Neonatal Adaptations (Fetal Adaptations and Important Adaptations to extra-uterine Life in the Neonate)

What hormones increase in newly born animals?

What are they responsible for?

• Cortisol

• Catecholamines

• Thyroid hormones

Are responsible for organ maturation, metabolic preparations for survival immediately after birth and subsequently, and non-shivering thermogenesis

What common issues may newborn animals encounter at the start of their extra-uterine life? Why?

They need to prepare for the hypoxia, hypoglycaemia and hypothermia

• Warm environment with readily available (and much increased) nutrient, glucose and oxygen supply

• Placental supply of oxygen, energy and nutrients (including calcium) is abruptly removed, temperature drops by 30°C

After the birth of an animal, what does it need to begin to be able to regulate on its own?

• Initiate breathing

• Thermogenesis

• Glycolysis

• Gluconeogenesis

• Adult Circulation

• Maturation of Organs

Why is a cortisol rise before birth essential?

Cortisol from adrenal cortex essential for:

• Lung maturation and surfactant synthesis

• Clearance of fetal lung fluid

• Gut maturation

• Thyroid axis maturation and more conversion T4 to T3 (The active thyroid hormone)

• Energy stores for response to cold and hypoglycemia

Describe the hormone profile in the late fetus that enables it to build fat and glycogen stores before birth.

• High insulin and low glucagon (Pancreas)

Cortisol prepares the body for the response to _________.

• This hormone does what to the body?

Catecholamines (From adrenal medula)

→ Surge within minutes of birth, due to hypoxia and cold shock

• Increases in blood pressure (cardiovascular changes) → to adult circulation

• Thermogenesis from brown adipose tissue

• Increased glucose availability

  • Via high glucagon, suppressed insulin, causing glycolysis, lipolysis and gluconeogenesis

Cortisol also causes a perinatal rise in ______ hormone.

• This hormone does what?

Thyroid Hormone from thyroid gland - increase seen in first 24h

• Due to cortisol, catecholamines after hypoxia, cold shock

• Stimulates thermogenesis

• Regulates maturation of the cardiovascular, respiratory, nervous, and musculoskeletal systems

Why is hypothermia a danger for neonatal animals?

• Within placenta the fetus is at 38.8 °C

• Birth means exposure of wet skin to much lower air and ground temperatures well below 20 °C

• Danger of hypothermia, thus neonatal requirement for thermogenesis!

How can heat be generates by the newborn animal?

• Energy expenditure via shivering (skeletal muscle activity) at least until hair coat is dry

• Energy expenditure via attempting to stand, and standing for the first time

• Colostrum is an excellent energy source in the first 12 hours

• Brown Adipose Tissue is responsible for non-shivering thermogenesis in hypothermic neonates in the first 5 hours

How much of fetal weight does brown fat make up?

Where is it locates in the fetus?

What percent of heat generation is it responsible for?

• 1-2% of fetal weight at term

• Located around kidneys and ribs

• 100% of heat generation

  • Can deplete in 5 hrs

How does brown adipose tissue generate heat?

• heat generation by uncoupling mitochondrial rrespiration from ATP synthesis via UCP1 (Uncoupling Protein 1)

• in response to the norepinephrine rise stimulated after birth

• consumes oxygen, glucose and fatty acids released from stored fat, but instead of ATP generation, we generate heat only

• UCP1 protein synthesis stimulated by perinatal and postnatal hormone changes (cortisol rise, catecholamines enhancing T4 to T3 conversion, T3, increased free fatty acids due to lipolysis)

What must the neonate’s lungs quickly gain the ability to do following birth?

Clear fluid, mature and be perfused for efficient gas exchange

What are the three important lung adaptations taking place after birth?

1. Clearance of Fetal Lung Fluid

2. Surfactant in Alveoli

3. Continuous Breathing Pattern

How does the fetus clear fetal lung fluid from the alveoli following birth?

• aeration (air enters lungs)

• cortisol, catecholamines, thyroid hormones will suppress lung fluid production and support clearance

• increase in pulmonary blood flow (decreasing lung vascular resistance), becoming more perfused or dilated

• increase in oxygen and carbon dioxide exchange between pulmonary capillary blood and alveolar gas

Describe the newborn’s first breath.

Newborn takes its first breath → air enters alveoli

fluid moves into distal airspace → absorbed

In 3 breaths 50% of the lungs become aerated

Oxygen → transit into pulmonary vessels

How do the newborn lungs adapt to produce surfactant from alveoli after birth?

• new alveolar lining layer via enhanced surfactant synthesis, secretion and recycling

• secreted into the lung fluid before and after birth

• stimulated by cortisol, catecholamines, alveolar stretch

Describe how newborns develop a continuous breathing pattern.

• development only ex-utero

• following tactile and cold stimuli

• following hypoxia

*Practice breathing in utero during REM sleep

What does surfactant in the lungs do?

• Reduces inflation resistance and ensures alveoli do no collapse after expiration

• Reduces surface tension, so it allows expansion and prevents collapse as well

Describe the normal route of fetal circulation.

The fetal circulation bypasses the liver and, importantly, the lungs due to high pulmonary vascular resistance, while the placenta offers low resistance (and is the where gas exchange occurs in utero)

Why type of hemoglobin do fetuses have?

Additionally describe the flow of blood through the fetus.

• Fetal hemoglobin shows left Bohr shift so it loads O2 at low O, tension (it will take > 3 weeks until adult hemoglobin has replaced fetal Hb)

• Adult shifts to right, higher O2 partial pressure

• Umbilical vein O, saturation is 80%, with some flow bypassing liver to enter caudal vena cava via the Ductus Venosus

• Caudal vena cava flow is directed through right atrium and Foramen Ovale to left atrium and ventricle, then pumped into aorta

• Cranial vena cava and cardiac flow directed into right ventricle exiting in pulmonary artery, but high PVR causes bulk of flow to be diverted to aorta via Ductus Arteriosus (DA)

• DA joins aorta downstream of arteries to head and forequarters (receive blood with highest O2 saturation) - aortic blood 02 saturation is reduced to 58%

• Placenta receives ¾ of fetal aortic stream for reoxygenation, only ¼ supplies fetal hindquarters

Describe how blood circulates through the fetus.

• Umbilical vein O2, saturation is 80%, with some flow bypassing liver to enter caudal vena cava via the Ductus Venosus

  • High pulmonary vascular resistance (PVR) in the fetal lungs due to low oxygen tension and low pulmonary blood flow

• Caudal vena cava flow is directed through right atrium and Foramen Ovale to left atrium and ventricle (The two atria are essential “one”), then pumped into aorta

• Cranial vena cava and cardiac flow directed into right ventricle exiting in pulmonary artery, but high PVR causes bulk of flow to be diverted to aorta via Ductus Arteriosus (DA)

  • Since there is no need for lungs

• DA joins aorta downstream of arteries to head and forequarters (receive blood with highest O2 saturation) - aortic blood O2 saturation is reduced to 58%

• Placenta receives ¾ of fetal aortic stream for reoxygenation, only ¼ supplies fetal hindquarters

What ductile holes must close in the heart now that newborn does not rely on the placenta for oxygenated blood, but instead it’s own lungs?

The increased lung perfusion, oxygen pressure and peripheral resistance will separate the right and left side of the heart, with closure of the Foramen Ovale and the Ductus Arteriosus

• Ductus Venosus in Liver as well

How does the change in blood flow in the fetus to newborn animal change the pO2?

Changes left atrium from 65% to 90% in 5 minutes

• Doubling of cardiac output with rise in oxygen consumption due to increased metabolism, breathing effort, thermogenesis

• Increased blood pressure

• More blood flow to lungs, heart, kidneys, GIT

What cardiac pathologies might derive from non-closure of fetal ductus or foramen in young animals?

• Patent ductus arteriosis (Parent Ductus Botalli)

  • Failure of Ductus Arteriosus

• Ventricular Septal Defect (VSD)