Lecture 10 - Acid/Base Balance In The Kidney Flashcards
What happens if the plasma pH is not maintained within a tight range?
Proteins/enzymes denature
What is the healthy pH range of the blood plasma?
7.35 - 7.45
What is the pH range that the urine varies between?
4.5 - 8.5
How does Alkalemia affect plasma free calcium levels?
Decreases free levels of calcium
Describe the mechanism by which alkalosis causes lower free calcium levels:
When the blood is alkalotic the hydroxyl group of albumin dissociates its H+, this makes more Ca2- bind to albumin
What plasma protein is the main plasma protein in the blood?
Albumin
Describe the mechanism by which alkalosis causes lower free calcium levels:
When blood is alkalotic the hydroxyl group on the albumin dissociates releasing H+ to try and decrease blood pH
This change on the albumin leads to Ca2+ binding to t he albumin making it no longer free decreasing plasma Ca2+ levels
So if alkalosis causes decreased free plasma Ca2+, how does this affect nerves?
Increased neuronal excitability ( so action potentials fired at slightest signal)
Sensory changes like numbness/tingling with muscle twitches
Can lead to sustained contractions/paralysis
How does acidosis change free calcium levels in the plasma?
Increases free calcium levels in the plasma
Describe the mechanism by which acidosis causes higher free calcium levels:
When the blood is acidotic the H+ binds to the O- of the what once was the hydroxyl group on the albumin
This leads to Ca2+ being released from the album in and less Ca2+ binding to the albumin
So plasma levels of free Ca2+ increases
What affect does increased free plasma Ca2+ have on other ion levels and why is this dangerous?
Increases plasma [K+] levels
Leads to cardiac excitability being affect leading to Arrythmias
What are the 2 sources of H+ in the body?
Diet
Metabolism
What are some examples of how acids can be obtained?
Proteins = amino acids
Lipids = fatty acids
Carbs = lactic acids
What are the 3 different buffer systems to buffer the H+ in the body?
HCO3– in blood/ECF
Proteins, Hb and Phosphates in cells
Phosphates and ammonia in urine
What are the 2 organs/systems that regulate plasma pH?
Lungs/respiratory
Kidneys/renal system
What is the relative speed by which the ventilation system and the renal system can compensate for plasma pH levels?
Lungs/ventilation = rapid response
Kidneys/renal = slower
How do the lungs help regulate blood pH?
Changing ventilation rate changes levels of CO2 present in the blood
How do the kidneys alter blood pH?
Excreting and reabsorbing H+
Changing rate at which HCO3- is reabsorbed pr excreted in the urine
How much of the HCO3- does the body try and reabsorb from the filtrate in the PCT?
All of it
What form is HCO3- absorbed from the filtrate into the PCT cell as?
CO2 + H20
HCO3- + H+ = H2CO3
H2CO3 becomes CO2 + H2O with help of Carbonic anhydrase
Describe how HCO3- is reabsorbed into the blood from filtrate:
Na+/K+ ATPase on basolateral membrane pumps Na+ into blood establishing Na+ gradient
Carbonic acid broken down to CO2 + H2O by carbonic anhydrase
CO2 and H2O diffuses into the cell
CO2 + H2O remade into H+ + HCO3- in cell with help from C.A
HCO3- symported into blood across basolateral membrane with Na+
H+ in the cell antiported into blood across apical membrane and Na+ brought into cell
What are the 2 buffer systems present in the plasma that help prevent blood being too acidic?
Phosphate buffer
Ammonia (NH3) buffer
How does the phosphate buffer system in the urine act to prevent blood becoming to acidic?
H+ reacts with HPO4(2-) forming H2PO4(-)
H2PO4(-) can then be excreted in the urine
How does the ammonia buffer system in the urine act to prevent plasma pH becoming to acidic?
NH3 + H+ forming NH4+
This is now charged (ammonium) preventing it entering into any cells which constricts it to the lumen ensuring it is excreted
What is the process by which the PCT cells can produce HCO3- to prevent blood becoming too acidic?
Cell makes glutamine
Glutamine converted to alpha ketoglutarate and 2NH4+
Alpha ketoglutarate converted to 2HCO3- to be reabsorbed into blood
Ammonium (2NH4+) broken down into ammonia (2NH3) and 2H+
2NH3 then diffuses back into lumen to join monitor buffer system
H+ then removed back into lumen
What are the cells that deal with acidosis in the DCT/CD?
Alpha intercalated disc cells
What are the cells that deal with alkalosis in the DCT/CD?
B intercalated cells
What ion can be heavily influenced by the pH/ being acidotic or alkalotic?
Why is this dangerous?
Potassium levels
Hyperkalaemia and hypokalaemia
Can lead to cardiac arrhythmias
How can acidosis affect potassium levels in the blood and explain why?
Hyperkalaemia
High H+ in plasma exchanged with K+, H+ moved into cell and K+ into the blood from the cell
How can alkalosis affect potassium levels in the blood and explain why?
Hypokalaemia
Since H+ levels in blood low
H+ moved from inside of cells into blood and therefore K+ moved from blood into cells
What is the main cause of respiratory alkalosis?
Hyperventilation
Lots of CO2 breathed out (hypocapnic) so less carbonic acid
What is the form of compensation that occurs with respiratory alkalosis?
Renal/metabolic compensation
Less HCO3- reabsorbed in PCT
HCO3- secreted in DCT/CD
H+ reabsorbed with K+
What is the most common cause of Respiratory acidosis?
Hypoventilation
More CO2 retained so (Hypercapnic) so higher levels of Carbonic acid
What is the form of compensation that occurs with respiratory acidosis?
Renal/metabolic compensation
More HCO3- reabsorbed in kidneys and H+ secreted
What can cause Metabolic alkalosis?
Excess vomiting of acidic stomach contents
Ingesting excess HCO3- like through antacids
What are the compensatory mechanisms for a Metabolic Alkalosis?
Resp compensation = Hypoventilation (more CO2 retained to make more acidic blood)
The hypoventilation leads to more HCO3- being made from the extra CO2 so some RENAL compensation occurs so less HCO3- reabsorbed in PCT
What can cause metabolic acidosis?
Dietary and metabolic input of H+ exceeds excretion
Or losing to much HCO3- (diarrhoea)
E.g:
Lactic acidosis
Ketoacidosis
What compensation occurs with metabolic acidosis?
Respiratory compensation = hyperventilation to increase removal of CO2
Renal compensation = inc reabsorption of HCO3- and DCT/CD secretion of H+
Look at the last slide, look at 1. Investigations and describe what type of acid base disturbance has occured:
Metabolic acidosis with respiratory compensation (partial)
PH low
PCO2 low so not the cause of the acidosis but HCO3- is low so its the cause
Look at the last slide, look at 1. Investigations and describe what type of acid base disturbance has occured:
Metabolic acidosis with respiratory compensation (partial)
PH low
PCO2 low so not the cause of the acidosis but HCO3- is low so its the cause
What is the anion gap?
The difference between measured cations and anions
How do you determine the anion gap?
([Na+] + [K+]) - ([Cl- + [HCO3-])
Basically sum of major cations - sum of major anions
What form of acidosis is the anion gap remaining unchanged?
Why?
Metabolic acidosis
Not enough HCO3- but is replaced by Cl-
What are some of the common causes of hypokalaemia?
Alkalosis
GI loses
Renal loses
What are some examples of renal loses that can cause hypokalaemia?
Diuretics like furosemide
Too much aldosterone production/over activation of RAAS
Renal tubular acidosis
