CIPO, Chronic idiopathic intestinal pseudo obstruction entities

Synonyms of CIPO

• CIIP or CIP: Chronic idiopathic intestinal pseudo-obstruction
• Pseudo-obstruction syndrome
• CIPO Sign/ Symptoms are very similar to IBS. Fatalistically its underlying mechanism is also very similar. Now we could say that both are categorized as GI Motility disorder.

Clinic

• CIP is a rare, potentially disabling GI disorder characterized by abnormalities affecting the involuntary peristalsis of GI tract.
• CIP usually results from abnormalities affecting the Muscles or Nerves that are involved in peristalsis. Consequently, peristalsis becomes altered and inefficient.
• Symptoms resemble mechanical obstruction of the small bowel, while there is no physical obstruction in CIP.
• Common symptoms include nausea, vomiting, abdominal pain, Distention and constipation.
• Mal absorption leading to unintended weight loss and malnourishment.
• CIP can potentially cause severe, even life-threatening complications.

• There is no agreed upon classification system for CIP
• Generally, CIP is broken down into two main forms Myopathic and Neuropathic.

Signs & Symptoms

• Wide range of symptoms due to involvement of different area of GI tract
• Chronic in nature with recurrent episodes

Common symptoms

• Nausea and vomiting,
• Abdominal distention or bloating
• Abdominal Cramps / Pain: Sharp or stabbing versus a dull ache or general discomfort.
• Constipation
• Complete lack of bowel movements and have no gas in the GI tract (lack of flatus).
• Early fullness (satiety), an aversion to food and eating, and unintended weight loss or poor weight gain.
• Malnutrition
• Less often diarrhea

Disease progression

• The progression and natural history of CIP is not well studied in adults.
• Most likely, affected individuals have vague, non-specific gastrointestinal complaints for years before a diagnosis of CIP is suspected. Recurrent and severe abdominal pain may be the most common symptom in adults. Adults may also experience nausea and vomiting, constipation, and abnormal swelling or bloating of the abdomen. Unintended weight loss and loss of appetite may also develop.
• Eventually, affected individuals may experience bacterial infections, malabsorption and malnutrition. In severe cases, affected individuals can develop cachexia – a physical wasting syndrome characterized by loss of weigh and muscle mass.

Additional symptoms

• In both children and adults additional symptoms can occur.
• Involvement of the esophagus can result in difficulty swallowing (dysphagia), chest pain and heartburn.
• In some cases, CIP may affect the urinary tract or bladder causing symptoms such as widening of the small tubes that carry urine from the kidneys (ureters) and difficulty urinating (dysuria). This occurs more often in myopathic CIP than in neuropathic CIP.

Causes

CIP has two forms (primary vs secondary). Primary CIP could be:

1. Myopathic CIP
2. Neuropathic CIP

Primary Myopathic CIP

• When the abnormality results in weakened or absent contractions.
• Myopathic CIP is caused by injury to the smooth muscle of the GI tract.
• Smooth muscles react involuntarily to various stimuli. Smooth muscle lines the walls of the GI tract and helps to control the wave-like contractions (peristalsis) that aids in the digestion and transport of food.

Primary Neuropathic CIP

• When the abnormality results in unsynchronized contractions.
• Neuropathic CIP is usually caused by damage to the enteric nervous system, which is sometimes referred to as the brain in the gut.
• The nerves of the enteric nervous system are embedded in the walls of the digestive tract all the way from the esophagus to the anus.
• ENS (Enteric nervous system) is involved in various processes in the GI tract including peristalsis and is vital to overall health and well-being.
• Less often, neuropathic CIP can be caused by abnormalities affecting other nerve cells in the GI tract.In some cases, CIP is caused by damage to the interstitial cells of Cajal (ICC), which are the pacemaker cells of the GI tract. These cells are now known to be critical for proper GI motility. Interstitial cells of Cajal help to generate and maintain electrical rhythmic activity within the GI tract. Interstitial cells of Cajal also play a role in amplifying signals from nerve cells (neurons) to smooth muscle cells. Individuals with CIP due to abnormalities of these cells have signs of both muscle and nerve disease in the GI tract

Also, primary CIP may also be separated by three additional subcategories:

1. Congenital (present at birth)
2. Familial (most likely genetic)
3. Sporadic (seemingly occurring at random)

Secondary CIP

Secondary CIP associated diseases including

1. A group of autoimmune disorders called collagen vascular diseases including scleroderma, SLE, dermatomyositis, mixed connective tissue disorder and RA
2. Endocrine disorders including diabetes mellitus, hypothyroidism or hypoparathyroidism
3. Neurological disorders including Parkinson disease, MSA, and Hirschsprung’s disease
4. Certain cancers causing paraneoplastic syndromes such as small cell carcinoma of the lung
5. Muscle disorders (myopathies), including desmin myopathy, Duchenne muscular dystrophy or myotonic dystrophy
6. Additional disorders such as amyloidosis, Celiac disease, Ehlers-Danlos syndrome or mitochondrial neurogastrointestinal encephalopathy (MNGIE).
7. CIP can also develop before birth (in utero) in select cases due to toxins or insults affecting the developing fetus. One such cause of CIP developing in utero is fetal alcohol syndrome.

Infectious causes

EBV

Two pathogenetic mechanisms have been hypothesized:

1. Viral injury of autonomic ganglia or postganglionic neurons ,
2. Abnormal T-cell- and B-cell-mediated immune response with damage to neuronal tissue cross-reacting with a viral antigen

CMV

Paralytic ileus due to visceral neuropathy and myopathy

JCV

Enteric neuropathy

VZV

• Peripheral somatic and visceral motor neuropathies.