Endocrinology Flashcards
Location of adrenal glands
Superior to kidney
Arterial blood supply to adrenal glands
Superior adrenal artery
Middle adrenal artery
Inferior adrenal artery
Origin of
Superior adrenal artery
Middle adrenal artery
Inferior adrenal artery
superior = inferior phrenic artery middle = abdominal aorta inferior = abdominal aorta
Venous drainage of the adrenal glands. Where do they drain into?
Right adrenal vein -> drains directly into inferior vena cava
Left adrenal vein -> drains into left renal vein
Nerve supply of the adrenal glands
Splanchnic nerves
The adrenal gland secretes FIVE main hormones
- Aldosterone
- Cortisol
- Corticosterone
- Dehydroepiandrosterone (DHEA)
- Androstenedione
The cortex is divided into 3 layers (From outside in). What is the name of each layer ?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What does each layer of the adrenal cortex produce?
Zona glomerulosa (mineral corticoids - aldosterone) Zona fasciculata (glucocorticoids i.e. cortisol and small amount of androgens) Zona reticularis (androgens - sex hormones. Small amount of cortisol)
GFR - Makes Good Sex
Which hormones does the adrenal MEDULLA secrete?q
adrenaline and noradrenaline which cause the cortex to secrete further hormones
What do the adrenal medullary hormones respond to? What is their physiological effect as a result?
- They respond to stress
- Dilated pupils, increases glycogenesis, increase lipolysis, increased sweating, increased heart rate and inhibited insulin release
What is a precursor for ALL corticosteroids?
cholesterol
Solubility of corticosteroids
lipid soluble - can pass through biological membranes
What do corticosteroids bind to?
intracellular receptors
Effect of corticosteroids on gene?
Alter gene transcription
How are different steroids classified?
- 21 C = progesterone, corticoids
- 19 C = androgens
- 18 C = oestrogens
- Small structural modifications can substantially alter specificity for steroid receptors
What is the role of mineralcorticoids?
to regulate body electrolytes (minerals)
What is the most predominant mineralcorticoid? What is it important for?
aldosterone
Maintaining salt balance and important for blood pressure as in the RAAS
What triggers the secretion of aldosterone?
the release of renin by juxtaglomerular cells in the afferent arterioles of the kidney
What is the predominant glucocorticoid in humans? What is its role?
- Cortisol
- Facilitates the bodies responses to stress and regulation of the immune system
What are examples of stress/threat which pose a real or perceived threat to homeostasis?
physical trauma, prolonged exposure to cold, prolonged heavy exercise, infection, shock, decreased oxygen supply, sleep deprivation, pain and emotional stress
Stress triggers an increase in the release of …
cortisol
- sympathetic nervous system activity
- release of adrenaline from adrenal medulla
Process of stress detection and subsequent homeostatic response
- Stress is detected and transmitted neuronally to the HYPOTHALAMUS
- This stimulates the secretion of CRH from the hypothalamus
- CRH is carried by the hypothalami-hypopheal portal vessels to the anterior pituitary where it stimulates the release of adrenocorticotropic hormone (ACTH)
- ACTH in turn circulates through the blood and travels to the zona fasciculata, where it binds to the GPCRs. Protein Kinase A (PKA) stimulates the synthesis of cholesterol.
- Cholesterol is converted to pregnenolone in mitochondria and undergoes further processing in the endoplasmic reticulum
- The final conversion to cortisol takes place in the mitochondria
- Once released, CORTISOL enters circulation
% distribution of cortisol in the circulation
- 90% bound to corticosteroid-binding globulin
- 5% bound to albumin
- 5% free - only this is bioavailable
How does cortisol help maintain blood pressure?
It has permissive actions on the reactivity to adrenaline (Vasoconstrictor) and noradrenaline (vasodilator) of smooth muscle scells that surround the lumen of blood vessels
What does cortisol maintain?
Maintain cellular concentrations of enzymes involved in metabolic homeostasis which are expressed mainly in the liver and act to increase hepatic glucose production between meals; thereby preventing glucose concentrations from significantly decreasing below normal.
What doe cortisol inhibit?
Inhibits the production of leukotriene and prostaglandins both of which are involved in inflammations
What does cortisol stabilise?
lysosomal membranes in damaged cells thereby preventing the release of their proteolytic contents
What does cortisol reduce?
capillary permeability in injured areas, thereby reducing fluid leakage to the interstitium
It also suppresses the growth and function of certain key immune cells such as lymphocytes
How does cortisol act as a developmental hormone?
- Responsible for the proper differentiation of numerous tissues and glands including parts of the brain, adrenal medulla, intestines and lungs
- Cortisol is essential for the production of SURFACTANT (reduces the surface tension in the lungs thereby making it easier for the lungs to inflate)
Stress functions of cortisol
- increases organic metabolism (more lipolysis, amino acid generation, and gluconeogenesis)
- This is because when animal is faced with a threat its usually forced to go without eating
- Free amino acids can also help with tissue repair
- Cortisol increases the ability of vascular smooth muscle to contract (vasoconstriction) in response to adrenaline
- Reduces inflammatory response to injury or infection thereby protecting against possible damage as a result of inflammation
- inhibits nonessential functions e.g. reproduction and growth
What can chronic stress result in?
severe decrease in bone density, immune functions and reproductive fertilise due to increased catabolism that is elicited from increased cortisol
Main androgens produced in the zona — are….
Which is the most abundant?
reticularis
- Dehydroepiandrosterone (DHEA)
- Androstenedione
DHEA = most abundant
Do androgens have a stronger effect in males or females?
DHEA and androstenedione have a much less potent effect than testosterone and play less of a role in the adult male yet play a larger role in the adult female, but these weaker androgens can be CONVERTED to testosterone
The production of androgens in the adrenal glands are regulated by the actions of — secreted by the — —
- ACTH
- Anterior pituitary
Adrenaline and noradrenaline are —
catechloamines
Which nervous system is adrenal medulla connected to? It has specialised ganglia that are supplied by — — — with — neurotransmitter
autonomic nervous system
- sympathetic preganglionic neurones
- ACh
What is the proportion of adrenaline vs noradrenaline
- 20% nor
- 80% adrenaline
Normal catechloamine synthesis is dependent on high levels of …
cortisol
Role of catecloamines in “fight or flight” (6)
- gluconeogenesis in the liver and muscle
- lipolysis in adipose tissues
- tachycardia and cardiac contractility
- redistribution of circulating volume
- more adrenaline release - vasoconstrict
- LESS noradrenaline released - vasodilation
Which receptors have a higher affinity for noradrenaline and which have higher affinity for adrenaline
- Alpha - noradrenaline
- Beta - adrenaline
Spinal level thyroid
C5-T1
How many lobes does the thyroid have? What connects them?
2
isthmus
What does the thyroid straddle?
trachea
What does the thyroid lie behind?
sternohyoid and sternothyroid muscles
What does the thyroid wrap around?
cricoid cartilage
superior tracheal rings (2-3 is covered by isthmus)
What does the thyroid lie inferior to?
inferior to thyroid cartilage of the larynx
Arterial supply of the thyroid
superior thyroid artery (1st branch of external carotid artery; supplies the superior and anterior portions)
inferior thyroid artery arises from the subclavian artery; supplies the posterior and inferior portions
Venous drainage of the thyroid
middle + inferior thyroid vein
Thyroid innervation
sympathetic trunk
Hormone release in thyroid is controlled by the …
pituitary gland, NOT sympathetic innervation
When do thyroid glands appear as an epithelial proliferation at the base of the pharynx?
3-4 weeks
When do thyroid glands begin producing thyroxine?
18-20 weeks
What are the two iodine-containing molecules of physiological importance that the thyroid gland produces?
Thyroxine (T4; four iodines)
Triiodothyronine (T3)
T4 is generally converted to T3 by …
In which cells?
deiodinase enzymes
target cells
Is there a higher concentration of T4 or T3 in the blood?
T4, although T3 is considered the major thyroid hormone; T4 can be thought of as a RESEVOIR for T3
Within the thyroid gland are numerous — each composed of an enclosed sphere of — cells surrounding a core containing a protein-rich material called the —
In this material, which protein is there large amounts of?
follicles
follicular
COLLOID
thyroglobulin
Which cells participate in almost all phases of thyroid hormone synthesis and secretion?
follicular epithelial cells
THYROID HORMONE SYNTHESIS
1) circulating iodide is actively co-transported with Na+ ions across the basolateral membranes of the follicular cells (IODIDE TRAPPING) and the Na+ is pumped back out of the cells via the Na+/K+ ATPases.
2) The negatively charged iodide ions diffuse to the apical membrane of the follicular cells and are transported into the colloid.
3) Once inside the colloid, the iodide is oxidised => IODINE which then binds to TYROSINE RESIDUES on the thyroglobulin molecules
4) Tyrosine may bind to 1 or 2 iodine molecules thus either becoming T1 or T2
5) When the thyroid is stimulated to produce thyroid hormone, the T1/2 molecules are cleaved from tyrosine and join to create T3 or T4.