USMLE STEP 2, Individualized Tutorial Demonstration—Sept. 2012 Session 1

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AUDIO PODCAST Available Contact Dr Cray, USMLE STEP 2, Individualized Tutorial Demonstration—Sept. 2012 Session 1

AUDIO PODCAST Available Contact Dr Cray, USMLE STEP 2, Individualized Tutorial Demonstration—Sept. 2012 Session 1

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  • 1. USMLE Steps 1 and 2 Integration Individualized Tutorial Demonstration Sept. 3, 2012Tutor: Marc Imhotep Cray, M.D Session 1Website: 770-322-1050Resources Used:First Aid USMLE Step 1/ 2012First Aid Q & A for the USMLE Step 1USMLE Step 2 Secrets - Brochert, Aid Q & A for USMLE Step 2 CK
  • 2. “Teacher-Learner Contract Statement”Using the word document provided by …….as a guide, and making anassessment of the Tutoree’s current medical didactic needs, the Tutor(Dr. Cray) has designed this customized study series that integratesmultiple familiar learning tools and includes the following8 Learning/Teaching Objectives (next 2 slides)Session 1 (first 4 hours) is presented hereinMIC/Sept, 02, 2012 2
  • 3. Learning/Teaching Objectives Dimension 11. To engage in a deep-layered horizontally and vertically integrated review of concepts, mechanism and MCQs to build medical fund of knowledge per se, i.e., the factual database2. To interpret graphic and tabular material, to identify gross and microscopic pathologic and normal specimens using acquired medical fund of knowledge,1. To solve problems through application of basic science and clinical medicine principles using both subjected-based and organ-system based approaches2. To study principles of clinical science that are deemed important for the practice of medicine under supervision in postgraduate training dealing with normal growth and development, basic concepts, and general principles.3. To review the germane basic medical science concepts and mechanisms that serve as the foundations of clinical medicine 3
  • 4. Learning/Teaching Objectives Dimension 2To focusing on individual disorders according to 4 Physician Task5. The first set of physician tasks, Promoting Preventive Medicine and Health Maintenance, encompasses the assessment of risk factors, appreciation of epidemiologic data, and the application of primary and secondary preventive measures.6. The second set of tasks, Understanding Mechanisms of Disease, encompasses etiology, pathophysiology, and effects of treatment modalities in the broadest sense.7. The third set of tasks, Establishing a Diagnosis, pertains to interpretation of history and physical findings and the results of laboratory, imaging, and other studies to determine the most likely diagnosis or the most appropriate next step in diagnosis.8. The fourth set of tasks, Applying Principles of Management, concerns the approach to care of patients with chronic and acute conditions in ambulatory and inpatient settings focusing on the same topics covered in the diagnosis sections. 4
  • 5. USMLE STEP 2 TEST QUESTIONS Session 1 4 Hours Reading, USMLE Step 2 Secrets – Brochert Chapter 1 : Acid-Base and Electrolytes and Chapter 21: Laboratory Medicine Chapter 22: Nephrology 5
  • 6. 1.carbonic anhydrase inhibitors Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress the activity of carbonic anhydrase. Their clinical use 1. antiglaucoma agents, 2. diuretics, 3. antiepileptics, 4. in the management of mountain sickness, 5. gastric and duodenal ulcers, 6. neurological disorders, 7. osteoporosis 6
  • 7. Types of Drugs1. Acetazolamide is an inhibitor of carbonic anhydrase. It is used for glaucoma, epilepsy (rarely), idiopathic intracranial hypertension, and altitude sickness. It can act as a mild diuretic by reducing NaCl and bicarbonate reabsorption in the proximal tubule. However, the distal segment partially compensates for the sodium loss, and the bicarbonaturia will produce a metabolic acidosis, further reducing the effect.2. MethazolamideIt has a longer elimination half-life than acetazolamide and is less associated withadverse effects to the kidney3. Dorzolamide is a sulfonamide) and topical carbonic anhydrase II inhibitorindicated for reduction of elevated intraocular pressure in open-angle glaucoma orocular hypertension and who are insufficiently responsive to beta-blockers.MOA open-angle glaucoma- Inhibition of carbonic anhydrase II in the ciliary processesof the eye decreases aqueous humor secretion, by slowing the formation of 7bicarbonate ions with subsequent reduction in sodium and fluid transport.
  • 8. CO2 TransportFirst Aid Step 1 2012, Pg. 590 8
  • 9. First Aid Step 1 2012, Pg. 532 9
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  • 15. 17. A 67-year-old woman with osteoporosis is given a diuretic to treat her hypertension. This particular diuretic has the adverse effect of limiting calcium excretion by the kidney. Referring to the image, where along the nephron does this drug act?First Aid Q & A for the USMLE Step 1 Pg. 351 15
  • 16. First Aid Q & A for the USMLE Step 1 Pg. 35117. The correct answer is E. The only diuretics that specifically limit calcium loss are thethiazides. They act in the early distal tubule, which is marked as region E in the image.Answer A is incorrect. There are no diuretics that act at the glomerulus.Answer B is incorrect. Carbonic anhydrase inhibitors, which act in the proximalconvoluted tubule, do not affect calcium excretion.Answer C is incorrect. Osmotic diuretics act in the loop of Henle (as well as the proximalconvoluted tubule and collecting duct), but they do not affect ion channels.Answer D is incorrect. Loop diuretics, which encourage calcium excretion, act in the thickascending limb.Answer F is incorrect. Potassium-sparing diuretics and ADH antagonists such as lithiumand demeclocycline act along the collecting tubule, although neither class affectscalciumexcretion. 16
  • 17. 2. bicarbonate levels – why would they be low , why would they be high in case scenario5. Monitoring acid-base status is very important in individuals withkidney pathology. Which of the following diuretics causes metabolic alkalosis?(A) Acetazolamide and potassium-sparing diuretics(B) Loop diuretics and acetazolamide(C) Loop diuretics and potassium-sparing diuretics(D) Loop diuretics and thiazides(E) Thiazides and acetazolamide(F) Thiazides and potassium-sparing diureticsFirst Aid Q & A for the USMLE Step 1 Pg. 348 17
  • 18. First Aid Q & A for the USMLE Step 1 Pg. 348The correct answer is D. Thiazides and furosemide lead to metabolic alkalosis.There are two components to the development of metabolic alkalosis: volumedepletion and electrolyte imbalance; specifically hypochloremia and hypokalemia.Volume contraction leads to increased sodium reabsorption and bicarbonateretention. The diuretic-induced hypochloremia and hypokalemia lead topersistence of the alkalosis because the hypokalemia causes hydrogen to beexchanged for sodium rather than potassium at the distal convoluted tubule.First Aid Q & A for the USMLE Step 1 Pg. 348 Pop Quiz 7 . Should you give bicarbonate to a patient with acidosis? USMLE Step 2 Secrets –Pg.35 18
  • 19. Pop Quiz Answer: For purposes of the Step 2 boards, almost never. First try intravenous fluids and correction of the underlying disorder. If all other measures fail and the pH remains less than 7.0, bicarbonate may be given.Answer A is incorrect. Neither potassium-sparing diuretics nor acetazolamide cause metabolicalkalosis. Potassium-sparing diuretics cause metabolic acidosis by inhibiting sodium hydrogenexchange channels, and acetazolamide promotes the loss of bicarbonate in the urine, causing metabolicacidosis.Answer B is incorrect. Acetazolamide inhibits the enzyme carbonic anhydrase, which is important in thereabsorption of sodium, bicarbonate, and chloride at the proximal tubule.Since it promotes the loss of bicarbonate in the urine, it tends to cause metabolic acidosis.Answer C is incorrect. The potassium-sparing diuretics, such as spironolactone, inhibit aldosterone-sensitivesodium channels that excrete hydrogen or potassium in exchange for sodium. Inhibition of these channelsmay lead to hyperkalemia and metabolic acidosis.Answer E is incorrect. Thiazides do cause metabolic alkalosis by causing volume depletion,hypochloremia, and hypokalemia. However, acetazolamide promotes the loss of bicarbonate inthe urine, causing metabolic acidosis.Answer F is incorrect. Thiazides do cause metabolic alkalosis by causing volume depletion, hypochloremia,and hypokalemia. However, potassium-sparing diuretics cause metabolicacidosis by inhibiting sodium-hydrogen exchange channels. 19
  • 20. Pharmacology Summary Side Effects2. What are the side effects of diuretics?Thiazide diuretics cause calcium retention, hyperglycemia, hyperuricemia,hyperlipidemia, hyponatremia, hypokalemic metabolic alkalosis, and hypovolemia;because they are sulfa drugs, watch out for sulfa allergy.Loop diuretics cause hypokalemic metabolic alkalosis, hypovolemia (more potentthan thiazides), ototoxicity, and calcium excretion; with the exception of ethacrynicacid, they also are sulfa drugs.Carbonic anhydrase inhibitors cause metabolic acidosis.Potassium-sparing diuretics (e.g. spironolactone) may cause hyperkalemia. USMLE Step 2 Secrets - Brochert, Adam & Theodore X. OConnell, Pg. 458 20
  • 21. 3. Acute Asthma 3. Pt. with asthma having respiratory attack in ED and patient begins to calm breathing down. What is the next best step….i deducted that the patient was crashing b/c my professor and I went over this in class YEAH! A emergency intubation B b2 agonists C steroids D oxygen5 What should you think if a patient with acute asthma stops hyperventilatingor has a normal carbon dioxide (CO2) level?Beware the asthmatic who is no longer hyperventilating or whose CO2 is normal or rising. Thepatient should be hyperventilating, which causes low CO2. If the patient seems calm or sleepy,do not assume that he or she is “okay.” Such patients probably are crashing; they need animmediate arterial blood gas analysis and possible intubation. Fatigue alone is sufficient reasonto intubate. Remember also that any patient with COPD may normally live with a higher CO2and lower oxygen (O2) level.Treat the patient, not the lab value. If the patient is asymptomatic and talking to you,the lab value should not cause panic. USMLE Step 2 Secrets – Brochert Pg. 494 21
  • 22. 3. Acute Asthma cont. 6. When should you intubate? As a rough rule of thumb, think about intubation in any patient whose CO2 is *greater than 50 mmHg or whose O2 is less than 50 mmHg, especially if the pH in either situation is less than 7.30 while the patient is breathing room air. Usually, unless the patient is crashing rapidly, a trial of oxygen by nasal cannula or face mask is given first. If it does not work or if the patient becomes too tired (use of accessory muscles is a good clue to the work of breathing), intubate. Clinical correlation is always required; patients with chronic lung disease may be asymptomatic at lab value levels that seem to defy reason. Alternatively, lab values may look great, but if the patient is becoming tired from increased work of breathing, intubation may be needed.USMLE Step 2 Secrets – Brochert Pg. 495* (error on CO2, says less, but should be greater) 22
  • 23. 3. Acute Asthma cont. 8. The blood gas of a patient with asthma has changed from alkalotic to normal, and the patient seems to be sleeping. Is the patient ready to go home? For Step 2 purposes, this scenario means that the patient is probably crashing. Remember that pH is initially high in patients with asthma because they are eliminating CO2. If the patient becomes tired and does not breathe appropriately, CO2 will begin to rise and pH will begin to normalize. Eventually the patient becomes acidotic and requires emergency intubation if appropriate measures are not taken. If this scenario is mentioned on boards, the appropriate response is to prepare for possible elective intubation and to continue aggressive medical treatment with beta2 agonists, steroids, and oxygen. Fatigue secondary to work of breathing is an indication for intubation. Asthmatic patients are supposed to be slightly alkalotic during an asthma attack. If they are not, you should wonder why.USMLE Step 2 Secrets – Brochert Pgs. 35-36 23
  • 24. 4. Hyperglycemia-induced hyponatremia 93. Causes of “false” lab disturbances: hemolysis (hyperkalemia), pregnancy (elevated sedimentation rate and alkaline phosphatase), hypoalbuminemia (hypocalcemia), and hyperglycemia (hyponatremia).14. What causes spurious (false) hyponatremia? Hyperglycemia (once glucose is greater than 200 mg/dL, sodium decreases by 1.6 mEq/L for each rise of 100 mg/dL in glucose) Hyperproteinemia HyperlipidemiaIn these instances, the lab value is low, but the total body sodium is normal.Do not give the patient extra salt or saline. Cause a “false” hyponatremia? Hyponatremia may be caused by hyperglycemia, hyperproteinemia, or hyperlipidemia. The hyponatremia resolves with correction of the glucose, lipid, or protein levels. USMLE Step 2 Secrets – Brochert Pgs. 25 and 37 24
  • 25. 4. hyponatremia – why was patient hyponatremic? b/c hyperglycemicHyperglycemia-induced hyponatremia: metabolic considerations in calculation of serumAbstractHyperglycemia is associated with a decrease in serum sodium concentration. Previousmethods of estimating the degree of decrease have not considered the fact that glucose willenter certain cells despite relative insulin deficiency; thus, glucose will not contributedirectly to the osmotic gradient responsible for water shifts into or out of these tissues.The expected decrease in serum sodium concentration is 1.35 meg/l for every 100mg/dlincrease in blood glucose concentration - the metabolic correction factor. Although thenumerical difference between this factor and that calculated by others is small, themetabolic implications could be critical. In the hyperglycemic state the water content oftissues not requiring insulin for glucose transport could increase, and where tissue swellingis physically restricted (for example, in the brain) this expansion could seriously affect organfunction.Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression.Can Med Assoc J. 1975 February 22; 112(4): 452–453.PMCID: PMC1956157J. M. Roscoe, M. L. Halperin, F. S. Rolleston, and M. B. Goldstein(PDF file) of the complete article 25
  • 26. pseudohyponatremiaHyperglycemia in the setting of diabetes (diabetic ketoacidosis or hyperosmolarhyponatremic nonketosis) can lead to hyperosmotic hyponatremia.Mechanism: High plasma glucose levels pull water out of cells, resulting in adilutional hyponatremia. At the same time the increased osmotic pressure leadsto an osmotic diuresis. The resultant hypovolemic, hyperosmolar hyponatremiamust be corrected by volume replacement and insulin.Adjusted plasma sodium levels (2 mEq/L for every 100 mg/dL of glucose >200mg/dL) may actually show hypernatremia in these cases.See: (Problems with the term) 26
  • 27. 5. schizophrenic patient – what specific area of the brain was affectedThe underlying mechanisms of schizophrenia, a mental disorder characterized by adisintegration of the processes of thinking and of emotional responsiveness, are complex.A number of theories attempt to explain the link between altered brain function andschizophreniaMost important is the dopamine hypothesis. This attributes psychosis to the faultydistribution, regulation, and function of dopaminergic neurons.Specifically, atypicallity is observed within the D2 subtype, a common target for allantipsychotic drugs. Along with glutamate, dopamine is involved in the advancement andreinforcement of the abnormal thought patterns in schizophrenia.Similarly, dopamine facilitates abnormal long term potentiation within the striatum, basalganglia, cingulate cortex (specifically the cingulate gyrus), and prefrontal cortex, amongother limbic system structures. 27
  • 28. 5. What Brain Structures Are Involved in Schizophrenia?  Prefrontal Cortex  Amygdala  Grey Matter  White Matter Articles:Schizophrenia Bulletin, "Brain Structure and Function Changes During the Development of Schizophrenia:The Evidence From Studies of Subjects at Increased Genetic Risk," Lawrie et al.The American Journal of Psychiatry, "Connecting Brain Structure and Function in Schizophrenia," JasonTregellas, Ph.D. 28
  • 29. dopamine hypothesis of schizophreniaThe dopamine hypothesis of schizophrenia or the dopamine hypothesis ofpsychosis is a model attributing symptoms of schizophrenia (like psychoses) toa disturbed and hyperactive dopaminergic signal transduction.The model draws evidence from the observation that a large number ofantipsychotics have dopamine-receptor antagonistic effects.The theory, however, does not posit dopamine overabundance as a completeexplanation for schizophrenia.Rather, the overactivation of D2 receptors, specifically, is one effect of theglobal chemical synaptic disregulation observed in this disorder. 29
  • 30. First Aid Q & A for USMLE Step 2 CK, Pg 49725. A 29-year-old man is brought into the emergency department by his sister, whoindicates that the patient has been extremely agitated and has not moved his head fornearly an hour.She notes that he currently lives at home with her, after a month-long stay in a psychiatryfacility for schizophrenia. She provides a list of his medications, which she updated thismorning after his psychiatrist increased the dosage of one of his medications. Which of thefollowing medications is the most appropriate management at this point?(A) Alprazolam(B) Diphenhydramine(C) Haloperidol(D) Muscle relaxants(E) Sertraline 30
  • 31. First Aid Q & A for USMLE Step 2 CK, Pg 49725. The correct answer is B. Contraction of the neck muscles in an unnatural position is known as torticollis;in this case, the patient is experiencing an acute dystonic reaction as an adverse effect of one of hisantipsychotic medications, most likely a high-potency typical antipsychotic such as haloperidol, droperidol,fluphenazine, or thiothixene. Treatment of acute dystonia is with an anticholinergic agents such asbenztropine or with diphenhydramine; the patient will literally “loosen up” within a matter of seconds.Prophylaxis for acute dystonic reactions can be provided with benztropine.Answer A is incorrect. Alprazolam is a shortactingbenzodiazepine that is used to treat anxiety. It has no role in the treatment of acutedystonia.Answer C is incorrect. Haloperidol and other typical antipsychotic medications are responsiblefor causing acute dystonias such as in this patient. Initiating haloperidol would onlyworsen the patient’s torticollis.Answer D is incorrect. Although it would appear that the neck muscles are in spasm,muscle relaxants are not indicated; an acute dystonic reaction warrants administration ofdiphenhydramine.Answer E is incorrect. Sertraline is a selective serotonin reuptake inhibitor used primarily totreat depression and anxiety disorders. It has no role in the treatment of acute dystonia. 31
  • 32. 6. know all about SIADH, and also demeclocyline and its multiple uses.41. Define the syndrome of inappropriate antidiuretic hormone secretion(SIADH). How is it diagnosed?The name says it all: ADH is released inappropriately.SIADH is a consideration in patients with hyponatremia and normal volume status(euvolemic).In SIADH, serum osmolarity is low, but urine osmolarity is high (inappropriate urineconcentration).Look for the values of all electrolytes and lab tests to be low (the classic example isuric acid) because of dilution of the serum with free water secondary toinappropriate ADH. USMLE Step 2 Secrets – Brochert Pgs. 136-137 32
  • 33. SIADH (2)42. What causes SIADH?Central nervous system causes: stroke, hemorrhage, infection, traumaMedications: narcotics, oxytocin (watch for pregnant patients), chlorpropamide,antiepileptic agents.Trauma: pain is a powerful stimulus for ADH. Watch for the postoperativepatient who is receiving fluids (and often narcotics) and has pain to develop SIADH.Lung problems: simple pneumonia or ADH-secreting small cell cancer of thelung. USMLE Step 2 Secrets – Brochert Pgs. 136-137 33
  • 34. SIADH (3)43 How is SIADH treated?Treat with water restriction.Stop intravenous fluids and restrict oral fluid intake.For Step 2 purposes, do not give hypertonic saline unless the patient has activeseizures before your eyes.You may cause brainstem damage or central pontine myelinolysis from too rapidcorrection of sodium level.Demeclocycline is sometimes used to treat SIADH if water restriction fails because itinduces nephrogenic diabetes insipidus, which allows the patient to get rid of freewater. 34
  • 35. SIADH (4)First Aid Step 1 2012, Pg 352 35
  • 36. First Aid Q & A for USMLE Step 2 CK, Pg.31137. A 27-year-old pedestrian is brought to the emergency department by ambulancefollowing an accident in which he was struck by a moving car. Among other injuries he isfound to have a large laceration over the occipital area of his head. He is stabilized, givenadequate lactated Ringer’s solution and blood transfusions for hypovolemia due to acuteblood loss, and taken to the intensive care unit. Two days later he is lethargic and has aserum sodium level of 118 mEq/L. What is this patient’s expected plasma osmolality, urineosmolality, and clinical volume status? 36
  • 37. First Aid Q & A for USMLE Step 2 CK, Pg.31137. The correct answer is A.This description is consistent with a patient who is hyponatremic due to SIADH. ADH acts onthe collecting tubules to increase the retention of free water.SIADH, therefore, is not caused by a lack of sodium, but by excess free water, which explainswhy this patient is hyponatremic in spite of the administration of isotonic sodium-containingfluids. Plasma osmolality is decreased (<280 mOsm/kg) in SIADH due to free water retentionand urine is inappropriately concentrated (>100 mOsm/kg water). Patients appear euvolemicand signs such as ascites, peripheral edema, and heart failure are absent. This is becausemost of the free water concentrates intracellularly, where it impairs cell function. In thebrain, this results in seizures, cerebral edema, and brain stem herniation. Water restriction isthe major modality of therapy for SIADH, but should be used very cautiously in patients withSIADH and SAH since they rely heavily on maintaining blood pressure for continued cerebralperfusion. 37
  • 38. First Aid Q & A for USMLE Step 2 CK, Pg.311Answer B is incorrect. This description is not consistent with SIADH. Patients with SIADHhave decreased plasma osmolality due to free water retention and inappropriatelyconcentrated urine. In spite of the free water retention, most of the free water concentratesintracellularly, and patients therefore do not appear hypervolemic or display signs such asperipheral edema, ascites, and heart failure.Answer C is incorrect. This description may have applied to the patient at the time of hisinitial presentation: his plasma would have been normal (isotonic), his urine would haveconcentrated in response to acute volume loss, and clinically he was severely hypovolemic.However, it is now 2 days later and his initial volume losses have been replaced by crystallinesolutions and blood products.Answer D is incorrect. This description is consistent with diabetes insipidus, not SIADH. Indiabetes insipidus there is a loss of either central production of ADH (or arginine vasopressin)or renal sensitivity to ADH. Consequently, urine cannot be concentrated and is inappropriatelydilute. Plasma may be nearly isotonic to severely hypertonic, depending on the patient’sability to drink large amounts of water. Similarly, patients may appear euvolemic tovery dehydrated. While diabetes insipidus can result from head trauma, this would not account 38for the patient’s low serum sodium level. Instead, he should be hypernatremic.
  • 39. First Aid Q & A for USMLE Step 2 CK, Pg.311Answer E is incorrect. This description could suggest a patient with normal endocrine andrenal function, leading one to suspect a pseudohyponatremia due to hyperglycemia orglycerol / mannitol administration for intracranial hypertension. This patient is not describedas receiving either of these solutions. In addition, his change in mental status is bestexplained by true hyponatremia due to SIADH, not by pseudohyponatremia. 39
  • 40. 7. central pontine myelinosis – b/c of too rapid infusion of saline solution due to a hyponatremic state.3. What may result from rapid correction of hyponatremia?Brainstem damage (central pontine myelinolysis). For this reason you shouldgenerally not give hypertonic saline to correct hyponatremia except in severe orsymptomatic cases, and then it should be given in limited quantities.USMLE Step 2 Secrets - Brochert,, Pg. 37 40
  • 41. Central pontine myelinolysis (2)Central pontine myelinolysis (CPM) isneurological disease caused by severedamage of the myelin sheath of nerve cellsin the brainstem, in the area termed thepons, predominately of iatrogenic etiology.Clinical Presentation: by acute paralysis,dysphagia (difficulty swallowing), anddysarthria (difficulty speaking), and otherneurological symptoms.The term "osmotic demyelinationsyndrome" is similar to "central pontinemyelinolysis", but also includes areasoutside the pons.Learn more: Central pontine myelinolysis, MRI FLAIR 41
  • 42. Central pontine myelinolysis (3)CPM presents most commonly as a complication of treatment of patients withprofound, life-threatening hyponatremiaMechanism/pathophysiologyIt occurs as a consequence of a rapid rise in serum tonicity following treatment inindividuals with chronic, severe hyponatraemia who have made intracellularadaptations to the prevailing hypotonicity.PreventionHyponatremia should be corrected at a rate of no more than 8-10 mmol/L of sodiumper day to prevent central pontine myelinolysis.Learn more: 42
  • 43. 8. acid-base electrolyte ques. 12 in usmle step 2 secrets top 100 Hyponatremia Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal Sodium is the dominant extracellular cation and cannot freely cross the cell membrane. Its homeostasis is vital to the normal physiologic function of cells Normal serum sodium levels are between 135 and 145 mEq/L Hyponatremia is defined as a serum level of less than 135 mEq/L and is considered severe when the serum level is below 125 mEq/L In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodiumOnline Reference: Hyponatremia in Emergency Medicine 43
  • 44. Hyponatremia Hyponatremia is most often a complication of other medical illnesses in which excess water accumulates in the body at a higher rate than can be excreted• Examples congestive heart failure, syndrome of inappropriate antidiuretic hormone(SIADH) Polydipsia Overhydration Lack of sodium is virtually never the cause of hyponatremia, although it can promote hyponatremia indirectly.• Sodium loss can lead to a state of volume depletion, with volume depletion serving as signal for the release of ADH (anti-diuretic hormone).• As a result of ADH-stimulated water retention, blood sodium becomes diluted and hyponatremia results Exercise-associated hyponatremia (EAH), is not uncommonResearchers have found that 13% of the athletes who finished the 2002 BostonMarathon were in a clinically hyponatremic state. (Why?) 44
  • 45. Hyponatremia Signs and symptoms Symptoms of hyponatremia include• nausea and vomiting,• headache, confusion,• lethargy, fatigue,• appetite loss,• restlessness and irritability,• muscle weakness, spasms, or cramps,• seizures, and• decreased consciousness or coma. The presence and severity of symptoms are associated with the level of serum sodium,• lowest levels of serum sodium prominent and serious symptoms However, emerging data suggest that mild hyponatremia (serum sodium levels at 131 mEq/L or above) is associated with numerous complications and undiagnosed symptoms (Schrier, Robert W. "Does asymptomatic hyponatremia exist?" Nature Reviews Nephrology. Vol 6, Apr 2010; p 185.) 45
  • 46. Hyponatremia Causes Hypervolemic hyponatremia - both sodium & water content increase, but the water gain is greater• cirrhosis• congestive heart failure• nephrotic syndrome• massive edema of any cause Euvolemic hyponatremia - total body water increases, but the bodys sodium content stays the same• states of severe pain or nausea• in the setting of trauma or other damage to the brain• SIADH (and its many causes)• Hypothyroidism• Glucocorticoid deficiencyHypovolemic hyponatremia - water & sodium are both lost from body, but the sodium loss isgreater• any cause of hypovolemia such as prolonged vomiting, decreased oral intake, severe diarrhea, diuretic use (due to the diuretic causing a volume depleted state and thence 46 ADH release, and not a direct result of diuretic-induced urine sodium loss)
  • 47. Hyponatremia Diagnosis Examination should include orthostatic vital signs and an accurate assessment of volume status This determination (i.e. hypervolemic, euvolemic, hypovolemic) guides treatment decisions Assessment of medical comorbidity also is essential, with particular attention paid to cardiopulmonary and neurological components of the examination 47
  • 48. Hyponatremia PathophysiologyThe etiology of hyponatremia can be categorized pathophysiologically in three primaryways, based on the patients plasma osmolality1. Hypertonic hyponatremia, caused by resorption of water drawn by osmols such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion)2. Isotonic hyponatremia, more commonly called "pseudohyponatremia," is caused by lab error due to hypertriglyceridemia (most common) or hyperparaproteinemia3. Hypotonic hyponatremia is by far the most common type, and is often used interchangeably with "hyponatremia." Hypotonic hyponatremia is categorized in 3 ways based on the patients blood volume status (Next slide) Each category represents a different underlying reason for the increase in ADH that led to the water retention and thence hyponatremia: 48
  • 49. Hyponatremia Pathophysiology (2) Hypotonic hyponatremia categorized:1. Hypervolemic hyponatremia, wherein there is decreased effective circulating volume even though total body volume is increased (by the presence of edema)• Decreased effective circulating volume stimulates the release of ADH, which in turn leads to water retention• Hypervolemic hyponatremia is most commonly the result of congestive heart failure, liver failure (cirrhosis), or kidney disease (nephrotic syndrome).2. Euvolemic hyponatremia, wherein the increase in ADH is secondary to either physiologic but excessive ADH release (as occurs with nausea or severe pain) or inappropriate and non-physiologic secretion of ADH, i.e. syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).• Often categorized under euvolemic is hyponatremia due to inadequate urine solute as occurs in beer potomania or "tea and toast" hyponatremia, hyponatremia due to hypothyroidism or adrenal insufficiency, and those rare instances of hyponatremia that are truly secondary to excess water intake (i.e., extreme psychogenic polydipsia)3. Hypovolemic hyponatremia, wherein ADH secretion is stimulated by volume depletion49
  • 50. Hyponatremia Pathophysiology (3) The volemic classification fails to include spurious and/or artifactual hyponatremia, which is addressed in the osmolar classification• This includes hyponatremia that occurs in the presence of massive hypertriglyceridemia, severe hyperglycemia, and extreme elevation of immunoglobulin levelsIn chronic hyponatremia, sodium levels drop gradually over several days or weeks andsymptoms and complications are typically moderate Chronic hyponatremia is often called asymptomatic hyponatremia in clinical settings becauseit is thought to have no symptoms; however, emerging data suggests that "asymptomatic"hyponatremia is not actually asymptomatic (See slide 42 reference)In acute hyponatremia sodium levels drop rapidly, resulting in potentially dangerous effects,such as rapid brain swelling, which can result in coma and death 50
  • 51. Hyponatremia Pathophysiology (3) Treatment of hyponatremia will depend on the underlying cause and whether the patients volume status is hypervolemic, euvolemic, or hypovolemic In the setting of hypovolemia, intravenous administration of normal saline may be effective, but caution must be exercised not to raise the serum sodium level too quickly (Why?) Euvolemic hyponatremia is usually managed by fluid restriction and treatment to abolish any stimuli for ADH secretion such as nausea• Likewise, drugs causing SIADH should be discontinued if possible• Patients with euvolemic hyponatremia that persists despite those measures may be candidates for a so-called vaptan drug Hypervolemic hyponatremia should be treated by treating the underlying cause (e.g. heart failure, cirrhosis)• In practice, it may not be possible to do so, in which case the treatment of the hyponatremia becomes the same as that for euvolemic hyponatremia (i.e. fluid restriction and/or use of a vaptan drug) (See• Learn more: 51
  • 52. Hyponatremia Review USMLE Step 2 Secrets - Brochert,, hyponatremia search and readFirst Aid Q & A for USMLE Step 2 CK, Pg. 46214. A 62-year-old police officer is brought to the emergency department after having a seizurethat began spontaneously while he was sitting at his desk. He has no history of seizures or neurologic disorders. Histemperature is 37.3 °C (99.2°F), blood pressure is 110/90 mm Hg, andheart rate is 100/min. He localizes pain on deep palpation of the nail beds and sternal rub but isstill in a state of altered consciousness.Laboratory tests show:Na+: 120 mEq/LK+: 4.5 mEq/LCl−: 94 mEq/LCO2: 24 mmol/LBUN: 20 mg/dLCreatine: 1.0 mg/dLGlucose: 88 mg/dLA urine specimen obtained by Foley catheter shows a urine osmolality of 300 mOsm/kg andurine sodium level of 40 mEq/L. After treatment of the acute hyponatremia with slow administration of hypertonicsaline, an extensive work-up reveals a neoplasm. Which of the following is the most likely neoplasm based onthe patient’s hyponatremia?(A) Insulinoma(B) Multiple myeloma(C) Small cell lung cancer(D) Testicular embryonal tumor(E) Thymic carcinoid 52
  • 53. First Aid Q & A for USMLE Step 2 CK, Pg. 46214. The correct answer is C. Syndrome of inappropriate ADH secretion (SIADH) occurs in about50% of patients with small cell lung cancer. This inappropriate production of vasopressin doesnot always cause the overt symptoms of hyponatremia that this scenario depicts. The patientmay compensate for the hyponatremia by decreasing water intake, and thus increasingproduction of atrial natriuretic peptide. Tumors that secrete ADH include those withneuroendocrine features, such as carcinoids, non-small cell lung cancer, central nervoussystem neoplasms, and cancers of the head and neck and genitourinary and gastrointestinaltracts.Answer A is incorrect. Insulinomas need to be considered when working up hypoglycemia.The hypoglycemia often occurs during fasting. The patient’s normal glucose level makes thisunlikely. Insulinomas are unrelated to hyponatremia.Answer B is incorrect. Multiple myeloma is an aberrant proliferation of plasma cells in thebone marrow, resulting in the clonal production of a monoclonal immunoglobulin. Invasionof the bone can lead to osteolytic lesions, osteopenia, and pathologic fractures. Multiplemyeloma is frequently accompanied with anemia, hypercalcemia, and renal insufficiency.This patient does not have any of these findings. Furthermore, multiple myeloma is notassociated with SIADH or hyponatremia. 53
  • 54. First Aid Q & A for USMLE Step 2 CK, Pg. 462Answer D is incorrect. Testicular embryonal tumors can cause a paraneoplastic syndrome.However, they do not cause SIADH. These tumors can be a source of intact human chorionicgonadotropin, which can lead to elevated steroidogenesis and aromatase activity. Elevatedhuman chorionic gonadotropin levels can lead to gynecomastia in men, while women areusually asymptomatic.Answer E is incorrect. Thymic carcinoma is not frequently associated with SIADH butis the second most common cause of ectopic ACTH production. Fifteen percent of casesof ectopic ACTH production are attributed to thymic carcinoma, while more than 50% ofcases are attributed to small cell lung cancer. End of Session 1 54