18. The Cardiovascular System I

Heart Anatomy, Cardiac Cycle, and Electrical Conduction

Learning Objectives

18.1 Location, Orientation, and Coverings

Where it actually is

Almost everyone points to the wrong place. Ask a class of new students to indicate the heart and most hands go to the left chest, near the armpit. The heart is a midline organ that happens to be tilted. It sits in the mediastinum — the central compartment of the thoracic cavity you met in §1.7 — between the two pleural cavities, behind the sternum, in front of the vertebral column, and on top of the diaphragm.

Its dimensions in an average adult: about 12 cm long, 9 cm wide at its broadest, 6 cm thick front to back, and 250–350 g — roughly the size of a closed fist, and lighter than most people guess. Approximately two-thirds of its mass lies to the left of the midline. That asymmetry, not a leftward position of the whole organ, is what makes the heartbeat palpable on the left side of the chest.

The heart is not oriented the way textbook diagrams draw it. It lies obliquely, rotated so that the right ventricle faces mostly forward and the left ventricle sits mostly behind and to the left. This matters clinically: the chamber closest to the anterior chest wall — and therefore the one damaged by penetrating trauma or compressed during CPR — is the right ventricle, even though the left ventricle is the one everyone worries about.

Two landmarks organize everything:

• The base is the broad superior surface, formed mostly by the left atrium, where the great vessels enter and leave. It sits deep to the 2nd and 3rd costal cartilages at the level of vertebrae T5–T8. Counterintuitively, the base is at the top: the heart is a cone standing on its point.
• The apex is the blunt inferolateral tip, formed by the left ventricle, directed anteriorly, inferiorly, and to the left. In a healthy adult it lies in the 5th intercostal space at the left midclavicular line, about 8–9 cm from the midline.

     ANTERIOR VIEW OF THE CHEST — surface projection of the heart
     (clinician's view: the patient's RIGHT appears on YOUR LEFT)

          patient RIGHT ◄──────────  MIDLINE  ──────────► patient LEFT
                                        ║
                                  ┌─────╨─────┐
                                  │  TRACHEA  │
                                  └─────┬─────┘
   rib 2 ─────────────────────╔═════════╧═════════════════╗──────────────
                       SVC ──►║   B  A  S  E  (left atrium mostly)║
                              ║   ┌────────┐    ┌────────┐        ║
                              ║   │ RIGHT  │    │  LEFT  │◄─ pulmonary
   rib 3 ────────────────────╔╝   │ ATRIUM │    │ ATRIUM │  veins  ║─────
                             ║    └────┬───┘    └───┬────┘        ║
                             ║    ┌────┴───┐    ┌───┴─────┐       ║
   rib 4 ──────────────────╔═╝    │ RIGHT  │    │  LEFT   │      ╔╝─────
                           ║      │VENTRICLE│   │VENTRICLE│      ║
                           ║      │ (most   │   │ (behind │      ║
   rib 5 ────────────────╔═╝      │ anterior)│  │ and left)│    ╔╝───────
                         ║        └─────────┘   └─────┬───┘     ║
                         ║                            ▼         ║
   rib 6 ───────────────╚════════════════════════════ ★ ═══════╝─────────
                                                    A P E X
                                    5th intercostal space,
                                    left midclavicular line
                                    = POINT OF MAXIMAL IMPULSE

   ── right border = RIGHT ATRIUM      ── left border = LEFT VENTRICLE
   ── inferior border = RIGHT VENTRICLE (rests on the diaphragm)

   ═══════════ THE PERICARDIAL SANDWICH (enlarged, one wall) ═══════════

     outside ──►  FIBROUS PERICARDIUM      dense irregular connective
                  ▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓▓     tissue; tough, inelastic,
                                           anchored to diaphragm + sternum
                  PARIETAL SEROUS layer    simple squamous mesothelium
                  ─────────────────────
                  ░░ PERICARDIAL CAVITY ░░  15–50 mL serous fluid
                  ─────────────────────
                  VISCERAL SEROUS layer  = EPICARDIUM
                  ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒     (coronary vessels run here,
                                              embedded in fat)
     inside  ──►  MYOCARDIUM

The point of maximal impulse

Place your fingertips in the fifth intercostal space at your left midclavicular line and you will usually feel a small, discrete tap once per beat. This is the point of maximal impulse (PMI), also called the apex beat: the moment in early systole when the contracting left ventricle twists, shortens, and knocks its apex forward against the chest wall.

The PMI is a free physical examination finding of surprising power, because its position and character both carry information.

• Displaced laterally and inferiorly (say, the 6th space in the anterior axillary line): the left ventricle has dilated. The chamber is bigger, so its apex sits farther out. This is the signature of volume overload or a failing, enlarged ventricle.
• In normal position but sustained and forceful — a heave that lasts most of systole instead of tapping briefly: the left ventricle has thickened without dilating. This is the signature of pressure overload, and it is what an experienced examiner feels in a long-standing hypertensive.

Amara's PMI was described in her chart as "non-displaced, sustained." Hold that observation; it is a bedside preview of her echocardiogram, and it is part of the answer to Question 3.

The pericardium

The heart is enclosed in a triple-layered bag, the pericardium, which is a specific instance of the serous membrane arrangement introduced in §1.7. From the outside inward:

1 · The fibrous pericardium. A tough, inelastic sac of dense irregular connective tissue (Chapter 4). It fuses inferiorly with the central tendon of the diaphragm, attaches anteriorly to the sternum by sternopericardial ligaments, and blends superiorly with the outer coats of the great vessels. Its three jobs follow directly from its material properties: it anchors the heart so that it does not swing around inside the chest, it provides a friction-free outer boundary against the sternum and lungs, and — critically — it prevents acute overfilling, because a bag that will not stretch sets a physical ceiling on how large the heart can become in the next few seconds.

2 · The parietal layer of the serous pericardium. A sheet of simple squamous mesothelium lining the inner surface of the fibrous pericardium.

3 · The visceral layer of the serous pericardium, which is the same membrane folded back on itself at the great vessels to cover the heart's surface. In this location it is called the epicardium, and it is simultaneously the outermost layer of the heart wall.

Between the parietal and visceral layers lies the pericardial cavity holding 15–50 mL of serous fluid — a film thinner than a sheet of paper, spread across the entire heart surface. That film is the difference between a heart that slides silently through 2.5 billion beats and one that grinds.

18.2 The Heart Wall and the Four Chambers

Three layers, three tissue types

Four chambers, four pressures, four wall thicknesses

Here is the single most productive exercise in cardiac anatomy. Do not memorize wall thicknesses. Derive them.

The two ventricles are also different in shape, and for the same reason. The left ventricle is a thick-walled cone with a circular cross-section, the optimal geometry for generating high pressure (by Laplace's law, wall tension for a given pressure is minimized by a small radius and a thick wall). The right ventricle is a thin crescent wrapped around the outside of the left, which sweeps blood forward efficiently at low pressure with much less muscle — a bellows rather than a piston. The right ventricle handles the same stroke volume as the left, every beat, for about one-fifth of the work.

Inside the chambers

The atria. Each atrium has a wrinkled, ear-like flap projecting anteriorly, the auricle (or atrial appendage), which increases atrial volume by roughly 20%. Inside the right atrium and both auricles, the wall is ridged by parallel muscle bundles called pectinate muscles (pecten = comb). The posterior wall of the right atrium is smooth; the boundary between rough and smooth is a ridge called the crista terminalis, and it is an embryological seam — the smooth part derives from the absorbed sinus venosus, the rough part from the true embryonic atrium. The left atrium is almost entirely smooth except for its auricle, because most of its wall derives from absorbed pulmonary veins.

The interatrial septum carries a shallow oval depression, the fossa ovalis, which is the sealed remnant of the fetal foramen ovale (see the Development sidebar in §18.4). In roughly 25% of adults the seal is incomplete — a patent foramen ovale — which is usually harmless but can allow a venous clot to cross directly into the systemic circulation and cause a stroke, a phenomenon called paradoxical embolism.

The left atrial appendage deserves a special note, because it is the reason atrial fibrillation causes strokes. It is a blind, trabeculated pouch. When the atrium contracts normally, it is flushed each beat. When the atrium fibrillates and stops contracting, blood stagnates there, and stagnant blood clots (Chapter 17).

The ventricles. The internal surface is anything but smooth. Irregular muscular ridges called trabeculae carneae ("meaty beams") cover the walls. They are not decorative: they reduce the surface area in contact with blood, they prevent the walls from sticking together by suction at end-systole, and they add mechanical strength for the same mass of muscle in the way that a corrugated sheet is stiffer than a flat one.

Projecting into each ventricular cavity are cone-shaped papillary muscles — three in the right ventricle, two in the left — from whose tips arise thin, tough, collagenous cords, the chordae tendineae ("heart strings"), which fan out and attach to the free edges of the atrioventricular valve cusps. This apparatus is the subject of §18.3.

One structure deserves its own mention: the moderator band (septomarginal trabecula), a muscular bridge running from the interventricular septum to the anterior papillary muscle of the right ventricle. It looks like a random strut. It is not — it carries a branch of the right bundle branch across the cavity so that the anterior papillary muscle is activated early, tightening its chordae before the ventricle develops pressure. A structure that appears to be a mechanical accident is in fact a piece of electrical wiring, and this is one of the more satisfying examples of anatomy refusing to make sense until you know the physiology.

The septa. The interatrial septum separates the atria; the interventricular septum separates the ventricles. The interventricular septum is not uniform: its upper portion is a thin membranous part (a connective-tissue sheet, and the most common site of congenital ventricular septal defects), while the rest is thick muscular septum that functionally belongs to the left ventricle and thickens along with it in hypertension.

18.3 Valves and the Fibrous Skeleton

Four valves, one job, zero muscles

The heart contains four valves, and the first thing to understand about all of them is that none of them is actively operated. There is no muscle that opens a valve and no nerve that closes one. Every valve in the heart is a passive flap that moves in whichever direction the pressure difference across it pushes. Once you internalize that, valve behavior at every point in the cardiac cycle becomes derivable rather than memorizable.

The atrioventricular (AV) valves sit in the fibrous rings between atria and ventricles.

• Right AV valve = tricuspid valve, three cusps.
• Left AV valve = mitral valve (also called bicuspid), two cusps — named for a bishop's mitre, which it resembles.

The semilunar (SL) valves guard the ventricular outflows. Each has three pocket-like cusps shaped like half-moons.

• Pulmonary valve, between right ventricle and pulmonary trunk.
• Aortic valve, between left ventricle and aorta.

Their operation:

Note that there are two moments in every cycle when all four valves are shut. Those are the isovolumetric phases, and they exist because pressure has to be built up before a valve will open and bled off before another will.

Why the AV valves need strings and the semilunar valves do not

The AV valves face a brutal mechanical problem. During ventricular contraction, the pressure beneath their cusps rises to 120 mm Hg while the pressure above them is about 10 mm Hg. A 110 mm Hg pressure differential across a floppy sheet of connective tissue will invert it — blow it backwards into the atrium — unless something holds it down.

That something is the papillary muscle and chordae tendineae apparatus. Here is the elegant part: the papillary muscles are myocardium, and they contract at the same time as the rest of the ventricle — in fact, slightly before, thanks to their early activation. They do not pull the cusps closed. They take up slack, holding the chordae taut like the shrouds of a sail, so that as the cusps balloon upward under pressure they meet edge to edge and stop. The result is a valve that seals tightly under load without prolapsing.

The semilunar valves need no such apparatus for a purely geometric reason. Their cusps are pockets, not flaps. Backpressure fills each pocket, and three filled pockets pressing against each other in the middle of a circular orifice form a self-supporting structure — a tripod of fluid pressure. Backflow closes them more tightly the harder it pushes. Behind each aortic cusp is a small dilation of the aortic wall, the aortic sinus (sinus of Valsalva), which sets up a small vortex that prevents the cusp from plastering against the aortic wall and occluding the coronary artery ostium sitting in it. Two of the three aortic sinuses contain a coronary ostium; the third is called the non-coronary sinus.

The fibrous skeleton and its three jobs

Wrapped around the four valve orifices, at the plane where atria meet ventricles, is a dense network of collagen and elastin: the fibrous skeleton of the heart. It consists of four interconnected rings (the annuli fibrosi) — one around each valve — joined by two thickened masses called the right and left fibrous trigones. It has three functions, and all three matter.

Function 1 — Anchorage. The valve cusps and the myocardial bundles both attach to it. Cardiac muscle has to pull against something; the fibrous skeleton is the origin and insertion for the whole myocardium, playing the role that bone plays for skeletal muscle.

Function 2 — Structural limit. The rings are collagen, and collagen does not stretch. They therefore prevent the valve orifices from dilating under pressure. This is not a trivial job: if a valve ring stretches, the cusps can no longer reach each other and the valve leaks even though the cusps themselves are perfectly normal. This is exactly what happens in a chronically dilated ventricle — so-called functional mitral regurgitation — and it is the reason a failing heart tends to acquire a leaking valve, which then worsens the failure. Another positive feedback loop hiding inside a normal structure.

Function 3 — Electrical insulation. This is the one that makes §18.5 and §18.6 possible. Collagen does not conduct action potentials. The fibrous skeleton is therefore a complete electrical barrier lying between the atria and the ventricles, and there is exactly one gap in it: a small bundle of specialized muscle called the atrioventricular bundle, or bundle of His, which pierces the right fibrous trigone.

Consider what this architecture buys. Because atria and ventricles are electrically isolated, an impulse cannot spread from atrial muscle to ventricular muscle directly. It must pass through the AV node and bundle of His. Since the AV node conducts slowly, it functions as a mandatory checkpoint, and everything downstream is under its control:

• The ventricles cannot contract until the atria have finished — because the only route in has a built-in delay.
• Rapid, chaotic atrial rhythms cannot be transmitted beat-for-beat to the ventricles, because the single narrow gateway can only conduct so fast. In atrial fibrillation the atria depolarize 400–600 times a minute; the ventricles typically respond 100–160 times a minute. The patient is uncomfortable rather than dead, and the fibrous skeleton is why.
• Because the entire electrical connection is a single small bundle, disease of that one structure produces a specific, recognizable syndrome — heart block — which is a clean demonstration of the whole design.

18.4 The Pathway of Blood and the Coronary Circulation

Two circuits in series

The cardiovascular system is not one loop but two loops joined at the heart, arranged in series so that every drop of blood must pass through both, alternately.

The pulmonary circuit carries blood from the right side of the heart to the lungs and back to the left side. The systemic circuit carries blood from the left side of the heart to every tissue in the body and back to the right side. The heart is a double pump built into one organ, with the right pump serving the pulmonary circuit and the left pump serving the systemic circuit.

Two consequences follow immediately, and both are worth stating out loud because students routinely get them backwards.

First, the pulmonary artery carries deoxygenated blood and the pulmonary veins carry oxygenated blood. These are the only vessels in the body where this is true. The definitions of artery and vein are about direction relative to the heart — arteries carry blood away, veins carry it toward — and have nothing whatever to do with oxygen content.

Second, the two circuits must have identical outputs. They are in series. If the right ventricle ejected even 1% more per beat than the left, blood would accumulate in the lungs at about 50 mL per minute, and the patient would drown in pulmonary edema within hours. The matching is not achieved by any central controller; it emerges automatically from the Frank–Starling mechanism (§18.8), which is one of the most elegant pieces of self-regulation in the body.

Trace one red blood cell, and say the names out loud:

Superior and inferior venae cavae (and coronary sinus) → right atrium → tricuspid valve → right ventricle → pulmonary valve → pulmonary trunk → right and left pulmonary arteries → lung capillaries (gas exchange) → four pulmonary veins → left atrium → mitral valve → left ventricle → aortic valve → aorta → systemic arteries → systemic capillaries (gas exchange) → systemic veins → back to the venae cavae.

   THE HEART IN CORONAL SECTION — anterior wall removed, ► = blood flow
   (patient's RIGHT appears on YOUR LEFT)

        SUPERIOR VENA CAVA         AORTA           PULMONARY TRUNK
        ► from head & arms       ► to body          ► to lungs
                ║                    ║                    ║
                ║      ╔═════════════╝                    ║
                ║      ║   ARCH OF THE AORTA              ║
      ┌─────────╨──────╨──────────────────────────────────╨────────┐
      │                                   ╔══ PULMONARY VEINS      │
      │  ┌─────────────────┐  ┃      ┃  ┌─╨───────────────────┐    │
      │  │  RIGHT ATRIUM   │  ┃  IA  ┃  │    LEFT ATRIUM      │    │
      │  │  pectinate m.   │  ┃ SEPT ┃  │  smooth-walled      │    │
      │  │  wall 2–3 mm    │  ┃fossa ┃  │  wall 2–3 mm        │    │
      │  │                 │  ┃ovalis┃  │  ◄ from lungs (4)   │    │
      │  └────────┬────────┘  ┃      ┃  └──────────┬──────────┘    │
      │           ▼                                ▼               │
      │   ╍╍╍ TRICUSPID VALVE ╍╍╍        ╍╍╍ MITRAL VALVE ╍╍╍      │
      │      (3 cusps, right AV)            (2 cusps, left AV)     │
      │           │                                │               │
      │  ┌────────▼────────┐  ┌──────┐  ┌──────────▼──────────┐    │
      │  │ RIGHT VENTRICLE │  │ INTER│  │   LEFT VENTRICLE    │    │
      │  │  wall 3–5 mm    │  │ VENT-│  │   wall 8–11 mm      │    │
      │  │  peak 25 mm Hg  │  │RICULAR  │   peak 120 mm Hg    │    │
      │  │  crescent shape │  │SEPTUM│  │   cone, circular    │    │
      │  │  trabeculae ▓▓  │  │      │  │   trabeculae ▓▓▓▓   │    │
      │  │  papillary ▲▲▲  │  │      │  │   papillary ▲▲      │    │
      │  │  chordae ///    │  │      │  │   chordae ////      │    │
      │  └────────┬────────┘  └──────┘  └──────────┬──────────┘    │
      └───────────┼──────────────────────────────┬─┼───────────────┘
                  ▲                              │ ▲
          PULMONARY VALVE                        │ AORTIC VALVE
          (3 semilunar cusps)                    │ (3 semilunar cusps;
                                                 │  coronary ostia sit
      INFERIOR VENA CAVA ► from trunk & legs ────┘  in 2 of its sinuses)
      CORONARY SINUS     ► from heart muscle  ───┘  both enter the RA

   THE CIRCUIT (say it out loud):
      body  ► RA ► tricuspid ► RV ► pulmonary valve ► trunk ► LUNGS
      lungs ► LA ► mitral    ► LV ► aortic valve    ► aorta ► BODY

   WALL THICKNESS IS A STATEMENT ABOUT PRESSURE:  2–3 mm atria (they
   push into an open, relaxed chamber) · 3–5 mm RV (25 mm Hg, short
   low-resistance pulmonary circuit) · 8–11 mm LV (120 mm Hg, the
   whole body).  Same stroke volume, five times the work.

        CORONARY ARTERIES → MYOCARDIAL TERRITORY → ECG LEADS
        (anterior view; patient's right on your left)

                         AORTA
                           │
           ┌───────────────┴───────────────┐
      RIGHT CORONARY                  LEFT MAIN CORONARY
       ARTERY (RCA)                    ARTERY  (~1 cm long)
           │                                │
   ┌───────┴────────┐              ┌────────┴─────────┐
   │                │              │                  │
 SA nodal      right marginal    LEFT ANTERIOR    LEFT CIRCUMFLEX
 branch (60%)  branch            DESCENDING (LAD)  ARTERY (LCx)
   │                │              │                  │
 AV nodal      POSTERIOR         diagonal          obtuse marginal
 branch (90%)  DESCENDING        branches          branches
               (in 70% of                          │
                people)                          posterolateral
                                                   branch

  ┌──────────────┬───────────────────────────┬────────────────────┐
  │ ARTERY       │ MYOCARDIUM SUPPLIED       │ ECG LEADS LOOKING  │
  │              │                           │ AT THAT WALL       │
  ├──────────────┼───────────────────────────┼────────────────────┤
  │ LAD          │ anterior LV wall          │ V3, V4  (anterior) │
  │              │ anterior 2/3 of septum    │ V1, V2  (septal)   │
  │              │ apex                      │ (V1–V4 together)   │
  ├──────────────┼───────────────────────────┼────────────────────┤
  │ CIRCUMFLEX   │ LATERAL LV wall           │ I, aVL  (high lat) │
  │ (LCx)  ◄──── │ posterolateral LV wall    │ V5, V6  (low lat)  │
  │  AMARA       │                           │                    │
  ├──────────────┼───────────────────────────┼────────────────────┤
  │ RCA          │ right atrium + ventricle  │ V1, V4R            │
  │              │ INFERIOR LV wall          │ II, III, aVF       │
  │              │ posterior 1/3 of septum   │ (reciprocal V1–V2) │
  │              │ SA node 60%, AV node 90%  │ — rhythm effects — │
  └──────────────┴───────────────────────────┴────────────────────┘

        CROSS-SECTION OF THE VENTRICLES (transverse, from below)
        showing which artery owns which wall

                          ANTERIOR
                      ▓▓▓▓▓▓▓▓▓▓▓▓▓▓        ▓ = LAD territory
                    ▓▓              ▓▓
         SEPTAL   ▓▓    ┌────────┐    ▓▓
         ▓▓▓▓▓▓▓▓▓      │   LV   │      ░░  ░ = CIRCUMFLEX
       ▓ ┌────┐ ▓       │ cavity │       ░░     territory
       ▓ │ RV │ ▓       └────────┘        ░░    (LATERAL)
       ▓ └────┘ ▓▓                       ░░
         ▓▓▓▓    ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒░░░
                    ▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒▒          ▒ = RCA territory
                          INFERIOR                (INFERIOR)

The coronary arteries in detail

The heart is 300 g of continuously working muscle and cannot be nourished by the blood passing through its chambers — the myocardium is far too thick for diffusion from the endocardial surface to reach beyond the innermost fraction of a millimetre. It has its own arterial supply, the coronary circulation, and it is the first branch off the aorta: the two coronary ostia sit in the aortic sinuses, immediately above the aortic valve cusps.

The left main coronary artery is a short trunk, typically less than 1 cm, that divides almost immediately into:

• The left anterior descending artery (LAD), which runs down the anterior interventricular groove toward the apex, giving diagonal branches to the anterior left ventricular wall and septal perforator branches into the anterior two-thirds of the interventricular septum. It supplies roughly 45–55% of the left ventricular mass, which is why occlusion of a proximal LAD has been called the "widow-maker."
• The left circumflex artery (LCx), which curves left in the coronary sulcus around to the back of the heart, giving obtuse marginal branches to the lateral wall of the left ventricle. This is Amara's vessel.

The right coronary artery (RCA) runs in the right coronary sulcus, giving:

• The sinoatrial nodal branch (in about 60% of people; from the circumflex in the rest).
• The right marginal branch to the right ventricle.
• The atrioventricular nodal branch (in about 90% of people).
• In about 70% of people, the posterior descending artery (PDA), which supplies the inferior wall and posterior third of the septum. Whichever artery gives the PDA is said to determine dominance: 70% of people are right-dominant, 10% left-dominant (PDA from the circumflex), and 20% co-dominant.

Amara is co-dominant: her circumflex gives a large posterolateral branch that also supplies the inferolateral wall. That single anatomical variant is why her ECG showed changes in the inferior leads (II, III, aVF) as well as the lateral leads, from a single circumflex lesion.

Coronary veins

Venous drainage runs alongside, and mostly returns through one large vessel.

All four empty into the coronary sinus, a wide venous channel lying in the posterior coronary sulcus, which drains directly into the right atrium — making it the third opening into that chamber alongside the two venae cavae. A small amount of blood bypasses this system entirely: anterior cardiac veins drain the right ventricle straight into the right atrium, and tiny thebesian veins empty directly from the myocardium into all four chambers.

Those thebesian veins are worth a moment, because they explain a small physiological oddity. They dump a trickle of deoxygenated blood directly into the left ventricle, downstream of the lungs. Together with a similar trickle from the bronchial circulation, this is the anatomical shunt that prevents arterial oxygen saturation from ever reaching 100% in a normal person. Amara's SpO₂ of 96% in Chapter 1 was normal partly for this reason.

Coronary flow happens in diastole

This is the most consequential fact in the chapter, and it explains Amara's entire clinical course.

Every other organ in the body is perfused during systole, when arterial pressure is highest. The left ventricle is not — because the left ventricle is the thing generating the pressure. During systole, the contracting myocardium squeezes the coronary vessels running through it. Intramyocardial pressure in the subendocardial layers of the left ventricular wall approaches or exceeds intracavitary pressure, which is 120 mm Hg — higher than the aortic pressure trying to push blood in. Left coronary flow therefore falls almost to zero during systole and surges during diastole, when the muscle relaxes and the vessels reopen while aortic pressure is still around 80 mm Hg.

Three enormous clinical consequences follow.

1 · The relevant perfusion pressure is the aortic diastolic pressure, not the systolic. This is why a patient with a systolic pressure of 90 and a diastolic of 40 may be starving their myocardium despite an apparently adequate blood pressure.

2 · Anything that shortens diastole reduces coronary supply. As heart rate rises, systole shortens only slightly (it has a fixed contractile duration), while diastole is compressed dramatically. At 60 beats per minute the cardiac cycle is 1.0 s, of which about 0.65 s is diastole. At 150 beats per minute the cycle is 0.4 s, of which barely 0.15 s is diastole. Coronary perfusion time has fallen by more than three-quarters — at the very moment when myocardial oxygen demand is highest.

That is the loop Chapter 1 previewed and could not yet explain. Amara arrives with a heart rate of 104 driven by sympathetic activation intended to protect her. The tachycardia raises myocardial oxygen demand and cuts the time available to meet it. It is why a beta-blocker — a drug that slows the heart — is correct treatment for a heart that is not getting enough blood, and why it attacks both halves of the supply–demand equation at once.

3 · The subendocardium is always the first to die. It is the layer under the highest compressive stress during systole and the farthest from the epicardial arteries. When coronary supply becomes marginal, the inner third of the wall becomes ischemic first, while the outer two-thirds hold on. That is the anatomical basis of subendocardial infarction — which, as §18.6 will show, is exactly what produces ST depression rather than ST elevation, and exactly what Amara had.

Two more numbers make the picture complete. Resting coronary blood flow is about 250 mL/min, roughly 5% of cardiac output for an organ that is 0.5% of body weight. And the myocardium extracts about 70–80% of the oxygen delivered to it at rest — compared with about 25% for the body as a whole. Because extraction is already nearly maximal, the heart has almost no reserve on the extraction side. The only way the myocardium can get more oxygen is to receive more flow. A tissue that can only increase supply by increasing flow is exquisitely vulnerable to anything that limits flow, which is the whole tragedy of coronary artery disease in one sentence.

18.5 Cardiac Muscle and the Conduction System

Cardiac muscle: a refresher with the cardiac details added

You met cardiac muscle in Chapter 9. Recall the essentials and note what makes it different from the skeletal muscle you studied alongside it.

The functional consequence of that last point deserves emphasis. In cardiac muscle, the calcium that triggers contraction is not simply released from internal stores on command. Depolarization opens L-type calcium channels in the T-tubule membrane; a small amount of calcium enters from outside the cell; that calcium binds ryanodine receptors on the sarcoplasmic reticulum and triggers release of a much larger internal store. This is calcium-induced calcium release, and it makes cardiac contractile force graded and tunable in a way that skeletal muscle twitch force is not. More calcium entry, stronger beat. That is the molecular basis of contractility (§18.8), and it is the target of a remarkable number of cardiac drugs.

Two kinds of cardiac cell

About 99% of cardiac muscle cells are contractile cells: they do mechanical work.

About 1% are autorhythmic cells (also called pacemaker or conducting cells). They are smaller, contain few myofibrils, contract feebly or not at all, and have one extraordinary property: they depolarize spontaneously. They set the rhythm and distribute it. The heart's beat does not come from the nervous system at all — a heart removed from the body, denervated, and perfused with warm oxygenated solution will beat rhythmically for hours. This property is called autorhythmicity, and it is the reason heart transplantation is possible.

The pacemaker potential

An autorhythmic cell has no stable resting membrane potential. This is the key difference, and everything else follows.

   PACEMAKER CELL (SA node)                 CONTRACTILE CELL (ventricle)
   ────────────────────────────────         ────────────────────────────────

  mV                                       mV
 +20 ┤          ╭─╮                       +30 ┤    ╭──────────────╮
   0 ┤         ╱   ╲                        0 ┤   ╱ 1     2       ╲
     │        ╱     ╲                         │  ╱ plateau ~200 ms ╲
 -20 ┤       ╱       ╲                     -20┤ ╱                   ╲
     │      ╱  Ca2+   ╲  K+                   ││  0        (Ca2+ in  ╲ 3
 -40 ┼┈┈┈╭─╯ THRESHOLD ╲┈┈┈┈┈┈┈┈┈┈┈       -40 ┤│  Na+     = K+ out)   ╲
     │  ╱                ╲                     ││ in                   ╲
 -60 ┤╭╯ PACEMAKER        ╰╮  ╭─             -60┤│                      ╲
     │╯  POTENTIAL          ╰─╯               │ │              4        ╰──────
 -80 ┤   (unstable —                       -80 ┤─╯   stable resting potential
     │    never rests)                          │      (K+ leak, IK1)
 -90 ┤                                      -90 ┤

  PHASE 4 (pacemaker potential)             PHASE 0  fast Na+ influx (upstroke)
   • I_f "funny current" — HCN channels     PHASE 1  brief K+ efflux (I_to) —
     open on HYPERPOLARIZATION, let Na+              small early dip
     in slowly                              PHASE 2  PLATEAU: L-type Ca2+ IN
   • T-type Ca2+ channels add to drift               balanced by delayed
  PHASE 0 (upstroke)                                 rectifier K+ OUT
   • L-type Ca2+ influx at −40 mV           PHASE 3  Ca2+ channels shut,
     — SLOW upstroke, Ca2+-based                     K+ efflux dominates
  PHASE 3 (repolarization)                  PHASE 4  resting, −90 mV
   • K+ efflux, then I_f restarts

  ══════════ WHY THE PLATEAU MATTERS ══════════════════════════════════════

   SKELETAL MUSCLE:  AP  ▮ 2 ms                                   
                     twitch  ╭──╮ 100 ms   → refractory period ENDS long
                     refract ▮▮                before twitch ends
                     → stimuli SUMMATE → TETANUS possible

   CARDIAC MUSCLE:   AP      ▮▮▮▮▮▮▮▮▮▮▮ 250 ms
                     twitch  ╭─────────╮  300 ms   → refractory period
                     refract ▮▮▮▮▮▮▮▮▮▮▮ 250 ms       covers nearly the
                     → stimuli CANNOT summate         whole contraction
                     → TETANUS IMPOSSIBLE  ← this is why you are alive

Work through the pacemaker potential mechanistically, because every drug that changes heart rate acts somewhere in this sequence.

Phase 4 — the pacemaker potential. The cell repolarizes to about −60 mV and immediately begins drifting upward again. Two currents drive the drift:

• The funny current (I_f), carried by HCN channels (hyperpolarization-activated, cyclic-nucleotide-gated). These channels are "funny" because, uniquely, they open when the membrane hyperpolarizes rather than when it depolarizes. They admit sodium (and some potassium), producing a slow inward positive current. Crucially, HCN channels are directly gated by cyclic AMP: more cAMP shifts their activation so they open faster, and less cAMP slows them.
• T-type (transient) calcium channels open near −55 mV and add to the drift over the final stretch to threshold.

Phase 0 — the upstroke. At about −40 mV, L-type calcium channels open. The upstroke of a pacemaker action potential is carried by calcium, not sodium, and calcium channels open and conduct more slowly than fast sodium channels. This is why the SA and AV nodes have slow, rounded upstrokes and slow conduction velocity — a fact with large consequences in a moment.

Phase 3 — repolarization. Calcium channels inactivate, delayed-rectifier potassium channels open, potassium leaves, and the membrane repolarizes back toward −60 mV, whereupon the funny current restarts. There is no phase 1 or 2 in a pacemaker cell.

Now the autonomic control, which is simply modulation of that drift (Chapter 14):

This is the entire mechanism of heart rate control, and it is a single slope on a single graph.

The intrinsic rates and the hierarchy

Autorhythmic tissue exists at several levels, each with its own intrinsic firing rate. The fastest one wins, because it depolarizes the others before they reach their own threshold.

This hierarchy is a safety system: three redundant backups, each slower than the last. A complete failure of the SA node does not stop the heart; it produces a junctional rhythm at around 45 beats per minute. Complete heart block does not stop the heart; it produces a ventricular escape rhythm at around 30. Slow, but alive — and enough to reach a hospital.

The conduction pathway

   THE CARDIAC CONDUCTION SYSTEM — route, velocity, and cumulative time

                              ┌──────────────────────┐
     ① SA NODE                │ 0.05 m/s             │  t = 0 ms
        in the RA wall, at    │ intrinsic 60–100/min │
        the superior end of   └──────────┬───────────┘
        the crista terminalis            │
                                         ▼
     ② ATRIAL MYOCARDIUM + internodal pathways      0.5–1.0 m/s
        ═══════════════════════════════════════     ATRIA DEPOLARIZE
        Bachmann's bundle carries it to the LA      → the P WAVE
                                         │          t ≈ 30–50 ms
                                         ▼
     ╔═══════════ FIBROUS SKELETON — NO CONDUCTION ═══════════════╗
     ║  the ONLY gap is the AV bundle, at the right trigone       ║
     ╚═══════════════════╤════════════════════════════════════════╝
                         ▼
     ③ AV NODE   ┌────────────────────────────────────┐
        in the   │ 0.05 m/s — the SLOWEST tissue      │  ≈ 100 ms
        floor of │ Why slow? Small cells, few gap     │  DELAY HERE
        the RA   │ junctions, Ca2+-based upstroke     │
                 └───────────────────┬────────────────┘  t ≈ 130–150 ms
                                     ▼
     ④ BUNDLE OF HIS                 1.0–2.0 m/s
        pierces the fibrous skeleton
                         │
              ┌──────────┴──────────┐
              ▼                     ▼
     ⑤ RIGHT BUNDLE          LEFT BUNDLE BRANCH        ~2.0 m/s
        BRANCH               (splits: anterior +
        (thin; runs in the    posterior fascicles)
         moderator band)
              │                     │
              ▼                     ▼
     ⑥ PURKINJE FIBRES   ┌────────────────────────────┐
        subendocardial   │ 2.0–4.0 m/s — the FASTEST  │  t ≈ 175 ms
        network          │ Large diameter, glycogen-  │
                         │ rich, many gap junctions   │
                         └──────────────┬─────────────┘
                                        ▼
     ⑦ VENTRICULAR MYOCARDIUM           0.3–0.5 m/s
        APEX FIRST, then base;          VENTRICLES DEPOLARIZE
        endocardium → epicardium        → the QRS COMPLEX
                                        complete by t ≈ 225 ms

   ══ WHY APEX-FIRST MATTERS: contraction begins at the bottom of the
      cone and sweeps upward, so blood is squeezed TOWARD the outflow
      valves at the base — like squeezing a toothpaste tube from the end.

Why the AV nodal delay exists

The AV node is the slowest-conducting tissue in the heart, and this is not a design flaw. It does two indispensable jobs.

Job 1 — It sequences the pump. The atria must finish contracting before the ventricles begin, or atrial contraction would simply push blood against closed AV valves and back into the veins. The delay of roughly 100 ms is precisely the time the atria need to complete their contribution to ventricular filling. On the ECG, this delay is the flat segment between the end of the P wave and the start of the QRS.

Job 2 — It protects the ventricles from the atria. Because the AV node has a long refractory period as well as slow conduction, it acts as a low-pass filter on atrial rate. When the atria fire at 400–600 per minute in atrial fibrillation, or 300 per minute in atrial flutter, the AV node simply cannot pass every impulse. Some arrive while the node is still refractory and are extinguished — concealed conduction. The ventricles receive a fraction of the atrial impulses and continue to fill and eject.

This filtering function is also the target of the commonest drugs in cardiology. Beta-blockers, non-dihydropyridine calcium-channel blockers, and digoxin all slow AV nodal conduction, converting a dangerously fast ventricular response into a manageable one — treating the gateway rather than the arrhythmia.

18.6 Electrocardiography

What the ECG actually records

Start by discarding the commonest misconception. The ECG does not record contraction. It records electrical events — and only electrical events. A heart in ventricular fibrillation produces a wildly abnormal but perfectly real tracing while generating zero output; a heart in pulseless electrical activity produces a normal-looking tracing while the patient is dead. The ECG tells you what the conduction system is doing, and contraction is inferred, never measured.

What the electrodes detect is this. When a wave of depolarization sweeps through a mass of myocardium, it creates, at every instant, a boundary between depolarized (electrically negative outside) and still-polarized (positive outside) tissue. That separation of charge is a dipole with a direction and a magnitude — a vector. Body fluids are excellent conductors, so this vector generates tiny potential differences, on the order of 1 millivolt, all over the body surface. An electrode records the projection of the summed cardiac vector onto its own axis.

Three rules follow, and they are the whole of ECG interpretation:

1. A depolarization wave travelling toward a positive electrode produces an upward deflection.
2. A wave travelling away produces a downward deflection.
3. The size of the deflection depends on the mass of muscle involved and on how closely the wave's direction aligns with the electrode's axis. A wave perpendicular to the axis produces nothing at all.

Repolarization reverses the polarity of the dipole, so a repolarization wave moving toward an electrode produces a downward deflection — which is why the normally upright T wave is a puzzle until you know that ventricular repolarization travels in the opposite direction to depolarization (epicardium to endocardium, because the subepicardium has a shorter action potential). Two reversals cancel, and the T wave points the same way as the QRS.

The waves, segments, and intervals

   THE NORMAL ECG COMPLEX (lead II) — waves, segments, intervals
   Paper speed 25 mm/s   ·   1 small box = 0.04 s wide, 0.1 mV tall
                             1 large box = 0.20 s wide, 0.5 mV tall

                              R
                              ╱╲
                             ╱  ╲
                            ╱    ╲                 ╭──╮
              ╭───╮        ╱      ╲               ╱    ╲
       ──────╯  P  ╰──────╱        ╲─────────────╱   T  ╲──────
                         │Q        ╲            ╱        ╲
                                    ╲S         ╱
                                     ╲________╱

       │◄─PR──►│         │◄QRS►│    │◄ST►│
       │ 120–  │         │ 80– │    │seg │
       │ 200ms │         │120ms│    │    │
       │◄──────── QT interval 350–440 ms ─────────►│

  WAVE / SEGMENT     WHAT IT IS                          NORMAL
  ─────────────────  ───────────────────────────────────  ─────────────
  P wave             ATRIAL depolarization                <120 ms,
                                                          <2.5 mm tall
  PR segment         impulse held in the AV node          isoelectric
                     (the AV nodal delay, §18.5)
  PR interval        start of P → start of QRS =          120–200 ms
                     atrial depol. + AV nodal delay       (3–5 small
                                                           boxes)
  QRS complex        VENTRICULAR depolarization           80–120 ms
                     (atrial REpolarization hides here)   (2–3 boxes)
  ST segment         ventricles fully depolarized;        isoelectric
                     the PLATEAU phase (phase 2)          (flat)
  T wave             VENTRICULAR repolarization           upright where
                                                          QRS is upright
  QT interval        total ventricular depolarization     350–440 ms;
                     + repolarization = "electrical       corrected for
                     systole"                             rate as QTc

  RATE:  300 ÷ (number of LARGE boxes between two R waves)
         or 1500 ÷ (number of SMALL boxes).   Regular rhythm only.

  ISCHEMIA / INJURY / INFARCTION — three patterns, three meanings
  ───────────────────────────────────────────────────────────────────
   T-WAVE INVERSION    ischemia; repolarization abnormal    reversible
        ╲    ╱
         ╲__╱

   ST DEPRESSION       SUBENDOCARDIAL injury               ← AMARA
    ────╮    ╭────     (partial thickness) — vector of      1.5 mm in
        ╰────╯          injury current points AWAY from     V4–V6,
                        the surface electrode               II/III/aVF

   ST ELEVATION        TRANSMURAL injury (full thickness)  STEMI
        ╭─────╮        — vector points TOWARD the electrode
    ────╯     ╰──

   PATHOLOGIC Q WAVE   ESTABLISHED INFARCT — dead muscle    permanent
    ──╮  ╱             conducts nothing, so the electrode
      ╰─╯              "sees through" the wall to the
      >40 ms wide      depolarization moving away on the
      >25% of R        far side

Twelve leads are twelve viewpoints

Here is the answer to Case File Question 1, and it is simpler than students expect.

Ten electrodes are placed: one on each limb (four) and six across the chest. From these ten electrodes the machine computes twelve leads. A "lead" is not a wire — it is a vector of view, a defined axis along which the summed cardiac dipole is measured. Six leads look at the heart in the frontal plane (up-down, left-right); six look at it in the transverse plane (front-back, left-right).

• Bipolar limb leads I, II, III measure the potential difference between two limb electrodes, forming Einthoven's triangle around the heart.
• Augmented limb leads aVR, aVL, aVF measure each limb against the average of the other two.
• Precordial (chest) leads V1–V6 march across the chest from just right of the sternum (V1) around to the left mid-axillary line (V6), each looking at the heart from a different angle in the horizontal plane.

Because each lead looks from a fixed direction, a lead is nearest to — and most sensitive to — the wall of the heart it faces. Group the leads by the wall they face, and the map of the heart falls out:

That table is the whole answer to Question 1. Ten stickers on skin become twelve directional viewpoints; a wall that is injured produces an abnormal current in a specific direction; and the leads that face that direction report it while the others do not. Localization is geometry, not magic.

It also explains an important limitation. There is no lead that looks directly at the posterolateral or posterior wall on a standard 12-lead ECG — the left arm is too far away and the chest leads stop at the mid-axillary line. Circumflex territory is the electrically quietest region of the heart. Circumflex occlusions are therefore the ones most likely to produce a "non-diagnostic" ECG, most likely to be missed, and most likely to present as depression in the anterior leads (a reciprocal view of a posterior injury) rather than elevation anywhere. Amara's ECG showed ST depression and T inversion, not elevation, partly because her infarct was subendocardial and partly because the wall involved is one the standard lead set sees poorly.

Reading rate and rhythm

A disciplined five-step read handles most tracings:

1. Rate. 300 divided by the number of large boxes between consecutive R waves. Under 60 is bradycardia, over 100 tachycardia. Amara: R waves about 2.9 large boxes apart → 104/min.
2. Rhythm. Regular or irregular? Are the R–R intervals constant?
3. P waves. Is there one P wave before every QRS, and one QRS after every P? If yes, and if the P is upright in II, the rhythm originates in the SA node — sinus rhythm.
4. Intervals. PR (120–200 ms), QRS (under 120 ms), QT.
5. ST segments and T waves, lead by lead, grouped by territory.

Amara's tracing: rate 104, regular, one upright P before every QRS, PR 168 ms, QRS 92 ms — so sinus tachycardia with normal conduction. The abnormality is entirely in step 5.

18.7 The Cardiac Cycle

The cardiac cycle is everything that happens from the beginning of one heartbeat to the beginning of the next. At a resting rate of 75 beats per minute, one cycle lasts 0.8 s: roughly 0.3 s of systole and 0.5 s of diastole. Every event in it is driven by one principle — blood moves down pressure gradients, and valves open and close passively in response to those gradients. If you know the pressures, you know the cycle.

  THE WIGGERS DIAGRAM — one cardiac cycle at 75 beats/min (0.8 s)
  All four panels share ONE time axis.

  PHASE      │  1   │ 2 │        3         │ 4 │        5         │
             │ATRIAL│IVC│   VENTRICULAR    │IVR│    VENTRICULAR   │
             │SYSTOL│   │    EJECTION      │   │     FILLING      │
  duration   │0.10 s│.05│      0.25 s      │.08│      0.42 s      │
  ═══════════╪══════╪═══╪══════════════════╪═══╪══════════════════╡
  PRESSURE   │      │   │                  │   │                  │
  (mm Hg)    │      │   │                  │   │                  │
   120 ──    │      │   │    ╭────────╮    │   │                  │
   100 ──    │      │  ╱│╲──╯  AORTA   ╲   │   │                  │
    80 ──    │      │ ╱ │            LV ╲──┼╮  │                  │  AORTIC
    60 ──    │      │╱  │                  ╰┼──┼──────────────────│   ↓
    40 ──    │      ╱   │                   ╲  │                  │  drains
    20 ──    │    ╭╱    │                    ╲ │                  │  through
    12 ──   ╭╯    │     │                     ╲│                  │  arterioles
     8 ──  ╱ LA   │     │                      ╲╮_________________│
     0 ── ╯       │     │                       ╰──────────────────
             ▲    ▲     ▲                       ▲
        atria   MITRAL  AORTIC              AORTIC │   MITRAL
        contract CLOSES  OPENS               CLOSES│    OPENS
                 (S1)    (LV>80)             (S2)  ▼  (LA>LV)
  ═══════════╪══════╪═══╪══════════════════╪═══╪══════════════════╡
  LV VOLUME  │      │   │                  │   │                  │
  (mL)       │      │   │                  │   │                  │
   130 ──    │   ╭──┼───┼╮  EDV = 130 mL   │   │             ╭────│
   110 ──    │  ╱   │   │ ╲                │   │         ╭───╯    │
    90 ──    │ ╱    │   │  ╲               │   │     ╭───╯        │
    70 ──    ╱      │   │   ╲   STROKE     │   │  ╭──╯  rapid     │
    60 ── ───╯      │   │    ╰─────────────┼───┼──╯    filling    │
             ▲      │   │  VOLUME = 70 mL  │   │       (E wave)   │
        "atrial kick"│   │  ESV = 60 mL    │   │                  │
        +20–25 mL    │   │                 │   │                  │
  ═══════════╪══════╪═══╪══════════════════╪═══╪══════════════════╡
  ECG        │ ╭╮   │╭╮ │                  │   │                  │
             │╱ ╲   ││││ │    ╭───╮        │   │                  │
       ──────╯ P ╰──╯└┴┘╯────╯  T  ╰───────┼───┼──────────────────│
             │      │QRS│                  │   │                  │
  ═══════════╪══════╪═══╪══════════════════╪═══╪══════════════════╡
  SOUNDS     │      │S1 │                  │S2 │   (S3)      (S4) │
             │      │▮▮ │                  │▮  │    ▮         ▮   │
             │      │AV │                  │SL │  rapid    atrium │
             │      │clos│                 │clos│ filling  into a  │
             │      │    │                 │    │  gallop  STIFF LV│
  ═══════════╧══════╧═══╧══════════════════╧═══╧══════════════════╛

  RIGHT SIDE: identical volumes, identical timing, ONE-FIFTH the pressures
     RV peaks at ~25 mm Hg · pulmonary artery 25/10 · RA mean 0–8 mm Hg

The five phases, in order

1 · Atrial systole (0.1 s). The P wave has just occurred. Both atria contract. The AV valves are already open and about 70–80% of ventricular filling has already happened passively, so this contraction is a top-up — the atrial kick — contributing the final 20–25 mL, roughly 15–25% of end-diastolic volume in a normal heart. At its end the ventricle holds its end-diastolic volume (EDV), about 130 mL, and left atrial pressure has risen to about 12 mm Hg (the a wave of the venous pulse).

2 · Isovolumetric contraction (0.05 s). The QRS has fired and the ventricle begins to contract. Ventricular pressure instantly exceeds atrial pressure, so the mitral and tricuspid valves slam shut — this produces S1. But ventricular pressure is still far below aortic pressure (80 mm Hg), so the aortic valve stays shut. All four valves are closed. The ventricle contracts around an incompressible fluid it cannot expel: volume does not change (hence isovolumetric), pressure rockets from 8 to 80 mm Hg, and the muscle shortens not at all — it generates tension isometrically. It is the most oxygen-expensive phase of the cycle relative to the work it accomplishes, which is exactly why afterload matters so much (§18.8).

3 · Ventricular ejection (0.25 s). Ventricular pressure crosses aortic pressure and the aortic valve opens. Blood is ejected — about 70% of it in the first third (rapid ejection), the remainder more slowly as ventricular pressure begins to fall (reduced ejection). Left ventricular and aortic pressure rise together to a peak near 120 mm Hg. Volume falls from 130 mL to the end-systolic volume (ESV) of about 60 mL. The difference — 70 mL — is the stroke volume. Note that the ventricle never empties: 60 mL remains, and that residual volume is the reserve the heart draws on when contractility increases.

4 · Isovolumetric relaxation (0.08 s). The T wave has passed; the ventricle relaxes. Pressure falls below aortic pressure, blood momentarily starts to flow backwards, and this backflow snaps the semilunar valves shut — producing S2 and a small upward blip on the aortic trace called the dicrotic notch. Ventricular pressure is still above atrial pressure, so the AV valves remain shut. Again all four valves are closed, and again volume does not change, while pressure plummets from 120 to near zero.

Relaxation is an active, ATP-consuming process — calcium must be pumped back into the sarcoplasmic reticulum by SERCA and out of the cell by the sodium–calcium exchanger against their gradients. This is the single most important sentence in the chapter for understanding Amara. A heart short of ATP relaxes badly before it contracts badly, because relaxation is the energy-dependent step. Diastolic dysfunction is the earliest manifestation of ischemia, appearing before any fall in ejection fraction and before any ECG change.

5 · Ventricular filling (0.42 s at rest). Ventricular pressure falls below atrial pressure and the AV valves open. Filling occurs in three sub-phases: rapid filling as the accumulated atrial blood rushes in (the E wave on Doppler echocardiography), diastasis — a slow trickle as atrial and ventricular pressures equalize — and then the next atrial systole (the A wave). At rest, diastasis is long; as heart rate rises, diastasis is what disappears first, which is how the heart preserves rapid filling and the atrial kick while shortening the cycle. Beyond about 180 beats per minute even that fails, and stroke volume falls.

The heart sounds

A stethoscope picks up turbulence and vibration, not valve leaflets clicking. Both normal sounds are made by the sudden deceleration of a column of blood when a valve shuts and by the vibration of the surrounding structures.

• S1 ("lubb") — closure of the mitral and tricuspid valves at the onset of isovolumetric contraction. Lower-pitched and longer, because the ventricular walls and the large blood mass vibrate slowly. Marks the beginning of systole.
• S2 ("dupp") — closure of the aortic and pulmonary valves at the onset of isovolumetric relaxation. Higher-pitched and shorter, because the arterial walls are stiffer. Marks the end of systole.

Physiological splitting of S2 is worth understanding because it is derivable. On inspiration, negative intrathoracic pressure increases venous return to the right heart, so right ventricular stroke volume and therefore ejection time increase slightly; the pulmonary valve closes a few milliseconds later than the aortic. You hear "lubb, T-dupp." On expiration the two coincide again. Splitting that widens on expiration ("paradoxical splitting") indicates delayed left ventricular emptying — aortic stenosis or left bundle branch block — and is an abnormal finding derivable from exactly the same logic.

Two extra sounds are diagnostically valuable:

• S3 — a low-pitched sound in early diastole, during rapid filling, produced when blood rushing into a dilated, volume-overloaded ventricle is abruptly decelerated. Normal in children, young adults, and athletes; in an adult over 40 it usually means a dilated failing ventricle. The cadence sounds like "Ken-tuc-ky."
• S4 — a low-pitched sound in late diastole, produced when the atrium contracts against a stiff, non-compliant ventricle. It cannot exist in atrial fibrillation, because it requires atrial contraction. The cadence sounds like "Ten-nes-see." Amara has an S4, documented on her admission examination, and it is the acoustic signature of the answer to Question 3.

Where to listen. Sound travels in the direction of blood flow, so each valve is best heard downstream of itself rather than over its anatomical location: Aortic — right 2nd intercostal space; Pulmonary — left 2nd; Tricuspid — left lower sternal border, 4th–5th; Mitral — apex, left 5th space midclavicular line.

Murmurs

A murmur is the sound of turbulent flow. Blood normally moves in smooth laminar layers and is silent; turbulence occurs when velocity rises past a critical point, when a stream passes through a narrowing, or when viscosity falls. So a murmur means one of three things:

1. Flow through a narrowed opening — a stenotic valve, forward.
2. Flow through a valve that should be closed — a regurgitant valve, backward.
3. High flow through a normal valve — anemia (low viscosity), fever, pregnancy, exercise, or a child with a thin chest. These are "innocent" murmurs and are extremely common.

Timing localizes the lesion with no equipment at all. A murmur between S1 and S2 is systolic: the AV valves should be closed and the semilunar valves open, so the possibilities are AV regurgitation or semilunar stenosis. A murmur between S2 and the next S1 is diastolic: AV valves should be open and semilunar closed, so the possibilities are AV stenosis or semilunar regurgitation. Two sounds and a clock, and you have halved the differential diagnosis.

18.8 Cardiac Output

The master equation

Cardiac output (CO) is the volume of blood ejected by one ventricle per minute. It is the single number that determines whether tissues are perfused, and almost everything the cardiovascular system does is in service of defending it.

CO = HR × SV

At rest: 75 beats/min × 70 mL/beat = 5,250 mL/min ≈ 5 L/min

Two observations make that number vivid. Five litres per minute is approximately the entire blood volume, so your complete circulation turns over about once a minute at rest. And cardiac reserve — the ratio of maximum to resting output — is 4–5× in an untrained adult and 7–8× in a trained endurance athlete.

Because output must be matched to body size, it is often normalized as the cardiac index: CO divided by body surface area, normally 2.5–4.0 L/min/m². Amara, at 165 cm and 80 kg, has a body surface area of about 1.9 m². With a heart rate of 88 and a stroke volume of 52 mL, her output is 4.6 L/min and her index is 2.4 L/min/m² — at the very bottom of normal, at rest, in a woman who used to walk 10 km on a shift.

Only two variables can be adjusted, so we take them one at a time.

Regulating stroke volume, part 1 · Preload and the Frank–Starling mechanism

Stroke volume = EDV − ESV. So stroke volume rises if the ventricle fills more (higher EDV) or empties more completely (lower ESV). Preload governs the first; contractility and afterload govern the second.

Preload is the degree of stretch of the ventricular myocardium immediately before contraction. Operationally it is end-diastolic volume, and clinically it is estimated from filling pressures.

The Frank–Starling mechanism states that within physiological limits, the more the ventricle is filled during diastole, the more forcefully it contracts. Stretch it, and it responds by ejecting more.

Chapter 9 gives the reason, and it is the same length–tension relationship you learned for skeletal muscle, with a cardiac twist. At short sarcomere lengths, thin filaments from opposite ends of the sarcomere overlap each other and interfere; at excessive lengths, thick and thin filaments barely overlap and few cross-bridges can form. Peak force occurs at a sarcomere length of about 2.2 µm. The crucial fact is that resting cardiac sarcomeres sit at about 1.8–2.0 µm — on the ascending limb of the curve. Filling the ventricle stretches them toward optimum, so force rises. (Resting skeletal muscle, by contrast, already sits near optimum, which is why skeletal muscle has no equivalent mechanism.)

Modern work adds a second, arguably more important mechanism: length-dependent activation. Stretching cardiac muscle increases the calcium sensitivity of troponin C, so the same calcium transient produces more cross-bridge cycling. Stretch does not merely improve geometry; it changes the chemistry.

Why does this matter so much? Because it makes the two circuits self-balancing without any controller. If the right ventricle ejects slightly more than the left for a few beats, the extra blood arrives in the left atrium, raises left ventricular EDV, stretches the left ventricle, and the left ventricle ejects more — automatically, within one beat, with no nerve involved. That is why a transplanted, fully denervated heart still matches its two outputs perfectly.

What determines preload? Venous return, essentially. And venous return is determined by blood volume, venous tone, the skeletal muscle pump, the respiratory pump, and — critically — the time available to fill, which falls as heart rate rises. All of these belong to Chapter 19.

Regulating stroke volume, part 2 · Contractility

Contractility (inotropy) is the force of contraction at any given preload. It is the intrinsic vigour of the muscle, independent of how full the chamber is, and on a graph it appears as a shift of the entire curve, not a movement along it.

The molecular currency is intracellular calcium (§18.5). Anything that raises the calcium available to troponin during systole increases contractility.

Note the sympathetic effect is dual: it makes the heart contract harder and relax faster. That second effect is easy to overlook and is essential during exercise, when diastole is short and the ventricle must fill in 150 ms.

Regulating stroke volume, part 3 · Afterload

Afterload is the load the ventricle must overcome to eject — essentially the arterial pressure it must exceed before the semilunar valve opens (about 80 mm Hg for the left ventricle, about 10 for the right). Raise afterload and, at constant preload and contractility, stroke volume falls and end-systolic volume rises: the ventricle spends longer in isovolumetric contraction and has less time and less energy left for shortening.

The deeper quantity is wall stress, given by Laplace's law: wall stress is proportional to (pressure × chamber radius) ÷ (2 × wall thickness). Three predictions fall out of that single relationship, and all three matter later in this chapter:

• Higher pressure raises wall stress — so hypertension increases the load on every beat.
• A larger radius raises wall stress — so a dilated ventricle is working harder at the same blood pressure than a normal-sized one. This is why dilation is self-perpetuating.
• A thicker wall lowers wall stress — which is precisely why a ventricle facing chronic pressure overload hypertrophies. Thickening is not a malfunction; it is a correct solution to Laplace's law that carries a fatal side effect (§18.9).

Regulating heart rate

The SA node's intrinsic rate is about 100/min. Your resting rate is around 70 because parasympathetic (vagal) tone dominates at rest — cut both vagi and the heart speeds up. "Increasing heart rate" is therefore usually withdrawal of vagal tone first, and sympathetic activation second.

Ejection fraction

Ejection fraction (EF) is the fraction of end-diastolic volume ejected per beat:

EF = (SV ÷ EDV) × 100 = ((EDV − ESV) ÷ EDV) × 100

Normal: (130 − 60) ÷ 130 = 70 ÷ 130 = 54% … normal range 55–70%

Amara: (108 − 56) ÷ 108 = 52 ÷ 108 = 48%

EF is popular because it is easy to measure and it predicts outcomes in systolic heart failure. But notice what it is: a ratio, not a volume. It says nothing about how much blood was there to begin with. A ventricle holding 60 mL and ejecting 30 has an EF of 50% and a stroke volume of 30 mL — a catastrophic output at a number that reads "moderately reduced." This is the crack through which the answer to Question 3 walks.

     THE FRANK–STARLING CURVE — three hearts, one relationship

   STROKE
   VOLUME
   (mL)
    140 ┤                                    ╭────────────  ENHANCED
        │                              ╭─────╯              CONTRACTILITY
    120 ┤                        ╭─────╯                    (sympathetic
        │                   ╭────╯                           stimulation,
    100 ┤              ╭────╯          ╭──────────────       digoxin)
        │          ╭───╯          ╭────╯               NORMAL
     80 ┤       ╭──╯          ╭───╯
        │    ╭──╯         ╭───╯
     70 ┤  ╭─╯        ╭───╯  ◄── RESTING POINT (EDV 130, SV 70)
        │ ╭╯      ╭───╯
     50 ┤╭╯   ╭───╯                    ╭──────────────  DEPRESSED
        ││ ╭──╯                 ╭──────╯                CONTRACTILITY
     30 ┤│╭╯            ╭───────╯                       (HFrEF, ischemia,
        │╭╯      ╭──────╯                                beta-blockade)
     10 ┤╯───────╯
        └────┬────┬────┬────┬────┬────┬────┬────┬────┬────►
             60   90  120  150  180  210  240  270  300
                   PRELOAD = END-DIASTOLIC VOLUME (mL)

   ══ HOW TO READ IT ══════════════════════════════════════════════════

   MOVING ALONG one curve   = changing PRELOAD (venous return, volume)
   SHIFTING to another curve = changing CONTRACTILITY (inotropic state)

   Note the DEPRESSED curve is flat: a failing ventricle gains little
   stroke volume from extra filling, so it retains fluid to no benefit
   — and the extra volume is transmitted BACKWARD into the lungs.
   That is the mechanism of congestion.

   The NORMAL curve has no descending limb in an intact heart:
   the pericardium and the stiffness of the myocardium itself
   prevent overstretch (§18.1). This is a real difference from
   isolated skeletal muscle preparations.

18.9 Advanced Topic · Heart Failure, and the Ventricle That Cannot Fill

Two ways for a pump to fail

Heart failure is the state in which the heart cannot deliver output sufficient for the body's needs, or can do so only at abnormally high filling pressures. That second clause is the one everyone forgets, and it is where Amara lives.

There are exactly two ways to fail.

Systolic dysfunction — the heart cannot EJECT. Contractility is reduced. The ventricle dilates (eccentric remodelling), end-systolic volume rises, and ejection fraction falls. This is HFrEF: heart failure with reduced ejection fraction, conventionally EF ≤ 40%. Causes: large myocardial infarction, dilated cardiomyopathy, chronic volume overload from valve regurgitation, myocarditis, toxins.

Diastolic dysfunction — the heart cannot FILL. Contractility is normal or near normal, but the ventricle is stiff: it resists being filled, so achieving a normal end-diastolic volume requires an abnormally high filling pressure — and often the normal volume is never achieved at all. Ejection fraction is preserved because the ventricle still ejects a normal fraction of what little it holds. This is HFpEF: heart failure with preserved ejection fraction, conventionally EF ≥ 50%, with EF 41–49% designated mildly reduced.

Look at the last two rows. The symptoms are identical, because the symptoms come from the elevated filling pressure and the inadequate output, not from the ejection fraction. Both diseases raise left atrial pressure, which raises pulmonary venous and capillary pressure, which pushes fluid into the alveoli (§19.3). Both reduce forward output on exertion. A patient cannot tell you which one they have, and neither can a stethoscope with confidence — which is exactly why the echocardiogram is not optional.

Why a stiff ventricle is stiff

Two distinct processes, both present in Amara.

1 · Impaired active relaxation. Diastole is not passive. Calcium must be actively pumped back into the sarcoplasmic reticulum (SERCA) and out of the cell, and this consumes ATP. Ischemia, hypertrophy that outgrows its capillary supply, and diabetes all impair it. Slower calcium removal means cross-bridges detach more slowly, and the ventricle is still partly contracted when it should be accepting blood.

2 · Increased passive stiffness. Chronic pressure overload causes concentric hypertrophy — sarcomeres added in parallel, thickening the wall without enlarging the cavity — and, alongside it, interstitial fibrosis: fibroblasts, driven largely by angiotensin II and aldosterone (Chapter 16 and §19.6), lay down collagen between the myocytes. Collagen is stiff. The ventricle now has more muscle and more scaffolding in a smaller cavity, and its pressure–volume relationship steepens: each additional millilitre of blood raises pressure far more than it should.

The consequences cascade:

Stiff LV → high filling pressure needed → left atrium must generate more pressure and dilates (Amara's LA volume index 39 mL/m²) → pressure is transmitted backward to the pulmonary veins and capillaries → exertional dyspnea, then orthopnea → the dilated atrium becomes electrically unstable → atrial fibrillation → loss of the atrial kick, on which a stiff ventricle depends for up to 40% of filling → abrupt decompensation.

The compensations, and why each eventually harms

When output falls, three compensatory systems engage. All three are homeostatically correct in the short term and destructive in the long term — the clearest example in this book of Thread 2 turning against the patient.

That last row is the punchline of the whole chapter. Hypertrophy is a correct solution to a mechanical problem that creates a filling problem. Amara's left ventricle thickened to 13 mm because it spent years generating 168 mm Hg instead of 120. By Laplace's law that was the right answer: a thicker wall lowers stress per unit muscle. The price is a chamber that will not fill.

This also explains why modern heart failure therapy consists almost entirely of blocking compensations: beta-blockers block the sympathetic arm, ACE inhibitors and ARBs block angiotensin II, mineralocorticoid antagonists block aldosterone, and SGLT2 inhibitors act through mechanisms still being characterized. Each reduces mortality. Each looks, superficially, like weakening a struggling heart.

Chapter Summary

§18.1 The heart sits in the mediastinum, two-thirds to the left of midline, tilted so that the right ventricle lies most anteriorly. Its base is superior (mostly left atrium) and its apex inferolateral (left ventricle), palpable at the 5th intercostal space in the left midclavicular line as the point of maximal impulse — displaced if the ventricle has dilated, sustained if it has thickened. The pericardium is a fibrous outer sac lined by a serous membrane whose parietal and visceral (epicardial) layers enclose 15–50 mL of fluid. Because the fibrous layer will not stretch acutely, rapid filling of that space produces tamponade by preventing filling, not ejection.

§18.2 The wall is epicardium, myocardium (spiralling cardiac muscle bundles that wring rather than squeeze), and endocardium (endothelium continuous with every vessel). Chamber wall thickness is derivable from the pressure each chamber must generate: atria 2–3 mm, right ventricle 3–5 mm at 25 mm Hg, left ventricle 8–11 mm at 120 mm Hg. Internal features — pectinate muscles, trabeculae carneae, papillary muscles, chordae tendineae, the moderator band, the fossa ovalis — each have a mechanical or electrical function.

§18.3 Four valves, all passive, all opened and closed by pressure gradients alone. The AV valves need the papillary muscle–chordae apparatus because they face a 110 mm Hg differential; the semilunar valves do not, because their cusps are self-supporting pockets. The fibrous skeleton anchors valves and myocardium, prevents orifice dilation, and — decisively — electrically insulates atria from ventricles, leaving the AV bundle as the sole gateway.

§18.4 Blood traverses the pulmonary and systemic circuits in series, so their outputs must match. The LAD supplies the anterior wall, anterior septum, and apex (leads V1–V4); the circumflex the lateral wall (I, aVL, V5, V6); the RCA the inferior wall and the nodal tissue (II, III, aVF). Venous return is via the coronary sinus. Left coronary flow occurs in diastole, so tachycardia cuts supply while raising demand; and because myocardial oxygen extraction is already 70–80% at rest, the heart can increase supply only by increasing flow.

§18.5 Cardiac muscle is striated, branched, mononucleate, mitochondria-rich, and coupled by intercalated discs whose gap junctions make it a functional syncytium. Autorhythmic cells have no resting potential: the funny current and T-type calcium channels drive a pacemaker drift to a calcium-based upstroke. Contractile cells have a fast sodium upstroke and a 200 ms plateau from balanced calcium influx and potassium efflux, giving a refractory period that covers the whole twitch and makes tetanus impossible. The impulse runs SA node → atria → AV node (100 ms delay) → bundle of His → bundle branches → Purkinje fibres (2–4 m/s) → ventricular myocardium, apex first.

§18.6 The ECG records summed depolarization vectors, not contraction. P is atrial depolarization, QRS ventricular depolarization, T ventricular repolarization; PR 120–200 ms, QRS under 120 ms, QT 350–440 ms. Twelve leads are twelve viewpoints, grouped as inferior (II, III, aVF), lateral (I, aVL, V5, V6), anterior (V3, V4), and septal (V1, V2), so localization is geometry. T inversion signals ischemia, ST depression subendocardial injury, ST elevation transmural injury, and a pathologic Q wave established scar.

§18.7 Five phases: atrial systole (the atrial kick, 15–25% of filling), isovolumetric contraction (S1, all valves shut, volume constant), ejection (SV 70 mL, ESV 60 mL), isovolumetric relaxation (S2, dicrotic notch), and filling (rapid filling, diastasis). Relaxation is ATP-dependent, so ischemic hearts relax badly before they contract badly. S3 means a dilated ventricle; S4 means a stiff one. Murmurs are turbulence: stenosis forward, regurgitation backward, or high flow through a normal valve.

§18.8 CO = HR × SV, about 5 L/min at rest. Stroke volume is set by preload (the Frank–Starling mechanism, resting sarcomeres on the ascending limb at 1.8–2.0 µm plus length-dependent calcium sensitization), contractility (intracellular calcium; β₁ signalling), and afterload (arterial pressure; wall stress by Laplace). Heart rate is set by the balance of vagal and sympathetic tone acting on the pacemaker drift. EF = SV/EDV, normally 55–70% — a ratio, not a volume.

§18.9 Heart failure is failure to deliver output, or to do so only at high filling pressures. HFrEF is a contraction problem with a dilated ventricle; HFpEF is a filling problem with a thick, stiff, fibrotic ventricle. The symptoms are identical because both raise filling pressure. Compensations — Frank–Starling, sympathetic activation, RAAS, hypertrophy — are all correct in the short term and harmful in the long term, which is why treatment consists of blocking them.

Case File 18 · Resolution

Question 1 — How can ten stickers on the skin localize damage to one wall of the heart?

Because the ECG measures vectors, and vectors have direction.

When myocardium depolarizes, it creates a moving boundary between depolarized and polarized tissue — a separated charge with a direction and a magnitude. Body fluids conduct, so that dipole generates measurable potential differences at the skin. Each of the twelve leads is a defined axis of view computed from the ten electrodes: six in the frontal plane (I, II, III, aVR, aVL, aVF) and six in the transverse plane (V1–V6). A lead records the projection of the cardiac vector onto its own axis, so a lead is most sensitive to the wall it faces.

Now add injury. Ischemic myocardium fails to repolarize normally and holds a different resting potential from healthy muscle, so during the ST segment — when normal myocardium is uniformly depolarized and the tracing should be flat — a current of injury flows between the injured region and the healthy tissue around it. Its direction depends on which layer is injured. In subendocardial injury the vector points from the surface inward, away from the overlying electrode, so the ST segment is pulled down. In transmural injury the vector points outward, toward the electrode, and the ST segment is pushed up.

Amara's tracing showed ST depression of 1.5 mm in V4–V6 and in II, III, aVF, with T inversion in I, aVL, V5, V6. Reading by lead group: V5, V6, I and aVL are the lateral leads; II, III, aVF are the inferior leads. Depression rather than elevation means the injury was subendocardial, not full-thickness. The physician's phrase "lateral and inferior ischemia" was a direct translation of which viewpoints reported an abnormality into which wall those viewpoints face — and the coronary angiogram the following day confirmed it independently.

Localization from the skin is not an inference about depth. It is triangulation.

Question 2 — Why did blocking the circumflex artery damage the lateral wall?

Because the coronary arteries are end-arteries with fixed territories, and the myocardium downstream of a given vessel has no meaningful alternative supply.

The left circumflex artery curves leftward in the coronary sulcus and sends obtuse marginal branches into the lateral wall of the left ventricle. That is the wall it feeds, in essentially every human being. The LAD feeds the anterior wall, anterior septum, and apex; the RCA feeds the right ventricle, the inferior wall, and the nodal tissue. Coronary anastomoses exist but are small and, in the absence of slowly progressive disease that has had years to grow collaterals, carry far too little flow to rescue an acutely occluded territory.

So a 90% proximal circumflex stenosis limits flow to the lateral wall specifically. At rest, with a resting coronary flow of about 250 mL/min and a coronary flow reserve of 4–5×, a 90% lesion can still supply resting needs — which is why Amara was working full shifts. As soon as demand rose, the reserve that a healthy artery would have provided was gone. And when the plaque surface ruptured and a platelet-rich thrombus formed on it (Chapter 17, and §19.9), flow fell below even resting requirement in the subendocardium — the layer farthest from the epicardial artery and most compressed during systole. Those cells died first, released troponin, and produced hypokinesis of exactly that wall on the echocardiogram.

Her inferior lead changes have an anatomical explanation too. Amara is co-dominant: her circumflex gives a large posterolateral branch supplying the inferolateral wall, so one lesion produced changes in two lead groups.

The chain is therefore: named artery → named wall → named leads. Once you have the territory table in §18.4, the reasoning runs in any direction. Given the leads, name the artery. Given the artery, predict the leads. Given the wall motion abnormality, predict both.

Question 3 — Why is her ejection fraction only mildly reduced while her symptoms are severe?

Because ejection fraction measures the wrong thing for her disease.

EF is a ratio: the fraction of end-diastolic volume ejected. It reports how well the ventricle empties. Amara's problem is that her ventricle will not fill.

Twenty years of untreated hypertension forced her left ventricle to generate 168 mm Hg where it should generate 120. By Laplace's law, wall stress rises with pressure and falls with wall thickness, so the correct mechanical response was to thicken: sarcomeres added in parallel, producing concentric hypertrophy, wall thickness now 13 mm against a normal 6–11. Alongside the muscle, angiotensin II and aldosterone drove fibroblasts to lay down interstitial collagen between the myocytes.

The result is a ventricle that is thick, small, and stiff. Three consequences:

1. It fills poorly. Its pressure–volume relationship is steep, so a normal filling pressure produces a subnormal volume. Her EDV is 108 mL where a woman her size should have 120–140. Because stroke volume is EDV minus ESV, a small EDV means a small stroke volume — 52 mL — even though the fraction ejected is nearly normal. Her cardiac index is 2.4 L/min/m², at the bottom of the normal range at rest, with essentially no reserve for exertion. That is why she is breathless walking down a corridor: forward output cannot rise.
2. Filling requires high pressure. To get even 108 mL in, her left atrium must generate abnormal pressure — her E/e′ of 15 says so, and her dilated left atrium (volume index 39 mL/m²) is the structural record of years of doing it. That pressure is transmitted backwards to the pulmonary veins and capillaries, so fluid is forced into the lung interstitium (§19.3). That is the other reason she is breathless.
3. The stiff ventricle depends on the atrial kick, which supplies up to 40% of its filling rather than the usual 15–25%. She is one episode of atrial fibrillation away from acute decompensation.

Two more contributors complete the picture. Her lateral wall is hypokinetic from the infarct, which is a genuine but modest systolic contribution and accounts for most of the seven points her EF sits below normal. And her hypertrophied muscle has outgrown its capillary supply, so the subendocardium is chronically ischemic even between events — which impairs the ATP-dependent relaxation that was already failing.

Put together: Amara has heart failure with a nearly normal ejection fraction. In twelve weeks, when her stunned lateral wall recovers, her EF will likely read 55% and her chart will say her heart function is "normal." She will still be breathless. The number will have improved and the patient will not, because the number was never measuring her disease. Learning to distinguish a heart that cannot eject from a heart that cannot fill is one of the most consequential things this chapter has to teach.

Systems Integration Case File · Entry 18

Review

Level 1 · Recall

16.1 The apex of the heart is normally located at the:

a) 2nd intercostal space, left sternal border    b) 5th intercostal space, left midclavicular line    c) 4th intercostal space, right sternal border    d) xiphoid process

16.2 Which structure electrically insulates the atria from the ventricles?

a) the interatrial septum    b) the epicardium    c) the fibrous skeleton    d) the pericardial fluid

16.3 During isovolumetric contraction:

a) the aortic valve is open    b) all four valves are closed    c) the mitral valve is open    d) ventricular volume is falling

16.4 The plateau phase of the ventricular action potential is produced mainly by:

a) fast Na⁺ influx    b) K⁺ efflux alone    c) inward Ca²⁺ current balanced by outward K⁺ current    d) Cl⁻ influx

16.5 ST-segment depression in leads V5 and V6 most likely indicates injury to the:

a) inferior wall    b) anterior wall    c) lateral wall    d) right ventricle

16.6 Which change would increase stroke volume?

a) increased afterload    b) increased venous return    c) beta-blockade    d) tachycardia at 200 beats/min

16.7 The first heart sound (S1) is produced by:

a) opening of the semilunar valves    b) closure of the AV valves    c) closure of the semilunar valves    d) atrial contraction

16.8 A patient has an EF of 62%, a thick-walled left ventricle, an S4 gallop, and severe exertional dyspnea. The most likely diagnosis is:

a) HFrEF    b) HFpEF    c) cardiac tamponade    d) aortic regurgitation

Level 2 · Comprehension

16.9 Explain why the myocardium is uniquely dependent on increased flow rather than increased extraction to meet a rise in oxygen demand, and give two clinical consequences.

16.10 Two patients have identical ejection fractions of 50%. One has an EDV of 180 mL, the other an EDV of 90 mL. Compare their stroke volumes and explain why ejection fraction alone can be misleading.

16.11 Why does the AV node conduct slowly, and what two problems does that slowness solve?

16.12 Explain why relaxation of cardiac muscle requires ATP, and why this makes diastolic dysfunction an early sign of ischemia.

Level 3 · Clinical Application

16.13 A 68-year-old man has ST elevation in II, III, and aVF. His heart rate is 42 with intermittent dropped QRS complexes, and his blood pressure falls sharply after a dose of nitroglycerin. Explain all three findings from the coronary anatomy.

16.14 A 24-year-old marathon runner has a resting heart rate of 44, an enlarged left ventricle on echocardiography, and an S3. A 62-year-old with long-standing hypertension has a thick-walled left ventricle and an S4. Both are asymptomatic. Which one worries you, and why?

16.15 A patient collapses. The monitor shows a chaotic, irregular waveform with no identifiable QRS complexes and no pulse. A second patient collapses and the monitor shows a flat line. Both receive CPR. Explain why only the first should be defibrillated.

Level 4 · Integration and Synthesis

16.16 Construct the complete causal chain from Amara's twenty years of night-shift work to her E/e′ of 15, naming every intermediate step and every system involved. Then identify the two points in that chain at which a drug could intervene, and say what it would do.

16.17 The Frank–Starling mechanism automatically matches right and left ventricular outputs without any neural input. Design an experiment, using only the concepts in this chapter, that would demonstrate this in a transplanted (denervated) heart. Then explain why the mechanism fails to help a patient with severe HFrEF.

16.18 A drug is proposed that blocks the sodium–calcium exchanger in cardiac myocytes. Predict its effects on contractility, on relaxation, and on arrhythmia risk, and decide whether you would want it in a patient like Amara.

Concept Map to Complete

Copy this onto blank paper and fill in every bracket from memory before checking the chapter.

                          CARDIAC OUTPUT
                     CO = [ ______ ] × [ ______ ]
                                │
              ┌─────────────────┴─────────────────┐
        HEART RATE                          STROKE VOLUME
              │                                   │
      ┌───────┴───────┐              ┌────────────┼────────────┐
  SYMPATHETIC   PARASYMPATH.     [ _______ ]  [ _______ ]  [ _______ ]
   β1 → ↑[____]  M2 → ↓[____]    = EDV        = force at   = pressure
   → pacemaker   → pacemaker      via the      any given    that must be
     drift [___]   drift [___]    [ __________ ]  preload   overcome
                                   mechanism        │            │
                                        │       molecular    Laplace:
   INTRINSIC RATES                  sarcomere    currency =  stress ∝
   SA node    [ ____ ]/min          length       [ ______ ]  (P × [__])
   AV node    [ ____ ]/min          [ ___ ] µm                ÷ (2 × [__])
   Purkinje   [ ____ ]/min
                                        │
   ══════════════════════════════════════════════════════════════════
   TWO WAYS TO FAIL
                  ┌───────────────────┴──────────────────┐
        CANNOT [ _______ ]                    CANNOT [ _______ ]
        = HF with [ ____ ] EF                 = HF with [ ____ ] EF
        ventricle is [ _________ ]            ventricle is [ ________ ]
        extra sound = [ __ ]                  extra sound = [ __ ]
        typical cause = [ __________ ]        typical cause = [ _________ ]
   ══════════════════════════════════════════════════════════════════
   ARTERY → WALL → LEADS
        LAD        → [ __________ ] wall → leads [ ___________ ]
        Circumflex → [ __________ ] wall → leads [ ___________ ]
        RCA        → [ __________ ] wall → leads [ ___________ ]

Lab / Self-Exploration

1. Find your own PMI. Lie on your left side and place your fingertips in the 5th intercostal space at the left midclavicular line. Feel for a discrete tap. Note that it is one small area, not the whole left chest — the apex is a point.
2. Listen to your own valves. With a stethoscope (or by pressing an ear against a partner's chest), find all four auscultation points: right 2nd space, left 2nd space, left lower sternal border, and the apex. Identify S1 and S2 by feeling the carotid pulse at the same time — the pulse arrives just after S1.
3. Demonstrate S2 splitting. Listen at the left 2nd intercostal space while the subject breathes slowly and deeply. Hear whether S2 becomes two sounds during inspiration and one during expiration. Then explain the mechanism to yourself in terms of venous return.
4. Measure your cardiac reserve, indirectly. Record resting heart rate. Do 60 seconds of vigorous stair climbing, then measure heart rate immediately and at 1, 2, and 3 minutes. Plot the recovery curve. The rate of fall in the first minute is a rough index of vagal reactivation and correlates with fitness.
5. Estimate your own maximal cardiac output. Predict maximum heart rate as 208 − (0.7 × your age). Assume a stroke volume of 100 mL if untrained or 140 mL if you train endurance sport regularly. Multiply. Compare with your resting output of about 5 L/min and calculate your cardiac reserve ratio.
6. Time the cardiac cycle. With a metronome or a stopwatch, set a rhythm at your resting heart rate and work out the cycle duration in seconds. Then divide it into systole (roughly 0.3 s, nearly fixed) and diastole (the remainder). Repeat the arithmetic for 150 beats per minute and note how much of the loss falls on diastole. You have just derived why tachycardia is dangerous in coronary disease.

Key Terms

Next: Chapter 19 · The Cardiovascular System II — where the pressure this chapter's pump generates is decomposed into its parts, and where Amara's 168/98 finally becomes an explanation rather than a number.