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2nd March [15th-21st] > Thursday [endocrinology] > Flashcards

Thursday [endocrinology] Flashcards

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1
Q

Where are the adrenal glands located?

A

Posterior abdomen between the superomedial kidney and the diaphragm.
They are retroperitoneal, with parietal peritoneum covering anterior surface only.

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2
Q

Shape of the adrenal glands

A

Right is pyramidal, left is lunar-shaped

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3
Q

Outer connective tissue layers of the adrenals

A

Capsule, cortex and medulla

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4
Q

Where do the veins/lymphatics/arteries/nerves enter the glands?

A 
Veins/lymphatics = hilum
Arteries/nerves = numerous sites
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5
Q

Which are the functional parts of the gland and how are they embryologically different?

A 
Crotex = dervied from the embryonic mesoderm
Medulla = derived from the ectodermal neural crest cells
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6
Q

How can the cortex be spit up in the adrenals?

A

Three regions [ascending to descending order]

  1. Zona glomerulosa = mineralocorticoids like aldosterone
  2. Zona fasciculata = corticosteroids like cortisol [and small amount androgens]
  3. Zona reticularis = androgens like DHES [small amount corticosteroids too]
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7
Q

What does the medulla secrete?

A

Chromaffin cells whcih secrete catecholamines [like adrenaline] into the bloodstream in response to stress.

Chromaffin cells also secrete enkephalins which function in pain control.

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8
Q

Vasculature of the adrenal glands

A

Three main arteries

  1. Superior adrenal artery [arises inferior phrenic artery]
  2. Middle adrenal artery [abdominal aorta]
  3. Inferior adrenal artery [renal arteries]

Right and left adrenal veins drain the glands. The right adrenal vein drains into the inferior vena cava, whereas the left adrenal vein drains into the left renal vein

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9
Q

Innervation of the adrenals

A

Adrenal glands innervated by the coeliac plexus and greater splanchnic nerves.

Sympathetic innervation to the adrenal medulla is via pre-synaptic fibres, mainly from the T10 to L1 spinal cord segments.

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10
Q

Lymphatic drainage adrenals

A

Lymph drainage is to the lumbar lymph nodes by adrenal lymphatic vessels. These vessels originate from two lymphatic plexuses – one deep to the capsule, and the other in the medulla.

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11
Q

What is th emesentery?

A

Double fold peritoneal tissue that suspends the small intestine and large intestine from the posterior abdominal wall

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12
Q

What is the emesentery?

A

Double fold peritoneal tissue that suspends the small intestine and large intestine from the posterior abdominal wall

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13
Q

Function of the mesentery

A
  • Suspends the small and large intestine from the posterior abdominal wall; anchoring them in place, whilst still allowing some movement.
  • Provides a conduit for blood vessels, nerves and lymphatic vessels.
  • Postulated to play a pathological role in inflammatory diseases such as Crohn’s disease
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14
Q

What is the ‘bare area’ of the mesentery?

A

The ‘root’ of the mesentery is the point where the mesentery attaches to the posterior abdominal wall, and is therefore a ‘bare area’. Due to the range of abdominal organs the mesentery envelopes, the root is long, narrow and has an oblique orientation, from the left side of the L2 vertebra to the right sacroiliac junction roughly

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15
Q

What are the 6 GI flexures of note?

A

In the gastrointestinal tract, there are six flexures of note: duodenojejunal, ileocaecal, hepatic, splenic, and those between the descending and sigmoid colon and the sigmoid and rectum.

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16
Q

How are there flexures used to distinguish different parts of the mesentery? List them

image

A

Mesentery of the small intestine – connects the loops of jejunum and ileum to the posterior abdominal wall and is a mobile structure. (1)
Right mesocolon – flattened against the posterior abdominal wall (2)
Transverse mesocolon – a mobile structure and lies between the colic flexures (3)
Left mesocolon – flattened against the posterior abdominal wall (4)
Mesosigmoid – has a medial portion which is flattened against the posterior abdominal wall, whereas the region of mesentery associated with the sigmoid colon itself is mobile. (5)
Mesorectum – assists in anchoring the rectum through the pelvis.(6

image

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17
Q

What is Toldt’s fascia?

A

The areas of the mesentery that are flattened against the posterior abdominal wall (the right and left mesocolon and the medial mesosigmoid) are attached to the abdominal wall via an additional layer of connective tissue known as Toldt’s fascia. The fascia contains several lymphatic channels.

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18
Q

Most commonly affected area of bowel in intestinal volvulus

[bonus; disease that is a high RF for volvulus]

A

A volvulus occurs when a loop of intestine twists around itself and its mesentery, causing obstruction of the bowel. It is possible that the bowel will twist tightly enough to prevent the blood supply to the intestine, and result in bowel infarction.

The most commonly affected area of bowel is the sigmoid colon. The risk of intestinal volvulus is increased in children with intestinal malrotation, a congenital defect in which the embryological intestinal rotation is incomplete, resulting in improper anchoring of the intestines to the posterior abdominal wall.

Medical imaging (abdominal x-ray, CT abdo-pelvis) is frequently used to confirm a diagnosis, and serious cases require surgical intervention

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19
Q

What is a pheochromocytoma?

A

A pheochromocytoma is a tumour of the adrenal medulla or preganglionic sympathetic neurones. It secretes adrenaline and noradrenaline uncontrollably, causing blood pressure to greatly increase. Patients may present with palpitations, headaches and diaphoresis (profuse sweating).

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20
Q

What can be used to treat pheochromocytoma?

A

Phenoxybenzamine, a competitive, irreversible antagonist of adrenaline, can be used in treatment to reduce blood pressure by binding to adrenaline receptors, making less available for adrenaline to act upon.

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21
Q

What XR is this of?

A

image

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22
Q

What can be used to treat pheochromocytoma?

A

Phenoxybenzamine, a competitive, irreversible antagonist of adrenaline, can be used in treatment to reduce blood pressure by binding to adrenaline receptors, making less available for adrenaline to act upon.

Surgical resection of the tumour is then carried out of the tumour after giving the alpha adrenoreceptor blockers.

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23
Q

What XR is this of?

A

image

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24
Q

In the adrenal medulla, what is secreted and by what cells/activation?

A

Chromaffin cells are activated by sympathetic nervous system to release adrenaline/noradrenaline

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25
What is adrenaline and noradrenaline produced from?
Tyrosine through multiple reactions
26
How does adreanline exhibit its actions?
Through a and b adrenorecpetors [G protein coupled receptors] both in the central nervous sytem and in the periphery
27
What does the fight or flight response lead to physiologically?
Increased CO, increased glycogenolysis in the liver and muscle tissue
28
Sx of phaechromocytoma
Tachycardia, hypertension, aqnxiety, palpitations, weight loss, hyperglycaemia
29
What is the definition of a hypertensive crisis in the context of phaeochromocytoma?
Intermittent attacks of headaches, excessive sweating and tachycardia. These patients present with extremely high BP, typicaly greater than 180-120. Can lead to increase BP vital ciruclations such as brain and kidney -> lethal.
30
What additional chemical is secreted byt eh adrenal meduall?
Dopamine
31
Which is the thickest of the adrenal zones?
The Zona Fasciculata is the middle zone of the Adrenal Cortex, deep to the Zona Glomerulosa and superficial to the Zona Reticularis. It is the thickest of the three Zonas, measuring approximately 0.9mm and making up 50% of the mass of the Adrenal Gland.
32
What type of cells is the zona fasciculata made up of?
parenchymal cells known as spongiocytes arranged into columns [sometimes called fascicles] with venous sinuses in between.
33
How does blood into the adrenal gland at the zona fasciculata?
Blood flows into the adrenal gland from the adrenal arteries, which are branches of the phrenic and renal arteries as well as the aorta. From here, blood flows through the adrenal tissue from superficial to deep, draining into sinusoids in the adrenal medulla and eventually into the central adrenal vein
34
What does the zona fasciculata secrete?
The cells of the Zona Fasciculata secrete the glucocorticoids Cortisol and Corticosterone.
35
Function of the glucocorticoids
These hormones regulate carbohydrate metabolism, particularly when an individual is in a time of stress (as part of the “fight-or-flight” response).
36
Approximately how much cortisol/corticosteroid are secreted over a 24-hour period?
In an adult human, approximately 10mg of Cortisol and 3mg of Corticosterone are secreted over a 24-hour period.
37
What is the major precursor of all steroids secreted?
Cholesterol
38
How does cholesterol reach the multi-step enzyme-assisted pathway?
Cholesterol is the major precursor for all steroids secreted. The first step is initiated by the actions of ACTH and Angiotensin II activating adenylyl cyclase and phospholipase C respectively. Cholesterol can then be converted to a steroid called Pregnenolone via an enzyme of the cytochrome P450 superfamily called cholesterol desmolase
39
Steps in the multi-step enzyme assisted pathway
From Pregnenolone, all the major secreted mineralocorticoids, glucocorticoids and androgens can be synthesised in a multi-step enzyme-assisted pathway. The metabolites of the synthesis pathway are moved in and out of the mitochondria, the smooth endoplasmic reticulum and the cytoplasm.
40
What determines which hormones are secreted in each Zona? [bonus: for the zona fasciculata]
It is the presence or lack of specific enzymes in each Zona that determines which hormones are secreted. In the Zona Fasciculata, the enzyme 11β-hydroxylase catalyses the final step of the reaction that forms Cortisol and Corticosterone.
41
Type of pattern does cortisol follow for secretion?
Additionally the secretion of cortisol follows a diurnal pattern with more being secreted in the mornings.
42
Where and what is produced in Cushing's syndrome?
In a steroid-producing adrenal tumour (or Anterior Pituitary adenoma), large concentrations of glucocorticoids are secreted in the body. When in high concentrations, glucocorticoid steroids activate mineralacorticoid receptors due to the similarity in shape of the receptors.
43
Sx of high glucocorticoid secretion,Sx of high mineralocorticoid concentrations
Therefore, a patient with Cushing’s Syndrome will have symptoms of high glucocorticoid secretion (fat build-up on back of neck and around face, wasting of limb muscles with central obesity, purple striae, hyperpigmentation) as well as show effects of high mineralocorticoid concentrations (hypertension, hypokalaemia).
44
Tx of pituitary adenoma
Treatment of Cushing’s depends on the underlying cause, for example a pituitary adenoma may be surgically removed, as can a metastatic lung tumour secreting ACTH.
45
Brief overview of Cushing syndrome Sx
image
46
What hormone is involved in Addison's disease?
Addison’s disease is the opposite disease to Cushing’s disease in many ways. Whereas Cushing’s disease is due to an excess of cortisol, Addison’s disease is due to a lack of cortisol, commonly due to autoimmune destruction of the adrenal cortex. This in turn causes hypotension and anorexia, in contrast to hypertension and truncal obesity in Cushing’s disease.
47
Name a unique Sx in Addison's disease
A unique symptom of Addison’s disease is hyperpigmentation, particularly in the creases of the hand and in the mouth. This can be explained via the hypothalamic – pituitary – adrenal (HPA) axis. The decrease in cortisol leads to an increase in ACTH via negative feedback.
48
Why does ACTH increase lead to skin darkening?
ACTH stems from a precursor molecule called pro-opiomelanocortin (POMC). POMC is also a precursor to Melanocyte Stimulating Hormone (MSH), causes darkening of skin. Therefore, an increase in ACTH, leads to an increase in POMC and as a byproduct, an increase in MSH and therefore leads to skin darkening
49
Briefly describe a Addisonian crisis
A very serious complication of Addison’s disease is an Addisonian crisis. As discussed above, cortisol is linked to the “fight or flight” response and is released in times of stress to the body.
50
Briefly describe a Addisonian crisis
A very serious complication of Addison’s disease is an Addisonian crisis. As discussed above, cortisol is linked to the “fight or flight” response and is released in times of stress to the body. Therefore, in patients suffering from Addison’s disease, they are unable to mount an adequate response to these stresses. It is a life threatening complication, resulting in numerous symptoms such as severe hypotension and electrolyte dysfunction
51
A deficiency in what enzyme can lead to increase secretion of DHEA?
A deficiency in the enzyme 3β-hydroxysteroid dehydrogenase causes an increased secretion of DHEA
52
Characteristic Sx of this enzyme deficiency in DHEA
DHEA - a weak androgen that causes masculinisation in females but is not strong enough to drive male genital development alone. As such, male neonates with this deficiency are likely to have hypospadias, where the opening of the urethra is found on the underside of the penis rather than at the tip.
53
What is the most common adrenal insufficiency?
The most common adrenal enzyme deficiency is 21β-hydroxylase deficiency, making up 90% of the deficiency cases.
54
Simple PP of 21B-hydroxylase
Production of Cortisol and Aldosterone are reduced, causing a raised ACTH secretion. Precursor steroids are converted to androgens which then drive masculinisation, although this may not become apparent until later life. The lack of aldosterone results in massive loss of Na+ which manifests as severe hypovolaemia.
55
Which enzyme catalyses the final step on the synthesis pathway for cortisol?
11B-hydroylase
56
What is the "salt and pepper" sign?
Radiographs in those with parathyroid issues
57
Which layer is the zona glomerulosa and how much does it acccount for the thickness of the cortex/
Outermost layer and acounts for around 15%
58
How are the secretory cells arranged?
The secretory cells of the zona glomerulosa are arranged in oval-shaped clusters – its name comes from the latin word glomus, meaning ball. These clusters are divided by connective tissue bands called trabeculae which extend down into the cortex from the adrenal capsule. The blood supply to the secretory cells travels within these trabeculae.
59
primary function of the zona glomerulosa
The primary function of the zona glomerulosa is the synthesis of mineralocorticoid hormones, which play an important role in the maintenance of electrolyte and water balance in the body. Mineralocorticoids are steroid hormones, and so are synthesised from cholesterol
60
What are mineralocorticoids synthesised from?
Mineralocorticoids are steroid hormones, and so are synthesised from cholesterol.
61
What is the most important mineralocorticoid ? Describe it's responsibility
The most important mineralocorticoid is aldosterone, which is responsible for controlling the uptake of Na+ and secretion of K+ in the collecting duct of the renal tubule.
62
Where does aldosterone act?
Aldosterone acts within the tubule cell to increase the transcription of Na+/K+-ATPase and ENaC (epithelial sodium channels), promoting re-absorption of Na+ and excretion of K+
63
List four factors that increase the rate of aldosterone production within the zona glomerulosa
Increase in plasma concentration of Angiotensin-II Increase in plasma K+ concentration Decrease in plasma pH (acidosis) Decreased blood pressure, as detected by atrial stretch receptors
64
What type of secretion does aldosterone follow?
It is also worth noting that aldosterone secretion follows a diurnal rhythm, with higher levels typically being released during sleep.
65
Which is the most important factor in the production and secretion of aldosterone?
Whilst all the above factors are important in the production and secretion of aldosterone, one of the most important is the plasma concentration of Angiotensin-II. The release of aldosterone is therefore an important part of the renin-angiotensin-aldosterone system (RAAS) which is fundamental in the long-term regulation of blood pressure.
66
Briefly describe the RAAS system
image
67
When does Conn's syndrome occur?
Conn’s syndrome occurs when patients develop an adenoma (benign tumour) of the zona glomerulosa which secretes excess aldosterone, leading to primary hyperaldosteronism
68
Common presentation of Conn's syndrome
This condition is usually asymptomatic, however some patients will experience muscle cramps, headaches and lethargy due to electrolyte disturbances.
69
Dangerous Cx of Conn's syndrome
Most importantly, the increased reabsorption of sodium and water by the kidneys leads to hypertension, which increases the patient’s risk of diseases such as strokes and ischaemic heart disease.
70
Tx of Conn syndrome
Conn’s syndrome is usually treated by surgical removal of the tumour. The patient may also be given spironolactone (an aldosterone antagonist) to reduce their blood pressure and relieve any symptoms prior to surgery.
71
Conn's syndrome is caused by what?
Excess aldosterone secretion
72
Arrangement of the zona reticularis
The zona reticularis is the innermost layer of the adrenal cortex, lying just above the adrenal medulla. It comprises of cylindrical masses of epithelia arranged in an irregular, net-like pattern. In comparison to the zona fasciculata, the cells contain fewer vacuoles as well as appearing more irregular and smaller in size
73
Main function of the zona reticularis
The zona reticularis is the site of biosynthesis of androgen precursors such as dehydroepiandrosterone (DHEA) and androstenedione from cholesterol. These androgens are released into the bloodstream and transported to gonads where they are converted into testosterone or oestrogen
74
Which stages of life is the Zona Reticularis particularly important for?
These are largely responsible for the normal development of sexual characteristics during puberty. Further information on the effects of adrenal androgens during puberty can be found here. In postmenopausal women, the conversion of adrenal androgens to oestrogen is the only source of oestrogen synthesis and hence is a significant source.
75
Briefly go through the synthesis of hormones in the adrenal cortex
image
76
How are adrenal androgens regulated?
Adrenal androgens are regulated by ACTH (adrenocorticotropic hormone) secreted from the anterior pituitary gland which is stimulated by the release of CRH (corticotrophin releasing hormone) from the hypothalamus.
77
Why is there a particular issue in cases where there is a dramatic increase in ACTH?
However, the adrenal androgens along with their potent metabolites such as testosterone do not negatively feedback to ACTH or CRH. Therefore, in cases where there is a dramatic increase in ACTH, this leads to excess production of androgens which cannot be regulated.
78
Type of inheritance is CAH
Congenital adrenal hyperplasia (CAH) can result from one of several autosomal recessive diseases. There is typically a mutation in an enzyme mediating one of the steps necessary in the production of mineralocorticoids or glucocorticoids from cholesterol
79
hormonal profile in CAH
This results in a lack of mineralocorticoids and glucocortoids, as well as an excess of testosterone and its derivatives
80
CF of CAH
``` Virilisation of female babies Neonatal salt-losing crisis Hypotension Hypoglycaemia Hyponatraemia ```
81
How may CAH present later in life?
It may present as a milder form in later life, however in an acute situation, urgent confirmation is needed. Babies born with CAH will show high levels of testosterone, androstenedione and ACTH.
82
Two part of the adrenal gland
Cortex and medulla
83
How is the stimulation of the adrenal medulla diffferent to the cortex?
medulla stimulated by the brain from the NS -> increase in adrenaline and adrenaline [ fight or flight] cortex = long-term stress response, hypothalamus release CTRH -> anterior pitatuiry ACTH -> cortex stiulated -> G for aldosterosterone, F for cortisol, A for androgens
84
Acronym for remembering crotex
GFR [like in the kidneys]
85
Which hormones have an important role in negative feedback signal?
Glucocorticoids [like cortiosol]
86
What are nephrons?
Functional units kidney [millions of these] responsibility for reabsorption/filtration/secreting etc. So have big role in blood pressure control
87
What acts on the nephrons?
Mineralocorticoids
88
How does blood pressure get increased by the adrenal cortex?
image
89
Where does aldosterone act?
alodosterone stimulates Na+ and H20 retention -> increase in BP
90
How does cortisol work on the liver?
image
91
Other functions of cortisol
Increase BP immune suppression [decrease pain, increase infection risk] osteoclastic activity [osteoporosis risk increase]
92
What role does androgens have in stress?
No role!
93
Role of androgens in males
Prostate growth, masculine characteristics -> hair
94
role of androgens in females
important in female libido
95
How nephrons work very simply
image
96
What happens when BP decreased in the nephron?
Renin decreased produced from nephron -> then activation of angiotensin II -> activation aldosterone then increase in BP

2nd March [15th-21st] (5 decks)

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