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| ==Pathophysiology== | | ==HIV-TB Coinfection== |
| The most common cause for ''cardiogenic shock'' is [[left ventricular failure]] in the setting of acute [[myocardial infarction]]. It usually takes a considerable area of [[MI|infarcted myocardium]] (around 40%) to lead to cardiogenic shock nevertheless, a smaller [[infarct]] may also originate this condition in a patient with a previously compromised [[ventricle]] function. However, there may also be other [[etiologies]], either alone or in combination, for the [[shock]] of [[cardiac]] origin, such as:
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| *'''Systolic Left Ventricular Dysfunction''' - acute [[myocardial infarction]], [[CHF]], [[Cardiomyopathy]], [[Coronary artery bypass grafting]], [[Myocarditis]], [[Myocardial contusion]] and [[Hypophosphatemia]]
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| *'''Diastolic Left Ventricular Dysfunction''' - [[Ischemia]]
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| *'''Obstruction of Left Ventricular Outflow, with Increased Afterload''' - [[Aortic stenosis]], [[Hypertrophic Cardiomyopathy]], [[Coarctation of the Aorta]] and [[Malignant Hypertension]]
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| *'''Reversal of flow into the left ventricle''' - Acute [[aortic insufficiency]] and [[Endocarditis]]
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| *'''Inadequate left ventricular filling due to mechanical causes''' - [[Tamponade]], [[Pulmonary Embolism]]
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| *'''Inadequate left ventricular filling due to inadequate filling time''' - [[Tachycardia]] and [[Tachycardia]]-mediated [[Cardiomyopathy]]
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| *'''Conduction abnormalities''' - [[Atrioventricular block]] and [[Sinus Bradycardia]]
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| *'''Mechanical defect''' - [[VSD]] and [[Free wall rupture|Left ventricle free wall rupture]]
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| *'''Right ventricular failure''' - [[Pulmonary embolism]] and [[Hypoxic pulmonary vasoconstriction]]
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| ===The Pathophysiologic "Spiral" of Cardiogenic shock===
| | Recommendations for the treatment of tuberculosis in [[HIV]]-infected adults: |
| The pathologic process begins with [[myocardial]] [[ischemia]] that leads to an abnormal function of the [[cardiac muscle]]. This abnormality worsens the initial [[ischemia]], which then deteriorates even further the [[ventricular function]], creating the so called ''downward spiral''.<ref name="pmid10391815">{{cite journal| author=Hollenberg SM, Kavinsky CJ, Parrillo JE| title=Cardiogenic shock. | journal=Ann Intern Med | year= 1999 | volume= 131 | issue= 1 | pages= 47-59 | pmid=10391815 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10391815 }} </ref> When [[ischemia]] reaches a point that the [[left ventricle]] [[myocardium]] fails to pump, parameters like [[stroke volume]] and [[cardiac output]] will therefore decrease. The pressure gradient produced between the pressure within the [[coronary arteries]] and within the [[left ventricle]], along with the duration of the [[diastole]], will dictate [[myocardial]] [[perfusion]]. This will then be compromised by the [[hypotension]] and the [[tachycardia]], worsening the [[myocardial]] [[ischemia]]. The pump failure will decrease the ability to pump the blood out of the ventricle, thereby increasing the ventricular diastolic pressures. This will not only reduce the [[coronary]] [[perfusion pressure]], as it will also increase the [[ventricle]] wall stress, so that the [[myocardial]] [[oxygen]] requirements will also increase, which will consequently propagate the [[ischemia]].
| | The recommended treatment of TB disease in HIV-infected adults (when the disease is caused by organisms that are known or presumed to be susceptible to first-line drugs) is a 6-month regimen consisting of: |
| | *For the first 2 months: An initial phase of [[isoniazid]] (INH), a [[rifamycin]], [[pyrazinamide]] (PZA), and [[ethambutol]] (EMB). |
| | *For the last 4 months: A continuation phase of INH and a rifamycin. |
| | *Patients with advanced HIV (CD4 counts < 100/µl) should be treated with daily or three-times-weekly therapy in both the initial and the continuation phases. |
| | *Twice weekly therapy may be considered in patients with less-advanced immunosuppression (CD4 counts ≥ 100/µl). |
| | *Once-weekly INH/rifapentine in the continuation phase should not be used in any HIV-infected patient. |
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| The [[ischemia]] generated by all these processes increases the [[diastolic]] stiffness of the [[ventricle]] wall and this, along with the [[left ventricular dysfunction]], will increase the [[left atrial]] pressure. The increased [[left atrial]] pressure will propagate through the [[pulmonary veins]], generating [[pulmonary congestion]], which by decreasing [[oxygen]] exchanges, leads to [[hypoxia]]. The [[hypoxia]] will further worsen the [[ischemia]] in the [[myocardium]] and the [[pulmonary congestion]] will propagate its effect through the [[pulmonary arteries]] to the [[right ventricle]], hence jeopardizing its performance.
| | Recommendations for the treatment of tuberculosis in [[HIV]]-infected adults are, with a few exceptions, the same as those for HIV-uninfected adults. The [[INH]]--[[rifapentine]] once weekly continuation phase is contraindicated in HIV-infected patients because of an unacceptably high rate of relapse, frequently with organisms that have acquired resistance to [[rifamycin]]s. The development of acquired [[rifampin]] [[drug resistance|resistance]] has also been noted among HIV-infected patients with advanced [[immunosuppression]] treated with twice weekly rifampin- or [[rifabutin]]-based regimens. Consequently, patients with [[CD4]]+ cell counts <100/µl should receive daily or three times weekly treatment. DOT and other adherence-promoting strategies are especially important for patients with HIV-related tuberculosis. |
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| ===Inflammation and Hemodynamics===
| | Management of HIV-related tuberculosis is complex and requires expertise in the management of both HIV disease and tuberculosis. Because HIV-infected patients are often taking numerous medications, some of which interact with antituberculosis medications, it is strongly encouraged that experts in the treatment of HIV-related tuberculosis be consulted. A particular concern is the interaction of [[rifamycin]]s with [[antiretroviral agent]]s and other antiinfective drugs. [[Rifampin]] can be used for the treatment of tuberculosis with certain combinations of antiretroviral agents. [[Rifabutin]], which has fewer problematic drug interactions, may also be used in place of rifampin and appears to be equally effective although the doses of rifabutin and antiretroviral agents may require adjustment. As new antiretroviral agents and more pharmacokinetic data become available, these recommendations are likely to be modified. |
| *(SIRS, iNOS, LV DYSFUNCTION)
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| ===Pathology===
| | On occasion, patients with HIV-related tuberculosis may experience a temporary exacerbation of symptoms, signs, or radiographic manifestations of tuberculosis while receiving antituberculosis treatment. This clinical or radiographic worsening (paradoxical reaction) occurs in HIV-infected patients with active tuberculosis and is thought to be the result of immune reconstitution as a consequence of effective [[antiretroviral therapy]]. Symptoms and signs may include high [[fever]]s, [[lymphadenopathy]], expanding [[central nervous system]] lesions, and worsening of [[chest radiographic]] findings. The diagnosis of a paradoxical reaction should be made only after a thorough evaluation has excluded other [[etiologies]], particularly tuberculosis treatment failure. [[Nonsteroidal antiinflammatory agent]]s may be useful for symptomatic relief. For severe paradoxical reactions, [[prednisone]] (1--2 mg/kg per day for 1--2 weeks, then in gradually decreasing doses) may be used, although there are no data from controlled trials to support this approach. |
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| ====Myocardium====
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| *INFARCT EXTENSION AND EXPANSION
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| *REMOTE ISCHEMIA
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| *DIASTOLIC DYSFUNCTION
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| *VALVULAR ABNORMALITIES
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| ====Cellular====
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| *ENERGY METABOLISM
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| *ION PUMPS
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| *NECROSIS
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| *APOPTOSIS
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| ===Myocardial dysfunction===
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| *STUNNING
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| *HIBERNATING
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| ===Reperfusion Injury===
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| ===The Impact of Cardiogenic shock on the [[Pressure-Volume Loop]]===
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| Cardiogenic shock shifts the pressure volume loop to the right: that is to say at a given pressure, the heart is able to eject less blood per heart beat, and [[stroke volume]] is reduced. Diastolic compliance is reduced, and left ventricular volumes are increased. This leads to the classic observation that an increased left ventricular end diastolic pressure is required to maintain adequate [[cardiac output]]. The rise in end diastolic pressure increases the wall stress and oxygen demands of the myocardium. These hemodynamic abnormalities contributes to the pathophysiologic spiral described below.
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| ===Cardiogenic shock and Inflammatory Mediators===
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| Myocardial infarction or ischemia lead to production of superoxide radicals which combine with nitrous oxide to form perioxinitrite which in turn causes myocardial depression and [[hypotension]].
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| [[Image:Cardiogenic_shock.JPG|center|500px]]
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| ===The Pathophysiologic "Spiral" of Cardiogenic shock===
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| Among patients with acute MI, there is often a downward spiral of hypoperfusion leading to further ischemia which leads to a further reduction in cardiac output and further hypoperfusion. The [[lactic acidosis]] that develops as a result of poor systemic perfusion can further reduce cardiac contractility. Reduced cardiac output leads to activation of the sympathetic nervous system, and the ensuing [[tachycardia]] that develops further exacerbates the myocardial ischemia. The increased left ventricular end diastolic pressures is associated with a rise in wall stress which results in further myocardial ischemia. [[Hypotension]] reduces epicardial perfusion pressure which in turn further increases myocardial ischemia.
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| Patients with cardiogenic shock in the setting of [[STEMI]] more often have multivessel disease, and myocardial ischemia may be present in multiple territories. It is for this reason that multivessel angioplasty may be of benefit in the patient with cardiogenic shock. Non-culprit or remote territories may also exhibit [[myocardial stunning]] in response to an ischemic insult which further reduces myocardial function. The pathophysiology of myocardial stunning is multifactorial and involves calcium overload in the sarcolemma and "stone heart" or [[diastolic dysfunction]] as well as the release of myocardial depressant substances. Areas of stunned myocardium may remain stunned after revascularization, but these regions do respond to inotropic stimulation. In contrast to stunned myocardium, [[hibernating myocardium]] does respond earlier to revascularization.
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| The multifactorial nature of cardiogenic shock can also be operative in the patient with critical [[aortic stenosis]] who has "spiraled": There is impairment of left ventricular outflow, with a drop in [[cardiac output]] there is greater [[subendocardial]] ischemia and poorer flow in the coronary arteries, this leads to further [[left ventricular systolic dysfunction]], given the subendocardial ischemia, the left ventricle develops [[diastolic dysfunction]] and becomes harder to fill. Inadvertent administration of [[vasodilator]]s and [[venodilator]]s may further reduce cardiac output and accelerate or trigger such a spiral. | |
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| ===Pathophysiologic Mechanisms to Compensate for Cardiogenic shock===
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| [[Cardiac output]] is the product of [[stroke volume]] and heart rate. In order to compensate for a reduction in stroke volume, there is a rise in the heart rate in patients with cardiogenic shock. As a result of the reduction in [[cardiac output]], peripheral tissues extract more oxygen from the limited blood that does flow to them, and this leaves the blood deoxygenated when it returns to the right heart resulting in a fall in the mixed venous oxygen saturation. | |
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| ===Pathophysiology of Multiorgan Failure===
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| The poor perfusion of organs results in [[hypoxia]] and [[metabolic acidosis]]. Inadequate perfusion to meet the metabolic demands of the brain, kidneys and heart leads to multiorgan failure.
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HIV-TB Coinfection
Recommendations for the treatment of tuberculosis in HIV-infected adults:
The recommended treatment of TB disease in HIV-infected adults (when the disease is caused by organisms that are known or presumed to be susceptible to first-line drugs) is a 6-month regimen consisting of:
- For the first 2 months: An initial phase of isoniazid (INH), a rifamycin, pyrazinamide (PZA), and ethambutol (EMB).
- For the last 4 months: A continuation phase of INH and a rifamycin.
- Patients with advanced HIV (CD4 counts < 100/µl) should be treated with daily or three-times-weekly therapy in both the initial and the continuation phases.
- Twice weekly therapy may be considered in patients with less-advanced immunosuppression (CD4 counts ≥ 100/µl).
- Once-weekly INH/rifapentine in the continuation phase should not be used in any HIV-infected patient.
Recommendations for the treatment of tuberculosis in HIV-infected adults are, with a few exceptions, the same as those for HIV-uninfected adults. The INH--rifapentine once weekly continuation phase is contraindicated in HIV-infected patients because of an unacceptably high rate of relapse, frequently with organisms that have acquired resistance to rifamycins. The development of acquired rifampin resistance has also been noted among HIV-infected patients with advanced immunosuppression treated with twice weekly rifampin- or rifabutin-based regimens. Consequently, patients with CD4+ cell counts <100/µl should receive daily or three times weekly treatment. DOT and other adherence-promoting strategies are especially important for patients with HIV-related tuberculosis.
Management of HIV-related tuberculosis is complex and requires expertise in the management of both HIV disease and tuberculosis. Because HIV-infected patients are often taking numerous medications, some of which interact with antituberculosis medications, it is strongly encouraged that experts in the treatment of HIV-related tuberculosis be consulted. A particular concern is the interaction of rifamycins with antiretroviral agents and other antiinfective drugs. Rifampin can be used for the treatment of tuberculosis with certain combinations of antiretroviral agents. Rifabutin, which has fewer problematic drug interactions, may also be used in place of rifampin and appears to be equally effective although the doses of rifabutin and antiretroviral agents may require adjustment. As new antiretroviral agents and more pharmacokinetic data become available, these recommendations are likely to be modified.
On occasion, patients with HIV-related tuberculosis may experience a temporary exacerbation of symptoms, signs, or radiographic manifestations of tuberculosis while receiving antituberculosis treatment. This clinical or radiographic worsening (paradoxical reaction) occurs in HIV-infected patients with active tuberculosis and is thought to be the result of immune reconstitution as a consequence of effective antiretroviral therapy. Symptoms and signs may include high fevers, lymphadenopathy, expanding central nervous system lesions, and worsening of chest radiographic findings. The diagnosis of a paradoxical reaction should be made only after a thorough evaluation has excluded other etiologies, particularly tuberculosis treatment failure. Nonsteroidal antiinflammatory agents may be useful for symptomatic relief. For severe paradoxical reactions, prednisone (1--2 mg/kg per day for 1--2 weeks, then in gradually decreasing doses) may be used, although there are no data from controlled trials to support this approach.