Anorexia

Food intake is regulated by complex central and peripheral mechanisms. The central mechanisms act via the hypothalamus. There are two hypothalamic centres:

Destruction of the brain’s feeding centre can result in failure of the person to eat, leading to starvation and death. Conversely, injury to the satiety centre can lead to hyperphagia (exaggerated appetite) and obesity.

Satiation signals that are multiple (and redundant) help lead to the cessation of food intake. During meals, signals arising from the gastrointestinal tract (from gastric distension and intestinal hormone release including cholecystokinin [CCK], glucagon-like peptide [GLP-1] and peptide YY) help lead to meal cessation by inducing satiation, probably acting via sensory nerves travelling to the hindbrain. Additional adiposity signals (from body fat itself such as leptin, and hormones released in response to a meal such as insulin) circulate to the brain and interact with these other signals to regulate meal size. On the other hand, there are few known signals that control the initiation of meals (orexigenic signals) although increased ghrelin (from the stomach and duodenum) precedes increased food intake, and probably acts via the vagus nerve and directly on the brain.

Anorexia alone is not a symptom of diagnostic value and can occur in many gut and systemic diseases (Box 17.1). Anorexia should be differentiated from ‘sitophobia’, which is a term used to describe a fear of food because of subsequent abdominal pain. Sitophobia can occur with chronic mesenteric vascular insufficiency (abdominal angina) or small intestinal Crohn’s disease with partial obstruction. Anorexia should also be distinguished from early satiation (a feeling of fullness after eating a small amount such that a normal meal cannot be finished), such as occurs after a partial gastrectomy and in patients whose gastric fundus fails to relax (e.g. after a vagotomy, and in some patients with functional dyspepsia).

Weight loss

Involuntary weight loss is a common manifestation of a variety of disease processes (Table 17.1). Although the precise pathophysiological mechanisms inducing weight loss are unclear, multiple factors have been implicated.

Table 17.1 Selected causes of weight loss

Cancer patients may be unable to eat or may not feel like eating (secondary to treatment or depression). Failure to down-regulate energy expenditure in the face of decreased caloric intake can lead to energy imbalance, which may be one of the main mechanisms of weight loss in some cancers. Increased caloric utilisation by tumour tissue may also be a factor, although increases in resting energy expenditure have not been shown to occur in all patients with tumours. In the acquired immune deficiency syndrome (AIDS), poor oral intake, malabsorption, tumour development and repeated infections coupled with a relatively high resting energy expenditure may all have a role. In elderly people, preferential oxidation of fatty acids and an increase in anaerobic glucose metabolism result in inefficient expenditure or wastage of adenosine triphosphate.

At a molecular level, various mediators may be important in promoting loss of weight. Tumour necrosis factor (TNF) is a cytokine produced from activated lymphocytes and macrophages in cancer patients or in patients with emphysema or severe heart failure; in animal studies it gives rise to anorexia and weight loss. Pentoxifylline, an inhibitor of TNF, can reverse the above effects in animal studies. Interleukin-1, IL-1-beta and IL-6 are potent anorexic cytokines, increasing resting energy expenditure and promoting skeletal wasting.

Although reductions occur from both adipose tissue and muscle (lean mass) in weight loss, the extent from each source can differ. Obese people lose less lean mass than those who are not obese. In uncomplicated starvation, fat tissue is selectively depleted to spare muscle proteins. However in patients with AIDS or cancer, weight loss occurs predominantly from the muscle compartment.

History

Determine whether the problem is acute or chronic and when it began. Enquire about any loosening of the patient’s clothes or changes in belt size. Also ask whether weight loss is ongoing. Previous records or photographs may be helpful for comparison. There are rare situations in which patients claim to have lost weight without having done so.

Next, determine the patient’s appetite and eating habits. Ask about the number of meals per day and their composition, and usual daily physical activity.

About one-third of patients with involuntary weight loss plus anorexia have a cancer; up to a quarter have no cause uncovered by tests. Depression is a common cause of weight loss.

Weight loss does not always accompany anorexia. Patients may actually have weight loss with an increase in appetite in malabsorption, hyperthyroidism, uncontrolled diabetes mellitus, phaeochromocytoma or occasionally with lymphoma or leukaemia.

Ask about other gastrointestinal symptoms. For example, recurrent vomiting may indicate bowel obstruction, while dysphagia may suggest oesophageal cancer. The occurrence of diarrhoea immediately after eating can occur in patients with a high intestinal fistula or malabsorption.

Ask whether the patient is afraid to eat because eating precipitates pain or other gastrointestinal symptoms. Abdominal pain that usually occurs after eating suggests peptic ulcer disease, chronic pancreatitis or chronic mesenteric ischaemia (abdominal angina). Pain after eating may also occur in patients with the irritable bowel syndrome or functional dyspepsia (Chs 6 and 7).

In elderly patients, poor dentition is a common but often overlooked problem. Oral disease resulting from conditions such as vitamin deficiencies, candidiasis or gingivitis can affect mastication. Ask about alterations in taste (dysgeusia), which may make food seem unpalatable. Zinc deficiency may sometimes be responsible for dysgeusia (Ch 3).

A detailed current drug history is important. Various medications, including digoxin (especially in toxic doses), amphetamines, chemotherapeutic agents and narcotic analgesics, can cause anorexia and associated nausea and vomiting, which may lead to subsequent weight loss. It is important to look up the side effects of drugs being taken if you are unsure.

Ask about previous medical conditions (e.g. pulmonary tuberculosis, renal disease, previous cancer, cardiac disease) and past surgery. Postgastrectomy syndromes can cause malabsorption (Ch 6). Prior abdominal surgery causes adhesions that can lead to chronic incomplete intestinal obstruction.

Cigarette smoking and alcohol use may be important (e.g. due to the associations with lung and other cancers and cirrhosis, respectively). The patient’s involvement in high-risk behaviour may be relevant (e.g. acquisition of HIV infection).

Ask about social isolation and symptoms of depression (including depressed mood, apathy, insomnia, fatigue, feelings of worthlessness, diminished ability to think and suicidal ideation). Depression, not malignancy, is the most common cause of weight loss in elderly patients and institutionalised patients, and is often missed. It may not always present in its ‘typical’ form. Ask about body image and self-induced vomiting; anorexia nervosa and bulimia nervosa are important causes of weight loss in young people.

Physical examination

Weigh the patient and measure the patient’s height, then calculate the BMI. Milder degrees of weight loss can exist with little or no wasting. In severe weight loss, muscle wasting will usually be obvious—look particularly at the temporalis, deltoid and quadriceps muscles. Body fat loss is suggested by hollowness of the cheeks and buttocks, and by subcutaneous fat content on pinching a fold of skin.

Measure the waist circumference—locate the upper hip bone and the top of the right iliac crest. Place the tape in a horizontal plane around the abdomen at the level of the iliac crest; make sure it is snug (but not too tight), is parallel to the floor and the patient has expired normally before taking the reading. In overweight adults (BMI 25 to 34.9 kg/m²), a waist circumference greater than 102 cm for men (or 88 cm for women) is associated with a greater risk of heart disease and metabolic syndrome. Assess hydration status and look for fluid overload (oedema).

Examine for specific features of vitamin and mineral deficiencies (Table 17.2). Glossitis, cheilosis or perioral dermatitis can result from deficiency of vitamins such as riboflavin, pyridoxine or niacin, whereas peripheral neuropathy or ataxia can occur due to lack of thiamine or vitamin B₁₂.

Figure 17.1 Mini nutritional assessment

Reproduced with permission from Guigoz, Y, Vellas, B, Garry, PJ. Assessing the nutritional status of the elderly: The Mini Nutritional Assessment as part of the geriatric evaluation. Nutr Rev 1996; 54(1 Pt 2):S59. Copyright © 1996 International Life Sciences Institute.

Next, conduct a careful gastrointestinal examination. For instance, in a patient with weight loss and jaundice (Ch 23), a pancreatic cancer with biliary obstruction may be the explanation. If stigmata of chronic liver disease are present and abdominal examination reveals a liver mass with or without a bruit, cirrhosis with development of a hepatoma should be considered. Large abdominal masses can occasionally compress the stomach or small bowel, inducing anorexia (Ch 19).

Look for other clues on the general examination. Although usually not pathognomonic, they can help direct investigations of a particular organ system. For instance, clubbing may suggest the presence of co-existing chronic lung infection or cancer, whereas lymphadenopathy could point towards a possible lymphoma, metastatic cancer or chronic infection. In a febrile patient, the presence of a newly detected murmur may suggest a diagnosis of infective endocarditis, whereas localised bony tenderness could occur in osteomyelitis or with bone metastases.

Investigations

The diagnostic work-up needs to be directed towards defining the extent of malnutrition and detecting the underlying cause of weight loss.