Physiological Adaptations Through the Life Course

• These notes cover physiological adaptations through the life course, including growth, development, and aging

Learning Activities

• Session 1 includes an introduction, objectives, regulation of human growth/development, and intra- to extra-uterine transition
• Session 2 focuses on the intra- to extra-uterine transition further
• Session 3 covers puberty and adolescence
• Session 4 includes biological aging, a conclusion, and a knowledge check

Session 1 Overview

• The theme will explore physiological milestones, factors, and adaptations throughout the human lifespan, from the intra-uterine period to old age
• Focuses on regulation of human growth and development, intra- to extra-uterine transition, puberty/adolescence, and hallmarks of biological aging
• Learning uses lectures, a theme-specific study guide, PowerPoint slides, and relevant articles
• A compulsory knowledge check will be completed at the end of the 4th lecture

Phases of Human Lifespan

• Prenatal: Conception to birth
• Neonatal: Birth to 28 days
• Infancy: 1 month to 2 years
• Childhood: 3 years to 11 years
• Puberty/Adolescence: 12 years to 19-24 years
• Adulthood: Prime
• Adulthood: Senescence

Regulating Factors

• Hormonal factors regulate human growth and development
• Nutritional factors regulate human growth and development
• Environmental and genetic factors regulate human growth and development
• Mechanical factors (bone) regulate human growth and development

Human Growth

• It's a complex process from conception to adolescence, ending with growth plate fusion
• Growth is divided into four phases

Fetal Phase

• Predominant endocrine factors controlling growth are insulin and insulin-like growth factors

Infancy Phase

• Primarily dependent on nutrition

Childhood Phase

• The GH-IGF-I axis and thyroid hormones are most important

Puberty Phase

• Activation of the hypothalamo-pituitary-gonadal axis generates sex steroid secretion, which is vital to completion of growth along with the GH-IGF-I axis

Hormonal Regulation

• Adequate growth hormone, thyroid hormones, insulin, and sex hormones at puberty are required for growth
• These hormones play both direct and permissive roles
• A deficiency in any one of these hormones leads to abnormal growth and development
• Growth hormone (GH) regulates growth and development
• Insulin-like growth factors (IGF-I and IGF-II) regulate growth and development
• Thyroid hormones (T3 / T4) regulate growth and development
• Insulin regulates growth and development
• Sex hormones (estrogen and androgens) regulate growth and development

Growth Hormone and IGFs

• GH and IGFs potently stimulate growth
• Pulses of GHRH, released from the hypothalamus, stimulate GH release
• In adults, the largest GHRH-GH pulse occurs during early phases of sleep
• GH is secreted throughout life, with the biggest growth-promotion role in in children playing only a minor role in fetal growth.
• Too much GH before puberty leads to Gigantism.
• Too much GH after puberty leads to Acromegaly
• A GH deficiency before puberty leads to stunted growth (short stature / dwarfism)
• IGFs are essential for fetal growth, growth-promoting postnatally, and in children; IGF production in utero is independent of GH
• Mutations of the IGF-I-receptor gene results in severe intra-uterine growth retardation.

Thyroid Hormones

• Important for regulating body metabolism, non-shivering heat production, and increasing oxygen consumption
• In the fetus, thyroid hormones promote normal growth and development, fetal maturation and play a role in the nervous system development
• Also important for normal bone growth
• Infants with deficiency (cretinism) will be developmentally delayed, dwarfism, with decreased mental capacity unless treated promptly
• Children who develop hypothyroidism postnatally have slow bone/tissue growth, shorter than normal, and puberty is often delayed

Growth

• Growth = Soft Tissue Growth + Bone Growth

Soft Tissue

• Soft tissue includes muscle, adipose tissue, connective tissue, fibrous tissue, and blood vessels
• GH, IGFs, thyroid hormones, and insulin control it
• Hypertrophy and hyperplasia are stimulated by these hormones
• GH and IGFs are required for tissue protein synthesis and cell division
• Thyroid hormones play a permissive role for GH function, and directly stimulate nervous system development
• Insulin supports soft tissue growth by promoting protein synthesis and provides energy via glucose oxidation as well playing a permissive role for GH

Bone Growth

• Primarily influenced by GH and the IGFs, with thyroid hormones giving a permissive role
• Sex hormones, especially estrogen, play a key role in the adolescent growth spurt, stimulating bone growth and eventually inducing epiphyseal (growth) plate closure in long bones
• An epiphyseal plate (growth plate) is the bone growth site where chondrocytes are actively dividing and producing cartilage

Nutrition

• Adequate diet is necessary for normal human growth and development like protein, sufficient energy (caloric intake), vitamins and minerals
• Essential amino acids, which cannot be synthesized by the body, must come from dietary sources
• Calcium intake is critical for proper bone growth and formation
• Preconception nutritional status of both parents helps determine fitness of germ lines
• Maternal nutritional status is important for intra-uterine growth and development of fetus
• Breastfeeding is essential postnatally and for child growth and development
• Malnutrition can delay childhood growth and permanently impact final adult height
• Chronic malnutrition / undernutrition results in GH resistance (downregulation of GH receptors in liver and insensitivity of the epiphyseal growth plate to GH)
• This results in increased GH and is indicated by reduced circulating IGF levels
• Undernutrition leads to increased circulating cortisol levels, chronic stress, and decreases thyroid hormone and sex hormone levels

Environment and Genetics

• Children in stressful environments show the condition “failure to thrive”, marked by slow growth
• Stressful environments: socio-economic conditions/poverty, food shortage, societal/interpersonal violence, poor sanitation, air pollution, substance use
• Cortisol from the adrenal cortex is released in times of stress, causing catabolic effects
• Maternal substance use during pregnancy causes fetal alcohol spectrum disorder (FASD)
• Genetics: Each human's potential adult size is genetically determined at conception.
• 70-90% of adult stature is determined genetically.
• Human stature determined by many genetic factors, which affect epiphyseal (growth) plate function

Bone Growth

• Mechanical stress on the bone plays major role in bone mass
• Weight-bearing activities and exercise help build bone (osteogenesis)
• Osteocytes and chondrocytes act as mechanosensors, transducing mechanical stimuli into intercellular signals to lay down new bone

Maternal And Paternal Factors

• Puberty: beginning of reproductive life with a transition to functional gamete production
• Pre-conception period: male and female gamete maturation.
• Parental nutrition, obesity, substance use, stress, endocrine disruptors and physical activity may influence gamete health
• Post-conception: direct maternal effects mediated through the in utero environment along with postnataly nutrition and the maternal-infant relationship
• Direct paternal influences develop postnatally- paternal-infant relationship and risk: paternal tobacco use
• Maternal/paternal health, behavior, social and economic circumstances: indirect effect on offspring development in both antenatal/postnatal phases

Changes

• There are physiological adaptation in the newborn are often complicated by modern medical interventions, such as cesarean sections, anaesthetics/analgesics, early clamping of the umbilical cord, and increased frequency of pre-term deliveries
• The transition from the intra-uterine (fetus) to extra-uterine (neonate) environment during birth requires the most complex physiological adaptations.
• The most striking adaptations occur in the lungs and circulatory systems with changes observed in endocrine function, substrate metabolism and thermogenesis

Fetus-Neonate Transition

• Clearance of lung fluids is an essential milestone
• Pulmonary adaptations: Establishment of Air Breathing through Surfactant secretion and breathing is a milestone
• Circulatory / Cardiovascular adaptations through a Transition from fetal to neonatal circulation are a milestone
• Decreased pulmonary vascular resistance
• Increased pulmonary perfusion
• Endocrine support of the transition

Fetal Lungs

• The lungs are filled with "lung fluid" which impedes breathing, however is necessary for normal fetal lung growth and is increased during mid- to late-gestation
• Lung fluid must be cleared for normal air breathing to occur during delivery.
• physiological lung fluid clearance is mediated during labour by cortisol, thyroid hormones, and catecholamines.
• Hormones allow expression of Na+/K+/ATPase membrane transporters in type 2 alveolar cells where Na+ is actively pumped into the lung interstitial space, creating an osmotic gradient for water to follow/remove fluid
• Subsequent clearance requires high negative pressures in the lungs and fluid being transported to the interstitial space
• Preterm infants usually have an inadequate lung fluid clearance because it lacks Na+/K+/ATPase membrane transporters.

The Law of Laplace

• If two bubbles have the same surface tension, the smaller bubble will have higher pressure, says the law of Laplace
• Surfactant can reduce surface tension
• Surfactant is a detergent-like substance made of proteins and phospholipids, secreted by Type II alveolar cells
• Lines the inside alveoli and acts to reduce the surface tension of the air-fluid
• Prevents the alveoli from collapsing
• Promotes compliance
• Stimuli for secretion: increased catecholamine levels (under cortisol control)
• Stimuli for secretion: increased ATP levels
• Stimuli for secretion: post-delivery alveolar stretch from air ventilation

Intra- to Extra-Uterine transition

• Stimulates initiate air breathing in the newborn like umbilical cord clamping, maternal prostaglandin reduced, tactile, cold, in-blood postnatally

Preterm Babies

• Immature lung, structurally, functionally speaking
• Lung gas V low vs body rate, metabolic rate
• Preterm babies often develop (NRDS) w/ "stiff lungs" and collapsing alveoli
• Must glucocorticoid treat mother pre-delivery to speed fetal lung maturation and positive pressure ventilation
• Low surfactant production equals to high surface tension means they cannot breathe properly

Circulation

• Physiological adaptations is major, CVS adaptation after birth!
• Removal of low-resistance
• Major changes such as high cardiac needed
• Higher output = oxygen and body heat

Fetal Heart

• Delivered via placenta with oxygenated blood via umbilical
• After this, right atrium/arteriosus shunt blood via brain
• High pulmonary vascular and low pulmonary perfusions (Before delivery)

Transition

• Ventilation, O2 triggers NO
• Shortly after, pressure facilitates functional over ovale

Metabolism and Thermo

• Before birth, energy by maternal glucose to fetus
• Glcogen and fats made for birth
• Thermo produces Brown fat, thermogenesis and cortisol

Hormones!

• Prepare for the world/regulated by thyroid and hormones
• Ultimately cortisol is the controller

Puberty and Adolescence

• Adolescents is when growth takes maturation and expands to third decade
• Sexual and period sexual

Hormones

• Female precocity is related to early estrogen
• Males is just gonadal (hormones)

Adrenarch

• 6 to 8 year production increase

Key Hallmarks of aging

• Biological and molecular
• Telometer, altered, and dysfunction
• Stability and loss of protein

Hallmarks of aging Part2

• Process is genetically predetermined to occur
• Errors and mutations occur through damage

Cardiovascular during aging

• Increases/increase stiff and hypertension
• Rate increases
• Atrio block show
• Cardio reduces and stenosis occurs

Lungs during aging

• Decreases, maximum declines at 70
• Tissue goes too
• Increased reduced vital
• Pneumonia, breathing is increased which shows up

Renal system during aging

• Decreases
• Acid is too

Neuron During aging

• Decreases, global functions
• D decreases
• Nerugendation increases

Reproductive syste during aging

• First is declension of body
• Rebound, at end is decreased