SN6
SHORT NOTE
5M
★ High-yield
Define lactic acidosis. Describe its biochemical basis and classify its causes.
Definition
Lactic acidosis = metabolic acidosis with a raised anion gap caused by accumulation of lactic acid, with blood lactate above 5 mmol/L and pH below 7.35.
- Normal blood lactate is 0.5–2 mmol/L
Biochemical Basis
Tissue hypoxia or a metabolic block → Pyruvate cannot enter the TCA cycle → NADH accumulates — cannot be reoxidised → Lactate dehydrogenase: pyruvate + NADH → lactate + NAD+ → Regenerates NAD+ so glycolysis can continue → Lactate accumulates
- Lactate formation is therefore protective in the short term — it allows glycolysis and hence ATP production to continue without oxygen
Classification
| Type | Mechanism | Causes |
|---|---|---|
| Type A | Tissue hypoxia — the common form | Shock (any kind), severe anaemia, cardiac arrest, severe hypoxaemia, carbon monoxide poisoning |
| Type B | No hypoxia — impaired metabolism | B1 — diabetes, liver failure, sepsis, malignancyB2 — metformin, ethanol, methanol, salicylate, antiretrovirals, cyanideB3 — inborn errors: PDH deficiency, pyruvate carboxylase deficiency, Von Gierke disease, mitochondrial disease |
Contribution of Specific Blocks
| Defect | Why lactate rises |
|---|---|
| Thiamine deficiency | PDH and α-KG dehydrogenase need TPP → pyruvate accumulates |
| Alcohol | ↑ NADH:NAD+ ratio drives pyruvate to lactate |
| Metformin | Inhibits hepatic gluconeogenesis → lactate is not cleared |
| Cyanide, CO | Block the respiratory chain → NADH cannot be reoxidised |
| Liver failure | The Cori cycle fails — lactate cannot be converted back to glucose |
Clinical Features and Diagnosis
- Kussmaul breathing (deep sighing respiration), tachycardia, hypotension, confusion
- Raised anion gap = Na+ − (Cl− + HCO3−); normal 8–16 mEq/L
- Arterial blood gas — low pH, low bicarbonate, compensatory low PCO2
- Blood lactate is the confirmatory test
Applied Aspects
- Treat the cause, not the number — restore tissue perfusion and oxygenation; bicarbonate is reserved for severe acidosis and is controversial
- Metformin is contraindicated in renal impairment, and withheld before contrast studies and surgery
- Lactate clearance is used to judge the adequacy of resuscitation in sepsis and shock — a falling lactate is a good prognostic sign
- D-lactic acidosis — a rare form from bacterial fermentation in short bowel syndrome; not detected by the standard L-lactate assay
All questions in Carbohydrate Metabolism I: Glycolysis, TCA & Gluconeogenesis
- Q1Define glycolysis. Describe its reactions, energetics and regulation. Add a note on its significance in the red blood cell. ★
- Q2Describe the reactions of the TCA cycle with its energetics and regulation. Explain its amphibolic role and add a note on anaplerotic reactions. ★
- Q3Define gluconeogenesis. Describe its substrates, the key enzymes bypassing glycolysis, and its regulation. ★
- Q4Describe the sources and fates of blood glucose. Explain the hormonal regulation of blood glucose in the fed and fasting states. ★
- Q5Describe the pyruvate dehydrogenase complex with its components, coenzymes and regulation. Explain its metabolic significance. ★
- SN1Describe the Cori cycle and its significance. Add a note on the glucose–alanine cycle. ★
- SN2Describe the Rapoport–Luebering shunt and the significance of 2,3-BPG. ★
- SN3Define substrate-level phosphorylation. Give the reactions and compare it with oxidative phosphorylation. ★
- SN4Define anaplerotic reactions. Give examples and explain their importance. ★
- SN5Classify the glycogen storage diseases. Describe Von Gierke and McArdle disease. ★
- SN6Define lactic acidosis. Describe its biochemical basis and classify its causes. ★
- SN7Describe the glucose transporters with their sites and functions.