5.6 Cardiac Output, Venous Return & the Lymphatic System

Cardiac Output and Its Determinants

Quick Answer: Cardiac output (CO) = stroke volume (SV) × heart rate (HR). Stroke volume depends on preload (the Frank-Starling mechanism), afterload, and contractility. Venous return must equal CO over time and is aided by skeletal muscle and respiratory pumps. The PA-CAT Bulletin of Information, rev. 20240815, places this under Circulation and "The Heart."

Cardiac Output Equation

CO = SV × HR. At rest, a typical adult has SV ≈ 70 mL and HR ≈ 72 bpm, giving CO ≈ 5 L/min. The cardiac index normalizes CO to body surface area: CI = CO / BSA ≈ 3 L/min/m². During exercise, CO can rise 4–6 fold in trained athletes, mainly through increased HR and SV (the latter via increased preload and contractility).

Determinants of Stroke Volume

Stroke volume is the difference between end-diastolic volume (EDV) and end-systolic volume (ESV): SV = EDV − ESV. Three factors govern SV:

1. Preload (Frank-Starling Mechanism)

Preload is the ventricular wall stress at end diastole, practically indexed by EDV. The Frank-Starling law states that the ventricle contracts more forcefully when it is filled more — within limits. Increased venous return stretches sarcomeres toward their optimal length (~2.2 μm), increasing the sensitivity of troponin C to calcium and the number of cross-bridges formed. The relationship is captured by a ventricular function curve: as EDV rises, SV rises, until the curve plateaus and, at very high volumes, falls (decompensation).

2. Afterload

Afterload is the pressure the ventricle must overcome to eject blood — roughly systemic arterial pressure for the left ventricle, pulmonary arterial pressure for the right. Higher afterload increases ESV and reduces SV because the ventricle cannot fully empty. Hypertension chronically raises LV afterload, leading to compensatory hypertrophy; aortic stenosis raises afterload at the valve level.

3. Contractility (Inotropy)

Contractility is the intrinsic vigor of contraction at a given preload, independent of stretch. It is increased by sympathetic stimulation (β₁ receptors → Gs → cAMP → PKA → phosphorylates L-type Ca²⁺ channels → more Ca²⁺ entry → more Ca²⁺ released from the sarcoplasmic reticulum) and by positive inotropes such as digoxin (inhibits Na⁺/K⁺ ATPase → intracellular Na⁺ rises → Na⁺/Ca²⁺ exchanger works less → intracellular Ca²⁺ rises). Contractility is decreased by β-blockers, calcium channel blockers, acidosis, and hypoxia.

Venous Return

Venous return is the flow of blood back to the heart and must equal CO over any extended interval. The systemic filling pressure (Psf) (~7 mmHg) drives blood from the venous compartment toward the right atrium; the pressure gradient Psf − right atrial pressure sets venous return. Three mechanisms assist:

• Skeletal muscle pump — contracting leg muscles compress veins; one-way valves prevent backflow, propelling blood upward.
• Respiratory pump — inspiration lowers intrathoracic pressure (right atrial pressure falls) and raises intra-abdominal pressure, enhancing venous return.
• Venous valves — prevent retrograde flow; incompetence causes varicose veins.

Anything that lowers Psf (e.g., hypovolemia, venodilation) or raises right atrial pressure (e.g., right heart failure, tension pneumothorax, positive-pressure ventilation) reduces venous return. Standing pools blood in the legs, lowering preload — the explanation for orthostatic hypotension and syncope after prolonged standing.

The Guyton Model

Arthur Guyton framed the circulation as a balance between the cardiac function curve (rising CO with rising right atrial pressure up to a plateau) and the venous return curve (falling venous return with rising right atrial pressure). The intersection is the operating point. Increasing contractility shifts the cardiac curve upward; increasing blood volume shifts the venous return curve rightward (more Psf). This framework explains hemorrhage, heart failure, and exercise as movements of these curves.

The Lymphatic System

Lymphatics perform three functions:

1. Fluid balance — return ~3 L/day of filtered fluid and protein to the bloodstream via the thoracic duct (left subclavian vein) and right lymphatic duct (right subclavian vein).
2. Fat absorption — lacteals in intestinal villi absorb dietary triglycerides as chylomicrons.
3. Immune surveillance — lymph nodes filter lymph and host immune cell interactions.

Lymph flow is low pressure and relies on skeletal muscle contraction, one-way valves, and arterial pulsations. Lymphedema arises from:

• Surgical lymph node dissection (e.g., after mastectomy with axillary node removal).
• Filariasis (Wuchereria bancrofti — elephantiasis).
• Radiation therapy causing fibrosis.
• Congenital absence (Milroy disease).

Lymphedema is protein-rich, in contrast to the low-protein edema of hypoalbuminemia, because protein-rich interstitial fluid accumulates when lymphatic return fails.

Edema Revisited

Recall the edema mechanisms from Section 5.5: increased Pc (heart failure), decreased πc (hypoalbuminemia), increased Kf (inflammation), and lymphatic obstruction. Right heart failure raises systemic venous pressure, increasing Pc and producing dependent edema and jugular venous distention. Left heart failure raises pulmonary venous pressure, producing pulmonary edema. Distinguishing these patterns is a PA-CAT-style clinical application of venous return and cardiac output physiology.

Integrated Example: Exercise

During exercise: sympathetic output raises HR and contractility; venoconstriction and the muscle pump raise preload; metabolic vasodilation lowers afterload in active beds. The result is a several-fold rise in CO that is matched by a similar rise in venous return — a coordinated application of every concept in this section.