Hypotension case 5

Hypotension case 5


A 45-year-man was brought in by paramedics for vomiting blood. He was not responding to the questions by the medical staff. The patient had a heavy odor of alcohol on his breath. On examination, his temperature is 37.7 C (99.8 F), blood pressure is 75/35 mm Hg, and pulse is
120/min. There is blood crusting around the patient's mouth and he is only oriented to person, but not place or time. His neck veins are flattened, and his heart examination shows tachycardia without any murmurs. His lung and abdomen examinations are not significant. Rectal
examination is guaiac negative. No peripheral edema is seen. A nasogastric tube is placed and about 1.5 Iiter of normal saline is used until the nasogastric lavage is clear of blood. Laboratory results show:

Sodium 143 mEq/L
Potassium 4.3 mEq/L
Chloride 96 mEq/L
Bicarbonate 19 mEq/L
BUN 36 mg/dL
Creatinine 1.3 mg/dL
GIucose 89 mg/dL

A complete blood count (CBC) and a chest x-ray film are pending. His ECG shows normal sinus rhythm at 117/min, and no other changes.

Q 1
Which of the following is the most likely diagnosis?
/ A. Adrenal insufficiency
/ B. AIcohol withdrawal
/ C. Cardiogenic shock
/ D. Hypovolemic shock
/ E. Septic shock

Q 2
Which of the following would rule out shock?
/ A. AItered mental status
/ B. Cold extremities
/ C. Low systolic pressure
/ D. Metabolic acidosis
/ E. Urine output > 40 cc/hr

Q 3
Which of the following is the most appropriate initial therapy?
/ A. Dopamine
/ B. Hydrocortisone
/ C. IV FIuids
/ D. Nitroglycerin
/ E. Norepinephrine

Q 4
Which of the following is the patient's mean arterial pressure?
/ A. 35
/ B. 40
/ C. 48
/ D. 60
/ E. 75

Q 5
Which of the following would most likely represent this patient's pulmonary artery catheterization (Swan-Ganz) values?
/ A. A
/ B. B
/ C. C
/ D. D
/ E. E

Q 6
Which of the following is the best treatment for Patient C in the chart above?
/ A. Dopamine
/ B. Hydrocortisone
/ C. IV FIuids
/ D. Nitroglycerin
/ E. Norepinephrine


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Hypotension case 5 answers

A1
The correct answer is D. The patient is suffering from hypovolemic shock secondarily from an upper GI bleed.
Adrenal insufficiency (choice A) can present with severe hypotension in the setting of a patient who stopped taking his chronic steroid dosage. It can occur after severe stress, trauma, or infections. It is often associated with hyponatremia and hyperkalemia.
Alcohol withdrawal (choice B) should be considered in the management of this patient; he may go into delirium tremens (DTs) in the next 24-48 hours.
Cardiogenic shock (choice C) is suggested by symptoms of heart failure, e.g., bulging neck veins and crackles on lung examination. There may be some old or acute changes on the ECG.
Septic shock (choice E) can be a possibility for investigation if the patient does not respond to fluids/blood products.


A2
The correct answer is E. Patients in shock tend to be oliguric (urine output < 20 cc/hr).
Patients in shock can have altered mental status (choice A), cold and clammy extremities from peripheral vasoconstriction (choice B), low systolic pressure (choice C), and metabolic acidosis (choice D) from the buildup of the serum lactate from anaerobic metabolism.


A3
The correct answer is C. IV fluids are the first and foremost important intervention for hypovolemia; whole blood products would be the next step for hypovolemic shock from hemorrhage.
Dopamine (choice A) is used in patients with cardiogenic shock or pump failure.
Hydrocortisone (choice B) is necessary, in addition to fluids, for patients with suspected adrenal insufficiency.
Nitroglycerin (choice D) is used to relieve chest pain, and may be used in hypertensive crises and urgencies.
Norepinephrine (choice E) has alpha adrenergic/vasoconstricting properties used in septic shock in which the SVR (systemic vascular resistance) is low.

A4
The correct answer is C. The mean arterial pressure (MAP) estimates the perfusion of the body and brain; a pressure > 60 (choice D) ensures sufficient perfusion. It is measured by 2/3 diastolic + 1/3 systolic pressure = 2/3 (35) + 1/3 (75) = 70/3 + 25 = 48.3 The normal ranges are 75 to 110.
Choice A is the diastolic blood pressure.
Choice B is the pulse pressure = systolic bp-diastolic bp.
Choice E is the systolic blood pressure.


A5
The correct answer is B. Hypovolemic shock is characterized by a low wedge pressure (PCWP) because of low LV preload/filling leading to low stroke volume, leading to low cardiac output (CO), leading to high systemic vascular resistance (SVR).
Patient A has normal pulmonary artery catheterization values: normal PCWP (12-15 mm Hg), CO (3.5-5.5 L/min), and SVR (800-1200 dyne/sec/cm2).
Patient C is in cardiogenic shock; the hallmark is low CO, leading to high PCWP (pump backs up) and high SVR.
Patient D has septic shock with the distinguishing low SVR, leading to low PCWP, leading to high CO for compensation.
Patient E has obstructive shock (from massive pulmonary embolus/tension pneumothorax) with low filling pressure, leading to low wedge pressure, leading to low CO, leading to high SVR as compensation.

A6
The correct answer is A. Patient C has cardiogenic shock, and therefore dopamine would be appropriate to increase pump activity.
Hydrocortisone (choice B) is used in patients with adrenal insufficiency.
IV fluids (choice C) would cause even further cardiac pump failure.
Nitroglycerin (choice D) is used to relieve chest pain, and may be used in hypertensive crises and urgencies.
Norepinephrine (choice E) has alpha adrenergic/vasoconstricting properties, and is used in septic shock in which the SVR is low.

Hypotension case 4

Hypotension case 4


A 63-year-old man is brought into the emergency department with shortness of breath over the past 4 hours, although the patient's family
states that he had complained of some shortness of breath and dry cough over the past 2 months. The patient denies any significant past medical history, fever, chills, or chest pain, and has not been taking any medications. Review of systems is positive for a 10 pound weight loss
in the last 5 months and social history pertinent for a 20-pack-year smoking history, but the patient had quit smoking 10 years prior. Physical examination reveals a thin man who is alert and awake but in obvious distress and breathing shallowly. His temperature is 37.2 C (99 F),
blood pressure is 90/75 mm Hg, pulse is 122/min, and respirations are 20/min. The neck veins are prominent with a decline during inspiration.
The cardiac examination is significant for tachycardia and distant heart sounds, but no murmurs/gallops/rubs are heard. Lung examination is significant for decreased breath sounds at the bases, but no crackles or wheezes are heard. No peripheral edema is seen. Labs are sent.
ECG reveals a sinus tachycardia at 118/min, Iow voltage QRS complexes, and electrical alternans of the P, QRS, and T waves. A chest x-ray
film shows an enlarged cardiac silhouette, but minimal pulmonary vascular congestion.


Q 1
Which of the following is characteristic of the patient's condition?
/ A. Pulsus alternans
/ B. Pulsus bisferiens
/ C. Pulsus et tardus
/ D. Pulsus paradoxus
/ E. Quincke's pulses


Q 2
Which of the following features on the echocardiogram would be diagnostic?
/ A. Anterior wall hypokinesis
/ B. Collapse of the right ventricle during diastole
/ C. Diastolic dysfunction
/ D. Left ventricular hypertrophy
/ E. Pericardial fluid collection



Q 3
Which of the following is the most appropriate immediate treatment for this patient?
/ A. Antibiotics
/ B. Diuresis
/ C. Heparin
/ D. Pericardiocentesis
/ E. Pericardial window



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Hypotension case 4 answers


A1
The correct answer is D. This patient has cardiac tamponade. This disorder is characterized by elevation of intracardiac pressures, limitation of ventricular filling, and reduction of cardiac output. The patient's presentation is highly suggestive of this disorder, with dyspnea, tachycardia, hypotension, neck vein distention with pulsations, and muffled heart sounds. Severe, acute tamponade is characterized by falling arterial pressure, and rising venous pressure, but slowly developing tamponade may resemble congestive heart failure. The jugular venous pressure shows a prominent x descent; in constrictive pericarditis, the y descent is prominent. The ECG in tamponade tends to show tachycardia, but with small QRS complexes because the pericardial fluid hinders the transmission of the impulses. Electrical alternans (beat-to-beat alternation in ECG components) of the P, QRS, and T waves is suggestive of effusion, often with tamponade. The chest x-ray film tends to show a globular heart, but minimal pulmonary edema. Pulsus paradoxus can be present in patients with cardiac tamponade. It is present if a > 10 mm Hg decline in systolic pressure is measured during inspiration, and is caused by impaired left ventricular filling.
Pulsus alternans (choice A) is a regular alteration in pulse pressure amplitude in severe left ventricular dysfunction.
Pulsus bisferiens (choice B) refers to two palpable peaks in the pulse of those with mixed aortic regurgitation and stenosis and hypertrophic obstructive cardiomyopathy.
Pulsus et tardus (choice C) is a delayed carotid upstroke seen in aortic stenosis.
Quincke's pulses (choice E) are subungual capillary pulsations seen in patients with aortic regurgitation.


A2
The correct answer is B. A patient with cardiac tamponade has pericardial effusion (choice E) on echocardiography, but right ventricle/atrium collapse during diastole is specific for tamponade. Patients with pericardial effusion only (no tamponade) can be asymptomatic.
Anterior wall hypokinesis (choice A) can occur in patients with anterior myocardial infarction.
Diastolic dysfunction (choice C) is impaired right or left ventricular filling from long-standing hypertension.
Left ventricular hypertrophy (choice D) is enlargement of the left ventricular wall, often from hypertension.


A3
The correct answer is D. The most immediate treatment for this disorder is pericardiocentesis (placing a needle into pericardial space to aspirate fluid) if a patient shows any signs of hemodynamic compromise.
Antibiotics (choice A) are not indicated unless there are any other signs of infections.
Diuresis (choice B) is important for heart failure, but is not appropriate for this patient with pending cardiovascular collapse if not treated.
Heparin (choice C) is used for anticoagulation for pulmonary embolus and deep vein thrombus.
Pericardial window (choice E) is used in chronic pericardial effusion and constrictive pericarditis to drain the recurrent fluid accumulation.

Hypotension case 3

Hypotension case 3

A 20-year-old college student presents to the campus health service complaining of a purulent penile discharge. When his culture reveals
gonococcal infection, he returns to the clinic for treatment, and is given an intramuscular injection of ceftriaxone. While checking out, he tells the
receptionist that he feels ilI. He complains of feeling weak, dizzy, and short of breath, as well as a "funny" sensation around his mouth. On
physical examination, he is sweaty and pale. His lips appear swollen. His blood pressure cannot be auscultated; via palpation, his systolic
pressure is estimated at 74 mm Hg. His pulse is 116/min, and respirations are 30/min.

Q 1
This is an example of which of the following types of hypersensitivity reactions?
/ A. Type l
/ B. Type ll
/ C. Type lll
/ D. Type IV


Q 2
Which of the following immunoglobulins initiates this patient's disease process?
/ A. IgA
/ B. IgD
/ C. IgE
/ D. IgG
/ E. IgM


Q 3
As resuscitation efforts begin, 0.5 mg of epinephrine is administered subcutaneously. Which adrenergic receptors, in which tissues, are
responsible for the beneficial effect of epinephrine in this patient?
/ A. AIpha-1 receptors in vascular smooth muscle, alpha-2 receptors in the heart, and beta-1 receptors in bronchial smooth muscle
/ B. AIpha-1 receptors in vascular smooth muscle, alpha-2 receptors at presynaptic nerve terminals, beta-1 receptors in bronchial smooth
muscle
/ C. AIpha-1 receptors in vascular smooth muscle, beta-1 receptors in the heart, and beta-2 receptors in bronchial smooth muscle
/ D. AIpha-2 receptors in vascular smooth muscle and beta-2 receptors in vascular smooth muscle
/ E. Beta-1 receptors in the heart alone


Q 4
The patient is also given a dose of hydrocortisone. Which of the following is the most likely molecular mechanism by which steroids have their
effect?
/ A. Adenosine receptor blockade
/ B. Direct mast cell stabilization
/ C. Histamine receptor blockade
/ D. Inhibition of cyclooxygenase
/ E. Inhibition of phospholipase A2
/ F. Leukotriene receptor blockade


Q 5
At discharge from the hospital several days later, the patient is warned that he is allergic to cephalosporins. Which other drug should he be
warned not to take in the future?
/ A. Aztreonam
/ B. Gentamicin
/ C. Indomethacin
/ D. Penicillin
/ E. Trimethoprim-sulfamethoxazole

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Hypotension case 3 answers

A1
The correct answer is A. IgE antibody is produced in response to an initial challenge by an antigen, and binds to Fc receptors on mast cells and basophils. Reexposure to the antigen causes degranulation of mast cells and release of vasoactive amines (e.g., histamine and adenosine), chemotactic cytokines, and enzymes (e.g., proteases and kinins). Mast cells go on to synthesize and release arachidonic acid metabolites (leukotrienes, prostaglandin D2) and platelet-activating factor. These multiple mediators, in turn, initiate a rapid inflammatory response, resulting in recruitment of neutrophils and eosinophils, and production of increased vascular permeability, tissue edema, and epithelial cell injury. The clinical manifestations of anaphylaxis are urticaria, tissue swelling and angioedema, laryngeal edema, bronchoconstriction, and hypotension, as well as abdominal cramping and diarrhea. Other Type I type hypersensitivity reactions are more localized, as in some forms of bronchial asthma, allergic rhinitis, and allergic gastroenteritis.
Type II hypersensitivity reactions (choice B) include antibody-dependent cytotoxic responses, in which antibody (IgG or IgM) binds to antigen on a cell surface, resulting in either the activation of complement, or cell-mediated cytotoxicity via nonspecific neutrophils, monocytes, eosinophils, and NK cells that bind to the Fc fragment of IgG. Examples of Type II reactions are transfusion reactions, autoimmune hemolytic anemias, erythroblastosis fetalis, and Goodpasture syndrome. Type II hypersensitivity also includes noncytotoxic antibody-mediated dysregulation such as the anticholinergic receptor antibodies of myasthenia gravis and the anti-TSH receptor antibodies of Graves disease.
Type III hypersensitivity reactions (choice C) are immune-complex mediated reactions in which antibody-antigen complexes are formed, thereby activating complement. The antigen may be endogenous or exogenous. Examples are serum sickness, systemic lupus erythematosus, and some acute glomerulonephritides.
Type IV hypersensitivity (choice D) also called delayed-type hypersensitivity, is entirely cell-mediated and requires the presentation of antigen on a cell surface, resulting in CD4 cell activation followed by CD8 cell-mediated direct cytotoxicity. The most common example of this is the cutaneous tuberculin reaction: this is also involved in contact dermatitis and in rejection of solid organ transplants


A2
The correct answer is C. Antigen binds to IgE on the surface of mast cells and basophils, initiating anaphylaxis.
IgA (choice A) is secreted primarily by mucosal plasma cells and is the principal immunoglobulin present in secretions. It is a major component of immunologic defense against viruses. Approximately 1 in 800 people is IgA-deficient.
IgD (choice B) acts as an antigen-binding receptor on B cells, although very small quantities also circulate.
IgG (choice D) represents approximately 75% of circulating antibody and is the predominant antibody made after rechallenge of a host with antigen, as well as a major component of antibacterial immunity, initiating neutrophil and monocyte responses as well as activating complement.
IgM (choice E) is the antigen-binding receptor on the B cell. IgM also circulates as a pentamer. Since no class-switching is required to form it, IgM constitutes the primary antibody response on initial host antigen challenge. IgM activates complement efficiently, and is an important mediator of rheumatoid arthritis and of immune complex diseases.


A3
The correct answer is C. Epinephrine is a nonselective adrenergic agonist and a valuable resuscitative drug because of its effects at multiple adrenergic receptor subtypes. In the treatment of anaphylaxis, epinephrine increases myocardial contractility, accelerates heart rate, causes constriction of vascular smooth muscle, and causes relaxation of bronchial smooth muscle. The principal pharmacologic effects of epinephrine that are beneficial in anaphylaxis are mediated via: alpha-1 receptors in vascular smooth muscle, resulting in vasoconstriction, beta-1 receptors in the heart, resulting in increased contractility, and beta-2 receptors in bronchial smooth muscle, resulting in relaxation and relief of bronchoconstriction. (One simple mnemonic for the respective locations of beta-1 and beta-2 receptors is "one heart, two lungs.") Beta-2 receptors are also found, however, in vascular smooth muscle (especially in skeletal muscle beds), where, just as in bronchial smooth muscle, they promote relaxation. (Epinephrine dilates skeletal muscle vascular beds to maximize oxygen delivery for the "fight-or-flight" response.) The resulting vasodilation in skeletal muscle vascular beds would, by itself, tend to decrease blood pressure, which might tend to worsen the effects of anaphylactic shock, but this effect is mitigated by the intense alpha-1 receptor stimulation, causing vasoconstriction in multiple beds. The principal action of alpha-2 receptors is at the presynaptic nerve terminal, where receptor stimulation reduces the release of norepinephrine from the nerve terminal. Epinephrine does stimulate these receptors, but it does not really contribute to the beneficial actions of epinephrine in resuscitation.
Alpha-2 receptors are not located in the heart (except at presynaptic nerve terminals), alpha-2 receptors do not have a significant beneficial effect in resuscitation, and beta-1 receptors are not located in bronchial smooth muscle, but are located in the heart (compare with choice A).
Beta-1 receptors are located in the heart, not in bronchial smooth muscle. The adrenergic receptor that produces bronchial smooth muscle relaxation is beta-2 (compare with choice B).
Alpha-2 receptors are located primarily at presynaptic nerve terminals, and because the beta-2 receptors in vascular smooth muscle cause vasodilation, this not a helpful effect of epinephrine in this case (compare with choice D).
In the patient with anaphylaxis, epinephrine is resuscitative also by raising blood pressure via alpha-1 receptors in vascular smooth muscle and relieving bronchoconstriction via beta-2 receptors in bronchial smooth muscle (compare with choice E).


A4
The correct answer is E. Steroids inhibit phospholipase A2, which cleaves cell membrane phospholipids into arachidonic acid. Inhibition of this enzyme, in turn, prevents the formation of thromboxane, as well as all the prostaglandins and leukotrienes.
Adenosine receptor blockade(choice A) is one of the mechanisms of action of the methylxanthines, including caffeine, theophylline, aminophylline, and theobromine. Adenosine is a potent bronchoconstrictor. Theophylline and aminophylline are used in the treatment of asthma.
Prevention of mast cell degranulation (choice B) is thought to be the mechanism of action of cromolyn sodium, an inhaled drug used in asthma.
Histamine receptor blockade (choice C) is a central part of the therapy for anaphylaxis, and is accomplished by using both H1 receptor blockers such as diphenhydramine as well as H2 receptor blockers like cimetidine.
Inhibition of cyclooxygenase (choice D) is the principal mechanism of action of the nonsteroidal anti-inflammatory agents, which generally inhibit both the COX1 (constitutive) and COX2 (inducible) isoforms of this enzyme, preventing the conversion of arachidonic acid into prostaglandin and thromboxane precursors. Newer NSAIDs are relatively selective for COX2, and therefore do not inhibit prostaglandin formation in normal tissue to the same degree that they do in inflamed tissues.
Leukotriene receptor blockade (choice F) is the mechanism of action of a new class of asthma drugs such as montelukast and zafirlukast.


A5
The correct answer is D. Penicillins and cephalosporins share a common beta-lactam ring, which is the most likely antigen responsible for triggering the anaphylaxis cascade in this patient.
Aztreonam (choice A) is a monobactam antibiotic which, although closely related to the penicillins and cephalosporins, does not appear to have antigenic cross-reactivity.
Gentamicin (choice B) is an aminoglycoside antibiotic and is not chemically related to cephalosporins. Aminoglycosides are frequently prescribed in conjunction with beta-lactam antibiotics because of their synergy against gram-positive bacteria.
Indomethacin (choice C) is a nonsteroidal anti-inflammatory agent, not an antibiotic or related to the cephalosporins. NSAIDs and aspirin can, however, trigger severe bronchospasm and upper airway obstruction, as well as angioedema in susceptible individuals, most frequently asthmatic patients, probably as the result of an imbalance in prostaglandin and leukotriene production. This is not an IgE-mediated reaction and this patient should not be at significantly increased risk.
The combination of trimethoprim, (a diaminopyrimidine) and sulfamethoxazole (a sulfonamide) (choice E) provides two antimicrobials with different targets in the bacterial folic acid synthesis pathway, to create a synergistic and widely prescribed combination. There is no chemical relation to or cross-reactivity with cephalosporins or penicillins.

Hypotension case 2

Hypotension case 2


A 32-year-old woman goes to the local emergency department because she has been feeling increasingly ilI. When she tries to stand to go
into the examining room, she loses consciousness and falls to the floor. Her blood pressure is 70/40 mm Hg. Her temperature is 40.1 C (104
F), and her skin shows a diffuse, sunburn-Iike, erythema. IV fluids are started, and the woman's husband is questioned. He reports that her
symptoms began approximately 24 hours previously and that she has been experiencing headache, sore throat, profound lethargy, vomiting,
profuse diarrhea, muscle pain, and the rash. Examination of the patient's vagina demonstrates a blood-filled tampon. Gram's stain of a vaginal
smear shows nearly complete replacement of the normal vaginal flora by gram-positive cocci.


Q 1
Which of the following is the most likely diagnosis?
/ A. Kawasaki syndrome
/ B. Meningococcemia
/ C. Reye syndrome
/ D. Rocky Mountain spotted fever
/ E. Toxic shock syndrome


Q 2
This condition is most closely associated with which of the following organisms?

Moraxella catarrhalis.
Neisseria gonorrhoeae
Staphylococcus aureus
Streptococcus agalactiae
Streptococcus pyogenes

Q 3
The exotoxin implicated in this patient's disease is unusual in that it is a superantigen. This means which of the following?
/ A. It can bind to the inside surfaces of the normal peptide grooves of both lgA and the TCR molecule
/ B. It can bind to the inside surfaces of the normal peptide grooves of both lgE and the TCR molecule
/ C. It can bind to the inside surfaces of the normal peptide grooves of both the MHC class l molecule and the TCR molecule
/ D. It can bind to the outside surfaces of the normal peptide grooves of both lgG and the TCR molecule
/ E. It can bind to the outside surfaces of the normal peptide grooves of both the MHC class ll molecule and the TCR molecule


Q 4
One of the compounds that has been implicated in the severe hypotension seen in this patient's disease is tumor necrosis factor (TNF)-alpha.
This molecule is produced by which of the following cell types?
/ A. B Iymphocytes
/ B. Eosinophils
/ C. Macrophages
/ D. Neutrophils
/ E. T Iymphocytes

Q 5
Which of the following is the most appropriate pharmacotherapy?
/ A. Chloramphenicol
/ B. Gentamicin
/ C. Nafcillin
/ D. Penicillin
/ E. Tetracycline


Q 6
The mortality in this patient's condition is high, in large part because multi-organ failure may develop. Which of the following serum laboratory
results would suggest developing renal failure?
/ A. AIanine aminotransferase (ALT) 105 U/L
/ B. Aspartate aminotransferase (AST) 100 U/L
/ C. Creatinine 2.5 mg/dL
/ D. Serum sodium 141 mEq/L
/ E. Total creatine kinase 550 U/L


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Hypotension case 2 answers

A1
The correct answer is E. This woman's presentation is typical for toxic shock syndrome. In patients who survive, the rash eventually becomes desquamating. Toxic shock syndrome is a rare, but very dangerous disease with a 5% mortality rate, primarily related to the complications of shock. Many cases have been related to the use of super absorbent tampons, which favor bacterial overgrowth. Since removal of some of the more strongly implicated tampons from the market, the incidence of toxic shock syndrome has dropped and now appears to be about 3 cases/100,000 menstruating women. Cases can also be seen complicating postpartum or postoperative infections. Gram-positive cocci would not cause any of the other conditions listed.
Kawasaki syndrome (choice A) usually occurs in children, and while it causes severe rash, it does not usually cause shock.
Meningococcemia (choice B) and Rocky Mountain spotted fever (choice D) both usually cause macular rashes.
Reye syndrome (choice C) can cause rash, but it is almost always seen in individuals less than 18 years of age.


A2
The correct answer is C. Almost all cases of classic toxic shock syndrome have been associated with exotoxin-producing strains of phage group 1 Staphylococcus aureus. Streptococcus pyogenes can also, less commonly, produce a toxic shock-like syndrome. The toxin implicated in staphylococcal toxic shock syndrome has been called toxic shock syndrome toxin-1 (TSST-1). It is thought that women who develop toxic shock syndrome following tampon use have vaginas that were previously colonized by small numbers of the toxin-producing bacteria, and that then as the vaginal conditions change, bacterial overgrowth with the staphylococci occurs. Toxic shock syndrome is unusual, in that sepsis-like systemic effects are seen even though true bacteremia does not occur, just absorption of a very potent toxin. Antibiotic therapy is usually included in treatment of toxic shock, but the intent is to eradicate the colonization and prevent recurrence, rather than treat an active, true infection.
Moraxella catarrhalis(choice A) is a gram-negative coccus that forms part of the normal nasal flora, and has been occasionally implicated as a cause of otitis media, bronchitis, and bronchopneumonia.
Neisseria gonorrhoeae(choice B) is a gram-negative coccus that causes gonorrhea.
Streptococcus agalactiae(choice D) is a group B, beta-hemolytic streptococcus that colonizes the vagina (with no harm to the mother) and causes neonatal septicemia and meningitis.
Streptococcus pyogenes(choice E) is a group A, beta-hemolytic streptococcus that also produces potent toxins, and has been implicated in pharyngitis, scarlet fever, impetigo, rheumatic fever, and acute glomerulonephritis.


A3
The correct answer is E. Both the staphylococcal toxic shock syndrome toxin-1 (TSST-1) and the streptococcal super antigen (SSA) are unusual in that they tend to trigger a massive release of cytokines in response to relatively small amounts of toxin. The reason is that, unlike normal antigens that bind inside the normal peptide grooves of the MHC class II molecule on the antigen presenting cell and the T cell receptor (TCR) molecule of the T lymphocyte, these antigens recognize sites outside the grooves on these two molecules. The result is that they can, in effect, "turn on" almost every T cell they find, thereby producing the massive release of cytokines.
IgA (choice A), IgE (choice B), MHC class I molecules (choice C), and IgG (choice D) are not involved in these processes.


A4
The correct answer is E. Tumor necrosis factor alpha is produced by T lymphocytes, and it acts by increasing the fluid leakage out of the vasculature as part of its more generalized stimulation of inflammatory processes. It is also thought the TSST-1 may directly alter capillary permeability. Macrophages (choice C) produce IL-1, which is also important in triggering the severe hypotension by a similar mechanism to that of TNF-alpha.
B lymphocytes (choice A), eosinophils (choice B), and neutrophils (choice D) do not produce TNF-alpha and are not as important in triggering the hypotension of toxic shock.


A5
The correct answer is C. Treatment measures for TSS include rehydration, management of cardiac and renal failure (if present), administration of antistaphylococcal agents (e.g., nafcillin), as well as removal of the source of the toxin, such as removal of the tampon or drainage of an abscess.
Chloramphenicol (choice A) is an older antibacterial agent used in the treatment of severe infections only when less toxic agents cannot be used. Examples of such infections include Salmonella infections, H. influenzae infections, and various types of meningitis.
Gentamicin (choice B) is a bactericidal aminoglycoside antibiotic used primarily in the treatment of serious gram-negative infections. This agent requires active transport across the cell membrane to exhibit activity. In an acidic environment, the drug becomes ionized and less is transported to the interior of the cell. Gentamicin is a concentration-dependent killer: the drug only needs to be in contact with the bacteria for a short period of time to exert a killing effect (a property that may help minimize toxicity). It also exerts a postantibiotic effect in which the antimicrobial action is "seen" after drug concentration falls below minimum inhibitory concentration.
Penicillin (choice D) is a bactericidal antibiotic with broad gram-negative and gram-positive coverage as well as moderate anaerobic coverage. It inhibits the biosynthesis of cell wall mucopeptides. Most hospital isolates of Staph aureus are resistant to penicillin.
Tetracycline (choice E) has mild-to-moderate gram-negative and gram-positive coverage. It provides coverage for many rickettsial, spirochetal, and chlamydial infections. Tetracycline acts by inhibiting protein synthesis by binding to the 30S ribosome. It is primarily used for uncomplicated gonococcal infections and acne.


A 6
The correct answer is C. The multi-organ failure seen in toxic shock syndrome is, in large part, due to the very difficult-to-manage hypotension as fluid shifts out of the vascular space and into the tissues. This produces the paradox that you can get a markedly edematous patient who is actually hypotensive secondary to fluid losses within the body. Patients may require 10 liters or more of IV fluids per day in order to prevent multiorgan failure. Impending renal failure is indicated by dropping urine output and rising BUN and serum creatinine levels.
The liver is also very vulnerable, and damage is indicated by rising ALT (choice A) and AST (choice B) levels.
Serum sodium (choice D) is usually not affected, since the fluid replacement is usually with normal saline or similar isotonic fluids.
Muscle damage may be a prominent feature and cause leakage of creatine kinase (choice E).

Hypotension case 1

Hypotension case 1

A 32-year-old woman presents to an emergency department and loses consciousness while going through the financial screening process.
According to her husband, she has been having severe vomiting and diarrhea. He took her to the emergency room when she also began to
have severe pain in her back, abdomen, and legs. Physical examination demonstrates marked hypotension, dry mucus membranes, Ioss of
skin turgor, and a generalized hyperpigmentation of the skin that is most noticeable on scars, skin folds, knees, knuckles, and lips.

Q 1
Which of the following features of this woman's presentation is most suggestive of the likely diagnosis?
/ A. Abdominal pain
/ B. Hyperpigmentation
/ C. Hypotension
/ D. Loss of consciousness
/ E. Vomiting

Q 2
Which of the following is the most likely diagnosis?
/ A. Addison disease
/ B. Diabetes mellitus type 2
/ C. Hyperthyroidism
/ D. Hypoparathyroidism
/ E. Pheochromocytoma

Q 3
This patient's severe hypotension is most likely related to abnormal serum levels of which of the following hormones?
/ A. AIdosterone
/ B. Epinephrine
/ C. Insulin
/ D. Parathyroid hormone
/ E. Thyroxine

Q 4
Which of the following is the most common cause in the United States of this patient's probable condition?
/ A. Amyloidosis
/ B. Autoimmune disease
/ C. Metastatic cancer
/ D. Surgical removal
/ E. Tuberculosis

Q 5
If this patient had been a child who had a familial form of this disease, which of the following would most likely also be affected?
/ A. Exocrine pancreas
/ B. Pancreatic islets
/ C. Parathyroid gland
/ D. Salivary glands
/ E. Thyroid gland

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Hypotension case 1 answers

A1
The correct answer is B. One of the tricks of physical diagnosis is to have a sense of which features of a patient's presentation are most suggestive of specific illnesses. This woman is obviously severely ill, but the majority of her signs and symptoms (including those listed in choices A, C, D, and E) are very nonspecific and may be seen in many different diseases affecting a variety of organ systems. The most specific finding is the unusual pattern of hyperpigmentation.


A2
The correct answer is A. While roughly 75% of patients with Addison disease have been previously diagnosed when they develop a crisis, the remaining 25% have not. Most patients' symptoms are nonspecific (although usually severe) and many physicians have never seen a case (Addison disease is rare, with an incidence of 1 in 100,000). These facts together mean that this potentially fatal crisis is very often misdiagnosed, and vital time is wasted while working the patient up as a probable sepsis, surgical abdomen, gastrointestinal illness, or back pain case. An alert physician who notices the hyperpigmentation of both sun-exposed and unexposed skin and also knows to associate this with Addison disease could save this patient's life. (A helpful clue in patients with naturally pigmented skin is to look for the specific areas of hyperpigmentation mentioned in the case history.) Those patients who do not present with a crisis may come to medical attention because of chronic fatigue and muscle weakness, loss of appetite with weight loss, chronic nausea and vomiting, hyperkalemia picked up on routine serum chemistry screens, hypotension with fainting spells, or irritability and depression. Other features can include craving of salty foods, hypoglycemia, and irregular menstrual periods. The symptoms usually develop slowly, and may be ignored until exacerbated by illness or accident, thereby producing an Addisonian crisis. Once Addison disease is suspected, the diagnosis can be confirmed with an ACTH stimulation test, in which cortisol secretion is measured after exogenous ACTH is administered.
A patient with undiagnosed type 2 diabetes mellitus 2 (choice B) might also lose consciousness (most likely due to hyperosmolar coma) in the emergency room, but would not have the skin pigmentation, pain, or nausea and vomiting seen in this case. Hyperthyroidism (choice C) causes heat intolerance, nervousness, and can occasionally produce an arrhythmia severe enough to cause loss of consciousness, but would not cause the skin pigmentation, pain, or nausea and vomiting seen in this case.
Hypoparathyroidism (choice D) causes hypocalcemia with tetany, but would not cause this patient's symptom pattern.
Pheochromocytoma (choice E) could cause nausea and vomiting, abdominal pain, and loss of consciousness secondary to arrhythmia, but would not cause hyperpigmentation.


A3
The correct answer is A. The hormones that are deficient in Addison disease are cortisol (always) and aldosterone (sometimes). Aldosterone is a mineralocorticoid produced by the adrenal cortex that normally helps the body maintain blood pressure and water and salt balance. It acts by stimulating the kidney to retain sodium and excrete potassium. Hypotension and hyperkalemia can develop when aldosterone levels are too low. Cortisol also helps to maintain blood pressure and cardiovascular function, and has additional actions, including modulating the inflammatory response and opposing insulin's actions in the regulation of protein, carbohydrate, and fat metabolism. Treatment of patients with Addison disease usually includes glucocorticoid replacement (often with oral hydrocortisone) and may include mineralocorticoid replacement (typically with oral fludrocortisone).
Epinephrine (choice B) stimulates the adrenergic system and tends to increase blood pressure secondary to cardiotropic and vasoactive effects.
Insulin (choice C) affects the metabolism of carbohydrate, fat, and protein, but does not directly alter blood pressure.
Parathyroid hormone (choice D) affects serum calcium levels.
Thyroxine (choice E) tends to increase metabolic rate, and, when deficient, may be associated with low blood pressure, but would not produce the clinical presentation seen with this patient.



A4
The correct answer is B. Primary adrenal insufficiency, or Addison disease, only develops when at least 90% of the adrenal cortex has been destroyed. While, at the time that Addison initially described the disease, tuberculosis (choice E) was the most common cause (and still causes approximately 20% of cases), medical control of tuberculosis has made this cause much less likely, and a gradual autoimmune destruction of the adrenal cortex now causes approximately 70% of all cases of Addison disease in developed countries. Less common causes of Addison disease include chronic infections (usually fungal), metastatic cancer (choice C), amyloidosis (choice A), and surgical removal of the adrenal glands (choice D). Secondary adrenal insufficiency differs from primary adrenal insufficiency by the lack of skin pigmentation, and is usually due to a lack of pituitary-secreted ACTH, most commonly either following cessation of glucocorticoid therapy for other diseases, or removal of an ACTH-producing tumor of the pituitary gland. Secondary adrenal insufficiency often eventually resolves spontaneously, although interim hormonal support is usually required.

A5
The correct answer is C. The autoimmune form of Addison disease can occur either as an isolated condition or as part of a polyendocrine deficiency syndrome, which is possibly inherited, since multiple family members may develop endocrine deficiencies. These associations are important because patients with autoimmune Addison disease should be initially evaluated, and then periodically screened for development of other endocrine deficiencies. Type I polyendocrine deficiency develops in childhood, and may include adrenal insufficiency, hypoparathyroidism (choice C), pernicious anemia, chronic active hepatitis, chronic Candida infections, and slow sexual development. Type II polyendocrine deficiency (Schmidt syndrome) develops in young adults and may include adrenal insufficiency, hypothyroidism (choice E), diabetes mellitus type I (affecting the pancreatic islets, choice B), vitiligo, and slow sexual development. The exocrine pancreas (choice A) and the salivary glands (choice D) are not affected in either type

Hypertension Case 4

Hypertension Case 4


Case 4

A 19-year-old woman presents to her doctor's office for an annual physical examination. She has been previously healthy and is currently doing well without complaints. She is a non-smoker and has no significant past medical history or family history. Her temperature is 36.9 C (98.5 F),
blood pressure is 160/90 mm Hg (confirmed in all extremities), pulse is 84/min, and respirations are 16/min. Her pulses are symmetric and equaI, her cardiac and pulmonary examinations are unremarkable, and there is an abdominal bruit with a systolic and diastolic component.

Serum chemistry reveals:

Sodium 145 mEq/L
Potassium 3.1 mEq/L
Chloride 102 mEq/L
Bicarbonate 28 mEq/L
BIood urea nitrogen 14 mg/dL
Creatinine 1.0 mg/dL
GIucose 80 mg/dL


Q 1

Which of the following is the most likely cause of her elevated blood pressure?
/ A. Coarctation of the aorta
/ B. Cushing syndrome
/ C. Pheochromocytoma
/ D. Renovascular hypertension
/ E. Thyrotoxicosis


Q 2
Which of the following is the most likely cause of the low potassium in this patient?
/ A. Acidosis
/ B. Gastrointestinal wasting
/ C. Hyperaldosteronism
/ D. Inadequate nutritional intake
/ E. Thyrotoxicosis


Q 3
The patient is initially treated with atenolol to lower her blood pressure. Which of the following is the mechanism of action of this medication?
/ A. AIpha-1 receptor blockade
/ B. AIpha-2 receptor stimulation
/ C. Calcium channel blockade
/ D. Nonselective beta blockade
/ E. Selective beta-1 receptor blockade


Q 4
Which of the following tests would help confirm the diagnosis in this patient?
/ A. Bilateral arteriography with renal vein and systemic renin measurements
/ B. Renal biopsy
/ C. Thyroid function studies
/ D. Twenty-four hour urine evaluation for creatinine clearance
/ E. Urine catecholamine levels


Q 5
Biopsy of the affected tissue would likely reveal which of the following?
/ A. Adrenocortical adenoma
/ B. Atrophic thyroid follicles with dense, focal lymphocytic infiltration
/ C. Fibromuscular dysplasia
/ D. Hyperplasia of the zona glomerulosa of the adrenal gland
/ E. Psammoma bodies


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Hypertension Case 4 answers


A1
The correct answer is D. Secondary hypertension should be considered in a young previously healthy patient with new onset hypertension. In this case, renovascular hypertension should be highly suspected in the presence of an abdominal bruit on physical exam. Abdominal bruits, particularly those with a systolic and diastolic component, are specific for renovascular hypertension due to renal artery stenosis. Renovascular hypertension is the most common cause of correctable secondary hypertension.
Coarctation of the aorta (choice A) is a major cause of hypertension in young children. It is characterized by diminished peripheral pulses, particularly in the lower extremities. The hypertension is often limited to the upper extremities, as the narrowing usually occurs distal to the origin of the subclavian arteries.
Cushing syndrome (choice B) can cause hypertension, but one should find other suggestive findings on physical examination, including central obesity, moon facies, dorsal hump, purple striae, and ecchymoses.
Pheochromocytoma (choice C) can also cause secondary hypertension, but patients have paroxysms of blood pressure elevation, which correlate with symptomatic episodes of sweating and palpitations.
Thyrotoxicosis (choice E) can also cause secondary hypertension, but one should expect to find other symptoms of hyperthyroidism such as restlessness, tremor, heat intolerance, hyperdefecation, weight loss in spite of increased appetite, and menstrual abnormalities in females.


A2
The correct answer is C. In renovascular hypertension, there is decreased perfusion of the renal tissue, which activates the renin-angiotensin system. This, in turn, stimulates the oversecretion of aldosterone, which acts on the distal convoluted tubule to enhance sodium reabsorption in exchange for potassium excretion.
Alkalosis, rather than acidosis (choice A), is associated with hypokalemia.
Gastrointestinal wasting (choice B) can cause hypokalemia but there is no indication of diarrhea or vomiting in this patient.
Inadequate nutritional intake (choice D) can also cause hypokalemia, but this patient gives no history of poor nutrition.
Thyrotoxicosis (choice E) can cause hyperdefecation resulting in diarrhea, which could cause hypokalemia, but this patient does not have signs or symptoms suggestive of thyrotoxicosis.


A3
The correct answer is E. Atenolol is a selective beta-1 receptor blocker. It acts to decrease cardiac output, decrease heart rate, and decrease contractility, thus decreasing blood pressure. Metoprolol and esmolol are also selective beta-1 receptor blockers.
Alpha-1 receptor blockers (choice A), such as terazosin and doxazosin, are used in the treatment of hypertension and benign prostatic hypertrophy.
Alpha-2 receptor stimulation (choice B) is a mechanism of action used by clonidine. It is a centrally acting antihypertensive agent that lowers blood pressure and heart rate.
Calcium channel blockade (choice C) in vascular smooth muscle causes vasodilation, and in the heart, causes a decrease in contractility. Examples of calcium channel blockers include nifedipine, verapamil, and diltiazem.
Nonselective beta blockers (choice D) block beta-2 receptors in addition to beta-1 receptors. Examples of nonselective beta-blockers include propranolol, timolol, pindolol, and labetalol.


A4
The correct answer is A. Bilateral arteriography with renal vein and systemic renin measurements is the most definitive diagnostic procedure for the diagnosis of renal artery stenosis. Arteriography can demonstrate renal artery stenosis and comparison of renin levels help confirm the diagnosis.
Renal biopsy (choice B) would be done if renal parenchymal disease such as glomerulonephritis were suspected. In renovascular hypertension, the pathology occurs in the renal artery and/or one of its major branches.
Thyroid function studies (choice C) would be helpful if this patient had signs and symptoms suggestive of thyrotoxicosis.
Twenty-four hour urine evaluation for creatinine clearance (choice D) would estimate the glomerular filtration rate in this patient, but it would not be helpful in suggesting a possible cause of the hypertension.
Urine catecholamine levels (choice E) would be helpful if this patient were suspected of having a pheochromocytoma.


A5
The correct answer is C. Fibromuscular dysplasia is an intrinsic structural abnormality of the arterial wall. It generally occurs in young women. When it occurs in the renal vein and/or one of its major branches, it causes renal artery stenosis. The renal artery stenosis activates the renin-angiotensin system, causing an increase in aldosterone secretion and hypertension.
Adrenocortical adenoma (choice A) is an aldosterone-secreting tumor of the adrenal gland. Hyperplasia of the zona glomerulosa of the adrenal gland (choice D) also results in increased secretion of aldosterone. They both cause a primary hyperaldosteronism and hypertension, but are both associated with low renin levels. Patients with renovascular hypertension have increased release of renin, which causes secondary hyperaldosteronism.
Atrophic thyroid follicles with dense, focal lymphocytic infiltration (choice B) are seen in Hashimoto thyroiditis.
Psammoma bodies (choice E) are seen in papillary carcinoma, a malignant tumor of the thyroid gland.

Hypertension Case 3

Hypertension Case 3

A 34-year-old man undergoing a routine physical examination is found to have a blood pressure of 165/105 mm Hg. The measurement is repeated 40 minutes later, and is 162/103 mm Hg. The physician asks the patient to return the next week and the week following, and each
time repeats the evaluation yielding the following results: 170/102, 168/107, 175/108, 167/102 mm Hg.

Q 1
This patient's blood pressure should be classified as which of the following?
/ A. Optimal
/ B. Normal
/ C. High-normal
/ D. Stage 1 (mild) hypertension
/ E. Stage 2 (moderate) hypertension
/ F. Stage 3 (severe) hypertension

Q 2
How many Americans over the age of 5 have high blood pressure?
/ A. 50 thousand
/ B. 500 thousand
/ C. 5 million
/ D. 50 million
/ E. 150 million

Q 3
What percentage of these patients have essential hypertension?
/ A. Less than 5%
/ B. 10-15%
/ C. 40-50%
/ D. 70-80%
/ E. 90-95%


Q4
Years of untreated hypertension would be most likely to cause which of the following cardiac changes?
/ A. Large vegetations on cardiac valves
/ B. Left ventricular hypertrophy
/ C. Patent foramen ovale
/ D. Pericarditis
/ E. Pulmonary stenosis


Q 5
Patients with hypertension would be most likely to have which of the following findings on renal biopsy?
/ A. Crescent formation
/ B. Hyaline arteriosclerosis
/ C. KimmelstieI-Wilson nodules
/ D. Papillary necrosis
/ E. Subepithelial electron-dense humps


Q 6
Examination of the eye of a patient with long-standing hypertension shows "cotton wool spots." These are due to which of the following?
/ A. Crystal deposition in the lens
/ B. Hemorrhage in the lens
/ C. Hemorrhage in the retina
/ D. Ischemia of the lens
/ E. Ischemia of the retina


Q 7
The medical therapy of hypertension offers innumerable choices but, in this case, the decision was made to treat the patient with an ACE inhibitor. Which of the following drugs belongs to this class?
/ A. Atenolol
/ B. Diltiazem
/ C. Enalapril
/ D. Hydrochlorothiazide
/ E. Losartan


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Hypertension Case 3 Answers

A1
The correct answer is E. This patient has moderate hypertension. It is important not to try to diagnose hypertension based on the finding of a single abnormal blood pressure result, particularly since many patients feel uncomfortable during medical examination and may have transient blood pressure elevations. One protocol commonly used is to take two or more blood pressure readings on the first examination, and then have the patient come back twice, taking two or more blood pressure readings on the subsequent examinations. The average systolic and diastolic pressures from the visits after the first one are then used to stage the degree of hypertension:
Optimal blood pressure (choice A): systolic less than 120 and diastolic less than 80.
Normal blood pressure (choice B): systolic less than 130 and diastolic less than 85.
High normal (choice C): systolic 130-139 or diastolic 85-89.
Stage 1 (mild) hypertension (choice D): systolic 140-159 or diastolic 90-99.
Stage 2 (moderate) hypertension (choice E): systolic 160-179 or diastolic 100-109.
Stage 3 (severe) hypertension (choice F): systolic more than 180 or diastolic more than 110.
If the systolic and diastolic values fall into different stages, the patient is considered to have the higher stage.


A2
The correct answer is D. 50 million Americans aged 6 and older have high blood pressure. This corresponds to one in five Americans, or one in four adults. The incidence of hypertension is highest among African Americans, but other races known to have an increased incidence of hypertension include Mexican Americans, American Indians, native Hawaiians, and some Asian Americans. It is suspected that dietary salt intake, obesity, and genetic differences all play a role in these racial differences. About 30% of people with high blood pressure know that they have it, and only about 24% of patients with high blood pressure have it controlled to pressures of less than 140/90 mm Hg (considered optimal). The remainder are either untreated or inadequately treated. The medical implications of this are obvious.


A3
The correct answer is E. Major risk factors for essential hypertension (cause is unknown) include diabetes mellitus, family history of hypertension or cardiovascular disease, high cholesterol, obesity, smoking, high salt diet, alcohol use, and stress. Additionally, older individuals, African Americans, and males are at increased risk. Nonetheless, in 90-95% of individuals with hypertension, the cause is never identified, and the individual is considered to have essential or primary hypertension. This means that, in practice, although physicians should always keep in mind the possibility of other, specific causes of hypertension (e.g., renal artery stenosis, pheochromocytoma, other endocrine disease, coarctation of the aorta), these other conditions will not usually be found.


A4
The correct answer is B. High blood pressure directly killed 43,000 Americans, and contributed to the deaths of 227,000 additional Americans. Direct deaths are due to processes like stroke, ruptured berry aneurysm, and ruptured aortic aneurysm. Many of the indirect deaths are related to the vascular damage that high blood pressure causes. High blood pressure is a major contributor to the formation of atherosclerotic plaques, and has a much more than additive effect when added to other atherosclerotic risk factors, such as obesity and diabetes mellitus. In addition to the large vessel damage, small arterioles can also be damaged, which are most apparent in the kidney and eye. The cardiac complication of hypertension that you are most likely to be asked about on a USMLE examination is left ventricular hypertrophy. This occurs in 15 to 20% of patients with hypertension, apparently as a result of the response to the various stimuli that accompany blood pressure elevation. The left ventricular hypertrophy may be either concentric (involving the entire chamber) or eccentric (involving localized sites, often including the septum). Concentric hypertrophy is thought to be an indicator of poor prognosis, and may lead to the development of first diastolic, and then later systolic dysfunction of the cardiac muscle. In addition to the left ventricular hypertrophy, other changes have been associated with hypertension, including left atrial abnormalities, aortic insufficiency, heart failure, myocardial ischemia, and cardiac arrhythmias.
Large vegetations on cardiac valves (choice A) suggests endocarditis.
Patent foramen ovale (choice C) is a congenital lesion.
Pericarditis (choice D) can be due to infection, uremia, and inflammatory disorders.
Pulmonary stenosis (choice E) is usually congenital in origin.

A5
The correct answer is B. Hyaline arteriosclerosis is the characteristic lesion seen on biopsy in patients with essential hypertension. This lesion is associated with thickening of the wall (due to deposition of serum components) and narrowing of the lumen of the afferent arterioles that enter the glomerulus. The lesion may be associated with a secondary obsolescence of the glomeruli.
Crescent formation (choice A) is seen in rapidly progressive glomerulonephritis.
Kimmelstiel-Wilson nodules (choice C) are a feature of diabetic glomeruli.
Papillary necrosis (choice D) can be seen in analgesic abuse, diabetes mellitus, pyelonephritis, sickle cell disease, and urinary tract obstruction.
Subepithelial electron-dense humps (choice E) are a feature of post-infection glomerulonephritis.


A6
The correct answer is E. Early changes seen on ocular examination of hypertensive individuals can include narrowing of arteries and arteriovenous junction changes. Late changes seen can include deposits of lipids in the eye, cotton wool spots, bleeding in the eye (which may cause retinal detachment), venous occlusion (which may cause transient or permanent loss of vision), and new vessel growth. The cotton wool spots are actually small areas of transient retinal ischemia, and usually resolve within days. Cotton wool spots are also commonly seen in diabetics and HIV patients.
Crystal deposition in the lens (choice A) produces a cataract.
Choices B and D are distracters.
Hemorrhage in the retina (choice C) can produce "flame lesions" and retinal detachment.


A7
The correct answer is C. Life style modifications (decreased salt intake, weight reduction, more exercise) offer some help in reducing blood pressure, but most patients with high blood pressure eventually require medications. We now have an enormous array of medications that can be used in the treatment of hypertension. This is good for the patients, because it means that it is almost always possible to find (with enough time) some effective medication that a particular patient can tolerate. In actual practice, most physicians develop a few favorite drugs with which they often start patients, and then modify the medications based on blood pressure response, patient complaints, and coexisting diseases. Classes of hypertensive medications include diuretics, beta-blockers, long-acting Ca++ blockers, ACE-inhibitors, angiotensin II receptor blockers, and alpha-adrenergic blockers. Examples of ACE-inhibitors include captopril, benazepril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, and trandolapril. These agents act by disrupting the renin-angiotensin system by blocking angiotensin converting enzyme.
Atenolol (choice A) is a beta-1 blocker and has direct effects on blood vessels and cardiac function.
Diltiazem (choice B) is a calcium channel blocker, which partially inhibits smooth and cardiac muscle function.
Hydrochlorothiazide (choice D) is a diuretic and acts by decreasing the volume of blood in the vascular space.
Losartan (choice E) is an angiotensin II receptor blocker, and disrupts the renin-angiotensin system by blocking the actions of angiotensin II. Some patients who have trouble tolerating ACE inhibitors do well with angiotensin II receptor blockers.

Hypertension Case 2

Hypertension Case 2

A 41-year-old woman comes to the physician's office complaining of fatigue, muscle weakness, cramping, headaches, polydipsia, and
polyuria. She has been treated for hypertension for 6 years, and her doctors have told her that she has renal problems. Beta-blockers, calcium channel blockers, and diuretics have been used to control her hypertension. There is a family history of renal disease and hypertension. Her blood pressure is 240/140 mm Hg and her pulse is 85/min. The remainder of her examination is normaI. A routine chemical panel shows hypokalemia, hypernatremia, and metabolic alkalosis.


Q1
Pathologic examination of this patient would most likely reveal which of the following findings?
/ A. Adrenal adenoma
/ B. Adrenal carcinoma
/ C. Bilateral nodular hyperplasia
/ D. Multiple adrenal adenomas
/ E. Unilateral nodular adrenal hyperplasia


Q2
This patient is found to have an excessive amount of an adrenal hormone in her plasma. Which of the following factors is a major regulator of
the synthesis of this hormone?
/ A. ACTH
/ B. Atrial natriuretic peptide
/ C. Dopamine
/ D. Renin-angiotensin system
/ E. Sodium


Q3
Spironolactone is used in the treatment of patients with this disease. Which of the following is the most important adverse reaction of
spironolactone therapy?
/ A. Anti-androgen
/ B. Cardiac arrhythmia
/ C. Dehydration
/ D. Hyperkalemia
/ E. Skin reaction


Q4
The serum potassium level in this patient is found to be 2.5 mEq/L. Which of the following EKG changes would most likely be expected?
/ A. Prolonged QT interval
/ B. Prominent U waves, flattened T waves
/ C. Shortened QT interval
/ D. ST segment elevation, convex upwards
/ E. TalI, peaked T waves


Q5
The mineralocorticoid receptor (MR) displays the same affinity for glucocorticoid hormones as it does for the hormone that is in excess in this patient. The sensitivity of the MR to this hormone depends on which of the following enzymes?
/ A. AIdosterone synthase
/ B. C17,20-Iyase
/ C. 11-beta hydroxysteroid dehydrogenase type 2 (HSD2)
/ D. Na+/K+-ATPase
/ E. 17-alpha hydroxylase


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Hypertension Case 2 Answers

A1
The correct answer is A. 50% of patients with Conn syndrome present with a solitary adenoma of the adrenal cortex zona glomerulosa, which secretes aldosterone (aldosteronoma). Aldosterone-secreting adenomas are usually less than 2 cm in diameter with a bright yellow appearance. 60% of these lesions are found in the left adrenal gland. Histologically, these tumors are composed of lipid-laden zona glomerulosa cells in cords, although compact cells can also be seen. The unaffected cortex is not atrophic, since aldosterone does not feedback on the production of ACTH.
Rarely, aldosterone can be secreted by adrenocortical carcinoma (choice B).
Approximately 40% of patients with Conn syndrome have bilateral hyperplasia (choice C) of the zona glomerulosa. The hyperplasia may be micronodular, macronodular, or a mixture of both.
10% of the patients have multiple benign tumors (choice D), with the same appearance as a solitary adenoma.
A few patients have unilateral nodular adrenal hyperplasia (choice E) that is similar in function to adenoma.

A2
The correct answer is D. The major factors stimulating aldosterone production and release by the zona glomerulosa are angiotensin II and the serum potassium concentration. Angiotensinogen, the precursor of angiotensin peptides, is synthesized by the liver. In the circulation, renin, secreted by juxtaglomerular cells, cleaves four amino acids from angiotensinogen, forming the decapeptide angiotensin I (AI). AI is cleaved by angiotensin-converting enzyme (ACE) to form an octapeptide, angiotensin II (AII). In the zona glomerulosa of the adrenal cortex, AII stimulates the production of aldosterone. The mechanism of AII action involves an increase in activity of aldosterone synthase, the key enzyme in the biosynthesis of aldosterone. AII is the principal stimulator of aldosterone production when intravascular volume is reduced. Also found in the circulation, the des-ASP heptapeptide (angiotensin III) is as active as angiotensin II in stimulating aldosterone release but has much less pressor activity. Potassium is also a major physiologic regulator of aldosterone secretion; hyperkalemia also increases the activity of aldosterone synthase. The mechanism of potassium effect may involve depolarization and activation of voltage-gated calcium channels. AII produces quantitatively the most significant increase in aldosterone production, but the hormone secretion is most sensitive to small changes in serum potassium ion concentrations.
ACTH (choice A) stimulates aldosterone secretion, but does not appear to play a significant role in the physiological regulation of mineralocorticoid homeostasis.
Atrial natriuretic peptide (choice B) antagonizes the AII-stimulated release of aldosterone.
Dopamine (choice C), acting locally as a paracrine agent, inhibits secretion of aldosterone.
The extent of sodium (choice E) reduction that is necessary to alter aldosterone secretion is rarely seen in pathologic, let alone physiologic situations.

A3
The corrects answer is A. Spironolactone is a competitive antagonist of the aldosterone receptor. Hypokalemia and hypertension in patients with primary aldosteronism can be controlled by spironolactone, 50-100 mg/d. Although spironolactone is an effective aldosterone receptor antagonist, it is not without side effects that can limit its use in the chronic treatment of this disease. The most important are anti-androgenic reactions. Spironolactone acts as an anti-androgen by decreasing the production of testosterone by the adrenal gland and by preventing DHT (dihydrotestosterone) from binding to its androgen receptor. As a result of this, in the long run, gynecomastia occurs in more than 10% of the treated men. Impotence, loss of libido, and menstrual irregularities are also common side effects of spironolactone therapy. On the other side, these spironolactone features are the basis for its usage in the treatment of hirsutism, acne, and alopecia. Spironolactone is also used by transsexuals in the feminizing regimen because of its anti-androgenic actions. Eplerenone is a new aldosterone antagonist that may overcome the limitations of spironolactone.
Cardiac arrhythmia (choice B) is not a frequent adverse reaction to spironolactone treatment, and it is seen only in the presence of significant hyperkalemia.
Dehydration (choice C) is usually very mild, and can be prevented with adequate water intake.
Hyperkalemia (choice D) develops in 5-10% of treated patients, especially if renal function is compromised, or the patient is diabetic, or elderly.
Skin reactions (choice E), mostly urticaria, are rare side effects of spironolactone therapy.

A4
The correct answer is B. In hypokalemia, the triad of prominent U waves, low amplitude T waves, and ST segment depression is a typical finding. High-amplitude positive U waves are the usual EKG features that can be expected in this patient. The origin of the U wave is still unclear, although most authors correlate the U wave with the phenomenon of after depolarizations in the ventricles. U waves become as tall as T waves at a serum level of about 3.0 mEq/L, and at about 2.0 mEq/L, become taller than T waves. T waves begin to flatten at a serum potassium level of about 3.0 mEq/L, and eventually may either fuse with the U waves or become inverted. Ventricular arrhythmias may occur with hypokalemia in the presence of digitalis.
The EKG in hypocalcemia typically shows prolongation of the QT interval (choice A). T wave peaking or inversion can also be seen.
Shortening of the QT interval (choice C) is seen in patients with hypercalcemia.
ST segment elevation, convex upwards (choice D) is pathognomonic for acute myocardial infarction.
A hyperkalemic state is characterized primarily by tall, peaked T waves (choice E). There may be also wide, flat P waves, lowering of the R wave, and increased depth of the S wave.

A5
The correct answer is C. Mineralocorticoid receptors (MR) are members of a superfamily of steroid/thyroid/retinoid/orphan (STRO) receptors. MR are intracellular and act as ligand-activated transcription factors to regulate gene expression. The human MR is a 984 amino acid protein, and the cDNA has been cloned and sequenced. The MR shows the same affinity for aldosterone and glucocorticoids. Since the plasma concentration of cortisol is much higher than that of aldosterone, a mechanism is necessary to protect MRs from constant occupancy by glucocorticoid hormones. This mechanism depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), which converts cortisol (and corticosterone) into 11-dehydro metabolites in the endoplasmic reticulum. These are not ligands for MR. This permits the MR to be occupied by aldosterone as a function of its serum levels. In the absence of, or inhibition of HSD2, the MR will be occupied by glucocorticoids, and a permanent Na+ reabsorption will occur. This concept can be seen at work in patients with excessive ingestion of licorice. Glycyrrhizic acid, an active hypertensive component in licorice, and its derivative 18-beta-glycyrrhetinic acid, inhibit HSD2 activity. Cortisol activation of MR induces sodium retention, potassium excretion, and hydrogen ion excretion in the kidney, mimicking the symptoms of aldosteronism: hypertension, hypokalemia, and metabolic alkalosis.
Aldosterone synthase (choice A) converts a CH3 group at C18 of the steroid molecule to an aldehyde group, from whence comes the name aldosterone. This enzyme is expressed exclusively in zona glomerulosa of adrenal cortex. Aldosterone synthase is encoded by the gene CYP11B2 and has 11-beta-hydroxylase, 18-hydroxylase, and 18-hydroxy-dehydrogenase activity.
Activity of C17,20-lyase (choice B) is responsible for producing the androgens, dehydroepiandrosterone (DHEA) and androstenedione.
Na+/K+-ATPase (choice D) is located in basolateral membranes of the distal tubular cells and generates the electrochemical gradient that drives diffusion through the sodium and potassium channels. Aldosterone stimulates gene expression of mRNA for this enzyme.
The synthesis of cortisol requires 17-alpha hydroxylation of pregnenolone by 17-alpha hydroxylase (choice E), which is expressed only in the zona fasciculata.

Hypertension Case 1

Hypertension Case 1

A 35-year-old man has hypertension, which has been difficult to control with medication. Periodically, he experiences periods when he develops intense symptoms including racing heart, Iightheadedness, flushing, diaphoresis, clammy skin, headache, and a sense of impending
doom. He has gone to the emergency department of a local hospital several times during these episodes, but by the time he is seen several
hours later, the symptoms have long passed, and nothing can be found on physical examination or serum chemistry studies.

Q1
The patient's physician orders a 24-hour urine to be collected, which is found to contain significantly elevated levels of vanillylmandelic acid.
This compound is a degradation product of which of the following?
/ A. Acetylcholine
/ B. Cholesterol
/ C. Epinephrine
/ D. Serotonin
/ E. Testosterone


Q2
Which of the following is the most likely diagnosis?
/ A. Leiomyosarcoma
/ B. Lymphoma
/ C. Neuroblastoma
/ D. Pheochromocytoma
/ E. Small cell carcinoma


Q3
The tumors producing this patient's symptoms are usually found in which of the following sites?
/ A. Adrenal gland
/ B. Pancreas
/ C. Salivary gland
/ D. Thymus
/ E. Thyroid gland


Q4
Roughly what percentage of this patient's tumor type behave in a malignant fashion?
/ A. 5-10%
/ B. 20-30%
/ C. 50-60%
/ D. 70-80%
/ E. 90-95%


Q5
This patient's lesion has been associated with which of the following thyroid disorders?
/ A. Follicular carcinoma
/ B. Graves disease
/ C. Hashimoto disease
/ D. Medullary carcinoma
/ E. Papillary carcinoma


Q6
This patient is scheduled for surgical removal of the tumor. Which of the following agents should be administered before the surgery?
/ A. Iodide
/ B. Lorazepam
/ C. Phenoxybenzamine
/ D. Propylthiouracil
/ E. Spironolactone


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Hypertension Case 1 Answers

A1
The correct answer is C. Vanillylmandelic acid (VMA) is a degradation product of both epinephrine and norepinephrine. It is secreted into the urine, and 24 hour screening for this metabolite (often along with the dopamine degradation product homovanillic acid, HVA) is used to look for excessive catecholamine secretion. The half-lives of epinephrine, norepinephrine, and dopamine are all very short and consequently direct measurement in serum of these species only provides a clinical answer if a patient is having a hypertensive paroxysm at the time. Two enzymes in these degradative pathways of which you should be aware are catechol-O-methyl transferase (COMT: adds methyl groups to hydroxyl moieties) and monamine oxidase (MAO: removes amino groups, oxidizing the nearby carbon to an aldehyde).
Acetylcholine (choice A) is usually not measured in the clinical laboratory.
Cholesterol (choice B) is measured in serum, and is unrelated to this patient's disease.
Serotonin (choice D) is produced by carcinoid tumors, and can be measured directly in serum, or its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), can be measured in urine.
Testosterone (choice E) can be measured directly in serum, and its precursors and metabolites (including DHT, androstenedione, 3-alpha-androstenediol glucuronide, DHEA) can also be measured in serum.


A2
The correct answer is D. This patient most likely has a pheochromocytoma. Pheochromocytoma is a rare tumor that is often suspected and seldom found. (Its incidence on the USMLE is very much higher than its incidence in general practice.) The tumors can secrete catecholamines such as epinephrine, norepinephrine, and/or dopamine, and the urinary determination of metabolites (see previous question) is the most reliable method of specifically suggesting the diagnosis. The vast majority of patients with pheochromocytoma have either paroxysmal or persistent hypertension. Patients who have a strong paroxysmal character to the secretion may have episodes similar to those described in the question stem. Neuroblastoma (choice C) can also secrete catecholamines, but is a tumor of childhood.
Lymphomas (choice B) and leiomyosarcomas (choice A, malignant tumor of smooth muscle) do not secrete catecholamines.
Small cell carcinoma (choice E) is known for the large number of paraneoplastic syndromes it can produce, but does not usually secrete catecholamines and would be very unusual in a man this young


A3
The correct answer is A. Approximately 80% of pheochromocytomas are found in the adrenal medulla, with the remainder being found in a wide variety of other tissues derived from neural crest cells, including, among others, the paraganglia of the sympathetic chain, along the aorta, in the carotid body, in the genital urinary tract, and in the brain. The other sites listed in the choices are not particularly prone to develop pheochromocytoma.


A4
The correct answer is A. 5-10% of pheochromocytomas overall are malignant; the proportion of malignant cases is higher (30%) in the extra-adrenal pheochromocytomas. 10% (20% in children) of the adrenal tumors are bilateral. Pheochromocytomas typically weigh 50-200 grams (uncommonly up to several kilograms) and are composed of nests of chromaffin cells that often appear cytologically bizarre, even when the tumors do not metastasize. Surgical resection is the preferred treatment modality; alpha and beta blockers are used to block the effects of the excess catecholamines prior to and during surgery.


A5
The correct answer is D. Both pheochromocytoma and medullary carcinoma of the thyroid can occur as part of familial multiple endocrine neoplasia, types IIA (Sipple syndrome) and IIb (mucosal neuronal syndrome). The medullary carcinoma is derived from the parafollicular C cells that secrete calcitonin, rather than thyroxine. Pheochromocytoma also has associations with neurofibromatosis and von Hippel-Lindau syndrome.
Follicular carcinoma (choice A) and papillary carcinoma (choice E) of the thyroid are cancers of the thyroid follicular epithelium, and are not associated with pheochromocytoma.
Graves disease (choice B) and Hashimoto disease (choice C) are both autoimmune thyroid disorders with no association with pheochromocytoma.

A6
The correct answer is C. Phenoxybenzamine, a nonselective alpha-blocking agent related to the nitrogen mustards, is indicated for the treatment of pheochromocytoma. It binds covalently to both alpha-1 and alpha-2-adrenergic receptors. After this medication is injected, a few hours must elapse before actual blockade occurs. By blocking alpha-receptors, phenoxybenzamine prevents the constriction of peripheral blood vessels, producing a reflex tachycardia. The desired action in patients with pheochromocytoma is related to the "epinephrine reversal," seen in classic drug traces. In epinephrine reversal, unopposed epinephrine increases blood pressure. After administration of an alpha antagonist (e.g., phenoxybenzamine, phentolamine), subsequent epinephrine administration decreases blood pressure because of unopposed beta stimulation.
Iodide (choice A) inhibits the release and the biosynthesis of T4 and T3. Iodide decreases the size and vascularity of the thyroid gland, hence makes it the preoperative treatment of choice for Graves disease.
Benzodiazepines, such as lorazepam (choice B), potentiate the effects of gamma-aminobutyrate (GABA), and are used for sedation, hypnosis, muscle relaxation, and anxiolysis. Although these agents may help to calm the patient, they would not ameliorate the patient's condition.
Propylthiouracil (choice D) inhibits the synthesis of the thyroid hormones. This agent does not inactivate existing T4 and T3; however, it is able to inhibit the peripheral conversion of T4 to T3. It is indicated for long-term hyperthyroid therapy, which may lead to disease remission, as well as short-term treatment before thyroidectomy or radioactive iodine therapy.
Spironolactone (choice E) is indicated for the treatment of edematous states as well as the prophylaxis and treatment of hypokalemia. It is commonly combined with other non-potassium sparing diuretics to prevent the appearance of hypokalemia.

Palpitation case 4

Palpitation case 4

A 55-year-old man with a 30-year history of alcohol abuse is brought into the emergency department with palpitations and chest discomfort. His temperature is 37.1 C (98.8 F), blood pressure is 98/56 mm Hg, pulse is 130/min, and respirations are 26/min. Cardiac examination reveals tachycardia with a regular rhythm. An electrocardiogram reveals wide, monomorphic QRS complexes and P waves occurring independently of the QRS complexes.

Q1

What general classification of arrhythmia does this patient have?
/ A. Atrial fibrillation
/ B. Atrial flutter
/ C. Ventricular arrhythmia
/ D. 1st degree atrioventricular block
/ E. 2nd degree atrioventricular block

Q2

Which of the following is the actual cardiac rhythm?
/ A. Multifocal atrial tachycardia
/ B. Normal sinus rhythm
/ C. Sinus tachycardia
/ D. Ventricular fibrillation
/ E. Ventricular tachycardia

Q3

After cardioversion, the patient is treated with esmoloI. Which of the following is the mechanism of action of esmoloI?
/ A. Calcium channel blockade
/ B. CIass 1B sodium channel blockade
/ C. Nonselective beta receptor blockade
/ D. Potassium channel blockade
/ E. Selective beta-1 receptor blockade

Q4

The physician also starts the patient on bumetanide. Which of the following is bumetanide's mechanism of action?
/ A. Angiotensin converting enzyme inhibitor
/ B. Carbonic anhydrase inhibitor
/ C. Loop diuretic
/ D. Potassium sparing diuretic
/ E. Thiazide diuretic

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Palpitation case 4 answers

A1
The correct answer is C. Ventricular arrhythmias occur when the electrical impulse is generated in the ventricles. The presence of dissociative P waves also indicates that the impulse is originating in the ventricles. Because the conduction of the impulse polarizes the ventricles at different times, the QRS complex is seen as widened on the electrocardiogram.
Atrial fibrillation (choice A) is characterized by irregularly irregular QRS complexes. Furthermore, there is an irregular undulation of the baseline and an absence of P waves, which would indicate that the atria are not contracting in an organized manner.
Atrial flutter (choice B) is characterized by a rapid atrial rate between 240 to 400 beats per minute. It is often seen as a sawtooth pattern of F waves on the electrocardiogram. Because of the refractoriness of the atrioventricular node, the flutter waves are not generally all transmitted through to the ventricles. The conduction of these waves can vary from 2:1 conduction or higher.
Atrioventricular block refers to an abnormality in the electrical conduction between the atria and the ventricles. The degree of the block refers to the severity of the conduction. In 1st degree atrioventricular block (choice D), all electrical impulses are conducted with a delay. In 2nd degree atrioventricular block (choice E), only some of the impulses are conducted, and if they are conducted, they can be conducted with a delay.


A2

The correct answer is E. Ventricular tachycardia is usually a result of a reentrant pathway in the cardiac conduction system. It is defined as at least 3 consecutive QRS complexes originating from the ventricles and occurring at a rapid rate (over 100 beats per minute).
Multifocal atrial tachycardia (choice A) is an atrial arrhythmia characterized by different P wave shapes with varying PR intervals. It is associated with severe underlying lung disease.
Normal sinus rhythm (choice B) is a normal rhythm. It is produced by electrical impulses formed in the sinoatrial node. In the electrocardiogram, these impulses are seen as P waves followed by narrow QRS complexes. In ventricular tachycardia, the P waves are dissociated from the QRS complex.
Sinus tachycardia (choice C) is a rapid sinus rate of greater than 100 beats per minute. A QRS complex also follows each P wave. It is generally a cardiac response to pain, fever, infection, vigorous exercise, shock, dehydration, anxiety, heart failure, or anemia.
Ventricular fibrillation (choice D) occurs when the ventricles contract in an unorganized manner. There are no clearly formed QRS complexes or T waves. The patient is in cardiac arrest and does not have a pulse.


A3

The correct answer is E. Esmolol selectively antagonizes beta-1 receptors. Other selective beta-1 receptor blockers include metoprolol and atenolol. Nonselective beta receptor blockers (choice C) include propanolol, timolol, labetalol, and nadolol. Nonselective beta receptor blockers block beta-1 and beta-2 receptors relatively equally.
Calcium channel blockers (choice A) include verapamil, diltiazem, and bepridil. They decrease conduction velocity and increase the PR interval. They are used in the prevention of nodal arrhythmias.
Class 1B sodium channel blockers (choice B) include lidocaine, mexiletine, and tocainide. They act to depress the action potential and stabilize the cell membrane. They are used in acute ventricular arrhythmias and digitalis-induced arrhythmias.
Potassium channel blockers (choice D) act to prolong the action potential in phase 3. They include amiodarone, bretylium, and sotalol.


A4

The correct answer is C. Bumetanide is a loop diuretic. It inhibits the sodium, potassium, chloride cotransporter in the thick ascending limb of the loop of Henle.
Angiotensin converting enzyme inhibitors (choice A) include benazepril, captopril, fosinopril, and lisinopril. They interfere with the conversion of angiotensin I to angiotensin II.
Carbonic anhydrase inhibitors (choice B), such as acetazolamide, act in the proximal convoluted tubule. They cause a self-limited sodium bicarbonate diuresis. They are used to alkalinize the urine, and for the treatment of metabolic alkalosis and glaucoma.
Potassium-sparing diuretics (choice D) such as spironolactone, triamterene, and amiloride inhibit the action of aldosterone. They are used in the treatment of hyperaldosteronism and potassium depletion.
Thiazide diuretics (choice E), such as hydrochlorothiazide, inhibit sodium chloride reabsorption in the early distal tubule. They are used in the treatment of hypertension, congestive heart failure, and to inhibit renal calcium stone formation.

Palpitation case 3

Palpitation case 3

A 23-year-old college senior with type 1 diabetes was preparing for an 11 a.m. examination. He had taken insulin that morning, but was very nervous about the test and forgot if he had eaten anything for breakfast. With time, he felt his heart pounding, his palms were sweaty, his hands were shaking, and he felt dizzy. He wanted to take a sugar tablet, but at that moment, his friend arrived and they rushed to school. In the car, he developed a headache and difficulties concentrating on the conversation, but he thought all of these symptoms were the result of the nervousness caused by the approaching exam. He was confused, the speech became slurred, and finally he lost consciousness. His friend brought him to the emergency department. On site, his blood glucose level was 40 mg/dL. After medical intervention, he successfully recovered without sequelae.

Q1

Administration of which of the following pancreatic hormones would be expected to help this patient?
/ A. Amylin
/ B. GIucagon
/ C. Insulin
/ D. Pancreatic polypeptide
/ E. Somatostatin

Q2

Beta-receptor antagonists prevent many of the premonitory signs of this condition, which are caused by an epinephrine response. Which of the following signs will still be present despite beta blockade?
/ A. BIurred vision
/ B. Palpitations
/ C. Sweating
/ D. Tachycardia
/ E. Trembling

Q3

Which additional action occurs as a result of this epinephrine response?
/ A. Inhibition of glucose uptake
/ B. Stimulation of gluconeogenesis
/ C. Stimulation of glucose uptake
/ D. Stimulation of glycogenolysis
/ E. Stimulation of glycogen synthesis

Q4

After he is successfully treated and released from the hospitaI, which of the following compounds will be the major substrate for his brain metabolism?
/ A. Fatty acids
/ B. GIucose
/ C. Ketone bodies
/ D. Mannose
/ E. Triacylglycerols

A5

If this patient's symptoms were due to ingestion of a drug, which of the following agents would he have most likely ingested?
/ A. CIozapine
/ B. Diazoxide
/ C. GIucocorticoids
/ D. Pentamidine
/ E. Thiazide diuretic

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Palpitation case 3 answers

A1
The correct answer is B. Glucagon is a single-chain peptide of 29 amino acids, produced by alpha cells of the endocrine pancreas, and is structurally related to the secretin family of peptide hormones. Glucagon is synthesized as proglucagon and processed to give glucagon within the pancreatic islets. Within the intestinal tract, proglucagon is processed to a family of glucagon-like peptides. The major effect of glucagon is to stimulate an increase in glucose concentrations. The mechanism involves stimulation of hepatic glycogenolysis and hepatic gluconeogenesis, and inhibition of glycogen synthesis. In the liver, glucagon also activates the transport of long-chain free fatty acids into mitochondria for oxidation and ketogenesis. It appears to have a minor effect of stimulating lipolysis in adipose tissue, thereby providing fatty acid fuels to most cells and conserving blood glucose. The molecular mechanism of glucagon action involves activation of adenylate cyclase via Gs and an increase in cAMP, which induces gene expression of PEPCK (phosphoenolpyruvate carboxykinase), a key gluconeogenic enzyme. On the other hand, cAMP-activated PKA (protein kinase A) activates phosphorylase and inactivates glycogen synthase in the liver. Glucagon is used to treat severe hypoglycemic episodes when oral glucose is inadequate, and IV glucose is not available (emergencies away from medical settings). The usual dose of glucagon in adults is 0.5 to 1.0 U given SC, IM. or IV.
Amylin (choice A) is a beta cell hormone that is colocalized and cosecreted with insulin. It appears to work in concert with insulin to regulate glycemia, suppressing the postprandial secretion of glucagon and slowing the rate of gastric emptying.
Insulin (choice C) is the only hormone that causes hypoglycemia.
F or D1 cells produce pancreatic polypeptide (choice D). The function of this hormone is still uncertain, but it is suggested that it may influence gastrointestinal function and promote intraislet homeostasis.
D cells produce somatostatin (choice E), which inhibits insulin and glucagon secretion locally (paracrine effect) within the pancreatic islets.


A2
The correct answer is C. Beta receptor blockade prevents the warning signs of hypoglycemia caused by epinephrine release. However, sweating will still occur despite the beta blockade. Human skin contains two types of sweat glands: eccrine (merocrine) and apocrine sweat glands. Eccrine sweat glands are the predominant type. They are found all over the body, particularly on the palms of the hands, soles of the feet and forehead. Apocrine glands are located in the perigenital area, and in the axilla. They produce a viscous, more protein-rich secretion than eccrine glands, and are innervated by the sympathetic adrenergic nerves via alpha1 receptors. Eccrine sweat glands are activated by sympathetic cholinergic nerves (muscarinic M3 receptors). Therefore, hypoglycemic sweating will still be evident in the presence of beta-adrenergic blockade.
Beta2-mediated epinephrine responses an cause relaxation of the ciliary muscle and consequent blurred vision (choice A).
Palpitations (choice B) are unpleasant sensations of irregular/and or forceful beating of the heart. They are elicited through activation of beta1 and beta2 receptors that result in increased automaticity (phase 4 depolarization) and conduction velocity, and via a separate set of beta2 adrenergic receptors, an increase in contractility.
Tachycardia (choice D) is a result of epinephrine-induced activation of beta1 and beta2 receptors located at the cells of the SA (sinoatrial) node.
Trembling (choice E) is mediated through beta-adrenergic receptors.


A3
The correct answer is D. Under normal conditions, increased glycogen release is the major counterregulatory response to hypoglycemia. However, in patients with diabetes mellitus, glucagon secretion in response to hypoglycemia is defective, and under these circumstances, epinephrine secretion becomes the critical counterregulatory factor. The absent glucagon response results from the loss of the intraislet insulin-inhibition of glucagon release. Stimulation of glycogenolysis in liver provides the major source for circulating glucose, because liver cells contain glucose-6-phosphatase. Epinephrine stimulates hepatic glycogenolysis via adrenergic beta2 receptors, thereby increasing the delivery of glucose to the circulation. It activates adenylate cyclase, and the increased cAMP activates protein kinase A (PKA). PKA catalyzes the phosphorylation of phosphorylase kinase to convert it from the inactive form b to the active form a. Subsequently, activated phosphorylase kinase a then catalyzes the phosphorylation of glycogen phosphorylase-b to produce an active form of the enzyme. At the same time, PKA converts glycogen synthase to the inactive form, which prevents resynthesis of glycogen. The hormone also stimulates glycogenolysis in muscle through the activation of beta2-adrenergic receptors. Because muscle lacks the enzyme glucose-6-phosphatase, the glucose-6-phosphate enters the glycolytic sequence to give pyruvate. Pyruvate is converted to lactate, and lactate produced in muscle is released to the blood stream and transported to the liver, where it is converted to glucose in the process of gluconeogenesis. The glucose is then returned to the blood and can be used as an energy source by the brain and by muscle. This cycle is termed the Cori cycle. Epinephrine also stimulates lipolysis in adipocytes through activation of alpha-adrenergic receptors, and glycerol, the product of fat tissue lipolysis, serves as an additional gluconeogenic substrate.
Cortisol inhibits glucose uptake (choice A), stimulates hepatic gluconeogenesis, stimulates protein breakdown in muscle, and stimulates lipolysis, all of which help restore the glucose level in hypoglycemia. However, the cortisol response is delayed, and less critical than the epinephrine response.
Growth hormone stimulate lipolysis in adipocytes, and gluconeogenesis (choice B) in liver, thereby acting as a second-line counterregulatory hormone.
Insulin stimulates glucose uptake into cells (choice C), which leads to hypoglycemia.
Insulin increases glucose storage as glycogen in liver. In skeletal muscle, insulin promotes glycogen synthesis (choice E) by increasing glucose transport, inducing glycogen synthase and inhibiting phosphorylase.


A4

The correct answer is B. The brain represents 2% of body weight, but receives 15% of the cardiac output, consumes 20% of the total O2, and utilizes 25% of the total glucose. Glucose is the major, and nearly the sole source of energy for the brain. Therefore, plasma glucose is normally very carefully regulated to maintain the level that ensures glucose transport into the brain at adequate rates. Insulin is not required for brain cells to utilize glucose. The carbohydrate reserves in brain tissues are extremely limited, and normal function depends upon continuous glucose supply. Under normal conditions, the brain takes three times more glucose than it needs from the circulation. At some critical glucose concentration (approx. 70 mg/dL), centers in the hypothalamus sense a fall in the blood glucose level, and the release of glucagon and epinephrine is triggered. If the blood glucose level is below 30 mg/dL, coma develops, and below 15 mg/dL, permanent brain damage and/or death ensue.
Astrocytes, a major class of glial cells in mammalian brain, play a pivotal role in the regulation of brain metabolism by providing neurons with anaplerotic metabolites and substrates for energy generation. Glucose enters the brain via an insulin-independent GLUT 1 transporter in cerebral capillaries. The entrance of glucose into the CNS from the capillaries occurs primarily into astrocytes, which metabolize glucose through the glycolytic pathway. This mechanism seems to be coupled with the transport of glutamate into astrocytes by a Na+-cotransporter, and this secondary active transport produces ADP, which serves as a major allosteric effector for glycolysis. Glycolysis produces lactate, which is taken up and metabolized by neurons, and through oxidative phosphorylation, ATP is produced. Amino acids, lipids, and proteins derived from glucose can be metabolized for energy only during certain conditions.
The blood brain barrier excludes free fatty acids (FFA) (choice A), preventing them from entering into brain metabolism.
Acetoacetate, beta-hydroxybutyrate, and acetone are known as ketone bodies (choice C). The rate of ketone transport into the brain is too slow to meet its energy requirements unless fasting ketone body plasma levels are markedly increased. But, under particular conditions, such as starvation, diabetes, or in breast-fed neonates, plasma levels of ketone bodies increase markedly, and the brain cells can switch to ketone bodies as substrates for their metabolism. Without ketone bodies, most of us would be unconscious after 48 hours of fasting.
Mannose (choice D) theoretically can substitute for glucose as an alternative substrate for brain metabolism. It crosses the blood-brain barrier and it is converted to fructose-6-phosphate, a physiological intermediate of the glycolytic pathway. However, mannose is not normally present in the blood, and cannot be considered a physiologic metabolic substrate.
Brain cells can sometimes use triacylglycerols (choice E) for energy metabolism, but the quantitative importance of this pathway is negligible.


Q5
The correct answer is D. Pentamidine is used to treat the Pneumocystis carinii pneumonia that occurs commonly in immunocompromised patients, such as cancer patients, AIDS patients, and transplant patients. Pentamidine side effects include metallic taste, coughing, bronchospasm in heavy smokers and asthmatics, decrease in urination, unusual bleeding or bruising, and hypoglycemia. Some patients may develop sudden, severe low blood pressure after receiving pentamidine. Therefore, it is recommended that the patient lie down during the administration of the medicine. This agent is also used in patients with cutaneous and visceral leishmaniasis (kala-azar) caused by Leishmania donovani, and trypanosomiasis (Trypanosoma brucei, gambiense, and rhodesiense). The drug's hypoglycemic effect is due to lytic destruction of pancreatic beta cells, causing acute hyperinsulinemia and hypoglycemia. Later on, insulinopenia and hyperglycemia may develop. IV glucose should be administered during pentamidine administration, and during the period immediately after that.
Clozapine (choice A) is a dibenzodiazepine derivative and an atypical antipsychotic. Besides well known-side effects, such as agranulocytosis, seizures, weight gain, constipation, and hypersalivation, recent studies show an association of clozapine with hyperglycemia and diabetes.
Diazoxide (choice B) opens potassium channels in vascular muscle cells, stabilizing the membrane potential and preventing smooth muscle contraction. This leads to arteriolar dilatation and reduction of mean arterial blood pressure. The use of this agent has been associated with hyperglycemia and hyperosmolar nonketotic coma. Diazoxide inhibits insulin secretion, and is used to treat hypoglycemia secondary to insulinoma.
Glucocorticoids (choice C) stimulate gluconeogenesis and decrease insulin sensitivity, which both lead to hyperglycemia.
Hyperglycemia secondary to thiazide diuretics (choice E) is thought to be related to the depletion of potassium. Thiazides may decrease insulin secretion and contribute to the development of insulin resistance. Other drugs, such as furosemide, nicotinic acid, and oral contraceptives also can induce a hyperglycemic state.