Health and Disease Week 30 Flashcards
(88 cards)
1
Q
define neuroendocrine
A
when modified neurosecretory cells in the hypothalamus and pituitary release hormones directly into circulation to be transported to distance target cells
2
Q
define paraventricular nuclei
A
groups of nuclei in the hypothalamus with very long axons that synapse onto a blood vessel in the median eminance to release hormones directly into the blood
3
Q
define median eminance
A
a local capillary network in the hypothalamus and pituitary axis
4
Q
What is the secondary role of the hypothalamus?
A
it receives light inputs from the retina to synchronise circadian rhythms in the light-dark cycle
5
Q
What are the 2 separate functions of the hyopthalamus?
A
- it releases primary hormones
- it release regulatory hormones
6
Q
Which primary hormones does the hypothalamus release?
A
oxytocin and ADH
7
Q
Where do the primary hormones oxytocin and ADH go?
A
to the posterior pituitary to be release
8
Q
What do regulatory hormones do?
A
they act on the anterior pituitary, which can then release their own regulatory OR primary hormones
9
Q
What are the 5 main regulatory releasing hormones from the hypothalamus?
A
- CRF - corticotropin releasing factor
- TRH - thyrotropin releasing hormone
- GHRH - growth hormone releasing hormone
- GnRH - gonadotropin releasing hormone
- PRF - prolactin releasing factor
10
Q
What are the 5 main regulatory inhibiting hormones from the hypothalamus?
A
- GHIH - growth hormone inhibiting hormone
- PIH - prolactin inhibiting hormone
11
Q
What structure connects the hypothalamus to the pituitary?
A
the pituitary stalk
12
Q
What are the 4 tropic hormones produced by the ANTERIOR pituitary gland?
A
- TSH - thyroid stimulating hormone
- ACTH - adrenocorticotropic hormone
- FSH- follicle stimulating hormone
- LH - luteinising hormone
13
Q
What are the 2 primary hormones released by the ANTERIOR pituitary gland?
A
- GH - growth hormone
- PRL - prolactin
14
Q
What are the steps of hormone secretion by the anterior pituitary?
A
- hormones moves from the hypothalamus in the median eminance capillaries to the anterior pituitary
- transport is driven by arterial input, so flows one way
- hormones stimulate anterior pituitary to release either tropic hormones or primary hormones
15
Q
How does feedback control work in the hypothalamic-pituitary axis?
A
- pituitary hormones feedback to the hypothalamus to decrease release
- hormones can feedback to both the hypothalamus and pituitary to inhibit release
16
Q
What are the 4 main effects of growth hormone (GH)?
A
- increases cell size and number, also differentiation
- protein synthesis
- fat breakdown
- alters carbohydrate metabolism
17
Q
What is another name for growth hormone?
A
somatotropin
18
Q
What does growth hormone cause production of?
A
insulin-like growth factors
19
Q
What are insulin-like growth factors (IGF)?
A
polypeptide hormones mainly produced by the liver in response to GH
20
Q
What is another name for IGFs?
A
somatomedins
21
Q
What type of receptor does IGF-1 and growth hormone act on?
A
kinase-linked receptors
22
Q
What is IGF-1 particularly important for?
A
bone growth
23
Q
What are the steps of how growth hormone works?
A
- GH and IGFs both act through a kinase-linked receptor
- binding causing phosphorylation of second messengers
- causes intracellular cascade and cellular responses
24
Q
What are the 3 effects of GH on protein synthesis?
A
- increased uptake of amino acids into cells - due to increased activity of AA transporters
- increased translation of proteins due to increased synthesis of enzymes
- increased transcription of genes involved in cell growth
25
What are the DIRECT effects of GH?
1. metabolic effects
2. increased protein synthesis
3. increased fat breakdown
4. increased blood glucose
26
What are the INDIRECT effects (via IGFs) of GH?
1. increased cell size, number and differentiation
2. increased protein synthesis
3. increased bone growth
27
What stimulates GH secretion?
it is released in response to growth hormone releasing hormone (GHRH) from the hypothalamus
28
What is GH release inhibited by?
growth hormone inhibiting hormone (GHIH or somatostatin) from the hypothalamus
29
What does too little GH lead to?
1. dwarfism
2. accelerated ageing
30
What 3 factors can cause dwarfism?
1. anterior pituitary dysfunction
2. growth hormone deficiency
3. normal growth hormone but genetic IGF deficiency
31
What causes accelerated ageing?
loss of growth hormone after adolescence leading to decreased protein synthesis
32
What does too much GH lead to?
1. gigantism
2. acromegaly
33
What causes gigantism?
an early life pituitary tumour
34
What causes acromegaly?
a pituitary tumour after adolescence - like gigantism but later in life
35
What is the structure of thyroid gland tissue?
it is made up of 2 main cell types and organised into follicles
36
What is the structure of each follicle?
each follicle is filled with thyroglobulin and lined by follicular cells
37
What is thyroglobulin?
a precursor to thyroid hormones
38
Where are the parafollicular cells (C cells) found?
between follicles
39
What do the parafollicular cells do?
secrete calcitonin, which helps regulate calcium level
40
What are the 2 hormones of the thyroid gland?
1. triiodothyronine (T3)
2. thyroxine (T4)
41
Which mineral is essential in the diet for thyroid hormone synthesis?
iodine
42
What are the steps of the synthesis of thyroid hormones?
1. tyrosine is iodinated to make mono-iodotyrosine (MIT)
2. iodinated again to form di-iodotyrosine (DIT)
3. add together 2 diiodotyrosine, you get thyroxine (T4)
4. add together 1 mono-iodotyrosine and 1 di-iodotyrosine and you get T3, triiodothyronine
43
What are the steps of T3 and T4 release?
1. occurs in thyroid follicle cells
2. follicle cells actively accumulate iodine from iodine pumps
3. thyroid peroxidase catalyses oxidation of I- to I2
4. iodinated thyroglobulin contains T3 and T4 and is stored
5. lysosomal enzymes in the follicle cells break down thyroglobulin and release T3 and T4 into cytoplasm of follicle cells
6. hormones transported in blood
44
How much T3 and T4 is 'free' and unbound in the blood to enter target tissues?
only 10%
45
How is the release of T3 and T4 regulated?
1. hypothalamus releases TRH - thyrotropin releasing hormone
2. causes anterior pituitary to release TSH - thyroid stimulating hormone
3. somatostatin (GHIH) can inhibit release of TSH
4. TSH increases iodine uptake due to more transporters
5. increased T3 and T4 synthesis
6. T4 converted to T3 in target tissues - has most effects
7. negative feedback to hypothalamus and pituitary and positive feedback on somatostatin release
46
What are the 3 main effect of thyroid stimulating hormone (TSH)?
1. increases iodine uptake by increasing expression of ATP-dependent sodium-iodine transporter
2. increases thyroid peroxidase
3. increases thyroglobulin movement into follicle cells and breakdown by lysosomal enzymes
47
What is the main role of the thyroid hormones?
homeostatic regulators which stimulate protein, lipid and carbohydrate metabolism
48
How do thyroid hormones increase metabolism?
they act on mitochondrial receptors to regulate the rate of oxidative phosphorylation
49
Which 2 types of receptor can T3 and T4 bind to?
1. nuclear receptors
2. mitochondrial receptors
50
What are the effects of thyroid hormones on mitochondrial receptors?
1. T3/T4 binds to mitochondrial receptor (kinase-linked)
2. phosphorylation of a 2nd messenger causes enzyme cascade
3. stimulates ATP synthesis and increases energy output of cell
4. also increases the size and number of mitochondria
51
What are the effects of thyroid hormone on nuclear receptors?
1. T3/T4 binds to nuclear receptor
2. T3-TR complex binds to thyroid hormone response elements (TREs) on DNA
3. regulates gene transcription for genes involved in enzyme synthesis
4. increase in enzyme synthesis
52
How do thyroid hormones increase the basal metabolic rate (BMR)?
1. TH binding to mitochondrial receptors increase the size, number and SA of mitochondria
2. increased rate of ATP production
3. also TH binding to nuclear receptors causes increase in Na-K ATPase pump which uses ATP for oxidative phosphorylation
4. both effects lead to increase production of ATP, therefore heat and BMR
53
How do thyroid hormones stimulate protein metabolism?
1. TH increase synthesis of proteins and proteases
2. increases protein synthesis leads to tissue growth
3. increased protease synthesis leads to increased protein breakdown
4. protein breakdown means more energy is expended
5. increased BMR
6. the balance between anabolism and catabolism is thyroid-hormone dependent
54
How does thyroid hormone stimulate carbohydrate metabolism?
1. binding of TH to TH nuclear receptor increases general enzyme synthesis
2. leads to increased gluconeogenesis, glycogenolysis, glucose uptake and release of insulin
55
How does thyroid hormone stimulate fat metabolism?
1. binding of TH to nuclear TH receptor increase lipoprotein receptors on liver cells and lipase synthesis
2. lipase synthesis means more lipid metabolism
3. increase in free fatty acids
4. increased lipoprotein receptor on liver cells means increased bile cholesterol secretion
5. increased cholesterol secretion leads to decreased plasma cholesterol
56
What are the 5 main areas of the effects of thyroid hormone?
1. cardiovascular
2. muscle
3. body weight
4. GI tract
5. CNS
6. respiration
57
What are symptoms of hypOthyroidism?
increased weight, cold intolerance, mental sluggishness, fatigue
58
What are the symptoms of hyPERthyroidism?
decreased body weight, irritability, heat intolerance
59
What is the structure of an underactive thyroid follicle?
1. high storage of thyroglobulin
2. increased storage of TSH
3. flattened cells
60
What is the structure of a highly active thyroid follicle?
1. low colloid levels - not storing much thyroglobulin
2. columnar cells
61
What causes hypOthyroidism?
autoimmune disease or iodine deficiency or altered pituitary activity
62
What causes hyPERthyroidism?
thyroid tumour or Grave's disease
63
What is Grave's disease?
antibodies bind to TSH hormone receptors and cause the thyroid to release hormones - antibodies act as an agonist
64
What are the 3 types of hormone released by the adrenal gland?
1. catecholamines (adrenaline)
2. mineralocorticoids (aldosterone)
3. glucocorticoids (cortisol)
65
Where are the catecholamines release from?
adrenal medulla
66
Where are the mineralocorticoids released from?
the adrenal cortex
67
Where are the glucocorticoids released from?
the adrenal cortex
68
What are the steps of synthesising catecholamines?
1. tyrosine is converted to DOPA by tyrosine hydroxylase
2. DOPA is converted to dopamine by DOPA decarboxylase
3. dopamine is converted to noradrenaline by dopamine hydroxylase
4. adrenaline is formed by N-methl transferase and can be converted to different intermediates
5. adrenaline is metabolised to vanillylmandelic acid and excreted
69
How is the secretion of catecholamines regulated?
1. adrenal medulla is part of the sympathetic NS
2. can be considered as a group of postganglionic neurones
3. acetylcholine synapses onto adrenal medulla
4. causes release of adrenaline
70
What are the effects of catecholamines?
essentially the same as sympathetic nerve activation, but effects last much longer
71
What are the steps of synthesising mineralocorticoids and glucocorticoids in the adrenal cortex?
1. cholesterol is the main precursor
2. requires expression of many enzymes
3. cholesterol -> pregnenolone -> progesterone -> deoxycorticosterone -> corticosterone -> aldosterone
72
What are the actions of aldosterone (mineralocorticoids)?
binds to nuclear receptors and:
1. stimulates reabsorption of Na+ and excretion of K+ in collecting ducts
2. decreases ratio of Na+ to K+ in sweat and saliva to excrete it
3. increases reabsorption of Na+ in the colon and excretion of K+ in the faeces
73
What is the overall effect of aldoesterone?
to keep Na+ in the body, to ensure that water moves into the blood by osmosis to increase plasma volume and blood pressure
74
How does the renin-angiotensin system work?
1. blood pressure decrease detected by mechanoreceptors
2. kidneys release renin in response
3. renin is converted to angiotensin I in the liver
4. angiotensin I is converted to angiotensin II in the lungs
5. angiotensin II acts on the adrenal glands to release aldosterone
6. aldosterone increases Na+ reabsorption, increasing blood pressure
75
What are 3 types of drugs that affect aldosterone actions?
1. aldoesterone antagonist
2. angiotensin coverting enzyme (ACE) inhibitors
3. ATII antagonist
76
What is an example of an aldosterone antagonist?
spironolactone
77
What are examples of ACE inhibitors?
captopril, enalapril
78
What is an example of an ATII antagonist?
losartan
79
How is glucocorticoid secretion regulated?
1. hypothalamus releases CTRH - corticotropin releasing hormone
2. acts on pituitary gland to release adrenocorticotropic hormone (ACTH)
3. acts on adrenal medulla to release cortisol
4. negative feedback to hypothalamus and pituitary
80
How do cortisol levels change throughout the day?
they have a circadian rhythm and are highest when waking and lowest going to bed
81
What are the effects of glucocorticoids?
1. stimulate gluconeogenesis to increase glucose
2. increase plasma glucose
3. synthesis of enzymes involved in the breakdown of macromolecules to allow gluconeogenesis
82
What are the effects of cortisol on the liver?
1. cortisol binds to nuclear receptors
2. increases gene transcription for enzymes involved in metabolism - increased proteases and lipases for increase gluconeogenesis
3. increases amino acid transporters - more amino acids transported into liver cells for breakdown
4. increased plasma glucose
83
What is Addison's disease?
cortisol deficiency
84
What are some symptoms of Addison's disease?
hypoglyceamia, fatigue, hypotension, anaemia
85
What is Cushing's disease?
excess of cortisol
86
What happens if there is an excess of corticosteroids?
1. rise in plasma glucose
2. increase in protein breakdown, causing muscle wastage
3. rise in fatty acid plasma levels
87
What are the symptoms of cushing's disease?
hyperglycaemia, depression, hypertension, increased blood volume
88
