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Endocrine System > Normal Growth and Clinical Aspects > Flashcards

Normal Growth and Clinical Aspects Flashcards

1
Q

Name seven factors which regulate growth

A
  • Growth hormone release from anterior pituitary – which in turn is regulated by the balance of GHRH vs GHIH release from the hypothalamus
  • Thyroid hormones
  • Insulin
  • Sex steroids (esp. at puberty)
  • Availability of nutrients
  • Stress
  • Genetics
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2
Q

What is GH?

A

GH is a peptide hormone released from the anterior pituitary. Aka somatotropin (“trop” relating to growth).

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3
Q

What two hypothalamic neurohormones control the release of GH?

A
  • Growth Hormone Inhibiting Hormone (GHIH) (aka Somatostatin
  • Growth Hormone Releasing Hormone (GHRH)
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4
Q

What are the actions of GH?

A

Range of activities defined by two broad categories:

  1. Growth and development (indirect)
  2. Regulation of metabolism (direct)
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5
Q

What controls the growth in the foetal period and first 8-10 months of life?

A

Nutritional intake

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6
Q

What controls growth after the first 8-10 months of life?

A

GH is the dominant influence on the rate at which children grow

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7
Q

What does GH require?

A

Permissive action of thyroid hormones and insulin before it will stimulate growth.

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8
Q

As thyroid hormones and insulin are permissive to GH, what happens if a child has untreated hypothyroidism or poorly controlled diabetes?

A

They will have stunted growth despite normal GH levels

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9
Q

What mediates the growth-promoting effects of GH?

A

Through stimulation of both cell size (hypertrophy) and cell division (hyperplasia) in its many target tissues

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10
Q

Is the effect of GH on growth direct or indirect?

A

Indirect - achieved via action of insulin-like growth factor-1 (IGF-1) aka somatomedin C

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11
Q

What is somatomedin C?

A

Insulin-like growth factor-1

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12
Q

Describe IGF-1

A

Similar to proinsulin in that int binds to similar insulin receptors and has hypoglycaemic qualities (only uptake of Glc in muscle as liver and adipose tissue has few IGF receptors)

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13
Q

What stimulates the release of IGF-1?

A

Secreted by the liver in response to GH release, and IGF-1 control GH release through a negative feedback loop

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14
Q

Is IGF-2 function all throughout life?

A

No, limited to foetus and neonate

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15
Q

How are GH and IGF-1 transported/

A

They are peptide hormones but are transported in the blood bound to carrier proteins

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16
Q

What is only ~50% of GH in the bound form?

A

Helps to provide a “reservoir” of GH in the blood which helps to smooth out the effects of the erratic pattern of secretion and extends half life by protecting from excretion in the urine.

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17
Q

How does IGF-1 exhibit a negative feedback loop on GH?

A

By inhibiting GHRH and stimulating GHIH (somatostatin)

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18
Q

What is another name for somatoSTATIN?

A

GHIH

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19
Q

What is another name for somatoTROPIN?

A

GH

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20
Q

Where is GH released from?

A

The anterior pituitary

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21
Q

What are the two mechanisms by which GH release is inhibited?

A
  • IGF-1 negative feedback on GHIH and GHRH

* Negative feedback loop of GH on GH release from somatotropin in anterior pituitary

22
Q

What are the GH/IGF-I effects on bone growth?

A
  1. GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes
  2. During differentiation, the cells secrete IGF-I and become responsive to IGF-I
  3. IGF-I then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, which then becomes calcified (bone)
23
Q

What is responsible for the closure of the epiphyseal growth plate during adolescence?

A

Sex steroid hormones causing no further longitudinal growth

24
Q

How does GH regulate metabolism (direct effect)?

A
  1. Increases gluconeogenesis by the liver
  2. Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue (by reducing the number of insulin receptors)
  3. Makes adipocytes more sensitive to lipolytic stimuli (promotes lipolysis)
  4. Increases amino acid uptake and protein synthesis in almost all cells = anabolic effect
25
Why is GH said to be diabetogenic (increase blood glucose)?
Its metabolism actions release energy stores to support growth (bone does not require insulin for Glc uptake) It has 'anti-insulin' effect and synergises with cortisol in the respect But unlike cortisol, and like insulin, GH increases AA and protein synthesis (anabolic effect) - cortisol stimulate protein catabolism
26
Describe secretion rate of GH from pituitary gland
Secretion rate undergoes spontaneous fluctuations as well as increase or decrease in response to specific stimuli
27
When is most of the GH being released from the pituitary?
During first 2 hours of sleep (deep delta sleep). x20 increase in GH secretion in children during this period. General energy requirements low so energy diverted to growth. GHRH may have sleep inducing qualities.
28
What is used to determine hormone status in children?
Fluctuation in level of GH shown by repeated measurement over 24hrs
29
What controls GH secretion?
Nutritional status -> it is mediated via modulation of GHRH/GHIH release from hypothalamus
30
Name five stimuli that increase GHRH secretion (increases GH)
1. Actual or potential decrease in energy supply to cells 2. Increased amounts of AA in plasma 3. Stressful stimuli 4. Delta sleep 5. Oestrogen and testosterone
31
What are states which cause actual or potential decrease in energy supply to cells (stimulating GHRH)?
* Fasting and hypoglycaemia * Exercise * Cold
32
Why does delta sleep increase GRHR?
Increase in GH in delta sleep may be related to growth spurts in children and adolescents and tissue repair in adults.
33
Why does oestrogen and testosterone stimulate GHRH?
Stimulate GH release from the pituitary directly as well as decreasing IGF mediated negative feedback. Responsible for growth spurt in puberty
34
Name five stimuli in GHIH
1. Glucose 2. FFA 3. REM sleep (no REM sleep show increase in GH secretion) 4. Cortisol
35
What are three factors which determine growth
* Hormones * Nutrition * Genetics
36
Describe how growth is influenced by hormones
GH, IGF-1, TH, sex steroids, glucocorticoids and insulin * Different periods of growth are dominated by different hormones * Sex hormones influence is minor until puberty * GH is minor during foetal life, insulin and IGF-2 dominate it.
37
What is thyroid hormone important for?
Development of the nervous system in utero and early childhood Effects are permissible to GH/IGF-1
38
What is crenitism?
TH has effects on ossification of cartilage and teeth maturation and also contours of face and proportion of the body. It's a condition where children are hypothyroid from birth --> they have retarded growth because of the loss of TH’s permissive action on GH. They retain infantile facial features = hypothyroid dwarf. GH levels are normal
39
How does nutrition influence growth?
Adequate diet in terms of protein content and essential vitamins and minerals is just as important as enough calories. Important in utero and during development. Injury and disease stunt growth because --> increase protein catabolism (glucocorticoid effects)
40
How does genetic factors influence growth?
Helps determine maximum growth | • Interaction between genetic factors and nutrition
41
What are the two periods of rapid growth?
1. Infancy | 2. Puberty
42
What occurs in infancy period of growth?
Rapid growth spurts 2.5cm in a few days and then nothing i.e. episodic, mechanism not known
43
What occurs the puberty period of growth?
Due to androgens and oestrogens, produce spikes in GH secretion that increase IGF-I --> increase in growth. The same sex steroids also terminate growth by causing the epiphyses of the long bones to fuse
44
How does puberty cause bone growth?
In normal puberty, before the epiphyseal plates fuse, GH/IGF-I promote bone elongation and increased height, weight and body mass. Sex hormones in the later stages of puberty act to close the epiphyses and hence stop bone elongation.
45
What are two outcomes of hyper secretion of GH?
Gigantism and acromegaly
46
What is the usual cause of hyper secretion of GH?
Endocrine tumour usually the cause
47
What is gigantism?
XS GH due to a pituitary tumour before epiphyseal plates of long bones close excessive growth. May be more than 7ft tall (210cm), called pituitary giants.
48
What is acromegaly?
XS GH due to a pituitary tumour after epiphyseal plates have sealed. Long bones cannot increase so there is no longitudinal growth and no increase in height. However, can still grow in other directions and the characteristic features are enlarged hands and feet.
49
What is the classic sign of acromegaly?
In adults feet should NOT get bigger Normal height but enlarged hands and feet and facial features
50
What is the treatment of hypersection go GH causing abnormal growth?
Surgery to remove tumour or somatostatin analogues to treat
51
Name six possible causes of dwarfism?
1. Deficiency of GHRH 2. GH secreting cells may be abnormal 3. End organ unresponsive to GH (baron dwarfism) due to defective IGF-1 receptors 4. Genetic mutations - impairs ability of cells to produce IGF-1 in response to GH 5. Precocious puberty - XS GnRH release stimulates puberty via promoting sex hormone release (stunted growth as long bone fuses early) 6. Hypothyroid children retain infantile features with stunted growth due to loss of permissive effects of TH on GH - limits bone growth and promotes fat storage

Endocrine System (29 decks)

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