Streptococcus pneumoniae can escape phagocytic clearance by which mechanism?
Capsule-mediated inhibition of phagocytosis
Inhibition of phagolysosome fusion
Inhibition of opsonization mediated by protein A
Lysis of phagosome and replication in cytoplasm
Replication in fused phagolysosome
S. pneumoniae is covered with a complex polysaccharide capsule. This is the major virulence factor for these bacteria because the presence of the capsule prevents phagocytosis. Encapsulated strains are associated with disease in humans and experimental animals, whereas nonencapsulated strains are avirulent. Free capsular polysaccharides can be released from the bacteria and bind opsonic antibodies, further protecting the bacteria from phagocytosis
A newborn male has hypocalcemia and cardiac abnormalities. Which of the following immunologic disorders should be considered?
DiGeorge syndrome
Wiskott-Aldrich syndrome
Severe combined immunodeficiency syndrome
Adenosine deaminase deficiency
Chronic granulomatous disease
In DiGeorge syndrome, there is a defect in tissues derived from the third and fourth brachial arches. Hypocalcemia and cardiac abnormalities as well as distinct facial and jaw features are noted in affected individuals. The absence of a thymus has major immunologic consequences.
A 6-month-old male is exposed to respiratory syncytial virus (RSV) for the first time and develops signs and symptoms of infection. Which of the following will be most beneficial to clear his infection?
Apoptosis of virally infected cells by T cytotoxic cells
Antibiotic therapy to halt viral replication
Lysis of infected cells via the classical complement pathway
T helper (Th) cell–induced necrosis of virally infected cells
Generation of antibodies to neutralize free virus
Clearance of active viral infections occurs through the destruction of infected cells. The primary agents are cytotoxic T cells. Because this is the initial exposure, antibody levels against the virus have not had time to reach effective levels.
The type of congestive heart failure that occurs in association with beriberi is most accurately characterized as:
(a) Low-output left ventricular failure (b) High-output left ventricular failure
(c) Low-output right ventricular failure
(d) High-output right ventricular failure
Forms of Ventricular Dysfunction
Heart failure may be described in various ways: systolic or diastolic, acute or chronic, left sided or right sided, high output or low output. Early in the course of heart failure, the various categories may have different clinical and therapeutic implications. Ultimately, however, all forms of heart failure are characterized by high ventricular end-diastolic pressure because of altered ventricular function and neurohormonal regulation.
Systolic and Diastolic Heart Failure
Decreased ventricular systolic wall motion reflects systolic dysfunction, whereas diastolic dysfunction is characterized by abnormal ventricular relaxation and reduced compliance. There are differences in both myocardial architecture and function in systolic and diastolic heart failure, but clinical signs and symptoms cannot reliably differentiate between these two entities.
Systolic Heart Failure
Causes of systolic heart failure include coronary artery disease, dilated cardiomyopathy, chronic pressure overload (aortic stenosis and chronic hypertension), and chronic volume overload (regurgitant valvular lesions and high-output cardiac failure). Coronary disease typically results in regional defects in ventricular contraction, which may become global over time, whereas all other causes of systolic heart failure produce global ventricular dysfunction. Ventricular dysrhythmias are common in patients with LV dysfunction. Patients with left bundle branch block and systolic heart failure are at high risk of sudden death.
A decreased ejection fraction, the hallmark of chronic LV systolic dysfunction, is closely related to the increase in the diastolic volume of the LV (Figure 6-1). Measuring the LV ejection fraction via echocardiography, radionuclide imaging, or ventriculography provides the quantification necessary to document the severity of ventricular systolic dysfunction.
Left ventricular dysfunction, regardless of cause, results in progressive remodeling of the ventricular chamber leading to dilation and a low ejection fraction. Cardiac dysrhythmias, progressive cardiac failure, and premature death are likely. Noncardiac factors such as neurohormonal stimulation, vasoconstriction, and renal sodium retention may be stimulated by left ventricular dysfunction and ultimately contribute to remodeling of the left ventricle and to the symptoms (dyspnea, fatigue, edema) considered characteristic of the clinical syndrome of congestive heart failure.
(Adapted from Cohn JN. The management of chronic heart failure. N Engl J Med. 1996;335:490-498. Copyright 1996 Massachusetts Medical Society. All rights reserved.)
Diastolic Heart Failure
Symptomatic heart failure in patients with normal or near-normal LV systolic function is most likely due to diastolic dysfunction. However, diastolic heart failure may co-exist with systolic heart failure. The prevalence of diastolic heart failure is age dependent, increasing from less than 15% in patients younger than 45 years of age to 35% in those between the ages of 50 and 70 to more than 50% in patients older than 70 years. Diastolic heart failure can be classified into four stages. Class I is characterized by an abnormal LV relaxation pattern with normal left atrial pressure. Classes II, III, and IV are characterized by abnormal relaxation as well as reduced LV compliance resulting in an increase in LV end-diastolic pressure (LVEDP). As a compensatory mechanism, the pressure in the left atrium increases so that LV filling can occur despite the increase in LVEDP. Factors that predispose to decreased ventricular distensibility include myocardial edema, fibrosis, hypertrophy, aging, and pressure overload. Ischemic heart disease, long-standing essential hypertension, and progressive aortic stenosis are the most common causes of diastolic heart failure. In contrast to systolic heart failure, diastolic heart failure affects women more than men. Hospitalization and mortality rates are similar in patients with systolic and with diastolic heart failure. The major differences between systolic and diastolic heart failure are presented in Table 6-1.
TABLE6-1 Characteristics of patients with diastolic heart failure and patients with systolic heart failure
Characteristic
Diastolic heart failure
Systolic heart failure
Age
Frequently elderly
Typically 50-70 yr
Sex
Frequently female
More often male
Left ventricular ejection fraction
Preserved, ≥40%
Depressed, ≤40%
Left ventricular cavity size
Usually normal, often with concentric left ventricular hypertrophy
Usually dilated
Chest radiograph
Congestion ± cardiomegaly
Congestion and cardiomegaly
Gallop rhythm present
Fourth heart sound
Third heart sound
Hypertension
+++
++
Diabetes mellitus
+++
++
Previous myocardial infarction
+
+++
Obesity
+++
+
Chronic lung disease
++
0
Sleep apnea
++
++
Dialysis
++
0
Atrial fibrillation
+ Usually paroxysmal
+ Usually persistent
+, Occasionally associated with; ++, often associated with; +++, usually associated with; 0, no association.
Acute and Chronic Heart Failure
Acute heart failure is defined as a change in the signs and symptoms of heart failure requiring emergency therapy. Chronic heart failure is present in patients with long-standing cardiac disease. Typically, chronic heart failure is accompanied by venous congestion, but blood pressure is maintained. In acute heart failure due to a sudden decrease in cardiac output, systemic hypotension is typically present without signs of peripheral edema. Acute heart failure encompasses three clinical entities: (1) worsening chronic heart failure, (2) new-onset heart failure (such as that caused by cardiac valve rupture, large myocardial infarction, or severe hypertensive crisis), and (3) terminal heart failure that is refractory to therapy.
Left-Sided and Right-Sided Heart Failure
Increased ventricular pressures and subsequent fluid accumulation upstream from the affected ventricle produce the clinical signs and symptoms of heart failure. In left-sided heart failure, high LVEDP promotes pulmonary venous congestion. The patient complains of dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, which can evolve into pulmonary edema. Right-sided heart failure causes systemic venous congestion. Peripheral edema and congestive hepatomegaly are the most prominent clinical manifestations. Right-sided heart failure may be caused by pulmonary hypertension or right ventricular myocardial infarction, but the most common cause is left-sided heart failure.
Low-Output and High-Output Heart Failure
The normal cardiac index varies between 2.2 and 3.5 L/min/m2. It may be difficult to diagnose low-output heart failure, because a patient may have a cardiac index that is nearly normal in the resting state but shows an inadequate response to stress or exercise. The most common causes of low-output heart failure are coronary artery disease, cardiomyopathy, hypertension, valvular disease, and pericardial disease.
Causes of high cardiac output include anemia, pregnancy, arteriovenous fistulas, severe hyperthyroidism, beriberi, and Paget’s disease. The ventricles fail not only due to the increased hemodynamic burden, but also due to direct myocardial toxicity (thyrotoxicosis and beriberi) or due to myocardial anoxia caused by severe and prolonged anemia.
Distinction between Cardiovascular Collapse, Cardiac Arrest, and Death
Term-
Cardiovascular collapse
Definition-
Sudden loss of effective blood flow due to cardiac and/or peripheral vascular factors that may reverse spontaneously (e.g., neurocardiogenic syncope, vasovagal syncope) or require interventions (e.g., cardiac arrest)
Qualifiers-
Nonspecific term: includes cardiac arrest and its consequences and transient events that characteristically revert spontaneously
Mechanisms-
Same as "Cardiac Arrest," plus vasodepressor syncope or other causes of transient loss of blood flow
Term-
Cardiac arrest
Definition-
Abrupt cessation of cardiac mechanical function, which may be reversible by a prompt intervention but will lead to death in its absence
Qualifiers-
Rare spontaneous reversions; likelihood of successful intervention relates to mechanism of arrest, clinical setting, and prompt return of circulation
Mechanisms-
Ventricular fibrillation, ventricular tachycardia, asystole, bradycardia, pulseless electrical activity, mechanical factors
Term-
Sudden cardiac death
Definition-
Sudden, irreversible cessation of all biological functions
Qualifiers-
None
1. A 1-day-old is noted
to be cyanotic. Physical examination reveals a grade 2-3/6 systolic murmur and
a single loud second heart sound. The chest radiograph reveals a normal-sized
heart and decreased pulmonary vascular markings. The electrocardiogram (ECG)
reveals left ventricular dominance. The next step in the management of this
neonate is to administer
A. sodium bicarbonate
B. morphine
C. prostaglandin E1
D. digoxin
E. positive-pressure
ventilation
2. The most likely
diagnosis in the patient described in Question 1 is
A 67-year-old man is brought to the Emergency Department by his wife. She explains that he fell suddenly, could not get out of his bed, and complained of feeling sick. The examination revealed a left-sided weakness of the upper and lower extremities, a lack of most movement of the right eye, and a dilated pupil on the right. MRI shows an infarcted area in the brainstem. Which of the following descriptive phrases best describes the constellation of signs and symptoms seen in this man?
The loss of most eye movement on one side (oculomotor nerve root involvement) coupled with a paralysis of the extremities on the contralateral side is a superior alternating hemiplegia (this is also known as Weber syndrome): “superior” because it is the most rostral of three; “alternating” because it is a cranial nerve on one side and the extremities on the other; and “hemiplegia” because half of the body below the head is involved.
