Human growth and short stature Flashcards
growth is
increase in size due to tissue accretion or increase in bone, soft tissue or organ size
accretion is
increase by external addition or accumulation
growth is dependent on?
coordinated, appropriate cellular function
growth is regulated by?
external factors like nutrition
internal cues like genotype, hormones, growth factors
basic function of cell cycle?
accurately duplicate chromsomes and prepare cell for division
what occurs in interphase
G1 grow and increase mass
S duplicate chromosomes
G2 growth and checking
what occurs in M phase
mitosis and cytokinesis
hypertrophy is
an increase in cell size without an increase in cell number
a paracrine cell acts on?
its neighbours
an endocrine cell acts on?
a distant site via blood- hormones
what hormones are behind growth
growth hormone
IGF-1
thyroid hormones
sex steroids
outline growth hormone and IGF-1 axis
hypothalamus secretes GHRH, Growth Hormone Releasing Hormone,
anterior pituitary releases growth hormone
growth hormone targets tissues via blood
growth hormone directly acts on: bones, fat, muscle, liver
Growth hormone acts on liver which then produces IGF-1
GH stimulates bones to produce IGF-1 which acts on bone itself
IGF-1 acts on bone, fat, muscle
IGF negative feedback to hypothalamus
why is growth hormone said to have direct and indirect effects on tissues
directly affects bone, muscle, fat, liver
indirectly as stimulates IGF-1 which acts on bone, muscle, fat
IGF-1 has paracrine or endocrine effects?
Endocrine as works on bone, muscle, fat from afar
AND
Paracrine as is produced by bone and works on bone itself
how is growth hormone secreted and why does this make blood sampling difficult
secreted in pulses, mainly at night
therefore difficult to determine levels as may be in peak or trough when take blood
give baseline sample
given stimulatory drug that cause GH to be produced
must repeat sample every 30 minutes for a day
what does IGF-1 stand for
insulin-like growth factor 1
significant homology with insulin, both structurally and functionally
what do IGF-1 and GH do to bones
stimulate all stages of bone growth in growth plate of long bones
how does Growth Hormone affect fat
growth hormones affect lipid metabolism
increase lipolysis in adipocytes
ie break down of fats, this increases fatty acids in circulation
how does Growth Hormone affect muscle
Growth hormone stimulates amino acid uptake into muscle and stimulates synthesis into protein
How does Growth Hormone affect liver
IGF-1 production obvi
affects carbohydrate metabolism in liver
increases hepatic glucose output and decreases glucose uptake by peripheral tissues
therefore increases plasma glucose concentration
How does IGF-1 affect muscle
much the same as growth hormone- stimulates amino acid uptake and synthesis into protein
How does IGF-1 affect adipose tissue
stimulates lipogenesis,
ie making fats, decreasing free fatty acids in circulation
How does IGF-1 affect liver
‘insulin like’
decreases glucose output to reduce plasma glucose concentration
In what ways does IGF-1 counteract GH
IGF-1 and GH work similarly on muscle
GH stimulates lipolysis (break down fats, release fatty acids) whereas IGF-1 stimulates lipgenesis (remake fats, decrease fatty acids)
GH stimulates increased hepatic glucose output from liver, increasing glucose conc, whereas IGF-1 decreases glucose output, decreasing glucose conc
what type of hormones are GH and IGF-1 and so how muct they act on cells
both protein hormones
so hydrophillic
can’t cross plasma membrane
act on receptors at cell surface
How does signalling by phosphorylation work
enzyme activates kinase cascade
a protein kinase activates nect in cascade via addition of 1 or more phosphate groups
signals next in cascade
deactivate by removing a phosphate
how does GH bind to receptor and recruit enzyme
GH receptor is a homodimer (made of 2 identical proteins), GH binds in 2 steps
- first binds to a high affinity site on 1st receptor
- then binds to lower affinity site on 2nd receptor
this causes conformational change, allows receptor to recruit its enzyme, kinase JAK2
how does the GH receptor work once the enzyme has been recruited
kinase JAK2 phosphorylates residues on intracellular portion of receptor
then able to bind to transcription factor STAT5 which is also then phosphorylated
phosphorylated STAT5 moves into cell nucleus, interacts with response elements of the target genes in DNA
this affects transcription of those genes, including the gene for IGF-1
IGF-1 production therefore stimulated
how does IGF-1 receptor work
when IGF-1 binds, intracellular portion of receptor automatically phosphorylated
one of 2 phosphorylation cascades may now be activated:
- PI3 kinase pathway= cellular metabolism and survival
- MAP kinase signalling pathway= proliferation
both the IGF-1 and GH receptors are x-coupled receptors, but how does this aspect differ
both enzyme-coupled receptors
GH receptor must recruit enzyme once GH binds
IGF-1 receptor has intrinsic enzyme activity
IGF-1’s ability to interact with receptor governed by?
binding proteins, there are 6
there is very little free IGF-1 in circulation as most bound to a binding protein
eg IGFBP-3 binds to IGF-1= very big molecule, IGF-1 unable to leave circulation, therefore storage site
if IGF-1 needs into cell, binds to a smaller binding protein that delivers it to binding site
how do binding proteins act as IGF-1 activity regulators
binding proteins act as IGF-1 activity regulators because the binding proteins IGF-1 has a greater affinity for the binding proteins than the receptors
only released from binding protein by protease at cell surface, this cleaves binding protein into fragments, releasing IGF-1 to receptor
what are the 3 functions of IGF binding proteins
store, transport, regulate
what things in life have a positive effect on growth hormone IGF axis
exercise positive for hypothalamus, stimulates GHRH
nutrition and ghrelin positive effect
deep sleep increases
REM sleep decreases
how are thyroxine (T4) and Triiodothyronine (T3) produced
Hypothalamus- TFH, thyrotropin releasing hormone
Anterior pituitary- TSH, thyroid stimulating hormone
Thyroid gland- T4 thyroxine, T3, triiodothyronine
in tissues, T4 will be converted to T3, most active form of thyroxine
what dietary factor is required for synthesis of thyroid hormones and which hormone from the axis stimulates uptake of this
TSH stimulates uptake of dietary iodide, is converted to iodine
deficiency in GH and IGF-1 will lead to
short stature
what are early and late puberty called, when do we call it early or late
early= central precocious puberty
late= consitutional delay in growth and puberty CDGP
call early/late if +/- 2SDs from mean
how is puberty tracked
Height vs predicted
Tanner staging
Bone age
Blood test hormones
Tanner Staging=
Stages of genital and pubic hair dev in boys, pubic hair and breast dev in girls
First sign of puberty is B2 stage:
in girls- budding
in boys- 4ml testic volume (measured with orchidometer)
male growth spurt usually when testicu volume is 10-12ml
in terms of tanner staging, male puberty is considered delayed if
testicular volume less than 4ml age 14 or no pubertal progress
height tracking/ predicted height puberty
plot height over age on percentile chart
calculate mid-parental height and plot. 80% will meet parental average, can track if not meeting
mum+dad height/
2 if boy, +7 if girl, -7
vary 5cm each way
why check bone age w short stature
x rays, computer analyses. Growth plates come together and mature through puberty.
Normal bone age is +/- a year
If haven’t puberty, bone age delay vs chron age
shows if have greater growth potential so can be reassuring
taking blood tests for delayed puberty/ short stature
measure IGF, GH, FSH, LH
IGF- consider in terms of bone age
GH- give chemical agents that provoke GH. take serial samples over 3 hrs as fluctuates. May need priming with sex steroids to see potential at puberty. difficult to do
very low baseline or ppor rise btwn basal and peak LH and FSH indicates gonadotrophin deficiency
puberty characterised by >5iu/L rise LH basal to peak
CDGP is
constitutional delay in growth and puberty
more common boys than girls but not gender specific
a tendency, not a disease
causes of poor growth?
CDGP familial short stature born small malnutrition system disease, often GI psychosocial deprivation abnormal bones chromosomal disorder pituitary tumour
causes late puberty?
CDGP
gonadotrophin deficiency eg Kallman syndrome
gonadal failure/ failure generate sex steroids
pituitary tumour
chromosomal- Turners, Klinefelter’s (tall)
things to consider consultation late puberty/ growth
system screen (esp GI)
impact on life- social, family, body
family stature and health
growth and puberty assessment
treatment for CGDP
reassurance w follow up that likely to grow
or if severely affecting life
testosterone short course (boys?) to prime gonadal system for puberty. low dose bc adverse effects on aggr
order most rapid growth periods
embryonic life
infancy
puberty
why are we reaching puberty at an earier age
in western due to better nutrition, health, standards of living
puberty assoc with critical body mass of 48kg and body fat, so reach sooner
avg age puberty boys and girls
girls 11
boys 12
what is increasingly more important to indiv in puberty
gendered and sexual identity
what age group takes the most risks
pubescent adolescents
what factors in BPS model contribute to body image
Bio= hormones, genetics, age, sex, BMI
Psycho= low self-esteem, negative affect, depressive symptoms, processing bias, behaviours
Social= social media, appearance comparisons, cultural ideals
how may short stature impact life
stature helps develop personality
tall people preferred for marriage whilst short people belittled in almost all settings, teased, bullied
social isolation, high risk for psychosocial distress, especially in teens
psych aspects body image puberty
teens likely to feel worse about their bodies in puberty and dissatisfied, add in consumer culture (thin/muscular/ pre-pub slenderness) worsens
girls dislike maturing early
boys like
girls more anger and depression
boys more anger and irritability
ways to improve consultations for the teen
be sensitive and remind info confidential as makes more likely they will disclose
consider triadic consultation if parents there, offer 1:1 time for teen too
make clear you are available on own if they want
guidance consultations with children
involve them in discussions listen and respond to their views/ questions explain to their level do not overburden talk directly to them
