17.3 Core Pathophysiology: Cellular Injury, Hypoperfusion & the Shock States
Key Takeaways
- Shock is inadequate tissue perfusion to meet cellular demand; hypotension is a late, unreliable finding and is frequently absent in children, pregnant patients, and fit young adults.
- The four shock categories map onto the determinants of blood pressure: hypovolaemic (preload), cardiogenic (contractility), obstructive (mechanical), and distributive (systemic vascular resistance).
- Neurogenic shock produces hypotension with bradycardia and warm dry skin below the lesion; the absent compensatory tachycardia is the discriminator and fluid alone often fails.
- Narrowing pulse pressure, tachypnoea, cool clammy skin, and subtle mental status change precede hypotension in compensated shock.
- Beta blockers, pacemakers, advanced age, pregnancy, hypothermia, and neurogenic shock all mask or remove the compensatory tachycardia, so a normal heart rate never excludes shock.
17.3 Core Pathophysiology: Cellular Injury, Hypoperfusion & the Shock States
CPCF Appendix A foundational knowledge #4 requires the PCP to understand pathology and pathophysiology: microbiology and infection, the impact of pathologies on physiology, structure and function, and common pathological processes and mechanisms. Every clinical chapter in this guide is an application of the same small set of mechanisms. Learning them once makes the whole of Area H — 70% of the examination — considerably smaller.
The Cell Is the Unit of Illness
Aerobic metabolism converts glucose and oxygen into roughly 32 molecules of adenosine triphosphate (ATP), carbon dioxide, and water. Remove oxygen and the cell switches to anaerobic glycolysis, which yields about 2 ATP and lactic acid. The consequences follow in sequence and explain most of what you see clinically:
- ATP falls. The sodium-potassium pump, which consumes a large share of cellular energy, begins to fail.
- Sodium and water enter the cell; potassium leaks out. The cell swells. Extracellular potassium rises — the mechanism behind hyperkalaemia in crush injury, burns, and prolonged ischaemia.
- Lactic acid accumulates. Systemic metabolic acidosis develops, depressing myocardial contractility and blunting the response to catecholamines — which is why prolonged shock becomes refractory.
- Lysosomal membranes rupture, releasing digestive enzymes into the cytoplasm.
- Cell death. Necrosis (uncontrolled, with inflammation) or apoptosis (programmed, orderly).
Reperfusion injury adds a further insult: restoring flow to ischaemic tissue washes out accumulated potassium, acid, and myoglobin, and generates reactive oxygen species. This is the reason a crush-injury release is a planned, monitored event rather than a simple extrication.
Inflammation and the Immune Response
The innate response — vasodilation, increased capillary permeability, and leucocyte migration — produces the cardinal signs of redness, heat, swelling, pain, and loss of function. Locally it is protective. When the same mediators are released systemically, they produce the vasodilation and capillary leak of septic shock.
Adaptive immunity adds antibody-mediated and cell-mediated responses with memory. Its failure modes are examinable: immunodeficiency (no fever, no localizing signs, rapid deterioration), hypersensitivity (anaphylaxis), and autoimmunity.
Microbiology essentials: bacteria (treated with antibiotics; the source of most sepsis), viruses (antibiotics useless), fungi (typically opportunistic in the immunocompromised), and prions. Transmission routes — contact, droplet, airborne, vector, and vehicle — determine the precautions selected during a point-of-care risk assessment (Section 8.4).
Hypoperfusion: One Definition, Four Mechanisms
Shock is inadequate tissue perfusion to meet cellular metabolic demand. It is a perfusion diagnosis, not a blood-pressure diagnosis. Hypotension is a late, unreliable, and frequently absent finding — particularly in children, pregnant patients, and healthy young adults.
Because mean arterial pressure equals cardiac output multiplied by systemic vascular resistance, and cardiac output equals heart rate multiplied by stroke volume, there are only four things that can fail.
| Category | Mechanism | Examples | Distinguishing features |
|---|---|---|---|
| Hypovolaemic | Loss of circulating volume (preload) | Haemorrhage, burns, vomiting, diarrhoea, DKA, third-space loss | Cool, pale, clammy; tachycardia; narrowing pulse pressure; flat neck veins |
| Cardiogenic | Pump failure (contractility) | Myocardial infarction, dysrhythmia, myocarditis, valve failure | Cool and clammy with signs of congestion: crackles, raised jugular venous pressure, peripheral oedema |
| Obstructive | Mechanical obstruction to filling or ejection | Tension pneumothorax, cardiac tamponade, massive pulmonary embolism | Raised jugular venous pressure with clear lungs; tracheal deviation or muffled heart sounds; sudden severe dyspnoea |
| Distributive | Loss of vascular tone (systemic vascular resistance) | Sepsis, anaphylaxis, neurogenic (spinal), adrenal crisis | Often warm, flushed, vasodilated, at least early; wide pulse pressure |
Two distributive subtypes are frequently keyed:
- Anaphylactic shock — rapid onset after exposure, with urticaria, angioedema, bronchospasm, and gastrointestinal symptoms. Epinephrine is the treatment and there is no absolute contraindication.
- Neurogenic shock — loss of sympathetic outflow below a spinal cord lesion, classically above T6. Hypotension with bradycardia and warm, dry, pink skin below the lesion. The absence of the expected compensatory tachycardia is the discriminator, and it is why fluid alone frequently does not correct it. Do not confuse neurogenic shock (a haemodynamic state) with spinal shock (a temporary loss of reflexes and function below the lesion).
Compensation, and the Moment It Fails
| Stage | What the body is doing | What you see |
|---|---|---|
| Compensated | Baroreceptor-driven sympathetic response: tachycardia, increased contractility, selective vasoconstriction to skin, gut, and kidney; renin-angiotensin-aldosterone and ADH conserve salt and water | Normal blood pressure, tachycardia, tachypnoea, cool pale clammy skin, delayed capillary refill, narrowing pulse pressure, anxiety or restlessness, falling urine output |
| Decompensated | Compensatory mechanisms exhausted; acidosis blunts catecholamine response | Hypotension, deteriorating level of consciousness, weak or absent peripheral pulses, mottling |
| Irreversible | Widespread cell death, microvascular failure, multi-organ injury | No response to intervention |
[!CAUTION] Narrowing pulse pressure and anxiety precede hypotension. The earliest reliable signs of shock are a rising heart rate, a rising respiratory rate, cool clammy skin, a narrowing pulse pressure, and a subtle change in mental status — restlessness, then confusion, then obtundation. Waiting for a low blood pressure is waiting for decompensation, and in a child, in a pregnant patient, or in a fit 22-year-old, it is waiting far too long.
Compensation That Is Masked or Absent
- Beta blockers and calcium channel blockers prevent the compensatory tachycardia. A normal heart rate in a bleeding patient on metoprolol is not reassurance.
- Pacemakers fix the rate.
- Older adults have a reduced maximal heart rate and stiff ventricles, and may be hypertensive at baseline — a "normal" blood pressure of 118/76 in a patient who usually runs 170/95 represents significant shock.
- Pregnancy masks blood loss until 30% to 35% of volume is gone.
- Children maintain blood pressure through vasoconstriction until they collapse abruptly.
- Neurogenic shock removes the tachycardic response entirely.
- Hypothermia blunts every compensatory mechanism.
Sepsis: Infection Plus Organ Dysfunction
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The prehospital recognition set is deliberately simple: a suspected or confirmed source of infection plus physiological abnormality — altered mentation, respiratory rate of 22/min or higher, systolic blood pressure of 100 mmHg or lower, fever or hypothermia, tachycardia, or a rising lactate where measurable.
Points that earn marks:
- Temperature is unreliable. Older adults and immunocompromised patients are often afebrile or hypothermic, and hypothermia carries a worse prognosis than fever.
- Altered mental status is frequently the presenting sign in older adults, with no localizing symptoms at all.
- Septic shock is distributive but often has a hypovolaemic component from capillary leak and poor intake, so these patients are both vasodilated and volume-depleted.
- Time matters. Early recognition, oxygen, fluid within scope, and early notification so antibiotics can be given promptly are what the prehospital phase contributes.
Applying the Framework
When a patient is poorly perfused, work the four categories rather than guessing a diagnosis:
- Are the neck veins flat or distended? Flat suggests hypovolaemic or distributive; distended suggests cardiogenic or obstructive.
- Are the lungs wet or clear? Wet with distended veins suggests cardiogenic; clear with distended veins suggests obstructive.
- Is the skin cool and clamped down, or warm and vasodilated? Cool suggests hypovolaemic, cardiogenic, or obstructive; warm suggests distributive.
- Is the heart rate appropriate? An inappropriately normal or slow rate suggests neurogenic shock, beta blockade, a pacemaker, or hypothermia.
A 26-year-old is found at the base of a fall with a suspected cervical spine injury. He is hypotensive at 82/44 mmHg, with a heart rate of 52/min, and warm, dry, pink skin in his lower limbs. Which shock state is this, and why does fluid alone frequently fail to correct it?
A 19-year-old with a stab wound to the thigh has a heart rate of 124/min, a respiratory rate of 26/min, a blood pressure of 118/94 mmHg, cool and clammy skin, and is anxious and repeatedly asking what happened. Which stage of shock is this, and which finding is most informative?
An 83-year-old nursing home resident has become confused over 12 hours. Temperature is 35.4 °C, heart rate 96/min (she takes bisoprolol), respiratory rate 26/min, blood pressure 104/60 mmHg with a documented baseline of 168/90 mmHg. What is the most likely process and which findings are most concerning?