Translational Physiology Block 3 Flashcards
What are heart murmurs and arterial bruits?
Normal blood flow across normal heart valves is silent; murmurs are heard with turbulent flow (Reynold’s number above 3000; increases in vessel diameter, pressure (velocity) and decreases in viscosity); grade I murmurs are barely audible (grade 6: loudest); with atherosclerosis (narrows vessel lumen and increases velocity) in arteries, an arterial murmur (bruit) is audible
Why is thallium scanning a good tool for assessing coronary blood flow?
in areas supplied by stenotic coronary vessels, the uptake is slower, and appear as defects on a thallium scan. Thallium scans are used to detect coronary artery disease during exercise stress tests (SPECT)
Describe the acute-phase response. What does enhanced erythrocyte sedimentation rate illustrate?
During the course of several hours, in response to inflammatory cytokines, the liver rapidly synthesizes and secretes into the circulatory system a number of proteins that aid in the host response to the threat (fibrinogen causes RBCs to cluster and effectively increases the density of RBCs); ESR is widely used by clinicians to assess the presence and severity of inflammation
What causes interstitial edema?
lack of muscle contraction during orthostasis; pulmonary hypertension or left-sided heart failure (pulmonary edema decreases lung compliance and compromises gas-exchange at the lung); right-sided heart failure (blood backs up in veins and increases capillary pressure; ascites in the liver); in proteinurea plasma colloid osmotic pressure decreases reducing the amount of reabsoprtion in the venular portion of the capillary (also seen in pregnancy when maternal plasma protein levels fall or with malnutrition); inflammation (histamine); reperfusion of ischemic tissue (with increased hydraulic conductivity and decreased reflection coefficient for plasma proteins) leads to edema; impairment of lymphatic drainage by either removal or lymph nodes or presence of a lymphatic neoplasm
What are the two vagal maneuvers?
valsalva: grunting (forced expiration against a closed airway) while lifting a heavy object raises the intrathoracic pressure. Opening of the airway allows intrathoracic pressure to fall; the increased transmural pressure stretches the aortic arch baroreceptors triggering bradycardia (or decreased heart rate); Digitalis compounds can be used to treat supraventricular tachycardias (atrial) because these drugs may increase vagal tone and decrease sympathetic tone (slowing conduction velocity at the AV node) (In patients with congestive heart failure increases myocardial contractility)
Describe the progression of early phase of myocardial infarction to late phase.
if blood flow is not restored in due time, ischemic tissue will become necrotic; The first electrical change associated with an acute myocardial infarction is peaking of the T waves, followed soon after by T-wave inversion (reversible if blood flow is restored); The next change, more characteristic of an acute myocardial infarction, is elevation of the ST segment. With irreversible cell death, the ECG typically shows the evolution of deep Q waves
What is the direction of the QRS complex vector in myocardial infarction?
Because action potentials cannot propagate into the infarcted area, the net vector of the remaining areas of ventricular depolarization points away from the infarcted area (reflected by a “deep” negative deflection on the ECG)
Describe atrial fibrillation.
loss of atrial contraction due to chaotic electrical activity
What are co-morbidities associated with atrial fibrillation?
atrial thrombosis and cerebral embolus (stroke)
What conditions compromise the myocardium (ventricles?)
ischemic heart disease (MI); prolonged hypertension (hypertrophy); mitral stenosis
Is atrial contraction important for patients with reduced ventricular function?
Yes; the loss of the atrial contraction may further reduce cardiac output just enough to send the patient into florid congestive heart failure or even shock (i.e., arterial pressure so low that it compromises perfusion of peripheral tissues (also crucial for patients with aortic stenosis and tachycardia)
How does blood flow during diastole? where it this phenomenon most apparent?
This sizeable diastolic component is largely the result of the high compliance of the vessel walls and the radial expansion of the vessels that occurs during ventricular ejection (Windkessel model); aorta and nearby arteries (carotid artery and renal artery)
Why does the myocardium hypertrophy?
Because cells of the adult heart are terminally differentiated, stimuli that might be mitogenic in other cells cannot elicit cell division in the heart but rather cause the cardiac myocytes to hypertrophy and increase muscle mass (muscles increase in width and length) (result of volume or pressure overload)
Describe how volume overload results in ventricular hypertrophy. pressure overload?
Volume overload leads to eccentric hypertrophy characterized by increases of myocyte length out of proportion to width; Pressure overload causes concentric hypertrophy with a relatively greater increase in myocyte width
What are mechanism of ventricular hypertrophy?
pathway: MAPK (zinc finger transcription factor GATA4; SRF; Sp1; TEF-1 family); catecholamines and angiotensin II activate MAPK; elevated intracellular calcium activates GATA4); alternate or additional branch: MLP and AP-1
What are features of ventricular hypertrophy?
Reduced levels of the mRNA encoding three critical proteins in the membrane of the SR: (1) the Ca 2+ release channel, (2) phospholamban, and (3) the SR Ca 2+ pump (SERCA2); Lower contractility/cross-sectional area
What are features of heart failure?
People whose hearts cannot sustain an adequate cardiac output become breathless (because blood backs up from the left side of the heart into the lungs) and have swollen feet and ankles (because blood backs up from the right side of the heart and promotes net filtration in systemic capillaries).
What cellular mechanism has been associated with heart failure?
In an animal model of hypertension-induced cardiac hypertrophy that leads to heart failure, the Cav1.2 channels exhibit an impaired ability to activate RYR2 through Ca 2+ -induced Ca 2+ release (depletion of calstabin 2 results in leaky RYR2 receptors and delayed afterdepolarizations and ventricular arrhythmias)
Does primary hypertension have a known cause?
No
What can cause secondary hypertension?
renal artery stenosis; tumor of adrenals
What must be ruled out when making a diagnosis of coronary artery disease? What is the crucial exam?
Physicians rule out gastroesophoageal reflux, hyperventilation, and costochondritis by ordering a stress test (with thallium scan)
What is the first sign of coronary artery disease?
For many patients with gradual narrowing of their coronal arteries by atherosclerotic plaque, the first sign of disease may be development of angina pectoris. Pain results when the metabolic demands of a region of myocardium exceed the ability of the compromised blood supply to satisfy those needs (when stressed)
What are therapies for coronary artery disease (angina)?
Nitrates induce vasodilation by releasing nitric oxide. The nitrates dilate peripheral veins, reducing venous return and thus preload to the heart; also dilate arteries and arterioles reducing blood pressure and afterload; finally, nitrates may increase coronary collateral flow to the involved region of myocardium; Beta blockers prevent the sympathetic nervous system from stimulating myocardial beta1 receptors, thereby reducing both heart rate and contractility and thus metabolic demand; Calcium channel blockers lessen the contractility of the heart muscle and vascular smooth muscle (reduce metabolic demands of the heart)
Does therapy change for patients with increasing frequency and severity of anginal attacks (when stressed)?
Yes; mechanical revascularization may be required (surgery or angioplasty)
Describe angioplasty. How is a stent different
physician advances a balloon-tipped catheter through a peripheral artery into the left ventricle and then loops the catheter back out the left ventricle to have a favorable angle for entering coronary vessels from the aorta. Inflation of the balloon at the site of obstruction flatten the plaque into the wall of the vessel and restores blood flow; a metal cage is retained.
