VF BSCI #1

**Anatomical position**.

Occurs when a venous thrombus bypasses the pulmonary circulation by crossing from the right atrium to the left atrium through an intracardiac shunt like a PFO, entering the systemic circulation and potentially causing a stroke

**Anterior/Ventral**.

**Posterior/Dorsal**.

**Medial**.

**Superficial**.

**Deep**.

**Supine**.

**Prone**.

**Lateral recumbent**.

**Abduction**.

A **transverse or horizontal plane** (also called **axial plane**).

A **coronal section**.

The **mediastinum** is the **centralized compartment of the thorax**.

The **fibrous pericardium**.

The **parietal pericardium**.

The **visceral layer of pericardium**.

The **pericardial cavity**.

Approximately **two-thirds of the heart resides just to the left of the midline**.

The **apex of the heart is located at the 5th intercostal space**, just lateral to the sternum.

On a **chest X-ray**, the majority of the heart visible is the **right ventricle**.

A small portion of the **right atrium**.

A sliver of the **superior vena cava**.

The **dense sternum obscures the heart shadow in the midline**.

The **ascending aorta**.

The **mitral valve** (bicuspid valve).

The **pulmonary semilunar valve**.

The **aortic semilunar valve**.

To auscultate heart valves, one should always listen **downstream of the valve**.

**Right 2nd intercostal space at the sternal margin**.

**Left 2nd intercostal space at the sternal margin**.

**Left 5th intercostal space at the sternal margin**.

**Left 5th intercostal space at the midclavicular line**.

**Specialized cardiac muscle cells that control the rate of the heartbeat, known as the SA node, are found in the wall of the right atrium near the opening of the superior vena cava on the anterior side**.

The **AV node is located along the posteromedial wall of the atrioventricular orifice**.

The **crista terminalis** of the right atrium **conveys cardiac conduction fibers from the SA node to the AV node**.

**Great cardiac vein**.

**Middle cardiac vein**.

**Small cardiac vein**.

The **right coronary artery**.

The **right atrium is primarily supplied by the right coronary artery**.

The **fibrous cardiac skeleton**.

It also acts as an **insulator for the heart's conduction system, directing action potential conduction from the atria to the ventricles**.

At the **superior border of the inferior rib**.

The **cardiovascular system is the first major organ system to develop and function in the embryo**.

Approximately **20% of congenital defects in newborns involve cardiovascular system malformations**.

The **fusion of two endocardial (or heart) tubes into a single primary heart tube**.

The **sinus venosus**.

The **primitive atrium**.

The **primitive ventricle**.

The **truncus arteriosus gives rise to the outflow channels of the heart, namely the aorta and pulmonary trunk**.

**Atrial septal defects (ASDs), ventricular septal defects (VSDs), or defects involving the great vessels**.

**Embryology terms** representing derivatives of key adult structures and those with direct clinical relevance.

A **zygote**.

The **conceptus**.

The **embryo**.

A **fetus**.

The **blastocyst period** (or Conceptus period).

The **embryonic period**.

**Ectoderm, mesoderm, and endoderm**.

The **embryonic period**.

The **ectoderm**.

The **ectoderm**.

**Neural crest cells**.

The **ectoderm**.

The **foramen ovale**.

A **Patent Ductus Arteriosus (PDA)**.

**Prostaglandin E1 can be used to maintain its patency and enhance blood mixing between parallel circulations**.

**Cardiac and smooth muscle**.

The **difference between pulmonary and systemic circulations**.

**CO = HR x SV**.

**The Wigger’s Diagram**.

The **relationship between intracellular Ca2+ and force of contraction** is that an increase in intracellular Ca2+ increases force of contraction, which increases stroke volume.

The **heart functions as a pump**.

A **normal resting cardiac output (CO) of approximately 5 L/min**.

**Cardiovascular diseases** can manifest at macroscopic or microscopic levels.

**Right atrium, right ventricle, left atrium, and left ventricle**.

The **tricuspid valve**.

The **mitral valve**.

**Pulmonary and aortic semilunar valves**.

Blood from the systemic circulation flows to the **right atrium**, then **right ventricle**, into the **pulmonary circulation** for gas exchange.

Blood returns to the **left atrium**, then **left ventricle**, and finally into the **systemic circulation via the aorta**.

**AV valves (mitral and tricuspid) open when atrial pressure exceeds ventricular pressure**.

**AV valves (mitral and tricuspid) close when ventricular pressure exceeds atrial pressure**.

**Semilunar valves (aortic and pulmonary) close when great artery pressure exceeds ventricular pressure**.

**Semilunar valves (aortic and pulmonary) open when ventricular pressure exceeds great artery pressure**.

**Stenotic valves are narrow and impede blood flow**, requiring higher upstream pressures.

Murmurs are heard with stenotic valves when **open**.

**Insufficient valves are leaky**, allowing blood to flow backward (regurgitation).

Murmurs are heard with insufficient valves when **closed**.

**Systole is the period of ventricular contraction and blood ejection**.

**Diastole is the period of ventricular relaxation and filling**.

The **pulmonary circulation** is highly compliant with **lower pressures** (right ventricular systolic pressure ~ **25 mmHg**).

The **systemic circulation** has **higher pressures** (left ventricular systolic pressure ~ **120 mmHg**).

The **inotropic state (contractility)** of the heart, the **filling of the heart (preload)**, and the **pressure against which the heart must work (afterload)**.

**Cardiac muscle is a syncytium**.

**Gap junctions**.

**Desmosomes**.

**Intercalated discs**.

An amplitude of about **110-120 mV**.

A duration of approximately **0.25-0.30 seconds**.

Its **long plateau phase is primarily due to voltage-dependent L-type Ca2+ channels**.

**Contraction of cardiac muscle is triggered by an increase in myoplasmic Ca2+ concentration**.

A larger **Ca2+ release from the sarcoplasmic reticulum (SR)**.

**Calcium-induced calcium release**.

Left ventricular pressure peaks around **120 mmHg** during systole.

Aortic pressure falls to about **80 mmHg** during diastole.

Typical **end-diastolic volume is about 135 ml**.

**End-systolic volume is about 65 ml**.

The **first heart sound (S1) is caused by the closing of the AV valves**.

The **second heart sound (S2) is caused by the closing of the semilunar valves**.

The **tricuspid valve**.

**P wave: atrial depolarization**.

**QRS complex: ventricular depolarization**.

**T wave: ventricular repolarization**.

The **interval between the P wave and the QRS complex is the AV nodal delay**.

The **ST segment** represents the plateau phase of the ventricular action potential, when the ventricle is uniformly depolarized.

**Isovolumic contraction**.

**Isovolumic relaxation**.

The **resting membrane potential** of ventricular and atrial contractile cells is about **-90 mV**.

**SA and AV node cells exhibit pacemaker activity**.

The **SA node normally being the heart's pacemaker because it has the fastest rate of depolarization**.

**Na+ (135-145 mM), K+ (3.5-5.0 mM), Ca2+ (2.0-2.6 mM)**.

**Na+ (~10-15 mM), K+ (~140 mM), Ca2+ (~50 nM at rest)**.

**SA node → atria → AV node (slow conduction) → Bundle of His → bundle branches → Purkinje fibers (fast conduction) → ventricular muscle**.

**Thick filaments are composed of myosin**.

**Thin filaments consist of actin, tropomyosin, and troponin**.

**Tropomyosin blocks actin binding sites**.

**Troponin C binds Ca2+**.

**ATP hydrolysis energizes the myosin head**.

**Ca2+ is removed from the myoplasm**, primarily by **SR Ca2+ pumps** and the **Na+/Ca2+ exchanger**.

**Increased stretch (from more blood filling) to generate additional force**.

**Contractility (inotropic state) is the force developed at a given fiber length**.

It is **increased by factors like catecholamines** and **cardiac glycosides**.

**Sympathetic nerves extensively innervate the ventricles, atria, SA node, and AV node**.

**Norepinephrine (NE)**.

**β1 adrenergic receptors**.

**Sympathetic stimulation produces increased heart rate (positive chronotropic effect), increased force of contraction (positive inotropic effect) in both atria and ventricles, and increased conduction velocity through the AV node**.

**β1 receptors activating Gs proteins, leading to increased cAMP and PKA activity, which phosphorylates Ca2+ and pacemaker channels, enhancing their activity. PKA also enhances SR Ca2+ pump activity**.

**Parasympathetic nerves (vagus nerve) innervate the atria, SA node, and AV node**.

**Acetylcholine (Ach)**.

**M2 muscarinic receptors**.

**Parasympathetic stimulation produces decreased heart rate, decreased conduction velocity at the AV node, and decreased force of contraction only in the atria**.

**M2 receptors activating Gi proteins, leading to decreased cAMP and PKA activity, and direct activation of K+ channels, which hyperpolarizes the membrane and slows depolarization in pacemaker cells**.

Both β1 adrenergic and M2 muscarinic receptors are **G-protein coupled receptors**.

**Inotropic drugs increase the force of ventricular contraction by increasing myoplasmic Ca2+ concentration during systole**.

**Cardiac glycosides (e.g., digitalis)** inhibit Na+/K+ ATPase, increasing intracellular Na+, which then inhibits the Na+/Ca2+ exchanger, leading to more Ca2+ stored in the SR and a more forceful contraction.

**Sympathomimetic amines (e.g., dobutamine)** activate β1 adrenergic receptors, mimicking sympathetic effects.

**Phosphodiesterase inhibitors** slow cAMP breakdown, leading to increased cAMP and enhanced Ca2+ entry/force of contraction.

**Skeletal, cardiac, and smooth**.

**Skeletal and cardiac are striated**.

**Smooth is unstriated**.

**Skeletal muscle is voluntary**.

**Cardiac and smooth are involuntary**.

**Single-unit smooth muscle**.

**Multiunit smooth muscle**.

**Tonic smooth muscle**.

**Phasic smooth muscle**.

**Dense bodies anchor thin filaments**.

**Increased myoplasmic Ca2+**, mostly from extracellular fluid.

**Smooth muscle myosin must be phosphorylated to bind actin**.

The **latch phenomenon**.

Smooth muscle exhibits a **stress relaxation response**.

**Vascular smooth muscle primarily receives sympathetic innervation**.

**β2 adrenergic receptors**
Epinephrine/Norepinephrine → β₂-Adrenergic Receptor (GPCR) → Gs Protein Activation → Adenylyl Cyclase Activation → ATP → cAMP → PKA Activation → Inhibition of MLCK → ↓ Myosin Phosphorylation → ↓ Actin-Myosin Interaction → Smooth Muscle Relaxation → Vasodilation

**α2 adrenergic receptors** inhibit adenylyl cyclase -> decreased cAMP/PKA -> activates myosin kinase -> contraction and vasoconstriction.

**α1 adrenergic receptors** activate PLC -> IP3 -> Ca2+ release from SR -> contraction.

**M3 muscarinic receptors** cause nitric oxide (NO) production, which diffuses to smooth muscle to increase cGMP, leading to relaxation and vasodilation.

**Arteriolar smooth muscle maintains vascular tone** due to sympathetic NE release and myogenic activity.

**Relaxation/vasodilation** of arteriolar smooth muscle.

The **ANS is an efferent system innervating every organ, controlling involuntary functions**.

The **sympathetic system prepares for 'fight or flight'**.

The **parasympathetic system promotes 'rest and digest'**.

**Reflex arcs are crucial for ANS function, operating involuntarily to maintain homeostasis**.

**Sympathetic preganglionic fibers are short and release Ach**.

Postganglionic fibers are long and typically release **NE**.

**Parasympathetic preganglionic fibers are long and release Ach**.

Postganglionic fibers are short and release **Ach**.

**Receptors convert stimuli into electrical receptor potentials, which generate action potentials**.

Receptors can be **phasic**, **tonic**, or **mixed**.

The **baroreflex is a key autonomic reflex that regulates blood pressure by altering sympathetic and parasympathetic tone in response to stretch in baroreceptors**.

**M3 receptors increase motility**.

**β2 receptors decrease motility**.

**α1 receptors decrease motility**.

**Presynaptic α2 receptors decrease ACh release**, reducing motility.

**ACh binds to M3 receptors**.

Leading to **increased secretion**.

**Congenital heart disease (CHD)**.

**Down syndrome** is a known risk factor for CHD.

**Tetralogy of Fallot (TOF)**.

**Pulmonary stenosis, right ventricular hypertrophy, an overriding aorta, and a ventricular septal defect**.

A "**boot-shaped**" heart on chest X-ray.

A **Patent Ductus Arteriosus (PDA)**.

**Eisenmenger syndrome**.

**Blood flow from the left ventricle to the right ventricle**.

**Increased right ventricular pressure**.

A **right-to-left shunt** (Eisenmenger syndrome).

**Coarctation of the aorta**.

**Complete atrioventricular canal defect**.

A **paradoxical embolism**.

A **Valsalva maneuver increases the risk of paradoxical embolism by increasing right atrial pressure**.

**Truncus arteriosus** is due to a **failure of septation of the truncus arteriosus**.

An **Atrial Septal Defect (ASD)**.

**Pulmonary hypertension**.

The **incomplete formation of the septum secundum**.

**Transposition of the Great Arteries (TGA)**.

**Congenital heart disease (CHD) affects approximately 0.8% of live births and remains the leading cause of death in children with congenital malformations**.

The **most common congenital heart defect is ventricular septal defect (VSD)**.

**Pulmonary vascular resistance (PVR) significantly decreases in the first several weeks of life**, leading to an **increase in left-to-right shunting**.

**Tetralogy of Fallot** results from an **Anterior displacement of the infundibular (conal) septum**, leading to **pulmonary stenosis, a malalignment VSD, an overriding aorta, and right ventricular hypertrophy**.

A "**tet spell**" is a **hypercyanotic episode** characterized by a **sudden increase in right ventricular outflow tract obstruction, resulting in increased right-to-left shunting of deoxygenated blood across the VSD into the systemic circulation**. This is often **triggered by crying and agitation**.

To **break a tet spell, the knee-to-chest position is used**. This maneuver **increases systemic vascular resistance (SVR), causing left-sided (systemic) pressures to exceed right-sided (pulmonary) pressures, thereby decreasing right-to-left shunting**.

**Large VSDs** typically cause **symptoms of heart failure** in infants at **1-2 months of age**.

Examples include **poor weight gain, difficulty breastfeeding, tachycardia, tachypnea, hepatomegaly**.

The **pulmonary overcirculation leads to pulmonary edema (tachypnea) and increased caloric expenditure (poor weight gain)**.

The **long-term consequence of uncorrected left-to-right shunts (like a VSD) is pulmonary vascular changes and pulmonary hypertension, leading to Eisenmenger’s Syndrome**.

**D-Transposition of the Great Arteries (D-TGA)** involves the **aorta arising from the right ventricle and the pulmonary artery from the left ventricle, creating two parallel circulations**.

Infants present with **unremitting cyanosis immediately at birth that does not improve with supplemental oxygen**.

**Connections between the circulations (ASD or PFO) are required for survival**.

**Prostaglandin E1 is used to maintain ductus arteriosus patency**.

A **Patent Ductus Arteriosus (PDA)** is a fetal structure that normally closes shortly after birth. If it remains patent, it causes **left-to-right shunting**, leading to **pulmonary overcirculation and potential heart failure**.

Clinical intolerance can manifest as a **continuous murmur, tachypnea, tachycardia, increased work of breathing, failure to thrive, and poor feeding**.

**Coarctation of the aorta** is a narrowing of the aorta that can be a **life-threatening emergency if the PDA is the sole source of blood to the lower body**.

Patients present with **upper extremity hypertension and delayed or absent femoral pulses**.

It is associated with **Turner’s syndrome**.

**Ebstein Anomaly** is a malformation of the **tricuspid valve**, causing regurgitation into the right atrium.

**Truncus Arteriosus** is caused by the **failure of the truncus arteriosus to divide into the pulmonary artery and aorta**, resulting in a single outflow artery.

**Total Anomalous Pulmonary Venous Return (TAPVR)** involves pulmonary veins draining into the right atrium instead of the left, leading to lower oxygen levels in systemic blood and **cyanosis**.

**VSD, ASD, Tetralogy of Fallot**.

**PDA, pulmonary artery stenosis**.

**AV septal defect, VSD, ASD, Tetralogy of Fallot, PDA**.

**Aortic aneurysm and dissection, aortic regurgitation, mitral valve prolapse**.

**Bicuspid aortic valve, coarctation of the aorta**.

**Supravalvular aortic stenosis, peripheral pulmonary artery stenosis**.

**Truncus arteriosus, Tetralogy of Fallot**.

**Ebstein anomaly**.

Tropomyosin

Ca2+

Troponin C

Tropomyosin

Myosin

Actin

Attached state

Attached state

Rigor mortis

Myosin

Myosin

Myosin

Power stroke

Actin and myosin

Low calcium

Tropomyosin

Myosin binding sites on the actin

The action potential propagates along the sarcolemma and into the T-tubular membrane, opening voltage-dependent L-type Ca2+ channels, which then triggers Ca2+ release from the SR through ryanodine receptors (RyR), a process known as Ca2+-induced Ca2+ release (CICR)

Pacemaker cells

Along the sarcolemma and into the T-tubular membrane

Voltage-dependent L-type Ca2+ channels

DHPR or dihydropyridine receptors

Ca2+ that enters the cell through L-type Ca2+ channels

Ryanodine receptor (RyR)

Ca2+-induced Ca2+ release (CICR)

RyR

Millimolar range

About 50-150 nM

Catecholamines (epinephrine and norepinephrine)

Ventricular action potential

Ca2+ binding to the myofilaments

SR Ca ATPase (pump)

Decreased Myosin Light Chain Kinase (MLCK) activity leading to vascular muscle relaxation

Increased intracellular Ca2+

Calmodulin

Ca2+‑calmodulin complex

Myosin kinase (myosin light chain-kinase, MLCK)

Phosphorylates myosin

Phosphorylated myosin

Contraction

By inhibiting the influx of calcium ions into smooth muscle cells

Calcium binding to calmodulin

Myosin light chain kinase

Relaxation of smooth muscle

Blood vessels, particularly cerebral arteries

Vasospasm and dilation associated with migraine headaches

ɑ1 agonist

Causes contraction

α₁ Agonist (e.g., phenylephrine)
↓
Binds to α₁ adrenergic receptor (Gq-coupled)
↓
Activates Gq protein
↓
Stimulates phospholipase C (PLC)
↓
PLC converts PIP₂ → IP₃ + DAG
↓
IP₃ binds to IP₃ receptors on SR
↓
Ca²⁺ released from sarcoplasmic reticulum
↓
↑ Intracellular Ca²⁺
↓
Ca²⁺ binds to calmodulin
↓
Activates myosin light chain kinase (MLCK)
↓
MLCK phosphorylates myosin
↓
Cross-bridge formation with actin
↓
**Smooth muscle contraction → Vasoconstriction**

By decreasing PKA activity

Causes less contraction by increasing PKA activity

Causes dilation

No

Cardiac muscle

Cause it to contract with less force

Acetylcholine

Norepinephrine

Acetylcholine

Acetylcholine

Acetylcholine

Acetylcholine

Sympathetic cholinergic activation

Increase

No, beta-1 receptors are primarily responsible for direct cardiac stimulation