Endocrine Organs Flashcards
1
Q
Which ectodermal groove of the pharyngeal arches is the only one that doesn’t fully zip up and why?
A
The ectodermal groove between the 1st and 2nd arch, because it forms the external auditory meatus.
2
Q
Why does the first pharyngeal arch divide in two?
A
It contributes to the maxilla and the mandible which are either side of the stomodeum.
3
Q
What are the three layers of a pharyngeal arch?
A
Endodermal pouch
Mesodermal arch
Ectodermal groove
4
Q
What does the oropharyngeal membrane separate?
A
Ectodermal derivatives (on the side of the primitive mouth cavity), from endodermal derivatives (on the side of the pharyngeal apparatus).
5
Q
What 4 things does each pharyngeal arch give rise to?
A
Muscle
Cranial nerve
Cartilage
Artery
6
Q
Which cranial nerves are each of the pharyngeal arches and all their muscle derivatives innervated by?
A
1st = trigeminal 2nd = facial 3rd = glossopharyngeal 4th = superior laryngeal branch of vagus 6th = recurrent laryngeal branch of vagus
7
Q
Which muscles does each pharyngeal arch give rise to?
A
1st = muscles of mastication
2nd = muscles of facial expression
3rd = stylopharyngeus muscles
4th + 6th = muscles of larynx and pharynx
8
Q
Which bones are formed from the cartilage derived from each pharyngeal arch?
A
1st = maxilla and mandible
2nd + 3rd = hyoid bone
9
Q
Which artery supplies the derivatives of each pharyngeal arch?
A
1st = maxillary and external carotid 2nd = hyoid artery 3rd = common carotid and internal carotid 4th = right subclavian artery and left aortic arch 6th = pulmonary arteries and ductus arteriosus
10
Q
What attaches the hypothalamus to the pituitary?
A
Infundibulum
11
Q
Which region of the brain is the hypothalamus part of?
A
Diencephalon
12
Q
What houses the pituitary?
A
Sella turcica (pituitary fossa) in sphenoid bone.
13
Q
What are the two lobes of the pituitary gland?
A
Anterior = adenohypophysis Posterior = neurohypophysis
14
Q
What is the adenohypophysis a derivative of?
A
Oral ectoderm, from the roof of the mouth
15
Q
What is the neurohypophysis a derivative of?
A
Neuroectoderm, from the diencephalon
16
Q
How does the pituitary gland form?
A
The hypophyseal diverticulum (Rathke’s pouch) grows up from the oral cavity, and the neurohypophysis grows down to meet it.
17
Q
How are intracranial, intraosseous, and pharyngeal accessory anterior lobe tissue formed?
A
If the stalk of the hypophyseal diverticulum doesn’t regress properly.
18
Q
Describe the hypothalami-hypophyseal portal system.
A
The superior hypophyseal artery (branch of internal carotid) supplies blood to the primary plexus of the portal system which is just at the junction between the median eminence of the hypothalamus and the infundibulum.
The neurosecretory cells of the hypothalamus release hormones into the primary plexus which are then carried in the hypophyseal portal veins to the secondary plexus in the anterior pituitary, where they stimulate the endocrine cells.
The anterior pituitary released hormones into the anterior hypophyseal veins which drain into the cavernous sinus.
19
Q
How are hormones released from the posterior pituitary gland?
A
Neurosecretory cells from the paraventricular cells store oxytocin in synaptic terminals in the posterior pituitary, and neurosecretory cells from the suprachiasmic nucleus store vasopressin in synaptic terminals in the posterior pituitary. The inferior hypophyseal artery (from the internal carotid artery) supplies blood to the capillary plexus of the infundibular process, into which oxytocin and vasopressin are released on nervous stimulation.
Blood then drains into the posterior hypophyseal arteries and into the cavernous sinus.
20
Q
What is the histology of the adenohypophysis?
A
Highly vascular, with cords of epithelial cells wrapped around capillary beds.
21
Q
What are some types of endocrine cells found in the adenohypophysis?
A
Somatotrophs - secrete growth hormone
Mammotrophs - secrete prolactin
Corticotrophs - secrete adrenocorticotropic hormone and melanocyte-stimulating hormone
Thyrotrophs - secrete thyroid stimulating hormone
Gonadotrophs - secrete luteinising hormone and follicle stimulating hormone
22
Q
What two types of cells make up the neurohypophysis?
A
Mostly unmyelinated axons, also pituicytes (specialised glial cells)
23
Q
At what level is the thyroid gland usually found?
A
Level of the cricoid cartilage (isthmus just at the top of the cricoid cartilage)
24
Q
What is the lobe of the thyroid gland that is the most common remnant of the thyroglossal duct, and why is it important to remember it may be there?
A
Pyramidal lobe, highly vascular so caution is needed in the event of an emergency tracheotomy.
25
What contributes to the capsule of the thyroid gland?
Pretracheal fascia
26
Where does the blood supply to the thyroid gland come from?
Superior thyroid artery from the external carotid artery, inferior thyroid artery from the thyrocervical trunk from the subclavian artery.
27
Where does blood from the thyroid gland drain?
Superior and middle thyroid veins into the internal jugular vein.
Inferior thyroid vein into the brachiocephalic vein.
28
Why does thyroidectomy carry a risk of leaving the patient with a hoarse voice?
Damage can be done to the recurrent laryngeal nerve, which paralyses part of the vocal cords.
29
What is the pit called from which the thyroid gland starts developing, and where is it?
Thyroid primordium, develops between the floor of the 1st and 2nd pharyngeal arch, and burrows down through the developing tongue to the hypobranchial mesoderm.
30
As the thyroid primordium burrows down, what does it form, and what is the lumen of this structure called?
Thyroid diverticulum.
| Lumen = thyroglossal duct
31
What is the opening of the thyroglossal duct called?
Foramen cecum
32
What is the difference between where the thyroid gland develops and where the parathyroid glands develop?
The thyroid gland develops in the midline, the parathyroid glands develop on either side and migrate down and medially.
33
What do you call remnants of the thyroglossal duct which remain as thyroid tissue but are not attached to the thyroid itself?
Ectopic remnants of thyroid descent (accessory thyroid tissue) e.g lingual thyroid, cervical thyroid
Always solid midline swellings
34
What do you call the fluid-filled swellings formed by incomplete closure of the thyroglossal duct?
Thyroglossal duct cysts e.g lingual thyroglossal duct cyst, cervical thyroglossal duct cyst
Midline fluid filled swellings
35
What makes the thyroid different to other endocrine tissue?
It stores a precursor to its secretory product extracellularly.
36
What is a thyroid follicle comprised of?
Colloid, surrounded by a layer of follicular cells, surrounded by a basement membrane.
37
What type of epithelium are the follicular cells in the thyroid?
Cuboidal epithelium
38
What are the cells other than follicular cells in the thyroid?
Parafollicular (C) cells, which are larger, more darkly staining and found in between the follicles. They secrete calcitonin which is involved in calcium homeostasis.
39
How many parathyroid glands are there in total?
4 - 2 superior and 2 inferior
40
Where are the parathyroid glands, and where do they get their blood supply?
Enclosed in the capsule of the thyroid gland posteriorly, although position is variable, and usually supplied by superior and inferior thyroid arteries.
41
What are the two types of cells in the parathyroid gland?
Majority = chief/principal cells which secrete parathyroid hormone, and are found in a cord-like structure wrapped around a capillary bed
Also oxyphil cells, which have uncertain function
42
Where do the superior and inferior parathyroid glands originate?
Inferior parathyroid glands = endodermal groove below 3rd pharyngeal arch
Superior parathyroid glands = endodermal groove below 4th pharyngeal arch
43
What do you call the remnant of an ectodermal groove that hasn't fully zipped up, and how are they different to thyroglossal duct cysts?
Cervical sinus/cyst - will be on one side or the other, not in the midline like thyroglossal duct cysts
44
What is formed from where the ectoderm and endoderm of the groove under the first pharyngeal arch meet?
Tympanic membrane (ear drum)
45
Where do the palatine tonsils form?
Endodermal groove under 2nd pharyngeal arch
46
Where does the thymus form?
Endodermal groove under 3rd pharyngeal arch
47
What is endocrinology?
The study of glands and the hormones they produce.
48
What is the difference between exocrine and endocrine?
Exocrine is when the molecules are emptied into a lumen or onto a surface. Endocrine is when the product is secreted internally into the blood.
49
What is homeostasis?
Physiological factors held to a precise value called the Set Point
50
What are hormones?
Chemical messengers produced by an endocrine gland which have a specific effect on a target tissue. The purpose of hormones is to maintain homeostasis.
51
What are the two classifications of hormones based on their solubility?
```
Lipid-soluble = hydrophobic, require transport proteins in the blood, receptors in cytosol of cell, affect gene transcription
Water-soluble = hydrophilic, don't need transport proteins in the blood, receptors on cell surface, GPCR triggers second messengers to control changes inside the cell
```
52
What are the two classifications of hormones based on the molecule they are derived from?
Tyrosine-derived hormones = catecholamines (dopamine, noradrenaline, adrenaline), and thyroid hormones
Cholesterol-derived hormones = prostagens, androgens, oestrogens, corticosteroids
53
How many rings are there in the typical steroid structure?
4
54
Where are the cell bodies of the neurosecretory cells that control the neurohypophysis?
```
Paraventricular nucleus (release oxytocin)
Suprachiasmic nucleus (release vasopressin)
```
55
Name some functions of the hypothalamus.
```
Regulates appetite
Regulates body temperature (via TRH)
Regulates Circadian Rhythms
Interacts with Limbic system
Hormone production
Endocrine regulation
Autonomic nervous system regulation
```
56
What controls the adenohypophysis?
Tropic hormones in the hypothalami-hypophyseal system.
57
What are the two inhibitory hormones released by the hypothalamus to the anterior pituitary?
Dopamine (prolactin inhibiting factor)
| Somatostatin (inhibits release of GH from somatotrophs)
58
What are some stimulating hormones released by the hypothalamus to the anterior pituitary?
GnRH - stimulates gonadotrophs
CRH - stimulates corticotrophs
TRH - stimulates thyrotrophs
GHRH - stimulates somatotrophs
59
Describe the Hypothalamo-Pituitary-Adrenal Axis.
The hypothalamus is stimulates by cortical areas or by the Limbic system (amygdala stimulates, hippocampus inhibits), and releases Corticotropin Releasing Hormone into the hypophyseal portal veins.
CRH stimulates the corticotrophs in the anterior pituitary to release Adrenocorticotropic Hormone.
ACTH acts on the cortex of the adrenal glands and stimulates the release of cortisol.
Cortisol has a negative feedback effect on the hypothalamus.
60
In what physiological response is the HPA axis required to maintain blood pressure and blood glucose?
The stress response
61
What does too little cortisol cause?
Addison's disease (hypoadrenalism)
62
What does too much cortisol cause?
Cushing's syndrome
63
What is it called when destruction of the adrenal cortex leads to reduced output of the adrenal hormones (glucocorticoids and mineralocorticoids), and what is the most common cause?
Primary adrenal insufficiency (hypoadrenalism/Addison's)
| Most common cause = autoimmunity
64
What is a symptom of Addison's that is not present in secondary adrenal insufficiency, and what causes it?
Hyperpigmentation of lips, elbows, gums (buccal mucosa), scars, palmar creases.
Caused by the positive feedback leading to an increase in ACTH production by the anterior pituitary, but the precursor of ACTH is proopiomelanocortin (POMC) which also forms melanocyte-stimulating hormone (aMSH). aMSH increases production of melanin which leads to darkened skin.
65
What are the 4 things all derived from POMC?
Adrenocorticotropic Hormone
Melanocyte Stimulating Hormone
Melanocortin Stimulating Hormone
Enkephalins (endogenous opioid peptides)
66
What is an example of secondary adrenal insufficiency?
A pituotary tumour that crushes the pituitary cells by growing in the confined space of the sella turcica.
67
Why does hyperpigmentation not occur in secondary adrenal insufficiency?
There is a problem with the pituitary gland so POMC is not produced.
68
What is the stimulation test used to diagnose secondary adrenal insufficiency?
Administer exogenous ACTH and measure whether there is a rise in cortisol level.
69
What is it called when there is a problem with the hypothalamus causing inadequate stimulation of the adrenal cortex?
Tertiary adrenal insufficiency
70
Why is dynamic function testing needed to test these hormones?
The hormones tend to be produced cyclically, with peaks and troughs, so one random test of the level may give misleading information as to their overall function. Instead, test the levels over a time period.
71
What sort of dynamic function test is used if you suspect insufficiency, and what type if you suspect over functioning?
Suspect insufficiency - stimulation test
| Suspect over functioning - suppression test
72
What stimulation test is used to diagnose primary adrenal insufficiency?
Measure baseline cortisol
Inject SYNACTHEN intramuscularly
Measure cortisol after 30 minutes
Cortisol should have increased if adrenal cortex responds normally
A suboptimal rise in cortisol confirms primary adrenal insufficiency
73
What is synacthen?
Synthetic ACTH, used in stimulation test to distinguish primary and secondary adrenal insufficiency
74
What is the insulin stress test used to diagnose, and how does it work?
Used to diagnose secondary primary insufficiency.
1) Baseline cortisol is measured
2) Insulin is administered to induce hypoglycaemia and activate the stress response
3) The stress response activates the HPA axis and leads to CRH release from the hypothalamus
4) A suboptimal rise in cortisol confirms secondary adrenal insufficiency
75
What is the test called where insulin and GnRH and TRH are all administered, and then the levels of cortisol, LH, FSH, T4 and T3 are measured to see if there has been an optimal rise?
Combined Pituitary Stimulation Test
76
What is the problem with using the Synacthen test to diagnose secondary adrenal insufficiency?
If ACTH is not being produced then the adrenal cortex will not be being stimulated and will atrophy. This means there could be a suboptimal rise in cortisol even though it is not primary adrenal insufficiency.
The solution is to administer Synacthen over a week and see if the adrenal cortex "wakes up".
77
What are some characteristics of hypercortisolaemia (Cushing's syndrome)?
```
Poor wound healing and muscle wasting due to protein depletion.
Hyperglycaemia.
Hyperlipidaemia.
Bone dissolution and osteoporosis.
Central obesity, with thin arms and legs.
Buffalo hump.
Thin skin.
Diabetes.
Hypertension.
Bruising.
```
78
What causes Cushing's disease?
A pituitary tumour secreting ACTH
79
What is the suppression test used to diagnose Cushing's disease?
Dexamethasone Suppression Test.
Administering dexamethasone should suppress endogenous glucocorticoid release due to the negative feedback effect. In Cushing's disease there will be no suppression because the pituitary tumour is autonomous and not controlled by negative feedback of the HPA axis.
80
What are the advantages of using dexamethasone in the suppression test for Cushing's disease?
Dexamethasone is a very potent glucocorticoid because it is so pure.
Dexamethasone is not detected by cortisol assays in the lab, so cortisol production can still be accurately measured even after dexamethasone has been administered.
81
What is one symptom of primary adrenal insufficiency that is also found in secondary hypercortisolaemia?
Hyperpigmentation, because excess ACTH is produced so there is increased POMC.
82
Describe the Hypothalamo-Pituitary-Thyroid axis.
Higher cortical areas stimulate the hypothalamus (e.g due to a exposure to cold) which releases Thyrotropin Releasing Hormone.
TRH acts on thyrotrophs in the anterior pituitary to stimulate release of Thyroid Stimulating Hormone.
TSH acts on the thyroid and increases activity of Thyroid Peroxidase enzyme to increase production of the thyroid hormones T4 and T3.
The thyroid hormones have a negative feedback effect on the hypothalamus and pituitary.
83
Describe the Hypothalamo-Pituitary-Gonadal axis.
The hypothalamus releases Gonadotropin Releasing Hormone.
GnRH acts on gonadotrophs in the anterior pituitary to stimulate release of Luteinising Hormone and Follicle Stimulating Hormone.
In the male, LH stimulates Leydig cells to secret androgens, and FSH stimulates Sertoli cells to express androgen receptors and secrete Inhibin B.
In the female, LH stimulates theca cells to secrete androgens and stimulates ovulation and eventually the switch from secreting oestrogen to secreting progesterone. FSH stimulates granulosa cells to produce aromatase to produce oestrogen, and also to secrete inhibin B and AMH.
84
What are the principal steroid hormones in the HPG axis?
Progestagens (21C)
Androgens (19C)
Oestrogens (18C)
85
What is the rate limiting step in the conversion of acetate to cholesterol to progesterone, and where in the cell does it occur?
Conversion of cholesterol to pregnenolone, which occurs in the mitochondria.
86
What is an example of primary hypogonadism?
Menopause
87
What happens to blood levels of oestrogen/testosterone and LH and FSH in primary hypogonadism?
The levels of oestrogen/testosterone decrease, but LH and FSH increase due to the positive feedback effect.
88
What is an example of secondary hypogonadism?
Klinefelter's syndrome
89
What happens to blood levels of oestrogen/testosterone and LH and FSH in secondary hypogonadism?
Low levels of oestrogen/testosterone, and low FSH and LH.
90
What happens to blood levels of oestrogen/testosterone and LH and FSH in anabolic steroid abuse?
High oestrogen/testosterone, and low LH and FSH.
91
How can the HPG axis be down regulated so that the blood levels of oestrogen/testosterone and of LH and FSH are all low?
Giving a CONSTANT infusion of GnRH analogues.
92
How can the HPG axis be up regulated so that the blood levels of oestrogen/testosterone and of LH and FSH are all high?
Giving a PULSATILE infusion of GnRH analogues.
93
How is release of prolactin by the anterior pituitary inhibited?
Dopamine binding to D2 receptors in the tubero-infundibular pathway.
94
What are the effects of prolactin?
Lactation, and amenorrhea (infertility).
95
What can cause hyperprolactinaemia?
D2 receptor antagonists (antipsychotics), or a prolactin secreting tumour in the anterior pituitary.
96
How does prolactin cause milk to be produced?
When the baby starts to suck, nerve cells in the mother's breast activate the hypothalamus, which activates the anterior pituitary to secrete prolactin.
Prolactin stimulates the production of milk from the milk glands in the mother's breast.
The more the baby sucks, the more prolactin is secreted, and the more milk is produced. This is a positive feedback system to ensure the ilk supply keeps up with demand.
97
What are metoclopramide, and bromocriptine?
```
Metoclopramide = D2 receptor antagonist (antiemetic and prokinetic) which can cause hyperprolactinaemia
Bromocriptine = dopamine agonist
```
98
Why is it hard to measure Growth Hormone levels in the blood and what is measured instead?
The level of Growth Hormone fluctuates, so instead we measure Insulin-Like Growth Factor 1 (IGF-1) which is produced in the liver and is the main mediator of the effects of Growth Hormone.
99
What does Growth Hormone have a role in?
Growth and development and the stress response.
100
Where is IGF-1 produced?
In the liver, on stimulation by GH.
101
What is the most common cause of acromegaly?
Excessive GH secretion from a pituitary adenoma.
102
What does acromegaly cause?
Overgrowth of all organ systems, bones, joints, soft tissues.
Typical features are abnormally large hands and feet, large prominent facial features, enlarged tongue, deep voice, abnormally tall height (if the acromegaly occurs before puberty).
103
What is ocreotide and what is it used for?
Ocreotide is an analogue of somatostatin that can be used to treat acromegaly.
104
How is release of vasopressin stimulated?
Osmoreceptors in the hypothalamus detecting that the blood is hypertonic, baroreceptors detecting the blood is hypovolaemic.
105
What is the role of vasopressin?
It is involved in the control of blood volume and acts on the nephron to increase water resorption.
106
Why will your ADH levels have already increased significantly by the time you actually feel thirsty?
ADH is controlled by the hypothalamus so is minutely sensitive to changed in fluid levels.
107
What two chemicals can cause polyuria?
Caffeine, alcohol
108
What is the synthetic peptide analogue of vasopressin used to distinguish between neurogenic and nephrogenic diabetes insipidus?
Desmopressin
109
What is the reflex called that is caused by oxytocin and what does it involve?
"Letdown" reflex - in breastfeeding mothers, oxytocin acts on the mammary glands to allow milk to be "let down" into the subareolar sinuses to be excreted via the nipple.
110
What effect does oxytocin have on the uterus and what stimulates it to be secreted?
Stretching of the cervix and uterus stimulates release of oxytocin, and oxytocin had a role in stimulating uterine contraction during labour.
111
What other things does oxytocin have a role in?
Social behaviour, anti-inflammation and wound healing, oxytocin increases contraction of smooth muscle.
112
Why can oxytocin be used to stop bleeding following delivery of a baby?
It causes vasoconstriction so prevents haemorrhage.
