Urinary L6.1 Flashcards
What is an acid, what is a base and what is pH?
Normal range of Plasma pH
-acidemia
-alkalemia
-acidosis
-alkalosis
What is a buffer?
Solution that resists changes in pH when small amount of acid is added.
What is the bicarbonate-carbon dioxide buffer system?
Used to maintain normal pH of 7.4
2 components:
1. Bicarobonate (HCO3-): weak base
Carbonic acid (H2CO3): weak acid, in equilibirium with CO2 dissolved in blood
To maintain pH of 7.4, body must maintain 20:1 ratio of bicarbonate (HCO3-) to carbonic acid (H2CO3)
What equation is used to calculate pH?
HENDERSON-HASSELBALCH EQUATION
What does the law of mass atraction tell us?
Rate (velocity) proportional to conc of reactants.
e.g. in buffer system, balance between CO2 (reatcant) and HCO3- (product) follows this principle: When CO₂ levels rise, more HCO₃⁻ is produced to buffer the excess acid, and vice versa.
How do changes in pCO2 or r [HCO3-] affect
pH?
If ratio of [HCO3 −] to pCO2 stays constant, pH also stays constant.
If [HCO3 −] : pCO2 ↑, then pH will ↑
If [HCO3 −] : pCO2 ↓, then pH will ↓
What factors cause [HCO3 −] : pCO2 to change?
What does the respiratory system do to adjust to metabolic acidosis?
What does the respiratory system do to adjust to metabolic alkalosis?
- Respiratory conditions
a) Respiratory acidosis:
-caused by hypoventilation (COPD)
-increases pco2 (hypercapnia) due to inadequate exhalation of CO2
-Decreased [HCO3 −] : pCO2 ratio,
leading to a decrease in pH (acidaemia)
b) Respiratory alkalosis
-Hyperventilation (anxiety, high altitude)
-decreased pco2 (hypocapnia) due to excessive exhalation of CO2
-Increased [HCO3 −] : pCO2 ratio,
leading to an increase in pH (alkalaemia)
- Metabolic conditons
a) Metabolic acidosis
-Loss of bicrabonate (diarrhea) / accumulation of acid (latcic acidosis)
Leads to decreased HCO3 −] due to bicarbonate buffering
the excess acid.
Decreased [HCO3 −] : pCO2 ratio, leading to a
decrease in pH.
Hyperventilation. To lower CO2. To make it more balanced.
b) Metabolic alkalosis
- excress bicarbonate (vomiting), or loss of hydrogen ions
- increased [HCO3 −]
- Increased [HCO3 −] : pCO2 ratio, leading to
an increase in pH.
Respiratory compensation: hypoventiltion to raise pCO2.
Describe HCO3− ion reabsorption in the PCT
- Sodium hydrogen exchanger (Na+/H+ exchanger 3 NHE3)
- H+ ions secreted into lumen (from cell) via NHE3.
- Combine with filtered bicarbonate.
Forms carbonic acid.
On luminal side, cabronic acid split into CO2, H2O in dissociation reaction catalysed by carbonic anhydrase IV.
Carbon dioxide + water now able to diffuse across into cell.
Once inside cell, recombine to form carbonic acid (catalysed by carbonic anhydrase II).
Carbonic acid then dissociates int HCO3- and H+. HCO3- transported into blood and H+ can be transported back to cell into lumen for cycle to start again
What is the whole purpose of the dissociation of carbonic acid on the luminal side of the cells?
This is to split the carbonic acid into CO2 and water so that they can diffuse across the membrane. Carbonic acid is not able to diffuse across the membrane.
How do the HCO3- ions leave the cell to be transported to the blood?
They leave the cell from across the basolateral membrane via the 3HCO3-Na+ symporter.
What are the 2 types of carbonic anhydrase?
Carbonic anhydrase 4 which is found in the PCT lumen and is membrane bound
Carbonic anhydrase 2 which is found in the cell
Describe HCO3- reabsorption in collecting duct
Why is this clinically important?
Metabolic acidosis triggers H⁺ excretion but may lead to hyperkalemia.
Hyperkalemia triggers K⁺ excretion but may worsen acidosis.
1) What is the limitimg pH and why do we need buffers?
1) Max conc of h+ that can be secreted into tubular fluid (pH 4.5). After this, no more H+ can be secreted.
However, we have buffers: Prevent rapid H+ build up. Therefore, allow more H+ excretion (beyond limiting pH 4.5)
What are the two buffering mechanisms for H+ in the urine?
- Ammonia buffering system (NH₃ → NH₄⁺)
-H+ reacts with ammonia (NH3) to form ammonium (NH₄⁺)
-60% of non-volatile acid excretion
- NH3 is the buffer: allows excretion of h+ in form of NH4+ which does not lower urine pH - Phosphate buffering system ((HPO₄²⁻ → H₂PO₄⁻)
-H+ reacts with dibasic phosphate (HPO₄²⁻) to form monobasic phosphate (H₂PO₄⁻).
-KNOWN AS TITRABLE ACID system - 40% non-volatile excretion
- H+ excreted in form of H₂PO₄⁻, prevents excessive drop in urine pH
When secreted H+ combines with urinary buffer, new HCO3 created. How?
What is titratable acid?
How do we quantify titratable acid?
RENAL COMPENSATION
- Trapping of H+ ions IN URINE (though buffering systems, AP)
- Prevents H+ reacting again with HCO3- in tubular fluid
- Kidney tubular cells generate new HCO3-
- Newly formed HCO3- reabsorbed into blood, increasing total bicarbonate circulation
- Amount of H+ excreted into urine that is bound to buffers.
- Urine titrated with alkali (base) to raise pH to 7.4. This tells you how much H+ excreted with urinary buffers.
1) What happens during glutamine metabolism in the kidney?
1) Glutamine metabolised in PCT
Glutamine broken down into NH4+ and HCO3-
NH4+: excreted in urine, acts as buffer. Some NH4+ returns to blood. Converted to urea (urea cycle)
New HCO3- : newly synthesised not reabsorbed. Restore bloods pH balance (H+ also generated in this process)
Acidosis vs Alkalosis
Acid Base MAP
Common causes of metabolic alkalosis
H+ loss through GI tract - Vomiting
Renal H+ loss: Diuretic usage (THIAZIDE, LOOP)
