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BS - Gastrointestinal System pt.1 > Metabolic Rate, Growth & Disease > Flashcards

Metabolic Rate, Growth & Disease Flashcards

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1
Q

How is acute regulation of plasma glucose maintained?

A

Through the action of insulin and glucagon

There are some modifications by adrenaline

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2
Q

What is the role of growth hormone in children?

A

It promotes growth

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3
Q

What does deficiency and excess growth hormone in children lead to?

A

Deficiency leads to dwarfism after birth

Excess leads to gigantism

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4
Q

Why does growth deficiency only lead to dwarfism after birth?

A

Before birth, there are hormones related to growth hormone that produce the same growth response

Maternal insulin is also important

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5
Q

Why does growth hormone not have the same effect in adults?

A

The epiphyses of the long bones are closed, so there is no change in stature

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6
Q

What does an excess of growth hormone cause in adults?

A

Acromegaly

Bones become excessively thickened, soft tissues and other tissues overgrow

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7
Q

How does someone with acromegaly often die?

A

Through heart failure

This is due to the extra strain on the cardiovascular system from tissue overgrowth

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8
Q

What does growth hormone deficiency cause in adults?

How does this change when growth hormone is administered?

A

Deficiency gives no obvious disease

When GH is administered:

  1. increase in lean body mass
  2. decrease in fat
  3. increase in vigour and wellbeing
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9
Q

What is the role of the hypothalamus in GH regulation?

A

It integrates signals that are driving or suppressing expression of GH

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10
Q

What are the 2 nuclei of the hypothalamus involved in GH regulation?

How do they affect each other?

A
  1. paraventricular nucleus secretes somatostatin
  2. arcuate nucleus secretes GRH

They inhibit each other, leading to an episodic cyclic response

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11
Q

How will the paraventricular and arcuate nuclei influence GH production?

A

Somatostatin from the paraventricular nucleus suppresses anterior pituitary GH

GHR from the arcuate nucleus increases anterior pituitary GH

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12
Q

What factors will increase growth hormone secretion?

A
  1. low glucose
  2. amino acids
  3. TRH
  4. Ghrelin
  5. androgens/oestrogens
  6. sleep, exercise and stress
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13
Q

How does Thyroid hormone (T3) influence GH production?

A

It increases growth hormone production

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14
Q

What is the main result of growth hormone secretion?

A

It will increase metabolic activity and produce IGFs (insulin-like growth factors)

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15
Q

What is the role of IGFs?

A

They provide feedback inhibition and longer-term growth

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16
Q

How does growth hormone release change during the day?

A

There are lots of rapid pulses of release

More is released at night

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17
Q

What is the mechanism behind growth hormone secretion?

A
  1. GRH binds to the receptor
  2. This causes activation of adenylate cyclase
  3. adenylate cyclase activates protein kinase a
  4. this causes a enzymatic cascade leading to Ca2+ influx
  5. Growth hormone is released by exocytosis
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18
Q

What is the effect of somatostatin on growth hormone release?

A

It will inhibit adenylate cyclase

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19
Q

What are the 2 variants of growth hormone?

A

22 kDa form predominates

20 kDa form

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20
Q

What happens to growth factor after it is released into the circulation?

A

About 40% of the molecule binds to a carrier protein in the plasma

This protein is made by cleaving its receptor

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21
Q

What is the half-life of growth hormone?

How does binding to a carrier protein in the plasma affect this?

A

25 minutes

Binding to a carrier protein increases half-life as GH is protected from cleavage by proteases

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22
Q

What receptor does growth hormone bind to?

A

It acts via a tyrosine kinase associated receptor

This leads to protein phosphorylation

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23
Q

Why is growth hormone said to have “diabetogenic effects”?

A

It antagonises the effect of insulin to increase blood glucose concentration

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24
Q

How fast are the effects of growth hormone?

How are longer-term effects mediated?

A

Rapid effects in minutes to hours

Longer term effects on growth are mediated via insulin-like growth factor 1 (somatomedin)

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25
How does growth hormone affect: i. liver ii. fat iii. muscle iv. insulin?
i. increased gluconeogenesis ii. increased lipolysis iii. decreased glucose uptake iv. creates insulin-resistance
26
Why does growth hormone antagonise the effects of insulin receptors?
If muscles take up less glucose, this can be used for the RBCs and the brain The muscles can use the fatty acids produced from lipolysis
27
When is somatomedin released? What must be present?
It is released from many tissues in response to GH It requires insulin to be present as well
28
What are the 2 IGFs (somatomedins)?
1. IGF1 is the main active IGF that is stimulated by GH | 2. IGF2 is not stimulated by GH
29
What is significant about IGF1 having a strong homology to insulin?
The receptors are similar and work in the same way IGF1 will work okay on the insulin receptor and vice versa
30
What is the role of IGF1? What happens if it is present in excess?
It enhances protein synthesis and growth In excess, it can cause hypoglycaemia
31
Other than growth hormone, what other 3 factors affect growth?
1. insulin - especially in utero 2. steroids 3. thyroid hormones
32
How do sex steroids and glucocorticoids affect growth?
Sex steroids accelerate growth but hasten maturity (this is bc they increase rate of growth as well as fusion of the epiphyses) Glucocorticoids slow growth
33
Why are thyroid hormones involved in growth?
They are essential for normal growth and response to GH
34
What are the 2 forms of thyroid hormones?
T3 - triiodothyronine T4 - thyroxine
35
What is strange about the mechanism of action of thyroid hormones?
They are peptide hormones but have intracellular receptors They will enter the nucleus to affect transcription (they act like steroids)
36
How is T4 carried in the blood?
It is tightly bound to carrier proteins These are thyroid binding globulin and transthyretin
37
How does being bound to proteins affect the activity and half-life of T4?
It has a low free concentration in the circulation It is also very stable and the half-life is prolonged Half life = 8 days
38
What is the half-life of T3? Why is it different to T4?
1 day T3 is less bound to protein and less stable It is the active form that enters cells to produce effects
39
What will stimulate production and release of thyroid hormones?
Thyrotropin from the anterior pituitary gland | this is TSH
40
What are the roles of thyroid hormones?
1. increase metabolic rate 2. increase heat generation 3. essential for normal growth and development
41
What is the structure of the thyroid gland like?
It is anchored to thyroid cartilage and moves on swallowing It contains follicles which contain thyroglobulin
42
What are C cells?
Clear cells They secrete calcitonin, which is involved in calcium handling
43
What is the role of TSH on the basolateral membrane of the thyroid follicular cell?
It increases the activity of the Na/I cotransporter (NIS) This enhances the uptake of iodine by the follicular cell so that the ratio of follicular cell iodine:plasma iodine increases
44
What happens to iodide after it has entered the follicular cell? What happens at the same time?
It is transported into the follicular lumen The follicular cell also secretes thyroglobulin
45
What happens during iodination? What stimulates this process?
TSH stimulates iodination of thyroglobulin in the follicular lumen
46
What happens after iodination is completed?
CONJUGATION TSH stimulates the conjugation of iodinated tyrosines to form T4 and T3 linked to thyroglobulin
47
What happens after conjugation is completed?
TSH stimulates endocytosis of iodinated thyroglobulin into the follicular cells
48
What happens after endocytosis is completed?
PROTEOLYSIS TSH stimulates the proteolysis of the iodinated thyroglobulin, forming T3 and T4
49
What happens after proteolysis is completed?
TSH stimulates secretion of T4 and T3 into the circulation
50
What other type of thyroid hormone is produced?
rT3 which is inactive
51
What is meant by TSH having a trophic effect on cells?
The thyroid gland becomes enlarged (hyperplasia) if TSH levels are high
52
What are the 2 enzymes that will deiodiniate T4 into T3? Where are they found?
1. Type I found in liver, kidney and thyroid 2. Type II found in pituitary, CNS and placenta
53
What is the role of the Type III enzyme?
It cleaves T4 to rT3
54
What will inhibit Type I and Type II?
Type I is inhibited by stress and caloric restriction Type II is constitutive (active all the time)
55
What happens to T3 once it has entered a cell?
It migrates to the nucleus, where it binds to the thyroid hormone receptor This then binds to the response element of the relevant gene to activate or suppress transcription
56
How does T3 affect the Na+/K+ pump and the beta adrenergic receptors?
1. increases activity of Na+/K+ pump | 2. activates beta-adrenergic receptors which increases sympathetic stimulation
57
How does thyroid hormone acutely increase metabolic rate and heat production?
1. increases metabolic rate via "futile cycles" that do not actually achieve anything 2. mitochondrial decoupling only generates heat, and no ATP is produced
58
How does thyroid hormone affect activities in the liver?
Increases gluconeogenesis (glucose production) Increases glycogenolysis (glycogen breakdown)
59
What is an example of a futile cycle involving fats?
Thyroid hormone causes both lipolysis and lipogenesis Lipolysis provides free glycerol for gluconeogenesis
60
What is an example of a futile cycle involving proteins? What is the overall effect of this?
Thyroid hormone increases proteolysis, but also protein synthesis Proteolysis provides amino acids for gluconeogenesis Net effect is muscle wasting
61
How does thyroid hormone affect the Na+/K+ pump?
it causes a sodium leak this increases Na+/K+ ATPase activity which wastes energy
62
Why is there usually no hyperglycaemia under the action of thyroid hormones?
Insulin control is normal Thyroid hormones enhance the insulin response as everything is just running a bit faster than normal, and more heat is generated
63
What organ depends on thyroid hormone for development? What does deficiency in infancy lead to?
The brain depends on thyroid hormone for development and growth deficiency leads to cretinism and dwarfism
64
What is cretinism?
A marked impairment of brain function
65
What does deficiency of thyroid hormone cause in later childhood?
Severe impairment of growth Catch-up growth is possible if the thyroid hormone is replaced
66
What is a goitre and what is it caused by?
It is a lump in the neck It is caused by low thyroid hormone leves, as this means more TSH is produced This causes the thyroid gland to enlarge
67
What usually causes a goitre?
it is common in areas with low environmental iodine
68
How does autoimmunity affect the thyroid gland?
It can cause both hyperthyroidism or hypothyroidism
69
How can autoimmunity cause hyperthyroidism? What condition is this?
Antibodies against the TSH receptor may activate it, driving excess TH production and cause hyperthyroidism This is Graves disease
70
What are the symptoms of Graves disease?
1. weight loss 2. tremor 3. sweating 4. tachycardia 5. dislike of hot weather
71
Why do people with Graves disease have double vision?
Graves disease is a consequence of excess tissue growth Exophthalmos develops - eyeballs project out of the front of the face
72
What is pretibial myxoedema in Graves disease?
Excess hypertrophy of tissue down the front of the shins
73
What is the difference between pretibial myxoedema and myxoedema?
Myxoedema is thickening of the tissue, which occurs in hypothyroidism
74
How can autoimmunity cause hypothyroidism? What condition is this?
Antibodies that destroy TSH receptors or other thyroid targets cause hypothyroidism This is Hashimoto's thyroiditis
75
What are the symptoms of Hashimoto's thyroiditis?
1. weight gain 2. hypothermia 3. tiredness 4. constipation 5. skin thickening and oedema 6. bradycardia 7. dislike of cold weather
76
What is secondary anovulation in Hashimoto's thyroiditis?
Ovulation terminates - it is amenorrhea
77
What is the main glucocorticoid in humans?
Cortisol
78
What causes the hypothalamus to release CRH?
It will integrate stress factors and diurnal rhythm to release CRH
79
What is the action of CRH?
It induces ACTH release from the anterior pituitary gland
80
What is the role of ACTH?
It stimulates adrenal cortex hypertrophy and cortisol production
81
What is the effect of iatrogenic steroids on cortisol production?
They will feedback into the pituitary and the hypothalamus to suppress ACTH (and glucocorticoid) production They cause adrenal atrophy
82
What happens if someone takes steroids for too long?
The body is not in a position to replace the steroids after they have stopped being taken This is due to atrophy
83
What are the key drivers for glucocorticoid production?
Physical, emotional and biochemical stress
84
What is the mechanism of action of glucocorticoids? How rapid is their effect?
They act via a nuclear receptor to induce gene transcription They take hours/days to exert an effect
85
What is the main effect of glucocorticoids?
They inhibit insulin responses and enhance SNS responses This targets glucose to the brain, whilst other tissues use fatty acids
86
How do glucocorticoids affect the liver?
They promote gluconeogenesis and glucose release
87
How do glucocorticoids affect fat and muscle?
In fat, they stimulate lipolysis This gives glycerol for gluconeogenesis andfree fatty acids for energy In muscle they stimulate protein breakdown to release amino acids for gluconeogenesis
88
What type of effect do glucocorticoids have and why?
Diabetogenic effect They act against insulin to increase glucose availability
89
What are the main 2 beneficial chronic effects of glucocorticoids?
1. immunosuppression | 2. reduction in inflammation and cytokine production
90
How do glucocorticoids affect the CNS and blood cell production?
1. they have complex CNS effects ranging from euphoria (smaller doses) to psychosis (increased doses) 2. they stimulate haematopoiesis and GI tract mucosa
91
How do glucocorticoids affect the skin and fat distribution?
They cause truncal obesity - fat is distributed from peripheral to central They cause skin thinning, muscle wasting and osteoporosis
92
What does excess glucocorticoids cause?
Cushing's disease
93
What does adrenocortical insufficiency cause?
Addison's disease This leads to a high ACTH which gives a slate grey pigmentation

BS - Gastrointestinal System pt.1 (22 decks)

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