Sodium Flashcards
(36 cards)
1
Q
How does water move and its relation to sodium?
A
- Water will move from an area of low osmolality to an area of high osmolality
- As sodium moves, water will move
2
Q
What is the location of the Kidneys?
A
- Located between the 11th thoracic and 3rd lumbar vertebrae in the retroperitoneum on either side of vertebral column
- The right kidney is lower than the left kidney
3
Q
What are parts of the kidneys?
A
- Renal Capsule
- Renal Pelvis
- Ureter
- Renal Vein
- Renal Artery
- Renal Medulla
- Renal Cortex
4
Q
What is the gross anatomy of the kidneys?
A
- Dimensions: 13 x 6 x 4 cm
- Weight: ~150 g each
- Cardiac output: Receives 20 – 25% of which 90% supplies the renal cortex
5
Q
What are parts of the nephron?
A
Functional unit of kidney and contains approx 1 million
- Renal Artery and Vein
- Glomerular Capsule/Bowmans Capsule
- Proximal Convoluted Tubule
- Loop of Henle: Thin descending loop, Thin ascending loop, Thick Ascending loop
- Distal Convoluted Tubule
- Collecting Duct
6
Q
How does sodium reabsorption take place?
A
- <1% filtered Na+ is excreted in the urine
- Therefore, >99% filtered Na+ must be reabsorbed via a process of tubular reabsorptiom which involves PROTEIN CARRIERS and ION-SPECIFIC CHANNELS
7
Q
How does Sodium reabsorption take place in the Proximal Convuluted Tubule?
A
There is secondary active transport in PCT. Energy from basolateral through Na+-K+-ATPase. This creates favourable inward gradient for Na+
- Na+-H+ ANTIPORTERS: Most Na+ reabsorbed in exchange for H+. It also allows reabsorption of HCO3-
- Na+-SOLUTE CO-TRANSPORTERS: Allows simultaneous reabsorption of various organic & inorganic solutes
8
Q
How does the Loop of Henle absorb Sodium?
A
Basolateral membrane
- Secondary active transport due to energy from basolateral Na+-K+-ATPase. This creates favourable inward gradient for Na+
- Cl- leaves cell via channel which creates favourable inward gradient for Cl-.
Apical membrane
- NKCC2 CO-TRANSPORTER: Na+ reabsorbed with K+ & 2x Cl-. Potassium is recycled back via ROMK1
- Mg2+ & Ca2+ REABSORPTION: K+ movement drives reabsorption of Mg2+ & Ca2+
9
Q
How does the Counter-Current System work?
A
- Descending limb is permeable to H2O and some NaCl
- The Ascending limb is impermeable to H2O and able to transport NaCl into the interstitium via NKCC2
- This helps create a gradient within the medulla that gets more concentrated as the loop enlongates.
10
Q
How does efficiency of the counter current system change?
A
- Efficiency depedns on the length of the loop of Henle
- JUXTAMEDULLARY NEPHRONS are more important for this process as they are longer
- Cortical nephrons make little contribution due to them being shorter in length
11
Q
How does the DCT reabsorb Sodium?
A
Basolateral
- Secondary active transport through energy from basolateral Na+-K+-ATPase. This creates favourable inward gradient for Na+
- Cl- leaves cell via channel which creates favourable inward gradient for Cl-
Apical
- Na+ reabsorbed with Cl-
12
Q
How does the Collecting Duct reabsorb Sodium?
A
- In CD, luminal concentration of Na+ can be lower than intracellular Na+ so can’t set up concentration gradient!!
APICAL SODIUM CHANNEL
- Na+ channel is electrogenic. Electronegativity allows Na+ entry into the cell. K+ is secreted simultaneously to balance charge
- Intracellular electronegativity generated by Na+-K+-ATPase
- Controlled by ALDOSTERONE
13
Q
Which conditions are diuretic prescribed?
A
- Hypertension
- Heart failure
- Liver cirrhosis
- Nephrotic syndrome
14
Q
What is the effect of Diuretics?
A
- Cause NEGATIVE FLUID BALANCE
- Decreases renal NaCl reabsorption and increases urinary losses of Na+ and therefore H2O
15
Q
What are the main classes of Diuretics?
A
- Loop Diuretics
- Thiazide Diuretics
- Potassium-sparing
16
Q
What is the action of Loop Diuretics?
A
Promote excretion of 20-25% filtered Na+ at max dose
- TARGET: Thick ascending limb of the Loop of Henle
- INHIBIT: NKCC2
- ACTION: Compete with Cl- for binding sites on NKCC2
17
Q
What is the action of Thiazide Diuretics?
A
Promote excretion of 3-5% filtered Na+ at max dose (Less potent than Loop Diuretics)
- TARGET: Distal convoluted tubule
- INHIBIT: NaCl cotransporter
- ACTION: Compete with Cl- for binding sites on NaCl cotransporter
18
Q
What are Potassium Sparing Diuretics?
A
Promote excretion of 1-2% filtered Na+ at max dose. Avoid renal K+ wasting
- TARGET: Principle cells of collecting duct
- INHIBIT: ENaC
- ACTION: Decrease the number of open Na+ channels inhibiting the channel directly (amiloride) or competitively inhibiting aldosterone binding to MR (spironolactone, eplenerone)
19
Q
What is the Renin-Angiotensin Alsoterone system?
A
- Renin released which cleaves angiotensinogen to angiotensin 1
- Angiotensin is converted to angiotensin 2 by the Angiotensin converting enzyme (ACE)
- Angiotensin 2 leads to proudction of Aldosterone which leads to sodium and water rentention.
- This leads to systemic volume expansion
20
Q
Where is Renin secreted from?
A
- Synthesized and secreted by juxtaglomerular cells which are part of juxtaglomerular apparatus (JGA
- They are specialised smooth muscle cells that are sensitive to arteriolar stretch ie. sense changes in ECF volume
- Sodium is the main determinant of Renin Secretion
21
Q
Where is ACE mainly found and which proteins does it act on?
A
Dipeptidyl carboxypeptidase highly concentrated in the lungs. It acts to cleave dipeptides from a range of substrates:
- Angiotensin I
- Bradykinin
- Substance P
- Enkephalins
22
Q
Describe the Angiotensinogen metabolism
A
Angiotensinogen
- 60 kDa, α2-globulin
- Produced by the liver
- Normally present in the plasma at a concentration of 1 mmol/L
Angiotensin 1
- Formed from the cleavage of a decapeptide from angiotensinogen which is catalysed by RENIN
- INACTIVE
Angiotensin 2
- Formed from the cleavage of a dipeptide from angiotensin I
- Catalysed by ACE
- ACTIVE
23
Q
What are the main effects of Angiotensin 2?
A
SYSTEMIC VASOCONSTRICTION
- Increases blood pressure
Na+ AND H2O RETENTION
24
Q
How does Angiotensin 2 increase Na+ and H2O retention?
A
- Stimulates ALDOSTERONE release
- Stimulates ADH release (H2O retention)
- Increases tubular reabsorption of Na+ & H2O
25
What is Aldosterone?
* Steroid hormone produced by the zona glomerulosa cells in the Adrenal Glands that acts as a mineralcorticoid
* Aldosterone freely diffuses into CD cells and binds to mineralocorticoid receptor (MR)
26
What is the effect of Aldosterone?
* Increase in number of open Na+ channels so increased Na+ reabsorption & hence H2O reabsorption
* Increased Na+ transport out of cell via Na+-K+-ATPase so Intracellular K+ increases
* Increased K+ secretion as a result
27
How can the RAAS mechanism be altered for therapy?
ACE Inhibitors (e.g. captopril, lisinopril, ramipril)
* Produce vasodilation by inhibiting production angiotensin II
* Block breakdown of bradykinin therefore increased levels contribute to vasodilator action of ACE-I
Angiotensin II receptor blockers (e.g. candesartan, losartan)
* Receptor antagonists, dilate arteries and veins reducing arterial pressure and load on heart
* Promote renal excretion Na and H2O
Aldosterone receptor blockers (e.g. spironolactone, eplerenone)
* Antagonise actions of aldosterone in DCT resulting in excretion of Na and H2O
28
What is structure of ADH?
* Nonapeptide
* MW = 1084 Da
* Rapidly metabolized by Liver and Kidney
* **t1/2 = 15 – 20 mins**
29
What is the role of ADH?
Decrease the amount of urine produced by increased reabsoprtion of H2O
30
How is ADH synthesised and secreted?
Synthesized by HYPOTHALAMUS
* Supraoptic nuclei (SON)
* Paraventricular nuclei (PVN)
Secreted by:
* POSTERIOR pituitary
31
What is action of ADH?
* Binds to ADH receptor (V2) in the kidneys
* This increases the aquaporin channels inserted into the apical membrane of the collecting duct
* This increases the amount of water reabsorption
32
Where are ADH receptors located?
* **V1**(v1a)**:** Located in smooth muscle of mesenteric artery. It causes vasoconstriction
* **V2:** Located in Kidney. It leads to anti-diuresis
* **V3**(v1b)**:** Located in Pituitary Gland. It leads to release of ACTH
33
What are 'other' causes of ADH secretion?
* Nausea
* Pain
* Surgery
* Pregnancy
* Angiotensin II
* Low Cortisol
34
How is ADH secretion controlled?
* **Increased Extracellular fluid osmolality:** increase in plasma osmolality stimulates ADH release & thirst
* **Decreased Extracellular fluid volume:** decrease in plasma volume (without a change in osmolality) stimulates ADH release
* **Others**
35
How does increased ECF osmolality cause ADH release?
* Increase ECF osmolality
* ALL cells in the body become dehydrated and ALL cells in the body shrink including hypothalamic osmoreceptors
* Loss of H2O from hypothalamic osmoreceptors leads to activation of “stretch-inactivated cation channels”
* There is depolarization of the cell
* This leads to stimulation of ADH secretion and synthesis
36
How does decrease in ECF volume cause ADH release?
* Detect decrease ECF volume
* Massive increase in ADH secretion
* Maximum urine concentration achieved
