Lecture 31: Renal 5, Calcium And Acid Base Balance Flashcards
What are the 3 hormones that regulate plasma calcium levels?
- Parathyroid hormone (PTH) -primary regulator of Plasma Ca2+
- Calcitrol
- Calcitonin (lesser extent)
Why do we need calcium?
How is its plasma concentration regulated? (Basic)
Calcium is added to the plasma by?
Calcium is removed by?
Why do we need calcium? Critical to function of all cells, particularly important in heart, muscle and bones.
How is its plasma concentration regulated? (Basic)
Kidneys, digestive tract, bone and skim and hormones
Calcium is added to the plasma by?
-absorption from digestive tract
-resorption of bone
Calcium is removed by?
-calcification of bone
-filtration at kidneys
Calcium balance is highly regulated by hormonal control
Renal Handling of calcium.
What are the 3 ways calcium is transported in the plasma?
- Free as ionised Ca2+
- Complexes with anions
- Bound to carrier proteins (about 40%)
Ionised and complexed Ca2+ freely filtered at glomerulus but protein bound Ca2+ is not filtered.
99% of filtered Ca2+ is reabsorbed
- 70% PCT
- 20% ascending LOH
- 10% DCT and CD
Reabsorption at DCT and CT is under hormonal control
- Tell me about the parathyroid hormone and its affects?
Released from the parathyroid glands in response to ⬇ plasma ca2+
PTH acts to increase plasma by?
- Stimulating resorption of bone
- Stimulating Ca2+ reabsorption in distal nephron
- Stimulating activation of 1,25-(OH)2 D3 at kidneys (which then stimulates Ca2+ absorption from the intestines
- Tell me about 1,25-(OH)2D3= active D3 and its affects.
What’s the role of this in calcium balance?
Also termed 1-25-dihydroxycholecalciferol or calcitroil
- it’s a steroid hormones synthesised from vitamin D3
- synthesised from vitamin D3 in several steps, the final one occurring in kidney (cells of the PT)
- increases plasma calcium by primarily stimulating Ca2+ absorption from digestive tract
- additional weak effect stimulating Ca2+ reabsorption in kidneys
Role in calcium balance
- Vitamin D3 either synthesised from 7-dehydrocholestrol in the skin or absorbed from diet.
- Converted to 25-OH D3 in liver (25-hydroxyvitamin D3)
- 25-hydroxyvitamin D3 converted to active form 1,25- OH2) D3 in the kidneys, stimulated by PTH in response to low plasma Ca2+
- Calcitonin
What is it and What’s its effect?
- hormone secreted from the thyroid gland
- secretion triggered by high plasma Ca2+
- increased Ca2+ uptake by bone and also decreases renal Ca2+ reabsorption
- net effect: decreased plasma Ca2+ levels
- calcitonin has much less important role
- more important in children for bone growth
The Kidneys and Acid- base balance
-metabolism creates Co2 which adds H+ ions to the blood
-If all this CO2 is exhaled by the lungs, no nett H+ gain
-about 30 mmol H+ absorbed from intestines/day
-phosphoric acid, sulphuric acid from protein digestion
-citric acid, etc
Cellular metabolism produces 40mmol H+ ions a day
-fat metabolism (ketoacids)
-protein catabolism (phosphoric and sulphuric acids)
-anaerobic metabolism (lactic acid)
Kidneys must secret about 70mmol H+/day to prevent acidosis, under normal circumstances
Acidosis: blood pH decreases 7.42 (H+ concentration too low)
3 systems regulate H+ concentration, what are they?
- Chemical buffers:
- bind or release H+ within seconds
- cannot correct problem, only minimise it
- a buffer system consists of H+ donor (acid) in equilibrium with H+ acceptor (base)
- most important is bicarbonate buffer system
- eg HB and phosphate buffer
Bicarbonate buffer system:
- for blood pH to be maintained at 7.4, the ratio of HCO3- to CO2 must be 20:1
- to maintain this ratio, respiratory system regulates CO2 levels, and kidneys regulate HCO3 levels
2. Respiratory system: - act within minutes
- change in ventilation rate will change PCO2 and that will change H+ concentration
- can only partially compensate for pH changes
3. Renal system: - takes hours to days
- most powerful acid-base regulator
- changes H+ and HCO3-
3 systems regulate H+ concentration
Respiratory regulation of PH
Respiratory compensation:
-chemoreceptors detect change in H+ concentration and change ventilation rate appropriately
-in acidosis (H+): ⬆ ventilation➡⬇ PCO2➡⬇H (back towards normal
In alkalosis: it’s opposite to above
Respiratory dysfunction: can cause acid-base disturbances
- hypoventilation➡⬆ PCO2➡⬆ H+= acidosis
- hyperventilation: ⬇PCO2 = ⬇ H+ = alkalosis
- respiratory compensation not possible when the respiratory system is the cause of the acid-base disturbance.
3 systems regulate H+ concentration
Renal system
Kidneys regulate plasma H+ concentration by 3 mechanisms:
- Secretion and therefore excretion of H+
- Reabsorption of filtered HCO3-
- Production of new HCO3-
Kidneys may completely compensate for non-renal acid- base disturbances
Reabsorption of HCO3-
- vital in preventing and compensating for acidosis
- 85% filtered HCO3 is reabsorbed in PT
- 10% meh
- it’s coupled with H+ secretion so where HCO3- is reabsorbed, H+ is secreted
Mechanisms of H+ secretion
Mechanism of H+ secretion
1. Secondary active counter-transport
- Active transport
- H+ secreted by secondary active counter-transport with Na+ on luminal membrane
- occurs in PT and thick ascending limb of loope of Henle.
- note that H+ are formed within the tubular epithelial cells from CO2 and H2O
- carbonic Anhydrase present in these cells
- the HCO3 formed crosses the basolateral membrane and enters the blood
- Active transport
•H+ actively secreted (H+-ATPase ) on luminal membrane.
•Occurs in the intercalated cells of the Distal Tubule & Collecting Duct
•Also to a lesser extent in Proximal Tubule & LOH
•Again HCO3- is formed along with H+ in the tubular epithelial cell.
•HCO3- crosses the basolateral membrane by exchange with Cl-.
Mechanisms of HCO3- reabsorption
- Secreted H+ combines with filtered HCO3- to form CO2 + H2O.
- Carbonic anhydrase present on luminal membrane as well as in cell cytoplasm.
- CO2 enters cell and recombines with H2O in cell.
- HCO3- cannot cross the luminal membrane but CO2 can.
- HCO3- formed within the cell crosses basolateral membrane (along with Na+) and enters blood = “reabsorption” of HCO3-.
- This process does not result in net excretion of H+ because for each secreted H+ a new H+ is formed in the tubular cells.
HCO3- reabsorption
•In the PT & LOH most of the secreted H+ combines with filtered HCO3-.
•This results in “HCO3- reabsorption” with no net H+ secretion
•In the DT & CD, there is not much filtered HCO3- left in the tubular fluid, so not much “HCO3- reabsorption” occurs.
•If the secreted H+ don’t combine with filtered HCO3- they combine with other buffers e.g.phosphate.
•This results in generation of “new” HCO3- and net H+ secretion.
Production of new HCO3- and net H+ secretion
1. Phosphate buffer
- Ammonium formation
- If the secreted H+ don’t bind with filtered HCO3-, they mostly bind to other buffers such as filtered phosphate.
- This process results in new HCO3- being added to the plasma and net secretion of H+.
- There is little free H+ in the urine – this prevents urine pH from falling too low. (If pH < 4.5, H+ secretion stops).
Ammonium formation:
•Glutamine is an amino acid made in the body.
•In the cells of the PT, it is broken down to HCO3- and NH4+ (ammonium).
•HCO3- diffuses across basolateral membrane so new HCO3- added to blood.
•NH4+ enters the tubular fluid by counter-transport with Na+.
•As NH4+ is acidic this is net secretion/ excretion of H+.
Renal compensation for acidosis
- Acidosis (pH, H+) changes the number and activity of many membrane transporters in the kidneys, leading to:
- Increased (often complete) reabsorption of filtered HCO3-
- Increased H+ excretion (mainly through increased NH4+ production)
- Increased production of new HCO3- (mainly through increased NH4+ production).
- These changes help to bring the pH back up to normal (bring H+ concentration back down to normal)
Renal compensation for alkalosis
- In alkalosis ( pH, H+) the kidneys respond by:
- Reduced reabsorption of filtered HCO3-
- Reduced H+ excretion
- Reduced production of new HCO3-
- These changes help to bring the pH back down to normal (bring H+ concentration back up to normal).
