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Semester 1 > Human growth and short stature > Flashcards

Human growth and short stature Flashcards

1
Q

growth is

A

increase in size due to tissue accretion or increase in bone, soft tissue or organ size

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2
Q

accretion is

A

increase by external addition or accumulation

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3
Q

growth is dependent on?

A

coordinated, appropriate cellular function

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4
Q

growth is regulated by?

A

external factors like nutrition

internal cues like genotype, hormones, growth factors

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5
Q

basic function of cell cycle?

A

accurately duplicate chromsomes and prepare cell for division

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6
Q

what occurs in interphase

A

G1 grow and increase mass
S duplicate chromosomes
G2 growth and checking

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7
Q

what occurs in M phase

A

mitosis and cytokinesis

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8
Q

hypertrophy is

A

an increase in cell size without an increase in cell number

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9
Q

a paracrine cell acts on?

A

its neighbours

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10
Q

an endocrine cell acts on?

A

a distant site via blood- hormones

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11
Q

what hormones are behind growth

A

growth hormone
IGF-1
thyroid hormones
sex steroids

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12
Q

outline growth hormone and IGF-1 axis

A

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

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13
Q

why is growth hormone said to have direct and indirect effects on tissues

A

directly affects bone, muscle, fat, liver

indirectly as stimulates IGF-1 which acts on bone, muscle, fat

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14
Q

IGF-1 has paracrine or endocrine effects?

A

Endocrine as works on bone, muscle, fat from afar
AND
Paracrine as is produced by bone and works on bone itself

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15
Q

how is growth hormone secreted and why does this make blood sampling difficult

A

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

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16
Q

what does IGF-1 stand for

A

insulin-like growth factor 1

significant homology with insulin, both structurally and functionally

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17
Q

what do IGF-1 and GH do to bones

A

stimulate all stages of bone growth in growth plate of long bones

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18
Q

how does Growth Hormone affect fat

A

growth hormones affect lipid metabolism
increase lipolysis in adipocytes
ie break down of fats, this increases fatty acids in circulation

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19
Q

how does Growth Hormone affect muscle

A

Growth hormone stimulates amino acid uptake into muscle and stimulates synthesis into protein

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20
Q

How does Growth Hormone affect liver

A

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

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21
Q

How does IGF-1 affect muscle

A

much the same as growth hormone- stimulates amino acid uptake and synthesis into protein

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22
Q

How does IGF-1 affect adipose tissue

A

stimulates lipogenesis,

ie making fats, decreasing free fatty acids in circulation

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23
Q

How does IGF-1 affect liver

A

‘insulin like’

decreases glucose output to reduce plasma glucose concentration

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24
Q

In what ways does IGF-1 counteract GH

A

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

25
Q

what type of hormones are GH and IGF-1 and so how muct they act on cells

A

both protein hormones
so hydrophillic
can’t cross plasma membrane
act on receptors at cell surface

26
Q

How does signalling by phosphorylation work

A

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

27
Q

how does GH bind to receptor and recruit enzyme

A

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

28
Q

how does the GH receptor work once the enzyme has been recruited

A

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

29
Q

how does IGF-1 receptor work

A

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
30
Q

both the IGF-1 and GH receptors are x-coupled receptors, but how does this aspect differ

A

both enzyme-coupled receptors

GH receptor must recruit enzyme once GH binds

IGF-1 receptor has intrinsic enzyme activity

31
Q

IGF-1’s ability to interact with receptor governed by?

A

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

32
Q

how do binding proteins act as IGF-1 activity regulators

A

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

33
Q

what are the 3 functions of IGF binding proteins

A

store, transport, regulate

34
Q

what things in life have a positive effect on growth hormone IGF axis

A

exercise positive for hypothalamus, stimulates GHRH
nutrition and ghrelin positive effect
deep sleep increases
REM sleep decreases

35
Q

how are thyroxine (T4) and Triiodothyronine (T3) produced

A

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

36
Q

what dietary factor is required for synthesis of thyroid hormones and which hormone from the axis stimulates uptake of this

A

TSH stimulates uptake of dietary iodide, is converted to iodine

37
Q

deficiency in GH and IGF-1 will lead to

A

short stature

38
Q

what are early and late puberty called, when do we call it early or late

A

early= central precocious puberty

late= consitutional delay in growth and puberty CDGP

call early/late if +/- 2SDs from mean

39
Q

how is puberty tracked

A

Height vs predicted
Tanner staging
Bone age
Blood test hormones

40
Q

Tanner Staging=

A

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

41
Q

in terms of tanner staging, male puberty is considered delayed if

A

testicular volume less than 4ml age 14 or no pubertal progress

42
Q

height tracking/ predicted height puberty

A

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

43
Q

why check bone age w short stature

A

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

44
Q

taking blood tests for delayed puberty/ short stature

A

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

45
Q

CDGP is

A

constitutional delay in growth and puberty
more common boys than girls but not gender specific

a tendency, not a disease

46
Q

causes of poor growth?

A 
CDGP
familial short stature
born small
malnutrition
system disease, often GI
psychosocial deprivation
abnormal bones
chromosomal disorder
pituitary tumour
47
Q

causes late puberty?

A

CDGP
gonadotrophin deficiency eg Kallman syndrome
gonadal failure/ failure generate sex steroids
pituitary tumour
chromosomal- Turners, Klinefelter’s (tall)

48
Q

things to consider consultation late puberty/ growth

A

system screen (esp GI)
impact on life- social, family, body
family stature and health
growth and puberty assessment

49
Q

treatment for CGDP

A

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

50
Q

order most rapid growth periods

A

embryonic life
infancy
puberty

51
Q

why are we reaching puberty at an earier age

A

in western due to better nutrition, health, standards of living

puberty assoc with critical body mass of 48kg and body fat, so reach sooner

52
Q

avg age puberty boys and girls

A

girls 11

boys 12

53
Q

what is increasingly more important to indiv in puberty

A

gendered and sexual identity

54
Q

what age group takes the most risks

A

pubescent adolescents

55
Q

what factors in BPS model contribute to body image

A

Bio= hormones, genetics, age, sex, BMI

Psycho= low self-esteem, negative affect, depressive symptoms, processing bias, behaviours

Social= social media, appearance comparisons, cultural ideals

56
Q

how may short stature impact life

A

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

57
Q

psych aspects body image puberty

A

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

58
Q

ways to improve consultations for the teen

A

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

59
Q

guidance consultations with children

A 
involve them in discussions
listen and respond to their views/ questions
explain to their level
do not overburden
talk directly to them

Semester 1 (18 decks)

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