Cachexia, anorexia and wasting in disease
- Mechanism
- Exam priority: medium
In starvation the body saves muscle and slows down; in cachexia inflammation keeps burning muscle, so food alone does not fix it.
Also called: Inanition, Protein-energy wasting, Cancer cachexia
What it is
Inanition is simple lack of food: metabolism slows, fat becomes the main fuel and protein is spared until late. Cachexia is a disease-driven syndrome in which cytokines and tumour or organ signals break down skeletal muscle (with or without fat) and raise energy use, and normal feeding does not fully reverse it. Anorexia, loss of appetite, often comes with it.
Key facts
- In fasting, liver glycogen lasts about a day; then fat supplies most energy, and after some days the brain uses ketones, which cuts gluconeogenesis from muscle protein.
- When fat stores run out, protein breakdown accelerates sharply; loss of muscle and organ protein (including the heart and diaphragm) is what kills in late starvation.
- In cachexia, muscle protein synthesis falls and breakdown rises at the same time; muscle-specific ubiquitin ligases are up-regulated.
- Tumours can release factors such as PTHrP that turn white fat brown or beige (UCP1), raising heat production and energy loss.
- Disease anorexia arises from cytokine effects on hypothalamic appetite circuits (more anorexigenic, less orexigenic signalling), plus taste change, nausea, early satiety and pain.
- Cortisol, catecholamines, glucagon and angiotensin II add to catabolism; low testosterone and IGF-1 remove anabolic drive.
How it works, step by step
- A chronic disease (tumour, failing organ, infection) keeps the immune system active and releases cytokines.
- Cytokines reach the hypothalamus and reduce appetite, so intake falls (anorexia).
- The liver switches to acute-phase protein synthesis, using amino acids taken from muscle.
- Inflammation causes insulin resistance and blunts the anabolic effect of insulin and amino acids on muscle.
- Ubiquitin–proteasome activity and autophagy rise in muscle, while synthesis falls: net loss of muscle protein.
- Fat lipolysis and browning increase; resting energy expenditure stays normal or high instead of falling as in starvation.
- Muscle loss weakens respiratory and cardiac muscle and the immune system, which worsens outcome and treatment tolerance.
Simple starvation compared with cachexia
| Feature | Starvation (inanition) | Cachexia |
|---|---|---|
| Cause | Too little food | Underlying disease and inflammation |
| Appetite | Strong | Low (anorexia) |
| Resting energy use | Falls | Normal or raised |
| Insulin and response | Low insulin, sensitive tissues | Insulin resistance |
| Main tissue lost early | Fat; protein spared | Muscle, and fat |
| CRP / albumin | Normal CRP; albumin often preserved | High CRP; low albumin |
| Response to feeding | Reverses | Only partly reverses |
Clinical notes
- Body weight can hide muscle loss when edema or obesity is present (sarcopenic obesity); muscle mass and strength are better markers.
- Low serum albumin in an inflamed patient reflects the acute-phase response and capillary leak, not only poor intake.
- Appetite stimulants (megestrol, short courses of corticosteroids) can raise intake and weight, but mostly fat and water rather than muscle.
- Cardiac cachexia and kidney protein-energy wasting predict mortality independently of the underlying disease severity.
Test yourself
Think of the answer, then tap the question to see it.
Why does resting energy expenditure fall in starvation but not in cancer cachexia?
In starvation low insulin, low T₃ and less sympathetic drive slow metabolism; in cachexia cytokines, tumour factors and fat browning keep energy use normal or high.
Which adaptation spares muscle protein after several days of fasting?
The brain switches to ketone bodies made from fat, so less glucose (and less gluconeogenesis from muscle amino acids) is needed.
Which cellular system is mainly responsible for muscle protein breakdown in cachexia?
The ubiquitin–proteasome system, driven by muscle-specific ubiquitin ligases, with a contribution from autophagy.
A patient with pancreatic cancer eats more with nutritional support but keeps losing muscle. Why?
Cachexia is driven by inflammation and insulin resistance that keep breakdown high and block anabolism, so extra calories alone cannot restore muscle.
Connections
In Biochemistry1
In Pharmacology2
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: Cancer Cachexia: Its Mechanism and Clinical Significance (International Journal of Molecular Sciences (PMC), 2021); Weight loss - unintentional: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Malnutrition: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.