Microcirculation

Clinical relevance in anaesthesia & critical care

Microcirculation is the site of tissue oxygen delivery and extraction; global haemodynamics (MAP/CO) can appear “normal” while microcirculatory flow is impaired (loss of haemodynamic coherence).
- Examples: sepsis (heterogeneous flow/shunting), cardiogenic shock, major haemorrhage, trauma, CPB, severe anaemia, vasopressor-heavy resuscitation.
Determinants of capillary perfusion: precapillary resistance, capillary recruitment, RBC deformability, blood viscosity, and venous outflow pressure.
- Clinical correlates: hypothermia ↑viscosity; polycythaemia ↑viscosity; acidosis/hypoxia impair RBC deformability; raised CVP/venous congestion reduces capillary driving pressure.
Fluid therapy: capillary hydrostatic pressure and glycocalyx integrity influence oedema; excessive fluid can worsen interstitial oedema and diffusion distance.
- Sepsis/ischemia-reperfusion can damage glycocalyx → increased permeability and oedema.
Vasoactive drugs: improving MAP does not guarantee improved microvascular flow.
- Noradrenaline may recruit microcirculation in vasodilatory shock by restoring perfusion pressure, but excessive vasoconstriction can reduce capillary flow in some beds.
- Vasopressin: may preferentially constrict some beds; can worsen skin/splanchnic microflow in susceptible patients.
- Inodilators (e.g., dobutamine) may improve microvascular flow via increased CO and local vasodilation (context-dependent).

Bedside assessment (what you can infer about microcirculation)

Clinical surrogates: capillary refill time, skin mottling score, peripheral temperature gradient, urine output, mental state, lactate trend.
- Limitations: influenced by ambient temperature, vasopressors, pain/anxiety, age; lactate is not a pure marker of hypoperfusion.
Advanced/experimental: sublingual microcirculatory imaging (SDF/IDF), NIRS (thenar/cerebral), venous-to-arterial CO2 gap (as a flow surrogate).
- Microcirculatory indices: total vessel density, perfused vessel density, microvascular flow index, heterogeneity index.

Definition and components

Microcirculation: vessels typically <100 μm: arterioles, metarterioles, capillaries, venules; includes lymphatics and interstitium for exchange context.
Primary roles: distribution of flow, exchange of gases/nutrients/waste, fluid balance, immune trafficking, thermoregulation.

Anatomy and functional organisation

Arterioles (small arteries → terminal arterioles): major site of resistance and active tone (smooth muscle).
- Terminal arterioles supply capillary networks; precapillary sphincter concept is useful but anatomically variable.
Capillaries: single endothelial layer + basement membrane; largest total cross-sectional area → low velocity → exchange.
- Types: continuous (muscle, skin, lung), fenestrated (kidney, endocrine, gut), sinusoidal/discontinuous (liver, spleen, marrow).
Venules: key site for leukocyte adhesion and transmigration; contribute to capacitance; postcapillary venules important in inflammation and oedema formation.
Arteriovenous shunts: bypass capillary exchange; important in skin thermoregulation; can contribute to shunting/ineffective oxygen extraction in pathology.

Haemodynamics in the microcirculation

Driving pressure for organ perfusion approximates MAP − venous pressure (or downstream critical closing pressure); raised venous pressure (e.g., high CVP) can reduce microvascular flow.
- Venous congestion: can impair renal/hepatic/gut microcirculation despite adequate MAP.
Poiseuille’s law (laminar flow): Q ∝ (ΔP · r^4) / (η · L). Radius is the dominant variable; arteriolar tone strongly controls flow distribution.
- In vivo, blood is non-Newtonian; viscosity changes with shear rate and haematocrit.
Reynolds number is low in microvessels → laminar flow predominates.
Fåhræus effect: tube haematocrit < systemic haematocrit in small vessels due to axial migration of RBCs.
Fåhræus–Lindqvist effect: apparent viscosity decreases as vessel diameter decreases down to ~10–30 μm (then rises in very small capillaries).
- Mechanism: RBC axial streaming and cell-free plasma layer near vessel wall reduces friction.
Plasma skimming: at bifurcations, RBCs preferentially enter some branches → heterogeneous haematocrit and oxygen delivery at capillary level.

Exchange: diffusion and convection

Diffusion (Fick’s law): rate ∝ (Area · diffusion coefficient · concentration gradient) / thickness.
- Oedema increases diffusion distance → impaired O2 delivery even with adequate capillary flow.
Convection: bulk flow of solutes with fluid movement across capillary wall; depends on filtration/reabsorption and permeability.

Capillary fluid exchange: Starling forces (modern view)

Classic Starling: net filtration ∝ (Pc − Pi) − σ(πc − πi).
- Pc: capillary hydrostatic pressure; Pi: interstitial hydrostatic pressure; πc: plasma oncotic; πi: interstitial oncotic; σ: reflection coefficient (0–1).
Revised Starling principle: glycocalyx and subglycocalyx oncotic pressure are key; steady-state reabsorption along venous end is limited—excess filtered fluid is largely returned via lymphatics.
- Clinical implication: raising plasma oncotic pressure (e.g., albumin) may not “pull” oedema fluid back reliably; preventing glycocalyx damage and avoiding excessive Pc may matter more.
Factors increasing filtration/oedema: ↑Pc (fluid overload, venous congestion), ↓πc (hypoalbuminaemia), ↑permeability/↓σ (sepsis, burns), impaired lymphatic drainage.

Regulation of microvascular tone and flow distribution

Myogenic response (Bayliss effect): increased transmural pressure → arteriolar constriction; helps autoregulation.
Metabolic control: local hypoxia/↑CO2/↑H+/adenosine/K+ → vasodilation and capillary recruitment; matches flow to demand (functional hyperaemia).
Endothelial factors: NO (vasodilation), prostacyclin (vasodilation/anti-platelet), endothelin (vasoconstriction), EDHF (vasodilation in small arteries).
- Shear stress stimulates NO release; endothelial dysfunction reduces NO bioavailability (e.g., diabetes, sepsis, atherosclerosis).
Neurohumoral: sympathetic α1 constriction (arterioles/venules), β2 dilation (some beds); angiotensin II and vasopressin constrict; ANP promotes permeability and natriuresis.
Capillary recruitment: opening previously unperfused capillaries increases exchange surface area and reduces diffusion distance; prominent in skeletal muscle during exercise.

Microcirculatory dysfunction (key patterns)

Heterogeneous perfusion: some capillaries flow well, others stagnant → impaired extraction despite normal/raised DO2.
Shunting: blood bypasses exchange units (AV shunts or non-nutritive flow) → low SvO2 may not occur early; lactate may rise.
Endothelial activation/injury: glycocalyx shedding, increased permeability, leukocyte adhesion, microthrombi (immunothrombosis).
RBC and rheology issues: reduced deformability (acidosis, oxidative stress), altered aggregation; affects capillary transit.

Define the microcirculation and list its main functions.

Aim for a definition + roles in flow distribution and exchange.

Definition: network of vessels typically <100 μm (arterioles, capillaries, venules) plus the exchange interface with interstitium/lymphatics.
Functions: control of tissue perfusion, exchange (O2/CO2, nutrients, waste), fluid balance (filtration/lymphatic return), inflammation/immune trafficking, thermoregulation (skin shunts).

Describe the structure of a capillary bed and how flow is regulated within it.

Upstream: small arteries → arterioles → terminal arterioles supplying capillary networks; downstream: postcapillary venules → venules/veins.
Regulation mainly at arterioles (smooth muscle tone) via myogenic, metabolic, endothelial and neurohumoral influences.
Capillary recruitment changes the number of perfused capillaries, affecting exchange surface area and diffusion distance.

State Poiseuille’s law and explain its relevance to microcirculatory flow.

Poiseuille: Q = (ΔP · π · r^4) / (8 · η · L) for laminar flow in a rigid tube.
Relevance: small changes in arteriolar radius cause large changes in flow (r^4).
Limitations in vivo: vessels are distensible; blood is non-Newtonian; viscosity varies with shear rate and haematocrit; network effects and critical closing pressure exist.

Explain the Fåhræus effect and the Fåhræus–Lindqvist effect.

Fåhræus effect: in small vessels, tube haematocrit is lower than systemic haematocrit due to axial migration of RBCs and faster RBC velocity relative to plasma.
Fåhræus–Lindqvist: apparent blood viscosity decreases as vessel diameter decreases (down to ~10–30 μm) because of a cell-free plasma layer and RBC alignment; in very small capillaries viscosity rises again as cells must deform and move single-file.

What is plasma skimming and why might it matter for oxygen delivery?

At microvascular bifurcations, RBCs may preferentially enter one branch while plasma preferentially enters another → unequal downstream haematocrit.
This contributes to heterogeneity of capillary oxygen delivery, especially relevant in shock states where flow is already patchy.

Describe Starling forces governing capillary fluid movement and how the modern (glycocalyx) view modifies this.

Classic: net filtration ∝ (Pc − Pi) − σ(πc − πi).
Modern: the endothelial glycocalyx creates a subglycocalyx space with low protein; oncotic gradient across the glycocalyx is more important than πi; sustained reabsorption is limited and excess filtered fluid returns via lymphatics.
Implications: venous congestion/raised Pc and glycocalyx injury (sepsis, ischaemia-reperfusion) promote oedema; increasing πc alone may not reverse oedema reliably.

List factors that increase tissue oedema formation in critical illness.

↑Capillary hydrostatic pressure (fluid overload, venous congestion, heart failure).
↓Plasma oncotic pressure (hypoalbuminaemia).
↑Permeability / ↓reflection coefficient σ (sepsis, burns, anaphylaxis, inflammation; glycocalyx shedding).
Impaired lymphatic drainage (raised venous pressure, obstruction, immobility).

How does the endothelium regulate microvascular tone?

Vasodilators: NO, prostacyclin (PGI2), EDHF; stimulated by shear stress and agonists (e.g., acetylcholine, bradykinin).
Vasoconstrictors: endothelin-1, thromboxane A2; balance determines tone.
Barrier function: tight junctions + glycocalyx regulate permeability and leukocyte/platelet interactions.

Explain why capillary refill time and lactate can be misleading as markers of microcirculatory perfusion.

Capillary refill: affected by ambient temperature, pain/anxiety, vasopressors, age, peripheral vascular disease; reflects skin flow which may not mirror splanchnic/renal flow.
Lactate: may rise due to adrenergic stimulation, impaired clearance (hepatic dysfunction), mitochondrial dysfunction, seizures; not specific for hypoperfusion.
Hence microcirculatory failure can exist with normal MAP/CO and vice versa.

What is meant by ‘loss of haemodynamic coherence’ in sepsis?

A dissociation between improvements in macrocirculatory variables (MAP, CO, SvO2) and microcirculatory perfusion (capillary density/flow).
Mechanisms: heterogeneous flow, microthrombi, endothelial/glycocalyx injury, impaired RBC deformability, altered vasoreactivity.
Clinical consequence: persistent organ dysfunction despite “normalised” haemodynamics.

Describe the determinants of tissue oxygen delivery and how the microcirculation influences oxygen extraction.

Global DO2 = CO × CaO2 (CaO2 depends on Hb, SaO2, PaO2).
Microcirculation determines whether delivered oxygen reaches cells: capillary density, transit time, flow heterogeneity, diffusion distance (oedema), and shunting.
Impaired microflow can reduce VO2 by limiting extraction even when DO2 is adequate (supply-independent VO2 becomes supply-dependent).

How can raised venous pressure impair microcirculatory perfusion? Give clinical examples.

Perfusion pressure is roughly MAP − venous pressure; if venous pressure rises, the driving pressure across the microcirculation falls.
Raised venous pressure also increases capillary hydrostatic pressure → oedema → increased diffusion distance.
Examples: RV failure/PE, tamponade, high PEEP with elevated CVP, fluid overload, abdominal compartment syndrome (impairs venous return/organ venous drainage).