Lecture 16: Acid-Base Balance and Disorders 1

Question 1

Definition of pH

Answer 1

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

Question 2

pH related calculations

Answer 2

pH = -log10 [H+]
Note: [H+] hydrogen concentration units molL-1
Note 2: [H+] = 10^-pH molL-1
Normal pH –> [H+] = 10^-7 = 40nmolL-1

Question 3

Intracellular vs Extracellular/Plasma Fluid pH

Answer 3

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

Question 4

Acidosis and Alkalosis pH total range

Answer 4

< 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

Question 5

Accuracy of acidosis and alkalosis

Answer 5

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

Question 6

Causes of Acidosis and alkalosis

Answer 6

Normally has a Primary acid/base disorder

- but can be mixed –> even 3x acid/base disorders possible

Question 7

Buffer equations

Answer 7

(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]

Question 8

Concept of a buffer

Answer 8

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])

Question 9

Bicarbonate as a buffer in blood

Answer 9

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

Question 10

Proteins as a buffer in blood

Answer 10

1. albumin
2. Hb haemaglobin
   H+ + A- HA
   ** draw molecules

Question 11

Henderson-Hasselback equation

Answer 11

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

Question 12

kPa conversion into pressure

Answer 12

1 kPa = 7.5 mmHg
–>
CO2 = 5.3 kPa = 1.2 mmolL-1

Question 13

Respiratory control of pCO2

Answer 13

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

Question 14

Clinical reelvance of HH equation

Answer 14

ICU

Operating theatre with anaethesised patients

Question 15

Changes in pCO2 on pH

Answer 15

Increased pCO2 –> acidosis

Decreased pCO2 –> alkalosis

Question 16

Methods of Blood gas measurement

Answer 16

1. Venous or Arterial blood collection
2. Anaerobic blood sample (no air)
3. Blood gas analyses

Question 17

Importance of specificity of Anaerobic blood sample

Answer 17

Important not to contain air in Anaerobic blood sample

- as wont be anaerobic –> will effect pCO2 and pO2 concentrations

Question 18

Blood-gas measured and calculated quantities

Answer 18

Measured quantities:
1) pH
2) pCO2
3) pO2
Calculated quantities:
1) bicarbonate HCO3-
2) base excess

Question 19

3x Respiratory CO2 distrubances

Answer 19

HH equation = pH = 6.74 + log (HCO3- / pCO2)

1. Normal:
   a) HCO3- = 24mmolL1 b) CO2= 5.3 kPa –> pH 7.4
2. CO2 retention –> increased [H+] –> Respiratory acidosis
   a) HCO3- same b) CO2 increased = 9 kPa –> pH lower 7.15
3. Hyperventilation –> decreased [H+] –> excessive CO2 loss
   a) HCO3- same b) CO2 decreased = 3kPa –> pH increased 7.6

Question 20

Acute asthma clinical example

Answer 20

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

Question 21

Hypercarbia

Answer 21

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

Question 22

Hyperventilation clinical example

Answer 22

Increased pH --> alkalEMIA
Decreased pCO2 --> Hypocarbia
pO2 (relatively higher)
Same HCO3- (metabolism not affected)
1. Respiratory Alkalosis
Treatment: breathe into a plastic bag

Question 23

Hyperventilation Treatment via breathing into a plastic bag

Answer 23

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

Question 24

3x Metabolic HCO3- distrubances

Answer 24

HH equation: pH = 6.74 + log (HCO3- / pCO2)

1. Normal: HCO3= 24 mmolL-1 pCO2= 5.3 kPa
2. Metabolic acidosis:
   a) Decreased HCO3- = 10mmolL-1 Same pCO2 Decreased pH
3. Metabolic Alkalosis
   b) Increased HCO3- = 40mmolL-1 Same pCO2 Increased pH

Question 25

Diabetic Ketoacidosis

Answer 25

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

Question 26

Role of Kidney in acid-base balance

Answer 26

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

Question 27

Causes of Metabolic Acidosis

Answer 27

1. Increased acid production 2. Decreased renal acid excretion 3. Bicarbonate loss

Question 28

Metabolic causes of Increased acid production

Answer 28

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

Question 29

Metabolic causes of Decreased acid secretion

Answer 29

a) renal failure (end stage kidney diseases) | b) renal tubular acidosis (specific defects in renal tubular acid secretion)

Question 30

Metabolic causes of Bicarbonate loss

Answer 30

a) Severe diarrohea or vomiting --> as gut contents are rich in bicarbonate

Question 31

Rare causes of metabolic acidosis

Answer 31

4. Methanol and ethylene glycol poisoning - methanol metabolises --> formic acid (glycolic and oxalic acids) 5. Glue and paint sniffing - toluene metabolised --> hippuric acid 6. Alcoholic Ketoacidosis - increased ketone. complex mechanism 7. Genetic Metabolic disorders (organic acidemias) + Anatomical causes - propionic acidemia - metabolemia aciduria

Question 32

Causes of metabolic alkalosis:

Answer 32

1. Ingestion of Sodium Bicarbonate --> high pH + high bicarbonate 2. Loss of acid due to vomiting (stomach juice HCl) --> high pH

Question 33

Where does bicarbonate come from

Answer 33

Especially in regards to metabolic alkalemia | Bicarbonate comes from the conversion of CO2 --> there is a limitless supply of CO2

Question 34

Text examples

Answer 34

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Question 35

Respiratory compensation in metabolic acidosis

Answer 35

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

Question 36

Methods of compensation for metabolic acidosis

Answer 36

Response to pH changes: 1. Metabolic buffers (proteins + bicarb) : within sec-mins 2. Ventilation: mins-hours 3. Kidney renal: longer

Question 37

Return of pH after respiratory compensation of metabolic acidosis

Answer 37

Returns CLOSE to original pH (7.4), but NOT ENTIRELY compensated - Fully compensated = suggests 2 Secondary/Mixed acid-base disorder

Question 38

Role of Kidney in Acid-base balance

Answer 38

Overall: finding ways to decrease acidity of acidic urine 1. Reabsorption of Bicarbonate ( PT proximal tubule) 2. Generation of new Bicarbonate ( PT proximal tubule) 3. H+ secretion (DT distal tubule) (via Diffusion trapping of K+ and H+ , due to Na+ transmembrane difference)

Question 39

Bicarbonate Reabsorption

Answer 39

PT Proximal Tubule Filtered bicarbonate is reabsorbed HCO3- + Na+/other cation --> reabsorbed from urinary tubule into vasorecta

Question 40

Bicarbonate Generation

Answer 40

PT Proximal Tubule Carbonic Anhydrase: Allows CO2 to enter PT --> HH equation inside PT --> increased HCO3- reabsoption and H+ secretion into lumen

Question 41

PT Bicarbonate generation counteracted

Answer 41

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

Question 42

H+ Secretion by Kidney

Answer 42

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

Question 43

Method of Diffusion trapping

Answer 43

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