Lecture 20 - Na+ handling by the Kidney II Flashcards
Summarise the reabsorption of the Na+ of the nephron
Proximal tubule - 67% of filtered Na+
Loop of Henle - 25% of filtered Na+
Distal Tubule - 5% of filtered Na+
Collecting Duct - 2.5% of filtered Na+
What is the relationship between the regulation of body Na+ and Na+ homeostasis?
Na+ Excretion = Filtered Na+ - Tubular reabsorption of Na+
The kidneys try to adjust excretion to match ingestion of Na+
What factors affect the tubular reabsorption of Na+? (6)
Changes in Starling forces
Renin-angiotensin-aldosterone system
Renal nerve activity
Prostaglandins
Atrial natriuretic peptide
Inhibitors of Na+/K+-ATPase
How does renal nerve activity affect the tubular reabsorption of Na+?
By constriction or dilation of either afferent or efferent arterioles next to glomerulus.
How do prostaglandins affect the tubular reabsorption of Na+?
PGE2 is stimulated after high BP and it inhibits the tubular Na+ reabsorption
How does atrial natriuretic peptide affect the tubular reabsorption of Na+?
When high BP, ANP is released from cardiac atria and reduces Na+ reabsorption by increasing cGMP in the collecting ducts which reduces Na+/K+-ATPase activity, decrease Na+ transport across the CD cells.
Which of the following statements is TRUE?
A. If the afferent arterioles are constricted the GFR will increase.
B. Atrial naturietic peptide decreases the tubular reabsorption of Na+.
C. If the efferent arterioles are constricted the GFR will decrease.
D. Na+ can be actively secreted by the cells of the collecting ducts
B. Atrial naturietic peptide decreases the tubular reabsorption of Na+.
What cells do we have at the juxtaglomerular apparatus (JGA)?
At the JGA we have the macula densa and granular (juxtaglomerular) cells
Where are the macula densa cells in the JGA?
In the thick ascending limb
Where are the Granular (Juxtaglomerular)
cells in the JGA?
In the smooth muscle of the
afferent arteriole
What is the function of the granular (Juxtaglomerular)
cells?
baroreceptor function
produces renin and angiotensin II
What is Angiotensin converting enzyme a major target for?
BP medication
What is aldosterone stimulated by?
Angiotensin II
What does aldosterone do?
Aldosterone increases Na+ reabsorption at the level of the late distal tubule and collecting duct
What is the Renin-Angiotensin-Aldosterone pathway?
Renin is released in low BP
Renin converts angiotensinogen from liver to angiotensin I (ANG I)
ANG I converts to ANG II via angiotensin converting enzyme
ANG II then goes on to stimulate the release of aldosterone
What is aldosterone and where is its receptor?
Aldosterone is a steriod hormone with a receptor inside the cell
What is the short term effect of aldosterone?
Upregulation of quiescent Na+ channels
What are the long term effects of aldosterone?
The further synthesis of Na+ channels, Na+/K+-ATPases and other induced proteins (genomic effects)
What are the aldosterone 3 phases of action?
Phase 1 – ‘latent’ period 0.5 - 1 hr
Phase 2 – ‘early response’ 1.5 - 3 hr
Phase 3 – ‘late response’ 6 - 24 hr
What happens in Phase 1 – ‘latent’ period in the action of aldosterone?
0.5 - 1 hr:
de novo protein synthesis; induce proteins (SGK)
What happens in Phase 2 – ‘early response’ in the action of aldosterone?
1.5 - 3 hr:
Activation of pre-existing Na+ channels and Na+/K+-ATPases
What happens in Phase 3 – ‘late response’ in the action of aldosterone?
6 - 24 hr:
Induction of ‘new’ Na+ channels and Na+/K+-ATPases
What is SGK?
Serum glucocorticoid simulating kinase - Enable channels to remain in membrane
What does de novo mean?
the formation of any of the various complex biomolecules from simple molecules or precursors via a certain biochemical pathway.
How is ENaC removed?
ENaC as it is removed by Nedd4-2.
Nedd4-2 activates the ubiquitination of ENaC by tagging it to be destroyed
What the mechanism of action for SGK?
SGK phosphorylates Nedd4-2 so it cannot remove the ENaC
What is ubiquitination?
Ubiquitination is a process through which ubiquitin molecules are attached to protein substrates for protein degradation.
Which of the following statements is TRUE?
A. The macula densa cells function as baroreceptors.
B. Aldosterone is a steroid hormone and binds to a receptor on the basolateral membrane of Late Distal Tubule and Collecting Duct cells.
C. Angiotensin II is cleaved by renin to produce Angiotensin I.
D. Renin is released from the granular (juxtaglomerular) cells of the afferent arteriole.
D. Renin is released from the granular (juxtaglomerular) cells of the afferent arteriole.
What is the major stimulus of Angiotensin II?
Increase in renin
What is the major stimulus of Aldosterone?
Increase in ANG II or increase in [K+]p
What is the major stimulus of ANP and BNP?
Increase in ECF volume
What is the major stimulus of AVP/ADH?
Increase in plasma osmolarity or decrease in ECF volume
What is AVP?
Arginine vasopressin is the same as ADH
Where is nephron site of action for ANG II?
PT
TAL
DT/CD
Where is nephron site of action for aldosterone?
TAL
DT/CD
Where is nephron site of action for ANP and BNP?
CD
Where is nephron site of action for AVP/ADH?
DT/CD
What hormones regulate NaCl and water reabsorption?
ANG II
Aldosterone
ANP and BNP
Sympathetic nerves
Dopamine
AVP/ADH
What is the effect of ANG II on NaCl and water reabsorption transport?
Increases NaCl and water reabsorption
What is the effect of aldosterone on NaCl and water reabsorption transport?
Increases NaCl and water reabsorption
- does not increase H2O transport in TAL
What is the effect of ANP and BNP on NaCl and water reabsorption transport?
Decrease in H2O and NaCl reabsorption
What is the effect of AVP/ADH on NaCl and water reabsorption transport?
Increase H2O reabsorption
What is the major stimulus for the renal sympathetic nerves for NaCl and water reabsorption?
Decrease in ECF volume
Where are the sympathetic nerves site of action in the nephron?
PT
TAL
DT/CD
What is the sympathetic nerves effects on NaCl and H2O reabsorption?
Increase NaCl and H2O reabsorption