Jipmer Previous Exam Questions

Explanation
There are clinical and pathologic similarities between HUS and thrombotic thrombocytopenic purpura (TTP). Both conditions manifest microangiopathy with thromboses. Thrombotic microangiopathies are characterized by the involvement of widespread occlusive microvascular thromboses resulting in thrombocytopenia, microangiopathic hemolytic anemia, and variable signs and symptoms of end-organ ischemia.

The arteriolar and capillary microthrombotic process found in most cases of HUS is the result of the activity of specific toxins with ensuing injury to endothelial cells. On the other hand, most cases of TTP are the result of abnormalities of platelet function. Microangiopathic anemia is not associated with Coombs positivity in either condition.

Two predominant types of HUS are identified: one type involves diarrhea (D+) and the other, D- or atypical, does not. D+ HUS is the classic form, accounting for 95% of cases of hemolytic uremic syndrome in children. This form of hemolytic uremic syndrome occurs predominantly in children and is preceded by a prodrome of diarrhea, most commonly caused by an infection by shiga-toxin producing Escherichia coli. Specifically, E coli serotype O157:H7 has been associated with more than 80% of infections leading to hemolytic uremic syndrome. The shiga-like toxin affects endothelial cells and initiates intravascular thrombogenesis. After entering the circulation via the gastrointestinal mucosa, the toxin preferentially localizes to the kidneys, inhibiting protein synthesis and eventually leading to cell necrosis or apoptosis. Endothelial cell damage subsequently potentiates renal microvascular thrombosis by promoting activation of the blood coagulation cascade. Platelet aggregation results in a consumptive thrombocytopenia. Microangiopathic hemolytic anemia results from mechanical damage to red blood cells circulating through partially occluded microcirculation.

In contrast to hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP) presents with the classic pentad of microangiopathic hemolytic anemia, thrombocytopenia, prominent neurologic symptoms, fever and a milder form of renal failure. The pathophysiology of thrombotic thrombocytopenic purpura is different. As opposed to endothelial cell injury in HUS, thrombotic thrombocytopenic purpura is caused by a deficiency in the metalloprotease ADAMTS13, which is involved in the regulation of von Willebrand factor. A lack of this protein results in spontaneous platelet aggregation and the widespread deposition of platelet-rich thrombi in the microvasculature of various organs, most notably the heart, brain, and kidneys.

HUS is predominantly a disease of children younger than 5 years. TTP is predominantly a disease of adults. Renal manifestations are more prominent than neurologic ones in HUS, whereas neurologic findings are more prominent than renal findings in TTP. Fever precedes the onset of TTP more commonly than it precedes HUS. Dysentery is an important hallmark of HUS.

Platelet counts tend to be somewhat higher in HUS than in TTP because they are not consumed quickly by clot formation. However, in some cases of HUS, thrombocytopenia may be severe.

Chapter 70. Thrombotic Thrombocytopenic Purpura, Hemolytic Uremia Syndromes, and the Approach to Thrombotic Microangiopathies
o Principles of Critical Care, 3e

Chapter 286. Vascular Injury to the Kidney > Hemolytic-Uremic Syndrome (HUS)/Thrombotic Thrombocytopenic Purpura (TTP)
o Harrison's Online

Chapter 34. Thrombotic Microangiopathies > Symptoms and Signs
o CURRENT Diagnosis & Treatment: Nephrology & Hypertension

Explanation
Transfusion-transmitted viral infections are increasingly rare due to improved screening and testing. The prevalence for cytomegalovirus antibodies in the general population is between 50% to 80%; therefore, a transfusable unit is not tested routinely for cytomegalovirus unless the recipient is seronegative and either pregnant, a potential or present transplant candidate, immunocompromised, or a premature infant. The organism's transmission is prevented by transfusing leukocyte-depleted blood products, which is consistent with the fact that CMV is a leukocyte-associated pathogen.

Blood Disorders > Infectious Diseases Transmitted Through Transfusion
o Current Medical Diagnosis & Treatment 2015

Chapter 233. Transfusion Therapy > Infectious Complications of Blood Transfusion
o Tintinalli's Emergency Medicine

Chapter 113. Transfusion Biology and Therapy > Adverse Reactions to Blood Transfusion
o Harrison's Online

Explanation
Crohn disease
Antibiotics

Both ciprofloxacin (500 mg twice daily) and metronidazole (1–1.5 g/day) are widely used in the treatment of mild to moderate Crohn disease. Uncontrolled trials have suggested a clinical benefit for these two antibiotics in colonic and perianal Crohn disease, but convincing randomized placebo-controlled evidence is lacking.
Corticosteroids

Oral and intravenous corticosteroids are effective in inducing clinical remission in Crohn disease. Oral prednisone (40–60 mg/day) is a common option for patients with moderate disease. For patients with severe disease or in whom enteric absorption is a concern, intravenous methylprednisolone (40–60 mg/day) or hydrocortisone (200–300 mg/day) is an option. Although useful in achieving remission, steroids are not effective in maintaining it. Therefore, once a satisfactory clinical response has been achieved (usually within 2 weeks), steroids should be tapered gradually.
5-Aminosalicylates

There is a modest benefit of sulfasalazine for achieving remission in patients with colonic Crohn disease. Other 5-ASA drugs that lack the sulfa moiety of sulfasalazine have yielded more equivocal results, with some studies suggesting a modest clinical benefit. Neither sulfasalazine nor other 5-ASA agents have been shown to be effective in maintaining clinical remission in Crohn disease. Certain mesalamine preparations allow release of the drug in the small bowel, theoretically allowing therapy to be directed there rather than the colon. Unfortunately, evidence that such treatment alters disease course is lacking. Despite the limited evidence supporting their use, the favorable safety profile of 5-ASA medications has made them a popular choice for the treatment of patients with mild to moderate disease.

Cholestyramine

Patients with terminal ileal disease or previous terminal ileal resection may not absorb bile acids normally, and this abnormality can lead to secretory diarrhea in the colon. These patients may benefit from bile acid sequestrants (eg, cholestyramine or colestipol). Those who have extensive ileal disease or have undergone resection of more than 100 cm of the ileum have defective bile salt absorption and develop steatorrhea; they benefit from a low-fat diet and medium-chain triglyceride preparations. Bile sequestrants exacerbate this type of diarrhea.

Chapter 3. Inflammatory Bowel Disease: Medical Considerations
o CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 2e

http://emedicine.medscape.com/article/172940-treatment#showall

Chapter 295. Inflammatory Bowel Disease
o Harrison's Online

Explanation
Management of COPD

Smoking cessation continues to be the most important therapeutic intervention for COPD. Currently, no treatments aside from lung transplantation have been shown to significantly improve lung function or decrease mortality.

Approaches to management by stage include the following:
 Stage I (mild obstruction): Short-acting bronchodilator as needed
 Stage II (moderate obstruction): Short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation
 Stage III (severe obstruction): Short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation; inhaled glucocorticoids if repeated exacerbations
 Stage IV (very severe obstruction or moderate obstruction with evidence of chronic respiratory failure): Short-acting bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation; inhaled glucocorticoids if repeated exacerbation; long-term oxygen therapy (if criteria met); consider surgical options such as lung volume reduction surgery (LVRS) and lung transplantation.

Bronchodilators (beta2 agonists and/or anticholinergics) are the backbone of any COPD treatment regimen. These drugs provide symptomatic relief but do not alter disease progression or decrease mortality.

Theophylline is a nonspecific phosphodiesterase inhibitor and is now limited to use as an adjunctive agent.
Oxygen administration reduces mortality rates in patients with advanced COPD because of the favorable effects on pulmonary hemodynamics. Long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD.

Chapter 260. Chronic Obstructive Pulmonary Disease
o Harrison's Online

Chapter 7. Chronic Obstructive Pulmonary Disease
o CURRENT Diagnosis & Treatment in Pulmonary Medicine

Explanation
Obstructive sleep apnea (OSA)

OSA is a sleep disorder that involves cessation or significant decrease in airflow in the presence of breathing effort. It is the most common type of sleep-disordered breathing and is characterized by recurrent episodes of upper airway collapse during sleep. These episodes are associated with recurrent oxyhemoglobin desaturations and arousals from sleep.

OSA is defined as the coexistence of unexplained excessive daytime sleepiness with at least five obstructed breathing events (apnea or hypopnea) per hour of sleep. Apneas are defined in adults as breathing pauses lasting ≥10 s and hypopneas as events ≥10 s in which there is continued breathing but ventilation is reduced by at least 50% from the previous baseline during sleep.
Polysomnography

A PSG is necessary to accurately diagnose OSA and to assess treatment benefit. Obstructive apnea is the cessation of airflow for at least 10 seconds with persistent respiratory effort. Central apnea is the cessation of airflow for at least 10 seconds with no respiratory effort.

The apnea-hypopnea index (AHI) is derived from the total number of apneas and hypopneas divided by the total sleep time. Recommendations for cutoff levels on AHI include 5-15 episodes per hour for mild, 15-30 episodes per hour for moderate, and more than 30 episodes per hour for severe.

Weight loss, avoidance of alcohol for 4-6 hours prior to bedtime, and sleeping on one’s side rather than on the stomach or back may help.

People with moderate-to-severe apnea should be treated with nasal continuous positive airway pressure (CPAP). Nasal CPAP therapy is the most effective treatment for OSA. All patients with an apnea-hypopnea index (AHI) greater than 15 are considered eligible for CPAP. For patients with an AHI of 5-14.9, CPAP is indicated only if the patient has one of the following: excessive daytime sleepiness, hypertension, or cardiovascular disease.

Surgery is indicated only if noninvasive types of therapy have not worked or are rejected by the patient. Surgical management of snoring and OSA is indicated when a surgically correctable abnormality is believed to be the source of the problem and the patient has tried continuous positive airway pressure (CPAP) without success. Uvulopalatopharyngoplasty (UPPP) is indicated for retropalatal obstruction. Tracheostomy is the only operation shown to be nearly 100% effective as a sole procedure for OSA.
Mandibular Repositioning Splint (MRS)

Also called oral devices, MRSs work by holding the lower jaw and the tongue forward, thereby widening the pharyngeal airway. This is not as effective as CPAP.


Chapter 265. Sleep Apnea > Obstructive Sleep Apnea
o Harrison's Online

Chapter 19. Sleep and Its Abnormalities > Obstructive Sleep Apnea
o Adams & Victor's Principles of Neurology, 10e

Chapter 26. Chronic Ventilatory Failure > Hypoventilation Disorders or Obstructive Sleep Apnea
o CURRENT Diagnosis & Treatment in Pulmonary Medicine


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