Toxins and changes in their absorption, modification and excretion by the body

 

Introduction

The body is continuing absorbing and producing compounds that it does not want to remain within the blood.  The liver and lungs are the major enzyme producing site through which this is commonly done.   Common mechanisms are by the modification of the toxic compound into a highly soluble one that can be excreted in the urine, or by the breakdown of the compound such that it either no longer is toxic or again can be easily excreted.

 

Quite a large proportion of autistic children show symptoms of gut problems: diarrhoea and constipation when compared to control children  and the reason for this is unclear currently.

In autism there appears to be an odd inability for certain compounds to be excreted in the same way as in a control.

To a large degree the reason for this is unknown and currently what we have is few suggestions:

 

 

 

 

Paracetamol (top left) alteration with sulphate or glucuronide for excretion. If the dose of paracetamol is too large the pathway to toxicity is seen

 

 

Poor digestion of food

This is not clear currently as no adequate research has been done despite the methods having been set up and understood. Because of this the evidence can only take fragments of data put forward by individual researchers.  The major research is that biopsies taken from the duodenum and ileum by Horvath et al, showed that there was a shortage of the enzymes that were required for the breakdown of specific foods e.g. dipeptides.

 

85% of autistics meet criteria for malabsorption (B.Walsh, 500 pts)

 

Goodwin MS, Cowen MA, Goodwin TC. Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children.J Autism Child Schizophr. 1971 Jan-Mar;1(1):48-62.  freq. reports acholic stools, undigested fibers, positive Sudans.

 

Maldigestion--elevated urinary peptides and lack of gut enzymes:  see opioids: P Shattock (Brain Dysfunct 1990; 3: 338-45 and 1991; 4: 323-4),  KL Reicheldt (Develop Brain Dys 1994; 7: 71-85, and others,  Z Sun and R Cade (Autism 1999; 3: 85-96 and 1999; 3: 67-83

 

Kushak R and Buie T “Disaccharidase deficiencies in patients with autistic spectrum disorders,” presented at DAN! New Orleans Jan 2004.  They  found that children with autism may have low levels and/or underactive digestive enzymes for complex sugars, which reduces the ability to fully digest starches and sugars.

 

Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr. 1999 Nov;135(5):559-63 

 

Horvath K, Perman JA. Autistic disorder and gastrointestinal disease. Curr Opin Pediatr. 2002 Oct;14(5):583-7. Review

 

Horvath K, Perman JA. Autism and gastrointestinal symptoms. Curr Gastroenterol Rep. 2002 Jun;4(3):251-8. Review. (discusses the chronic gut symptoms and the histopathology, particularly of the small bowel).

 

Abnormal Intestinal Permeability

 

P D'Eufemia.  Lactulose, mannitol ratios showing higher intestinal permeability and hence uptake of a large molecule that was normally not absorbed. Acta Pediatr 1995; 85; 1076-9.  This is a major finding as it does to some degree explain why so many other compounds in the body are either inadequate or working too hard. 

 

Liu Z, Li N, Neu J. Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr. 2005 Apr;94(4):386-93.  Tight junctions (TJs) represent the major barrier within the paracellular pathway between intestinal epithelial cells. Disruption of TJs leads to intestinal hyperpermeability (the so-called "leaky gut") and is implicated in the pathogenesis of several acute and chronic pediatric disease entities that are likely to have their origin during infancy. AIM: This review provides an overview of evidence for the role of TJ breakdown in diseases such as systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes, allergies, asthma, and autism.

 

 

 

Modification of paracetamol

 

This is an important finding in that there is no good reason for this to be a reliable finding in autism.  It is as if there is either a shortage of sulphate, or there is an overload of other compounds being absorbed and being supplied to the poorly specific sulphation enzymes as substrates.   The findings here with paracetamol will almost certainly represent changes in the metabolism of other compounds.

 

Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in "low-functioning" autistic children: a pilot study.

Biol Psychiatry. 1999 Aug 1;46(3):420-4. (this shows that the normal sulphation of paracetamol that takes place did not happen in autism, but rather a much lower proportion was sulphated and other forms of the paracetamol were ecreted.

 

Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ming Ji. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: The results of a parent survey. Autism. 2008 May;12(3):293-307. (they found that the use of paracetamol following the MMR vaccine was associated with autism!  It was not clear about the clinical condition of the children before the MMR but this was an important finding)  The reason behind it was not clear currently.

 

 

Hepatic encephalopathy

 

This is a well known phenomenon that has been shown for many years in people that are in chronic hepatic failure.  It can be treated to some degree using antibacterials given orally, which will decrease the bacterial flora dramatically.   It is considered to take place due to a lack of the liver to adequately metabolise the bacterial products that are absorbed from the gut.   The consideration is that the liver simply cannot cope with the flood of bacterial toxins that arrive and they are allowed into the systemic blood circulation and cause changes in brain activity.  Notably, to some degree, if the bacteria are removed the psychiatric effects seen.  The finding of inadequacy and modification of hepatic action in autism may be of significance.

 

Wakefield AJ, Puleston JM, Montgomery SM, Anthony A, O'Leary JJ, Murch SH. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Aliment Pharmacol Ther. 2002 Apr;16(4):663-74. Review

 

Williams R. Review article: bacterial flora and pathogenesis in hepatic encephalopathy. Aliment Pharmacol Ther. 2007 Feb;25 Suppl 1:17-22. Review  (they discuss the effect of ammonia that cannot  be dealt with by the liver, and a new set of compounds much like diazepine that are not dealt with either.  A major subject)

 

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