Endocrinology Flashcards
what are the two nuclei that contribute to the posterior pituitary and what hormones do they release, and where are their cell bodies located
cell bodies of the nuclei are located in the hypothalamus and send their axons down to the posterior pituitary
Supraoptic nucleus: release ADH
Paraventricular nucleus: release Oxytocin
how is the signal conveyed in the supraoptic nucleus to the release of ADH
Prepropressophysin is cleaved and pacakged into Propressophysin in the Hypothalamus (cell body of neuron
then travels down the hypothalamic hypophyseal tract to the posterior pituitary where it cleaves the neurophysins to release ADH
ADH targets the kidney and arterioles to regulate body fluid
Full pathway of signal for ADH
Baroreceptor input from the carotid sinus or aortic arch
travels in the vagus and glossopharyngeal nerves to the vasomotor center (medulla oblongata)
travels to the supraoptic nerve to then tell it to release ADH/Vassopressin from the posterior pituitary
what are the triggers for ADH secretion
decrease in blood pressure (carotid and aortic baroreceptors)
decrease in arterial stretch due to low volume (atrial stretch receptors)
increase in osmolality (below 280 mOsM) (hypothalamic osmoreceprots) (MOST SENSITIVE)
increase in angiotensin II
sympathetic stimulation
what does ADH act on and what are their receptors
Blood vessels to vasoconstrict
-V1 recpetors
Kidney to reabsorb water
-V2 receptors
how does volume contraction/expansion affect the extracellular fluid volume
less extracellular volume there is an increase in ADH secretion
more extracellular fluid volume means there is a decrease in ADH secretion
as Osmolality increases, there is an increase in ADH secretion
Mechanism of action of ADH in the kidney
affects the renal collecting duct!
bind V 2 receptors on a G-coupled protein to activate adenyl cyclase to make cAMP to increase the amounto of Aquaporin 2 transporters on the apical membrane (facing lumen of the collecting duct)
this allows for the retention of water from the tubular lumen back into the cell
then will go through aquaporin 3 back into the peritubular fluid (ECF) and bloodstream
sodium will still travel down the collecting duct and be excreted out
what is the physiological process under Hyperosmolarity
dehydration
increase amount of ADH in the blood stream
kidneys will increase permeabillity in collecting duct and late distal tubule, more retention of water from the urine so less water is lost (more concentrated urine)
also body will increase thirst drive
leads to decrease in plasma osmolarity
what is the physiological process under Hypoosmolarity
hypervolemia
too much water
decrease of ADH in the blood
decrease in permeabillity of principle cells in collecting duct
decrease of H2O reabsorption
increase urine volume
decrease urine osmolarity
increase in plasma osmlarity
Diabetes insipidus and what are the two kinds
lack of an effect of ADH on the renal collecting duct
- causes frequent urination
- large volume of urine that is diluted
Central DI: lack of ADH in the plasma
- damage to pituitary or hypothalamus
- treat with desmopressin that prevents water excretion
Nephrogenic DI: kidneys cant respond to ADH (even with high levels of plasma ADH)
- caused by drugs like lithium
- or chronic kidney disorders
- desmopressin treatment does not work
how to tell the difference between the Central diabetes insipidus vs Nephrogenic
if given a water deprivation test and the urine Osm increases with desmopressin then it is central, also have a low level of plasma ADH
if high level of ADH and desmopressin does not change the urine osm significantly then is a nephrogenic disorder
Syndrome of Inappropriate ADH secretion (SIADH)
- excessive secretion of ADH
- excessive water retention
- Hypoosmolality fails to inhibit ADH release
caused from a lung carcinoma releasing vasopressin, or adrenal insufficiency
water retention
sodium loss
hyponatremia
Plasma osmolality decrease
urinary osmolality increase
what are the two ways that aldosterone is secreted
Hypothalamus sends CRH to the anterior Pituitary to release ACTH what goes to the zona glomerulosa to release aldosterone which then acts on the kidneys to increase absorption of Na+ and water and excrete K+
the other way is through the RAAS system
- BP decreases so the kidney releases renin
- renin converts angiotensinogen (produced by liver) to angiotenson I
- ANgiotensin I is converted to angiotensin II via ACE in the lungs
- Angiotensin II acts on the adrenal cortex to release aldosterone to increase absorption of Na+ and water and excrete K+
how does aldosterone act on the kidney?
- combines with an cytoplasmic receptor in the distal nephron to increase transcription of new channels and pumps for the apical side of the cell
- from the lumen of the distal nephron, the neew transporters will absorb Na+ and excrete K+
- on the basal side, the Na+/K+ ATPase will pump the sodium back into the blood
- also water will be retained as well since it will follow the concentration of Na+
how does angiotensin II affect the arterial pressure
- increase thirst
- increase vasoconstriction to increase TPR
- increase aldosterone
- increase Na+ reabsorption
- Increase ECF volume
what are the affects of an primary adrenal insufficiencu
decrease in both cortisol and aldosterone secretion
what are affects of a secondary or tertiary adrenal insufficiency
decrease in cortisol
but still have aldosterone since there is the RAAS system functioning!
what is the function of ANP and where is it secreted? what is Urodilatin
ANP secreted from the myocytes of the atria
- atrial natriuretic peptide
- release when atria distended and reduces blood pressure by increaseing secretion of NaCl of and water via the kidneys (Collecting duct)
- BNP as well in brain
- both decrease BP
- vasodilate afferent and vasoconstrict efferent arterioles to increase in GFR and filtered load of sodium
- inhibit renin
- inhibit aldosterone
- inhibit ADH secretion
Urodilatin: renal natriuretric peptide
- secreted by the distal tbule and collecting duct
- it influences only the function of the kidney
- stimulated by increase in BP or ECF volume
- inhibits NaCl reabsorption
How does the sympathetic nerve activity contribute to the regulation of NaCl and water reabsorption
- Catecholamines release from the sympathetic nerves stimulate reabsorption of NaCl and water by the proximal tubule, thick ascending limb, distal tubule and collecting tube
- decrease GFR
- increase renin
- Increase reabsorption Na+ along the nephron
How does the body respond to increase in sodium intake
- increase in ECF volume
- increase in ANP (constriction of efferent arterioles increase in GFR)
- decrease in capillary oncotic pressure
- decrease in renin
- decrease in sympathetic activity (dilation of afferent arterioles increase of GFR)
all leads to an increase in Na+ excretion
How does the body respond to an decrease in sodium intake
- Decrease in ECF volume
- Increase in sympathetic activity (constriction of afferent arterioles (decrese in GFR)
- decrease in ANP dilation of efferent arterioles (decrease in GFR)
- increase in capillary oncotic pressure
- increase in renin
what causes a K+ shift out of the cells
Hyperkalemia
- Insulin deficiency
- B2 adrenergic antagonists
- alpha adrenergic agonists
- acidosis
- hyperosmolarity
- cell lysis
- excersise
what causes a K+ shift into the cells
Hypokalemia
- insulin
- B2 adrenergic agonists
- alpha-adrenergic antagonists
- alkalosis
- hyposmolarity
how does insulin affect the internal K+ balance
Insulin stimulates K+ uptake into cells by increasing the activity of Na+/K+ ATPase
deficiency of insulin leads to hyperkalemia because cells wont uptake K+
what is the aldosterone paradox
undesired losses of potassium is caused when sodium retention is required to maintain extracellular volume
undesired retention of sodium is caused when potassium loading alone provides the stiumuls to aldosterone secretion
the negative feedback that couples aldosterone with serum potassium is fundamental in potassium regulation
Hyperaldosteronism results in potassium loss
hypokalemia reduces aldosterone production
hyperkalemia increases aldosterone production facillitating potassium secretion
what are causes of increased K+ excretion and hypokalemia
Liddle syndrome: increased ENaC
- low renin, aldosterone
- high BP/ECF
Decreased B-hydroxysteroid dehydrogenase: excess mineralcorticoid
-low renin
low aldosterone
-high BP/ECF
Adrenal tumor
- Low renin
- high aldosterone, ECF and BP
COndenital adrenal hyperplasia (17)
- low renin
- high aldosterone, BP/ECF
Renin secreting factor
-high renin, aldosteone, ECF/BP
how is the aldosterone cascade protected from activation via cortisol
11B-HSD2 enzyme
Mineralcorticoids, cortisol, sex hormones, BP, K+, labs, other presentations: 17a enzyme deficiency
Mineralcorticoids: increase
Cortisol: decrease
sex hormones: decrease
Blood pressure increase
Potassium: decrease
Labs: decrease in androstenedione
other: lack of secondary sexual characteristics
Mineralcorticoids, cortisol, sex hormones, BP, K+, labs, other presentations: 21B
Mineralcorticoids: decrease
Cortisol: decrease
sex hormones: increase
Blood pressure decrease
Potassium: increase
Labs: increase of renin
increase of 17-hydroxy-progesterone
other: salt wasting
precocious puberty
virilization
Mineralcorticoids, cortisol, sex hormones, BP, K+, labs, other presentations: 11B
Mineralcorticoids: decrease in aldosterone
increase in DOC
Cortisol: decrease
sex hormones: increase
Blood pressure increase
Potassium: decrease
Labs: decrease renin
other:
virilization
Causes of decreased K+ excretion and hyperkalemia
Decreased ENaC
- high renin, aldosterone
- low ECF/BP
Hypoaldosteronism: adrenal insufficiency
- High renin
- low aldosterone, ECF/BP
Hyporenin-hypoaldosteronism: B blockers, autonomic neuropathy
-low renin, aldosterone, ECF and BP
Hypocalcemia
decreased plasma Ca+ concentration
- hyperreflexia, twitching, muscle cramp
- chostek sign, trosseu sign
reduces the activation threshold for Na+ channels
- easier to evoke AP
- spontaneous AP
- tingling and numbness and muscle twitches
Hypercalcemia
increased plasma Ca+ concentration
- decreased QT interval, constpation, lack of appetite, polyuria, polydpsia, hyporeflexia, lethargy
- decreased membrane excitabillity
- harder for action potentials
How does acids and base abnormalities affect ionized Ca+ concentrations
Albumin binds to free ionized Ca+ depending on the levels of H+
acidemia: lots of H+ bound to albumin therefore more free circulating Ca+ increased
alkalemia: less H+ so free ionized concentration decreased because bound to albumin
Relationship between Ca+ and Phosphate and what is the hormone that regulates Ca+
extracellular concentration of Pi is inversely related to Ca+
-both are regulated by same hormones
regulated by PTH
How does PTH affect the levels of calcium
decrease in plasma Calcium leads to an increase in PTH
-increase bone resorption
at kidney:
- decrease Pi reabsorption
- increase Ca reabsorption
- increase urinary cAMP
at intestine:
-increase Ca absorption via vitamin D
what does calcitonin do
stop bone resorption
Mechanisms of PTH on kidney
inhibit NPT2 by PTH at the proximal tubule stops the resorption of Phospate
-also excretes cAMP
PTH stimulates reabsorption in the TAL (thick) and distal tubule
what is the regulation of PTH gene expression and secretion
increase of the Ca+ concentration inhibits PTH synthesis and secretion via CaSR and vitamin D levels
how is vitamin D activated and regulated
after eating Vitamin D (cholecalciferol)
-liver converts to 25-OH-cholecalciferol (circulating form)
in kidney
-CYP1a hydroxylase convrts 25-OH-cholecalciferol to active form 1,25-OH2-cholecalciferol
CYP1a is reguulated at the transcriptional level via the amount of Ca+ in blood by binding to CaSR and inhibiting the CYP1a gene
Familial Hypocalciuric hypercalcemia
Autosomal dominant disorder
-mutations that inactivate CaSR in parathyroid gland and in the ascending limb of the kidney
- decrese in urinary Ca+
- increase in serum Ca+
PTH: normal or increased serum Ca: increased urine Ca: decreased Pi: normal Vitamin D: normal
