Comprehensive Physiology: Structure and Function of the Human Heart

Introduction to the Circulatory System and Homeostasis

The circulatory system constitutes the essential transport framework of the organism, functioning as a vital mechanism for maintaining homeostasis. It is composed of three fundamental parts: the heart, the blood vessels, and the blood. The heart serves as a central pump that provides the blood with the mechanical energy required for its flow toward the peripheral tissues. This movement follows the physical principle that fluids flow from regions of higher pressure to zones of lower pressure. The blood vessels act as the specialized communication pathways through which blood travels from the heart to the tissues and subsequently returns. The blood itself is the liquid medium responsible for the long-distance transport of dissolved or suspended materials, including oxygen ($O_2$), carbon dioxide ($CO_2$), nutrients, metabolic waste products, electrolytes, and hormones, as well as various cell types.

Homeostasis depends on the continuous supply of essential materials, such as $O_2$ and nutrients, which are harvested from the environment, balanced against the persistent removal of metabolic wastes. Because all tissues have a vital and continuous need for blood supply, they depend entirely on the rhythmic contractions or beats of the heart. The heart dynamically adjusts its output to ensure that blood is distributed in appropriate quantities between various tissues and organs, whether the body is at rest or engaged in intense physical activity. This remarkable muscle, typically the size of a closed fist and weighing between $250\,g$ and $300\,g$ in an adult, beats more than $100,000$ times per day to propel blood through a network of vessels spanning more than $100,000\,km$.

Macroscopic Anatomy and Situation of the Heart

The heart is a red-brown muscle situated within the thoracic cavity, specifically within the mediastinum, which is the space located between the two lungs. It is positioned behind the sternum and is enveloped by a protective membrane known as the pericardium. The heart is oriented obliquely, with its apex or tip pointing toward the front, downward, and to the left. The apex rests upon the diaphragm, the primary muscle separating the thoracic and abdominal cavities, at the approximate level of the fifth dorsal vertebra. Opposite the apex is the base of the heart, which points toward the rear, upward, and to the right.

The external surfaces of the heart include the sterno-costal or anterior face, located behind the sternum and ribs, and the diaphragmatic or inferior face, which rests on the diaphragm covering the region between the apex and the right border. The heart is suspended within the mediastinum by a vascular pedicle comprised of several major structures: the aorta, the pulmonary artery, the four pulmonary veins, the two venae cavae, and a network of sympathetic and parasympathetic nerves. Adipose tissue is often found in the sub-epicardial regions, filling the furrows between superficial muscular bundles and coronary arteries, which helps to give the organ its rounded shape.

Cardiac Cavities and Internal Morphology

The heart is a hollow muscular organ divided into two distinct parts known as the right heart and the left heart. Although they are anatomically and functionally separate, they operate in a synchronized manner. Each part is further subdivided into two chambers, resulting in a total of four cavities: the right atrium (OD), the right ventricle (VD), the left atrium (OG), and the left ventricle (VG). The atria are located at the superior portion of the heart and possess thin walls, measuring approximately $1\,mm$ in thickness. Their internal surfaces are characterized by pectinate muscles. In contrast, the ventricles are located inferiorly and are significantly larger and thicker than the atria. The right ventricle has a wall thickness of approximately $5\,mm$, while the left ventricle, which must overcome higher resistance to pump blood throughout the entire body, has a wall thickness ranging from $10\,mm$ to $15\,mm$ and is piriform in shape. The internal ventricular surface is marked by a complex muscular network known as trabeculae, including fibrous "mountain rope" structures and papillary muscles or pillars.

The two atria are separated by the interatrial septum, which contains a central depression called the fossa ovalis. This area is the site of the former foramen ovale, a fetal orifice that allowed oxygenated maternal blood to bypass pulmonary circulation; this opening typically closes at birth in about $70\%$ of individuals. The two ventricles are separated by a robust muscular wall known as the interventricular septum. A non-conductive fibrous ring serves to electrically isolate the atrial walls from the ventricular walls, ensuring coordinated electrical signaling. Functionally, the right pump (RA and RV) receives deoxygenated venous blood from the body and propels it toward the lungs for oxygenation, while the left pump (LA and LV) receives oxygenated blood from the lungs and propels it to all the organs of the body.

Vascular Connections and Valvular Systems

The heart's chambers are connected to the systemic and pulmonary circulations through specific vascular landmarks. The right atrium receives blood from the superior vena cava (VCS) and the inferior vena cava (VCI). At the opening of the VCI, a sickle-shaped fold called the Eustachian valve (valvule d'Eustachi) is present, which served to direct blood flow toward the foramen ovale during fetal life. The right ventricle empties through the pulmonary orifice into the pulmonary artery (AP). On the left side, the left atrium receives oxygenated blood from the four pulmonary veins (VP), and the left ventricle ejects blood through the aortic orifice into the aorta (Ao).

A sophisticated system of four valves ensures the unidirectional flow of blood through the heart. The atrioventricular (AV) valves are located between the atria and the ventricles. On the right, the tricuspid valve consists of three membranous cusps (anterior, septal, and posterior). On the left, the mitral valve (also known as the bicuspide) consists of two main cusps, each further divided into three segments ($A1$, $A2$, $A3$ and $P1$, $P2$, $P3$). These valves are anchored to the papillary muscles by chordae tendineae (cordage), which prevent the valves from prolapsing into the atria during ventricular contraction. The semilunar or sigmoid valves are located at the origins of the great arteries. Both the aortic and pulmonary valves consist of three "pigeon's nest" leaflets that prevent the reflux of arterial blood back into the ventricles. Notably, the venous inlets (VCS, VCI, and VP) do not possess a valvular system. The sounds produced by the closing of these valves can be auscultated at specific points on the chest wall: the aortic focus at the $2^{nd}$ right intercostal space, the pulmonary focus at the $2^{nd}$ left intercostal space, the mitral focus at the $5^{th}$ left intercostal space, and the tricuspid focus in the $4^{th}$ to $5^{th}$ intercostal space in the xyphoid region.

Histology of the Heart Wall

The cardiac wall is organized into three distinct layers or tunics from the internal to the external surface: the endocardium, the myocardium, and the pericardium. The endocardium is a thin layer of endothelium resting on connective tissue that lines the cavities, valves, pillars, and tendons, providing a smooth surface to reduce blood friction. The myocardium is the thick, active middle layer composed of specialized striated muscle fibers arranged in a complex network of layers (external longitudinal, middle circular/radial, and internal longitudinal). This muscle tissue is incapable of regeneration and is highly vascularized by the coronary system. The pericardium consists of an outer dense fibrous portion and an inner serous portion. The serous pericardium is divided into a parietal layer and a visceral layer (also called the epicardium), separated by the pericardial cavity containing a lubricating fluid film that allows for smooth sliding during heart beats. Inflammation of these layers is referred to as endocarditis, myocarditis, or pericarditis; an accumulation of fluid in the pericardium can lead to cardiac tamponade.

Myocardial Cell Types and the Functional Syncytium

The myocardium is composed of three types of cells, known as myocytes. The majority, about $90\%$ of the heart's mass, consists of undifferentiated contractile myocytes. These are cylindrical striated fibers, approximately $100\,\mu m$ in length and $15\,\mu m$ in diameter. They are arranged in series and connected by intercalated discs. These discs contain desmosomes and fascia adherens that act as rivets to hold cells together, as well as gap junctions (nexus) made of connexin proteins that allow for low-resistance ion diffusion. This connectivity makes the myocardium a functional syncytium, where electrical impulses spread rapidly. Internally, these cells feature a sarcolemma with transverse tubules (T-tubules) that form triads with the sarcoplasmic reticulum (RS), the primary site for intracellular calcium storage. The cytoplasm is rich in mitochondria, which occupy $30\%$ of the cell volume, as well as myofibrils, ribosomes, and glycogen. A second cell type consists of specialized nodal cells, which are poor in contractile structures but are responsible for generating and conducting the electrical signals that govern cardiac rhythm. The third type consists of endocrine myocytes.

The Nodal System and Cardiac Automatism

The nodal tissue is the anatomical basis for cardiac automatism, organized into nodes, bundles, and networks. The sequence starts at the sinoatrial node, or the node of Keith and Flack, located in the wall of the right atrium near the superior vena cava. This node acts as the primary pacemaker and contains P cells (pacemaker cells) and transitional cells that facilitate impulse transmission. The signal then travels to the atrioventricular node, or the node of Aschoff-Tawara, located in the lower interatrial septum above the tricuspid valve. This node connects to the Bundle of His, which passes through the interventricular septum and divides into right and left branches. These branches descend toward the heart's apex and then turn upward into the ventricular walls, giving rise to the Purkinje network. This network distributes the electrical impulse throughout the ventricular myocardium, ensuring coordinated contraction.

Coronary Circulation and Vascular Systems

The heart's own blood supply is managed by the coronary circulation. The right and left coronary arteries originate from the sinus of Valsalva just above the aortic valve. The left coronary artery typically arises from the antero-left sinus and supplies the anterior and lateral walls of the left ventricle. The right coronary artery arises from the antero-right sinus and supplies the right ventricle and the posterior wall of the heart. The myocardial demand for oxygen is very high, and because this vascularization is terminal in nature, any obstruction or narrowing (such as from atherosclerosis or clots) lead to ischemia. Venous blood is collected by coronary veins that run parallel to the arteries and drain into the coronary sinus, which opens into the right atrium.

The broader circulatory system is divided into two circuits. The systemic or "great" circulation moves from the left heart to the right heart, involving the aorta, systemic capillaries, and systemic veins to nourish the body's tissues. The pulmonary or "little" circulation moves from the right heart to the left heart, involving the pulmonary artery, pulmonary capillaries, and pulmonary veins to facilitate gas exchange. The cardiovascular system is further classified by pressure. The high-pressure system includes the systemic arteries and the left ventricle during systole; it is characterized by low distensibility and a capacity of approximately $700\,ml$, and its behavior is governed by Poiseuille's law. The low-pressure system includes the systemic veins, both atria, the right ventricle, segments of the pulmonary circulation, and the left ventricle during diastole. It is highly distensible, acts as a reservoir, and has a large capacity of approximately $5000\,ml$.

Cardiac Endocrine Function and Diagnostic Markers

Beyond its mechanical function, the heart operates as an endocrine gland. The atrial walls contain secretory granules that produce Atrial Natriuretic Peptide (ANP), a molecule composed of $28$ amino acids ($AA$). ANP has potent diuretic and natriuretic effects, increasing sodium excretion and counteracting the renin-angiotensin-aldosterone and sympathetic systems. The ventricular myocytes, particularly those of the left ventricle due to its larger mass, secrete Brain Natriuretic Peptide (BNP). BNP is a molecule of $32\,AA$ that shares $11\,AA$ in its structure with ANP. It is released into the general circulation via the coronary sinus. The measurement of BNP levels is a critical diagnostic tool in clinical practice, as its concentration rises significantly during cases of acute heart failure. Such functional and structural details are essential for understanding various pathologies, including congenital defects like interatrial or interventricular shunts, hypertensive cardiopathy, and physiological adaptations such as myocardial hypertrophy seen in athletes.