Acid-base balance and buffers Flashcards
Define an acid
Proton donor
Strong acid - fully dissociated
Weak acid - partially dissociated
Define a base
Proton acceptor
Strong base - fully dissociated
Weak base - partially dissociated
What is an acid-base buffer
it is comprised of a weak acid and its conjugate base. A conjugate base is the dissociated anionic product of the acid.
Or
It is comprosed of a weak base and its conjugate acid.
A buffer solution resists a change in pH when a small amount of strong acid or base is added to the system.
What is a buffer
A buffer limits the effect of a proton load in any physiological solution, i.e. converting a strong acid to a weak acid.
What is pH
pH is the negative logarithm to base 10 of the concentration of the hydrogen ions in nanomoles per litre
pH = potential of Hydrogen
What is the normal pH of the following
- Gastric Juices
- Urine
- Arterial blood
- Venous blood
- CSF
- Pancreatic fluid
- Gastric Juices: 1 -3
- Urine: 5 - 6
- Arterial blood: 7.4
- Venous blood: 7.37
- CSF: 7.32
- Pancreatic fluid: 8
What is the definition of acidosis vs acidaemia
Acidosis is the excess of acid moieties within a physiological system.
Acidaemia is an arterial pH less than 7.4
Acidosis can be present in the absence of acidaemia (e.g. COPD)
What chemical process do the acids produced by the body come from
- Volatile acids: Metabolism of glucose: CO2 ! (14 000 mmol)
- Non-volatile acids: Protein metabolism
Why is the maintenance of normal Hydrogen ion concentration important?
- Homeostasis
- Maintenance of a constant physiological environment - Metabolism
- Hydrogen ions may be the products of metabolism - Ionic flux
- H+ has a high charge density and can influence ionic flux - Other functions
- H bonds are an integral part of molecular structure hence ionic H ion concentration influences function of:
a) Enzymes (bell curve with mean pH 7.4)
b) Proteins
c) Ions
d) Organ function
What is pKa?
It is the negative logarithm to base 10 of the dissociation constant for a chemical reaction.
It is also the pH at which a buffer system is most efficient and which the system exists in ionic equilibrium i.e. 50% ionized.
Name the key buffer systems in the following compartments:
- Blood
- Interstitium
- Intracellular
Blood
- Bicarbonate
- Hb (histidine)
- Plasma proteins (amino and carboxyl)
Interstitium
1. Bicarbonate
Intracellular
- Proteins
- Phosphate
What is the Henderson Hasselbach equation and how is it derived
pH = pKa + log [HCO3}/CO2
H + A = HA
k1 [H] x [A] = k2 [HA] and k2/k1 = K
[H] = K[HA}/[A] (then - log both sides and solve
What is the predominant buffer system within the tubules of the kidneys?
Phosphate buffer system
pK = 6.8
Describe the protein buffer systems
Cell and plasma proteins
- Carboxyl groups dissociate
- amino groups dissociate
Haemoglobin
- Histidine residues
Apart from HCO3 and Protein buffer systems, what other buffer systems are there
Carbonate buffer systems
- Carbonate in bone acts as a buffer (prolonged metabolic acidosis)
Which is the most powerful buffer system in the human body
Haemoglobin (Histidine residues)
What is the isobydric principle
Isohydric principle means that when a solution contains more than one buffer, all buffer pairs in the system are in equilibrium with the same proton concentration. Only those buffers with a pK within in 1 pH unit of that in the solution participate effectively in the buffering of the solution pH
What is meant by control effectiveness? In the context of the lungs capacity to respond to acid base imbalance
The efficiency of a physiological homeostatic mechanism to deal with a change in the parameter it controls.
E.g. Lungs control effectiveness = 50 - 75%
Will only deal with 5 - 7.5 nmol of a 10 nmol change in H ion concentration.
How do the kidneys affect acid base balance
H+ excretion
HCO3- filtered and reabsorbed
Generation of HCO3
How is H+ eliminated in the kidney
- Secondary active transport
- Primary active transport
- H ion and HCO3 interacting in the collecting system,
How and where does secondary active transport of H occur in the kidney
Proximal Convoluted Tubule (PCT)
CO2 diffuses into tubule cell via the ECF side
Converted to HCO3 + H+
H+ is then secreted into tubule lumen in exchange for reabsorption of Na
How and where does primary active transport of H ions take place in the kidney
Distal collecting duct in intercalated cells
Specific H transporting ATPase enzyme and transport protein.
CO2 enter tubule. HCO3 and H made. HCO3 reabsorbed into ECF in exchange for Cl-. ATP used to transport H+ into tubule lumen with Cl- (electroneutrality)
How significantly can the primary active transport mechanism concentrate H in the urine
900 fold
What happens when excess H is filtered
During acidemia –> excess filter of H
HCO3 saturated. Urinary buffers are used: H2PO4 and NH4+ (from Glutamine: enzyme: glutaminase)
(Urate, citrate, and creatinine play a minor role.
What is the role of the Liver in acid-base - list 5 aspects
- CO2 production (metabolically active)
- Metabolism of organic anions (lactate)
- Production of plasma proteins (buffers)
- Metabolism of ammonium
- Ureagenesis
Describe the role of ureagenesis in acid base regulation
There is no net acid or base production if CO2 is removed by the lungs.
The liver regulates the degree to which ureagenesis occurs, in the face of the need either to conserve or consume bicarbonate.
Amino acid metabolism –> HCO3 + NH4+
2HCO3- + 2NH4+ –> NH2CONH2 + CO2 + 3H20
How many ATP does aerobic vs anaerobic metabolism produce
Anaerobic: 2 ATP + H2O + Lactate
Aerobic: 36 ATP
Define and Classify hyperlatataemia
Lactate > 2 mmol/L and pH < 7.35
Type A: Impaired O2 delivery
Type B: No impaired O2 delivery
Describe the mechanisms for hyperlactataemia
- Increased cellular production
- Reduced uptake/use O2
- Reduced lactate clearance
(4. Increased glycolysis d/t adrenergic stimulation)
How is it possible to determine if elevated lactate is secondary to tissue hypoxia and why?
Lactate:pyruvate ratio > 10:1.
In the absence of O2 –> the electron transport chain is dysfunctional as NAD+ and FAD+ cannot be regenerated –> citric acid cycle is halted. Pyruvate conversion to lactate.
How does time delay for sample processing affect the calculation of the anion gap?
Time delay –> Leukocyte cellular metabolism proceeds –> Increases HCO3- concentration resulting in a mild reduction of the anion gap.
Apart from time delay of sample processing, what else affects the calculation of the anion gap
Renal dysfunction
What does a high anion gap mean
The anion gap represents the unmeasured anions in the solution. The equation (Na + K) - (HCO3- + Cl-) leaves out these unmeasured anions. Albumin is the anion that accounts for about 80% of these unmeasured anions. Other anions include: lactate, beta-hydroxybutyrate, acetoacetate, PO4 and SO4.
High anion gap indicates that there is a decrease in HCO3 without a concurrent increase in Cl-. To maintain electroneutrality, there are elevations in the above unmeasured anions to replace the HCO3 that is decreased.
What causes HAGMA
AC MUDPILES
Aspirin | Cyanide
Methanol Uraemia DKA Paraldehyde (IM sedative/hypnotic without analgaesia) + Phenformin (metformin) Isoniazid | Iron Lactate Ethanol | Ethylene glycol Salicylates
What is meant by a normal anion gap metabolic acidosis
The drop in HCO3- is almost completed compensated by a rise in Chloride (hyperchloraemic metabolic acidosis). Therefore anion gap is normal.
What are the causes of NAGMA
Loss of HCO3
- GIT - Diarrhoea
- Kidneys - Proximal RTA
- Kidneys - Distal RTA / failure / hyperaldosteronism
- Toxins - Ammonium Chloride / Acetazolamide / TPN
- Iatrogenic hyperchloraemic acidosis
Which substance can cause HAGMA and/or NAGMA
Ethanol
What causes a low anion gap
- Low albumin
- Increased Cations:
a) organic: paraproteins in multiple myeloma
b) Inorganic: Lithium / Iodine / Polymyxin B
Classify the causes of hypoalbuminaemia
Decreased synthesis (Liver)
Increased catabolism (Starvation/SIRS)
Increase loss: Kidneys / Burns / Haemorrhage / GIT
Redistribution: Haemodilution / Capillary leak
What are the directly measured versus calculated parameters on a blood gas report
Directly measured:
- pH
- PaO2
- PaCO2
Calculated
- stHCO3
- Actual HCO3
- Base excess
What is the problem with air bubbles in an blood gas sample
Cause a time dependent change in PaO2 and SaO2
Small bubbles worse than big bubbles as have larger surface area.
What does a time delay to analysis of a sample cause
More time for air bubbles to affect PaO2
pH decreases by 0.05/hour due to ongoing cellular metabolism
How does the heparin in the syringe affect the sample
Potential for dilution - 0.2 ml of a 5ml syringe
Modern syringes account for this
Which is better to obtain a sample: Plastic or glass
Plastic more cost effective and safer
Glass is technically better as it absorbs less O2 than some plastics
What affect does leucocytosis have on the report
Increased cellular metabolism –> increasing decline in pH and increasing PaCO2
How does Halothane affect ABG analysis
Halothane interferes with PaO2 electrodes in the blood gas machine
How does temperature affect blood gas result
Cooling –> CO2 becomes more soluble in blood and hence PaCO2 falls
pH rises 0.015 per degree celsius because Hb accepts more H ions when cooled
What is Standard bicarbonate versus measured bicarbonate?
This is the true metabolic picture of the patient as it reflects the HCO3 at normal temperature and PaCO2
What is the base excess/deficit
The amount of acid or base that must be added to a sample of WHOLE BLOOD in vitro to restore the sample pH to 7.4 while the PaCO2 is held at 5.3.
pH = 7.4 and Hb = 15 and PaCO2 = 5.33 –> BE = 0
Describe the three ways that the kidneys affect acid-base status
- Increase reabsorption HCO3- in PCT
- Increase H ion secretion
- Increase NH3 formation –> urinary buffer which augments HCO3 regeneration
In summary:
- HCO3- reabsorption
- HCO3- regeneration
- H+ secretion
Why does anaerobic metabolism cause metabolic acidosis
Pyruvate cannot proceed into the Citric Acid Cycle and is therefore converted into lactate. Two H+ ions are produced during this process which are normally reutilised during the Citric acid cycle. The citric acid cycle does not occur in the absence of oxygen as the electron transport chain is halted preventing recycling and availability of NAD and FAD.
Therefore, under anaerobic conditions there is an accumulation of lactate accompanied by metabolic acidosis
What are the principle causes of metabolic acidosis and metabolic alkalosis
Metabolic acidosis
- Kidney failure
- Excessive acid formation (Lactic acidosis/ketoacidosis)
- Administration of acid (Hyperchloraemic/toxic alcohol)
- Loss of base (diarrhoea)
Metabolic alkalosis
- Diuretics
- Loss of chloride (vomiting)
- Ingestion of alkali
- Excess aldosterone
Discuss the pH of the urine in patients with pyloric stenosis prior to surgery and subsequent to prlonged projectile vomiting
Profound loss of HCl –> Alkalaemia + Alkalosis
–> would expect urine to be alkaline. BUT profound hypovolaemia leads to activation of RAAS. Increased aldosterone –> excretion of H+ in urine and paradoxical aciduria
What acid base disturbance would be expected in a patient subsequent to total cystectomy?
Hyperchloraemic metabolic acidosis
Ureteroileal anastomosis: Cl- in urine is absorbed in the ileum and large intestine.
Can the urea and creatinine be normal in a patient with renal tubular acidosis
Yes.
Do diuretics cause acidosis or alkalosis
Most diuretics –> hypovolaemia –> increased RAAS –> alkalosis.
Acetazolamide –> carbonic anhydrase inhibitor –> prevents regeneration of HCO3- in the kidney –> metabolic acidosis
Why do salicylates cause a unique acid base disturbance
- Stimulate respiratory center: Resp Alkalosis
- Uncouple oxidative phosphorylation –> metabolic acidosis
The final picture depends on the balance of the two features
What are the dependent and independent variables according to Stewart’s theory of acid base
Dependent variables that produce ‘effects’:
- H+
- pH
- HCO3-
Independent variables that act as ‘controllers’
- PCO2
- Strong ion difference (net strong ion change)
- Total weak acid
What is the strong ion difference
Sum of the positively charged ions minus the sum of the negatively charged ions.
Normal SID = 40 - 42 mEq/L (Normal Saline has a SID of 0)
Equally: standard base excess can be used to quantify the SID.
(Na + K + Ca + Mg) - (Cl + lactate)
What does an increased SID lead to and why
increase pH - due to a decreased water dissociation
Explain the acid base disturbance (using Stewarts theory) that occurs from prolonged vomiting
Loss of HCl
Water in the body provides an inexhaustible supply of H ions
Cl- (a strong ion) is lost and therefore there are more strong cations relative to strong anions and the SID increases –> increased pH / alkalosis
According to the stewart model, explain the acid base disturbance that occurs in hypoalbuminaemia
Albumin = weak acid ( Atot)
If albumin is lost –> alkalosis
Explain the acid base disturbance caused by excessive administration of 0.9% NaCl
Acidosis
Dilution of the bodies SID (as NaCl has no SID) therefore causing an acidosis as there is ‘less space for OH’
How does Sodium Bicarbonate cause an alkalosis according to stewarts model
The sodium load associated with the administration of NaHCO3 leads to an increase in the SID –> Electroneutrality achieved by increase OH- relative to H+
Stewart would argue the HCO3- cannot influence the plasma pH as it is a dependent variable
