Heart and Respiratory System Development

Cardiovascular System Development

  • The cardiovascular system, which encompasses the heart and blood vessels, develops from the embryonic mesoderm, specifically the splanchnic layer of the lateral plate, and contributions from the neural crest.

  • Initially, there exist two heart (endocardial) tubes. These tubes fuse in the midline forming a single heart tube.

  • The heart begins to beat by day 22 of development.

  • The heart tube elongates and forms five dilatations, which develop in this sequence from caudal to cranial:

    • Sinus Venosus

    • Atrium

    • Ventricle

    • Bulbus Cordis

    • Truncus Arteriosus

Looping and Folding of the Heart Tube

  • By day 23 (week 4), the heart tube initiates its looping and folding process.

  • The cranial portion of the tube bends:

    • Ventral

    • Caudally

    • To the right

  • The caudal portion shifts:

    • Dorsocranially

    • To the left

  • This process results in an 'S'-shaped loop completing by day 28:

    • Atrium: Moves to dorsal and cranial position

    • Ventricle: Displaced to the left

    • Bulbus Cordis: Moves inferiorly, ventrally to the right

Derivatives of the Heart Tube

  • The derivatives of the heart tube include:

    • Sinus Venosus

    • Right horn: Smooth part of the Right Atrium

    • Left horn: Coronary sinus & Oblique vein of the Left Atrium

    • Primitive Atrium: Rough parts of the Right & Left Atria

    • Primitive Ventricle: Rough part of the Left Ventricle

    • Bulbus Cordis:

    • Proximal part: Rough inflow part of the Right Ventricle

    • Distal part: Smooth outflow part of both Ventricles

    • Truncus Arteriosus: Aorta and Pulmonary trunk

  • Note: The smooth part of the left atrium develops from the absorption of the pulmonary veins.

Atrioventricular Canal Development

  • The AV canal forms from the atrioventricular portion of the primitive heart tube.

  • Endocardial cushions develop on the dorsal and ventral walls of the AV canal, which grow and fuse to:

    • Divide the single AV canal into right and left AV orifices

    • Contribute to the septation of the heart, resulting in:

    • Tricuspid Valve

    • Mitral Valve

    • Atrioventricular (membranous) part of the interventricular septum

    • Lower part of interatrial septum (contribution from septum primum)

  • Tricuspid Atresia: A condition caused by the failure of formation of the tricuspid valve due to abnormal development of the AV canal and endocardial cushions.

Development of the Ascending Aorta and Pulmonary Trunk

  • Both structures develop from the truncus arteriosus, initially a single tube.

  • A spiral septum, named the Aorticopulmonary septum, arises from migration of neural crest cells and grows spirally inside the truncus, dividing it into:

    • Aorta

    • Pulmonary Trunk

  • Positioning: The pulmonary trunk lies anterior to the aorta at its beginning.

Aorticopulmonary Septal Defects

  • Caused by abnormal neural crest cell migration, resulting in partial development of the A-P septum and endocardial cushions:

    • Persistent Truncus Arteriosus: Involves one single large vessel leaving the heart, receiving blood from both right and left ventricles, usually accompanied by ventricular septal defect (VSD), resulting in a right-to-left shunt and cyanosis.

    • Transposition of the Great Arteries: Occurs due to non-spiral development of the A-P septum, where the aorta arises from the right ventricle and the pulmonary trunk arises from the left ventricle; this condition also leads to cyanosis and is incompatible with life unless accompanied by a shunt.

Persistent Right Dorsal Aorta

  • The right 4th aortic arch regresses except for parts forming the right subclavian artery.

  • Persistence of the right dorsal aorta (RDA) represents a developmental anomaly where the right side of the dorsal aorta, normally regressing, remains, potentially leading to variations in the aortic arch system:

    • Right Aortic Arch (RAA)

    • Double Aortic Arch (DAA)

    • Aberrant Subclavian Artery

  • These variations can potentially cause vascular rings that may constrict the trachea or esophagus; however, many individuals remain asymptomatic.

Dextrocardia and Ectopia Cordis

  • Dextrocardia: A condition characterized by the heart being located on the right side of the chest, caused by genetic defects during development. It may be associated with:

    • Pulmonary Hypoplasia

    • Situs Inversus: Transposition of all the viscera.

  • Ectopia Cordis (Exstrophy of the Heart): Caused by failure of fusion of the two embryonic lateral folds in the midline, leading to exposure of the heart.

Development of the Respiratory System

  • The epithelium of the larynx, trachea, bronchi, and lungs originates as an endodermal outgrowth from the ventral wall of the foregut known as the Respiratory Diverticulum (Lung Bud), occurring by the 4th week of intrauterine life (IUL).

  • The cartilaginous, muscular, and connective tissue components of the trachea, bronchi, and lungs (as well as the visceral pleura) are derived from the splanchnic layer surrounding the foregut, while the parietal pleura derives from the somatic layer of the lateral plate mesoderm.

Tracheoesophageal Septum Formation

  • The respiratory diverticulum separates from the foregut by forming bilateral longitudinal ridges known as the tracheoesophageal folds.

  • These folds fuse to form the tracheoesophageal septum, which separates the ventral trachea from the dorsal esophagus, allowing the pharynx to connect with the larynx through the future laryngeal inlet.

Esophageal Atresia and Tracheoesophageal Fistula

  • Tracheoesophageal Fistula: Results from improper division of the foregut by the tracheoesophageal septum, leading to abnormal communication between the trachea and esophagus.

  • Esophageal Atresia with Tracheoesophageal Fistula: The most common type, where the upper part of the esophagus ends in a blind pouch visible in X-rays as a coiled tube in the upper esophagus, typically associated with polyhydramnios.

Development of the Laryngeal Structures and Nerve Supply

  • Muscles and Cartilage of the Larynx:

    • Derived from the mesenchyme of the 4th and 6th Pharyngeal Arches.

    • 4th Arch Muscles: Cricothyroid muscle, innervated by the external laryngeal branch of the superior laryngeal nerve (CN X); structures such as the Thyroid Cartilage and the Epiglottis.

    • 6th Arch Muscles: All laryngeal muscles except the cricothyroid, innervated by the recurrent laryngeal nerve (CN X); structures involved include Cricoid, Arytenoid, and Corniculate cartilages.

  • Tracheal smooth muscles and cartilages derive from the splanchnic layer of the lateral plate mesoderm.

  • Laryngeal Atresia: A rare condition in which the larynx fails to recanalize, requiring immediate tracheostomy to prevent asphyxiation.

  • Laryngomalacia: A condition where congenital weakness of laryngeal cartilages leads to collapse during inspiration, usually resolving spontaneously.

Development of the Lungs

  • The lung development is divided into four periods:

    • Pseudoglandular Period: Weeks 5-16

    • Canalicular Period: Weeks 16-26

    • Saccular Period: Week 26 to Birth (type I squamous pneumocytes for gas exchange; type II pneumocytes produce surfactant)

    • Alveolar Period: Prenatal to Childhood

  • Lungs have a later maturation stage compared to other organs; thus, developmental maturity is critical for survival in premature infants.

  • Lung Buds develop at the end of week 4 as two lateral outpouchings of the laryngotracheal diverticulum, leading to the formation of bronchi and the bronchial tree between the 2nd and 7th months (pseudoglandular and canalicular periods).

  • Formation of terminal sacs and alveoli begins at week 26, with surfactant production commencing between weeks 25 and 28 (saccular and alveolar periods).

  • By birth, there are 20-50 million alveoli.

Respiratory Distress Syndrome (RDS)

  • Occurs predominantly in premature babies due to the delayed production of surfactant by type II pneumocytes (phospholipoprotein) during weeks 25-28 IUL, essential for reducing surface tension to facilitate alveolar expansion.

  • Infants born before 25 weeks face significant survival challenges due to surfactant deficiency.

  • The inability of the lungs to fully inflate causes the formation of hyaline membranes (necrotic debris from type II pneumocytes mixed with fibrin), leading to symptoms of rapid superficial breathing (tachypnea) and cyanosis.

  • Treatment includes antenatal maternal steroids and surfactant replacement.

Breathing in Utero

  • Primitive alveoli formed during the alveolar period enable “breathing” in utero via aspiration and expulsion of amniotic fluid.

  • Pulmonary vascular resistance remains high throughout gestation, attributed to fluid accumulation in the lungs.

  • At birth, the lungs are half-filled with amniotic fluid, which must be cleared through the mouth or absorbed into the blood/lymph.

  • Replacement of fluid with air causes a marked reduction in pulmonary vascular resistance at birth.

  • Alveoli continue to grow and mature until approximately age 8.

Pulmonary Hypoplasia

  • Defined as a poorly developed lung, commonly involving the right lung and often associated with right-sided obstructive congenital heart defects.

  • Left-sided pulmonary hypoplasia is linked with congenital diaphragmatic hernia and bilateral renal agenesis, conditions that contribute to insufficient amniotic fluid levels, also known as Oligohydramnios.