Friday 23 August 2013

Gastroparesis (part 1)

Brandenburg gate with two people dressed as Star Wars characters in the foreground
Berlin, March 2013 - no idea about the Star Wars characters...
I saw a patient recently who is suffering with gastroparesis, and I say 'suffering' for a good reason. Gastroparesis is 'a chronic disorder of gastric motility that is characterized by delayed emptying of either solids or liquids from the stomach in the absence of any mechanical obstruction.'

Food is normally chewed and mixed with saliva to form the bolus that you swallow. The bolus passes down the oesophagus into the stomach, where it is mechanically, chemically and enzymatically digested to form chyme: an acidic slurry of food, fluid and enzymes. The pyloric sphincter at the bottom of the stomach is prompted to release chyme from the stomach into the small intestine in small bursts, where the acid is neutralized and further digestion takes place by enzymes released from the intestinal wall and the pancreas. [The release of digestive enzymes into the intestine is the exocrine function of the pancreas, and is usually unaffected by diabetes, which is a disorder of the endocrine system.]

Food normally starts to leave the stomach within minutes of ingestion. After one hour 10% or more will have passed through to the small bowel, after two hours at least 40% should have gone, and four hours post-meal more than 90% of the meal should have left the stomach heading for the intestines. The final products of digestion are nutrients - fatty acids, amino acids, sugars, vitamins and minerals - that are absorbed through the wall of the gut into the body, and the indigestible fraction passes on through to be excreted as faeces.

The symptoms of gastroparesis include nausea, reflux, bloating, early satiety and post-prandial fullness, abdominal discomfort and pain. Putting a camera down into and beyond the stomach, which is usually the first line of investigation in most disorders of the gastrointestinal tract, is done to see if there's mechanical obstruction (from a tumour, for example), and in the patient that I saw, showed the remains of a meal that had been eaten the day before.

So the symptoms of gastroparesis simply arise because the stomach is not emptying - the pyloric sphincter is not being prompted appropriately to allow the chyme through to the small bowel. The next diagnostic test might be to follow a radioactive meal through the GI tract. Using this technique, delayed gastric emptying has been found in 25-55% of people with Type 1 diabetes, and in 30% of people with Type 2 diabetes.

Hyperglycaemia, or high blood glucose, is pretty toxic to the smallest blood vessels in the body, found in the retina and the kidneys, and also damages nerves. Often the nerves that are damaged are the smallest ones furthest from the brain, which is why foot care is so important. For some very unlucky people, the nerve that is affected is the vagus nerve, which transmits the signals that manage the extremely complex processes going on in the intestinal tract. But it turns out that hyperglycaemia affecting the vagus nerve is not usually the culprit in diabetes, but more often it is due to destruction of the pacemaker cells ('cells of Cajal') that link the vagus nerve with the smooth muscle of the stomach, and the result is the absence of peristalsis and atrophy of gastric smooth muscle.

Let's look next at what happens to the food once it has been digested, and glucose from carbohydrate in food has been transferred from the gut to the bloodstream. Insulin is secreted from the pancreas in order to allow the glucose to enter cells of the body where it is used for energy. In someone without diabetes, the pancreas simply responds to the level of glucose in the blood: lots of glucose leads to lots of insulin, little glucose means little insulin. It's automatic, and maintains tight control of blood glucose levels very effectively, to prevent those toxic effects of hyperglycaemia (or the unpleasant and potentially dangerous effects of hypoglycaemia, low blood sugar).

Now, we'll throw Type 1 Diabetes into the mix. Insulin secretion by the pancreas is non-existent, so the diabetic patient has to supply the insulin by injection. Usually it takes about the same time for glucose to reach the bloodstream from digested food as it takes for rapid-acting insulin to reach the bloodstream from the injection site. This type of insulin is effective over about 4 to 6 hours, which is about the time it usually takes for the whole meal to leave the stomach, be digested, and all the glucose to be delivered to the bloodstream.

With gastroparesis, there is a delay. Some glucose may turn up in the bloodstream straight away, but there is no way of knowing how much, or how long it will take for the whole lot to come through, and at what rate. So you can calculate the insulin that is needed to match the carbohydrate in the meal, but if you inject it all at once, it will arrive in the bloodstream before the glucose, and your blood glucose level will drop. The way to deal with low blood glucose from too much insulin is to consume some sugary carbohydrate that should be quickly digested, but - will it reach the bloodstream in time, given that the pyloric sphincter is mostly stuck shut? Later, when the rest of the carbohydrate from the meal finally gets through to the bloodstream, the insulin will no longer be there to deal with it, and your blood glucose level will rise. And there is no reliable way to predict how long this will take. The insulin and blood glucose graphs look like roller coasters.

Meanwhile, you feel uncomfortably full all the time and find it difficult to eat even a small amount of food. Eating is no longer pleasurable, you're losing weight, your family are initially sympathetic but you keep vomiting after a trivial amount of food, your breath smells terrible and with the constipation alternating with diarrhoea, the bathroom is never free. The diabetes team give the impression that your terrible glycaemic control is because of something you're doing wrong with the carb counting or insulin dosage, but you're doing everything you can think of to try and avoid high or low blood sugar, it's just that nothing's working. The high and low blood sugars make you feel awful too. Depression is a well-documented side effect of diabetes, and if you have gastroparesis too, well, there aren't many happy days.

Although part 1 ends on a low note, part 2 should provide some reassurance that treatments are available and can help.

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