Tanner Marshall, MS, Rishi Desai, MD
Hirschsprung disease is also known as congenital aganglionic megacolon, so Hirschsprung’s is a disease that’s present since birth, in which a ganglion, or cluster of nerves is missing, which ultimately leads to a blocked colon, causing it to enlarge.
Alright, so the intestines move waste through the bowels via peristalsis, which is this series of coordinated wave-like muscle contractions that helps move feces in one direction, and this is essentially automatic, happening without you even having to think about it. The type of muscle that causes these contractions is smooth muscle, as opposed to skeletal muscle or cardiac muscle. In the gut, there’s a layer of smooth muscle just under the submucosa, which sits under the mucosa, which is the innermost layer of the gut nearest to the lumen. On the other side of the smooth muscle layer is the serosa. Now if we look closer at the smooth muscle layer, it’s actually composed of the circular muscle layer, arranged in circular rings which contract and constrict the gut behind the feces, which keeps it from moving backward, while the longitudinal muscle layer, arranged along the length of the gut, relaxes which lengthens and therefore pulls things forward.
Also though, within these layers are two plexuses, or networks of nerves, which are made up of ganglia—which are clusters of individual nerves, which help coordinate muscle contraction and relaxation. First there’s the myenteric plexus, also known as Auerbach’s plexus, which when activated, primarily causes smooth muscle relaxation. The myenteric plexus connects with the second plexus—the submucous plexus, or also known as Meissner’s plexus, which is buried in the submucosa and is responsible for helping to control blood flow and epithelial cell absorption and secretion. These groups of nerves are clearly super important for normal bowel function. For people with Hirschsprung’s disease, both these plexuses are gone—they’re completely absent in some parts of the gut. Why is that? Well during fetal development, there are cells called neural crest cells, which are basically a group of fetal cells that migrate away and differentiate into a variety of different cell types. In this case, some of them become neuroblasts, and eventually the nerve fibers of the plexuses in the gut. Starting from the mouth, the neuroblasts start migrating toward the anus. Around week 8 of development the neuroblasts get to the proximal colon of the gut, and pass through the distal colon, and around week 12 they finally the reach rectum. A disruption of that neuroblast journey in that time window, means that nerve fibers don’t develop in the rectum and parts of the colon. Two specific genes that are thought to be important for migration and development of these nerve fibers are RET and EDNRB, so mutations in either could lead to an absence of the plexuses. Also, mutations in the RET gene have also been linked to Down syndrome, which might help explain why Down’s syndrome is associated with Hirschsprung disease.
Okay, so without these nerves, peristalsis in the gut is seriously impaired, because those muscles tend to lose the ability to relax, and they stay in their default contracted position, which essentially blocks the movement of feces. Babies that are born with Hirschsprung therefore fail to pass the meconium, their first stool, a process that usually happens within the first 2 days after birth. The rectum and the distal sigmoid colon, which are the areas closest to the anus are usually affected, so feces builds up before the obstruction, which causes serious constipation as well as colon dilation, or megacolon, which is a risk for rupture.
For diagnosis, an abdominal X Ray with contrast dye might shows an enormous megacolon full of stool that can’t be easily pushed out, but a definitive diagnosis is by rectal suction biopsy of the narrowed area in the colon, where both the mucosa and submucosa are extracted, as opposed to a normal biopsy where just the mucosa is taken. Remember that those plexuses are in the muscle layer or submucosal layer, so a normal biopsy with just the mucosa wouldn’t cut it, you need a sample of submucosa to see if the submucosal plexus is there or not. Treatment is typically surgical resection of the area that’s lacking the nerve fibers, and then the healthy end is connected to the anus.
Alright, so as a recap, Hirschsprung disease is a congenital condition where the nerve plexuses don’t develop quite right in the colon, which leads to dysfunctional peristalsis and a plugged up colon.
Resources edit
Robbins Basic Pathology (text)
Pathoma (text/video)
First Aid USMLE Step 1 (text)
Costanzo Physiology (text)