Sodium regulation responds primarily to changes in what?
blood volume
What is the primary effector for controlling sodium?
RAAS
Water regulation responds to changes in…
osmolarity and ECF volume
what is the primary effector for water regulation?
ADH
This hormone stimulates sodium reabsorption in the late distal tubule and collecting duct.
Aldosterone
Aldosterone regulates sodium reabsorption, but also stimulates the secretion of…
potassium
What stimulates the release of aldosterone?
increased [ATII] or plasma [K+]
Aldosterone accounts for 2-3% of filtered sodium… this amounts to how many grams of NaCl per day?
30g
What is an aldosterone antagonist?
spironolactone
To what cells in the late distal tubule does aldosterone bind?
principal cells
on the principal cells, what receptor does aldosterone bind to?
intracellular mineralcorticoid receptor (MR)
The Aldosterone-MR complex up regulates…
apical ENaCs and K+ channels
sodium/potassium ATPase, hydrogen-ATPase
Mitochondrial metabolism
Increased ATII concentration is sensed by the ______ whch stimulates release of aldosterone.
adrenal cortex
Angiotensin II stimulates what channel protein in the proximal nephron?
sodium hydrogen exchange (NHE)
This hormone’s general function is to increase salt retention and increase arterial blood pressure…
Angiotensin II
What hormone stimulates the release of aldosterone?
ATII
ATII has what effect on thirst?
increases thrist
What effect does AT II have on RBF?
reduces RBF
Which arteriole does ATII act upon?
efferent arteriole
At low levels of ATII, what happens to GFR?
maintained or slightly increases
At high levels of ATII, what happens to GFR?
GFR decreases
Why does GFR decrease with high dose of ATII?
effect on afferent arterioles which reduces RBF
Why is GFR maintained at low dose of ATII?
vasoconstriction of efferent arterioles ensures GFR is maintained.
ATII stimulates the production of two vasodilator that act on the afferent and efferent arterioles, thus protecting RBF… what are those two vasodilators?
PGE2 and PGI2
Where is renin released?
juxtaglomerular apparatus
ATII levels are primarily controlled by what hormone?
renin
What are the three broad components to renin release?
intrarenal baroreceptors (BP)
macula densa (Sodium Conc.)
renal sympathetic nerves (SNS stim/Epi)
The intrarenal baroreceptors are what type of JGA cell?
granular cells
granular cells act as ______ which respond to what change in the afferent arterioles
baroreceptors
stretch
renin release from the intrarenal baroreceptors has a ______ relationship with pressure in the afferent arterioles
inverse
The macula densa senses GFR changes via changes in flow to the distal tubule. What relationship does MD renin release have with GFR?
inverse
Renal sympathetic nerve stimulation via _______ receptors increases what?
beta receptors
increase renin release
In a hemorrhage, low BP stimulates renin production via…
intrarenal baroreceptors
in a hemorrhage, what SNS receptor is stimulated on which cells?
Beta receptors on granular cells
In a hemorrhage, the macula densa senses a decreased renal blood flow/GFR which stimulates granular production of…
renin
Which region of the nephron is responsible for sensing and initiating the integrated response that leads to renin secretion?
the JGA
A decreased renal arteriole stretch and decreased tubular sodium load stimulates the release of…
renin
Increased plasma renin causes increased presence of ___
ATI
What enzyme is responsible for converting ATI to ATII
ACE
ATII stimulates the secretion of_________, which lowers sodium excretion and therefor eincreases blood volume
aldosterone
This hormone is released from the atria when blood pressure is high
ANP
ANP has what effects on the renal arterioles?
dilates afferent
constricts efferent
ANP will have what effect on GFR and the FL of sodium?
increases GFR and sodium filtered load
What are the two ways by which ANP decreases NaCl reabsorption?
inhibits renin/aldosterone secretion
inhibits sodium uptake by medullary collecting ducts
Does ADH have an effect on NaCl excretion?
very small
Which hormone is the most important for regulating water balance?
ADH
ADH stimulates adenylate cyclase and cAMP to increase the expression of…
aquaporins
Hypothalmamic osmoreceptors are sensitive to small changes in…
plasma osmolarity
Hypovolemia has what effect on ADH secretion?
stimulates ADH secretion
ADH has three main affects that impact water balance… they are…
increase CD water and urea permeability
increase NKCC2 transporters to increase medullary gradient
Decreased plasma volume leads to decreased BP. What mediates ADH secretion in this scenario?
cardiovascular baroreceptors
Increased ADH means _______ H2O excretion
decreased
Excess water leads to decreased fluid osmolarity, leading to decreased ADH secretion. This reflex is mediated by…
osmoreceptors
Does drinking a large amount of water lead to increased solute excretion?
no… large volume of dilute urine excreted, but solute excretion remains constant
This measure is the ml/min of blood plasma that is cleared of osmotically active particles…
osmolar clearance
osmolar clearance is expressed by what equation…
Cosm = Uosm(V) / Posm
Normal Cosm is…
1 to 2 ml/min
Reduced Cosm leads to…
positive osmolar balance–gaining osmoles and water
What can cause a reduced Cosm?
decreased GFR, increased aldosterone
Increased Cosm leads to…
dumping of osmolytes and a loss of ECF
What causes increased Cosm?
diuretics and/or low aldosterone
Dehydration results in ___osmotic volume ______
hyperosmotic volume contraction
What type of fluid shift occurs from diabetes insipidus?
hyperosmotic volume contraction
This condition presents with the following characteristics:
high plasma osmolality
low urine osmolality
polyuria
polydipsia
Diabetes insipidus
What is the major cause of the sxs of diabetes insipidus?
low or ineffective ADH
Neurogenic cause of diabetes insipidus is due to…
hypothalmic-pituitary injury
insufficient ADH secretion
Will neurogenic diabetes insipidus patients respond to exogenous ADH?
yes
Nephrogenic diabetes insipidus is due to…
insufficient renal response to ADH
What are some common causes of nephrogenic diabetes insipidus?
defective V2 receptor
lithium toxicity
hypercalcemia
Describe the plasma concentration of ADH in nephrogenic diabetes insipidus?
high plasma ADH
An acute water load causes what type of fluid shift?
hyposmotic volume expansion
What is the mechanism of hyposmotic volume expansion in acute water load?
Excess water –> decreased plasma osmolality –> decreased ADH –> decreased CD water permeability –> increased diuresis
SIADH leads to what type of fluid shift?
hyposmotic volume expansion
What are common causes of SIADH?
head injury and lung tumors causing excessive ADH secretion
SIADH results in chronic ECF ______ and ______natremia
dilution
hyponatremia
What causes the excess renal sodium loss in SIADH?
decreased aldosterone and increased ANP
What cation determines the volume of the ECF compartment?
sodium
Sodium loss from diarrhea, vomiting is ____tonic
isotonic
Changes in sodium concentration in the ECF are generally caused by changes in ________
body water content
Hyponatremia is sodium concentration of…
< 135 mEq/L
What causes hyponatremia due to blood volume depletion
excess ADH
Thirst
What causes hyponatremia due to excessive water conservation?
SIADH
What causes hyponatremia secondary to excessive water intake
water intoxication
Hypernatremia is rarely chronic because…
excess sodium causes thirst
Hypernatremia is defined as sodium concentration of…
> 145 mEq/L
What are two common causes of hypernatremia?
loss of water from dehydration or diabetes insipidus
gain of sodium
Muscle stretch in the kidneys causes _______ which stimulates _________ to force urine into bladder…
causes pacemaker activity
stimulates peristalsis
What causes the urge to urinate?
stretching of trigone
When is the urge to void felt?
150 ml
What is the max volume of the bladder?
500-800 ml
SNS predominates the bladder during…
filling
PNS predominates in the bladder during…
micturition
SNS causes the detrusor to _____ during filling and the internal sphincter to ______
detrusor relaxation
sphincter contraction
The PNS causes the detrusor to _________ and the internal sphincter to ________
detrusor contract
sphincter relaxation
Is the external sphincter under ANS or voluntary control?
voluntary
What SNS receptor type is responsible for detrusor relaxation?
Beta 2
What SNS receptor type is responsible for the internal sphincter contraction?
alpha 1
What PNS receptor types are responsible for micturition?
muscarinic