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

1. USMLE Steps 1 and 2 Integration
Individualized Tutorial Demonstration
Sept. 3, 2012
Tutor: Marc Imhotep Cray, M.D
Session 1
Website:
http://www.imhotepvirtualmedsch.com/
E-Mail:
drcray@imhotepvirtualmedsch.com
Ph.: 770-322-1050
Resources Used:
First Aid USMLE Step 1/ 2012
First Aid Q & A for the USMLE Step 1
USMLE Step 2 Secrets - Brochert, et.al.
First Aid Q & A for USMLE Step 2 CK

2. “Teacher-Learner Contract Statement”
Using the word document provided by …….as a guide, and making an
assessment of the Tutoree’s current medical didactic needs, the Tutor
(Dr. Cray) has designed this customized study series that integrates
multiple familiar learning tools and includes the following
8 Learning/Teaching Objectives (next 2 slides)
Session 1 (first 4 hours) is presented herein
MIC/Sept, 02, 2012
2

3. Learning/Teaching Objectives
Dimension 1
1. 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 database
2. 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 approaches
2. 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 2
To focusing on individual disorders according to 4 Physician Task
5. 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 et.al.
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
http://www.drugs.com/drug-class/carbonic-anhydrase-inhibitors.html
6

7. Types of Drugs
1. 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. Methazolamide
It has a longer elimination half-life than acetazolamide and is less associated with
adverse effects to the kidney
3. Dorzolamide is a sulfonamide) and topical carbonic anhydrase II inhibitor
indicated for reduction of elevated intraocular pressure in open-angle glaucoma or
ocular hypertension and who are insufficiently responsive to beta-blockers.
MOA open-angle glaucoma- Inhibition of carbonic anhydrase II in the ciliary processes
of the eye decreases aqueous humor secretion, by slowing the formation of
7
bicarbonate ions with subsequent reduction in sodium and fluid transport.

8. CO2 Transport
First Aid Step 1 2012, Pg. 590
8

9. First Aid Step 1 2012, Pg. 532
9

10. 10

11. 11

12. 12

13. 13

14. 14

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. 351
17. The correct answer is E. The only diuretics that specifically limit calcium loss are the
thiazides. 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 proximal
convoluted tubule, do not affect calcium excretion.
Answer C is incorrect. Osmotic diuretics act in the loop of Henle (as well as the proximal
convoluted tubule and collecting duct), but they do not affect ion channels.
Answer D is incorrect. Loop diuretics, which encourage calcium excretion, act in the thick
ascending limb.
Answer F is incorrect. Potassium-sparing diuretics and ADH antagonists such as lithium
and demeclocycline act along the collecting tubule, although neither class affects
calcium
excretion.
16

17. 2. bicarbonate levels – why would they be low ,
why would they be high in case scenario
5. Monitoring acid-base status is very important in individuals with
kidney 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 diuretics
First Aid Q & A for the USMLE Step 1 Pg. 348
17

18. First Aid Q & A for the USMLE Step 1 Pg. 348
The correct answer is D. Thiazides and furosemide lead to metabolic alkalosis.
There are two components to the development of metabolic alkalosis: volume
depletion and electrolyte imbalance; specifically hypochloremia and hypokalemia.
Volume contraction leads to increased sodium reabsorption and bicarbonate
retention. The diuretic-induced hypochloremia and hypokalemia lead to
persistence of the alkalosis because the hypokalemia causes hydrogen to be
exchanged 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 metabolic
alkalosis. Potassium-sparing diuretics cause metabolic acidosis by inhibiting sodium hydrogen
exchange channels, and acetazolamide promotes the loss of bicarbonate in the urine, causing metabolic
acidosis.
Answer B is incorrect. Acetazolamide inhibits the enzyme carbonic anhydrase, which is important in the
reabsorption 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-sensitive
sodium channels that excrete hydrogen or potassium in exchange for sodium. Inhibition of these channels
may 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 in
the 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 metabolic
acidosis by inhibiting sodium-hydrogen exchange channels.
19

20. Pharmacology Summary
Side Effects
2. 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 potent
than thiazides), ototoxicity, and calcium excretion; with the exception of ethacrynic
acid, 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. O'Connell, 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 oxygen
5 What should you think if a patient with acute asthma stops hyperventilating
or has a normal carbon dioxide (CO2) level?
Beware the asthmatic who is no longer hyperventilating or whose CO2 is normal or rising. The
patient 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 an
immediate arterial blood gas analysis and possible intubation. Fatigue alone is sufficient reason
to intubate. Remember also that any patient with COPD may normally live with a higher CO2
and 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 et.al. 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 et.al. 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 et.al. 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
 Hyperlipidemia
In 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 et.al. Pgs. 25 and 37 24

25. 4. hyponatremia – why was patient
hyponatremic? b/c hyperglycemic
Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum
Abstract
Hyperglycemia is associated with a decrease in serum sodium concentration. Previous
methods of estimating the degree of decrease have not considered the fact that glucose will
enter certain cells despite relative insulin deficiency; thus, glucose will not contribute
directly 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/dl
increase in blood glucose concentration - the metabolic correction factor. Although the
numerical difference between this factor and that calculated by others is small, the
metabolic implications could be critical. In the hyperglycemic state the water content of
tissues not requiring insulin for glucose transport could increase, and where tissue swelling
is physically restricted (for example, in the brain) this expansion could seriously affect organ
function.
Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression.
Can Med Assoc J. 1975 February 22; 112(4): 452–453.
PMCID: PMC1956157
J. M. Roscoe, M. L. Halperin, F. S. Rolleston, and M. B. Goldstein
(PDF file) of the complete article
25

26. pseudohyponatremia
Hyperglycemia in the setting of diabetes (diabetic ketoacidosis or hyperosmolar
hyponatremic nonketosis) can lead to hyperosmotic hyponatremia.
Mechanism: High plasma glucose levels pull water out of cells, resulting in a
dilutional hyponatremia. At the same time the increased osmotic pressure leads
to an osmotic diuresis. The resultant hypovolemic, hyperosmolar hyponatremia
must be corrected by volume replacement and insulin.
Adjusted plasma sodium levels (2 mEq/L for every 100 mg/dL of glucose >200
mg/dL) may actually show hypernatremia in these cases.
See: (Problems with the term)
http://www.aacc.org/members/nacb/NACBBlog/List
s/Posts/Post.aspx?ID=9
26

27. 5. schizophrenic patient – what specific
area of the brain was affected
The underlying mechanisms of schizophrenia, a mental disorder characterized by a
disintegration of the processes of thinking and of emotional responsiveness, are complex.
A number of theories attempt to explain the link between altered brain function and
schizophrenia
Most important is the dopamine hypothesis. This attributes psychosis to the faulty
distribution, regulation, and function of dopaminergic neurons.
Specifically, atypicallity is observed within the D2 subtype, a common target for all
antipsychotic drugs. Along with glutamate, dopamine is involved in the advancement and
reinforcement of the abnormal thought patterns in schizophrenia.
Similarly, dopamine facilitates abnormal long term potentiation within the striatum, basal
ganglia, cingulate cortex (specifically the cingulate gyrus), and prefrontal cortex, among
other limbic system structures.
27

28. 5. What Brain Structures Are Involved in Schizophrenia?
 Prefrontal Cortex
 Amygdala
 Grey Matter
 White Matter
http://www.livestrong.com/article/41048-brain-structures-involved-schizophrenia/
Journal 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," Jason
Tregellas, Ph.D.
28

29. dopamine hypothesis of schizophrenia
The dopamine hypothesis of schizophrenia or the dopamine hypothesis of
psychosis is a model attributing symptoms of schizophrenia (like psychoses) to
a disturbed and hyperactive dopaminergic signal transduction.
The model draws evidence from the observation that a large number of
antipsychotics have dopamine-receptor antagonistic effects.
The theory, however, does not posit dopamine overabundance as a complete
explanation for schizophrenia.
Rather, the overactivation of D2 receptors, specifically, is one effect of the
global chemical synaptic disregulation observed in this disorder.
29

30. First Aid Q & A for USMLE Step 2 CK, Pg 497
25. A 29-year-old man is brought into the emergency department by his sister, who
indicates that the patient has been extremely agitated and has not moved his head for
nearly an hour.
She notes that he currently lives at home with her, after a month-long stay in a psychiatry
facility for schizophrenia. She provides a list of his medications, which she updated this
morning after his psychiatrist increased the dosage of one of his medications. Which of the
following 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 497
25. 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 his
antipsychotic 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 as
benztropine 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 shortacting
benzodiazepine that is used to treat anxiety. It has no role in the treatment of acute
dystonia.
Answer C is incorrect. Haloperidol and other typical antipsychotic medications are responsible
for causing acute dystonias such as in this patient. Initiating haloperidol would only
worsen 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 of
diphenhydramine.
Answer E is incorrect. Sertraline is a selective serotonin reuptake inhibitor used primarily to
treat 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 urine
concentration).
Look for the values of all electrolytes and lab tests to be low (the classic example is
uric acid) because of dilution of the serum with free water secondary to
inappropriate ADH.
USMLE Step 2 Secrets – Brochert et.al. Pgs. 136-137
32

33. SIADH (2)
42. What causes SIADH?
Central nervous system causes: stroke, hemorrhage, infection, trauma
Medications: narcotics, oxytocin (watch for pregnant patients), chlorpropamide,
antiepileptic agents.
Trauma: pain is a powerful stimulus for ADH. Watch for the postoperative
patient who is receiving fluids (and often narcotics) and has pain to develop SIADH.
Lung problems: simple pneumonia or ADH-secreting small cell cancer of the
lung.
USMLE Step 2 Secrets – Brochert et.al. 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 active
seizures before your eyes.
You may cause brainstem damage or central pontine myelinolysis from too rapid
correction of sodium level.
Demeclocycline is sometimes used to treat SIADH if water restriction fails because it
induces nephrogenic diabetes insipidus, which allows the patient to get rid of free
water.
34

35. SIADH (4)
First Aid Step 1 2012, Pg 352
35

36. First Aid Q & A for USMLE Step 2 CK, Pg.311
37. A 27-year-old pedestrian is brought to the emergency department by ambulance
following an accident in which he was struck by a moving car. Among other injuries he is
found to have a large laceration over the occipital area of his head. He is stabilized, given
adequate lactated Ringer’s solution and blood transfusions for hypovolemia due to acute
blood loss, and taken to the intensive care unit. Two days later he is lethargic and has a
serum sodium level of 118 mEq/L. What is this patient’s expected plasma osmolality, urine
osmolality, and clinical volume status?
36

37. First Aid Q & A for USMLE Step 2 CK, Pg.311
37. The correct answer is A.
This description is consistent with a patient who is hyponatremic due to SIADH. ADH acts on
the 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 explains
why this patient is hyponatremic in spite of the administration of isotonic sodium-containing
fluids. Plasma osmolality is decreased (<280 mOsm/kg) in SIADH due to free water retention
and urine is inappropriately concentrated (>100 mOsm/kg water). Patients appear euvolemic
and signs such as ascites, peripheral edema, and heart failure are absent. This is because
most of the free water concentrates intracellularly, where it impairs cell function. In the
brain, this results in seizures, cerebral edema, and brain stem herniation. Water restriction is
the major modality of therapy for SIADH, but should be used very cautiously in patients with
SIADH and SAH since they rely heavily on maintaining blood pressure for continued cerebral
perfusion.
37

38. First Aid Q & A for USMLE Step 2 CK, Pg.311
Answer B is incorrect. This description is not consistent with SIADH. Patients with SIADH
have decreased plasma osmolality due to free water retention and inappropriately
concentrated urine. In spite of the free water retention, most of the free water concentrates
intracellularly, and patients therefore do not appear hypervolemic or display signs such as
peripheral edema, ascites, and heart failure.
Answer C is incorrect. This description may have applied to the patient at the time of his
initial presentation: his plasma would have been normal (isotonic), his urine would have
concentrated 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 crystalline
solutions and blood products.
Answer D is incorrect. This description is consistent with diabetes insipidus, not SIADH. In
diabetes 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 inappropriately
dilute. Plasma may be nearly isotonic to severely hypertonic, depending on the patient’s
ability to drink large amounts of water. Similarly, patients may appear euvolemic to
very dehydrated. While diabetes insipidus can result from head trauma, this would not account
38
for the patient’s low serum sodium level. Instead, he should be hypernatremic.

39. First Aid Q & A for USMLE Step 2 CK, Pg.311
Answer E is incorrect. This description could suggest a patient with normal endocrine and
renal function, leading one to suspect a pseudohyponatremia due to hyperglycemia or
glycerol / mannitol administration for intracranial hypertension. This patient is not described
as receiving either of these solutions. In addition, his change in mental status is best
explained 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 should
generally not give hypertonic saline to correct hyponatremia except in severe or
symptomatic cases, and then it should be given in limited quantities.
USMLE Step 2 Secrets - Brochert, et.al, Pg. 37
40

41. Central pontine myelinolysis (2)
Central pontine myelinolysis (CPM) is
neurological disease caused by severe
damage of the myelin sheath of nerve cells
in the brainstem, in the area termed the
pons, predominately of iatrogenic etiology.
Clinical Presentation: by acute paralysis,
dysphagia (difficulty swallowing), and
dysarthria (difficulty speaking), and other
neurological symptoms.
The term "osmotic demyelination
syndrome" is similar to "central pontine
myelinolysis", but also includes areas
outside the pons.
Learn more: Central pontine myelinolysis,
http://en.wikipedia.org/wiki/Central_pontine_myelinolysis MRI FLAIR
41

42. Central pontine myelinolysis (3)
CPM presents most commonly as a complication of treatment of patients with
profound, life-threatening hyponatremia
Mechanism/pathophysiology
It occurs as a consequence of a rapid rise in serum tonicity following treatment in
individuals with chronic, severe hyponatraemia who have made intracellular
adaptations to the prevailing hypotonicity.
Prevention
Hyponatremia should be corrected at a rate of no more than 8-10 mmol/L of sodium
per day to prevent central pontine myelinolysis.
Learn more: http://en.wikipedia.org/wiki/Central_pontine_myelinolysis
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 sodium
Online Reference: Hyponatremia in Emergency Medicine
http://emedicine.medscape.com/article/767624-overview#showall 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 uncommon
Researchers have found that 13% of the athletes who finished the 2002 Boston
Marathon 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 body's 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 deficiency
Hypovolemic hyponatremia - water & sodium are both lost from body, but the sodium loss is
greater
• 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
Pathophysiology
The etiology of hyponatremia can be categorized pathophysiologically in three primary
ways, based on the patient's plasma osmolality
1. 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 hyperparaproteinemia
3. 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 patient's 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:
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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 levels
In chronic hyponatremia, sodium levels drop gradually over several days or weeks and
symptoms and complications are typically moderate
Chronic hyponatremia is often called asymptomatic hyponatremia in clinical settings because
it 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
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51. Hyponatremia
Pathophysiology (3)
 Treatment of hyponatremia will depend on the underlying cause and whether the patient's
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 http://en.wikipedia.org/wiki/Conivaptan)
• Learn more: http://en.wikipedia.org/wiki/Hyponatremia#Treatment
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52. Hyponatremia Review
USMLE Step 2 Secrets - Brochert, et.al., hyponatremia search and read
First Aid Q & A for USMLE Step 2 CK, Pg. 462
14. A 62-year-old police officer is brought to the emergency department after having a seizure
that began spontaneously while he was sitting at his desk. He has no history of seizures or neurologic disorders. His
temperature is 37.3 °C (99.2°F), blood pressure is 110/90 mm Hg, and
heart rate is 100/min. He localizes pain on deep palpation of the nail beds and sternal rub but is
still in a state of altered consciousness.
Laboratory tests show:
Na+: 120 mEq/L
K+: 4.5 mEq/L
Cl−: 94 mEq/L
CO2: 24 mmol/L
BUN: 20 mg/dL
Creatine: 1.0 mg/dL
Glucose: 88 mg/dL
A urine specimen obtained by Foley catheter shows a urine osmolality of 300 mOsm/kg and
urine sodium level of 40 mEq/L. After treatment of the acute hyponatremia with slow administration of hypertonic
saline, an extensive work-up reveals a neoplasm. Which of the following is the most likely neoplasm based on
the patient’s hyponatremia?
(A) Insulinoma
(B) Multiple myeloma
(C) Small cell lung cancer
(D) Testicular embryonal tumor
(E) Thymic carcinoid
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53. First Aid Q & A for USMLE Step 2 CK, Pg. 462
14. The correct answer is C. Syndrome of inappropriate ADH secretion (SIADH) occurs in about
50% of patients with small cell lung cancer. This inappropriate production of vasopressin does
not always cause the overt symptoms of hyponatremia that this scenario depicts. The patient
may compensate for the hyponatremia by decreasing water intake, and thus increasing
production of atrial natriuretic peptide. Tumors that secrete ADH include those with
neuroendocrine features, such as carcinoids, non-small cell lung cancer, central nervous
system neoplasms, and cancers of the head and neck and genitourinary and gastrointestinal
tracts.
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 this
unlikely. Insulinomas are unrelated to hyponatremia.
Answer B is incorrect. Multiple myeloma is an aberrant proliferation of plasma cells in the
bone marrow, resulting in the clonal production of a monoclonal immunoglobulin. Invasion
of the bone can lead to osteolytic lesions, osteopenia, and pathologic fractures. Multiple
myeloma is frequently accompanied with anemia, hypercalcemia, and renal insufficiency.
This patient does not have any of these findings. Furthermore, multiple myeloma is not
associated with SIADH or hyponatremia.
53

54. First Aid Q & A for USMLE Step 2 CK, Pg. 462
Answer 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 chorionic
gonadotropin, which can lead to elevated steroidogenesis and aromatase activity. Elevated
human chorionic gonadotropin levels can lead to gynecomastia in men, while women are
usually asymptomatic.
Answer E is incorrect. Thymic carcinoma is not frequently associated with SIADH but
is the second most common cause of ectopic ACTH production. Fifteen percent of cases
of ectopic ACTH production are attributed to thymic carcinoma, while more than 50% of
cases are attributed to small cell lung cancer.
End of Session 1
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