Salt and water handling Flashcards
Renin angiotensin aldosterone system
- Renin released from kidneys n response to stimuli
- Converts angiotensinogen to Ang I in liver
- Ang I converted by ACE to ang II which has effect in body both directly and via aldosterone
Angiotensin II
- Na+ reabsorption in the proximal tubule and lielyi distal sites as well
- At higher concentration causes vasoconstriction
- releases aldosterone
What is the function of aldosterone
Allows Na+ reabsorption in the DCT/collecting duct in exchange for K+
Prostaglandins -formation
arachidonic acid released from phospholipids, is metabolized to PGs by cyclooxgenase
Prostaglandin action in the kidney
-main PG is PGI2 (i.e. prostacyclin)
PGI2 role
=afferent arteriole vasodilation and natriuress
Prostaglandins in healthy
-little or no basal PGI12 syntheiss
When do prostaglandin levels rise
-in low ECGV states (CHF or cirrhosis) PGI2 levels rise to maintain renal perfusion in the setting of high AII, SNS activity ect
NSAIDS in certain people -safety
NSAIDS will remove the counteregulation…
How renal sympathetic nerves regulate kidney function
- increase SNS activity leads to renin secretion
- greater activity of SNS also directly causes increase Na+ /H2O reabsorption
Kidney transplant patients - effect SNS
-lack renal innervation (cant attach sympathetic nerves during surgery) and therefore seem to be prone to ECF volume depletion
Natriuretic peptides
-atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)
Renal effects of natriuretic peptides
-increase GFR and natriuresis (latter effect similar to the poss)
Uroguanylin production
gut natriureti peptide
-produced in intestines in response to salt intake (probably as a prohormone)
Uroguanylin effect
- reduces renal sodium reabsorption, helping to compensate for ingestion of dietary sodium
- not a target for pharmacological intervention yet
Nitric oxide effect
-appears to have diuretic properties (separate from its vasodilatory powers) and NO deficiency or resistance has been implicated in some models of hypertension
Salt reabsorption –> major sites in nephron
- total 27000 mmol Na+ is filtered per day excreting 150 mmol of Na+ in a day
1. Proximal convolutedd tubule filter 27000 mmol –> takes back 18,00 and 9000 travelling more distally
2. Loop of henle –> reabsorbs 6000, 3000 goes more distally
3. In cortical collecting duct 700 reabsorbed, 300 remains
4. In medullary collecting duct 150 reabsorbed 150 remains
Water regulation -purpose
-regulated to maintain a physiological [Na+]
-disturbances of Na+ lead to change in ADH secretion
-loss of water = increase Na+ concentration = increase osmolarity leading to cell shrinkage in hypothalamus = increase release of arginine vasopressin (ADH) by posterior pituitary
+ increase thirst (same osmotic stimulus in hypothalamus leads to increased thirst)
Effect loss pituitary function
-can lead to loss of adh = central diabetes insipidus –> does not usually impair thirst so can still survive?
ADH receptors
2 main vasopressin receptors
V1
V2
(V3)
V1 receptor
- located in arterioles, glomerular mesangila cells, and the brain
- mediates vasoconstriction
V2 receptor
-located on the blood side…
ADH and V1 receptor activation
physiological adh nnot sufficient to cause activation of V1 receptor
Non osmotic stimuli of ADH
- Volume depletion
- Nausea/vomiting
- Pain
- Medications (narcotics, chlorpropamide, carbamazepine)
- Exercise
Half life of endogenous vasopressin
t1/2 of minutes
MOA of vasopressin drug
-a selective V1 agonist which can be used in the treatment of shok in the ICU setting
DDVP
??
What determines the extracellular fluid volume
The serum sodium content (number of Na+ particles)
What determines the serum sodium concentration
Determines the intracellular fluid volume (not under direct physiological control due to water permeability of cell mebranes)
-no hormones involved in this (automatic)
What does serum [Na+] reflect
- the ratio of Na+ to water
- it does not correlate wtih ECFV (volume status) or body sodium content
What do alteration in Na+ concentration reflect
- imbalances in the ratio of salt to water
- almost always this is because of disturbance in water content
Main intracellular ion vs. extracelluar
Na+ main extracellular, K+ main intracellular
What do change in body salt content result in
-corresponding change in body wter content such that ECF volume changes but sodium concentration…
MOA cerebral edema/coning
1) Loss Na+ (hyponatremia) –> decrease Na+ content in same volume of fluid = lower Na+ concentration
2) Water therefore flows into the cells to reach a new euiqlibrium (low extracellular osmolality compared with the intracellular space)
3) Water flows into cells to reach new equilibrium
4) Water expands in cells –> edema (conning why??)
CHF
1) Reduced CO
2) Decreased presure loading of arterial sensors =decreased effective circulating volume
3) Initiates several processes leading to Na+ retention
4) If the extracellular fluid becomes salty other signals act to retain water as well
Effect Na+
a) increased
b) decreased
a) edema
b) hypovolemia or shock
Effect H2O
a) increased
b) decreased
a) cerebral edema
b) osmotic demylination
How low sodium content leads to low Na+ concentration via ADH
1) Decreased Na+
2) Decreased sodium concentration (via ADH induced H2O retention)
What is being sensed
a) osmoregulation
b) volume regulation
1) plasma osmolarity
2) volume regulation
Sensors
a) osmoregulation
b) volume regulation
X
X
X
X
X
How to change the concentration of urine
X
x
- Prox tubule = lots of isotonic reabsorption
- Descending lumb = concentrating segment = water reabsorbed but salt isnt
- Ascending limb = diluting segment = solutes reabsorbed
- Distal tubule = some additional salt/H2O reabsorbtion but in general urine remains diluted (relative to the blood):
- Collecting duct: if ADH acting, water reabsorbed down its gradient, otherwise urine remains dilute
Diluting the urine - requirements
TAL must be functioning in order to create.
Concentrating the urine MOA
Water must be removed to leave behind a concentrated urine
