This chapter has some vague relevance for Section O1(i) from the 2017 CICM Primary Syllabus, which asks the exam candidate to "describe the composition, volumes and regulation of gastrointestinal secretions". Fortunately for the exam candidates, this topic has been largely ignored by the CICM examiners, who have only used it in two SAQs:
So, really, when the syllabus document says "gastrointestinal secretions", what they actually mean is "acid". Which is predictable and totally understandable, as the risk of stress ulceration and the use of PPI in ICU is an important topic, whereas saliva is not. Thus, emphasis here is on the mechanisms of acid secretion, and how it is controlled. Hopefully future exam questions remain faithful to the theme of acid instead of branching out into the other secretions. The full scale of this huge topic could easily overwhelm the emotional and physical reserves of an exam candidate if it appears late in the paper (last couple of questions, just as you're running out of time).
Volumes (ml/day) Composition Regulation Oral secretions 1500 ml
- 99.8% water; low in sodium
- high in calcium and phosphate to help remineralise tooth enamel
- Mucin, IgA, amylase, lipase
- Stimulated by eating; markedly decreased in patients who are fasted, asleep, sedated or intubated
Oesophageal secretions Minimal
- Thick bicarbonate-rich mucus
- Vagal regulation
Gastric acid 2000 ml
- Cl- 170mmol/L, K+ 12-20 mmol/L
- pH ~ 1.5
- Mucus, pepsin, gastric lipase, intrinsic factor
- Stimulated by gastrin, histamine, and vagal activity (M3 receptors)
- Inhibited by somatostatin, VIP, cholecystokinin and secretin
Bile 600 ml
- 95% water; concentrated (~ 600 mOsm/kg), alkaline (pH ~ 7.5-8.0)
- Bile acids, phospholipids, cholesterol and bilirubin
- Secretion is increased by catecholamines, secretin, cholecystokinin, gastrin and glucagon
- Release from the gallbladder is mainly mediated by cholecystokinin
Pancreatic exocrine secretions 2500 ml
- Isotonic with plasma, but markedly alkaline (pH up to 8.3)
- Cl- 30mmol, HCO3- 140 mmol
- Enzymes: lipase, amylase, trypsin, numerous others
- Stimulated by vagus, enteropancreatic reflexes, gastrin, cholecystokinin, and secretin
- Inhibited by sympathetic stimulation and somatostatin
Intestinal secretions 2000 ml
- Bicarbonate-rich mucus
- pH ~ 7.5-8.0
- Mainly originating from the duodenum
- Stimulated by gastrin, histamine, and vagal activity (M3 receptors)
- Inhibited by somatostatin, VIP, cholecystokinin and secretin
Unsurprisingly, this unsexy subject matter receives little attention in the literature. Thomas (2006) is probably the single best overview, even though his paper somehow got published without any references whatsoever. The content of that article is probably what the maximum amount of knowledge of this topic looks like, i.e. this is what the ICU trainees could reasonably be expected to carry into the exam. It represents the outermost edge of a massive and terrifying structure that nobody among the CICM trainees should feel compelled to explore, but if they really want to, Welcome (2018) will be the best-researched and most thorough reference, with over a hundred pages of extremely dense information.
Usually, textbooks that provide any detail about GI secretions produce a table where some kind of "daily fluid flux" through the gastrointestinal tract is presented, in terms of daily fluid flow. It usually looks like this one (from Camilleri, 2004):
|Oral intake of fluid||1500ml|
|Small bowel secretions||3000ml|
The numbers differ by 500ml or so, depending on which textbook you pick, and they are not important. Somebody at some stage must have measured these and published on it, but because the values will vary so widely between individuals, the exact figure is unimportant. All you need to understand is that all of these 7 - 9 litres of fluid end up being reabsorbed, mainly by the ileum and colon. Only about 1200ml per day reaches the colon, in fact. In case you're wondering, the maximum amount of water the colon can absorb is apparently about 5700ml, according to some horrible-sounding experiments by Debongnie & Phillips (1971)
"Saliva is a most valuable oral fluid that often is taken for granted", admonish Humphrey & Williamson (2001) in the opening statements of their comprehensive review. This is the product of minor (10%) and major (90%) salivary glands, which differ slightly in the composition of their secretions. The pedant would have to refer to it as a "mucoserous exocrine secretion".
Composition: This is not an ultrafiltrate of plasma; it is a hypotonic fluid from which the salivary ducts extract most of the sodium (the theory is that this is because it enhances the hydration of protective oral mucin glycoproteins). The tonicity and composition changes with flow rate, which makes it difficult to offer an authoritative list of ingredients (but people have tried); generally even experts charged with the task of reporting on saliva composition tend to limit themselves to a short list of electrolytes. The macromolecular components are multifunctional, redundant and amphifunctional (i.e. they all have multiple similar functions which could be simultaneously protective and detrimental), the complexity of which bedevils the makers of artificial saliva. Despite this appearance of complexity, all these extra protein molecules contribute minimally to its overall volume: saliva is 99.5% water by weight, unlike plasma (which is 7-8% protein).
Function: The functions of saliva are so numerous that to list them all would be a major undertaking. The reader who needs that list is referred to Humphrey & Williamson (2001). In brief:
Volumes: This is obviously going to be highly individual, and most authors give a range (500-1500ml). Of this, 90% is "stimulated" flow, which occurs in response to eating and chewing. At rest, the flow is minimal (around 0.1ml/min, or 6ml/hr, or about 150ml/day), and it slows to essentially zero during sleep. This does have some ICU relevance: our intubated patients are not going to be eating, and therefore will have minimal salivary flow. For example, Dennessen et al (2001) invaded the ICU with dental hygienists and found that they couldn't even measure the composition of the saliva, as there was not enough to sample. The implications for oral mucosal health and the microbiome of the posterior pharynx are considerable, and this is relevant because that's the microbiome that is festering around the top of the endotracheal tube cuff, preparing to invade the lung and cause VAP.
Regulation: The secretion of saliva is regulated by medullary nuclei in response to mechanical, gustatory and olfactory stimuli. The glands are innervated by both sympathetic and parasympathetic nerves, of which the latter seems to be the dominant force. Anticholinergic stimuli have a profound effect of reducing salivary flow, whereas the effects of sympathomimetic stimuli are fairly unimpressive (Ekström, 1989).
Yes, the oesophagus secretes stuff. No, it's not the stuff of legend. No epic sagas have been written to glorify this material. The oesophageal glands mainly secrete a thick bicarbonate-rich mucus which serves as an anti-reflux barrier. It is a reasonable amount of bicarbonate for an organ we often think of as just a gormless food tube. Meyers & Orlando (1992) were able to isolate ten-centimetre lengths of the oesophagi (oesophaguses?) of healthy volunteers by using two balloons, and measured a bicarbonate secretion rate of about 160 mmol/hr.
The stomach wall features glands that form deep tubular pits, lined with secretory cells. These cells all produce something slightly different, and it would probably be worthwhile to discuss them and their specific functions first before moving on to the content of the secretions and specifically the acid.
All this gets mixed up in the tube pits, and comes out of the glands as a combination product. The glands are distributed unevenly along the anatomical areas of the stomach, and the cells are distributed regionally within each gland, such that:
Now, that's just the gloop secreted into the stomach lumen. From the character of the college answer to Question 7(p.2) from the first paper of 2009, it seems like when the college say "describe the functions of the gastric secretions", they meant all the secretions, including the endocrine or paracrine hormones. That's probably not how the candidates would have interpreted it, which is why 60% of them failed that question. Anyway, the specific hormones mentioned by the examiners were:
Of course that's not all of them, as gut hormones are numerous. The only other one perhaps worth mentioning is ghrelin, a peptide hormone produced by epithelial cells of the stomach which influences satiety and appetite. Instead of going into excessive detail here, the reader can be left with links to comprehensive reviews by Gribble et al (2018) or Ahmed & Ahmed (2019) to fill in all the blanks.
You could probably just classify the main functions of exocrine gastric secretions into two main categories: digestive and protective.
For the intensivist, there is probably some hidden relevance here, as we are usually the people who a) disable the gastric acid secretion mechanisms, or b) bypass the stomach altogether by feeding patients nasojejunally. So:
As mentioned above, this is fairly random and feeding-dependent, but at least it varies less than saliva in the critically ill patient. Most textbooks and plain language reviews will confidently state that the stomach secretes a constant 1000-2000ml/day of mucus and acid, though these data appear to be largely derived from horrific pre-War dog studies. The exact volume does not matter overmuch. For the intensivist, the rate of gastric secretion production is important mainly by the way it influences the safety if intubation, and by what it says about gastric emptying:
Schubert (2015) is probably the best reference for this, as his article organises this topic by hormone. The alternative method would be to organise the discussion by effect (eg. "acid secretion" and "mucus secretion", or by phase of digestion (cephalic, gastric, intestinal). Some combination of these systems was attempted here:
Question 16 from the second paper of 2020 specifically wanted to focus on the mechanisms of acid secretion by parietal cells. Mainly to help himself understand what's happening here, the author had succumbed to the urge to illustrate this process using a primitive channel diagram.
Acknowledging that this is not the right way to explain anything to anybody, a wordy version is also offered, as well as the obligatory peer-review reference in the form of Engevik (2020).
Without getting carried away too much with bile, as it is treated with dignity in the liver section, the following brief comments can be made:
Composition, in summary, is an alkaline (pH ~ 7-8) and hyperosmolar (~600 mOsm/kg) soup, containing:
Volume: About 500-600ml of bile is produced per day
Regulation can be separated into secretion and release:
These come from the pancreatic acinar cells and ducts, which together comprise about 90% of the pancreas by volume. The acinar cells are responsible for the secretion of the digestive enzymes, and the ducts manage the electrolyte content. Owyang & Williams (2015) is the best review of this topic, in case anybody needs a level of detail much greater than what is necessary for CICM exams.
Composition is rather interesting. This fluid is essentially iso-osmolar with the body fluid, and contain about the same amount of sodium and potassium as the plasma, but a vastly larger amount of bicarbonate. The chloride is used by duct cells to exchange for bicarbonate, producing a fluid that is highly alkaline, with a minimal chloride content (40 mmol/L) and an absurdly high bicarbonate content (upwards of 90 mmol/L at rest, and up to 140 mmol/L immediately after a meal, with a maximum pH of 8.3).
So alkaline are these secretions, that their loss (eg. by a pancreaticoduodenal fistula) leads to metabolic acidosis. Alternatively, looking at things from a Stewart-like quantitative physicochemical perspective, the acidosis develops because of the loss of a strong cation (sodium) and the reabsorption of a strong anion (chloride), all of which leads to a decreased strong ion difference in the extracellular fluid, and therefore acidosis. This does have some relevance to the ICU trainee, as the uncontrolled leakage of pancreatic juice or duodenal contents is an important differential diagnosis of a normal anion gap metabolic acidosis, a popular topic for exam questions.
Function of pancreatic secretions is predominantly digestive, and all the extra bicarbonate carried by this fluid is necessary to buffer gastric acid. The digestive function is carried out by the enzymes, of which the most important and notable ones are trypsin, lipase, and amylase
Volume of pancreatic secretion is usually said to be about 2500ml.
Regulation is by a number of predictable endocrine and autonomic influences (Chandra & Liddle, 2009):
Those vago-vagal enteropancreatic reflexes are probably the most important here. This is basically a reflex arc that is mediated entirely by the vagus nerve, including all the processing which takes place in the dorsal brainstem (Niebergall-Roth et al, 2006). Of the hormonal influences, the most important is thought to be cholecystokinin. The relevance of these regulatory mechanisms to the intensivist is probably minimal, except where they intersect with our interest in pancreatitis. In severe pancreatitis, one historical approach was to fast the patient for a prolonged period of time, as the concern was that enteric feeding would stimulate more autodigestive secretions. It has been largely debunked by findings that pancreatitis only gets better with early nutrition, and the recommendation to commence early enteral nutrition has been incorporated into all the major guidelines (eg. ESPEN, 2020). The modern understanding seems to be that the necrotic pancreas, stewing in its own digestive juices, is hardly going to listen to normal neurohormonal secretory stimuli.
Most of the secretions in the intestine are the product of Brunner's glands in the duodenum (described beautifully by Krause, 2000) with a minor contribution from the crypts of Lieberkühn in the ileum (remember that the job of the ileum is mainly to absorb things, not secrete them). The crypts secrete various digestive enzymes and they do have mucus-producing goblet cells but the net direction of movement is in, not out. The duodenal Brunner's glands are therefore responsible for most of the secretions in the intestine.
Composition of this fluid is mainly bicarbonate-rich mucus. The bicarbonate content of these secretions is high enough that the overall pH of duodenal content ends up being around 7.4-7.8.
Function is mainly protective and buffering. The job of this mucus is to coat the duodenal epithelium and protect it by buffering the highly acidic chyme coming out of the stomach.
Volume is approximately 1000-2000 ml per day, though it is admittedly difficult to separate this from the secretions coming from the pancreas, as they empty directly into the duodenum.
Regulation is by the same basic mechanisms as gastric acid secretion, which makes logical sense as you would usually want both to be secreted at the same time. Specifically, the secretion of bicarbonate-rich duodenal mucus seems to be regulated by vagal cholinergic output (Odes et al, 1993)