Normal Growth and Clinical Aspects Flashcards

1
Q

How is growth regulated?

A
GH from anterior pituitary
Thyroid hormones
Insulin
Sex steroids
Nutrient availability
Stress
Genetics
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2
Q

Growth Hormone is what type of hormone?

A

Peptide hormone

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3
Q

What controls the release of growth hormone?

A

Growth Hormone Inhibiting hormone (somatostatin)

Growth hormone Releasing Hormone

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4
Q

Growth hormone is also known as what?

A

Somatotropin

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5
Q

What categories does the activity of growth hormone fall into?

A

Growth and development (indirect)

Regulation of metabolism (direct)

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6
Q

Growth hormone requires what before it will stimulate growth?

A

Permissive action of thyroid hormones and insulin

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7
Q

What is the primary controlling factor of growth in early life?

A

Nutrition (8-10 months)

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8
Q

What is the role of growth hormone in adult life?

A

Maintenance and repair of tissue

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9
Q

How is the growth promoting effect of GH mediated?

A

Stimulation of cell size
Stimulation of cell division
(hypertrophy + hyperplasia)

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10
Q

What is the indirect function of GH on growth?

A

Intermediate - insulin-like growth factor-1 (IGF-1)

Somatomedin C

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11
Q

What is the hypoglycemic quality of IGF-1?

A

Limited glucose uptake in muscles

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12
Q

IGF-1 is secreted by what?

A

Liver and other cells in response to GH release

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13
Q

What is the effect of IGF-1 on GH?

A

IGF-1 levels inhibit growth hormone (negative feedback)

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14
Q

What is the role of IGF-II?

A

Limited to foetus and neonate

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15
Q

How are GH and IGF-1 unique?

A

Bound to carrier proteins, despite being peptide hormones

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16
Q

What % of GH is bound?

A

50%

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17
Q

What is the benefit of binding GH to carrier proteins?

A

Smooth outs the effects of the erratic pattern of secretion

Protects from excretion

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18
Q

What is the negative feedback effect of IGF-1?

A
  • Inhibits GHRH
  • Stimulates GHIH (somatostatin)
  • Inhibits GH release from somatotrophs in pituitary
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19
Q

GH/IGF-1 effects on bone growth?

A

GH stimulates chondrocyte precursor cells in epiphiseal growth plate to differentiate into chondrocytes

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20
Q

What is the effect of IGF-1 on bone growth differentiation?

A

Cells begin to secrete IGF-1, and become more responsive to it

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21
Q

How does IGF-1 act as an auto/paracrine agent in bone growth?

A

Stimulating chondrocytes to undergo cell division and produce cartilage

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22
Q

What are the direct effects GH on metabolism?

A

Increases gluconeogenesis by liver
Reduces insulin ability to stimulate glucose uptake by muscle and adipose
Make adipocytes more sensitive to lipolytic stimuli
Increase muscle, liver, adipose uptake of AAs and protein synthesis

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23
Q

When is GH said to be diabetogenic?

A

When in excess

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24
Q

What is a diabetogenic?

A

Increases blood glucose

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25
Q

What does GH synergise with for its anti-insulin effect?

A

Cortisol

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26
Q

What needs insulin for glucose uptake?

A

Muscle and adipose tissue

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27
Q

What roles does GH share with insulin?

A

Increases aa uptake

Stimulates protein synthesis

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28
Q

What role does GH NOT share with insulin?

A

GH does not increase glucose uptake

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29
Q

GH has a main anabolic effect on what?

A

Everything but muscle and adipose tissue

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30
Q

What are the general roles of GH?

A

Mobilise glucose
Inhibits insulin action
Promotes lipolysis
Promotes aa uptake

31
Q

When is GH secretion highest?

A

Teenage years

32
Q

What is the nature of GH secretion?

A

Rapid and spontaneous up and down

33
Q

When is the majority of GH released?

A

First 2hrs of sleep (deep delta sleep)

34
Q

How much higher is GH secretion in children? When?

A

20x higher in children in the first 2hrs of sleep

35
Q

What other GH related hormone has sleep inducing qualities?

A

Growth Hormone Receptor Hormone

36
Q

How are GH levels evaluated?

A

Repeated measurements over 24hrs

37
Q

How does IGF-1 vary through the day? What does this tell us?

A

Consistent

IGF-1 buffers the pulsatile variance of GH

38
Q

What is the biggest influence on GH secretion?

A

Nutritional status

39
Q

How does nutritional control mediate GH release?

A

Modulation of GHRH/GHIH

40
Q

What are the stimuli that increase GHRH secretion?

A
  1. Actual or potential decrease in cell energy supply
  2. Increased amounts of AA in plasma
  3. Stressful stimuli
  4. Delta sleep
  5. Oestrogen and androgens
41
Q

What is the effect of exercise on GH?

A

Increased Growth hormone secretion

42
Q

Increased GH in delta sleep is related to what?

A

Growth spurts in children/adolescents

Tissue repair in adults

43
Q

Which stimuli increase GHIH secretion?

A
  1. Glucose
  2. FFA
  3. REM sleep
  4. Cortisol
44
Q

What hormonal effect is seen in REM sleep deprived subjects?

A

Increased GH secretion

45
Q

Physiology of growth is affected by which factors?

A

Hormones
Nutrition
Genetics

46
Q

Which hormones affect growth?

A
GH, IGF-1
Thyroid hormones
Androgens & estrogens
Glucocorticoids
Insulin
47
Q

What is the impact of sex hormones on growth?

A

Minor until puberty

48
Q

What is seen in babies deficient in GH and IGF-1?

A

Born normal size as GH influence is minor

49
Q

Which hormones may dominate intrauterine growth?

A

Insulin

IGF-II

50
Q

When are thyroid hormones most important?

A

Development of the nervous system in utero and early childhood

51
Q

What is the effect of thyroid hormones on GH/IGF-1?

A

Permissive effects

52
Q

What is the effect of thyroid hormones on bones?

A

Ossification of cartilage
Teeth maturation
Contours of the face
Proportions of the body

53
Q

What is cretinism?

A

Hypothyroid from birth

54
Q

What is the effect of cretinism on growth?

A

Stunted growth due to TH’s permissive effect on GH

Retain infantile facial features

55
Q

Why do injury and disease stunt growth?

A

Increased protein catabolism (glucocorticoid effects)

56
Q

When are the periods of rapid growth in humans?

A

Infancy

Puberty

57
Q

How does growth appear in infancy?

A

Episodic growth spurts of ~2.5cm

58
Q

How does puberty cause growth spurts?

A

Androgens + estrogens produce spikes in GH secretion that ↑IGF-1

59
Q

How do puberty hormones terminate growth?

A

Androgens and estrogens cause the epiphyses of the long bones to fuse

60
Q

What are the most common causes of hypersecretion syndromes?

A

Endocrine tumours

61
Q

What is gigantism?

A

Excess GH due to pituitary tumour BEFORE epiphyseal plates of long bones grow
Typically very tall

62
Q

What is acromegaly?

A

Excess GH due to pituitary tumour after epiphyseal plates of long bones grow
Typically have enlarged hands and feet

63
Q

What is the classic sign of acromegaly?

A

Adult foot growth

64
Q

How are endocrine tumours treated?

A

Surgery

Somatostatin analogues

65
Q

Dwarfism may be caused by what?

A
  1. GHRH deficiency
  2. GH secreting cell abnormality
  3. End organ unresponsive to GH
  4. Genetic mutations
  5. Precocious puberty
  6. Hypothyroid tumours
66
Q

If dwarfism is hypothalamic in origin, how is it treated?

A

GHRH deficient - normal response to administered GHRH

67
Q

If dwarfism is pituitary in origin, how is it treated?

A

GH secreting cells abnormal - less GH produced in response to GHRH

68
Q

What is Laron Dwarfism?

A

High [GH]plasma, defective receptors prevent IGF-1 release

69
Q

Why do Laron Dwarves have high [GH]?

A

Inability to release IGF-1 stops inhibition of GH

70
Q

Why do pygmy peoples have dwarfism?

A

Mutation impairing cells ability to make IGF-1 in response to GH

71
Q

How does precocious puberty cause dwarfism?

A

Excess GnRH release stimulates puberty by promoting sex hormone release.
These children have stunted growth because long bones fuse early

72
Q

Why does hypothyroid cause dwarfism in children?

A

Loss of permissive effect of TH on GH

73
Q

How do hypothyroid children differ from children deficient in GH?

A

Hypothyroid - retain infantile proportions

GH - proportionally normal