Lecture 20: Calcium and sodium regulatory disorder Flashcards
1
Q
The majority of the body fluid is located in which fluid compartment in the body?
A
Intracellular
2
Q
Within the body’s cells the principle cation is?
A
Potassium
3
Q
The majority of extracellular fluid is located in which fluid compartment?
A
Interstitium
4
Q
What are the two fluid compartments that make up the extracellular fluid?
A
Intravascular + interstitial
5
Q
Within the extracellular fluid, what is the principle cation?
A
Sodium
6
Q
The extracellular fluid and intracellular fluid has to be in what kind of equilibrium?
A
Osmotic equilibrium
7
Q
Which molecule moves freely across most membranes?
A
Water
Electrolytes do not
8
Q
Name these fluid compartments (in relation to their size)
A
9
Q
Plasma osmolality is the ratio of what?
A
Ratio of plasma solutes (sodium, glucose and urea) and plasma water
10
Q
Which electrolyte concentration mainly determines the amount of extracellular water?
A
Serum (blood) sodium concentration
11
Q
Name the two main mechanisms that regulate water status?
A
- Thrist (RAAS)
- Anti-diuretic hormone (ADH)
12
Q
Anti-diuretic hormone is produced by which part of the body?
A
Posterior pituitary
13
Q
Vasopressin refers to what?
A
Anti-diuretic hormone (ADH)
14
Q
Posterior pituitary produce anti-diuretic hormone in response to what?
A
- Low plasma volume
- High plasma osmolality
15
Q
Plasma volume is sensed by what that stimulates the release of anti-diuretic hormone?
A
Sensed by baroreceptors in atria/veins and carotids
16
Q
Plasma osmolality is sensed by what that stimulates the release of anti-diuretic hormone?
A
Sensed by osmoreceptors in hypothalamus
17
Q
Anti-diuretic hormone acts minaly via which receptor
A
AVP 2 receptor
18
Q
AVP 2 receptors are located where?
A
In the basolateral membrane in the kidney collecting ducts
19
Q
The term basolateral membrane refers to?
A
The cell membrane which is oriented away from the lumen of the tubule
i.e. between the cell and the interstitium (between the inside)
20
Q
The term luminal membrane refers to?
A
Also known as apical membrane
Refers to the cell membrane which is oriented towards the lumen.
i.e. between the cell and the intravascular e.g. endothelium and the blood vessel.
Refers to the membrane that is exposed to the “outside of the body”
21
Q
What does ADH cause in the kidneys?
A
Acts via AVP 2 receptors in the collecting ducts
AVP 2 receptor is a G protein coupled receptor and when activated by ADH, via downstream effects, it causes the insertion of aquaporin channels into the apical membrane
Overall, leads to an increase in renal water reabsorption causing the urine to be more concentrated.
22
Q
What type of receptor is the AVP 2 receptor?
A
G protein coupled receptor
23
Q
What receptor does the ADH act on?
A
AVP 2 receptor
24
Q
What receptor insertion into the apical membrane is stimulated by ADH?
A
Aquaporin
25
What membrane does the ADH act on?
The basolateral membrane acting on the AVP 2 receptor
26
What is the normal blood osmolarity rate?
280-300 mOsm/L
27
Name some causes of a rise in blood osmolality
Vomitting, diarrhoea, sweating etc
28
Describe the pathway when a rise in blood osmolality is detected
Blood osmolality is detected by osmoreceptors in the hypothalamus.
This stimulates the thrist response causing the person to feel thristy. Drinking reduces the blood osmolality
Blood osmolality is back to homeostasis
29
Aldosterone stimulates?
A) Sodium reabsorption, potassium reabsorption
B) Sodium reabsorption, potassium excretion
C) Sodium excretion, potassium reabsorption
D) Sodium excretion, potassium excretion
B) Sodium reabsorption, potassium excretion
30
Where in the kidney does aldosterone work?
In the distal nephron
31
Aldosterone acts on which receptor?
Mineralocorticoid receptor (MR), a type of nuclear receptor (as it is a steroid hormone)
32
Describe how aldosterone causes sodium reabsorption?
Aldosterone binds to the mineralocorticoid receptor (MR) inside the epithelial cells in the distal nephron.
This acts on the nucleus altering the transcription of the epithelial sodium channel (ENaC).
This causes the increase in expression of the ENaC on the apical membrane.
ENaC is highly permeable to sodium (hence the name) but has little permeablity to potassium.
Hence aldosterone causes an increase in sodium rebsorption and potassium excretion.
This increase in sodium also increase plasma volume (as water follows sodium)- raising the blood pressure
33
What is the effect of aldosterone on plasma volume?
Increases plasma volume and as a result increases blood pressure.
Does this by causing sodium reabsorption, and wherever sodium goes water follows.
34
Describe how aldosterone causes potassium excretion?
Aldosterone increases the expression of:
1. Sodium channels (ENaC), on the apical membrane
2. Sodium-potassium ATPase, on the basolateral membrane.
As more sodium enters the cell (via the ENaC), more sodium are pumped out to the interstitium in exchange for potassium (via the sodium-potassium ATPase). There are also potassium channels on the luminal side of the cell that allow passive diffusion out of the cell into the lumen of the kidney. As a result, there is a rise in potassium excretion.
35
Describe how aldosterone causes hydrogen ion excretion?
Indirectly.
Aldosterone causes sodium to be absorbed and potassium to be excreted into the lumen by principal cells in the distal nephron.
In alpha intercalated cells, located in the late distal tubule and collecting duct, hydrogen ions and potassium ions are exchanged. Hydrogen is excreted into the lumen in exchange for potassium, and the potassium is absorbed.
Aldosterone causes the concentration of potassium inside the lumen to be higher, resulting in more hydrogen ions being exchanged for potassium.
Overall, leading to an increase in hydrogen ion excretion
36
Define the term hyponatraemia
Defined as a serum sodium concentration below 135 mmol/l.
37
What is the commonest disorder of electrolyte balance in clinical practice?
Hyponatraemia (low serum sodium concentration)
38
What is the commonest cause of hyponatraemia?
Commonest reason is water imbalance
Surprising as you would think the reason would be lack of sodium
39
What would happen if you have an inability to suppress ADH release?
Anti-diuretic hormone (ADH) stimulates water reabsorption in the collecting ducts.
If you are unable to suppress ADH, there would be an inappropriate retention of water
Resulting in low serum sodium osmolality.
40
Which diuretic drug is most common in causing hyponatraemia?
Thiazides e.g. Bendroflumethiazide
Remember: thiazides act on the sodium chloride symporter in the distal convoluted tubules in the kidneys. Therefore, inhibits the reabsorption of sodium (Na+) and chloride (Cl−) ions.
Therefore, can result in hyponatraemia (low serum sodium concentration)
41
The term hypovolemia refers to?
**Sodium and water deficity**
Low total body water
Low total body sodium
42
The term euvolemia refers to?
**Water excess**
High total body water
Normal total body sodium
43
The term hypervolaemia refers to?
**Water and sodium excess**
High total body water
High total body sodium
44
What are the 3 classification of hyponatraemia in relation to extracellular fluid volume status
1. **Hypovolaemia** - low water; low sodium
2. **Euvolaemia** - high water; normal sodium
3. **Hypervolemia** - high water; high sodium
45
The majority of patients with hyponatraemia will be in which extracellular fluid volume status group?
Euvolemia (excess water with normal sodium)
46
Describe possible causes for the hypovolemia classification of hyponatraemia
Two types: Renal losses + Extrarenal losses.
**Renal** **losses** include mineralcorticoid deficiency, diuretic excess, osmotic diuresis.
**Extrarenal** **losses** includes vomiting, diarrhoea, pancreatitis, burns, norovirus.
Usually these patients are quite obvious as they look dry and dehydrated.
47
Describe possible causes for the euvolemia classification of hyponatraemia
Majority of patients will be in this group.
Most common is **syndrome of inappropriate ADH secretion.**
Other causes includes pain, hypothyroidism, glycocorticoid deficiency, drugs e.g. omeprazole.
48
Describe possible causes for the hypervolemia classification of hyponatraemia
Patient will appear with hypervolaemic symptoms such as peripheral pitting edema
Usually patients will have a clinical history of liver, cardiac and/or renal failure.
Therefore common causes include: nephrotic syndrome, renal failure, cardiac failure and cirrhosis.
49
Describe peripheral pitting edema
Edema refers to visible swelling caused by a buildup of fluid within tissues. When an indentation remains after the swollen skin is pressed, this is called pitting edema.
This condition is found in the peripheral regions ie. the lower body, particularly in the legs, ankles, and feet.
50
Define the syndrome of inappropriate anti-diuretic hormone (SIADH)?
Condition in which there is an excess ADH or iinappropriate ADH for the plasma osmolality.
51
What is the commonest cause of low plasma sodium
Syndrome of inappropriate anti-diuretic hormone (SIADH)
This is due to an increased body water (low sodium osmolality because of the increase in solute (water) instead of a decrease in solvent (sodium))
52
Name a condition that refers to when there is not enough ADH being produced?
diabetic insipidus
53
Name a condition that refers to when there is too much ADH being produced?
Syndrome of inappriopriate anti-diuretic hormone (SIADH)
54
What are the causes of syndrome of inappriopriate anti-diuretic hormone?
Cancer such as leukaemia.
Chest disease e.g. pneumonia
CNS disorders e.g. infections or injury
Drugs: opiates, thiazides, proton pump inhibitors, anti-depressants
55
How is syndrome of inappropriate anti-diuretic hormone diagnosed
Patients present with hyponatraemia with inappropriately low plasma osmolality
Therefore step one is to check the plasma osmolality
Urine osmolality \> plasma osmoallity.
Check the urine for sodium. Urine sodium \> 30mmol/L
56
Why is hyponatraemia so dangerous?
When the serum sodium is low, water moves into cells to increase the plasam osmolality. This causes cells to swell.
Moreover, water moves from the plasma into the CSF.
57
What happens neurologically when there is an acute sudden drop in sodium?
Swelling of the neurones and the brain
58
What happens neurologically when there is an acute sudden rise in sodium?
Osmotic demyelination
59
What are the key clinical features of hyponatreamia (low serum sodium levels)
* Often asymptomatic
* Mild confusion
* Gait instability
* Marked confusion
* Drowsiness
* Seizures (in severe cases)
60
What is the management plan for patients with severe and acute hyponatraemia
Patients are severe and acute if they are unconscious or seizuring and it has happened under 24 hours
They need salt but not volume
Hypertonic saline is infused in small amounts
In these patients you want the rise to be quickly
61
What is the management plan for patients with less severe and/or chronic hyponatraemia
**Treat the underlying cause + Fluid restrict patients**
Find the cause and treat
Fluid restrict so the sodium rises slowly to prevent demyelination (a result of a sudden rise in sodium)
62
A sudden fall in sodium causes?
A) Cerebral oedema
B) Demyelination
A) Cerebral oedema
63
A sudden rise in sodium causes?
A) Cerebral oedema
B) Demyelination
B) Demyelination
64
Define hypernatraemia
Defined as a serum sodium concentration exceeding 145 mmol/L
High serum sodium concentration
65
What is the body's mechanism that preventing hypernatraemia
Serum sodium concentration, and hence osmolality, is normally kept from rising significantly by the release of antidiuretic hormone (ADH) or vasopressin which limits water losses, and the stimulation of thirst which increases water intake
66
What is the most common cause of hypernatraemia
* Most usually due to water loss, 'dehydration', and inability to access water
* Don't have increased plasma sodium but a rise is water loss
* The main causes include:
* Insensible/sweat losses (severe burn/sepsis)
* GI loss (Diarrhoea, vomiting)
* Diabetes inspidus
* Osmotic diuresis due to hyperglycaemia
67
What is more common hyponatraemia or hypernatraemia?
Hyponatraemia
Sodium overload is rare
68
How is hypernatreamia managed?
* Step one is to treat the underlying cause.
* Estimate total body water deficit if possible
* Use IV 5% dextrose
* Avoid overly rapid correction
69
What are the 3 sources of calcium?
**GI tract**- absorbed throughout the small intestine from dietary sources.
**Bones**- calcium reservoir
**Kidney**- calcium filtered by glomerulus
70
The absorption of calcium through the small intestine is dependent on which factor?
Vitamin D
71
Calcium levels in the bones depend on the action of which two cells
Osteoblasts
Osteoclasts
72
What percentage of calcium is reabsorbed in the kidney
97-99%
73
What is the active form of vitamin D called
1,25- dihydroxyvitamin D
74
What is the major source of vitamin D
Sunlight
75
Describe how vitamin D is turned into its active form
Vitamin D main source is sunlight- in the cholecalciferol form.
Cholecalciferol (vitamin D3) is converted to 25-dihydroxyvitamin D3 in the liver.
25-dihydroxyvitamin D3 is converted to 1,25-dihydroxyvitamin D3 in the kidney.
1,25-dihydroxyvitamin D3 is the active form of vitamin D.
76
The major source of vitamin D is from \_\_\_\_\_. The initial form of vitamin D3 is cholecalciferol. Cholecalciferol is converted to _____ in the \_\_\_\_\_. Afterwhich, this form is converted to ______ in the \_\_\_\_\_\_.
1. Sunlight
2. 25-dihydroxyvitamin D3
3. Liver
4. 1,25-dihydroxyvitamin D3
5. Kidney
77
What effect does vitamin D have on calcium levels and how?
Increases serum calcium levels by:
* Increasing GI absorption
* Increasing bone resorption
* Increases renal reabsorption
78
The parathyroid gland sits ____ in relation to the thyroid gland
Posterior
79
How many parathyroid glands do we have?
4
80
When serum calcium levels are low, PTH production is?
A) High
B) Low
A) High
81
When serum calcium levels are high, PTH production is?
A) High
B) Low
B) Low
82
What is the function of parathyroid hormone?
Triggered when serum calcium level is low.
Acts on the osteoclasts and osteoblasts in the bones to cause **calcium and phosphate resorption.** Unable to resorb calcium without phosphate.
Acts on the kidneys to cause **phosphate** **excretion**, **calcium** **reabsorption** and **increase the formation of active vitamin D.**
83
Describe the why in which calcium circulates in the serum?
55% of circulating calcium is bound to albumin or other substances
45% is free (unbound)
84
What are the clinical features of hypercalcaemia
**Moans, Groans, Stones and Bones**
## Footnote
_Moans_: neurological and psychological manifestations.
_Bones_: boney pain, thinning of the body (predisposed to osteoporosis and osteopenia)
_Stones_: nephrolytitis (kidney stones)
_Groans_: GI effects. Predisposed to constipation.
85
What is the effect of hypercalcaemia on a patients ECG?
Shortened QTc interval
Bradycardia (i.e. slowing of the heart rate)
86
Define bradycardia
Slowing of the heart rate
87
Define hypercalcaemia
Increase calcium concentration in the plasma/serum
88
When the biochemistry comes back for hypercalcaemia. What is the first thing to think about?
Correct for albumin.
If albumin level is low, then there will be more free calcium level.
89
Name the 2 major causes of hypercalcaemia
1. Primary hyperparathyroidism
2. Malignancy
90
If a patient has hypercalcaemia with low levels of PTH. What is the most likely cause?
Malignancy
91
If a patient has hypercalcaemia with normal or high levels of PTH. What is the most likely cause?
Primary hyperparathyroidism
92
How does maligancy cause hypercalcaemia?
Independent from parathyroid glands.
Usually due to secretion of PTH-related peptide that is being produced by the malignancy cells.
The commonest tumours include: breast, lung and multiple myeloma
93
Describe the management plan for hypercalcaemia
Depends on severity (mild to severe)
Mild: relatively asymptomatic
Moderate/Severe: Life threatening
Initially, address the underlying cause
94
