Can you discuss oedema, its causes, pathophysiology, and clinical significance?

Oedema: Pathophysiology, Causes, and Clinical Significance

Definition and Fundamental Mechanism

Oedema is the abnormal accumulation of fluid in the interstitial compartment of tissues, resulting from disruption of the balance between hydrostatic and oncotic pressures across the microvascular barrier. 1, 2

The proximate cause of all oedema is increased vascular endothelial permeability, though the underlying mechanisms are heterogeneous and complex. 3 Ultimately, enhanced vascular permeability leads to tissue swelling through fluid extravasation from the intravascular to the interstitial space. 3

Core Pathophysiological Mechanisms

Oedema formation occurs through four primary mechanisms:

1. Decreased Intravascular Oncotic Pressure

• Hypoalbuminemia is the classic example, where plasma albumin falls below 25 g/L, reducing the oncotic pressure that normally retains fluid within vessels. 4
• In nephrotic syndrome with proteinuria exceeding 3.5 g/day, massive protein loss leads to hypoalbuminemia and subsequent oedema formation. 4
• The "underfill" theory suggests that decreased plasma oncotic pressure causes fluid transfer from plasma to interstitial space, creating relative hypovolemia and triggering secondary renal sodium retention. 4

2. Increased Intravascular Hydrostatic Pressure

• Elevated capillary hydrostatic pressure forces fluid out of vessels into the interstitium. 2
• In heart failure, venous congestion increases capillary hydrostatic pressure, leading to peripheral oedema. 5
• Peripheral oedema with raised jugular venous pressure and hepatic enlargement indicates cor pulmonale development. 3

3. Increased Capillary Permeability

• Inflammation causes hyperemia, increased vascular permeability, and net expansion of the extracellular space. 3
• Tissue oedema mediated by bradykinin, serotonin, and prostaglandins is a hallmark of inflammation in all soft tissues. 3
• Increased leakage of proteins across the capillary membrane reduces the oncotic pressure difference, making oedema more likely. 3

4. Impaired Lymphatic Drainage

• Obstruction or dysfunction of lymphatic vessels prevents normal fluid clearance from the interstitial space. 2

Primary Renal Sodium Retention

In most adult nephrotic syndrome cases and many other conditions, the primary event is intrinsic renal sodium retention rather than secondary hypoperfusion. 4

• This "overfill" mechanism involves a primary renal excretory defect leading to extracellular fluid expansion and oedema formation. 4
• Renal sodium retention is an important factor in generalized oedema across multiple etiologies. 2

Major Clinical Causes

Cardiac Oedema

• Heart failure patients present with lower extremity oedema due to elevated venous pressure and sodium retention. 5
• Myocardial oedema can result from venous congestion in acute decompensated heart failure. 3
• Peripheral oedema may indicate altered renal function, common in patients with hypoxaemia and hypercapnia. 3

Renal Oedema

• Nephrotic syndrome causes oedema in dependent areas (legs) that can progress to pulmonary oedema, ascites, and anasarca. 6
• Two mechanisms operate: the "underfill" theory (mainly in children with minimal change disease) and primary sodium retention (most adults). 4

Inflammatory Oedema

• Current evidence strongly supports that inflammatory oedema formation results primarily from decreased interstitial hydrostatic pressure that dramatically increases microvascular filtration. 7
• Tissue inflammation inevitably includes oedema of the affected tissue, with increased water content prolonging T1 and T2 relaxation times. 3

Post-Obstructive Pulmonary Oedema

• Negative intrathoracic pressure from forceful inspiratory efforts against an obstructed airway (commonly laryngospasm) causes non-cardiogenic pulmonary oedema. 3
• Occurs after 0.1% of general anaesthetics, more common in young muscular adults (male:female ratio 4:1). 3
• Negative pleural pressures increase the hydrostatic pressure gradient across pulmonary capillary walls, causing fluid leak into interstitial space. 3

Cerebral Oedema

Cerebral oedema is fundamentally divided into cytotoxic and vasogenic types, though most clinical situations involve a combination of both mechanisms. 8

Cytotoxic Oedema

• Results from altered water and ion transport across neuronal and glial cell membranes, causing intracellular water accumulation. 9, 8
• The collapse of the Na+/K+ gradient is the central mechanism, typically in acute ischemic injury. 9
• Peaks 3-4 days after injury, though malignant oedema can develop within 24 hours with early reperfusion of large necrotic volumes. 9, 8

Vasogenic Oedema

• Involves blood-brain barrier breakdown, allowing plasma constituents to leak into brain tissue. 8
• Represents increased extracellular fluid volume, contrasting with cytotoxic oedema's intracellular accumulation. 9

Clinical Assessment

Physical Examination Findings

• The sensitivity of physical examination for detecting moderately severe conditions is poor, and reproducibility of physical signs is variable. 3
• Visible accessory muscle activity or pursed-lip breathing usually implies severe underlying pathology. 3
• Central cyanosis indicates significant hypoxaemia but has low sensitivity. 3
• Peripheral oedema may have multiple causes beyond the obvious, requiring systematic evaluation. 3

Critical Pitfalls to Avoid

Oedema from different causes requires different treatments, and misidentification can worsen outcomes:

• Corticosteroids should only be used for vasogenic oedema, NOT cytotoxic oedema. 8
• Hypo-osmolar fluids (5% dextrose in water) worsen cerebral oedema formation. 8
• Excess glucose administration contributes to oedema development. 8
• Antihypertensive agents that induce cerebral vasodilation should be avoided as they may worsen intracranial pressure. 8

Management Principles by Etiology

Heart Failure-Related Oedema

• Thiazide or thiazide-type diuretics are preferred for blood pressure control and reversing volume overload in hypertensive heart failure patients with mild fluid retention. 5
• Diuretics must be used together with an ACE inhibitor/ARB and beta-blocker, as this combination improves outcomes. 5
• Follow-up within 1-2 weeks to assess response by checking edema improvement, weight loss, and blood pressure control. 5
• Consider cardiology referral if inadequate response to thiazide diuretic or signs of worsening heart failure. 5

Fluid Resuscitation Considerations

• In neonates and children with hypovolemia, isotonic saline is the first-choice fluid for initial resuscitation. 3
• Both colloids and crystalloids cause peripheral oedema, but no survival advantage exists for colloids over crystalloids. 3
• When large fluid volumes are required (e.g., sepsis), synthetic colloids may be used for longer circulatory duration. 3

Nephrotic Syndrome

• Therapy is specific for the underlying glomerular disease and symptomatic for oedema (diuretics). 4
• Many management options exist based on decades of experience; clinicians should choose based on careful monitoring of individual patient responses. 6

Prognostic Implications

• Weight loss in advanced disease is associated with more severe functional impairment. 3
• Clinical deterioration occurs in 25% of stroke patients, with 10% attributed to hemorrhage. 8
• Large-volume infarcts, particularly involving major intracranial artery occlusions, produce clinically significant oedema. 8
• Posterior fossa infarctions warrant careful observation due to risk of life-threatening oedema and brainstem compression. 8