Cardiomegaly Case 3

Cardiomegaly Case 3

A 78-year-old man had been previously active, but found that his health was declining. Over a four-month period, his ability to perform even very minimal exercise, such as walking around his yard, declined precipitously. The family took him from doctor to doctor, none of whom were
initially able to figure out what was wrong with him. Because of the patient's age, most of the physicians that the family consulted were unwilling to do much other than to listen to the family's story and then run a few screening tests. In some ways, he acted as if he were in
congestive heart failure, but he initially had no evidence of fluid overload and his lungs were clear. The cardiac profile on chest X-ray was slightly enlarged. His ECG studies were interpreted as within the normal range for his age. Angiography studies showed no evidence of
significant coronary artery occlusion. Pulmonary function studies were unrevealing.

Q1
Following a Thanksgiving meal, the patient's condition worsened markedly over the next few hours, and he was taken to an emergency
department. At that point, the patient was in obvious, severe, congestive heart failure with evidence of fluid overload and pulmonary edema.
Intravenous furosemide was started, which over the next few hours markedly improved his clinical condition. Furosemide is classified as
which of the following?
/ A. Carbonic anhydrase inhibitor
/ B. Loop diuretic
/ C. Osmotic diuretic
/ D. Potassium-sparing diuretic
/ E. Thiazide diuretic

Q2
The patient is seen the following morning by a cardiologist. The cardiologist does a very careful physical examination. He notes that the heart
sounds appear distant. He then has the patient lie at an angle of 30 to 45 degrees, and does a careful examination of the right jugular pulse,
which he finds very worrisome. The pulse is both very elevated and shows dramatic x and y descents. Further, he notes that the venous
distention paradoxically increases during inspiration. This last finding is sometimes called which of the following?
/ A. Chvostek's sign
/ B. Corrigan's sign
/ C. Homans' sign
/ D. KussmauI's sign
/ E. Murphy's sign
Q 3
This patient most likely has which of the following?
/ A. Acute myocarditis
/ B. Congestive cardiomyopathy
/ C. OId left ventricle myocardial infarction
/ D. Recent left ventricle myocardial infarction
/ E. Restrictive cardiomyopathy

Q 4
An endomyocardial biopsy is performed, which demonstrates eosinophilic acellular deposits within the myocardial biopsy. When recut,
histological sections are stained with Congo red and viewed under polarized light, and the deposits appear bright green. These deposits are
most likely to be composed of which of the following?
/ A. Amyloid
/ B. Fibrin
/ C. Hemosiderin
/ D. Melanin
/ E. Uric acid

Q 5
Which of the following features of proteins is most likely responsible for the bright green appearance of the Congo red-stained materiaI?
/ A. Beta pleated sheet configuration
/ B. Calcium binding
/ C. Iron containing heme moiety
/ D. Multiple alpha helices
/ E. Presence of multiple subunits

Q 6
Which of the following would most likely be found in the Congo red-stained extracellular deposits with the bright green appearance under
polarized light?
/ A. Amyloid AA
/ B. Beta-2-microglobulin
/ C. Beta protein precursor
/ D. Immunoglobulin light chains
/ E. Transthyretin

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Cardiomegaly Case 3 Answers

A1
The correct answer is B. Large, salty, holiday meals are notorious for setting off (potentially fatal) exacerbations of what might have been previously mild congestive failure. There are a number of drugs with diuretic activity that can increase the amount of urine that is produced. Pharmacologists subclassify these drugs based on the mechanisms by which they act. Furosemide is a diuretic that is commonly used in the hospital setting in intravenous form to rapidly reduce the degree of fluid overload present in a patient in severe congestive heart failure. This diuretic acts by inhibiting the Na/K/2Cl cotransporter on the luminal membrane of the thick ascending portion of the loop of Henle. It is consequently classified as a loop diuretic, as is ethacrynic acid, which has a similar mechanism of action.
Carbonic anhydrase inhibitors (choice A), such as acetazolamide and dorzolamide, act on the proximal convoluted tubule to reduce Na+ resorption secondary to an inhibition of CO2 formation with resulting decreased intracellular bicarbonate and H+ levels.
Osmotic diuretics (choice C), such as mannitol, inhibit water reabsorption throughout the nephron.
Potassium-sparing diuretics (choice D), such as spironolactone, amiloride, and triamterene, act at the level of the collecting tubules and ducts by acting as aldosterone receptor antagonists.
Thiazide diuretics (choice E), such as hydrochlorothiazide, indapamide, and metolazone, inhibit the Na/Cl cotransporter in the distal convoluted tubule


A2
The correct answer is D. The sign described is Kussmaul's sign. The act of inflating the lungs during inspiration lowers the pressure in the chest while increasing that in the abdomen, drawing blood from the abdomen into the chest (and increased abdominal pressure helps to directly drive blood toward the chest). If the right atrium cannot fill, then the jugular venous pressure rises paradoxically (not so much from blood flow from the head as from the abdomen, because the inferior vena cava and superior vena cava are functionally connected through the right atrium). Kussmaul's sign is seen in patients who have non-compliant right ventricles. It can also be seen in patients with severe ascites (which increases the intra-abdominal pressure). This case illustrates the importance of considering the jugular venous pulse as well as the arterial pulse, since the cardiologist was able to find a number of significant findings pertaining to the jugular venous pulse, which other physicians had missed. The jugular venous pressure can be used at the bedside to estimate the right atrial filling pressure. The jugular venous pressure is estimated by measuring the height of the visible venous pulse above the sternal angle, and then adding 5 cm (corresponding to how far below the sternum the right atrium is located). The jugular venous waveform has an A wave, which is followed by an X descent, then a V wave, and finally a Y descent. The A wave (first rise in pressure) reflects the right atrial contraction, while the X-descent reflects right atrial diastole, and then early right ventricular systole. The V wave is the second major positive wave, and reflects continued venous inflow into the right atrium in opposition to a closed mitral valve. The following Y-descent is the negative deflection that occurs when the tricuspid valve opens in early diastole.
Chvostek's sign (choice A) is seen in tetany, and is a facial muscle spasm occurring when the facial nerve is tapped anterior to the external auditory meatus.
Corrigan's sign (choice B), which suggests aortic regurgitation, is a full, hard arterial pulse, which is followed by a sudden collapse.
Homans' sign (choice C) is pain at the back of the knee or calf when the ankle is dorsiflexed, and suggests venous thrombosis of the leg.
Murphy's sign (choice E) is pain on palpation of the right subcostal area during inspiration, and is frequently seen in acute cholecystitis.

A3
The correct answer is E. The "distant" heart sounds and jugular venous pulse findings both suggest that this patient has restrictive cardiomyopathy that is limiting the heart's ability to fill during diastole and is also impairing ventricular contraction. Other findings that may be encountered on physical examination in patients with restrictive cardiomyopathy include S3 and/or S4 heart sounds, occasional mitral or tricuspid regurgitation murmurs, and, if the patient is in secondary congestive failure, peripheral edema and pulmonary rales. Restrictive cardiomyopathy is relatively rare and the findings on physical examination are subtle, and consequently this patient's history of missed diagnosis is unfortunately not all that uncommon. Underlying causes of restrictive cardiomyopathy include endomyocardial fibrosis, Loeffler eosinophilic endomyocardial disease, hemochromatosis, amyloidosis, sarcoidosis, scleroderma, carcinoid heart disease, and glycogen storage disease. Patients typically present at an advanced stage of the disease, and may have symptoms of angina, shortness of breath, peripheral edema, and ascites with abdominal discomfort (related to pooling of blood in the liver and other abdominal organs). Once the diagnosis is suspected, echocardiography typically demonstrates normal to symmetrically thickened heart chamber walls with rapid early-diastolic filling and slow late-diastolic filling (the cardiac chambers are acting more or less like poorly distensible plastic bags). Cardiac catheterization will more or less repeat the observations seen in the analysis of the jugular venous pulse, typically showing elevated ventricular end-diastolic pressure, normal to slightly decreased ejection fraction, and prominent x and y descents.
Acute myocarditis (choice A) can cause congestive cardiomyopathy (choice B), but the heart is usually larger and the constrictive findings seen in this case would not be present.
While recent and old myocardial infarctions affecting the right ventricle may produce similar jugular venous findings to those seen in this case, left ventricular infarction (choices C and D) would not impair right ventricular filling and contraction.

A4
The correct answer is A. Amyloid deposits are suspected when hematoxylin and eosin-stained histological sections show extracellular eosinophilic deposits. The presence of amyloidosis is confirmed when the characteristic "apple-green birefringence" on Congo red stain is demonstrated.
Fibrin deposits (choice B) are also red on hematoxylin and eosin stain, but show no fluorescence with Congo red stain.
Hemosiderin (choice C) causes yellow brown deposits; melanin (choice D) causes brown-black deposits; and uric acid (choice E) causes yellow crystalline deposits

A5
The correct answer A. It was originally assumed by biochemists that amyloid was always composed of the same material. It came as something of a shock when antibody techniques were developed that demonstrated that the antigenicity of amyloid in different clinical settings varied markedly. The common feature these proteins shared that accounted for both the affinity for Congo red and their characteristic regular fibrillar structure on electron microscopy turned out to be that the proteins all have a beta pleated sheet tertiary (secondary according to some biochemical purists) configuration, best demonstrated by X-ray diffraction.
Selective or non-selective binding to calcium (choice B) is common in proteins.
Heme moieties containing iron (choice C) are a part of myoglobin and hemoglobin.
Alpha helices (choice D) are a common secondary structure in proteins, but do not contribute to the protein forming amyloid.
The presence of multiple subunits (choice E) is also common in proteins, but does not contribute to a protein forming amyloid.

A6
The correct answer is D. Amyloidosis occurs in a large variety of forms. Primary amyloidosis is one of the more common forms of systemic amyloidosis, and can affect a variety of organs, including the heart, kidney, peripheral nerve, gastrointestinal tract, and respiratory tract. In primary amyloidosis, the amyloid is composed of immunoglobulin light chains, and the disease is now interpreted as a plasma cell disorder closely related to multiple myeloma. This interpretation is clinically significant, as it has led to modern treatments of primary amyloidosis (which formerly had a dismal prognosis) with the chemotherapies designed for multiple myeloma. The treatments are affective only if the disease is recognized and passed to the appropriate specialists as early as possible in the clinical course.
Amyloid AA (choice A) is seen in inflammation-associated amyloidosis and familial Mediterranean fever.
Beta-2-microglobulin (choice B) comprises the amyloid of dialysis-associated amyloidosis.
Beta protein precursor (choice C) comprises the amyloid seen in the brains of patients with Alzheimer's disease and Down syndrome.
Transthyretin (choice E) comprises the amyloid seen in familial amyloidosis and senile cardiac amyloidosis.