16.1 Introduction to the Heart, Circulation, and Blood Flow

Anatomy and Physiology of the Heart

The heart is a muscular pump responsible for moving blood to every tissue in the body. For pharmacology, understanding its structure and electrical system is essential because many cardiac drugs target specific chambers, valves, or parts of the conduction pathway.

Anatomical Structures of the Heart

The heart has four chambers, four valves, its own blood supply, and a built-in electrical system.

Chambers:

• Right atrium receives deoxygenated blood from the body through two large veins: the superior vena cava (drains the upper body) and the inferior vena cava (drains the lower body).
• Left atrium receives oxygenated blood returning from the lungs via the pulmonary veins.
• Right ventricle pumps deoxygenated blood out to the lungs through the pulmonary artery.
• Left ventricle pumps oxygenated blood out to the entire body through the aorta. This is the thickest-walled chamber because it has to generate enough force to push blood through the entire systemic circulation.

Valves prevent blood from flowing backward:

• Tricuspid valve sits between the right atrium and right ventricle
• Pulmonary valve sits between the right ventricle and pulmonary artery
• Mitral valve (also called the bicuspid valve) sits between the left atrium and left ventricle
• Aortic valve sits between the left ventricle and aorta

Coronary arteries branch off the base of the aorta and supply oxygenated blood to the heart muscle (myocardium) itself. If these become blocked, the result is a myocardial infarction (heart attack).

Conduction system coordinates each heartbeat in a specific sequence:

1. The sinoatrial (SA) node, located in the right atrium, fires an electrical impulse first. It's the heart's natural pacemaker, setting a resting rate of about 60–100 beats per minute.
2. The impulse travels through the atria, causing them to contract, and reaches the atrioventricular (AV) node at the junction between the atria and ventricles. The AV node briefly delays the signal so the atria finish emptying before the ventricles contract.
3. The impulse then travels down the Bundle of His, splits into left and right bundle branches, and spreads through the Purkinje fibers across the ventricles, triggering a coordinated ventricular contraction.

This sequence matters in pharmacology because antiarrhythmic drugs target different parts of this pathway to correct abnormal heart rhythms.

Circulation and Blood Flow

Blood moves through two connected loops: systemic circulation (body) and pulmonary circulation (lungs). These loops run simultaneously, driven by the right and left sides of the heart.

Blood Circulation Process

Systemic circulation delivers oxygen to the body's tissues:

1. Oxygenated blood enters the left atrium from the pulmonary veins.
2. It passes through the mitral valve into the left ventricle.
3. The left ventricle contracts, pushing blood through the aortic valve into the aorta.
4. Blood travels through progressively smaller vessels: arteries → arterioles → capillaries (the smallest vessels, where oxygen and nutrient exchange actually happens at the tissue level).
5. Now deoxygenated, blood collects into venules → veins and returns to the right atrium via the superior and inferior vena cava.

Pulmonary circulation picks up fresh oxygen and drops off carbon dioxide:

1. Deoxygenated blood flows from the right atrium through the tricuspid valve into the right ventricle.
2. The right ventricle contracts, sending blood through the pulmonary valve into the pulmonary artery.
3. In the lungs, gas exchange occurs across the alveolar-capillary membrane: $CO_2$ is released and $O_2$ is picked up.
4. Oxygenated blood returns to the left atrium via the pulmonary veins, and the cycle starts again.

Factors Influencing Blood Flow

Four main factors determine how much blood reaches the tissues. Many cardiovascular drugs work by manipulating one or more of these.

Vessel diameter has the biggest impact on resistance to flow:

• Vasoconstriction (narrowing) increases resistance and decreases blood flow. This happens with cold exposure or sympathetic nervous system activation. Drugs like phenylephrine cause vasoconstriction.
• Vasodilation (widening) decreases resistance and increases blood flow. This happens during exercise or with drugs like nitroglycerin.

Blood viscosity refers to how thick or thin the blood is:

• Higher viscosity means more resistance. Dehydration and polycythemia (excess red blood cells) both thicken the blood.
• Lower viscosity means less resistance. Severe anemia reduces viscosity because there are fewer red blood cells.

Pressure gradient is the difference in pressure between two points in a vessel:

• Blood always flows from higher pressure to lower pressure. A larger pressure difference means faster flow; a smaller difference means slower flow.

Cardiac output (CO) is the total volume of blood the heart pumps per minute:

$CO = Heart\;Rate \times Stroke\;Volume$

• Heart rate is beats per minute. Stroke volume is the amount of blood ejected with each beat (normally about 70 mL).
• A typical resting cardiac output is roughly 5 L/min. If either heart rate or stroke volume drops significantly (as in heart failure), blood flow to tissues decreases.

Arterial vs. Venous Pressure

The arterial and venous sides of the circulation operate under very different pressures, and understanding this distinction helps explain many cardiovascular conditions and drug effects.

Systemic arterial pressure:

• Normal resting value is approximately 120/80 mmHg (systolic/diastolic).
• Generated by left ventricular contraction and maintained by the elastic recoil of arterial walls between beats.
• Must stay high enough to perfuse organs. The brain and kidneys are especially sensitive to drops in arterial pressure.
• Chronically elevated arterial pressure (hypertension) damages vessel walls over time and increases the risk of stroke, heart attack, and kidney disease.

Venous pressure:

• Much lower, typically around 2–8 mmHg in the central veins near the heart.
• Blood return to the heart depends on three mechanisms: the skeletal muscle pump (leg muscles squeeze veins during movement), the respiratory pump (pressure changes during breathing pull blood toward the chest), and venous valves that prevent backflow.
• Elevated venous pressure can cause fluid to leak into tissues, resulting in edema (swelling). Chronic venous insufficiency leads to problems like varicose veins.

Hemodynamics and Cardiovascular Function

Hemodynamics is the study of the physical forces that govern blood flow. It ties together everything covered above.

• Blood pressure is the force blood exerts on vessel walls. It's the driving force behind circulation and is determined by cardiac output and systemic vascular resistance.
• Perfusion is the actual delivery of oxygenated blood to tissues. Adequate perfusion requires sufficient blood pressure, cardiac output, and open vessels. When perfusion drops below what tissues need, ischemia (oxygen deprivation) occurs.
• Cardiac output, as noted above, depends on heart rate and stroke volume. Pharmacologic interventions often target one or both: beta-blockers reduce heart rate, while positive inotropes (like digoxin) increase stroke volume by strengthening contraction.

These hemodynamic principles form the foundation for understanding why specific cardiovascular drugs are chosen for specific conditions.