Property:Explanation
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Pelvic inflammatory disease (PID) patients present with leukocytosis, lower abdominal pain and tenderness, fever, vaginal discharge, and cervical motion tenderness. The best way to manage these cases is to exclude the pregnancy, and then proceed with culturing the discharge and DNA prop for Chlamydia and gonorrhea, and prescribe the proper antibiotics. Laparoscopy is the most accurate test, but it is rarely needed. It is used with recurrent or persistent infection despite using the proper antibiotics, or when the diagnosis is not clear.<br/>
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'''References:''' +
Osteomyelitis is an infection of bone or bone marrow, usually caused by pyogenic bacteria or mycobacteria. It can be usefully subclassifed on the basis of the causative organism, the route, duration and anatomic location of the infection. It usually present with fever, chills, erythema, and swelling over the involved bone. The earliest X-ray finding will appear is periosteal elevation<br/>
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Coronary artery disease (CAD) present with chest pain that doesn’t change with body position and respiration. The presentation is very clearly a presentation of ischemic pain, and when the examiners ask about the first step, treatment like aspirin, nitrates, oxygen, and morphine always comes first before the confirmative test, although all are mandatory to be done.<br/>
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Salicylates are agents with analgesic and anti-inflammatory properties found in many OTC drugs and preparations. Since these agents are so ubiquitous, salicylate toxicity is an important cause of mortality. Patients usually present with tachycardia and tachypnea. Arterial blood gases would initially show significant respiratory alkalosis that progresses eventually into a combined disturbance of respiratory alkalosis and metabolic acidosis. Tinnitus is usually a common symptom of salicylate toxicity as well. Almost all patients with significant toxicity have fever on presentation. The mechanism behind the development of fever is the "uncoupling" nature of salicylates that increases the permeability of the inner mitochondrial membrane. This uncouples electron transport from ATP synthesis leading instead to a dissipation of energy as heat. Other examples of uncoupling agents include other salicylates like aspirin as well as thermogenin found in brown adipose tissue of infants, and 2,4-dinitrophenol.<br/>
'''Educational Objective:''' Salicylates like methyl salicylate (oil of wintergreen) are uncoupling agents that increase the permeability of the inner mitochondrial membrane leading to loss of energy as heat and decrease in ATP production.<br/>
'''References:''' Gutknecht J. Salicylates and proton transport through lipid bilayer membranes: a model for salicylate-induced uncoupling and swelling in mitochondria. J Membr Biol. 1990;115(3):253-60. +
Mesothelioma is a malignant tumor of the lung pleura associated with exposure to asbestos. Typically patients present with dyspnea, pleuritic chest pain, and weight loss. Patients can also have significant pleural effusions that are often hemorrhagic. Pathologically the tumor begins as discrete thickened plaques along the pleura that eventually coalesce into a single neoplasm. A characteristic finding in mesothelioma is psammoma bodies. Psammoma bodies are whorl shaped structures composed of calcium that are the result of tumor cell necrosis with associated dystrophic calcification. Psammoma bodies can be seen in other tumors as well including papillary thyroid carcinoma, ovarian serous cystadenocarcinoma, and meningioma. Tumors that cause psammoma bodies are memorized by the mnemonic '''PSaMMoma''': Papillary thyroid cancer - Serous cystadenocarcinoma of the ovaries - Meningioma - Mesothelioma<br/>
'''Educational Objective:''' Psammoma bodies are formed due to tumor cell necrosis and dystrophic calcification.<br/>
'''References:''' Kubota T, Sato K, Yamamoto S, Hirano A. Ultrastructural study of the formation of psammoma bodies in fibroblastic meningioma. J Neurosurg. 1984;60(3):512-7. +
The normal physiological response to high altitude comes secondary to a decrease in the inspired PaO<sub>2</sub>. The PaO<sub>2</sub> drops from approximately 150 mmHg to as low as 40 mmHg at around 2000 to 2400 meters(7000 to 8000 feet). As PaO<sub>2</sub> decreases hyperventilation ensues, leading acutely to respiratory alkalosis. Within a few hours, renal compensation kicks in to adjust the metabolic disturbance. The kidney increases bicarbonate loss to lower the pH. With chronic exposure to high altitude, processes related to chronic hypoxia begin to appear including increased EPO synthesis, polycythemia, and pulmonary vasoconstriction.<br/>
'''Educational Objective:''' With acute exposure to high altitude, initial respiratory alkalosis followed renal compensation via bicarbonate excretion is typical.<br/>
'''References:''' West JB. The physiologic basis of high-altitude diseases. Ann Intern Med. 2004;141(10):789-800. +
The pulmonary vasculature is peculiar in its response to hypoxia. Where hypoxia typically causes vasodialtion to increase tissue perfusion, alveolar hypoxia in the lungs causes local vasoconstriction. This physiologic mechanism is thought to be an adaptive process that decreases perfusion of the hypoventilated areas and shunts blood towards better perfused alveoli. This mechanism is the basis behind several disease processes including RVH in the context of chronic hypoxia where the latter leads to vasoconstriction and pulmonary hypertension.<br/>
'''Educational Objective:''' The pulmonary vasculature reacts to hypoxia by vasoconstriction to shunt blood to better perfused areas on the lung.<br/>
'''References:''' Moudgil R, Michelakis ED, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol. 2005;98(1):390-403. +
Type II pneumocytes are important structural and functional components of the lung parenchyma. Structurally, they are responsible for regenerating type I pneumocytes that create the alveolar membrane after damage. They are also the primary cells responsible for the secretion of the pulmonary surfactant. Surfactant is a functional term used to refer to dipalmitoylphosphatidylcholine (DPPT) a choline-based phospholipid that functions to lower alveolar surface tension preventing alveolar collapse. DPPT has the capability of lowering surface tension to approximately zero. Type II pneumocytes contain numerous cytosolic aggregations of DPPT known histologically as lamellar bodies or granules. These granules are also observed in the outer layers of the skin. They are released by keratinocytes an result in the formation of a lipid-containing outer covering that serves as a water barrier.<br/>
'''Educational Objective:''' Type II pneumocytes are cuboidal cells found interspersed among type I pneumocytes that contain high levels of DPPT (surfactant) a choline-based phospholipid.<br/>
'''References:''' Ryan US, Ryan J, Smith D. Alveolar type II cells: Studies on the mode of release of lamellar bodies. Tissue and Cell. 1975;7(3):587-599. +
Carbon monoxide (CO) is an odorless toxic gas released in the process of incomplete combustion. Hemoglobin binding sites have 250 times better affinity to CO than to oxygen. This would typically cause rapid binding of CO as well as cause conformational changes in the hemoglobin molecule leading to increased affinity to oxygen. While CO occupies oxygen binding sites, it decreases the oxygen saturation of hemoglobin. In addition, as it increases affinity of hemoglobin to oxygen it causes a left shift leading to a decrease in oxygen dissociation at the peripheral tissues. Both of those phenomena combined would lead to the red curve seen in the graph above.<br/>
'''Educational Objective:''' Carbon monoxide poisoning causes 2 distinct effects on the oxygen dissociation curve: a left shift and a decrease in hemoglobin oxygen saturation.<br/>
'''References:''' Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med. 1998;339(22):1603-8. +
Metabolic alkalosis is a classical complication of excessive vomiting. As excess acid is lost, the arterial pH increases gradually. Acutely, before renal compensation begins excreting excess bicarbonate, the increasing pH causes a left shift in the oxygen dissociation curve, increasing oxygen affinity and binding at the level of the lungs but also causing less oxygen dissociation at the level of the peripheral tissues. Other factors causing a left shift include hypothermia, CO poisoning (although with a decrease in Hb saturation - Curve E), and low CO<sub>2</sub> concentrations. A left shift in the oxygen dissociation curve signifies a lower P50, thus hemoglobin would reach 50% saturation at a lower partial pressure oxygen.<br/>
'''Educational Objective:''' Metabolic alkalosis causes a left shift in the oxygen dissociation curve leading to increased affinity of Hb to oxygen.<br/>
'''References:''' Astrup P, Engel K, Severinghaus JW, Munson E. The influence of temperature and pH on the dissociation curve of oxyhemoglobin of human blood. Scand J Clin Lab Invest. 1965;17(6):515-23. +
Rheumatic fever is a complication of group B streptococcal (GBS) pharyngitis that is not properly treated with antibiotics. Patient typically present with migratory polyarthritis and signs of heart failure. Classically patients have a mitral valve prolapse murmur on physcial examination. The disease itself is not caused directly by GBS bacteria, it is the result of antibodies against the M protein of Streptococcus pyogenes species that cross-react with human epitopes. It is a classical example of a Type II hypersensitivity much like pemphigus vulgaris. Pemphigus vulgaris is a disease of the skin characterized by antibodies against desmosomes leading to intraepidermal bullae with flaccid blister formation.<br/>
'''Educational Objective:''' Both rheumatic fever and pemphigus vulgaris are examples of Type II hypersensitivities.<br/>
'''References:''' Le T, Bhushan V. First Aid for the USMLE Step 1 2013. McGraw-Hill Medical; 2013. +
Bronchiolitis obliterans, a manifestation of chronic transplant rejection, is a fibrotic process that leads to progressive narrowing of bronchiolar lumens with eventual airflow obstruction. It is a pattern seen on histologic examination that typically represents transplant rejection with transplant failure within 5 years of initial diagnosis. Bronchiolitis obliterans is a form of chronic rejection similar to other organ transplants; however, it does not involve the blood vessels typically seen in chronic rejection of renal and liver transplants. Approximately half of lung transplant patients have bronchiolitis obliterans by five years following transplantation, and as high as three quarters of the population has some manifestation by ten years. Risk factors include prior episodes of acute rejection, as well as viral, bacterial, and fungal infections of the lung. Classical findings include shortness of breath and an obstructive pattern on pulmonary function testing (PFT). Diagnosis is by physical exam, PFT, and transbronchial lung biopsy for confirmation.<br/>
'''Educational Objective:''' Chronic rejection of lung transplants manifests as fibrosis with narrowing of the bronchilar lumens known as bronchiolitis obliterans.<br/>
'''References:''' Belperio JA, Lake K, Tazelaar H, Keane MP, Strieter RM, Lynch JP. Bronchiolitis obliterans syndrome complicating lung or heart-lung transplantation. Semin Respir Crit Care Med. 2003;24(5):499-530.<br>
First Aid 2015 page 217 +
Lipodystrophy is a condition involving the adipose tissue that leads to loss of fat in certain areas on the body with accumulation of fat in other locations. In the context of HIV, some form of lipodystophy occurs in around 15-20% of patients on protease inhibitor therapy although the exact mechanism is unknown. Patients can have manifestations resembling Cushing syndrome. Patients usually present with fat loss in the face and extremities with central fat accumulation and "buffalo hump"-like fat deposits in the upper back. Protease inhibitor associated lipodystrophy usually does not resolve after the agent is discontinued.<br/>
'''Educational Objective:''' An important side effect of protease inhibitors is lipodystrophy.<br/>
'''References:''' Martínez E, Mocroft A, García-Viejo MA, et al. Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study. The Lancet. 2001;357(9256):592-598.<br>
First Aid 2015 page 194 +
Henoch-Schönlein purpura (HSP) is a systemic disease characterized by vasculitis of the small vessels caused by immune deposits of IgA and C3 in arterioles, venules, and capillaries. Clinically the classic triad of HSP includes a skin rash mostly seen on the lower extremities and classically described as palpable purpura, arthralgias, and abdominal pain sometimes associated with vomiting, diarrhea, melena, or hematochezia. HSP is generally a pediatric disease although it can occur much less commonly in adults. HSP is closely related to IgA nephropathy as both diseases share a similar pathogenesis, with renal insufficiency being an important complication of HSP. In general, most cases are self-limited and only require supportive therapy. The abdominal pain usually subsides within a few days and most patients do not have recurrences.<br/>
'''Educational Objective:''' Henoch-Schönlein purpura (HSP) is a systemic disease characterized by vasculitis of the small vessels caused by immune deposits of IgA and C3 often presenting with a triad of palpable purpura, abdominal pain, and arthralgia.<br/>
'''References:''' Roberts PF, Waller TA, Brinker TM, Riffe IZ, Sayre JW, Bratton RL. Henoch-Schönlein purpura: a review article. South Med J. 2007;100(8):821-4. +
Caplan syndrome also known as rheumatoid pneumoconiosis is a combination of rheumatoid arthritis and pneumoconiosis particularly coal miner's type. Caplan syndrome usually presents with cough and dyspnea related to the lung disease associated with signs and symptoms of rheumatoid arthritis including arthralgias, morning stiffness, swollen MCP and PIP joints and rheumatoid nodules that can often be seen on chest radiography and confused with malignancy or mycobacterial infection. Patients with Caplan syndrome usually have positive rheumatoid factor (antibody against the Fc portion of IgG) although the finding is not specific for the disease. Management is targeted at pain control and immunosuppression.<br/>
'''Educational Objective:''' Caplan syndrome also known as rheumatoid pneumoconiosis is characterized by coal miner's pneumoconiosis with subsequent development of concomitant rheumatoid arthritis.<br/>
'''References:''' Schreiber J, Koschel D, Kekow J, Waldburg N, Goette A, Merget R. Rheumatoid pneumoconiosis (Caplan's syndrome). Eur J Intern Med. 2010;21(3):168-72. +
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood and produce glycogen (liver and muscle) and triglycerides (adipocytes). Insulin binding to its receptor causes downstream activation of 2 processes: The RAS/MAPK pathway and the PI3k pathway. Both glucose absorption and glycogen synthesis are due to the effects of PI3k pathway activation. PI3K leads to PIP3 formation that activates protein kinase B. PKB phosphorylates glycogen synthase kinase and inactivates it leading to increased activity of glycogen synthase. PKB also facilitates GLUT-4 expression leading to increased glucose uptake. The RAS/MAPK pathway is responsible for the effects of insulin on cell growth and DNA synthesis.<br/>
'''Educational Objective:''' Insulin activates the PI3k pathway that leads to increased glucose absorption and glycogen synthesis.<br/>
'''References:''' White MF, Kahn CR. The insulin signaling system. J Biol Chem. 1994;269(1):1-4. +
Ecthyema gangrenosum is a skin manifestation of ''Pseudomonas aeruginosa'' sepsis characterized by a round or oval lesion of varying size, with a necrotic center and a halo of erythema. The necrotic center represents an area of infarction due to blood vessel infection and invasion. Although ecthyema can be seen in patients with other gram negative bacteremias, it is classically associated with Pseudomonas aeruginosa and linked to exotoxin A producing strains. It is a rare finding but occurs more in patients with severe immunosuppression or neutropenia and neonates.<br/>
'''Educational Objective:''' Ecthyema gangrenosum is a skin manifestation of Pseudomonas aeruginosa sepsis characterized by a lesion of varying size, with a nectoric center and a halo of erythema.<br/>
'''References:''' Baro M, Marín MA, Ruiz-contreras J, De miguel SF, Sánchez-díaz I. Pseudomonas aeruginosa sepsis and ecthyma gangrenosum as initial manifestations of primary immunodeficiency. Eur J Pediatr. 2004;163(3):173-4. +
Primary hyperparathyroidism is the most common etiology of elevated serum calcium most often caused by a single functional adenoma excessively secreting parathyroid hormone. Clinically, most patients are asymptomatic with hypercalcemia found incidentally. Other possible presentations include recurrent nephrolithiasis, bone disease, and neuromuscular symptoms. Without proper intervention, frequent nephrolithiasis, decreased bone mineral density, and increased risk of death from cardiovascular causes ensue. Lab findings include hypercalcemia, hypercalciuria, elevated alkaline phosphatase, and elevated PTH. Another finding that can be used in the evaluation is elevated urinary cAMP. Treatment of primary hyperparathyroidism is usually surgical.<br/>
'''Educational Objective:''' Urinary cAMP is elevated in patients with primary hyperparathyroidism.<br/>
'''References:''' Marcocci C, Cetani F. Clinical practice. Primary hyperparathyroidism. N Engl J Med. 2011;365(25):2389-97.<br>
Broadus AE. Nephrogenous Cyclic AMP as a Parathyroid Function Test. Nephron. 1979;23(2-3):136-141. +
The hypothalamus is the main player in thermoregulation in mammals. It is involved in metabolic regulation, shivering, and sympathetic overdrive all important in maintaining a relatively constant body temperature. The most important nucleus involved in thermogenesis and regulation is the dorsomedial hypothalamic nucleus located in the posterior hypothalamus. The posterior hypothalamus acts mostly by provoking heat generation via sympathetic activation. It is important for non-shivering thermogenesis. Its ablation would lead to hypothermia in rats exposed to cold temperatures, a occurrence usually seen in cold-blooded organisms. The ventromedial nucleus, also involved in satiety, is an important player in thermogenesis.<br/>
'''Educational Objective:''' The dorsomedial hypothalamus in an important control center for thermogenesis.<br/>
'''References:''' Amir S. Activation of brown adipose tissue thermogenesis by chemical stimulation of the posterior hypothalamus. Brain Research. 1990;534(1-2):303-308.<br>
Dimicco JA, Zaretsky DV. The dorsomedial hypothalamus: a new player in thermoregulation. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R47-63. +
Parinaud syndrome, characterized by paralyis of conjugate upward gaze, is the most common presentation of pineal gland tumors particularly germinomas seen in approximately half of presenting patients. It is also known as dorsal midbrain syndrome, occuring secondary to compression of the tectum. Other signs of Parinaud syndrome include pseudo-argyll robertson pupils, and excessive eyelid retraction. Germinomas are the most common pineal gland tumors classically presenting with Parinaud syndrome, hydrocephalus, or precocious puberty in young children. Germinomas usually have a good prognosis, and most patients improve with radiation therapy.<br/>
'''Educational Objective:''' Germinomas are the most common form of pineal gland tumors usually presenting with Parinaud syndrome in up to 50% of patients.<br/>
'''References:''' Packer RJ, Cohen BH, Cooney K, Coney K. Intracranial germ cell tumors. Oncologist. 2000;5(4):312-20. +