy is usually indicated to differentiate between both conditions.
During normal fetal development, cells from the neural crest migrate into the colon to form Auerbach's plexus and Meissner's plexus. Hirschsprung's disease (HD) is characterized by incomplete migration of the neural crest cells, which results in the lack of nerve bodies in the distal segments of the colon. The affected segment of the colon cannot relax and pass stool through the colon, and patients typically manifest with meconium ileus after birth.
''RET'' is a proto-oncogene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo. It encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signalling molecules. Loss-of-function mutations are associated with Hirschsprung's disease, while gain-of-function mutations are associated with medullary thyroid carcinoma, pheochromocytoma, and multiple endocrine neoplasias type 2A and 2B.<br/>
'''Educational Objective:''' ''RET'' is a proto-oncogene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo. It encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signalling molecules. Loss-of-function mutations are associated with Hirschsprung's disease, while gain-of-function mutations are associated with medullary thyroid carcinoma, pheochromocytoma, and multiple endocrine neoplasias type 2A and 2B.<br/>
'''References:''' Edery P, Lyonnet S, Mulligan LM, et al. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994;367(6461):378-80.<br>
First Aid 2015 page 337
''Pneumocystis jiroveci''/''carinii'' pneumonia (PCP) is an opportunistic infection caused by ''Pneumocystis jiroveci''. The risk of PCP increases among HIV-positive patients when CD4+ cell concentrations are less than 200 cells/μl. Symptoms include fever, non-productive cough, shortness of breath, weight loss, and night sweats. Chest films typically demonstrate diffuse, symmetrical, perihilar interstitial infiltration that may progress to a homogenous, ground-glass opacification of the lung fields.
Hypoxemia, the most characteristic laboratory abnormality, may range from mild (room air arterial oxygen ≥70 mm Hg or alveolar-arterial O2 difference <35 mm Hg) to moderate (A-a DO2 ≥35 and <45 mm Hg) to severe (A-a DO2 ≥45 mm Hg).
TMP-SMX is the treatment of choice for PCP. For mild-to-moderate disease, alternative therapeutic regimens include either dapsone plus TMP, primaquine plus clindamycin, or atovaquone. For moderate-to-severe disease, either clindamycin-primaquine or pentamidine may be administered. Patients with moderate-to-severe disease should receive adjunctive corticosteroids as early as possible within 72 hours after starting specific PCP therapy.
This patient's hospital course is complicated by hemolytic anemia due to increased oxidative stress, which typically occurs among patients with glucose-6-phosphate dehydrogenase deficiency. Heinz bodies, bite cells, spherocytes, and reticulocytes may be evident on peripheral blood smear.<br/>
'''Educational Objective:''' For mild-to-moderate PCP, alternative therapeutic regimens include either dapsone plus TMP, primaquine plus clindamycin, or atovaquone. Common triggers of hemolytic anemia include sulfonamides and other drugs such as chloroquine, isoniazid, nalidixic acid, nitrofurantoin, and primaquine.<br/>
'''References:''' Kaplan JE, Benson C, Holmes KK, et al. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. Centers for Prevention and Disease Control. 2009;58(RR04);1-198.<br>
First Aid 2015 page 168, 170.
Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease that most commonly affects the renal and internal carotid arteries. Nonetheless, FMD has been described in virtually all arterial beds. On abdominal angiogram, FMD is characterized by a string-of-bead appearance that is suggestive of arterial beaing, typically in the middle-to-distal segment of the renal artery. On histopathological analysis of the vascular lesion, FMD demonstrates involvement of the media, with preservation of other vascular layers such as the intima, internal elastic lamina, and adventitia. Renovascular fibromuscular dysplasia tends to affect women between the age of 15 and 50 years. In the majority of cases, individuals with FMD remain asymptomatic for many years, and fibromuscular dysplasia is often discovered incidentally. Management of renovascular FMD includes pharmacologic therapy to control blood pressure, especially ACE-inhibitors. Percutaneous balloon angioplasty is usually reserved for patients who have uncontrollable blood pressure despite optimal pharmacologic therapy, patients who cannot tolerate pharmacologic therapy, or patients whose renal function is compromised.<br/>
'''Educational Objective:''' Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease that most commonly affects the renal and internal carotid arteries. Medial fibroplasia, which is characterized by its classic “string of beads” appearance, represents the most common type of fibromuscular dysplasia. On abdominal angiogram, FMD is characterized by a string-of-bead appearance that is suggestive of arterial beaing, typically in the middle-to-distal segment of the renal artery. Histologically, there is involvement of the media, whereas the intima, internal elastic lamina, and adventitia are preserved.<br/>
'''References:''' Poloskey SL, Olin JW, Mace P, et al. Fibromuscular dysplasia. Circulation. 2012;125:e636-9.<br>
Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med. 2004; 350:1862-71.<br>
First Aid 2015 page 290.
The patient is likely having an acute transmural myocardial infarction of the lateral wall, as suggested by the clinical findings (persistent, substernal chest pain) and as evidenced by the ECG changes (ST-segment elevation in the lateral leads I, aVL, V5-V6). Clinically, stable/unstable angina are differentiated from a myocardial infarction (MI) by the persistence and radiation of symptoms, hemodynamic changes, and the absence of relief with rest or with pharmacological therapy (e.g. sublingual nitroglycerin). In MI, patients typically report substernal chest pain, often felt as chest pressure, that radiates to either the jaw, the left arm, or the epigastric region. Given that a MI and other life-threatening conditions should always be ruled out when patients present with chest pain, clinical differentiation between angina and myocardial infarction is not very relevant since all patients end up with a diagnostic work-up.
The fatty streak is the the earliest evidence of atherosclerosis. It is characterized by non-obstructive, yellowish lesions in the arterial lumen. Although asymptomatic, fatty streaks often predispose to endothelial dysfunction, which subsequently results in a pro-inflammatory state that allows the aggregation of inflammatory mediators (leukocyte recruitment and foam cell formation from monocytes) and the entry and modification of lipids in the subendothelial intima. As lipids accumulate within the intima, they are trapped and oxidized, forming reactive oxygen species. The plaque progression is highly dependent on the smooth muscle cell migration into the intima following the formation of the fatty streak and the subendothelial changes that ensue. As the plaque grows, it can obstruct luminal blood flow, resulting in myocardial ischemia and clinical manifestations (e.g. stable angina). As the plaque grows further, its fibrous cap may rupture, and prothrombotic molecules (originally in the subendothelial within the lipid atheroma) are exposed. Once exposed, thrombosis occurs and an occlusive clot develops, resulting in a myocardial infarction.<br/>
'''Educational Objective:''' As the atherogenic plaque grows, its fibrous cap may rupture, and prothrombotic molecules (originally in the subendothelial within the lipid atheroma) are exposed. Once exposed, thrombosis occurs and an occlusive clot develops, resulting in a myocardial infarction.<br/>
'''References:''' Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868-74.<br>
First Aid 2015 page 292.
Pseudotumor cerebri is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases. The main symptoms are headache, nausea, and vomiting, as well as pulsatile tinnitus, double vision and other visual symptoms.
Intracranial pressure may be increased due to medications such as high-dose vitamin A derivatives (e.g. isotretinoin), long-term tetracycline antibiotics, lithium, or hormonal contraceptives. Following ingestion, vitamin A, a lipid soluble vitamin, undergoes hepatic metabolism, whereby hepatic parenchymal cells absorb vitamin A in the form of retinyl esters. Parenchymal cells metabolize the retinyl esters, which is subsequently transferred to the stellate cells for either storage with other long-chain fatty acids or mobilization into the plasma (bound to RBP). The advantage of vitamin A storage in the stellate cells is the capacity of the liver to maintain adequate supply of vitamin A by metabolizing stored vitamin A during periods of low dietary intake. In cases of hypervitaminosis, vitamin A saturates in the hepatic stellate cells and leaks from the liver into the bloodstream beyond the blood brain barrier. The mechanism by which vitamin A excess results in pseudotumor cerebri is poorly understood.<br/>
'''Educational Objective:''' Hepatic stellate cells, also known as either perisinusoidal cells or Ito cells (earlier lipocytes or fat-storing cells), are pericytes found in the perisinusoidal space of the liver also known as the space of Disse. Following ingestion, vitamin A, a lipid soluble vitamin, undergoes hepatic metabolism, whereby hepatic parenchymal cells absorb vitamin A in the form of retinyl esters. Parenchymal cells metabolize the retinyl esters, which is subsequently transferred to the stellate cells for either storage with other long-chain fatty acids or mobilization into the plasma (bound to RBP).<br/>
'''References:''' Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006;88(2):191-201.<br>
Morrice Jr, G, Havener WH, Kapetansky F. Vitamin A intoxication as a cause of pseudotumor cerebri. JAMA. 1960;173(16):1802-5.<br>
Toren G, Nilsson A, Norum KR, et al. Characterization of liver stellate cell retinyl ester storage. Biochem J. 1994;300:793-8.<br>
First Aid 2015 page 89, 468.
Mixed connective tissue disease (MCTD) combines features of scleroderma, myositis, systemic lupus erythematosus, and rheumatoid arthritis and is thus considered an overlap syndrome. MCTD commonly manifests with joint pain/swelling, malaise, Raynaud phenomenon, Sjögren's syndrome, muscle inflammation, and sclerodactyly. Distinguishing laboratory characteristics are a positive, speckled anti-nuclear antibody and an anti-U1-RNP antibody.<br/>
'''Educational Objective:''' Anti-U1-RNP antibodies are often elevated in patients with mixed connective tissue disease. Anti-U1-RNP antibody targets snRNP, which is a complex of snRNA (produced by RNAP II) and multiple proteins.<br/>
'''References:''' Ghirardello A, Doria A, Vesco P, et al. Blotting patterns of IgG anti-(U1)RNP antibodies in mixed connective tissue disease. Rheumatol Int. 1996;16(4):145-50.<br>
First Aid 2015 page 213. +