Salt and Water Handling powerpoint Flashcards
Natriuresis
Discharge of Na+ through urine
How Na+ is regulated on venous side
1) Right atrial sensors
- when stretched release ANP, inhibit release ADH, decrease vascular resistance
2) Pulmonary receptors
- nerves located adjacent to pulmonary capillaries
- may sense early pulmonary edema leading to inhibition of sympathetic activity ?
How Na+ is regulated on arterial side
1) senses effective circulating volume via carotid sinus baroreceptor stretch —> leads to natriuresis
2) Sense increased renal BP (also relates to effective circulating volume) –> leads to natriuresis
How Na+ is regulated via chemoreceptors
-senses Na+ concentration
Effectors of Na+ regulation (5)
1) RAAS
2) Prostaglandins
3) Renal sympathetic nerves
4) Atrial natriuretic peptide
5) Nitric oxide
RAAS
1) Release renin from kidneys
2) Acts on liver to convert angiotensinogen to angiotensin I
3) Angiotensin I converted to Angiotensin II via ACE
e
Effects of Ang II
1) Na+ reabsorption in the proximal tubule (and likely distal sites as well)
2) at high concentrations AII causes vasoconstriction
3) Secretion of aldosterone
What is the function of aldosterone
-allows Na+ reabsorption in DCT/collecting duct in exchange for K+
Origin of prostaglandins
Arachidonic acid released from membrane phospholipids is metabolized to PGs by cyclooxygenase (COX-1 and COX-2)
Main PG in the kidneys
PGI2 (prostacyclin)
Overall effect of PGI2
-afferent arteriolar vasodilation and natriuresis
PGI2 synthesis in healthy subjects
There is little to no basal PGI2 synthesis
Trigger for PGI2 synthesis
-low ECFV states (ex CHF or cirrhosis)
-levels rise to maintain renal perfusion in the settng of high AII, SNS activity
CHF = low CO –> want to vasodilate afferent arteriole to increase GFR of kidney (overall will be getting more natriuresis because of increase GFR)
Effect of use of NSAIDs in low ECFV states
- remove counterregulation to low ECFV by prostaglandins
- resulting in Na+ retention and renal failure
What triggers renin release
Low bp (detected at juxtaglomerular apparatus) –> because overall going to cause Na+ reabsorption and H2O follows to increase intravascular volume
Effect of increasing SNS activity
-renin secretion (leading to increase Na+/H2O reabsorption)
What are kidney transplant patients who lack renal innervation prone to
ECF volume depletion
Types of natriuretic peptides-
1) Atrial natriuretic peptide (ANP)
2) B-type natriuretic peptide (BNP)
Renal effects of ANP/BNP
- increase GFR and natriuresis
- antagonism of almost all actions of the RAAS
What type of diuretics are ANP/BNP like
-effects similar to K+ sparing diuretics that act on the distal tubule/collecting duct
Uroguanylin production
-produced in the intestines in response to salt intake
Uroguanylin effect
-reduces renal sodium reabsorption (helping to compensate for ingestion of dietary sodium)
Nitric oxide diuretic properties
- appears to have diuretic properties separate from its vasodilatory powers
- NO deficiency/resistance implicated in some models of hypertension
Water and Na+ reabsorption in the kidney - @ different sites in the nephron
1) 27000 mmol of Na+ filtered/day
2) 18000 reabsorbed @ proximal convoluted tubule - 9000 remaining, [Na+] = 150
3) 6000 reabsorbed @ loop of henle, 3000 remaining [Na+] = 45
4) 2000 reabsorbed @ distal convoluted tubule - 1000 remaining [Na+] = 100 (more concentrated by reabsorbed H2O)
5) Cortical collecting duct
-700 reabsorbed
-300 remaining
-[Na+] = 100
6) Medullary collecting duct
150 reabsorbed, 150 remaining [Na+] = 150
Purpose of water regulation
To maintain a physiological Na+
Effect of disturbances in [Na+]
- change in ADH secretion
1) Loss H20
2) Increase [Na+]
3) Increase osmo
4) Cell shrinkage hypothalamus (H2O moves out of cells)
5) Increase release of ADH by posterior pit + the same osmotic stimulus in the hypothalamus increases thirst
Effect loss of pituitary function on regulation of water
-can lead to loss of ADH (central diabetes insipidus) but does not usually impair thirst
2 main vasopressin (ADH) receptors
1) V1
2) V2
Location of V1 receptor
- arterioles
- glomerular mesangial cells
- brain
Effect of V1 receptor
Mediates vasoconstriction
Location of V2 receptor
-located on the blood side of cells in the TAL and the collecting duct
Effect of V2 receptor
Mediates water movement down its gradient (water reabsorption)
Effect of V3 receptor
May lead to ACTH release by the pituitary
Physiological concentrations of ADH and activation of V1 receptors
Physiological ADH concentrations do not appear to be sufficient to cause activation of the V1 receptors
Non-osmotic stimuli of ADH release
1) Volume depletion
2) Nausae/vomiting
3) Pain
4) Medications (narcotics, chlorpropamide, carbamazepine)
5) Exercise
t1/2 of ADH
-minutes
Vasopressin (drug) - MOA
Selective V1 agonist
DDAVP MOA
Selective V2 agonist -leading to water reabsorption
What determines ECFV
Serum Na+ content
What determines intracellular fluid volume
Serum sodium concentration
What does the serum [Na+ ]reflect
The ratio of Na+ to H2O
What does serum [Na+] not correlate with
- ECFV (volume status)
- body sodium content
What do alterations in [Na+] reflect
- reflect imbalances in the ratio of salt to water
- this imbalance is almost always due to disturbances in water content
Principal extracellular osmoles
- main = NaCl
- to lesser extent K+, HCO3-
Principal intracellular osmoles
- K+
- to lesser extent organic phosphates (DNA, RNA, ATP, phospholipids etc)
Na+ location
Is restricted to the extracellular compartment
Why changes in body salt content result in corresponding changes in body water content
1) Na+ restricted to extracellular compartment
2) Loss/gain Na+ changes osmolarity extracellular compartment - H2O moves in/out of extracell compart to balance intra/extracell
3) Overall = ECG volume changes but Na+ concentration remains fixed
Cerebral edema
- low extracellular osmolarity vs. intracellular space
- water flows into cells in brain to reach new equilibrium
How to avoid problem with water flowing into cells (causing lysis)/how Na+ content determines ECF volume
- excrete excess water
i. e. if Na+ is added/subtracted from the body water will be retained or excreted in order to keep osmolarity normal
Consequence of CHF
1) Reduced CO
2) Decrease pressure loading of arterial sensor (decreased effective circulating volume)
3) initiation of processes leading to salt retention
4) Water retention -increase intravascular volume (volume loading?)
Result increase Na+
Edema
Result decreased Na+
Hypovolemia, or shock
Result increase H2O
Cerebral edema
Result decreased H2O
Osmotic demyelination
Osmoregulation vs volume regulation (Na+ concentration vs. Na+ content)
a) what is being sensed
Osmoregulation:
-plasma osmolarity
Volume regulation
-effective circulating volume
Osmoregulation vs volume regulation (Na+ concentration vs. Na+ content)
b) sensors
Osmoregulation -hypothalamus Volume regulation -carotid sinus -atria renal circulation
Osmoregulation vs volume regulation (Na+ concentration vs. Na+ content)
c) effectors
Osmoregulation -ADH Volume regulation -sympathetic nerves -RAAS -natriuretic peptides -pressure natriuresis -ADH
Osmoregulation vs volume regulation (Na+ concentration vs. Na+ content)
d) what is affected
Osmoregulation -water excretion (via ADH) -water intake (via thirst) Volume regulation -Na+ excretion
What is happening to H20/solutes at each point in the nephron
- Prox. tubule = lots of isotonic reabsorption
- Descending limb = concentrating segment (water reabsorbed)
- Ascending limb = diluting segment (solutes reabsorbed)
- Distal tubule = some additional salt/H2O reabsorbed but urine is dilute
- Collecting duct = if ADH acting, water reabsorbed down its gradient, otherwise urine remains dilute
Concentrating segment
Descending loop of henle (H2O reabsorbed)
Diluting segment
Ascending loop of henle (Na+ reabsorbed)
Principles of concentrating urine (what does movement of H2O rely on)
- water is never pumped –> can only diffuse to area of higher tonicity
i. e. the kidney must maintain an area of high tonicity
What is responsible for getting water to diffuse from nephron
- active transport in the TAL (thin ascending limb)
- Na/ K ATPase –> create concentration in the interstitium
- water is not permeable at this segment (but sets up gradient for movement of water in adjoining segments that are permeable to water)
ie. in the DCT and CD ADH sensitive H2O channels allow water to leave as long as [urine] <[interstitium]
Max [urine]
-1200 mM (concentration in interstitial deep in the medulla)
Extremes of renal function in healthy people
a) water conservation
b) salt conservation
c) water excretion
d) salt excretion
1) as little as 450 ml of urine per day can be normal
2) as little as 1-2 mmol/L Na{
3) 10+ L/day of very dilute urine
4) up to 800 mmol/day or 18g
What is oncotic pressure equal to
= colloid osmotic pressure = osmotic pressure exerted by proteins (colloids)
Permeability of blood vessel walls and how this affects osmotic gradient
-blood vessel walls are permeable to salt and water (therefore no osmotic gradient
Albumin
- largest
- most plentiful pasma protein
Location of most of the body albumin
In the interstitium
-however concentration here is lower ue to high volume of interstitial vs. intracascular fluid
Net trans-capillary pressure -forces involved
1) Hydraulic pressure: Favours movement of fluid out of the capillaries
2) Oncotic pressure favours rention in the capillaries
What does balance of trans-capillary pressure cause (net result)
Slight movement out with lymphatics returning this fluid to venous circulation
Causes of trans-capillary fluid shifts + consequence
1) Increase capillary permeability (sepsis)
2) Increase hydraulic pressure (venous congestion)
3) Decrease albumin (decreased production, loss via GI tract or urine)
- all can lead to edema
Sodium content in people with edema
Always increased
