Endocrine Flashcards
Alpha cells of the pancreas produce?
Glucagon
Beta cells of the pancreas produce?
Insulin
Delta cells of the pancreas produce?
Somatostatin
Epsilon cells of the pancreas produce?
Ghrelin
Gamma / F cells of the pancreas produce?
Pancreatic polypeptide
What does Ghrelin stimulate?
Appetite, increase food intake and promotes fat storage
Also stimulates release of growth hormone from the pituitary gland
Glucagon MOA
Acts on G-protein coupled receptor to stimulate cAMP production
Impact of glucagon on blood levels:
Glucose
Fatty acid
Ketoacid
ALL INCREASE
Glucagon major actions:
Decrease glycogenesis
Increase glycogenolysis
Increase gluconeogenesis
Decrease fatty acid synthesis
Increase lipolysis
Increase ketoacid production
Impact of insulin on blood levels:
Glucose
Fatty acid
Ketoacid
K+
Aminoacid
DECREASE
Insulin MOA
Acts on tyrosine kinase receptor to activate the intracellular pathway that results in translocation of GLUT-4 transporter to the plasma membrane
Insulin major actions
Increase glucose uptake into cells
Increase glycogenesis
Decrease gylcogenolysis
Decrease gluconeogenesis
Increase protein synthesis (decrease degradation)
Increase fat deposition (reduce lysis)
Reduce ketoacid production
Increase K+ uptake
What simulates insulin release?
During eating by the parasympathetic system
Gut hormone secretin
Rise in plasma glucose concentration after a meal (most)
Where is somatostatin secreted from?
D cells n pyloric antrum, duodenum and pancreatic islet
What stimulates somatostatin secretion?
Inhibits?
H+ in GI lumen
Vagal stimulation
Actions of somatostatin?
Inhibits gastric acid secretion (directly on parietal cells and via G-protein coupled receptors, indirectly via inhibition of gastrin and histamine secretion)
Which hormones does somatostatin inhibit?
and therefore mediates ….
Insulin
Glucagon
Cholecystokinin
Secretin
GIP
DECREASED gastric and intestinal mobility
Decreased gastric and intestinal secretions
Decreased pancreatic endocrine and exocrine function
Decreased bile production
Main action of pancreatic polypeptide
The primary role of PP is to modulate digestion of food by inhibition of gastric emptying as well as biliary secretion
Hormones secreted by the ANTERIOR pituitary gland ?
FSH
Prolactin
TSH
ACTH
LH
GH
Fresh pituitary tastes almost like guinness…
Hormones secreted by the POSTERIOR pituitary gland ?
Oxytocin
ADH
POSTERIOR pituitary is a direct extension of?
Hypothalamus
Control most pituitary hormones except oxytocin is by which type of feedback mechanism?
Negative
Action of ACTH
acts on the adrenal cortex to stimulate glutococoticoid and
What stimulates ACTH release?
CRh
ACTH
Deficiency ->
Excess ->
Secondary adrenal insufficiency
Cushing’s disease
ADH action
Acts on the KIDENYS to increase water permeability in the DISTAL NEPHRON
Allowing greater water reabsorption and concentration of urine
Also acts on vascular smooth muscle causing vasoconstriction
What mainly stimulates ADH release?
Raised plasma osmolality detected by osmoreceptors in the Ant. hypothalamus
What inhibits ADH release?
Low plasma osmolality
Alcohol
Caffeine
Glutocorticoids
ANP
ADH deficiency ->
Excess ->
Central diabetes insipidus
SIADH
Three zones of the adrenal cortex
Outer glomerulosa
Middle zona fasciculata
Inner zone reticularis
Outer glomerulosa releases what? + example
Mineralcorticoids e.g. aldosterone
Middle zona fasciculata releases what? + example
Glucocorticoids e.g cortisol
Inner zone reticularis release what?
Androgens and stress hormones
Mineralcorticoids e.g aldosterone regulate?
Salt and water homeostasis
Glucocorticoids e.g. cortisol regulate?
Carbohydrate metabolism and response to stress
What regulates cortisol release?
ACTH
What regulates aldosterone release?
RAS
what does the adrenal medulla release ?
Catecholamines
Which zones of the adrenal cortex are typically affected in primary adrenal insufficiency (addisions)
All three
Aldosterone release stimulated by (3)
Angiotensin II (secondary to fall in blood volume, BP or plasma sodium)
High K+
ACTH (least important)
Where does aldosterone act in the kidney?
Distal convoluted tuble
Action of aldosterone at the DCT?
Sodium retention and potassium loss (increase synthesis of transport mechanisms)
Which part of the brain drives the stress response and what does it lead to?
amygdala
stimulates CRH neurons -> ACTH
stimulates sympathetic nervous system
stimulates parasympathetic nerves that cause acid secretion in the stomach
Fear
What stimulates tyrosine breakdown by specific enzymes to create catecholamines?
Cortisol
What receptors do catecholamines act on?
Alphas and beta G protein coupled receptors
Alpha 1 adrenergic receptors
Main stimulator
Actions
Noradrenaline > adrenaline
Vasoconstriction
Increase PVR
Increased B
Mydriasis
Increased closed bladder sphincter
Alpha 2 adrenergic receptors
Main stimulator
Actions
Adrenaline > Noradrenaline
Inhibits NA release
Inhibits ACh release
Inhibits insulin release
Beta 1 adrenergic receptors
Main stimulator
Actions
Adrenaline = Noradrenaline
Increase HR
Increased lipolysis
Increase myocardial contractility
Increases renin
Beta 2 adrenergic receptors
Main stimulator
Actions
Adrenaline»_space; Noradrenaline
Vasodilation
Decrease PVR
Bronchodilation
Glycogenolysis
Glugacon release
Relaxes uterine smooth muscle e
Common presenting sx of phaeochromocytoma?
Headache / sweating / pallor / palpitations
Phaeochromocytoma aetiology?
Catecholamine secreting tumour
diagnosis of Phaeochromocytoma
Biochemical confirmation of elevated catecholamines followed by radiological localisation of the tumour
Cushing’s syndrome =
Clinical signs & symptoms related to chronic glucocorticoid excess
Cushing’s disease =
Excess corticosteroids due to ACTH secreting pituitary adenoma
Causes of Cushing’s syndrome (3)
Excess ACTH (pituitary or ectopic ACTH secreting tumour)
Excess cortisol (adrenal tumur)
Exogenous steroids
Where is Ca2+ mainly absorbed?
Duodenum and proximal jejunum (some in S. intestine)
How to activated Vit D act in the gut?
To increased Ca2+ gut absorption
How does pH act on Ca2+ levels?
Increase in pH (alkalosis) promotes increased protein binding, decreasing free Ca2+ levels
(competes with H+ ions for binding sites on albumin etc)
What mainly drives Ca2+ reabsorption in the nephron?
Na2+ reabsorption
Where in the kidney is the main target for hormonal control of Ca2+?
Distal nephron
How does parathyroid hormone control Ca2+?
Acts on the kidney to increase calcium re-absorption in the distal tubule
Activates Ca2+ entry channels in the apical membrane and Ca2+ ATPase pumps in the basolateral membranes
Also stimulates osteoclasts to release Ca2+ from bone
How does activated Vit D control Ca2+?
Activates Ca2+ ATPase pumps in the basolateral membranes
PTH action on phosphate reabsorption?
Decrease phosphate reabsorption in the proximal tubule
Activated Vit D action on phosphate reabsorption?
Increase phosphate reabsoprtion
How does calcitonin control Ca2+?
Inhibits renal reabsorption of calcium
Osteoclast activity inhibited
What synthesises PTH?
Chief cells of the parathyroid gland
PTH is released in response to…
Decrease plasma Ca2+
Increased blood phosphate level
Action of PTH on the kidneys
Increase Ca2+ reabsorption
Increase phosphate excretion
Inhibit bicarb re-absorption -> metabolic acidosis -> favour dissociation of calcium from plasma proteins
Stimulate 1-alph-hydroxylase in the kidneys to produce MORE activated vit D
How does PTH act on the gut?
Increase calcium and phosphate absorption in the small intestine (via activated vit D)
How does PTH act on bone?
Increase calcium and phosphate resorption
Pre vit D3 -> activated Vit D
Pre Vit D -> cholecalciferol (D3) -> Calcitrol in the liver via enzyme -> Activated Vit D in the kidneys via enzyme
Action of activated Vit D on the gut?
Increase Ca2+ and phosphate absorption in the small intestine
Action of activated Vit D on the kidneys?
Increase calcium reabsorption
Increase phosphate reabsorption
Negative feedback on the enzyme in the kidney creating activated vit D
Enzyme in the kidney creating activated Vit D?
1-ALPHA-HYDROXYLASE
What secretes calcitonin?
C cells (parafollicular) cells of the thyroid gland
When is calcitonin secreted?
Rising levels of Ca2+
Actions of calcitonin?
Act on kidneys to inhibit renal absorption of calcium and phosphate
& on bones to inhibit resorption by osteocytes
ADH binds to which receptors (2)
V2 on renal principle cells -> increase water reabsorption via aquaporins
V1 receptor on vascular smooth muscle, causing vasoconstriction
What activates the baroreceptor reflex
A fall in blood pressure detected by a fall in CVP (atrial or other cardiopulmonary stretch receptors)
Sympathetic stimulation in baroreceptor reflex, actions:
Peripheral vasoconstriction, increased TPV
Renal vasoconstriction to decrease eGFR
Stimulate ADH to increase water reabsorption
Stimulate release of renin
Where are renin producing granular cells found?
Juxtaglomerular apparatus
What stimulates renin production
Fall in extracellular fluid volume, CVP or arterial BP
Decrease perfusion pressure in renal afferent arterioles
Decreased tubular NaCl concentration (detected by macula densa cells)
reduced eGFR
MOA of benzodiazepines
GABA receptor agonists, enhance inhibitory synaptic transmission throughout the CNS
Benzodiazepines duration of action:
Midazolam
Lorazepam / temazepam
Diazepam / chlordiazepoxide
<6hrs
12-18hrs
24-48hrs
Why do patients taking antipyschotic drugs get extra pyramidal side effects?
Blockage of dopamine receptors in the basal ganglia
Examples of extra pyramidal side effects
Parkinsonian symptoms - tremor, bradykinesia and rigidity
Dystonia
Dyskinesa
Akathsia - motor restlessness
Tardive dyskinesia - rhythmic, involuntary movements of the tongue / face / jaw
Treatment for acute dystonia
Acute dystonia should be treated with IM/IV anticholinergics (e.g. procyclidine).