Physiology of growth Flashcards
What are the 4 phases of growth?
Intrauterine phase
Infancy phase
Early childhood phase
Pubertal phase
Growth in intrauterine phase?
Depends on the genetic constitution of foetus + nutrition and function of the placenta.
Growth in the infancy phase?
First 2-3 years of life driven by nutrition, a continuation of intrauterine life.
Growth in the early childhood phase?
Driven by growth hormones.
What occurs in the pubertal phase?
Driven by both growth hormones and sex hormones.
What period does growth end?
Puberty
Which structures continue to grow until adulthood?
Skin, hair and nails.
What are the mechanisms of cellular growth?
Hyerplasia: increase in cell number
Hypertrophy: increase in cell size
Volume of intracellular fluid increase.
Which parts of the body do not generate new cells?
Nerve cells and muscle cells; they last for most of the lifetime
Which tissues of the body are replaced by new cells?
Skin, GI lining and blood cells because they contain a germinative zone (for blood cells, this is in the bone marrow.)
Which components are relatively stable in cell numbers?
Glands, Parts of the liver and kidney if tissue is damaged or requires increase in activity.
What is development?
A series of co-ordinated events where the complexity of an organism increases due to maturation of the nervous system, most rapid in childhood.
What influences growth and development?
Genetics determine overall height and pattern+ timing of growth spurts. Environmental influences have a lesser effect such as diet and socioeconomic factors.
What is apoptosis?
Programmed cell death and removal
What occurs in apoptosis foetal development?
Removal of webs between fingers
Formation of hollow organs such as the heart
Tissues with high cell turnover
What is the process of apoptosis?
Cell shrinks and chromatin condenses, cytoskeleton collapses, plasma membrane fragmentation occurs and nuclear DNA disintegrates.
Which pathway is involved in apoptosis?
Intrinsic pathway and extrinsic pathway
What is the intrinsic pathway of apoptosis?
Mitochondria-dependent pathway in response to lethal stimuli such as oxidative damage, regulated by anti-apoptotic proteins BCL-2. It is activated by the p53 protein and capsases.
What is the extrinisc pathway of apoptosis?
Involves transmembrane activation with death ligand to death receptors part of the TNF family (tumour necrosis factor). Capsases are important for cell breakdown in this pathway
What period of foetal growth is fastest?
16-20 weeks gestation where new proteins are laid down by cell division.
What is the peak of foetal weight gain?
Reaches peak at 34 weeks gestation in third trimester, where it eventually slows down.
What is the patterns of growth in adolescence?
In pre-natal and pre-pubertal stages, gender has a minimal impact on growth, which deviates at age 10 where girls achieve a greater velocity of growth that peaks at 13 and steadily declines. Boys achieve a peak at age 16 which then declines.
Sex hormones like androgens have an anabolic effect
What is the patterns of growth in the body tissues?
Lymphoid tissue grows and reaches peak velocity of growth rate around puberty
Steady growth which plateaus after age 3
Reproductive tissue has a steady growth with rapid increase in late teens
What is senescence?
Physical growth ceases but physiological changes continue to occur and at a molecular level, this leads to death, therefore impairing the ability of the elderly to regulate homeostatic functions.
What are the CNS changes in aging?
Impaired co-ordination, memory and intellectual function.
What are the circulatory changes in aging?
Reduced blood flow increases risk of atherosclerosis.
Reduced lung elasticity decreases lung function.
What are the GI changes in aging?
Decrease in muscle tone involved in GI tract, reducing peristaltic action and increasing the risk of constipation/
Which systems are affected in aging?
Functional impairment of reproductive system such as menopause.
Reduced sensitivity and responsiveness of the immune system.
Reduced activity of endocrine system.
Reduced kidney function causes drop in GFR.
What are the structural changes in aging?
Skin loses elasticity, with sagging and wrinkling.
Reduced muscle mass, strength and agility.
Reduced bone deposition rate, reducing mobility.
Decreased tone of urinary system (bladder), increasing incontinence risk.
When is ossification complete?
By 3rd decade.
How does height increase occur pre-adulthood?
Growth of long bones, via the proliferation of chrondroblasts beneath the epiphyseal growth plate giving rise to chondrocytes.
How does bone change post-puberty?
Epiphyseal growth plate located in the metaphysis is the site of longitudinal bone growth. It eventually thins and the diaphysis and epiphysis fuse.
What are the regions in the epiphyseal growth plate?
It contains 4 regions:
Proliferation zone where dividing chondroblasts separate the epiphysis and diaphysis.
Hypertrophic zone where chondrocytes enlarge and signal to extracellular matrix to begin calcification.
Calcification zone where extracellular matrix calcifies and causes chondrocytes to die, leaving behind trabeculae shape cartilage.
Ossification where osteoclasts digest dead calcified cartilage and osteoblasts replace it with bone cells in the same shape to form the bone trabeculae.
What mediates growth?
Growth Hormone
IGF-1
IGF-2
Placental lactogen
T3 and T4- thyroid hormones
Growth factors, eg FGF and PDGF.
Glucocorticoids
Which hormones are important for increasing bone and muscle growth?
Growth hormone and IGF-1
Which hormones decrease growth?
Glucocorticoids.
Which hormones are important for tissue and organ growth?
Placental lactogen
T3 and T4- thyroid hormones
Growth factors, eg FGF and PDGF.
Which sex hormones mediate growth?
Oestrogen and testosterone are involved in Pubertal growth spurt for long bone growth and height along with interaction with growth hormone and IGF-1.
Where are the sex hormones released?
Leydig cells produce testosterone
Granulosa cells produce oestrogen
What is growth hormone?
Produced by somatotroph cells in the anterior lobe of pituitary gland in pulsatile bursts during sleep. It promotes bone growth, free fatty acid and glucose availability and muscle growth especially in childhood.
GH stimulates the release of Insulin-like growth factor I and II to aid this process. It peaks in puberty and steadily declines.
Where is GHRH produced?
Arcuate nucleus of hypothalamus.
What increases the release of GHRH?
GABA
Ghrelin
Sex steroids
Alpha adrenergic receptor
What are the direct effects of growth hormone?
Acts on the JAKS-STATs growth hormone receptor to increases fat and carbohydrate metabolism which has an anti-insulin effect. It increases bone and muscle growth.
Growth hormone is similar in structure to prolactin.
What are the indirect effects of growth hormone?
Induces IGF-1 release for increased muscle and bone growth via driving protein synthesis and cartilage formation.
What factprs affects secretion of growth hormone?
Most of growth hormone secretion occurs at night in slow wave deep sleep.
Life stage- peaks at puberty and declines in adulthood
Levels of IGF-1 in blood.
Starvation and stress stimulates growth hormone to increase energy reserves.
What increases growth hormone release directly?
Ghrelin
GHRH
Thyroid hormones
What hormone inhibits GH release?
Somatostatin which is released from the hypothalamus and acts directly on the anterior pituitary gland to reduce growth hormone release, competing against GnRH. Function in the body is to reduce pancreatic secretions and GI activity.
What is IGF-1?
Production is via Growth hormone acting on GH receptors mainly in the liver, lesser in the kidneys and muscles. Aids growth hormone for increasing bone and tissue growth via the MAP kinase pathways. Levels peak at puberty and drop with age.
How does IGF-1 influence growth hormone?
High levels of circulating IGF-1 mediates growth hormone levels by stimulating somatostatin release from the periventricular nucleus of hypothalamus and suppressing GRH release from arcuate nucleus.
What is IGF-2?
Regulates foetal and placental growth during pregnancy; overexpression leads to disproportionate size of tongue, liver, kidney and muscles. It is independent of growth hormone regulation.
What is the role of glucocorticoids?
Steroid hormones such as cortisol produced by the adrenal gland with anti-inflammatory effects by suppressing immune system in short bursts. It inhibits secretion of growth hormone
How do glucocorticosteroids inhibit growth?
Increase skeletal maturation by interfering with cartilage and bone synthesis, reducing the potential for further growth.
Which conditions are associated with growth suppression?
Cushing’s syndrome with excess cortisol production
Excess intake of glucocorticoids in eczema, asthma, rheumatoid or kidney disease
-> Has no effect on levels of growth hormone or IGF-1
Role of thyroid hormones
Begins production from 15-20 weeks gestation and is important in brain growth in early foetal and childhood life via stimulating brain protein synthesis.
It is important in puberty for promoting linear bone growth.
In adulthood, it promotes differentiation and maturation of the musculoskeletal system.
What is the impact of thyroid hormone deficiency?
Results in Cretinism, mental retardation if this occurs in early life and goes untreated.
Lethargy, poor motor co-ordination and hyporeflexia
-> Due to reduced number and size of brain cortical neurons because of reduced blood supply to brain, decreased neuron myelination and dendrite branching.
Features of hypothyroidism
Dry thin hair, weight gain/puffy face, bradycardia
How is hypothyroidism screened?
Guthrie blood spot test
What are the causes of dwarfism?
Hypopituitary activity
Achondroplasia
Laron Dwarfism
What is achondroplasia?
Autosomal dominant genetic condition caused by mutation in chromosome 4 which results in dwarfism. There is early epiphyseal fusion in long bone.
What is the function of chromosome 4?
Decreases endochondral ossification, chondrocyte proliferation and cellular hypertrophy and matrix production.
What is hypopituitary dwarfism?
Deficiency in growth hormone in childhood due to pituitary/hypothalamic tumour, infection, infarction or insult due to head trauma. Skeleton fails to grow and may affect other structures controlled by the pituitary gland. It can be treated with growth hormone therapy
What is acromeglay?
Excess growth hormone secretion, occurs AFTER epiphyseal plate fusion in adulthood due to adenoma in the somatotroph region of pituitary gland. It causes growth in the terminal parts of the Skeleton, with large hands and feet, kyphosis of spine and spacing between the teeth. There will be organomegaly and soft tissue growth. Structural similarity to prolactin results in gynaecomastia.
What are the risks with acromegaly?
Increases hypertension, cardiovascular disease and type 2 diabetes mellitus because of promotion of carbohydrate and fat metabolism, while inhibiting insulin release.
What is Larson Dwarfism?
Mutation in growth hormone receptor results in retardation of growth. Levels of growth hormone are high to compensate for the lack of body’s responsiveness and there is downregulation of IGF-1 and IGF-binding protein 3 levels are low because of their inhibitory effects on growth hormone. It is treated with recombitant IGF-1.
What is the most common cause of growth failure worldwide?
Malnutrition due to lack of protein.
What is the embryonic origin of the anterior pituitary Gland?
Surface ectoderm which also gives rise to the epidermis, skin, hair and nails.
What is the embryonic origin of the posterior pituitary gland?
Neuroectoderm which also gives rise to the brain and CNS
What is gigantism?
Hypersecretion of growth hormone which occurs prior to the fusion of the epiphysis and diaphysis which results in proportional growth in height. This occurs due to a tumour in the adenophysis which can compress other structures and result in undersecretion, leading to conditions like delayed puberty. High growth hormone will result in hyperglycaemia, soft tissue growth and organ size increase.
What is the difference between acromegaly and gigantism?
Gigantism occurs before growth plate fuses; acromegaly occurs after growth plate fuses.
