Regulation of Sodium Flashcards
Part of the "Sodium and Potassium Balance" lecture
1
Q
What the normal plasma osmolarity?
A
- 285-295mmol/L
2
Q
What is the average osmolarity of sodium in plasma?
A
- 140mmol/L
3
Q
Which ion is the most prevalent in plasma?
A
- Sodium (Na+)
4
Q
What is the effect of an increase in dietary sodium?
A
- The increase in the amount of sodium within the extracellular fluid will result in an increase in water retention
- Weight increase
- There is a plateau in body weight gain
5
Q
What is the physiological response to an increase in total body sodium?
A
- Increased water intake & retention in response to an increase in osmolarity (Must be maintained within a homeostatic end point)
- This increases the ECF volume and subsequently blood pressure
Same case on the decrease in total body sodium:
* Decreased water intake & retention in response to a decrease in osmolarity (Must be maintained within a homeostatic end point)
* This decreases the ECF volume and subsequently blood pressure
6
Q
Describe the peripheral mechanism for regulating dietary intake.
A
- Bimodal (having or involving two modes)
Both central and peripheral mechanisms to regulate sodium intake
7
Q
Which nucleus within the brainstem regulates sodium intake?
A
- Lateral parabrachial nucleus
8
Q
Which neurotransmitters are responsible for increasing the appetite for sodium (2)?
A
- GABA
- Opioids
9
Q
Which hormones are involved with the inhibition of sodium intake (2)?
A
- Serotonin
- Glutamate
10
Q
What is the definition of euvolemia (Normal Na+)?
A
- Inhibition of sodium intake (Activity of serotonin and glutamate)
11
Q
Describe how dietary sodium intake is influenced at lower levels.
A
- Enhances the taste of food
12
Q
At high concentrations of meal sodium, what is the impact?
A
- Aversive (causing strong dislike or disinclination)
13
Q
Where is the majority of sodium ions reabsorbed within the nephron?
A
- Proximal convoluted tubule (67%)
14
Q
What proportion of sodium ions are reabsorbed in the proximal convoluted tubule?
A
- 67%
15
Q
What proportion of sodium is reabsorbed in the thick ascending limb of the loop of Henle?
A
- 25%
16
Q
Which transporter is responsible for sodium reabsorption within the thick ascending limb?
A
- Na+/K+/Cl- triple transporter
17
Q
How is sodium reabsorbed within the distal convoluted tubule (transporter)?
A
- Na+/Cl- transporter
Around 5% via the Na+/Cl- transporter
18
Q
What approximate proportion of renal plasma enters the tubular system?
A
- 20%
19
Q
Which transporter is concerned with the reabsorption of sodium within the collecting ducts?
A
- Sodium channel ENAC
Around 3%
20
Q
If the GFR increases, what happens to the proportion of sodium that is filtered?
A
- Remains the same (amount increases)
21
Q
What happens to renal perfusion flow with increasing blood pressure?
A
- 100mgHG RPF does not increase with increasing blood pressure → There is a plateau effect to minimise electrolyte and water loss
22
Q
Above a sodium tubular threshold, what happens in terms of the macula densa (8 steps)?
A
- High tubular sodium
- Increased sodium / chloride uptake via triple transporter
- Adenosine released from Macula Densa Cells
- Detected by Extraglomerular Mesanginal Cells
- Reduces renin production + Promotes afferent Smooth Muscle Cells contraction
- Reduce perfusion pressure & RPF
- Decrease GFR
- Decrease loss of Na+ & fluid
23
Q
Where is the macula densa located?
A
- Within the proximal part of the distal convoluted tubule separated from the glomerulus by extraglomerular mesangial cells and JG cells
24
Q
Which 2 cells are concerned with the macula densa?
A
- Extralglomerular mesangial cells
- JG cells
25
Which cells secrete renin?
* **Juxtaglomerular cells (JG)**
26
Above a tubular sodium threshold what is released by the macula densa (2)?
* Adenosine
* ATP
27
What effect does sympathetic stimulation have on tubular sodium regulation?
* **Increases uptake of sodium** by the cells of the **proximal convoluted tubule**
* **Promotes the contraction of smooth muscle** in the **afferent arteriole** to **reduce GFR**
* **Increased renin secretion**
28
How is an increase in renin promoted by the sympathetic system?
* Sympathetic stimulation increases the uptake of sodium by the cells in the proximal convoluted tubule
* **Activity of the sodium proton exchanger increases** (relies on RAAS)
* **Production of renin by the juxtaglomerular cells**
* **Reduce sodium reaching the distal tube** (measured at the JGA) → This **reduces the production of adenosine** from the macula densa, thus there is **reduced inhibition of renin release from the JG cells**
29
What effect does the sympathetic system have on extraglomerular cells?
* Sympathetic activity **overrides the effect of extraglomerular cells SMC relaxation of the afferent arteriole** - There is an overall **contraction of smooth muscle & reduced GFR**
30
What is the effect of renin?
* **Converted into angiotensin-II by RAAS**
* ****Angiotensin-II is a **potent vasoconstrictor** that **increases vascular resistance** + **stimulates sodium uptake in the PCT**
31
Where does angiontensin-II act within the nephron?
* Promotes **sodium reabsorption** within the **proximal convoluted tubule**
32
What hormone is produced by the stimulation of angiontensin-II on the adrenal cortex?
* Stimulates the **synthesis of aldosterone**
33
Where does aldosterone act on the nephron?
* Stimulates **sodium uptake in the DCT and collecting duct**
34
Which peptide opposes increased sodium retention / reabsorption?
* Atrial natruiretic peptide **(ANP)**
35
What does ANP do to the nephron (3)?
* Promotes **dilation of the afferent arteriole**
* **Inhibits renin release**
* **Reduces sodium uptake in the PCT, DCT and CT**
36
In response to low plasma sodium, what happens?
1. Upregulation in sympathetic activity
2. **Contraction of afferent arteriole SMC**
3. **Reduced GFR** → Reduced delivery of sodium and water to the nephron
4. **Increased renin production by JG cells** → **Angiotensin-II and aldosterone synthesis**
5. Renal NaCl and water reabsorption to **reduce volume loss**
6. **Vasoconstriction → Increase blood pressure**
37
Where within the adrenal cortex is aldosterone produced?
* **Zona glomerulosa**
38
Which enzyme is activated by angiotensin-II, in order to synthesise aldosterone?
* **Aldosterone synthase**
39
What type of hormone is aldosterone?
* A steroid
40
What is the function of aldsoterone (3)?
* **Increased sodium reabsorption** (Control’s reabsorption of 35g Na/day)
* **Increased potassium secretion** (A consequence of sodium reabsorption).
* **Increased hydrogen ion secretion**
* The change in voltage promotes an indirect stimulation of proton secretion, there are additional direct effects of aldosterone on the secretion of proton via alterations in the expression of anion exchanges as H+-ATPase
41
Which types of receptors does aldosterone bind onto?
* **Intracellular mineralocorticoid receptors**
42
An excess of aldosterone can mediate as what?
* **Hypokalaemia alkalosis**
43
Which protein dissociates from intracellular mineralocorticoid receptors upon aldosterone binding?
* HSP90
44
Upon HSP90 dissociation what happens to the aldosterone-MR complex?
* **Dimerises**
45
In which cells does aldosterone have an impact on regarding sodium reabsorption?
* Principal cells
46
In which cells does aldosterone have an impact on regarding proton secretion?
* Intercalated cells
47
What function is performed by aldosterone-MR complexes?
1. **Translocates to the nucleus**, binding to promoter regions downstream to target genes, stimulating expression/transcription
48
How does aldosterone increase sodium reabsorption within the cortical collecting duct?
* **Increases the transcription and ultimate synthesis of ENaC** (epithelial sodium channel)
* Coordinates increase in the number of sodium transporters, and their activity thereby **increasing sodium reabsorption**
49
What pathologies or iatrogenic causes are linked with hypoaldosteronism (4)?
* **NSAIDs**
* **Lead poisoning**
* **Diabetes**
* **Kidney disease**
50
What are the impacts of hypoaldosteronism (5 steps)?
1. **Reabsorption of sodium** in the distal nephron is **reduced** manifesting as **hyponatremia**
2. **Increased urinary loss of sodium**
3. **ECF volume falls**
4. Incresed renin, angiotensin-II and ADH
5. **Hyperkalaemia and alkalosis**
51
What are the symptoms associated with hypoaldosteronism (4)?
* Dizziness
* Low blood pressure
* Salt carving
* Palpitations
52
What is hyperaldosteronism?
* A disorder manifested by the **hypersecretion of aldosterone** from the adrenal gland
53
What occurs due to hyperaldosteornism (5)?
1. Hyperaldosteronism **increases the reabsorption of sodium** in the distal nephron
2. **Reduced urinary loss of sodium**
3. **ECF volume increases** (Hypertension)
4. Reduced renin, Angiotensin-II, ADH
5. **Increased ANP and BNP**
54
What the symptoms associated with hyperaldosteronism (4)?
* **High blood pressure**
* **Muscle weakness**
* **Polyuria** (Consequence of thirst and increased drinking)
* **Thirst**
55
What is Liddle's syndrome? How does the Liddle's syndrome cause hypertension (3 steps)?
* An **inherited disorder** characterised by **chronic hypertension** and exhibits the same phenotype of **hyperaldosteronism** (despite normal to low levels of aldosterone)
1. **Mutation in the aldosterone activated sodium channel** (Alters re-internalisation and degradation of the channel, or opening time of the channel → Increasing likelihood of it being open)
2. **ENaC activity has overall increased** (always ‘on’)
3. **Results in sodium retention → Leading to hypertension**
56
Which protein channel is always on in Liddle's syndrome?
* ENaC
57
What is the aldosterone level in Liddle's syndrome?
* Normal to low
58
# Practice Question
Describe the pathway involving the kidney though which increased sympathetic stimulation increases aldosterone levels. (4 marks)
Increased sympathetic activity stimulates the cells of the juxtaglomerular apparatus (0.5 mark) to release renin (0.5 mark). Renin activity cleaves angiotensinogen to angiotensin I (0.5 mark). Angiotensin I is cleaved by angiotensin converting enzyme (0.5 mark) to produce angiotensin II (0.5 mark). Angiotensin II stimulates the synthesis of aldosterone synthase (0.5 mark) in the zona glomerulosa (0.5 mark) to increase the synthesis (0.5 mark) of aldosterone.
59
# Practice Question
What would be the expected effect of spironolactone treatment on the blood pressure of a person with the conditions below? (1 mark for effect on Blood pressure and 1 mark for the explanation)
