Shock Physiology – Macro vs Microcirculation 

Shock is a state of acute circulatory failure leading to inadequate tissue oxygen delivery (DO₂) and impaired cellular oxygen utilization, resulting in cellular injury and organ dysfunction.

Modern critical care understanding emphasizes that shock is not merely a macrocirculatory problem (BP/CO) but also a microcirculatory and cellular disorder. Many patients normalize blood pressure and cardiac output but still die due to persistent microcirculatory failure.

 HEMODYNAMIC COHERENCE CONCEPT

 Definition-Relationship between macro- and microcirculatory response.

Patterns

Sepsis commonly shows incoherence.

OVERVIEW OF SHOCK PHYSIOLOGY

Shock progression occurs at three interconnected levels:

1. Macrocirculation (Systemic Hemodynamics)

 Large vessel and global cardiovascular function

2. Microcirculation

 Arterioles, capillaries, venules → tissue perfusion

3. Cellular & Mitochondrial Level

 Oxygen utilization & metabolic failure

 PART 1 – MACROCIRCULATION IN SHOCK

 Definition

Macrocirculation refers to global cardiovascular performance responsible for oxygen transport to tissues.

 Components of Macrocirculation

1. Cardiac Output (CO)

CO=HR×Stroke Volume

Determinants:

2. Systemic Vascular Resistance (SVR)

MAP=CO×SVR

3. Mean Arterial Pressure (MAP)

Represents global driving pressure for perfusion.

Typical target in shock: MAP ≥ 65 mmHg

4. Oxygen Delivery (DO₂)

DO2 =CO×CaO2

CaO2 =(Hb×1.34×SaO2 )+(PaO2 ×0.003)

—> Traditional Resuscitation Focus—Macrocirculatory resuscitation targets:

• Blood pressure
• Cardiac output
• Urine output
• Central venous oxygen saturation
• Lactate

BUT… Normalization of these parameters does NOT guarantee adequate tissue perfusion.

This leads to the concept of: Hemodynamic Coherence

Definition

Parallel improvement in macro and microcirculation.

Loss of coherence occurs when: MAP normal, CO adequate
, Tissue hypoxia persists-Common in septic shock.

 PART 2 – MICROCIRCULATION IN SHOCK

 Definition

Microcirculation consists of:

• Arterioles
• Capillaries
• Venules

Responsible for:

✔ Oxygen extraction
✔ Nutrient exchange
✔ Waste removal

🔴 MICRO CIRCULATORY FAILURE IN SHOCK

This is the central pathophysiological event leading to organ failure.

# Major Mechanisms

1️⃣ Heterogeneous Blood Flow

Key Feature of Septic Shock

Instead of uniform perfusion:

✔ Some capillaries hyperperfused
✔ Others completely shut

Result: Regional hypoxia despite normal global flow

2️⃣ Capillary Shunting

Blood bypasses oxygen exchange areas.

Consequences:

• Reduced oxygen extraction
• Increased venous oxygen saturation (ScvO₂ paradox)

3️⃣ Endothelial Dysfunction

Triggered by:

• Inflammatory cytokines
• Reactive oxygen species
• Glycocalyx destruction

Leads to:

✔ Loss of barrier function
✔ Increased permeability
✔ Tissue edema
✔ Impaired oxygen diffusion

4️⃣ Microvascular Thrombosis

Seen in:

• Septic shock
• Disseminated intravascular coagulation (DIC)

Mechanisms:

• Platelet activation
• Coagulation cascade activation
• Reduced fibrinolysis

5️⃣ Leukocyte-Endothelial Interaction

Leads to:

• Capillary plugging
• Tissue inflammation
• Flow obstruction

6️⃣ RBC Dysfunction

Changes include:

• Reduced deformability
• Aggregation
• Impaired oxygen delivery

 Clinical Consequences of Microcirculatory Failure

• Elevated lactate
• Organ dysfunction
• Persistent hypoxia
• Shock refractory to vasopressors

 PART 3 – CELLULAR & MITOCHONDRIAL DYSFUNCTION

Even when oxygen delivery is adequate, cells may fail to utilize oxygen.

# Cytopathic Hypoxia

Definition: Failure of mitochondrial oxygen utilization despite adequate oxygen supply.

Seen prominently in:

• Septic shock
• Severe trauma
• Burns

## CLINICAL MONITORING OF MICRO CIRCULATION

Bedside Surrogates

1. Lactate Clearance-Most widely used marker.

2. Capillary Refill Time (CRT)-Emerging resuscitation target.

3. Skin Mottling Score-Correlates with mortality.

4. Tissue Oxygenation Monitoring-Using near-infrared spectroscopy.

THERAPEUTIC IMPLICATIONS

Macrocirculatory Therapy

✔ Fluids
✔ Vasopressors
✔ Inotropes
✔ Blood transfusion

Microcirculatory Targeted Approaches (Emerging)

✔ Early sepsis control
✔ Avoid fluid overload
✔ Glycocalyx protection
✔ Optimize RBC transfusion
✔ Vasodilator microcirculatory modulation
✔ Adjunctive therapies (vitamin C, etc. – investigational)

 WHY PATIENTS DIE DESPITE NORMAL BP

Because: Shock is primarily a microcirculatory and cellular disease

Normalization of MAP alone:

❌ Does not ensure oxygen extraction
❌ Does not correct mitochondrial failure