What is Cachexia
Cachexia is a complex metabolic syndrome associated with underlying chronic illness and characterized by ongoing loss of skeletal muscle mass with or without loss of fat mass, driven by systemic inflammation and abnormal metabolism that cannot be fully reversed by conventional nutritional support alone. 1
Core Definition and Pathophysiology
Cachexia is synonymous with chronic disease-related malnutrition (DRM) with inflammation, though it is often incorrectly perceived as only end-stage malnutrition. 1 The prominent clinical feature is weight loss in adults, accompanied by reduced BMI and diminished muscle mass and function. 1
The syndrome results from:
- Negative protein and energy balance driven by reduced food intake combined with abnormal metabolism 2
- Systemic inflammatory response that redistributes the body's protein content, preferentially depleting skeletal muscle while increasing acute-phase protein synthesis 3
- Cytokine-mediated metabolic changes that increase protein degradation rates and limit the effectiveness of hypercaloric feeding to restore lean mass 3
Common Underlying Diseases
Cachexia occurs frequently in patients with end-stage organ diseases complicated by catabolic inflammatory responses, including: 1
- Cancer
- Chronic obstructive pulmonary disease (COPD)
- Congestive heart failure
- Chronic kidney disease
- Inflammatory bowel diseases
- Other chronic end-stage organ diseases
Diagnostic Criteria
The diagnostic criteria for cachexia require the same criteria as malnutrition PLUS the simultaneous presence of an underlying disease AND biochemical indices of ongoing or recurrent inflammation. 1
Specific Diagnostic Thresholds:
- Weight loss >5% alone, OR
- Weight loss >2% if BMI <20 kg/m² OR if appendicular skeletal muscle mass index is reduced (<5.5 kg/m² in women or <7.2 kg/m² in men)
For cardiac cachexia: 1
- Non-intentional and non-edematous weight loss >7.5% of premorbid normal weight
- Associated with abnormal neuroendocrine and immunologic function
Inflammatory Markers:
CRP >5 mg/L is suggested as the lower limit to define relevant inflammation in cachexia, though CRP seldom exceeds 40 mg/L in chronic disease-related cachexia (inflammatory flares may occur during disease exacerbations). 1 Other biochemical indicators include reduced serum albumin concentrations. 1
Progressive Stages
Cachexia can progressively develop through distinct stages: 1
- Pre-cachexia: Patients at risk due to inflammatory response from underlying chronic disease
- Cachexia: Meeting full diagnostic criteria
- Refractory cachexia: Advanced, irreversible stage
Clinical Significance and Outcomes
Cachexia is associated with: 4, 5
- Increased mortality risk
- Reduced chemotherapeutic effects and increased treatment toxicity in cancer patients
- Shorter time to tumor progression
- Reduced quality of life
- Progressive functional impairment 1
Critical Distinction from Starvation
The metabolic changes in cachexia differ considerably from simple starvation. 3 The systemic inflammatory response drives coordinated physiologic, metabolic, and behavioral changes that are tightly regulated by cytokines, making cachexia fundamentally different from nutritional deprivation alone. 3
Important Clinical Pitfall
Conventional nutritional support alone cannot fully reverse cachexia because the increased rate of protein degradation and cytokine-mediated metabolic alterations limit the ability of hypercaloric feeding to restore lean mass. 1, 3 This distinguishes cachexia from simple malnutrition and requires multimodal treatment approaches targeting the underlying inflammatory processes. 6