The physiology of eating disorders.

University Degree Medicine and Dentistry

The physiology of eating disorders

The erratic eating habits of those with eating disorders, including starvation, vomiting and diuretic or laxative abuse, can start a sequence of events leading to the medical consequences of eating disorders. These consequences reach every system of the body and some are serious enough to cause death. They are also not acute conditions and even after refeeding many conditions will remain.

Reproduction

Part of the diagnosis of anorexia nervosa involves the cessation of menses in women. This could either be primary amenorrhoea if the severe weight loss has occurred before menarche has occurred or secondary amenorrhoea if the patient has previously menstruated. The control of menstruation is very complex involving the hypothalamic-pituatory- gonadal axis. The process is shown on the flow chart below.

The hormones of FSH, LH, oestrogen and progesterone then interact to control the menstrual cycle and ovulation as seen below

Puberty and first menarche is controlled by an increase in pulsatile GnRH secretion. It is not known why this occurs but it is likely to be due to maturation of the central hypothalamic mechanisms. The most important factor for the occurrence of puberty seems to be body weight, with a critical weight for puberty beginning at 30kg and menarche occurring at 47kg. This is signalled by leptins, proteins produced by white fat cells in adipose tissues 2, 368. These are released into the plasma, acting on receptors in the brain to signal quantitative peripheral fat mass 3, 504. When leptins reach the critical level menarche can occur.

If BMI falls below 17-19 in anorexia nervosa then menstruation will cease 4, 23 .This occurs as release of GnRH reverts to pre pubertal levels of just a slow steady secretion. Consequently levels of LH, FSH and oestrogen are also low therefore not allowing the menstrual cycle to occur. Again it is thought that leptins are involved in affecting the hypothalamus and GnRH.

The same process explains the fertility problems experienced by anorexics as without sufficient hormones to cause the LH surge then ovulation won’t occur.

In Bulimia there is a less direct relationship with amenorrhoea and yet amenorrhoea or menstrual irregularities occur in many cases 5, 267. The reasons for this are likely to be psychogenic as a consequence of dieting, purging and stress affecting the hypothalamus by the relationships between the higher emotion centres of the brain and the Papez Circuit 6, 172.

Cardiovascular

In both Anorexia and Bulimia vomiting, diuretics and laxatives are used as methods of weight loss. This causes hypokalaemia. The usual extracellular concentrations of K+ are 3.5-5.5 mmol.l-1 and values below this cause problems with electrical events in the heart.

Concentrations of molecules inside and outside of cardiac cells (mmol.l-1) 3, 186

The action potential produced within the heart is shown below.

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Cardiovascular

Concentrations of molecules inside and outside of cardiac cells (mmol.l-1) 3, 186

The action potential produced within the heart is shown below.

First the sodium channels open by the depolarisation allowing sodium in. When the potential reaches the threshold all the channels open by voltage gated sodium channels causing the sharp depolarisation. They are inactivated and the calcium channels open more slowly allowing the plateau and the maintained contraction. Because the potassium channels are also open, allowing a potassium efflux, it allows the electrical potential to stay constant. As the calcium channels close the potassium channels stay open allowing repolarisation to the resting potential of –90mv. 3, 187-188

In the situation of hypokalaemia the resting potential will be more negative and the cells will be hyperpolarized as more potassium will be able to move out. In the hyperpolarized cell more sodium channels are activated and will be able to open on depolarisation. This increases excitability and leads to ectopic beats and arrhythmias. Ventricular arrhythmias are a common consequence of eating disorders 5, 279.

The ECG of an anorexic will be distinct due to the prolonged QT interval, inverted T wave and lowered ST segment of hypokalemia 3, 455

The reduced volumes consumed in anorexia or lost by vomiting or laxatives means that hypovolemia can occur. This will lead to low blood pressure, often presenting as orthostatic hypotension as this is when transmural pressure causes blood pooling in the legs.

Bradycardia results from hypothyroidism. It is thought this results from reduced peripheral conversion from T4 to T3 and increased conversion of T4 to inactive reverse T3. This process occurs in all starvation states as the body tries to cope with inadequate calorific intake 5, 268

Skeletal

Osteoporosis is a long-term consequence of anorexia nervosa that does not resolve with refeeding. It is defined as ‘a disease characterised by low bone mass density and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and an increase in fracture risk’ 7, 506. The world health organisation defines it as a bone density of more than 2.5 standard deviations below the matched young adult mean value, whilst results of between 1 and 2.5 are known as osteopenia 7, 506

In pre menopausal women oestrogen helps to maintain bone density . In the post menopausal women there is increased reabsorption relative to production. Because in anorexia nervosa there are lower levels of oestrogen there is reduced protective effect on bone and osteopenia or osteoporosis results. It is also thought that elevated cortisol may have an effect 5, 282 since cortisol decreases the synthesis of 1,25 hydroxyvitamin D and blocks its action. This reduces absorption of calcium from the gut and increases calcium excretion through the kidneys. The lower calcium available for bone mineralisation decreases bone formation 3, 566

Acid-base

To allow correct body function acid-base balance must be kept within a small range. The equation of:

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-

shows how bicarbonate and carbon dioxide control acid-base balance.

Bicarbonate should be 22-30mmol/litre and carbon dioxide 6.6KPa in venous blood with a ratio of 20:1 to retain the plasma pH of 7.4. Complex interactions between respiration and the kidneys allow the bicarbonate and carbon dioxide to compensate any changes between these.

With weight loss behaviours such as vomiting or laxative abuse then these levels can be seriously disturbed.

Vomiting

In the stomach the gastric parietal cells take Cl-, CO2 and H2O from the blood and with carbonic anhydrase form H2CO3. This dissociates into H+ and HCO3- so allowing HCl to be secreted into the stomach. This allows the stomach to be acidic which aids the process of digestion by denaturing proteins and destroying bacteria. The HCO3- returns to be blood to replace the Cl-. If vomiting occurs from the stomach then large amounts of acid are lost and a metabolic alkalosis is caused by the relative increase in HCO3-. The symptoms of metabolic alkalosis are tetany caused by a consequential reduction in blood calcium replacing the H+ and confusion and drowsiness caused by effect of alkalosis on the brain.

In the proximal tubules there are K+ secretory channels that are controlled by protons. If H+ in cells is high then these channels are blocked and less K+ will leave cells. With the low H+ in alkalosis then moiré K+ will be able to escape from these cells into the distal tubules leading to hypokalemia. This can cause cardiac disturbances.

Diarrhoea

Food in the gut has large amounts of NaHCO3 in it from the gut secretions. In diarrhoea, as could be caused by laxatives then this is lost. This leads to a metabolic acidosis that stimulates potassium loss from cells in normal renal function and therefore causes hypokalemia.

Since in diarrhoea the fluid content of the intestinal contents is increased the K+ in this is proportionally diluted. This increases the transmembrane concentration gradient and more K+ is lost from the intestinally lining cells. Hypokalemia results.

Gastrointestinal

Oral

Continuous vomiting causes changes within the oral cavity. The parotid gland undergoes hypertrophy due the increased saliva production, ptyalism, which occurs prior to vomiting 5, 280. The effect of stomach acid on the tooth enamel leads to perimylosis or erosion of the tooth surface. This can lead to increased cavities as the acid dissolves the calcium hydroxyapatite of the enamel, eventually penetrating the full thickness of the enamel. If this occurs the dentine is effected and eventually the pulp leading to acute pulpitus 8, 230

Oesophageal

Continuos vomiting allows stomach acid to come into regular contact with the oesophagus as would occur in gastro oesophageal acid reflux disease. First this causes oesophagitis, inflammation, as the acid causes irritation. Eventually oesophageal strictures can occur which will cause dysphagia.

At the lower oesophageal sphincter the mucosa changes from the oesophageal non keratinised stratified squamous epithelium to the gastric tall columnar epithelium. A condition known as Barrett’s oesophagus occurs as a result of acid reflux and causes metaplasia of oesophageal epithelium to gastric. This is pre malignant for adeno carcinoma 7, 229

Laxative abuse

Chronic laxative abuse causes loss of peristaltic function and causes cramping and bouts of diarrhoea and constipation 5, 280. It is possible for gastro-intestinal bleeding to occur and this can lead to anaemia.

Urinary

The hypovolaemic state that results from reduced fluid intake, diuretic and laxative abuse reduces the perfusion pressure to the kidneys. This is detected by the afferent arterioles and stimulates renin release. Renin forms angiotensin I from renin substate and this goes on to form angiotensin II with angiotensin converting enzyme. Angiotensin II acts to conserve fluid by stimulating thirst, stimulating aldosterone secretion and vasoconstricting smooth muscle. This hyperaldosterone will remain even after fluid levels are returned to normal and therefore a reflux oedema will occur for several weeks after substance abuse has ceased.

It is also thought that long term hypokalemia can cause interstitial renal disease eventually leading to chronic renal failure and dialysis. The pathogenesis of this is not known 7, 612.

Pregnancy

Infertility is a common complication of eating disorders but if pregnancy occurs it can cause a number of additional problems for foetus and mother.

The changing body shape that occurs with pregnancy can exacerbate body image problems and make eating disorders worse.

Reduced maternal nutrition can cause intrauterine growth retardation and low birth weights. It is also reported low APGAR scores in babies of anorexic and bulimic parents 5, 283 . The APGAR score is a way of assessing well being based on colour, tone, pulse, respiration and response.

Dermatology

Dry skin will result if hypothyroidism occurs.

In severe weight loss a fine, downy facial hair will develop called lanugo

In patients that self induce vomiting then Russel’s sign can be found. This is calluses, abrasions or bruising on the dorsum of the hand and the thumb from where the teeth injure the areas during manual stimulation of the gag reflex 5, 283.