Transcript NROSCI BIOSC 1070 MSNBIO 2070 December 11, 2015

NROSCI BIOSC 1070
MSNBIO 2070
December 9, 2016
Developmental Physiology &
Physiology of Aging
Developmental Physiology

During the first half of pregnancy, the fetus’ own
genetic program is the primary determinant of
growth.

During the second half of pregnancy, the patterns of
growth and development are altered by epigenetic
factors:
• placental
• hormonal
• environmental (e.g., maternal nutrition,
disease, drugs, altitude)
• metabolic (e.g., diabetes)
Development of Cardiovascular
System

Circulation begins at 4th week to provide adequate
nutrition to multicellular fetus.

Many tissues produce red blood cells in the fetus,
including blood vessel endothelium and liver.

Many early red blood cells are nucleated.

Fetal hemoglobin has a higher affinity for O2 than
adult hemoglobin. After ~1 postnatal year, offspring
starts synthesizing adult hemoglobin.
Development of Respiratory
System

Respiratory system development is not complete until near
the end of gestation. Thus, premature infants have difficulty
in breathing.

Surfactant is not present until near the time of birth.

Cortisol is a primary trigger for surfactant production.

Women expected to deliver at 24-34 weeks are provided
steroid therapy to induce surfactant production in the fetus.

Together, glucocorticoid therapy and infusion of surfactant
into the newborn trachea reduce the incidence of respiratory
distress syndrome in premature infants.
Development of Nervous
System

Spinal cord and brainstem reflexes are largely present
by 4 months gestation.

Cortical development lags, and requires environmental
inputs after birth.

Nervous system development is not complete until
several years after birth.
Development of Renal System

The fetal kidneys begin to secrete urine during the
second trimester.

Fetal urine constitutes most amniotic fluid.

However, transport properties of kidney are not as
developed as in the adult. Thus, less water is
reabsorbed, posing a dehydration risk.

Acid-base control by the kidney is particularly poor
in newborns.
Development of GI System

In general, the GI system
becomes functional near the
middle of a normal pregnancy.

The fetus consumes amniotic
fluid, and excretes a waste
product called meconium.

However, liver function is
diminished until after birth,
partly because blood is
shunted away from the liver
during development via
ductus venosus
Development of GI System

The delayed development of hepatic function poses
many problems for the infant:
• Bilirubin is not eliminated in bile; jaundice can occur,
and in rare cases bilirubin encephalopathy
• Plasma protein levels drop, which can result in
edema (due to retarded absorption by capillaries)
• Clotting factor levels drop in the blood; limited blood
clotting potential
• Limited potential for gluconeogenesis. Newborn
must receive nutrition often to avoid a drop in blood
glucose
Metabolic Function: Insulin

Insulin is not required for glucose transport by fetal tissues
until near the time of birth.

However, insulin is an essential growth hormone for the fetus.

Hyperglycemia in mothers with untreated Type I diabetes
results in a large production of insulin by the fetus. This can
result in an increased growth rate.


Overstimulation of b-cells by hyperglycemia in utero can
result in too much insulin secretion in the newborn, and
hypoglycemia.
Hyperglycemia and placental transfer of insulin in mothers
with Type II diabetes can have the same effect.
Metabolic Function: InsulinLike Growth Factor

Insulin-like growth factors from the fetal liver are necessary to
stimulate mitosis and development of the fetus.

Unlike in adults, secretion of these growth factors is not
regulated by growth hormone. The insulin-like growth factors
are even released in anencephalic fetuses with no growth
hormone.
Metabolic Function: Thyroid
Hormone

Thyroid hormone is necessary for normal development, particularly
of the nervous system.

Prior to development of the hypothalamic-pituitary portal system
during the second trimester, the thyroid hormone comes from the
mother.

Thus, hypothyroid mothers typically have offspring with diminished
intellectual capacity.

Mothers with autoimmune diseases that affect the thyroid gland
pass the problematic antibodies to the fetus

Lack of iodine results in diminished thyroid hormone production by
both the mother and fetus, and severe cretinism. ~20 million have
brain damage due to iodine deficiency during fetal life.
Ductus Arteriosus and Foramen Ovale
• In the developing fetus, two shunts divert
blood away from the lungs.
• The foramen ovale is a shunt between the left
atrium and right atrium.
• In addition, ductus arteriosus is a blood vessel
connecting the pulmonary artery to the
proximal descending aorta.
• Between the two, coupled with the extremely
high resistance of the pulmonary circulation,
practically no blood enters the lungs.
Ductus Arteriosus and Foramen Ovale
• Since practically no
blood is moving from
the lungs to the left
atrium, left atrial
pressure is extremely
low in the fetus.
• Thus, the pressure
gradient favors the
movement of blood
from the right to the
left atrium.
Ductus Arteriosus and Foramen Ovale
• Pressures in the pulmonary
artery and aorta are nearly
equal in the fetus, or
pressure is slightly higher in
the pulmonary artery.
• This is due to relatively weak
contractions of the
developing left ventricle, as
well as the fact that preload
to the left ventricle is
relatively low.
• Thus, blood moves from from the pulmonary artery to the
descending aorta through ductus arteriosus.
Ductus Arteriosus and Foramen Ovale

The trajectory of blood flow
from the inferior vena cava
favors movement through
foramen ovale into the left
atrium.

The trajectory of blood flow
from the superior vena cava
favors movement through the
tricuspid valve into the right
ventricle, and then through
ductus arteriosus to the
descending aorta and
placenta.
Ductus Arteriosus and Foramen Ovale
• At birth, the shunts must
close immediately to permit
the normal circulation to
commence.
• Once the fetus is born and
begins to breathe, pulmonary
circulatory resistance drops
precipitously.
• Blood thus begins to flow through the pulmonary circulation
instead of ductus arteriosus, as resistance in the ductus
arteriosus is higher.
Ductus Arteriosus and Foramen Ovale
• High pO2 after birth causes
constriction of the smooth
muscle in ductus arteriosus
• The patency of ductus
arteriosus is dependent on
prostaglandins that are
produced in part by the
placenta.
• The prostaglandins inhibit
the contraction of smooth
muscle within the wall of
ductus arteriosus.
• The prostaglandin levels drop markedly at birth, causing the
ductus to collapse as smooth muscle within contracts.
Development of GI System

Ductus venosus, which
shunts blood away from the
liver, closes within a few
hours of birth.

The closure of ductus
venosus allows portal blood
flow through the liver.

The mechanisms responsible
for closure of ductus venosus
are unknown. Failure of
closure is rare in humans.
The First Breath

Breathing movements start near the end of the 1st trimester.
Breathing ceases just before labor for an unknown reason.

In utero, the alveoli and airways are filled with fluid. Labor induces
increases in catecholamines and arginine vasopressin, which
cause resorption of the fluid. Fluid is also forced out of the lungs
as the fetus moves through the birth canal.

Hypoxia and hypercapnia are the main triggers for the first breath.

The first breath induces changes in cardiovascular pressures that
are responsible for closure of ductus arteriosus and foramen
ovale.

The first breath is normally the most difficult inspiration of a lifetime.
A considerable negative pressure within the intrapleural space is
necessary to overcome the effects of surface tension.
Immunity

The placenta actively transports IgG to the fetus, which is essential
to ward-off infections of the fetus. Maternal IgA, IgM, and IgE do
not cross the placenta.

The newborn receives IgA in colostrum and breast milk.

IgG falls in the newborn as the antibodies transferred from the
mother are eliminated. The infant slowly develops the ability to
generate its own antibodies.

Some maternal antibodies (e.g., to measles) decrease slower than
others (e.g., to pertussis). Vaccination schedules must take this
into account.
Physiological Effects of Aging

Height declines after adolescence because of compression of the
cartilaginous disks between the vertebrae and loss of vertebral
bone. A loss of 5% height at age 70 is normal.

Lean body mass declines during aging, while overall body mass
stays constant or increases. Even athletes have an increase in
adipose tissue during aging.

There is a loss of muscle fibers during aging. This is partly due to
death of motoneurons, which leaves muscle fibers uninnervated,
causing their atrophy.

Sometimes loss of motoneurons results in axonal sprouting and
innervation of many muscle fibers by a particular motoneuron. This
can affect the precision of movement.
Physiological Effects of Aging

Although men do not exhibit the rapid loss of bone in their 50s that
women experience, bone loss in the 60s and 70s in both sexes is
similar. Osteoporosis is a concern in both elderly men and women.

Articular (joint) cartilage thins and exhibits altered mechanical
properties during aging. This plays a role in development of
osteoarthritis, which often occurs when bones start rubbing
together after cartilage is lost.
Physiological Effects of Aging

Aging decreases the compliance of arteries, so systolic pressure
becomes higher and diastolic pressure is lower. Overall, there is
an increase in MAP, and the increased afterload results in
thickening of the left ventricular wall.

Aging increases the compliance of veins, so there is more
peripheral blood pooling and increased susceptibility for orthostatic
hypotension.
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