Metabolic Rate, Growth and Disease Flashcards
What is the key role of growth hormone (GH) in children?
Promotes growth
What can GH deficiency in children lead to?
Dwarfism (after birth)
What can GH excess in children lead to?
Gigantism
Why is the no change in stature in adults to GH?
As epiphyses are closed (end part of long bone)
What can excess GH adults lead to?
Acromegaly - bones become excessively thickened and other tissues overgrow (massive face and big hands)
What can acromegaly lead to?
Places strain on CVS –> heart failure if not treated
What can deficiency in GH in adults lead to?
No obvious disease but replacement increases lean body mass, decreases fat, increases vigour
What is released by the hypothalamus to stimulate release of GH?
GHRH
Where is GH released from?
Anterior pituitary
What else can affect release of GHRH?
Sleep, exercise, stress
What is effect of T3 on GH?
Enhancing effect
What is effect of somatostatin on GH release?
Suppresses secretion from anterior pituitary by inhibiting GHRH
What is effect of lots of GH?
Negative feedback –> enhances somatostatin which inhibits GHRH
What is effect of GH on target organs (especially liver)?
They release IGFs (insulin-like growth factors) which provide feedback inhibition on GH
When is GH released more?
During deep sleep
What are the short term effects of GH?
Diabetogenic –> antagonising effects of insulin, increasing glucose
How does GH act?
Via tyrosine kinase associated receptor, leading to protein phosphorylation
What are the rapid effects of GH on fat?
Increases lipolysis
What are the rapid effects of GH on insulin?
Insulin resistance
What are the rapid effects of GH on liver?
Increased gluconeogenesis
What are the rapid effects of GH on muscle?
Decreased glucose uptake
What are the long term effects of GH mediated by?
Via insulin-like growth factor 1 (somatomedin)
Released from many tissues in response to GH
What do somatomedins require?
Insulin to be present
Cross-reactivity of insulin and IGF1 as similar
What is the main active IGF (somatomedin)?
IGF1 (stimulated by GH production)
What is effect of IGF1?
Enhance protein synthesis and growth. Can cause hypoglycaemia if in high enough levels.
What other factors affect growth?
- Insulin (especially in utero)
- Steroids (sex steroids, glucocorticoids)
- Thyroid hormones
What is effect of sex steroids?
Accelerate growth, but hasten maturity
What is effect of glucocorticoids?
Typically slow growth
What are thyroid hormones essential for?
Normal growth and response to GH
What are the 2 forms of thyroid hormones (TH)?
T3 (active) and T4 (circulation)
How are TH carried?
Carried in the blood tightly bound (99.8%) to proteins, especially thyroid binding globulin and transthyretin (T4 in particular)
What is effect of T4 being bound to carrier protein?
More stable so increases half life
T4 8 days, T3 1 day
What is the secretion of TH stimulated by?
TSH from anterior pituitary
What are effects of TH?
Increases metabolic rate and heat generation
Also essential for growth and development
Where is the thyroid gland?
In the neck below the thyroid cartilage (moves on swallowing)
What do the follicles in the thyroid gland produce?
Thyroglobulin (protein secreted into lumen of follicle)
What do the C cells of the thyroid secrete?
Calcitonin (involved in calcium levels)
What do the parathyroid glands secrete?
PTH
Where are the parathyroid glands? How many are there?
4 - embedded in thyroid gland
How does TSH stimulate secretion of thyroid hormones?
The thyroid gland uses iodine to make thyroid hormones (enhances iodine uptake)
What is produced as well as T3 and T4?
rT3 (reverse T3 –> inactive)
What is a trophic hormones?
One that has a growth effect
TSH also has trophic effect on cells. What can this lead to?
Thyroid gland can become enlarged
What is consequence of exposure to radioactive iodine?
Will end up in thyroid –> can destroy thyroid
When can radioactive iodine be used?
In hyperthyroidism / thyroid cancer (danger of surgery if patient is elderly)
How can you protect yourself against radioactive iodine?
Give them iodine tables –> saturates thyroid
How is T4 deiodinated to T3?
By 2 enzymes: Type I and Type II
Where is type I found?
Found in liver, kidney and thyroid
What is type I inhibited by?
Stress and caloric restrition
Where is type II found?
In pituitary, CNS and placenta
is constitutive
What type of receptor is the thyroid hormone receptor?
Nuclear receptor –> initiates gene transcription
What is effect of thyroid hormones on beta adrenergic receptor?
Gets activated which enhances response to sympathetic nerve activity (again increases metabolic rate)
What is effect of thyroid hormones on liver?
Increases gluconeogenesis and glycogenolysis in the liver.
But usually no hyperglycaemia (insulin control normal)
What are acute effects of thyroid hormones?
Increase basal metabolic rate and heat production, via “futile cycles” and mitochondrial decoupling
What are effects of TH on fats?
Causes both lipolysis (to free glycerol for gluconeogenesis), and lipogenesis.
What are effects of TH on muscle?
Increases proteolysis (to produce AA for gluconeogenesis), but also protein synthesis. Net muscle wasting.
What is effect of TH on on Na+/K+ ATPase activity?
Increases
Main function of brown adipose tissue?
Generating body heat (prevalent in babies)
In the long-term, what are effects of TH?
Crucial for normal brain development and growth
What can a deficiency in TH in infancy lead to?
Cretinism and dwarfism
What is cretinism?
A condition characterised by physical deformity and learning difficulties that is caused by congenital thyroid deficiency.
What can a deficiency in TH in later childhood lead to?
Later in childhood there is severe impairment of growth: catch-up growth possible
How can a thyroid goitre come about?
TSH drives thyroid hypertrophy, so low TH (and lack of feedback so lots of TSH) leads to a goitre: common in areas with low environmental iodine
What is a goitre neck?
A swelling of the neck resulting from enlargement of the thyroid gland.
What are effects of autoimmunity on the thyroid?
Can cause hyper- or hypothyroidism
How can autoimmunity cause hyperthyroidism?
Antibodies against the TSH receptor may activate it, driving excess TH production and cause hyperthyroidism (e.g. Graves disease).
What is hyperthyroidism caused by autoimmune called?
Graves disease
What are the symptoms of hyperthryoidism?
Weight loss, tremor, sweating, tachycardia, dislike of hot weather
What are the additional symptoms of Grave’s disease?
Exophthalmos, double vision and pretibial myxoedema (due to increased tissue production)
What is exophthalmos?
Bulging of the eye anteriorly out of the orbit (bilateral in Grave’s, unilateral in orbital tumour)
How can autoimmunity cause hypothyroidism?
Antibodies that destroy TSH receptors or other thyroid targets cause hypothyroidism (e.g. Hashimoto’s thyroiditis).
What are symptoms of hypothyroidism?
Weight gain, hypothermia, tiredness, constipation, skin thickening & oedema, bradycardia, dislike of cold weather. Secondary anovulation
What are corticosteroids?
Hormones produced from the adrenal cortex
Class of steroid hormones
What are the 2 main categories of glucocorticoids?
- Mineralocorticoids
- Glucocorticoids
What is the main natural glucocorticoids in man?
Cortisol
What does the hypothalamus release of CRH affect?
Hypothalamus released CRH which induces ACTH (adrenocorticotropic hormone) release from the anterior pituitary
What does ACTH stimulate?
Cortisol production from adrenal cortex (also stimulates hypertrophy)
What are effects of iatrogenic steroids?
Strong feedback loop - suppresses ACTH and causes adrenal atrophy
What is adrenal atrophy indicative of?
Adrenal atrophy is indicative of a loss of ACTH and trophic support of the adrenal cortex, and this too may result in deficits in functional capability of the cortex to produce glucocorticoids
What is atrophy?
Waste away, especially as a result of the degeneration of cells
What are the key drives for CRH release?
Stress factors (emotional, hunger etc)
How do glucocorticoids act?
Via a nuclear receptor, inducing gene transcription
What are effects of glucocorticoids on insulin?
Inhibit insulin responses (enhance glucose production and targets glucose to brain)
What are effects of glucocorticoids on SNS responses?
Enhances SNS responses
What are effects of glucocorticoids on liver?
Promotes gluconeogenesis and glucose release
What are effects of glucocorticoids on fat?
Lipolysis (glycerol for gluconeogenesis), FFA for energy
What are effects of glucocorticoids on muscle?
Protein breakdown for gluconeogenesis
What is a diabetogenic effect?
Increase in glucose
What are effects of glucocorticoids on immunity?
- Immunosuppression
- Reduction in inflammation and cytokine production
What are effects of glucocorticoids on GI?
Stimulate GI tract mucosa
What are effects of glucocorticoids on fat distribution?
Fat redistribution – peripheral to central (truncal obesity)
What are effects of glucocorticoids on blood?
Stimulate haematopoiesis
What are negative effects of glucocorticoids?
- Fat redistribution – peripheral to central
- Skin thinning, muscle wasting, osteoporosis
- Complex CNS effects: euphoria to psychosis!
What can excess glucocorticoids cause?
Cushing’s disease
What is Cushing’s disease?
A condition in which the pituitary gland releases too much adrenocorticotropic hormone (ACTH)
What can adrenocortical insufficiency lead to?
Addison’s disease (high ACTH and MSH gives pigmentation)
What is nephrotic syndrome?
A kidney disorder that causes your body to pass too much protein in your urine
What is minimal change disease?
Minimal Change Disease (MCD) is a kidney disease in which large amounts of protein is lost in the urine. It is one of the most common causes of the Nephrotic Syndrome
What are the acute diabetogenic effects of GH?
Antagonising insulin and enhancing gluconeogenesis
What are the long term effects of GH?
Longer term, via IGFs, control of tissue and organism growth
What are the acute and long term effects of TH?
Thyroid hormone has acute hypermetabolic effects, and longer term involvement in growth and development.
How do GH, TH and insulin work together?
GH, TH and insulin work together to control growth, restricting it when food is short, and enhancing it when food is plentiful.
What are the acute and long term effects of glucocorticoids?
Glucocorticoids are essentially stress hormones. They also have “diabetogenic” effects acutely, as well as long-term trophic effects.
