Endocrine Flashcards
1
Q
describe the structure of the thyroid gland
A
2 lobes connected via the isthmus
2
Q
where is the thyroid gland located
A
in the anterior of the neck between C5 and T1
wrapped around the cricoid cartilage and the superior rings of the trachea
3
Q
describe the blood supply and drainage around the thyroid
A
- arterial supply =
- superior thyroid artery
- 1st branch of the external carotid artery
- supplies superior and anterior porteions of the gland
- inferior thyroid artery
- arises from the subclavian artery
- supplies the inferior portion of the gland
- superior thyroid artery
- venous drainage
- drained by the superior, middle and inferior thyroid veins
- The superior and middle veins drain into the internal jugular vein and the inferior empties directly into the brachiocephalic vein.
4
Q
how is the thyroid gland innervated
A
via the sympathetic trunk in the cervical ganglion BUT do not control secretion of hormones
5
Q
why is the thyroid gland highly vascularised
A
it secretes hormones directly into the blood
6
Q
what controls hormone release from the thyroid
A
the HPT axis
the anterior pituitary gland via TSH, which is stimulated by TRH from the hypothalamus
7
Q
label
A
8
Q
what are the major hormones of the thyroid
A
- T3 - triiodothyronine
- T4 - thyroxine
- 3 and 4 indicate the number of iodine molecules in each hormone
- Calcitonin
9
Q
where are thyroid hormones produced
A
in the follicle cells which are arranged in lobules with a lumen called colloid
10
Q
how do thyroid hormones take effect
A
via nuclear receptors in target tissues to increase metabolic rate
11
Q
give examples of processes affected by thyroid hormones
A
- Basal Metabolic Rate
- Gluconeogenesis
- Glycogenolysis
- Protein synthesis
- Lipogenesis
- Thermogenesis
12
Q
describe the process of thyroid hormone synthesis
A
ATE ICE
-
Active transport
- the sodium-iodide symporter [NIS] actively transports iodide into the follicular cell
- the iodide molecules pass into the colloid by pendrin
-
Thyroglobulin production
- the RER of the follicular cells produce thyroglobulin and it’s packaged by the golgi body
-
Exocytosis
- the packaged thyroglobulin is transported out of the cell by exocytosis into the follicular lumen = colloid
-
Iodination
- the iodide molecules are converted → iodine by thyroid peroxidase.
- the tyrosine molecules on the thyroglobulin have 1 or 2 iodine molecules attached to them → monoiodotyrosine MIT or diiodotyrosine DIT.
-
Coupling
- MIT + DIT = T3
- DIT + DIT =T4
- this occurs while still attached to thyroglobulin
-
Endocytosis
- the iodinated thyroglobulin molecules are endocytosed back into the follicular cells
- thyroglobulin then undergoes proteolysis → free T3 and T4.
13
Q
which is more active?
which is more abundant?
T3 or T4
A
T3 is 10 times more active than T4
T4 is more abundant as it is more stable and has a longer half-life than T3.
T4 is converted into T3 at the target tissue
14
Q
how is T4 converted to T3
A
via deiodinase
15
Q
describe the HPT axis [hypothalamic-pituitary-thyoid axis]
A
- the hypothalamus releases TRH
- TRH stimulates the anterior pituitary to release TSH
- TSH acts on the thyroid gland to synthesise and secrete T3 and T4
- T4 is converted to T3 at target tissue
- T3 inhibits the hypothalamus and stops the release of TRH
16
Q
when do the thyroid thyroid glands start producing thyroxine in utero
A
18-20 weeks
17
Q
overall actions of the thyroid hormones
A
increases metabolic rate
important in brain maturation
18
Q
how many parathyroid glands are there
where are they located
A
4
2 superior and 2 inferior
posterior lateral aspect of the thyroid glands
19
Q
how are the parathyroid glands innervated
A
by the sympathetic trunk
this does not control hormone secretion
20
Q
describe the blood supply to the parathyroid glands
A
the inferior thyroid artery - branch of the subclavian
drained by the thyroid plexus
21
Q
what hormone does the parathyroid secrete
what does it do
A
parathyroid hormone
it regulates phosphate and calcium levels
22
Q
what triggers release of PTH
A
- low calcium
- high phosphate
23
Q
function of calcitonin and which gland releases it
A
- regulates calcium levels, when present in large amounts it decreases calcium and vice versa
- released by the thyroid gland
24
Q
the anterior and posterior pituitary glands develop from the same tissue
T/F
A
False
they develop from different tissues grow next to each other then join together
25
what is the anterior pituitary gland formed from
the upward protrusion of ectoderm from Rathke's pouch = adenohypophysis
26
what is the posterior pituitary form from
it is a neuronal extension of the neural components of the hypothalamus
27
how does the hypothalamus communicate with the anterior pituitary
* using hypophysiotropic hormones
* these hormones reach the anterior pituitary via the hypothalamo-hypophyseal portal vessels
* their action in the anterior pituitary is to stimulate or inhibit release of 6 hormones
28
how many hypophysiotropic hormones are there,
what are they
what do they do
5
1. **corticotropin releasing hormone [CRH]**
* stimulates release of adenocorticotropic hormone ACTH → increased cortisol produced in the adrenal cortex - zona fasiculata
2. **Growth hormone releasing hormone [GHRH]**
* stimulates release of growth hormone → growth and protein synthesis
* inhibited by somatostatin [which is produced in the hypothalamus and pancreas]
3. **thyrotropin-releasing hormone [TRH]**
* stimulates release of TSH from the anterior pituitary → stimulates synthesis and secretion of T3 and T4
4. **Gonadotropin-releasing hormone [GnRH]**
* stimulates release of LH and FSH → production of oestrogen, progesterone and testosterone in the gonads
5. **dopamine**
* inhibits release of prolactin
6.
29
how does the hypothalamus communicate with the anterior pit gland
via the hypothalamo-hypophyseal portal vessels
they share a blood network which allows the hormones released by the hypothalamus to reach and affect the APG
30
function of hypophysiotropic hormones
control the secretion of anterior pituitary hormones hormones
31
general role of the hypothalamus
* Important for homeostasis + primitive functions :–
* appetite, thirst, sleep, temperature regulation
* Control of autonomic function via brainstem autonomic centres
* Control of endocrine function via pituitary gland
32
how many hormone producing cell types are there in the APG
and how many hormones are produced
* 5 cell types
1. gonadotropes cells → FSH and LH
2. corticotropes cells → adrenocorticotropic hormone ACTH
3. somatotropes → growth hormone (GH);
4. Lactotropes → prolactin (PRL)
5. thyrotropes → TSH
* 6 hormones in total
33
which APG hormones have a negative feedback loop
all of them except for prolactin feedback negatively
34
which hypothalamic hormone is not involved in the 1st step of the 3 hormone sequence
dopamine
it is an inhibitory regulator of prolactin
35
what is short loop negative feedback
which hormones exhibit this
* where the anterior pituitary hormone act on the hypothalamus for negative feedback
* prolactin acts on hypothalamus → secretion of dopamine which inhibits the release of prolactin from APG
* GH acts directly on the APG and hypothalamus to inhibit GH and GHRH
* IGF stimulates somatostatin which acts on the APG to inhibit release of GH from the APG
36
what is long loop -ve feedback
which hormones exhibit this
* where the endocrine gland hormone → negative feedback on the hypothalamus or the APG
* all but PRL and GH
* cortisol
* T3, T4
* oestrogen, progesterone, testosterone
37
function of growth hormone
stimulates growth and protein synthesis
released in a pulsatile manner throughout life
38
effect of cortisol
* regulates stress response
* increased energy mobilisation
* salt/water balance
* reduced immune response
* reduced growth
39
function of prolactin
* lactation
* breast development
* increased testosterone production
40
whaich hormones are produced by the posterior pituitary gland
* oxytocin
* vasopressin
41
where is vasopressin synthesised
in the supraoptic nucleus
42
what stimulates release of vasopressin
1. increased osmotic pressure in the blood
2. decreased blood volume
3. trauma/ stress
4. increased PCO2
5. decreased PO2
43
what effects does vasopressin have
* it increases the expression of aquaporin 2 on the apical membrane of the primary cells in the collecting ducts of the kidney
1. vasopressin binds to V2 receptors in primary cells of renal collecting duct
2. triggers an intracellular cascade →
3. upregulation of aquaporin 2 proteins which are inserted on the apical membrane → increased permeability of collecting duct cells
4. **Water is reabsorbed from the renal collecting duct and returned to the blood stream, decreasing the plasma osmolality**
44
describe the -ve feedback system in high blood volume and low plasma osmolality
define osmolality
osmolality = the amount of solutes per kilo of solvent
45
describe the -ve feedback system in high plasma osmolality
define osmolality
osmolality = the amount of solutes per kilo of solvent
46
where is oxytocin produced
in the paraventricular nucleus
47
what triggers oxytocin release
triggered by nipple stimulation
48
what are the effects of oxytocin
* milk let down = constriction of muscles of the breast to promote milk ejection
* uterine smooth muscle contraction
* promotion of labour
49
describe the feedback mechanism of oxytocin
positive feedback
* uterine contraction stimulates the paraventricular nucleus further until labour
* suckling stimulates the paraventricular nucleus further until milk ejection
50
what is the bodies response to high calcium levels
releases calcitonin from the thyroid gland
51
where is calcitonin produced
in the parafollicular cells [c cells]
52
how does T3 and T4 travel in the blood
they are insoluble therefore they travel via transport proteins:
* albumin
* TBG
* tranthyretin
53
where are the adrenal glands located
supramedial aspect of the kidneys
retroperitoneal
54
describe the arterial blood supply of the adrenal glands
* **Superior adrenal artery** – arises from the inferior phrenic artery
* **Middle adrenal artery** – arises from the abdominal aorta.
* **Inferior adrenal artery** – arises from the renal arteries.
55
describe the venous drainage of the adrenal glands
* right kidney drains directly into the IVC
* left kidney drains into the left renal vein then into the IVC
56
what is the innervation of the adrenal glands
splanchnic nerve [sympathetic]
57
what are the hormones produced by the anterior pituitary gland
FLAGTOP
* Follicle stimulating hormone
* Leutenising hormone
* Adrenocorticotropic hormone
* Growth hormone releasing hormone
* Thyroid stimulating hormone
* O- melanocyte stimulating hormone
* Prolactin
58
describe the anatomy of the adrenal glands
* capsule
* cortex
* zona Glomerulosa
* mineraolcorticoids synthesis
* Zona Fascicularis
* Glucocorticoids synthesis
* Zona Reticularis
* androgens synthesis
* medulla
* catecholamine synthesis
59
describe adrenal gland vasculature
* arteries x3
* superior artery = branch of the inferior phrenic artery
* middle artery = branch of the abdominal aorta
* inferior artery = branch of the renal artery
* one vein drains the gland = the adrenal vein
* the right adrenal vein drains directly into the IVC as its is in close proximity
* the left adrenal vein drains into the left renal vein first
60
give examples of catecholamines
adrenaline and noradrenaline
61
how is the adrenal gland innervated
the splanchnic nerve
62
where is ADH produced
hypothalamus
63
which cells does ADH take effect in
principal cells of the collecting duct
64
what effect does ADH have
1. it binds to the V2R receptors of the principal cells →
2. upregulation of aquaporin channels in the collecting tubule walls →
3. increased H2O reabsorption and less urine produced
65
where is erythropoietin produced
what is its function
in the kidneys
increases production of RBCs in the bone marrow
66
what hormones are produced in the adrenal glands
1. Aldosterone
2. cortisol
3. corticosterone
4. DHEA
5. androstenedione
1= glomerulosa
2+3=fasciculata
4+5 = reticularis
67
what is the role of the adrenal medulla
* part of the autonomic nervous system
* production of catecholamines
* adrenaline 80% and noradrenaline20%
* main site for adrenaline synthesis
* production of catecholamines is dependent on cortisol levels [permissive effect]
68
what is the effect of catecholamine release
1. lipolysis in adipocytes
2. gluconeogenesis in liver and muscles
3. tachycardia and increased cardiac contractility
4. redistribution of circulatory volume
69
where are corticosteroids produced
in the adrenal cortex
70
how do corticosteroids work
* they are lipid soluble so can pass through the lipid membrane and:
* act on intracellular receptors
* alter gene transcription directly or indirectly
71
what are steroids and steroid hormones made from
cholesterol
72
role of ACTH
ACTH stimulates the synthesis of corticosteroids and cortisol acutely
73
where are glucocorticoids produced
in the zona fasciculata and reticularis
(more-so in fascicularis)
74
glucocorticoids are essential to life
T/F
true
* glucocorticoids are essential to life
75
what stimulates the production of glucocorticoids
* hypothalamus releasing CRH - corticotropin releasing hormone
* CRH→ APG causing release of ACTH
* ACTH acts on the zona fasciculata in the adrenal cortex to produce cortisol
76
what are the effects of cortisol and glucocorticoids
* Increase glucose mobilisation
* Augment gluconeogenesis
* Amino acid generation
* Increased lipolysis Important during “stress”
* Maintenance of circulation
* Vascular tone
* Salt and water balance
* Immunomodulation
* Dampen immune response
77
how are glucocorticoids transported
* In the circulation glucocorticoids are mostly bound to proteins –
* 90% bound to Corticosteroid-Binding Globulin (CBG)
* 5% bound to albumin
* 5% “free”
78
what fraction of glucocorticoids in blood are bioavailable
the free glucocorticoids are bioavailable thus ~5%
when stressed level of binding reduces so there is more free cortisol as CBG is cleaved
79
how is cortisol production regulated
via negative feedback
80
cortisol has a diurnal rhythm - what does this mean
the the secretion follows a daily cycle
cortisol secretion is higher in the morning and early afternoon
81
what factors stimulate cortisol secretion
stress
diurnal / circadian rhythm
cytokines
82
what is calssified as stress
* “The sum of the bodies responses to adverse stimuli”
* Infection
* Trauma
* Haemorrhage
* Medical illness
* Psychological
* Exercise/exhaustion
83
how does the HPA axis change in acute illness
1. there is less negative feedback so more cortisol is produced
2. less CBG synthesised and more broken down → more free cortisol
84
what are mineralocorticoid -give example
where are they produced
aldosterone
produced in the zona glomerulosa
85
function of aldosterone
* critical for salt and water balance in the:
* kidneys
* pancreas
* colon
* salivary glands
* sweat glands
86
what triggers aldosterone secretion
renin from the juxtaglomerular cells
87
effects of aldosterone secretion
* salt balance in th kidneys, colon, pancreas, salivary glands and sweat glands.
* in the kidneys it acts on the distal convoluted tubule and collecting duct
* increases epithelial Na+ channels and Na/K ATPase expression
88
where are adrenal androgens produced
in the zona reticularis
89
what androgens are produced in the adrenal glands
* DHEA
* androstenadione
90
what is the most abundant adrenal steroid
DHEA
91
which androgen has 1/10th adrongenic activty as testosterone
androstenedione
92
what is a major source of androgens in women
androstenedione and DHEA
93
what stimulates production of DHEA anandrostenedione
ACTH [not ghrh]
94
effect of high cortisol on sex hormones
* High cortisol levels inhibit the gonadotropin releasing hormone (GnRH) leading to
* decreased progesterone and oestrogen in females.
* Decreased testosterone and sperm count in males
95
hypothalamus
96
why doesn't DKA occur in T2DM usually
* the low level of insulin secretion maintained suppress catabolism and prevent ketogenesis
* can however occur if levels of noradrenaline rise high enough - e.g. MI
97
how does obesity → T2DM
* obesity impairs insulin action → insulin resistance
* also lipid deposits in the pancreas islets reduce normal insulin secretion.
98
how does HHS differ from DKA
* presence of low levels of insulin prevent lipolysis and therefore the formation of FFA → no ketones
* thus no ketosis in HHS
* HHS seen in T2DM where as DKA usually seen in T2DM
* HHS more likely to present with confusion where as DKA = abdominal pain and N+V
* features of HHS can develop **over days**, whilst DKA often occurs over hours.
99
when prescribing IV glucose for a hypo, what considerations do you need to make
* in pts with suspected thiamine deficiency, IV glucose can deplete thiamine levels in metabolic processes → Wernicke's encephalopathy.
* alcoholics are at risk
* **If IV glucose is needed in a malnourished or alcoholic patient, it should be given after, or alongside thiamine**
100
what causes Graves' disease?
* Graves’ disease is caused by thyroid stimulating antibodies that may cross the placenta
* Graves’ disease is caused by thyroid stimulating antibodies that may cross the placenta
101
what condition is strongly associated with Graves' disease
opthalmopathy:
* inflammatory condition of the orbit and periorbital tissues →:
* lid retraction
* swelling
* redness
* bulging eyes
* conjunctivitis
* lid lag
102
T/F
TPO and thyroglobulin antibodies are sensitive and specific
FALSE
TPO and thyroglobulin antibodies are sensitive but not specific
103
what antibody is indicative of Graves' disease
TSH-receptor stimulating antibody
104
T/F
Goitre is indicative of Hyperthyroidism
False
a goitre can indicate that there is an abnormality causing the thyroid gland to grow
so it can be present in hyper/hypothyroidism or even euthyroidism
105
symptoms of agranulocytosis
* sore throat
* fever
* mouth ulcers
* ask pt to stop drug immediately and arrange an FBC ASAP
106
how odes radio iodine work
beta particles are emitted from the radio iodine → ionisation of the thyroid cells which →:
* direct damage to the DNA and enzymes
* indirect damage via free radicals.
107
which antibody is associated with Hashimoto's
TPO antibodies
108
where _and_ what are the actions of parathyroid hormone
It does this through its actions on the _kidneys_, _bones_ and _intestine_:
1. **Bones** – parathyroid hormone stimulates the release of calcium from large calcium stores in the bones into the bloodstream via bone resorption.
2. **Kidneys** – increased calcium reabsorption by reducing loss of calcium in urine.
1. PTH also stimulates the production of active vitamin D in the kidneys.
2. There is also reduced phosphate rebasorption in the kidneys due to PTH
3. **Intestine** – PTH indirectly increases calcium absorption from food in the intestine, via its effects on vitamin D metabolism.
109
decreased Ca2+ affect PTH how
what are the down stream effects?
* it increases secretion of PTH →
* increased calcium reabsorption in the kidney and absorption in the gut and increased bone resorption - all to increase calcium levels
* decreases serum phosphate and increases urinary phosphate excretion.
110
why is calcium ion levels so tightly controlled by PTH
calcium is needed for nervous and muscle function.
hypocalcaemia → ECG abnormalities [long qt] seizures etc.
hypercalcaemia → ECG abnormalities [short qt] renal stones confusion/ coma etc.
111
equation for corrected calcium
total serum calcium + 0.02 \* (40 – serum albumin)
112
potential consequences of hypOcalcaemia
* Parasthesia
* Muscle spasm
* Hands and feet
* Larynx
* Premature labour
* Seizures
* Basal ganglia calcification
* Cataracts
* ECG abnormalities
* Long QT interval
* Chvostek’s and Trousseau’s signs
113
what syndrome most commonly causes hypoparathyroidism
Di Georges syndrome
113
what syndrome most commonly causes hypoparathyroidism
Di Georges
114
function of aldosterone + where is it made
* sodium ion retention → water retention → increased BP
* secreted from adrenal glands
115
function of ADH + where is it produced
* ADH regulate urine volume and osmolality by causing water reabsorption from the nephrons back into the blood when secreted
* secreted from the posterior pituitary glands
116
what is a contraindication for radio iodine therapy
pre-existing heart disease
117
what test is used to show toxic multi nodular goitre and what are the results
* radioiodine uptake test
* shows numerous hotspots of uptake
118
first line + alternative treatment for toxic multi nodular goitre
* 1st = radioiodine therapy
* alternative = carbimazole or propylthiouracil
* used for pts with pre-existing heart disease who are CI for radioiodine
119
what is thelarche and how does it present
* **breast budding** in females, marking the beginning of secondary breast development.
* Thelarche is usually noticed as a firm, tender lump directly under the centre of the nipple.
120
At what level of HbA1c would you consider starting a type 2 diabetic (who has undertaken lifestyle and diet advice) on a first-line pharmacological treatment to better control their blood sugar?
48mmol/l
121
what are the HbA1c targets in T2DM
* For people who are managed by lifestyle and diet: 48 mmol/mol (6.5%).
* For people who are managed by lifestyle and diet combined with a single drug not associated with hypoglycaemia (such as metformin): 48 mmol/mol (6.5%).
* For people who are taking a drug associated with hypoglycaemia (such as a sulphonylurea): 53 mmol/mol (7.0%).
122
symptoms of high serum calcium
High serum calcium may lead to:
* constipation,
* nausea,
* bone pain,
* depression,
* polyuria + polydipsia,
* muscle cramps
123
what is the key blood test for acromegaly
insulin-like growth factor levels
124
symptoms of acromegaly
* Structural and bone changes, e.g., protruding jaw, large ears/nose, forehead "bossing" (anteriorly protruding), etc.
* Sleep apnoea
* Galactorrhoea
* Headache
* Sweating
* Hypertension
* Carpal tunnel syndrome
* Erectile dysfunction
* Gigantism, e.g., clothes not fitting anymore, enlarged fingers etc.
