General Physiology, Biochemistry and Immunology
Clinical Overview
Start from one idea: the body is a chemistry set that only works inside a narrow range of conditions, and almost everything in clinical medicine is the body defending that range or failing to. Hydrogen ion concentration, temperature, the concentration of sodium and water, the supply of oxygen and substrate, and the balance between attacking a threat and tolerating a friend are all controlled variables. When you understand how each one is held steady, you can predict what happens when illness, pregnancy or an intervention pushes it off target. Everything that follows is built on that single sentence.
This chapter is therefore the common language behind obstetric and gynaecological reasoning. A candidate who understands pH, enzyme behaviour, protein synthesis, temperature regulation, fluid-electrolyte physiology and immune response can usually reason through the clinical stem even when the named disease is unfamiliar. The point is not to memorise isolated facts. The point is to recognise a physiological pattern, place it in the pregnant or perioperative patient, and predict the clinical consequence.
In O&G, the same first principles recur. Lactic acidosis means inadequate oxygen delivery or utilisation, not simply an abnormal blood gas. Enzymes explain steroidogenesis, prostaglandin synthesis, drug metabolism, liver injury and laboratory "leaks" such as AST, ALT and LDH. Protein synthesis explains why steroid hormones act slowly, why clotting factors and receptors change during pregnancy, why malnutrition impairs wound healing, and why antibodies protect the neonate. Temperature is a controlled hypothalamic variable during fever but an uncontrolled heat-balance problem in hyperthermia. Sodium tells you about water and tonicity more than it tells you about total body sodium. Pregnancy immunity is not switched off; it is actively remodelled so that a semi-allogeneic fetus is tolerated while pathogen defence remains necessary.
The practical exam task is therefore to move from mechanism to bedside:
Shock -> anaerobic metabolism -> lactate -> metabolic acidosis -> reduced myocardial contractility -> worse uteroplacental perfusion -> fetal compromise.
Progesterone -> increased ventilation -> lower PaCO2 -> renal bicarbonate loss -> normal pregnancy respiratory alkalosis -> a "normal" non-pregnant PaCO2 may signal respiratory failure in pregnancy.
Fetal antigen exposure -> placental barrier and decidual immune regulation -> tolerance rather than rejection -> Rh alloimmunisation is the exception that proves maternal immunity can still respond.
Core Knowledge
Cellular Energy: Why Oxygen Matters and Where Lactate Comes from
Before acid-base makes sense, you need to know where the acid comes from. Almost every controlled variable in this chapter depends on the cell having enough adenosine triphosphate (ATP) to run its pumps, build its proteins and hold its shape. ATP is the cell's energy currency, and a cell cannot store much of it, so supply must continually match demand. The whole point of breathing, circulating blood and eating is to keep ATP being made.
The cell makes ATP from glucose in three linked steps, and where each step happens is itself an exam point.
- Glycolysis happens in the cytosol and does not need oxygen. It splits one glucose into two pyruvate molecules and yields a small amount of ATP quickly. This is why the red cell, which has no mitochondria, depends entirely on glycolysis.
- The citric acid cycle (Krebs cycle) happens inside mitochondria. It feeds the carbons from pyruvate through a series of reactions that capture energy as the electron carriers NADH and FADH2.
- Oxidative phosphorylation happens on the inner mitochondrial membrane and produces the great majority of the cell's ATP. It uses the electrons carried by NADH and FADH2 to pump protons, and the return flow of those protons through ATP synthase makes ATP. Oxygen is the final electron acceptor at the end of this chain. Without oxygen, the chain backs up and stops.
This explains the single most important chain in critical-care obstetrics. When oxygen delivery to a tissue fails — in haemorrhage, sepsis, uterine rupture or any low-flow state — oxidative phosphorylation cannot run. The cell falls back on glycolysis alone to keep some ATP coming. But glycolysis only continues if its NADH is recycled back to NAD+, and the way the cell does that without oxygen is to convert pyruvate into lactate. So lactate is not a poison the body produces by mistake; it is the chemical signature of cells running anaerobically because oxygen delivery or use has failed.
| Energy step | Location | Oxygen needed? | ATP yield | O&G relevance |
|---|---|---|---|---|
| Glycolysis | Cytosol | No | Small, fast | Red cells, brief hypoxia, the source of lactate when oxygen fails |
| Citric acid cycle | Mitochondrial matrix | Indirectly | Captures energy as NADH/FADH2 | Aerobic energy supply to myometrium, myocardium, brain |
| Oxidative phosphorylation | Inner mitochondrial membrane | Yes (final acceptor) | Large, most of cellular ATP | Fails first in shock; the reason hypoxia is rapidly lethal |
This is why a rising lactate or a worsening base deficit is read as inadequate oxygen delivery until proven otherwise, and why both are used as resuscitation endpoints. It also explains the bridge from a circulation problem to an acid problem: failed oxygen delivery forces anaerobic metabolism, anaerobic metabolism produces lactate, and lactate is the fixed acid that consumes bicarbonate and produces the metabolic acidosis described next.
pH and Acid-Base Physiology
pH is the negative logarithm of hydrogen ion concentration. A small pH movement therefore represents a large change in hydrogen ion concentration. Normal extracellular pH is held near 7.35 to 7.45 because protein shape, enzyme activity, potassium distribution, vascular tone, cardiac contractility, oxygen binding and cellular signalling all depend on it.
The clinically useful acid-base equation is the Henderson-Hasselbalch relationship:
The ratio is the point. PaCO2 is controlled quickly by ventilation. Bicarbonate is controlled more slowly by the kidney. The bicarbonate-carbon dioxide system is an "open" buffer because CO2 can be excreted through the lungs; haemoglobin, plasma proteins and phosphate provide additional buffering. In blood, haemoglobin is especially important because deoxygenated haemoglobin buffers hydrogen ions better than oxygenated haemoglobin, allowing tissues to unload oxygen and buffer acid at the same time.
| Variable | Main controller | Timescale | O&G relevance |
|---|---|---|---|
| PaCO2 | Alveolar ventilation | Minutes | Respiratory failure, opioid toxicity, sepsis hyperventilation, pregnancy baseline |
| Bicarbonate | Renal reabsorption/generation and acid excretion | Hours to days | Renal disease, vomiting, diarrhoea, DKA, starvation ketosis |
| Base excess/deficit | Non-respiratory buffer disturbance | Immediate measurement | Shock, haemorrhage, fetal acidaemia, resuscitation endpoint |
| Lactate | Tissue hypoxia/stress and clearance | Dynamic | Sepsis, haemorrhage, uterine rupture, major surgery |
| Disturbance | Primary change | Compensation | O&G example |
|---|---|---|---|
| Metabolic acidosis | Bicarbonate consumed/lost, or fixed acid added | Hyperventilation lowers PaCO2 | Haemorrhagic shock, sepsis, DKA, starvation ketoacidosis, renal failure |
| Metabolic alkalosis | Bicarbonate rises or hydrogen/chloride lost | Hypoventilation, limited by hypoxaemia | Hyperemesis, nasogastric losses, diuretics, hypokalaemia |
| Respiratory acidosis | PaCO2 rises from hypoventilation | Renal bicarbonate retention | Opioid excess, magnesium toxicity with respiratory depression, severe asthma, obesity hypoventilation |
| Respiratory alkalosis | PaCO2 falls from hyperventilation | Renal bicarbonate loss | Normal pregnancy tendency, anxiety, pain, pulmonary embolism, early sepsis |
Pregnancy normally produces a mild respiratory alkalosis because progesterone stimulates the respiratory centre and increases alveolar ventilation. The kidney compensates by excreting bicarbonate. This is why a PaCO2 that looks normal for a non-pregnant adult can be abnormal in pregnancy: the pregnant patient should usually be running a lower PaCO2. Loss of that expected hyperventilation may be an early sign of fatigue, sedative effect, magnesium toxicity or respiratory failure.
Acid-base disturbances rarely occur alone. Acidosis shifts potassium out of cells, impairs catecholamine responsiveness, depresses myocardial contractility and worsens coagulopathy. Alkalosis increases calcium binding to albumin, lowering ionised calcium and producing paraesthesiae, cramps or tetany despite a normal total calcium. Severe vomiting produces not only alkalosis but also chloride depletion, potassium depletion and contraction of extracellular volume.
Clinical interpretation should follow four questions:
- Is the primary disturbance metabolic or respiratory?
- Is compensation present and appropriate?
- Does the clinical context imply a mixed disturbance?
- Is the cause a ventilation problem, a perfusion problem, a renal/tubular problem, or a toxin/drug problem?
Anion Gap Logic
The anion gap is a quick way to decide whether a metabolic acidosis is due to addition of unmeasured acid or loss of bicarbonate. The usual bedside calculation is: