Chemical Pathology: Acid-base handling

Question 1

Outline the pathophysiology of metabolic acidosis

Answer 1

• Increased H+ concentration in circulation
• Bicarbonate is used up
• Can either be due to increased H+ production (Diabetic ketoacidosis, reduced H+ excretion (Renal tubular acidosis) or loss of bicarbonate (Intestinal fistula).
• Respiratory compensation can occur where more CO2 is excreted, to increase pH

Question 2

List the causes of metabolic acidosis

Answer 2

• Increased H+ production (eg Diabetic Ketoacidosis/ Lactic acidosis)
• Reduced H+ excretion (eg renal tubular acidosis)
• Bicarbonate loss (eg intestinal fistula)

Question 3

Outline the pathophysiology of respiratory acidosis

Answer 3

• Decreased respiratory activity causes increased CO2, producing increased H+ and a slight increase in bicarbonate
• This may be due to decreased ventilation, poor lung perfusion or impaired gas exchange
• The kidney may try to compensate slightly by increasing excretion of H+ and increasing bicarbonate. [Kidneys cant adapt very well or quickly]

Question 4

How is pH controlled?

Answer 4

• Bicarbonate is used a buffer

- It mops up free H+ ions

Question 5

Outline how H+ ions are excreted and HCO3- is regenerated

Answer 5

• H+ is excreted by the kidneys [as HCO3- is also regenerated]
• Na+K+ATPase moves Sodium from the renal tubule cell into interstitial fluid (circulation) in exchange for K+
• Na+ diffuses back into renal tubule cell from tubule lumen through Na+/H+ exchanger, causing secretion of H+
• Carbonic anhydrase converts CO2 and H2O into carbonic acid and then HCO3- and H+
• H+ is secreted as described (With Na+/H+ exchanger)
• HCO3- with Na+ (NaHCO3) diffuses into interstitial fluid, where it can act as a buffer for

Question 6

State the 2 ways in which the pH of the body is downregulated/ how H+ changes are minimised

Answer 6

• HCO3- buffer
• H+ excretion by the kidneys
• CO2 excretion by the lungs

Question 7

List the causes of respiratory acidosis

Answer 7

• Asthma
• Chronic obstructive pulmonary disorder
• Acute pulmonary oedema
• Essentially any respiratory disorder

Question 8

Outline the pathophysiology of metabolic alkalosis

Answer 8

• Decreased H+ with decreased bicarbonate
• Can be due to H+ loss (eg pyloric stenosis), hypokalaemia or ingestion of bicarbonate.
• Respiratory compensation can occur where pCO2 is increased, bringing pH back to baseline

Question 9

State the causes of metabolic alkalosis

Answer 9

• H+ loss (eg pyloric stenosis)
• Hypokalaemia (eg loop/thiazide diuretic use)
• Ingestion of bicarbonate (antacids)

Question 10

Outline the pathophysiology of respiratory alkalosis

Answer 10

• Excessive respiratory activity causes increased excretion of CO2.
• Due to hyperventilation, either voluntary, artificial ventilation, or stimulation of the respiratory centre
• Kidney compensation: low H+, low bicarbonate
• In chronic cases: H+ excretion may be reduced to compensate

Question 11

Case:
pH: 6.9 (7.35-7.45)
H+: 126nmol/l (35-46)
pCO2: 3.0 kPa (4.7-6.0)
pO2: 24.0 kPa (10.0-13.3)
Bicarbonate: 6 mmol/l (22-30)
What is the most likely diagnosis?

Answer 11

• Metabolic acidosis with partial respiratory compensation
• Decreased pH
• Decreased pC02m, increased pO2
• Causes: diabetic ketoacidosis, lactic acidosis, renal failure, intestinal fistula

Question 12

Case:
-64 year old lady, intermittent vomiting, abdominal pain, weight loss.
-O/E: Dehydrated, jaundiced, Hypotensive, oliguric (low urine out).
pH: 7.55 (7.35-7.45)
H+: 28 nmol/l (35-46)
pCO2: 8.2 kPa (4.7-6.0)
pO2: kPa 10.0 (10.0-13.3)
Bicarbonate: 51 mmol/l (22-30)
What is the most likely diagnosis?

Answer 12

• Metabolic alkalosis with respiratory compensation
• ↑ Urea and creatinine
• ↓ Sodium
• DDx: Hypokalaemia, H+ loss, ingestion of bicarbonate
• Renal impairment suggests hypokalaemia
• Hypokalaemia could be due to pyloric stenosis

Question 13

Explain how pyloric stenosis leads to metabolic alkalosis

Answer 13

• Pyloric stenosis causes increased vomiting.
• Loss of HCl in vomit produces a metabolic alkalosis (Low H+, high bicarbonate)
• [Loss of fluid causes dehydration (Raised urea, creatiniine and total protein)]
• [Dehydration stimulates renin/angiotensin/aldosterone system]
• [Potassium lost in vomit and urine]

Question 14

Case:
pH: 7.55 (7.35-7.45)
H+: 28 nmol/l (35-46)
pCO2: 3.0 kPa (4.7-6.0)
pO2: 14.4 kPa (10.0-13.3)
Bicarbonate: 20 mmol/l (22-30)
What is the most likely diagnosis?

Answer 14

Acute respiratory alkalosis

-Looks like it could also be mixed metabolic and respiratory alkalosis but I dunno apparently it isn’t

Question 15

Case:
pH: 7.41 (7.35-7.45)
H+: 39 nmol/l (35-46)
pCO2: 10.4 kPa (4.7-6.0)
pO2: 7.8 kPa (10.0-13.3)
Bicarbonate: 47 mmol/l (22-30)
What is the most likely diagnosis?

Answer 15

• Respiratory acidosis (eg caused by COPD)
• With metabolic alkalosis (eg hypokalaemia)
• Which is the primary causes is unknown. More information is needed.
• (eg 72 yr old man, long history of COPD, diuretic used)

Question 16

Case:
pH: 7.46 (7.35-7.45)
H+: 35 nmol/l (35-46)
pCO2: 2.0 kPa (4.7-6.0)
pO2: 17.8 kPa (10.0-13.3)
Bicarbonate: 10 mmol/l (22-30)
What is the most likely diagnosis?

Answer 16

• Respiratory alkalosis with metabolic acidosis
• Low pCO2: respiratory alkalosis
• Low bicarbonate: metabolic acidosis
• Associated with aspirin (metacid, respalk)

Question 17

Case:
pH: 6.93 (7.35-7.45)
H+: 116 nmol/l (35-46)
pCO2: 9.7 kPa (4.7-6.0)
pO2: 65.8 kPa (10.0-13.3)
Bicarbonate: 15 mmol/l (22-30)
What is the acid-base status of this patient?

Answer 17

• Mixed respiratory acidosis with metabolic acidosis

- High pO2 suggests artificial ventilation

Question 18

Case details-1 
A 45 year-old-female suffering from bronchial asthma was brought to emergency in a critical state with extreme difficulty in breathing.
The blood gas analysis revealed the following
pH- 7.3
PCO2- 46 mm Hg
PO2- 55 mm Hg
HCO3- 24meq/L
What is your Interpretation?

Answer 18

Case discussion

• Low p H – acidosis
• Low PO2 andPCO2 excess signify Primary respiratory problem
• HCO3: 24 -normal
• Thus, the patient is suffering from Acute respiratory acidosis.

Question 19

Case details -2
A 4 day old girl neonate became lethargic and uninterested in breast-feeding. Physical examination revealed tachypnea (rapid breathing) with a normal heart beat and breath sounds. Initial blood chemistry values included normal glucose, sodium, potassium, chloride, and bicarbonate (HCO3-) levels.
Blood gas values revealed a pH of 7.53, partial pressure of oxygen (PO2) was normal (103 mm Hg)but PCO2 was 27 mmHg.
What is the probable diagnosis?

Answer 19

Case discussion
The baby is suffering from Respiratory Alkalosis
Tachypnea in term infants may be due to brain injuries and metabolic diseases that irritate the respiratory center. The increased respiratory rate removes carbon dioxide from the lung alveoli and lowers blood CO2, forcing a shift in the indicated equilibrium towards left
CO2 + H2OçèH2CO3çèH+ + HCO3-
Carbonic acid (H2CO3) can be ignored because negligible amounts are present at physiological pH, leaving the equilibrium
CO2 + H2OçèH+ + HCO3-
The leftward shift to replenish exhaled CO2 decreases the hydrogen ion (H+) concentration and increases the pH to produce alkalosis. This respiratory alkalosis is best treated by diminishing the respiratory rate to elevate the blood [CO2], to force the above equilibrium to the right, elevate the [H+], and decrease the p

Question 20

Case details -3
A 60-year-old man was brought to hospital in a very serious condition. The patient complained of constant vomiting containing several hundred mL of dark brown fluid from the previous two days plus several episodes of melaena. Past history of alcoholism, cirrhosis, portal hypertension and a previous episode of bleeding varices was there.
Arterial Blood Gases revealed-
pH – 7.10
pCO2 – 13.8 mmHg
pO2- 103 mmHg
HCO3- 14.1 mmol/l
Laboratory Investigations
Na+131 mmol/l., Cl–85 mmol/l. K+4.2 mmol/l., “total CO2” 5.1, glucose 52mg/dl, urea 38.6mg/dl, creatinine1.24mg/dl, lactate 20.3 mmol/l Hb 6.2 G%, and WBC- 18x103/mm3

Answer 20

Case discussion
The patient is severely ill with circulatory failure and GI bleeding on a background of known cirrhosis with portal hypertension.
The very low pHindicates a severe acidosis. The combination of a low pCO2and low bicarbonate indicates either a metabolic acidosis or a compensatory respiratory alkalosis (or both). As this patient has a severe acidosis, so the most probable diagnosis is metabolic acidosis. The anion gap is 31 indicating the presence of a high anion gap disorder. The lactate level of 20.3mmol/l is extremely high and this confirms the diagnosis of a severe lactic acidosis. Hb is very low consistent with the history of bleeding and hypovolemia.Urea and creatinineare elevated (renal failure) but at these levels there would not be retention of anions sufficient to result in a renal acidosis. Hence,
Lactic acidosis can be suspected. The respiratory efforts may be due to the distress or as a consequence of a metabolic acidosis (ie compensatory).

Question 21

Summarise the relationship between CO2 +H2O and H+ and HCO3-

Answer 21

• CO2 + H2O is converted to carbonic anhydrase, then to H+ + HCO3-
• CO2 and H+ are produced by metabolism
• pCO2 excreted by the lungs
• H+ is escreted by the kidneys