Thyroid And Adrenal Hormones - 2 Hormones Affecting Metabolism Flashcards
(66 cards)
1
Q
What is the thyroid gland?
A
- located in the neck, in front of & below the level of the larynx
- consists of 2 lobes joined by the thyroid isthmus
2
Q
What does the thyroid make?
A
- thyroxine T4
- tri-ioodo thyroxine T3
- they regulate many aspects f our metabolism
- effecting how many calories we burn, how warm we feel, how much we weigh
- direct effects on cardiovascular system
3
Q
What is the follicular gland?
A
- makes T3 & T4 hormones
- it consists of spherical follicles that are filled with a proteinaceous colloid
- thyroid follicles differ in size depending on how active the gland is
4
Q
Why can thyroid follicles differ in size?
A
- depending on how active the gland is
5
Q
What size are the follicles when the gland is inactive?
A
- large and swollen
- with colloid and composed of flattish cells
6
Q
What size are the follicles when the gland is active?
A
- the follicles are quite small and indistinct
- they have very little stored material
- composed of cuboidal or columnar cells
7
Q
What are evident on the apices of the active cells?
A
- microvilli
- reabsorption lacunae
8
Q
How are the thyroid hormones formed?
A
- iodide is actively pumped from the extracellular space into the follicular cells
- the iodide is then oxidised to iodine, then transferred to the colloid
- where it is combined with the tyrosine residues of a binding protein - within the colloid which is = thyroglobulin
- moniodothrosine (MIT) and di-iodo tyrosine (DIT)
- are formed and can further become
= tri-iodotrynonine = T3 =MIT + DIT
= thyroxine = T4 = DIT + DIT
9
Q
What is the control of thyroid hormone secretion an example of?
A
- hypthalamo / anterior / pituitary / endocrine organ axis system
10
Q
What is thyroid hormone secretion controlled by?
A
- the production of thyrotropin releasing hormone (TRH) from the = hypothalamus, a structure at the base of the brain
11
Q
Where does TRH then travel?
A
- to the hypophyseal circulation, where it causes the anterior pituitary gland, to release thyroid stimulating hormone = TSH
12
Q
What does TSH stimulate?
A
- the production of thyroid hormone from the thyroid gland
- this causes an increase in circulation of T3 & T4
- causing a reduction in TRH & TSH production
- regulating the normal levels of T3 & T4
- this is a typical example of = a negative feedback loop
13
Q
What happens when thyroid hormone is released into the blood?
A
- most is bound to plasma proteins
- this prevents its excretion in the urine, while also maintaining a reserve of thyroid hormone
14
Q
What are the two binding proteins?
A
- throxine binding prealbumin = TBPA
- thyroid binding globulin = TBG
15
Q
Why is TBG the more important binder?
A
- even though TBPA has the greatest capacity to bind thyroxine, the TBG has a greater affinity for thyroid hormones
- this is why it is more important
- 99.98% plasma T4 and 99.8% of T3 is bound to
16
Q
What type of hormone is biologically active?
A
- only the unbound hormone
17
Q
Why do changes in the levels of binding hormones do not cause hypothyroidism or hyperthyroidism?
A
- since thyroid production is changed to maintain a euthyroid state
- important when using assays that measure total (bound and unbound) hormone
- as changes in protein binding occur naturally = during pregnancy or during drug therapy
18
Q
Mechanism of action of thyroid hormones and steroids:
A
- thyroid hormones enter cells and bind to nuclear receptors
- T3 binding much better than T4, it is 3-5 times more potent
- a large proportion of T4 is converted to T3 within the cell - before binding
- its binding with nuclear receptors = increases DNA transcription
- promoting protein synthesis
- increased enzyme activity
- better cell metabolic rate
19
Q
What are the metabolic effects of the thyroid hormone?
A
- secondary to calorigenesis = raising of metabolic rate
- basal metabolic rate is increased with concomitant increases in oxygen consumption & heat production
- carbohydrate metabolism is enhanced, with increases in intestinal and cellular absorption of glucose, glycolysis & gluconeogenesis
- fats are also metabolised quicker, breaking down fat stores into free fatty acids
- protein stores are turned over quicker as well
20
Q
What do thyroid hormones have direct systemic effects on?
A
- they exert a direct effect on the heart, increasing heart rate and cardiac contractility
- they also reduce peripheral resistance
- breathing is also increased
- in the CNS, thyroid hormones increase alertness, shorten reaction times and cause reflex delay
- in the GI system, motility and secretion is increased
21
Q
What developmental effects do the thyroid hormones cause?
A
- essential for stimulation of skeletal growth in childhood & normal CNS brain development in the early postnatal period
- mental retardation, motor rigidity & deaf-mutism are consequences of thyroid deficiency during development
22
Q
What is myxodema caused by?
A
- reduced production of thyroid hormone
- can be a problem with the gland itself, which is = primary hypothyroidism
- the most common cause of primary hypothyroidism = lack of iodine in the diet
- iodine is essential for the production of T3 & T4
23
Q
What are other causes of primary hypothyroidism?
A
- gland inflammation
- congenital thyroid enzyme deficiencies
24
Q
What do low T3 and T4 levels cause?
A
- increased TSH production, leading to goitre
25
What is secondary hypothyroidism due to?
- deficient TSH production and leads to thyroid atrophy
26
What happens in adults?
- body processes slow down
- voice can be slow and husky
- skin becomes coarse and puffy
- weight is gained
- cold tolerance reduced
- heart rate falls
- constipation
- blood sugar levels fall, blood lipid levels rise
- increases risk of atherosclerosis
27
What happens in children?
- mental and growth problems result from the lack of thyroid hormone
= cretinism
28
What is hyperthyroidism due to?
- due to a hormone secreting tumour (adenoma) within the thyroid gland
- most common form = Graves’ disease
29
What is Graves’ disease caused by?
- the body producing antibodies against the thyroid gland which act like TSH and stimulate it
- they are called TSI’s
30
What happens in Graves’ disease / hyperthyroidism?
- due to the increased metabolic rate, we get great weight loss in spite of overeating
- the cardiac consequences = rise in blood pressure, elevation in cardiac output, increased risk of arrhythmia, high output cardiac failure may result
- thyroid hormones have a calorigenic effect - you will feel warm and flushed
- excessive thyroid hormone results in myopathy, weakening the muscles
- diarrhoea = increased gut motility
- most distressing symptoms - mental ones = unable to relax, irritable etc
31
What are usually the physical signs?
- exopthalmus & goitre
- goitre can cause a blockage of the trachea, which can be diagnosed and seen via x-ray
32
Where are the adrenal corticosteroids secreted?
- in the adrenal glands
- just above the kidneys
33
How many layers of the adrenals is there?
- 2
- the adrenal cortex = outer layer
- the adrenal medulla = central layer
34
What does the adrenal medulla function as?
- an endocrine extension of the sympathetic nervous system
35
Where are the adrenal corticosteroids secreted exactly?
- the outer layer
- we need them to survive
36
Where do glucocorticoids = cortisol, corticosterone & cortisone come into play?
- play a major role in the control of blood glucose and other aspects of metabolism
- essential in the body’s reaction to stress, so it can survive a lot of abnormal conditions
37
Where are the mineralcorticoids (aldosterone) important?
- important in the control of extracellular fluid volume
- has an effect on sodium reabsorption
38
What are the three regions that the adrenal cortex is divided into?
- the zone glomerulosa = which secretes mineralocorticoids
- the zone fasciculata = secretes glucocorticoids
- the innermost layer, zona reticularis = where adrenal androgens are produced
39
When are all the corticosteroids produced?
- when cholesterol is converted to pregnenolone, a precursor of corticosteroids
40
What is the release of glucocorticoids controlled by?
- the hypothalamus in the brain
- the anterior pituitary gland
- the hypothalamus releases corticotrophin releasing hormone = CRH
- causing the anterior pituitary to release adrenocorticotrphic hormone = ACTH
- which releases the glucocorticoids from the adrenal cortex
- high plasma levels of glucocorticoids feedback to suppress production
- circadian rhythm = peaks between 7 & 9, trough at night time
41
How do glucocorticoids exert their effect?
- via nuclear receptors in appropriate cells
42
The glucocorticoids have many affects on glucose metabolism:
They are - catabolic hormones:
1. Gluconeogenic
2. Lipolytic
3. Proteolytic
43
What are the glucocorticoids primarily?
- they function in the break down of substances, they are catabolic
- they accelerate the rate of glucose synthesis and glycogen formation
44
What else do glucocorticoids cause?
- the breakdown of adipose tissue to form free fatty acids
- they break down proteins to form free amino acids in the bloodstream
- these amino acids can be converted to extra glucose via gluconeogenesis
- these affects are important in maintains blood glucose during fasting
45
Does glucocorticoid level rise during fasting?
- no
- the increases in amino acids mobilisation and gluconeogenesis don’t occur in the absence of glucocorticoids
46
Metabolic effect summary:
- protein
- to amino acids
- gluconeogenesis
- to glucose
- to glycogen
- lipids
- to fatty acids
- oxygen convert this to energy
- glucocorticoids act to have stuff taken out of storage for ready availability in the bloodstream
47
What do stressful situations do to glucocorticoid levels?
- increased glucocorticoid levels are stimulated
- it is thought to be due to 2 factors
48
What is the first factor?
- cortisol promotes a rapid supply of glucose and amino acids to the body tissues through its metabolic effects
49
What is the second factor?
- cortisol plays a permissive role in the cardiovascular response to stress
- increased sympathetic activity is reflexly activated by stresses such as exercise, anxiety, hypoglycaemia and blood loss
- this causes vascular constriction - which helps to maintain arterial pressure and directs blood towards the most vital organs
- vascular smooth muscle becomes unresponsive to catecholamines in the absence of glucocorticoids
50
What do glucocorticoids do on the immune system?
- they suppress the immune system
- which gives rise to an important use of steroids medically
- they do this by suppressing inflammation & inhibitng lymphocyte activation
- leading to a second medical use of glucocorticoids
- in reducing the risk of organ rejection in transplant patients
51
- the adrenal corticosteroids hormones are involved in the pathophysiology of stress, when we attempt to adapt it
- triphasic reaction
- general adaptation syndrome / GAS
- 1st response to stress = panic/alarm phase
- fight or flight response of the organism
- if stress is prolonged, we get the RESISTANCE phase
- where cortisol secreted by the adrenal cortex mobilises fuel and protein from body tissues, to help prolong the fight or flight reaction
- it ends when the fuel becomes exhausted
- we get the EXHAUSTION phase
- where failure of one or more organ systems becomes fatal
52
Stress is implicated in many diseases:
- heart disease
- strokes
- anorexia
- essential hypertension
- why?
- the sympathetic nervous system is hyperactive
- the body is continually breaking down reserves to keep blood glucose and amino acid levels high
53
What do mineralocorticoids do?
- largely responsible for the maintenance of extracellular fluid volume through their control of renal reabsorption of sodium ions
- the control of aldosterone secretion from the zona glomerulosa is dependent on changes in extracellular flow volume, detected by renal mechanisms
54
Renal mechanisms:
- hypothalamus secretes CRH
- anterior pituitary
- ACTH secreted
- high potassium ions concentration
- angiotensinogen
- renin
- angiotensin I
- ACE
- angiotensin II
- aldosterone
55
What is the most important regulator of aldosterone secretion?
- renin angiotensin aldosterone axis
- changes in ECF volume, blood pressure of plasma sodium ions
- are detected by the juxtaglomerular apparatus of the kidney
- this promotes angiotensin II production
- which stimulates aldosterone secretion
56
What is the second factor regulating aldosterone secretion?
- changes in extracellular fluid volume through = potassium ions concentration
- directly stimulates secretion
57
What is the third factor?
- ACTH secretion can affect levels of aldosterone
- not as important as the other two
58
What do mineralocorticoids stimulate?
- the active reabsorption of sodium ions from the distal convoluted tubule
- water then follows sodium by osmosis, effectively reabsorbing an isotonic solution
- this expands the total sodium ion concentration of the extracellular fluid, by osmostically attracting water to it
- increasing the extracellular fluid volume too
- they also increase active secretion of potassium ions and hydrogen ions into the tubular fluid
- promoting their urinary excretion
59
Adrenal androgens:
- male sex hormones produced in the zona reticularis of the adrenal cortex
- main source of androgen in the female
60
What is reduced secretion of the adrenal corticosteroids?
- addisons disease
- may be due to a problem with the gland itself = primary hypoadrenalism = surgery, antibodies etc
- failure of the gland to produce hormone, leads to a rise in the plasma levels of trophic hormones = ACTH and CRH
- these stimulate melanocyte activity, leading to pigmentation of the skin & buccal mucosa
- secondary hypoadrenalism = due to a problem with the anterior pituitary, decreasing ACTH secretion
61
Effects of hypoadrenalism:
- glucocorticoid levels reduced
- mineralocorticoids levels are reduced
- glucocorticoid deficiency = loss of weight, poor exercise tolerance
- fasting = hypoglycaemia
- stress resistance is reduced too
- patients on glucocorticoid therapy need increased doses before surgery
- mineralocorticoids deficiency - leads to lethal reduction in sodium ions and water
- reducing plasma volume,causing dehydration
- high plasma potassium results = leading to cardiac arrhythmias, metabolic acidosis can result from increased hydrogen ions levels
62
What does Cushing’s syndrome result from?
- increased glucocorticoid activity
- due to an excess secretion of ACTH, a glucocorticoid secreting tumour in the adrenal cortex, or prolonged periods of treatment with glucocorticoids
63
What are the main effects of Cushing’s syndrome?
- increase in blood glucose
- which is resistant to insulin treatment
- increased protein breakdown, leading to muscle wasting - osteoporosis in bone & stretch lines in the skin
- growth reduced in children
- weight gain = stimulation of appetite = buffalo hump, moon face
- hypertension = due to mineralocorticoid action of cortisol and hirsutism & acne
64
Primary hyperaldosteronism:
- the activity of a tumour in the adrenal cortex which secretes aldosterone
- main effects = sodium ion and water retention, increased blood volume, hypertension
- this reduces renin secretion from the juxtaglomerular apparatus, so angiotensin levels are low
- renal potassium ion loss leads to reduced plasma concentration
- hypokalaemia can cause muscle weakness
65
What is adrenogenital syndrome?
- genetically determined biochemical defect which results in increased secretion of androgens from the adrenals
- the effects depend on the sex of the individual effected
- the secretion of excess adrenal androgens in childhood leads to rapid growth & early puberty in young boys
- their adult height is often reduced, due to early epiphyseal fusion
- in females, they can become masculinised
66
Summary:
- thyroid hormones set the metabolic rate of the body by their calorigenic action, directly affect some organ systems and are vital in development
- glucocorticoids are important regulators of the metabolism of glucose, amino acids and proteins
- mineralocorticoids are essential in the regulation of ECF volume and sodium ions
- problems with the above systems can have significant and lethal effects on humans
