Lecture 16: Acid-Base Balance and Disorders 1 Flashcards
Definition of pH
Concentration of H+ ions in solution (pH = -log(10) x [H+]) ECF pH (extracellular plasma) --> tightly regulated --> maintained in narrow range --> Enzymes, structures, proteins etc able to continue PHYSIOLOGICAL PROCESSES (maintain correct Structure and Function) Normal pH = 7.4 (7.35 - 7.45) - when outside narrow range = disease state
pH related calculations
pH = -log10 [H+]
Note: [H+] hydrogen concentration units molL-1
Note 2: [H+] = 10^-pH molL-1
Normal pH –> [H+] = 10^-7 = 40nmolL-1
Intracellular vs Extracellular/Plasma Fluid pH
Acidity: Extracellular/Plasma pH higher/less acidic > intracellular pH
Note: Plasma = Liquid component of blood = 20% of ECF
Measurability:
1) Intracellular is largest body of fluid (2/3) –> measure directly
2) Measure plasma pH –> Indirect measure of ECF
Acidosis and Alkalosis pH total range
< 6.9 7.2 7.35 7.45 7.6 7.9 <
incompatible w. life severe acidosis acidosis normal alkalosis severe alkalosis incompatible w. life
Accuracy of acidosis and alkalosis
AcidOSIS and AlkalOSIS = Pathological processes –> cause a change in pH
AcidEMIA and alkalEMIA = acidic or alkaline blood plasma pH
Note: blood plasma pH is used as an indirect measure for ECF pH
Causes of Acidosis and alkalosis
Normally has a Primary acid/base disorder
- but can be mixed –> even 3x acid/base disorders possible
Buffer equations
(H+) Weak acid/base + Base (A-) Acid (HA)
Note: pK as Base and Acid concentrations are equal
Want to decrease pH/Increase acidity:
Added Weak Acid (H+) + Reduced Base [A-] Increased Acid [HA]
Concept of a buffer
Buffers:
Adds or Removes H+ –> Decreases range of pH changes
H+ are only temporarily removed –> Not eliminated from body
pK of a buffer –> pH when [A-] = [HA]
pH = pK + log ([A-] / [HA])
Bicarbonate as a buffer in blood
H+ + HCO3- H2O + CO2
(40nmol/L) + (24mmol/L) Ommol/L + (1.2mmol/L = 5.3 kPa)
CO2 tension pressure = 5.3 kPa = 1.2 mmolL-1
Proteins as a buffer in blood
- albumin
- Hb haemaglobin
H+ + A- HA
** draw molecules
Henderson-Hasselback equation
pH = 6.74 + log ([HCO3-] / pCO2)
- this ratio determines pH
if pH = Concentration of [H+] nmolL-1 –>
[H+] = 182 x (CO2 partial pressure (kPa) / [Bicarbonate])
–> [H+] = 182 x ( 5.3 kPa / 24 mmolL-1) = 40 nmolL-1 = [H+] nmolL-1
kPa conversion into pressure
1 kPa = 7.5 mmHg
–>
CO2 = 5.3 kPa = 1.2 mmolL-1
Respiratory control of pCO2
metabolism –> CO2 (15,000 mmol/day (acidic)) –>
1. Henderson-Hasselbach equation = allows bicarbonate to buffer natural system –> snatches up H+ created by dissociated HH equation –> No significant changes in bodily pH
2. Ventilation rate –> CO2 expired –> controls pCO2
Note: 3: insurance policy utilising ventilation: High [H+] –> acidosis/increased bodily acidity–> Low bodily pH –> stimulates increased ventilation –> increased CO2 expiration rate –> removal of [H+] /acidic CO2 –> Return to equilibrium
Clinical reelvance of HH equation
ICU
Operating theatre with anaethesised patients
Changes in pCO2 on pH
Increased pCO2 –> acidosis
Decreased pCO2 –> alkalosis
Methods of Blood gas measurement
- Venous or Arterial blood collection
- Anaerobic blood sample (no air)
- Blood gas analyses
Importance of specificity of Anaerobic blood sample
Important not to contain air in Anaerobic blood sample
- as wont be anaerobic –> will effect pCO2 and pO2 concentrations
Blood-gas measured and calculated quantities
Measured quantities: 1) pH 2) pCO2 3) pO2 Calculated quantities: 1) bicarbonate HCO3- 2) base excess
3x Respiratory CO2 distrubances
HH equation = pH = 6.74 + log (HCO3- / pCO2)
- Normal:
a) HCO3- = 24mmolL1 b) CO2= 5.3 kPa –> pH 7.4 - CO2 retention –> increased [H+] –> Respiratory acidosis
a) HCO3- same b) CO2 increased = 9 kPa –> pH lower 7.15 - Hyperventilation –> decreased [H+] –> excessive CO2 loss
a) HCO3- same b) CO2 decreased = 3kPa –> pH increased 7.6
Acute asthma clinical example
Decreased pH –> acidEMIA
Increased pCO2 –> Hypercarbic (–> verge of respiratory failure)
decreased pO2 (not relevant)
Same HCO3- (metabolism not affected)
1. Normal Asthma: High breathing rate –> increased expiration of CO2 –> decreased [H+] –> Respiratory Alkalosis
2. ACUTE asthma –> Acute Bronchiolar Constriction –> UNABLE to Ventilate properly –> Increased levels of CO2 –> Increased [H+] –> Respiratory acidosis
Note: Hypercarbia –> verge of Respiratory failure –> require ICU
Hypercarbia
Caused due to excessively high levels of CO2 (extremely acidic/low pH)
Due to e.g. Acute Bronchiolar constriction/acute asthma
Once Hypercarbic –> are on verge of respiratory failure –> require ICU
Hyperventilation clinical example
Increased pH --> alkalEMIA Decreased pCO2 --> Hypocarbia pO2 (relatively higher) Same HCO3- (metabolism not affected) 1. Respiratory Alkalosis Treatment: breathe into a plastic bag
Hyperventilation Treatment via breathing into a plastic bag
Hyperventilation –> decreased plasma CO2 levels and hence acidity –> respiratory alkalosis
Plastic bag –> Closed space –> High Ventilation into it increases concentration of expired CO2 within bag –> consumption of bag’s CO2 –> Increased plasma CO2 concentration and increased acidity –> return to Normal pH range –> Normal breathing rate
3x Metabolic HCO3- distrubances
HH equation: pH = 6.74 + log (HCO3- / pCO2)
- Normal: HCO3= 24 mmolL-1 pCO2= 5.3 kPa
- Metabolic acidosis:
a) Decreased HCO3- = 10mmolL-1 Same pCO2 Decreased pH - Metabolic Alkalosis
b) Increased HCO3- = 40mmolL-1 Same pCO2 Increased pH
Diabetic Ketoacidosis
Diabetes Type 1 –> complete lack of insulin –> glucose remain in plasma as unable to enter cells –> hyperglycaemic –> glucose undergoes anaerobic metabolism –> generate ketone bodies e.g. Betahydroxy-butyric acid –> increased metabolic acid production –> Metabolic acidosis
Increased metabolic acidity –> decreased pH –> Increased H+ –> Totally up HCO3- as a buffer
Acutely: Bicarbonate used up –> plasma [H+] > exceeds Renal H+ excretion –> Low pH + Low Bicarbonate
Cannot manipulate H2O –> so changes CO2 concentration
Role of Kidney in acid-base balance
Metabolism (proteins and dietary intake) –> Metabolic acid 100mmol/day –> HH equation –> Renal H+ excretion –> Urinary buffers
a) H+ + (phosphate) PO4(3-) H3PO4 (phosphoric acid)
b) H+ + (ammonia) NH3 NH4 (ammonium ions)
Urine pH = b/w 5 and 8
- diffusion trapping
- can vary depending on need
Causes of Metabolic Acidosis
- Increased acid production
- Decreased renal acid excretion
- Bicarbonate loss
Metabolic causes of Increased acid production
a) Lactic acidosis:
i) hypoxia
ii) poor tissue perfusion: drugs, airway metabolism, hypotension (blood loss, heart failure), ischaemia/MI/ruptured aortic anuerysm
iii) CO (carbonmonoxide) and Cyanide poisoning (pink but unable to utilise oxygen) (Hb cannot function)
b) Diabetic Ketoacidosis (DKA)
i) betahydroxbutyric acid + acetoacetic acids
Metabolic causes of Decreased acid secretion
a) renal failure (end stage kidney diseases)
b) renal tubular acidosis (specific defects in renal tubular acid secretion)
Metabolic causes of Bicarbonate loss
a) Severe diarrohea or vomiting –> as gut contents are rich in bicarbonate
Rare causes of metabolic acidosis
- Methanol and ethylene glycol poisoning
- methanol metabolises –> formic acid (glycolic and oxalic acids) - Glue and paint sniffing
- toluene metabolised –> hippuric acid - Alcoholic Ketoacidosis
- increased ketone. complex mechanism - Genetic Metabolic disorders (organic acidemias) + Anatomical causes
- propionic acidemia
- metabolemia aciduria
Causes of metabolic alkalosis:
- Ingestion of Sodium Bicarbonate –> high pH + high bicarbonate
- Loss of acid due to vomiting (stomach juice HCl) –> high pH
Where does bicarbonate come from
Especially in regards to metabolic alkalemia
Bicarbonate comes from the conversion of CO2 –> there is a limitless supply of CO2
Text examples
Respiratory compensation in metabolic acidosis
Metabolic acidosis uncompensated: Low HCO3 + Low pH Normal H+
Partially compensated metabolic acidosis: –> ACIDOTIC BREATHING
Occurs as Low pH –> stimulates ventilation –> increased CO2 expiration –> Lowers pCO2 –> Majorly compensated (but not fully compensated) pH
Methods of compensation for metabolic acidosis
Response to pH changes:
- Metabolic buffers (proteins + bicarb) : within sec-mins
- Ventilation: mins-hours
- Kidney renal: longer
Return of pH after respiratory compensation of metabolic acidosis
Returns CLOSE to original pH (7.4), but NOT ENTIRELY compensated
- Fully compensated = suggests 2 Secondary/Mixed acid-base disorder
Role of Kidney in Acid-base balance
Overall: finding ways to decrease acidity of acidic urine
- Reabsorption of Bicarbonate ( PT proximal tubule)
- Generation of new Bicarbonate ( PT proximal tubule)
- H+ secretion (DT distal tubule) (via Diffusion trapping of K+ and H+ , due to Na+ transmembrane difference)
Bicarbonate Reabsorption
PT Proximal Tubule
Filtered bicarbonate is reabsorbed
HCO3- + Na+/other cation –> reabsorbed from urinary tubule into vasorecta
Bicarbonate Generation
PT Proximal Tubule
Carbonic Anhydrase: Allows CO2 to enter PT –> HH equation inside PT –> increased HCO3- reabsoption and H+ secretion into lumen
PT Bicarbonate generation counteracted
Acetazolamide –> Carbonic Anhydrase inhibitor –> Decreased HCO3- production –> Decreased buffering/secretion of H+ by kidney –> Artificial Metabolic acidosis
Mountaineers –> hypoxic/low O2 enviro –> increased minute ventilation to get sufficient O2 supply –> increased CO2 expiration –> hyperventilation –> respiratory alkalosis
- Acute mountain sickness/significant respiratory alkalosis: effects Brain vasculature/lungs
H+ Secretion by Kidney
DT Distal Tubule
Diffusion Trapping: w. freely dispersed ammonia and phosphoric acid into cells from lumen
1. Epithelial Na Channel (ENaC) –> activated w. presence of aldosterone –> Na+ leaves DT into lumen via ENaC
2. Na membrane difference –> Increased positive charge in lumen –> Transepithelial difference in Electroneutrality (disturbed)
3. K+ and H+ pumped into DT (due to Na+ transmembrane difference) –> electroneutrality disturbed –> H+ now trapped in DT –> H+ (hence acid) excreted in urine –> Decreased acidity
Method of Diffusion trapping
**
