Bioenergetics

Also written as Cellular energetics, Metabolic biochemistry.

Bioenergetics studies how cells produce, store, and use energy. It links metabolism to clinical states like shock, sepsis, and mitochondrial disease, guiding diagnosis and treatment.

Overview

Cells obtain energy mainly from oxidation of glucose, fatty acids, and amino acids via glycolysis, the citric acid cycle, and oxidative phosphorylation (OXPHOS). ATP generated powers all cellular functions.

• ATP is the universal energy currency.
• Mitochondria are the powerhouses where OXPHOS occurs.
• Anaerobic glycolysis yields only 2 ATP per glucose.

Key concepts

Understanding the balance between ATP supply and demand explains many acute and chronic illnesses.

• Serum lactate: Is there anaerobic metabolism? High lactate indicates inadequate OXPHOS, seen in shock or mitochondrial failure.
• Arterial blood gas (ABG): Is tissue oxygenation sufficient? Low PaO2 or high A‑a gradient suggests impaired oxidative phosphorylation.
• Serum pyruvate/alanine ratio: Is glycolysis up‑regulated? Elevated ratio supports mitochondrial dysfunction.

• ATP demand rises in fever, tachycardia, and tissue repair.
• Supply falls with hypoxia, mitochondrial toxins, or nutrient deficiency.
• The NADH/FADH2 pool links substrate oxidation to the electron transport chain.

Clinical relevance

Disrupted bioenergetics manifests as lactic acidosis, hypoglycemia, or organ failure. Recognising patterns directs urgent care.

• Septic shock: mitochondrial inhibition → high lactate, refractory hypotension.
• Ischemic stroke: ATP depletion → cell death within minutes.
• Mitochondrial myopathy: exercise intolerance, elevated CK, normal lactate at rest.

Exam pearls

Focus on cause‑effect relationships and diagnostic thresholds.

• Lactate >2 mmol/L signals anaerobic metabolism; >4 mmol/L in sepsis predicts higher mortality.
• Inherited mitochondrial disease often shows ragged‑red fibers on muscle biopsy.
• Hypoglycemia with normal insulin suggests increased peripheral utilization (e.g., sepsis).

Common mistakes

Avoid oversimplifying energy failure as only ‘low oxygen’. Consider substrate, enzyme, and cofactor deficits.

• Assuming normal lactate rules out shock – early shock may have normal lactate.
• Ignoring drug‑induced mitochondrial toxicity (e.g., linezolid, antiretrovirals).
• Attributing fatigue solely to anemia without assessing ATP production.

Questions an examiner may ask

• Explain how impaired oxidative phosphorylation leads to lactic acidosis in septic shock.
• List three common drug classes that cause mitochondrial toxicity and describe their clinical presentation.
• Interpret a lactate of 6 mmol/L with a normal PaO2 in a patient with fever and hypotension.

When to seek help

• Severe lactic acidosis (lactate >5 mmol/L) with hypotension
• Rapidly falling glucose <2.5 mmol/L in a non‑diabetic patient
• Acute unexplained encephalopathy with metabolic acidosis

Quick questions

Why does lactate rise in sepsis?

Inflammatory mediators impair mitochondrial enzymes, forcing cells to rely on anaerobic glycolysis, producing lactate.

Can a normal lactate exclude mitochondrial disease?

No; early disease may have normal resting lactate; stress testing often reveals abnormal rise.

What bedside test helps assess cellular oxygen use?

Capillary refill time and central venous oxygen saturation give indirect clues to tissue oxygen extraction.