Acid Base Homeostasis Flashcards
How is the Plasma H+ maintained?
The maintenance of plasma [H+] in the face of enormous turnover depends very heavily on buffers, and excretion of CO2 and nitrogenous waste
- H+ ions are produced in mmol quantities, yet must be kept at nmol concentrations by BUFFERS
What is Plasma H+?
40 nmol/L
What are the acids Produced in the body?
- Carbon dioxide: Produced by Tissue respiration, Excreted by lungs
- Lactate: Produced in Glycolysis, Excreted by Gluconeogenesis
- Fatty acids: Produced by Lipolysis, Excrted by Re-esterification and oxidation
- Ketoacids: Produced by Ketogenesis, Excreted by Oxidation
- H+ generated from urea synthesis: Produced by Ureagenesis. Excreted by Oxidation of amino acids
- Sulphuric acid: Produced by Metabolism of Met and Cys, Excreted by Renal excretion
Why must H+ levels be kept low?
Plasma [H+] is low and cannot be allowed to rise or fall appreciably because H+ ions bind avidly to proteins, changing their conformation and therefore their actions
What is a Buffer?
A buffer is a solution which resists change in pH when an acid or base is added
What are buffering systems?
- Bicarbonate
- Phosphate
- Ammonia
- Haemoglobin
- Proteins
What are acids and bases?
- Acids are H+ donors. Strong acids readily donate H+
- Bases are H+ acceptors. Strong bases readily accept H+
What is pH?
Negative logarithm of the hydrogen ion concentration (mol/L)
pH = -log10[H+]
pH scale was devised to cope with the wide range of H+ concentrations encountered in chemistry
What is considered to devaitions of H+?
- If [H+] >45 nmol/L (pH <7.35), the patient is acidaemic
- If [H+] <35 nmol/L (pH >7.45), the patient is alkalaemic
What is Ka and pKa?
- Ka = acid dissociation constant
- pKa = negative logarithm of Ka
pKa = -log10Ka
How are pH and pKa related
pKa = pH when half of the acid has dissociated (i.e. when acid and conjugate base are in equal proportions so [base]/[acid] = 1)
What is the Henderson-Hasselbalch Equation?
pH = pKa + log10(base/acid)
What is Ka?
Ka = [H+][A-] / [HA]
How is the equilibrium equation involving Carbon dioxide and Bicarbonate written?
[H+] + HCO3- ⇌ H2CO3 ⇌ CO2 + H2O
- CO2 acting as an acid: When dissolved in plasma, CO2 becomes an acid (carbonic acid; H2CO3), which readily dissociates to release [H+].
- [HCO3-] acting as a base: [HCO3-] accepts a proton to form carbonic acid, which is converted to CO2 for excretion in the lungs
Which enzyme catalyses the equation for carbonic acid?
Carbonic anhydrase
- Found in high concentrations in RBCs and in the renal tubules – catalyses reaction both ways (formation of CO2 and H2O from carbonic acid [proximal tubule], and formation of carbonic acid from CO2 and H2O [RBCs])
pH = 6.1 + log10( [HCO3-] / pCO2 x α)
- pCO2 = partial pressure of CO2 (kPa)
- α = solubility constant (0.225 for CO2)
What is pH propotional to?
pH is proportional to [HCO3-] / pCO2
Blood pH depends not on absolute amounts of CO2 or HCO3-, but on the ratio of the two
Describe the Bicarbonate buffering system
- Bicarbonate (HCO3-) acts as a buffer, “mopping up” H+ ions
- However, it cannot buffer CO2, because of the above equation (buffering by bicarbonate would only result in the production of more CO2)
- Equilibration of CO2 therefore requires non-bicarbonate buffers (e.g. Hb, proteins – see later)
Describe the Phosphate buffering system
- Monohydrogen phosphate and dihydrogen phosphate form a buffer pair:
[HPO4]2- + H+ ⇌ H2PO4-
- Concentrations of these anions are too low in plasma to make an appreciable difference, but they are important buffers in urine
Describe the Ammonia Buffering system
- Ammonia and ammonium ions form a buffer pair:
[NH3] + [H+] ⇌ [NH4]+
- Vast majority of ammonia in the body is already in ammonium ([NH4]+) form, but NH3 is an important buffer in urine so provides a route for nitrogen excretion that does not result in the generation of H+
- Urea cycle results in generation of H+
How does Haemogobin provide a buffer?
Principal non-bicarbonate buffer - important for buffering CO2
- Reduction of CO2
- Production of HCO3-
- Formation of HHb
Describe the Protein buffering system
- Proteins contain weakly acidic and basic groups due to their amino acid composition, and can therefore accept and donate [H+] ions to some extent
- Albumin is the predominant plasma protein, and is the main protein buffer in this compartment (it has a net negative charge, so can “mop up” H+ ions)
Bone proteins also play a role in buffering
Which organs are involved in Acid-Base metabolism?
- Liver
- Lungs
- Kidneys
- GI Tract
How is Acid-Base regulated through the lungs?
- Gaseous exchange between the blood and the air, facilitated by alveoli in the lungs to excrete CO2
- Respiratory control mechanisms are extremely sensitive to pCO2 – respiratory rate can increase or decrease depending on pCO2
- In a healthy person, the rate of elimination is equal to the rate of production, so that blood pCO2 remains constant
How does Pulmonary Gash exchange take place?
- Inhale oxygen-rich air with low CO2 content
- As blood travels around the body, the oxygen is used by the tissues, and CO2 is produced
- CO2 is excreted when the blood is returned to the lungs, and more oxygen is taken on board
- As a result, different partial pressures of O2 and CO2 are expected in different sample types (arterial vs. venous vs. capillary)
What does the oxyhaemoglobbin dissociation curve describe?
Describes relationship between pO2 and %O2 saturation:
- ↑ pO2, O2 binds to Hb
- ↓ pO2, O2 is released from oxyHb
When does the Oxyhaemoglobin Dissociation curve shift to the right?
Curve shifts to the right. This means Hb has reduced affinity for O2. Higher pO2 required to maintain saturation when:
- Body temperature increases
- Patient is hypoxic or anaemic
- [H+] increases (Bohr effect)
How does the respiratory system compensate for Acidaemia?
- Respiratory compensation involves increasing the respiratory rate
- This increases the amount of CO2 blown off in expired air, and reduces the pCO2 in the blood
How does the respiratory system compensate for Alkalaemia?
- Respiratory compensation involves reducing the respiratory rate
- This decreases the amount of CO2 blown off in expired air, and increases the pCO2 in the blood
How does the kidney participate in Acid-Base balance?
- Excretion of H+ ions (distal tubule)
- Reabsorption of bicarbonate (proximal tubule)
- Regeneration of bicarbonate (distal tubule)
- Creates acidic urine containing almost no bicarbonate
How is Bicarbonate regenerated in the Kidneys?
- H2CO3 generated from CO2 and H2O under action of carbonic anhydrase. This dissociates into H+ and HCO3-
- H+ actively secreted into glomerular filtrate in exchange for Na+ (4), where H+ ions are excreted as dihydrogen phosphate (H2PO4-) (1)
- HCO3- and Na+ ions pumped into plasma
- Continued formation of H+ in renal tubular cells is accompanied by stoichiometric generation of bicarbonate so excretion of H+ results in regeneration of bicarbonate so maintains buffering capacity
How is Bicarbonate reabsorbed?
- Bicarbonate present in filtrate accepts a proton to form H2CO3 which forms CO2 and H2O
- CO2 diffuses into tubular cell, where it generates H2CO3, which then dissociates to form HCO3- and H+
- The bicarbonate formed in the cell is pumped into the plasma (along with Na+ for charge balance)
- H+ ions secreted into glomerular filtrate in exchange for Na+ (4)
What is the mineralcorticoid action in the kidney and how is it involed in acid base regulation?
- Excretion of potassium and hydrogen ions in the distal tubule, with concomitant reabsorption of sodium ions
- Under the control of aldosterone
- ↑ Aldosterone leads to ↑ sodium reabsorption and potassium/hydrogen ion excretion
How do the kidneys compensate for Acidaemia?
- Renal compensation involves increasing the bicarbonate concentration
- This is achieved by maximising bicarbonate reabsorption and regeneration in the kidney
How do the kidneys compensate for Alkalaemia?
- Renal compensation involves reducing the bicarbonate concentration
- This is achieved by reducing the regeneration of bicarbonate in the kidney
How is Acid-Base regulated in the GI tract?
- H+ secreted into stomach as HCl
- Bicarbonate secreted by pancreas into duodenum à needed to neutralise acid from stomach (contents of intestines are rich in bicarbonate)
How is Acid-Base regulated in the liver?
- Dominant site of lactate metabolism (Cori cycle). Increased production (e.g. anaerobic glycolysis) or decreased consumption (e.g. liver disease) lactate can causes Lactic Acidosis
- Only site of urea synthesis (waste product of ammonia metabolism). High concentrations of ammonia (hyperammonaemia) can cause tachypnoea, and lead to a respiratory alkalosis
What causes lactic acidosis?
Type A – tissue hypoxia
- Shock (septic and cardiogenic)
- Cardiovascular insufficiency
- Hypovolaemia
- Profound anaemia
- Asphyxia
Type B – tissue oxygenation normal
- Disease: DM, liver failure, renal failure, seizures
- Toxins: alcohols, CO, salicylates / paracetamol
- Congenital enzyme defects (e.g. pyruvate dehydrogenase deficiency)
D-lactic acidosis
- D-isomer produced by bacteria within GI tract
- Short bowel syndrome and bacterial overgrowth
What are clinical laboratory indications of Lactic Acidosis?
- Metabolic acidosis
- High anion gap (presence of lactate anions)
- High urate concentration (lactate competes with urate for renal tubular excretion)
- IncreasedWBC (sepsis)
