Circulatory System Flashcards
Arterioles vs Veins
Arterioles serve as control valves to regulate local blood flow. Arteries are not very distensible; consequently, large increases in the AP cause only small increases in arterial diameter.
Veins are a reservoir for blood. Highly distensible; therefore, small increases in venous pressure cause large increases in venous diameter.
The adult circulatory system contains 5L of blood, 64% of which is in systemic veins.
Vasodilation _______ resistance to blood flow, whereas vasoconstriction _______ resistance to flow.
reduces, increases
Three mechanisms that help ensure venous return
1) negative pressure in the right atrium sucks blood toward the heart
2) constriction of veins increases venous pressure, thereby driving blood toward the heart
3) Contraction of skeletal muscles, in conjunction with one-way venous valves, pumps blood toward the heart.
Starling’s Law and Maintenance of Systemic-Pulmonary Balance
The force of ventricular contraction is proportional to myocardial fiber length. Because of this relationship, when more blood enters the heart, more is pumped out. As a result, the healthy heart is able to precisely match output with venous return.
Because cardiac muscle operates under Starling’s law, the right and left ventricles always pump exaclty the same amount of blood (assuming the heart is healthy) in this way, the balance between the poulmonary and systemic circulation is maintained.
Heart rate is _______ by sympathetic nerve impulses and _______ by parasympathetic impulses.
increased, decreased
Preload vs Afterload
Preload: the amount of tension (stretch) applied to a muscle before contraction. In the heart, preload is determined by the force of venous return.
Afterload: the load against which a muscle exerts its force. For the heart, afterload is the AP that the left ventricle must overcome to eject blood.
Cardiac afterload is determined primarily by peripheral resistance, which in turn is determined by the degree of constriction in arterioles.
The most important determinant of venous return is…
the systemic filling pressure, which can be reaised by constricting veins and increasing blood volume.
Regulation of Arterial Pressure
- Two ways
- Baroreceptor Reflex
Regulated by the ANS, the RAAS, the kidneys, and the natriuretic peptides. The ANS regulates the AP in two ways: 1) through tonic control of thte heart rate and peripheral resistance and 2) through the baroreceptor reflex
The baroreceptor reflex is useful only for short-term control of the AP. When pressure remains elevated or lowered, the system resets to the new pressure within 1-2 days and ceases to respond.
The Renin-Angiotensin-Aldosterone System
The RAAS supports the AP by causing:
-Vasocontriction of arterioles and veins
-Retention of water by the kidneys.
Vasoconstriction is mediated by angiotensin II; water retention is mediated in part by aldosterone.
The kidneys provide long-term control of blood pressure by regulating blood volume.
Orthostatic hypotension
Postural (orthostatic) hypotension is caused by decreased venous return secondary to the pooling of blood in the veins, which can occur when a person assumes an erect position.
Drugs that dilate the veins intensify and prolong postural hypotension. As with other drugs that reduce the AP, vasodilators can trigger the baroreceptor reflex, thereby causing reflex tachycardia.
Natriuretic Peptides
Defend the cardiovascular system from volume overload, primarily by reducing blood volume and promoting vasodilation.
Physiology of the RAAS
Helps regulate blood pressure, blood volume, and fluid/electrolyte balance. Promotes cardiovascular pathology.
The RAAS acts through production of angiotensin II and aldosterone.
Angiotensin II has much greater biologic activity than angiotensin I or angiotensin III.
Angiotensin II is formed by the actions of two enzymes: renin and ACE.
Angiotensin II causes vasoconstriction (primarily in arterioles) and the release of aldosterone. In addition, it can promote pathologic changes in cardiovascular function.
How does the RAAS raise blood pressure?
By causing vasoconstriction and by increasing blood volume (secondary to aldosterone-mediated retention of sodium and water).
In addition to the traditional RAAS in which angiotensin II is produced in the blood and then carried to target tissues, angiotensin II can be produced locally by individual tissues.
Angiotensin-Converting Enzyme Inhibitors
Beneficial effects of ACE inhibitors result largely from the inhibition of ACE and partly from inhibition of kinase II (the name for ACE when the substrate is bradykinin).
By inhibiting ACE, ACE inhibitors reduce the production of angiotensin II. The result is vasodilation, decreased blood volume, and prevention or reversal of pathologic changes in the heart and blood vessels mediated by angiotensin II and aldosterone.
ACE Inhibitors are used to treat
HTN, HF, MI, and established diabetic neuropathy.
In addition, used to prevent MI, stroke, and death (from cardiovascular causes) in patients at high risk for a cardiovascular event. Of note, ACE inhibitors (and ARBs) are not effective for primary prevention of diabetic neuropathy.
Preliminary data indicate that ACE Inhibitors (and ARBs) can reduce the risk of developing diabetic retinopathy, although they cannot slow the progression of established retinopathy.
ACE Inhibitor SE
Serious first-dose hypotension by causing a sharp drop in circulating angiotensin II.
Cough secondary to the accumulation of bradykinin is the most common reason for the discontinuation of ACE inhibitors (change to ARBs).
Hyperkalemia- suppressing aldosterone release. Potassium sparing diuretics must be used with caution in patients taking these drugs, and these patients should not use potassium supplements or salt substitutes.
Because ACE inhibitors can cause major fetal malformation, they should be avoided during pregnancy. Until recently, that risk was thought to be limited to exposure during the second and third trimesters. However, new data indicate that exposure during the first trimester also may be dangerous.
ACE Inhibitors can cause a precipitous drop in blood pressure in patients with bilateral renal artery stenosis in the artery to a single remaining kidney.
Aliskiren- A Direct Renin Inhibitor
Aliskiren- binds tightly with renin, thereby inhibiting the cleavage of angiotensinogen into angiotensin I. As a result, the drug supresses the entire RAAS.
Similar to the ACE inhibitors and ARBs, aliskiren caues vasodilation, suppresses aldosterone release, promotes the excretion of sodium and water, reduces blood pressure, and causes birth defects and angioedema.
Despite their similarities, aliskiren, ARBs, and ACE inhibitors are not clinically interchangeable.
Aldosterone Antagonists
Eplernone, Spironolactone
Potassium sparing
Block receptors for aldosterone.
By blocking aldosterone receptors, aldosterone antagonists can promote renal excretion of sodium and water ( and can thereby reduce blood volume and blood pressure) and prevent or reverse pathologic effects of aldosterone on cardiovascular structure and function
Calcium Channels
Gated pores in the cytoplasmic membrane that regulate calcium entry into cells.
In blood vessels, calcium entry causes vasoconstriction; calcium channel blockade, therefore, causes vasodilation.
In the heart, calcium entry increases the heart rate, atroventricular conduction, and myocardial contractility; therefore, calcium channel blockade has the opposite effects.
In the heart, calcium channels are coupled to beta1 receptors, activation of which enhances calcium entry. As a result, calcium channel blockade and beta blockade have identical effects on cardiac function.
Calcium Channel Blockers: Classification and Sites of Action
At therapeutic doses, nifedipine and the other dihydropyridines act primarily on vascular smooth muscle; in contrast, verapamil and diltiazem act on VSM and the heart.
Verapamil and Diltiazem
All CCBs promote vasodilation and therefore are useful for hypertension and angina pectoris.
Because they suppress AV conduction, useful for treating cardiac dysrhythmias. HR
Because of their cardiosuppressant effects, cause bradycardia, partial or complete AV block and exacerbation of HF.
BB intensify cardiosuppression caused by verapamil and diltiazem.
Dihydropyridines
Agents that act mainly on vascular smooth muscle.
Nifedipine (Norvasc)
Can cause reflex tachycardia that is most intense with rapid-acting formulations and much less intense with sustained-release formulations.
BB can be used to suppress reflex tachycardia.
Because they cause vasodilation, all CCBs can cause dizziness, headache, and peripheral edema. Discontinue for swelling.
In toxic doses, can cause cardiosuppression, just as verapamil and diltiazem.
Rapid acting nifedipine associated with increased mortality in patients with MI and unstable angina, although a causal relationship has not been established. Use with great caution!
Selectivity of Vasodilators
Some are selective for arterioles, some are selective for veins, some dilate both types of vessels.
Drugs that dilate arterioles reduce cardiac afterload and thus can reduce cardiac work while increasing cardiac output and tissue perfusion.
Drugs that dilate veins reduce cardiac preload and thus can reduce cardiac work, cardiac output, and tissue perfusion.
Indications for Vasodilators
Essential HTN Hypertensive crisis Angina pectoris Heart failure MI
