Circulatory System

Question 1

Arterioles vs Veins

Answer 1

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.

Question 2

Vasodilation _______ resistance to blood flow, whereas vasoconstriction _______ resistance to flow.

Answer 2

reduces, increases

Question 3

Three mechanisms that help ensure venous return

Answer 3

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.

Question 4

Starling’s Law and Maintenance of Systemic-Pulmonary Balance

Answer 4

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.

Question 5

Heart rate is _______ by sympathetic nerve impulses and _______ by parasympathetic impulses.

Answer 5

increased, decreased

Question 6

Preload vs Afterload

Answer 6

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.

Question 7

The most important determinant of venous return is…

Answer 7

the systemic filling pressure, which can be reaised by constricting veins and increasing blood volume.

Question 8

Regulation of Arterial Pressure

• Two ways
• Baroreceptor Reflex

Answer 8

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.

Question 9

The Renin-Angiotensin-Aldosterone System

Answer 9

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.

Question 10

Orthostatic hypotension

Answer 10

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.

Question 11

Natriuretic Peptides

Answer 11

Defend the cardiovascular system from volume overload, primarily by reducing blood volume and promoting vasodilation.

Question 12

Physiology of the RAAS

Answer 12

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.

Question 13

How does the RAAS raise blood pressure?

Answer 13

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.

Question 14

Angiotensin-Converting Enzyme Inhibitors

Answer 14

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.

Question 15

ACE Inhibitors are used to treat

Answer 15

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.

Question 16

ACE Inhibitor SE

Answer 16

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.

Question 17

Aliskiren- A Direct Renin Inhibitor

Answer 17

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.

Question 18

Aldosterone Antagonists

Answer 18

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

Question 19

Calcium Channels

Answer 19

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.

Question 20

Calcium Channel Blockers: Classification and Sites of Action

Answer 20

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.

Question 21

Verapamil and Diltiazem

Answer 21

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.

Question 22

Dihydropyridines

Answer 22

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!

Question 23

Selectivity of Vasodilators

Answer 23

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.

Question 24

Indications for Vasodilators

Answer 24

Essential HTN
Hypertensive crisis
Angina pectoris
Heart failure
MI

Question 25

Adverse Effects of Vasodilators

Answer 25

Orthostatic hypotension d/t dilated veins

Dilation of arterioles or veins can cause reflex tachycardia, which increases cardiac work and elevates blood pressure. Reflex tachycardia can be blunted with BB.

Dilation of arterioles or veins can cause fluid retention, a response that can be blunted with a diuretic.

Question 26

Hydralazine

Answer 26

Vasodilator.
Causes selective dilation of arterioles.
Can cause a syndrome that resembles systemic lupus erythematosus.

Question 27

Minoxidil

Answer 27

Vasodilator.

Can cause hypertrichosis (excessive hair growth).

Question 28

Sodium Nitroprusside

Answer 28

Vasodilator.
Dilates arterioles and veins.
Prolonged infusion can result in toxic accumulation of cyanide and thiocyanate.

Question 29

Hypertension

Answer 29

Defined as SBP >140 mmhg or Diastolic > 90 mmHg

Question 30

Primary hypertension

Answer 30

(aka essential HTN)
No identifiable cause
Most common

Question 31

Consequences of Hypertension

Answer 31

Untreated HTN can lead to heart disease, kidney disease, and stroke.
In patients older than 50 y.o. elevated SBP represents a greater cardiovascular risk than an elevated diastolic BP.

Question 32

Management of Chronic Hypertension

Answer 32

Goal of antihypertensive therapy is to reduce mobidity and mortality without diminishing patients quality of life. For most patients, this goal is achieved by maintain a BP below 140/90 or below 130/80 for those with diabetes or CKD.

Two kinds of treatment may be used to reduce BP: drug therapy and lifestyle modification (smoking cessation, reduction of salt and alcohol intake, following the DASH diet, and increasing aerobic exercise.

Question 33

Lifestyle Modifications

Answer 33

Little cost, minimal risk. When implemented before htn develops, they may actually prevent htn. When implemented after they can lower BP thereby decreasing or eliminating the need for drugs.
Weight loss, sodium restriction, following the DASH diet, smoking cessation, and exercise.

Question 34

Baroreceptor Reflex

Answer 34

BR, kidneys and RAAS can oppose attempts to lower BP with drugs. The BR reflex can be countered with a beta blocker, the kidneys with a diuretic, and the RAAS with an angiotensin II receptor blocker ARB, direct renin inhibitor or aldosterone antagonist.

Question 35

Diuretics

Answer 35

Thiazide diuretics (hydrochlorothiazide) and loop diuretics (furosemide) reduce BP in two ways: 1) reduce blood volume (by promoting diuresis) and 2) reduce arterial resistance (by an unknown mechanism). 
Watch potassium, may need supplement. Take in the AM. 

Loop diuretics should be reserved for 1) patients who need greater diuresis than can be achieved with thiazides and 2) patients with a low glomerular filtration rate (Thiazides do not work when the GFR is low).

Question 36

Beta blockers

Answer 36

(e.g. propanolol) appear to lower BP primarily by reducing peripheral vascular resistance; the mechanism is unknown. They may also lower BP by reducing myocardial contractility and suppressing reflex tachycardia (through beta1 blockade in heart) and by reducing renin release (through beta1 blockade in the kidneys).

Question 37

Calcium Channel Blockers

Answer 37

(e.g. diltiazem and nifedipine) reduce BP by promoting dilation of the arterioles.

Question 38

ACE inhibitors, ARBs, and DRIs

Answer 38

lower BP by preventing angiotensin II-mediated vasoconstriction and aldosterone-mediated volume expansion. Whereas ACE inhibitors work by blocking the formation of angiotensin II, ARBs block the actions of angiotensin II. DRIs prevent the formation of angiotensin I, thereby shutting down the entire RAAS.

Question 39

Aldosterone antagonists

Answer 39

Lower BP by preventing aldosterone-mediated retention of sodium and water in the kidneys.

Question 40

Minimizing Adverse Effects of HTN therapy

Answer 40

Patients with stage 1 HTN often can be treated with one drug; patients with stage 2 HTN usually require 2 or more drugs.

Thiazide diuretics are the preferred drugs for therapy of uncomplicated HTN. When a combination of drugs are used for htn, each drug should have a different mechanism of action.

Dosages of antihypertenisve drugs should be low initially and then gradually increased. This approach minimizes adverse effects and allows baroreceptors to reset to a lower pressure.

Question 41

Promoting adherence

Answer 41

Lack of patient adherence is the major cause of treatment failure in antihypertensive therapy.
Adherence is difficult to achieve because
1) hypertension has no symptoms (therefore benefits are not obvious)
2)hypertension progresses slowly (so patients think they can postopone treatment)
3) treatment is complex and expensive, continues lifelong, and can have adverse effects

Question 42

Drugs for Hypertensive Emergencies

Answer 42

A severe HTN emergency exists when the diastolic BP exceeds 120mmHg.
Nitroprusside (IV) is a drug of choice for htn emergencies

Question 43

Drugs for HTN Disorders of Pregnancy

Answer 43

Caused by retaining fluid

Chronic htn is relatively benign, whereas preeclampsia can lead to life-threatening complications for the mother and fetus.

Methyldopa is a drug of choice for treating chronic htn of pregnancy.
HTN is the most common complication of pregnancy.
Preeclampsia is a multisystem disorder characterized by the combination of elevated BP )above 140/90mmHg) and proteinuria (300mg or more in 24 hours) that develops after the 20th week of gestation