Endocrinology Flashcards
Where is the pituitary gland located? How does it receive blood?
Pituitary gland sits in the bony fossa of the sphenoid bone in the brain - near to hypothalamus and optic chaism
It receives blood via the portal venous circulation from the hypothalamus
What hormones does the anterior pituitary secrete?
- Growth hormone, GH
- Thyroid stimulating hormones, TSH
- Adrenocorticotropic hormone (ACTH)
- Prolactin (PRL)
- Gonadal hormones, FSH, LH
What hormones does the posterior pituitary secrete?
Antidiuretic hormone (ADH, or vasopressin) Oxytocin
What is the Hypothalamic–pituitary–thyroid axis? (HPT)
Hypothalamus ↓ TRH (Thyrotropin-releasing hormone) ↓ Pituitary gland ↓ FSH (Follicle-stimulating hormone ) ↓ Thyroid - produces T3 AND T4 = -ve feedback on hypothalamus and pituitary
What hormones does the hypothalamus secrete?
- GHRH & SMS
- GnRH
- CRH
- TRH
- Dopamine
What controls prolactin, from where, what does it do
- Prolactin (PRL) is under -ve control by dopamine
- Causes milk production during lactation
- Produced by ant. pit.
How may a pituitary tumour present? (3)
- Pressure on local structure - eg, optic nerve
could cause headaches, hydrocephalus, damage to visual fields- (bitemporal homonymous hemianopia- damage to optic chiasm) CN damage - Pressure on normal pituitary
eg, hypopituitarism = pale, no body hair, central obesity - Functioning tumour
- prolactinoma (produces lactin = periods stop, infertile)
- acromegaly = thick skin, sweaty, greasy,
- crushing syndrome - increase steroids, cotisol = short and fat
What is the hypothalamic–pituitary–gonadal axis? (in females)
Hypothalamus ↓ GnRH ↓ Pituitary gland ↓ FSH and LH ↓ Oestrogen and progesterone
What is the hypothalamic–pituitary–gonadal axis? (in males)
Hypothalamus ↓ GnRH ↓ Pituitary gland ↓ FSH and LH ↓ LH acts on leydig = testosterone (-ve) FSH acts on sertoli = inhibin (-ve)
What is the hypothalamic–pituitary–adrenal axis?
Hypothalamus ↓ CRH (Corticotropin-releasing hormone) ↓ Pituitary gland ↓ ACTH (Adrenocorticotropic hormone ) ↓ Adrenal glands ↓ Cortisol (decreased immune system, breakdown of glucogen, proteins and fats) -VE FEEDBACK TO BOTH
*RESPONSE TO STRESS = SYMPATHETIC
Where is the pancreas located?
- Retroperitoneum
- Posterior to greater curvature of stomach
- Near C portion of duodenum
- small ducts then 2 larger ducts
Which cells associate with the exocrine function of the pancreas?
*exocine = glands that secrete their products through ducts opening onto an epithelium rather than directly into the bloodstream
pancreatic duct joins bile duct to form major duodenal papilla = into duodenum
Formed of small clusters of glandular
epithelial cells = Acini cells (98%)
manufacture and secretion of fluid and digestive enzymes - pancreatic juice - released into gut
Which cells associate with the endocrine function of the pancreas?
Islet cells (2-3%) Manufacture and release of several peptide hormones into portal vein
What is the effect of insulin?
- Reduces glucose output by the liver
- Increases storage of glucose, fatty acids and amino caids
(decreases glycogenolysis
decrease glucaneogensis = generation of glucose)
What is the effect of glucagon?
Glucagon mobilises glucose, fatty acids and amino acids from stores
(increases glycogenolysis
increase gluconeogenesis)
stimulated by low glucose levels
What is gluconeogenesis?
non-hexose substrates such as amino acids are converted to glucose (increase glucose)
What is glycogenolysis?
Glycogenolysis is the biochemical breakdown of glycogen to glucose (increase glucose)
What is glycogenesis>?
glycogenesis is the opposite, the formation of glycogen from glucose (decrease glucose)
How does the pancreas form embryologically?
At junction of foregut and midgut 2 pancreatic
buds (dorsal and ventral) are generated and
eventually fuse to form pancreas
Describe the microanatomy of Islet cells
-beta cell secretes insulin (proinsulin, then converted)
-alpha cell secretes glucagon
There is a paracrine ‘cross stalk’ between alpha and beta cells (ie local insulin increase, decrease glucagon)
How does somatostatin effect pancreatic hormones?
Suppresses the release of pancreatic hormones
Inhibits insulin release when somatostatin is released from delta cells of pancreas
Inhibits the release of glucagon
(secreted by delta cells)
Describe insulin secretion by beta cells
- Glucose enters cell via GLUT2 glucose transporter
- Glucokinase converts ADP to ATP
- K+ channel closes and depolarises membrane
- Ca2+ channel opens and causing Ca influx
- Ca activates insulin gene expression via CREB
(insulin acts on muscle and fats cells to reduce glucose conc)
Describe insulin action in muscle and fat cells
- Insulin binds to receptors on plasma membrane
- Intracellular signalling cascade
- GLUT4 vesicle mobilization to plasma membrane
- GLUT4 vesicle integration into plasma membrane
- Glucose uptake via GLU4
- Glucosa converted to glycogen
How do Bcells react the rising glucose?
- B cells sense rising glucose and aim to metabolise it
- First phase response is rapid release of stored product
- Second phase response is slower as it is the release of newly synthesised hormones
What are the short term and long term responses to low glucose?
Short-term response - split glycogen into glucose (glycogenolysis)
Long-term response - make glucose from amino acids/lactate (gluconeogenesis)
What are the short term and long term responses to high glucose?
Short-term response - make glycogen (glucose into glycogen)
Long-term response - make triglyceride (lipogenesis)
What are the primary glucose sensors?
- In the pancreatic islets
- also in medulla, hypothalamus and carotid bodies
-inputs from eyes, nose, taste buds and gut all involved in food regulation
-sensory cells in gut wall also stimulate insulin release from pancreas - incretins (incretins are gut hormones that stimulate glucose release)
(insulin response is far greater following oral glucose than IV glucose)
What affect does food have on insulin levels?
5 - 10 mins after eating rising glucose levels stimulate 5-10 fold increase in insulin and supresses glucagon
What is the effect of vasopressin?
- Synthesis of aqua proteins
- more water reabsorption
- less water excreted
(V2 affects renal collecting ducts)
- Vasopressin binds to vasopressin-2 receptor
- intracellular cascade (activation of cAMP)
- aqua porin proteins are synthesized and inserted into the apical membrane APQ-2
- this increase the permeability of renal collecting duct
- increased water reabsorption (osmolality decrease)
What is the effect of oxytocin?
- Milk release
- Uterus contractions during labour
Where are the secretory cells of the posterior pituitary gland?
In the hypothalamus, hormones are then transported to the posterior pituitary in the axoplasm of neuron
What controls the release of vasopressin?
- Osmoreceptors in the hypothalamus - day to day
- detects change is osmolality
* thirst effected - Baroreceptors - only after major trauma and blood loss
What three layers are in the adrenal cortex?
- Zona glomerulosa = mineralocorticoids, outermost layer (mainly aldosterone) = BP, K/Na
juxtaglomerular appatus - mascula densa = RAAS - Zona fasciculata = glucocorticoids (deoxycorticosterone,corticosterone, and cortisol) - stress
- Zona recticularis = sex hormones (andandrostenedione (the precursor to testosterone)
(Go Find Rex - make good sex)
How does Adrenocorticotropic hormone (ACTH) affect the adrenal cortex?
ACTH is released in response to stress
- it stimulates zona fasciculata to release cortisol
- ACTH binds to receptor
- intracellular cascade
- cortisol synthesis
cortisol = increased glucose metabolism, circulation, dampens immune system
Where is the thyroid located? Which hormones?
Between level of the thyroid cartilage (superiorly) and 4th tracheal ring (inferiorly)
- Two lateral lobes join by isthmus
- Thyroxine (T3 AND T4)
- Calcitonin (acts to decrease Ca / opposite action of PTH?)
What secretory cells do the islets of the pancreas contain? How are the hormones secreted out?
islets = endocrine cells embedded in exocrine pancreas (5% pass of pancreas)
- Beta cells - secrete insulin (70%) (at periphery of islets, form cords to centre)
- Alpha cells - secrete glucagon (20%)
- Delta cells - secrete somatostatin (8%)
- Pancreatic polypeptide secreting cells (2%)
(2-4, lie between cords, plexus of capillaries/veins)
hormones are then transported to HEPATIC PORTAL SYSTEM
What is the effect of the alpha cell secretion on the liver, what hormone has the antagonistic action -where is it secreted?
Alpha cells in the islets of the pancreas secrete glucagon -affects hepatocytes of liver to break down glycogen to release glucose into the blood stream - via the hepatic portal system
Insulin (secreted by beta cells of islets of pancreas has the antagonistic action)
Describe the structure of the supra renal glands - what is released from which layer
- Retro, in kidney’s capsule
- 3 arteries, 1 vein
- Narrow outer glomerular - mineral and aldosterone
- Thick intermediate fascicular - cortisol, glucocorticoids
- Inner reticular - sex hormones - testosterone
What secretory cells are in the medulla?
- Epinephrine = secretes adrenaline
- Norephineprine = secretes noradrenaline
Symp autonomic - excitement and stress
Chromaffin cells, medulla of kidney
What is at the centre of the medulla?
Large central vein - all secretions of super renal gland drain into, then discharge to hepatic portal system of veins (has smooth muscle to keep it open)
What occurs in diabetes mellitus (type 1)?
Autoimmune destruction of islets of pancreas -so absolute insulin deficiency (beta cells) - excess glucose in body
NAME 6 hormones of anterior pituitary, which hormone from the hypothalamus stimulates each one?
FSH - GnRH
LSH - GnRH
Adrenocorticotropic hormone - CRH, Corticotropin-releasing hormone
Thyroxine - TRH, Thyrotropin-releasing hormone
Prolactin - Prolactin releasing hormone
Growth Hormone - Growth Hormone releasing hormone
Describe the synthesis of thyroid hormone formation
- Iodine is actively taken up by the follicular cells of the thyroid gland (in the form of iodide) and transported into the follicles.
- In the follicles iodide binds to tyrosine residues on thyroglobulin molecules that have been produced by the follicular cells. The thyroglobulin either binds one iodine molecule or two, producing T1 or T2.
- When the thyroid is stimulated to produce thyroid hormone, the T1 and T2 molecules are cleaved from their thyroglobulin backbone
- They then join to create T3 (T1+T2) or T4 (T2+T2)
- These enter the blood stream after being released by
proteolysis. They join to thyroid hormone binding proteins for transport.
More T4 than T3 is produced in the thyroid = increased metabolism, growth and development, and increased catecholamine effect = F&F)
T3 is more active and produced peripherally from the conversion of T4 (T4 is a pro-hormone and is converted when it reaches its target tissues)
What cells are found on the thyroid?
Follicular cells – Produce hormones T3 and T4.
Follicles – Centre contains thyroglobulin rich colloid. Iodine
stored in thyroglobulin and actively taken up from blood.
Parafollicular/C cells – Produce calcitonin for Ca2+ homeostasis