05.29.09: The Fetus at Birth

Author: R. Schumacher, 2009

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The First Breath: M1 2009The First Breath: M1 2009

R. SchumacherM1 EmbryologySpring 2009

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BeakerBeaker

A

Pierre Simon LaplacePierre Simon Laplace

• French mathematician, French mathematician, physicist, and astronomerphysicist, and astronomer

• Taught Napoleon - Ecole Taught Napoleon - Ecole Militaire de ParisMilitaire de Paris

• Traite de Mecanique Traite de Mecanique Celeste Celeste – 1806-7 in Tome IV discusses 1806-7 in Tome IV discusses

capillary action and relates capillary action and relates surface tension and radius surface tension and radius of curvatureof curvature

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Laplace RelationshipLaplace Relationship• ∆∆P =2γ/r P =2γ/r • Trans-surface pressure = 2(surface tension) / radius of curvatureTrans-surface pressure = 2(surface tension) / radius of curvature

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Pulmonary SurfactantPulmonary Surfactant

• A liquid film that comes in contact with air A liquid film that comes in contact with air covers alveoli, hence surface tension forces covers alveoli, hence surface tension forces are at work in the lung. are at work in the lung.

• If surface tension can be lowered then the If surface tension can be lowered then the work of breathing should be easier. work of breathing should be easier.

• Since the forces are due to molecular forces Since the forces are due to molecular forces of attraction, one way to lower surface of attraction, one way to lower surface tension would be to physically separate the tension would be to physically separate the molecules. This is what pulmonary surfactant molecules. This is what pulmonary surfactant does.does.

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• If this surface film is compressed the phospholipids will be packed more tightly and more water excluded from the surface. This is ideal: the smaller the radius of curvature the more important surface tension forces become (LaPlace), the smaller the radius of curvature the tighter the surfactant molecular pack and the greater the reduction in surface tension forces.

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LAWS OF LUNG LAWS OF LUNG DEVELOPEMENTDEVELOPEMENT

• Law I- AirwaysLaw I- Airways– The airways are present by the 16th week of intrauterine The airways are present by the 16th week of intrauterine

lifelife

• Law II - AlveoliLaw II - Alveoli– Alveoli develop principally after birthAlveoli develop principally after birth

• At birth the alveoli are primitiveAt birth the alveoli are primitive• At birth there are 20,000,000 alveoli, at age eight At birth there are 20,000,000 alveoli, at age eight

years- 300,000,000years- 300,000,000

• Law III- VascularLaw III- Vascular– preacinar arteries follow the development of the airwayspreacinar arteries follow the development of the airways– intraacinar arteries appear as alveoli growintraacinar arteries appear as alveoli grow

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Jean L. PoiseuilleJean L. Poiseuille

Poiseuille, Jean Léonard Marie (1799-1869) Poiseuille, Jean Léonard Marie (1799-1869) was a French physiologist who made a key was a French physiologist who made a key contribution to our knowledge of the circulation of contribution to our knowledge of the circulation of blood in the arteries. blood in the arteries.

Poiseuille's Law of The Flow of Liquids Through a Tube:Poiseuille's Law of The Flow of Liquids Through a Tube:Where:Where:l = the length of the tube in cml = the length of the tube in cmr = the radius of the tube in cmr = the radius of the tube in cmp = the difference in pressure of the two ends of the tube in dynes per cm2p = the difference in pressure of the two ends of the tube in dynes per cm2c = the coefficient of Viscosity in poises (dyne-seconds per cm2)c = the coefficient of Viscosity in poises (dyne-seconds per cm2)

v = volume in cm3 per secondv = volume in cm3 per second

Then:Then: v = r v = r 4 4 p/8clp/8cl

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• Arteriogram:Arteriogram:– Newborn Newborn

lacks intra-lacks intra-acinar acinar arteriesarteries

– Lacks Lacks background background “haze” seen “haze” seen in the adult in the adult lunglung

– So resistance So resistance is highis high Source Undetermined

Pulmonary vascular Pulmonary vascular resistance “high” in the resistance “high” in the

newborn because:newborn because:1.There is a relative lack of alveoli and 1.There is a relative lack of alveoli and

intraacinar cross sectional area for intraacinar cross sectional area for blood flow (Pouseuille).blood flow (Pouseuille).

2. In smaller arterioles, pulmonary 2. In smaller arterioles, pulmonary vascular smooth muscle exists the vascular smooth muscle exists the medial thickness of the arteriole is medial thickness of the arteriole is higher than the adult. (not from laws higher than the adult. (not from laws of development)of development)

Pulmonary vascular Pulmonary vascular resistance low in the resistance low in the

newborn because:newborn because:1. Larger arteries are less muscular in 1. Larger arteries are less muscular in

the newborn than in the adult.the newborn than in the adult.

2. Vascular smooth muscle does not 2. Vascular smooth muscle does not exist/extend to the same vascular exist/extend to the same vascular “level” as it does in the adult.“level” as it does in the adult.

““THE FIRST BREATH”THE FIRST BREATH”

1.1. What has to happen?What has to happen?

Think big easy general ideasThink big easy general ideas

2. How does it happen? How does it happen?

Think: “In the body, how can I move Think: “In the body, how can I move water from one place to another”water from one place to another”

THE FIRST BREATH: THE FIRST BREATH: Goal #1: Fluid out, Air in.Goal #1: Fluid out, Air in.

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Fetal Pulmonary Fluid:Fetal Pulmonary Fluid:Chloride Secreting EpitheliumChloride Secreting Epithelium • Prior to birth the lung is a fluid filled Prior to birth the lung is a fluid filled

organ with transepithelial chloride organ with transepithelial chloride secretion as the major driving force for secretion as the major driving force for active production of lung fluid. There is active production of lung fluid. There is net flow of fluid out of the lungs. net flow of fluid out of the lungs.

• Multiple (but not all) studies suggest Multiple (but not all) studies suggest decrease in Cl pump activity is decrease in Cl pump activity is responsible for decrease in lung water responsible for decrease in lung water prior to labor.prior to labor.

Fetal Pulmonary Fluid:Fetal Pulmonary Fluid:Na “Reabsorption”Na “Reabsorption”• At birth lung epithelia change from Cl At birth lung epithelia change from Cl

secreting to Na reabsorption mode.secreting to Na reabsorption mode.• ENaC expression is developmentally ENaC expression is developmentally

regulated with peak expression in the alveolar regulated with peak expression in the alveolar epithelium achieved at term gestationepithelium achieved at term gestation

• ααENaC “pumps” increase activity. Why/ Not ENaC “pumps” increase activity. Why/ Not clear. Exposure to air?, Stretch?, Steroids?, clear. Exposure to air?, Stretch?, Steroids?, ββ adrenergic influences adrenergic influences

• (Nasal Na epithelial activity in premies……)(Nasal Na epithelial activity in premies……)

Fetal Pulmonary Fluid:Fetal Pulmonary Fluid:Na “Reabsorption”Na “Reabsorption”• At birth lung epithelia change from Cl At birth lung epithelia change from Cl

secreting to Na reabsorption mode.secreting to Na reabsorption mode.• ENaC expression is developmentally ENaC expression is developmentally

regulated with peak expression in the alveolar regulated with peak expression in the alveolar epithelium achieved at term gestationepithelium achieved at term gestation

• ααENaC “pumps” increase activity. Why/ Not ENaC “pumps” increase activity. Why/ Not clear. Exposure to air?, Stretch?, Steroids?, clear. Exposure to air?, Stretch?, Steroids?, ββ adrenergic influences adrenergic influences

• (Nasal Na epithelial activity in premies……)(Nasal Na epithelial activity in premies……)

What About the Squeeze?What About the Squeeze?

• 1917 radiographic studies suggest 1917 radiographic studies suggest compression of thorax in labor. compression of thorax in labor.

• 1935-56 German texts state lung water 1935-56 German texts state lung water is jetted from the mouth with is jetted from the mouth with squeezing.squeezing.

• Recent xray (rabbits) and MRI studies Recent xray (rabbits) and MRI studies still suggest squeezing plays a role still suggest squeezing plays a role

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• At the time of birth some (but not the majority) of lung At the time of birth some (but not the majority) of lung water may be squeezed from the fetal lung as the water may be squeezed from the fetal lung as the infant passes through the birth canal. This removes infant passes through the birth canal. This removes some fluid and “loads” the diaphragm (decrease some fluid and “loads” the diaphragm (decrease radius of curvature and aligns sarcomeres) for “the radius of curvature and aligns sarcomeres) for “the first breath.”first breath.”

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• Starling forces at work to clear lung fluidStarling forces at work to clear lung fluid

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• Functional Residual Capacity is established

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Goal #2. Blood InGoal #2. Blood In

• Fetal Fetal circulation:circulation:– “ “right-to-left right-to-left

shunting” at shunting” at the level of the level of the atria and the atria and the ductus the ductus arteriosus.arteriosus.

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Pulmonary Vascular Pulmonary Vascular Resistance Resistance Falls at Birth: Why?Falls at Birth: Why?• MechanicalMechanical

• BiochemicalBiochemical– Simple examples pH, pO2Simple examples pH, pO2– More……..More……..

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