Why microdosing GLP1a/GIP agonist (Tirzepatide) helps POTS/MCAS/Long COVID/Functional GI symptoms.

#POTS #MCAS #LC #DGBI #microdosing

I had an epiphany a few months ago. One of those “why didn’t I realize this sooner” moments. Why do microdosing GLP1a/GIP agonists help this cohort?

Before we delve further let’s look at how these drugs work. Whilst they are best known for their weight loss effects, they have lots of other beneficial actions

All things Gastric
Part 3 how to use GLP1a agonists.

GLP1a agonists work to reduce weight by the following mechanisms
1- they tell your brain you are not hungry
2- they slow down gastric emptying so you feel fuller for longer after eating, and therefore eat less 3- reduce inflammatory markers in particular IL-6, and TNF alpha
4- in some patients with MCAS they act like mast cell stabilizers

(Like all MCAS drugs they only work in some patients not all)

In normal patients (in whom calories in exceed calories out is driving weight)

All things Gastric
Part 2 Gastric Symptoms

The following symptoms can arise due to dysfunction in gastric function

Loss of appetite
Feeling full quickly when eating or for a long time after eating
Bloating
Belching
Pain
Nausea
Vomiting
Reflux acid or liquid I find it easier to break symptoms down into
1/ those occurring with or after eating due to abnormal Digestive phase
2/ those occurring in the inter digestive phase

Let’s start with the second one as it is easier

All things Gastric
I thought I would do a series of posts on the stomach
1/ Normal Gastric Function
2/ Gastric symptoms including Gastroparesis
3/ How to use GLP1a in patients with Gastroc symptoms INCLUDING Gastroparesis.

#POTS #MCAS #hEDS
#Gastroparesis 1/ Normal Gastric Function
The stomach has 3 anatomical regions (fundus, body, antrum (and pylorus)
But from a functional point of view the stomach has 2 regions.
Upper stomach
Lower stomach

The Upper Stomach includes the Fundus and part of the Gastric Body

@GI_Pearls Once you truly understand the gut brain axis and DGBI u realise the DGBI are the gut manifestations of POTS and MCAS. I treat all my DGBI with antihistamines and mast cell stabilizers. Mast cells release mediators that cause visceral hypersensitivity. @GI_Pearls The reason for the triad is that the ANS and mast cells are abundant in and control the integrity of the connective tissue. When dysfunctional they will cause an asymptomatic hEDS to become symptomatic.
And abnormal connective tissue will place abnormal shear stress

Abdominal pain in patients with FGID/DGBI/IBS
I see a lot of post where people complain of agonizing pain.
As well as lots of other symptoms.

So how do I approach abdominal pain?

Location and association with bowel motions.
Most cases of severe abdominal pain Associated with the urge to defecate, or feel better or slightly better after using your bowels (or passing wind) is a colonic symptom. And it is due to faecal loading. But when I say this people say, “but I have diarrhoea” or “I go regularly “

Why do my bowels not work?
For those that suffer constipation or painful diarrhoea due to faecal loading treatment needs to focus on three key elements.
Unless you address them all you will not have success
1/ a rectum that senses the faeces and provides The urge to defecate, teemed with a correct defecatory technique and adequate pelvic floor function.

Most of my pts have dyssynergia defecation. When the patient tries to push the faeces out, instead of relaxing the EAS

MALS and SMAS part 2

SMAS
Superior mesenteric artery compression of the third part of the duodenum.

This usually cooccurs with Left renal vein compression by the SMA, because they both “sit” under and between the SMA and the aorta. If MALS is thought to be then SMAS is thought to be a unicorn.
The irony is it is more common than MALS but…
Whilst the compression alone (ie not causing symptoms so can’t be called a VCS) is more common,
Symptomatic SMAS is less common than symptomatic MALS.

MALS and SMAS
I have previously posted on vascular compression syndromes in trifecta pts.
I left the best to last.
Going thru medicine and gastro training we were never taught about these two syndromes.
Occasionally in a radiology meeting someone would Through out MALS or SMAS as a cause of chronic unexplained pain and all the registrars and residents would quickly google it.
So what are these conditions?
In my previous post on VCS (vascular compression syndromes) I spoke about how they are almost universal

Diagnostic criteria for MCAS

I had an interesting letter back the other day from an immunologist looking after my pt. I had started her on Famotidine (H2 blocker) for her gut symptoms and as an antihistamine and Prucalopride (stimulates gut motility) I view IBS as the gut manifestation of POTS and MCAS and treat all pts as having both diseases

Whilst it is always ideal to stagger introducing new meds in MCAS pts as inc risk of drug reactions and want to know which drug it is, the pt started both together.

What a load of fucking bullshit.
1/100 cardiac arrhythmias. Bullshit
1/2000 bleeds requiring i patient admission. Bullshit
1/2000 req emergency surgery. Bullshit.
1/6000 splenic injury. Bullshit
1/1000 infections leading to sepsis. Bullshit

https://twitter.com/valerieanne1970/status/1901871907315560950

I have performed over 30,000 colonoscopies

1 perforation
1 splenic rupture req splenectomy
Since cold snare polypectomy for large polyps and the use of clips my post polypectomy admission rate dropped from 1 every three years to 0 in last 3 years.
0 sepsis

Vascular Compression Syndromes (VCS) in POTS patients
In my experience, VCS are present in ALL patients with POTS, and are usually multiple. For the purposes of this thread this also applies to hEDS and trifecta patients as well.
So what is a VCS? A 🧵 A VCS is when a vascular structure (artery or vein) is either
1/ Being compressed by an adjacent structure or
2/ Is compressing an adj structure leading to the generation of symptoms
If the compression is asymptomatic we call it Vascular Compression Anatomy

Another commone medication mistake in POTS
If I am using Ivabradine (or if on beta blockers, - I never use beta blockers) these drugs are usu given twice a day.
But what does twice a day mean to you and the pt, and why is twice a day diff for POTS pt? HR control is a symptomatic treatment, if you standing and walking around the house HR is under 100 you may not need the second dose,
Particularly as POTS is worse in the morning. SO by the afternoon, your HR may be better and you may not need the second dose.

DIVERTICULAR DISEASE
I think Diverticular disease, whilst very common, is very poorly understood.
Some definitions
Diverticulum - single
Diverticula - plural
Diverticular disease (DD) - presence of diverticula in the bowel

DD usually involves the sigmoid colon It can occur in any part of the gut however.
It arises when a section of the bowel lining forms a little outpouching of the bowel wall.
It is thought to arise at sites of weakness in the bowel wall.
They are more likely to occur in the sigmoid colon

MEDICATIONS TO AVOID IN POTS PATIENTS
There are many classes of drugs that I prefer to avoid in my POTS pts.
I believe that all POTS pts have all 3 mechanisms at play, it just depends on which mechanism is the predominant one.
Ie hypovolaemic, hyperadrenergic or neuropathic.
So I don’t like the treatment algorithms that say for hypovolaemic POTS use these drugs.
All mechanisms are at play, so address all mechanisms.
POTS and its comorbid MCAS are both disorders of the gut brain axis. So you have to also keep in mind

POTS treatments
In order to treat POTS you need to understand what is causing the symptoms.
There are 3 underlying pathophysiological contributors to POTS, I believe all are active in all POTS pts, it’s just which is the predominant one 1/ Hypovolaemic POTS
Despite low blood volume pts with POTS have been found to have inappropriately low activation of the renin angiotensin aldosterone system
Hence the use of compression stockings, inc water to 2-3L a day and salt to 10g a day

Low FODMAPS diet
Prior to the widespread adoption of a low FODMAPs diet we didn’t really have any effective diets for IBS
I used to be a big fan of a low FODMAPs diet in SOME circumstances.
However I now no longer recommend this approach.
Why? Firstly what is a low FODMAPs diet
F - Fermentable
O- oligosaccharides
D-disaccharides
M- monosaccharides
A- and
P- polyols
This doesn’t really clarify much though.
The premise of this diet is to remove fermentable substances from the diet.

Histamine intolerance
Histamine is a trigger for some patients with MCAS but not all. Histamine intolerance is just that an intolerance as opposed to an allergy.
What is the difference?
An intolerance causes symptoms vs an allergy which causes tissue damage and systemic effects.
I commonly see pts with dairy allergy. It is a non IgE allergy, meaning it can’t be detected on skin prick tests (rely on IgE).
These pts find when they eat Dairy they get worsened hayfever, mood changes, joint pain.

Treating POTS/MCAS - Getting off the Merry Go Round
General rules applicable to everyone
Danger can come from the external or internal world.
Most dangers come from the external world.
The gut has the largest surface area in contact with the ext world ?Huh I hear u thinking.
Think of a donut, the hole of the donut is not part of the donut, it is outside the donut, it just happens to be inside the donut ring. Now stack donuts on top of each other .U have a tunnel in the middle of the donut aka the gut, which is outside

Treating POTS/MCAS by addressing the DGBA
I like to think of the Disordered or chronically active GBA as a merry go round. Once it gets triggered, it tends to continue to go around and around.
Every time a pt develops a disorder of the GBA, I look back to their last 6-12m There will always be a danger or danger(s) that triggered the dysfunction and then the disease presentation. You just have to take a detailed enough history.
Take typical IBS for eg., the majority of pts (usu F)'s symptoms of IBS start within 1 year of menarche

The GUT BRAIN AXIS (GBA)
In order to effectively treat POTS, MCAS, u need an understanding of the GBA and how it becomes dysfunctional (DGBA).
So here is a brief intro to the GBA (I did a 1 hr webinar on this for Remission Biome which goes into more detail) The GBA refers to the way in which the Gut & Brain influence/control the functions of each other.
They do this thru the
1/ HPA axis (Hypothalamic - Pituitary - Adrenal)
2/ ANS (Autonomic Nervous System)
3/ Immune System