Renal Physiology - Acid-Base Balance Flashcards
- PB_BK_07 Definition of pH. Strong and weak acids - PB_BK_08 Acid base balance. Includes buffers, Henderson-Hasselbalch equation and anion gap - PB_BK_09 Ions e.g. Na+, K+, Ca++, Mg++, Cl-, HCO3- - PB_BK_54 Regulation of acid-base balance
What is the definition of normal acid-base balance?
pH 7.35-7.45
HCO₃⁻ 22-28 mmol/Litre
PCO₂ 4-6 kPa
Acidaemia is when the blood pH is below 7.35
Acidosis is where there is an underlying process that would cause the pH to be below 7.35 in the absence of any compensation
It is therefore possible to have an acidosis but not be acidaemic, given sufficient compensation
What defines an acid vs a base?
An acid is a compound that releases hydrogen ions in solution (a proton donor)
A base is a compound that will combine with hydrogen ions in solution (a proton acceptor)
A strong acid/base will completely dissociate, whereas a weak acid/base will only partially dissociate
The body produces 13,000 to 15,000 mmol/day of acid in the form of carbon dioxide (known as volatile acids), and 50-80mmol/day of acid from amino acid metabolism (fixed acids)
What is pH and why does it matter?
pH is the negative logarithm of the hydrogen ion concentration, and is therefore a measure of acidity
pH = -log10[H+]
For every pH change of 1 unit, there is a tenfold change in H+ ion concentration
pH matters because proteins denature and lose function outside of a certain range. Strict pH control is necessary for enzyme function, as well as ion channel and ion balance, including the mitochondrial protein pump required for oxidative phosphorylation.
Explain power and pKa with regards to buffer systems
A buffer is a substance that resists a change in pH by releasing or absorbing hydrogen ions, usually consisting of a weak acid and its conjugate base (For instance carbonic acid and bicarbonate ions)
The power of a buffer is how much acid or base from that buffer system needs to be added to change the pH by 1
pKA tells you the pH at which a buffer is most active.
Ka is the equilibrium constant for a buffer system (the ratio of concentrations within the buffer system where there is equilibrium)
pKa is the pH at which there is 50% dissociation (and therefore Ka is 50:50)
pKa is the negative log of Ka in the same way that pH is the negative log of hydrogen ion concentration.
What buffering systems in the body act to maintain control of pH?
Buffering (Act within seconds)
Intracellular (phosphates, proteins, haemoglobin)
Extracellular (bicarbonate, haemoglobin, proteins, phosphates)
Compensation: Respiratory within minutes, renal/hepatic within hours
Correction of causative pathophysiology (Antibiotics, BiPAP) can take between hours and days
Explain the efficacy of a buffer, and the isohydric principle.
The quantity of the buffer present
Hb is more important than plasma proteins, as there is 150g/L compared to 70g/L
pKa and pH
A buffer is most effective at its pKa, the closer the pKa to 7.4, the more effective
Open vs Closed buffer systems
An open system that can introduce more acid or base is more effective than one with limited reserves
Capacity of each buffer system in the body:
Haemoglobin 8mmol H+
Bicarbonate 18mmol H+
Plasma proteins 1.7mmol H+
Phosphate 0.3 mmol H+
Isohydric principle
All buffering systems within the same environment are all in balance with one another, and in equilibrium with the same H+ concentration.
Only the buffers with a pKa within 1 unit of the actual pH are actively involved in buffering the system
Discuss the bicarbonate-carbonic acid buffer system
The primary extracellular buffer
CO₂ dissolves in water to form carbonic acid, which dissociates to form bicarbonate ions and hydrogen ions
pKa 6.1 means it becomes more effective as the body becomes more acidotic
Open buffer system as both CO₂ and bicarbonate can be added or removed (by lungs/kidneys respectively)
Effective buffer because it is abundant, buffers in both directions, and is an open system regulated by two organ systems.
It is limited in that it cannot buffer hydrogen ions produced inside RBCs, so haemoglobin must buffer this instead.
Discuss the haemoglobin buffer system
The main buffer of H+ ions inside RBCs
Reduced Hb is a weak acid, and can dissociate to a greater extent than oxyhaemoglobin, making it a more effective buffer.
This enables the Haldane effect, where Hb releases this buffered CO₂ when it becomes oxygenated.
There are 38 negatively charged (anionic) histidine residues per molecule of Hb.
pKa = 6.8, making it effective at physiological pH, but is a closed system, and affected by both oxygenation and Hb concentration.
Haldane effect
Chloride shift
Discuss plasma proteins and phosphate as buffer systems
Thes contain negatively charged groups that can bind and therefore buffer H+ ions
Proteins are far more abundant than phosphate both intra- and extra-cellularly
Amino groups pKa 9
Hydroxyl groups pKa 2
Phosphate (pKa 6.8) is only present in very low quantities in the extracellular fluid, but present in higher concentrations, and in a lower pH environment intracellularly.
Explain the Henderson-Hasselbalch equation
The equation relates to the concentrations of dissociated/undissociated acids or bases, with the pH of the environment and the dissociation constant for that substance
pH = pKa + log₁₀([acceptor]/[donor])
Acceptor means the base (which will accept a proton)
Donor means the acid (which will donate a proton)
How would the body react to an IV bolus of acid?
Three main ways of responding to a pH change:
Buffers (Intracellular/Extracellular), immediate reaction
Bicarbonate-carbonic acid buffer - if prolonged insult, renal/respiratory can compensate
H⁺ + HCO₂⁻ -> H2CO₃ -> CO₂ + H₂O
Haemoglobin
Plasma proteins
Phosphates to a lesser extent
Compensation (Renal/Respiratory/Hepatic), within minutes
Peripheral chemoreceptors are triggered first, increasing MV, driving the buffering equation above to the right by removing excess CO₂ (20% of respiratory compensation). The excess CO₂ diffuses across the blood-brain barrier, forming carbonic acid again, triggering central chemoreceptors to further stimulate respiratory drive - Kussmaul breathing (80% of respiratory compensation)
Correction of underlying physiology
How does the kidney handle acids?
IMAGE
The kidney can selectively excrete or retain H⁺ and HCO₃⁻ ions.
Primary active transport:
Bicarbonate dissociates within the renal cells to form H⁺ and HCO₃⁻. The H⁺ is pumped into the renal tubule by hydrogen pump ATPase against the concentration gradient (concentrates by up to 900 times). Chloride diffuses into the renal tubule down the electrochemical gradient.
The excess HCO₃⁻ is exchanged for chloride and passes into the blood.
Secondary active transport:
Sodium is allowed into the cell down its concentration gradient (maintained by NaKATPase), pushing hydrogen ions out into the renal tubule.
Bicarbonate:
The bicarbonate ion (HCO₃⁻) is freely filtered into the glomerulus. There, it can bind with H⁺ ions to form carbonic acid again. Carbonic anhydrase in the brush border breaks this down into CO2 and H2O.
The CO2 can diffuse back into tubular cells, recombining with H2O to form carbonic acid (catalysed again by carbonic anhydrase), which dissociates again to H⁺ and HCO₃⁻ (which is transported back into the blood). The H⁺ is exchanged for Na⁺ from the renal tubule.
Through excretion of NH₄⁺ and other ions, incomplete titration means that 3.5 nmol/min of H⁺ are excreted for every 3.46nmol/min of HCO₃⁻ filtered, correcting pH disturbance.
If required, it is re-absorbed in the proximal tubule, loop of Henle and collecting ducts.
How does the liver contribute to buffering?
Largely via synthetic processes
Produces CO2 through metabolism
Metabolism of organic acids int he blood
Synthesis of plasma proteins
Regulation of ureagenesis (Which produces CO2, and is reduced in acidosis, and increased in alkalosis).
Amino acid -> HCO₃⁻ + NH₄⁺ 2NH₄⁺ + 2HCO₃⁻ -> NH₂CONH₂ + CO₂ + 3H₂O
What is base excess vs standard base excess?
Base excess: The amount of acid that would need to be added to return a sample of whole blood to pH 7.4, at 37°C and 5.3kPa of CO2
Standard base excess: The same process but for extracellular fluid rather than whole blood
This isn’t feasible to test, so the machine estimates this using anaemic blood at an Hb of 50g/L
The principle is that this indicates buffering for the entire extracellular fluid of the body, rather than just the blood.
What are the causes of metabolic acidosis
Increased acid
Lactate (sepsis)
Ketones (DKA)
Exogenous acid (Salicylate)
Failure to excrete acid (Renal failure/tubular acidosis, carbonic anhydrase inhibitor)
Decreased base
Bicarbonate loss (Diarrhoea or proximal renal tubular acidosis)
Explain the term anion gap
IMAGE - CATMUD PILES
The difference between the measurable cations and anions in the blood. It can indicate whether an excess of unmeasured anions are contributing to acidosis.
([Na⁺] + [K⁺]) - ([Cl⁻] + [HCO₃⁻)
Normal is 8-12 mmol, and a raised anion gap is greater than this.
The causes can be broken down into
Carbon monoxide, cyanide, congenital HF
Aminoglycosides
Toluene glue, Theophylline
Methanol
Uraemia
Diabetic Ketoacidosis
Paraldehyde, paracetamol
Iron, isoniazid, inborn errors of metabolism
Lactic Acidosis
Ethylene Glycol, ethanol
Salicylates
Some ABG machines cannot distinguish between lactate and glycolate, which builds up in ethylene glucol poisoning.
Very infrequently, low anion gap metabolic acidosis can occur, often because of albumin depletion, such as severe cachexia, nephrotic syndrome, severe burns or bleeding, or sepsis.
Categorise the different types of lactic acidosis
Pyruvate + NADH <-> Lactate + H⁺ + NAD⁺
Normal lacatate levels are <2mmol/L, with severe lactic acidoses occuring at >5mmol/L. It is a strong ion with pKa 4
The Cohen and Woods Classification is:
Type A - Inadequate O2 delivery to tissues - leading to glycolysis and anaerobic respiration.
Type B - Adequate delivery, but inability to use it effectively.
Type B1 - Underlying disease process
Leukaemia and lymphoma
Thiamine deficiency
Infection
Pancreatitis
Short gut syndrome
Liver and Kidney failure
Type B2 - Induced by drugs
Cyanide & nitroprusside
Paracetamol & salicylates
Adrenaline & beta-agonists
Ethanol & methanol
Ant–retrovirals
Phenformin
Isoniazid
Type B3 - Inborn errors of metabolism
How does sepsis cause a lactic acidosis?
With reference to the Cohen and Woods classification:
**Type A **- Microvascular dysfunction, hypoxia and shock
Type B1 - Mitochondrial dysfunction
Type B2 - Adrenaline (both endogenous and exogenous)
