What is the primary purpose of the secretory glands in the GI tract?

- secretion of digestive enzymes

- provide mucus for lubrication

What are the 4 different types of glands in the GI tract? What type of glands are salivary glands?

Goblet cells (which secrete mucous), pits, tubular and complex (or compound) glands.

Salivary glands are complex glands.

What is mucous and what are the important characteristics that make it a lubricant and protectant?

Mucous is made up of water, electrolytes and glycoroteins.

Properies of mucous:

- adherant to surfaces

- coats the wall of the gut to prevent contact of food particles with the gut wall

- low resisance allows particles to slide on the surface

- causes fecal particles to adhere together so that fecal mass can be expelled during a BM

- can buffer small amounts of acid or alkali

What is the structural unit of the salivary gland? What is the funciton of each unit? Which other gland has a simular structural unit?

- the structural unit is the acini and salivary ducts

Acini: produce ptyalin (salivary amylase), mucin and extracellular fluid.

Ductules: secrete K and HCO3 and absorb Na and Cl.

- the pancreal is also complex with a similar structure.

How much saliva do we make a day? How does the Na, K, and HCO3 content compare with serum?

- we make about 1L a day

- Na: 15 mEq (hypotonic compared with serum, so less)

- K: 30 mEq (hypertonic compared with serum, so more)

- HCO3: 60 mEq (hypertonic compared with serum, so more)

What oral/pharyngeal complications are ppl with Sjogren's syndrome at risk for?

- Remember Sjogren's is a chronic autoimmune disorder where there is diminished lacrimal and salivary secretion. The resulting dry oral caivty is called "xerostomia" and they get:

- oral ulcers/fissures at the side of the mouth due to lack of lubrication

- oral infections/infectious ulcers cause they loose the protective mechanism of salivary flow and saliva contains factors that destroy bacteria (Abs and thiocyanate ions)

- dental caries

- difficulty swallowing and chewing.

Define peristalsis

- the rhythmic contractions that propel contents forward.

- Neuronal control comes from CN IX and X

- 1ary peristalsis is induced by swallowing

- 2ary is induced by distention of the esophageal walls as the bolus moves down towards the stomach.

- Tertiary peristalsis is spontaneous occurences of peristalsis, and are considered abnormal.

Define and describe deglutition

- this is the term for 1ary peristalsis, where the food bolus is engulfed and pushed towards the esophagus by the pharyngeal constrictor muscles. There is also activation of musc that lift the palate and close off and elevate the larynx to prevent misdirection fo the bolus to the trachea.

- the UES opens breifly to allow the bolus to pass through, and then closes to prevent retrograde passage. This is the "oropharyngeal phase".

- The second part is the esophageal phase which involves the sequential contraction of the circular musc of the esophageal body, which results in a contractile wave which migrades towards the stomach, and the opening of the LES which allows the bolus to pass.

What causes the LES to relax? What is in charge of its tone?

- the esophagus should start to relax at the onset of swallowing with contraction occuring through cholinergic neurons via the vagus nerve.

- relaxation occurs through the actions of NO and VIP. (vasoactive intestinal polypeptide)

What is GERD?

- it results from the reflux of gastric contents into the esophageal lumen.

- it can be due to impaired esophageal clearance due to disorders of salivation or esophageal motor function. it can also occur due to delayed gastric emptying due to increses in gastric contents or increased gastric pressure as well as due to impairments in mucosal resistance.

What are the clinical findings of GERD?

- Typical esophageal: heartburn, acid regurg, water brash (regurg of sour fluid or almost tasteless saliva into the mouth).

- Atypical esophageal: chest pain, dysphagia (problem swallowing), odynophagia (painful swallowing)

- Typical resp: chronic cough, wheezing, aspiration pneumonia

- Atypical resp: sore throat, hoarseness, dental erosions

What investigations are needed for GERD?

- dx can usually be made through hx and relief through pharmacotherapy and lifestyle changes.

- you can do a 24 hours pH monitoring to determine presence of reflux, endoscopy to evaluate esophageal injury, acid perfusion to reproduce symptoms, and a barium swallow to determine the presence of strictures.

How do we treat GERD?

3 phases of tx:

1. elevate head of bed, small portions for meals, avoid aggravating foods, antacids, alginic acid.

2. if above don't work, continue but also add H2 receptor antagonists or prokinetics (domperidone) and a proton pump inhibitor (omeprazole)

3. if no response, then anti-reflux sx or Nissen fundulopication

What are the potential complications of GERD?

- esophageal inflammation, ulceration and bleeding for acid regurg.

- muscle spasms of the DES and/or strictures

- increased risk of Barrett's esophagus and adenocarcinoma

How can we differentiate between orophayngeal and esophageal causes of dysphagia?

- If they have difficulty initiating swallows (includes coughing, choking and nasal regurgitations), it's oropharyngeal

- If the food stops or "sticks" after swallowing, that's esophageal. Furthermore, if it's a problem with solid foods only it's probably a mechanical obstruction (ex; peptic stricture, carcinoma, lower esophageal ring). But if it's with solid or liquid food, it's most likely a neuromuscular disorder, like scleroderma, achalasia or diffuse esophageal spasm).

What is scleroderma and how does it relate to the esophagus.

- scleroderma is a chronic systemic autoimmune disease characterized by fibrosis, vascular alterations, and autoantibodies.

- damage to small blood vessels leads to intramural neuronal dysfunction, which in turn leads to progressive weakening of muscles in the distal 2/3 of the esophagus. This leads to aperistalsis and loss of LES tone, which in turn leads to reflux, then stricture, and ultimately dysphagia. It may be treated with agressive GERD prophylaxis with the last resort being anti-reflux surgery (gastroplasty)

Achalasia

- failure of relaxation of smooth muscle at any junction of the GI tract with another, usually seem as incomplete relaxation of the LES with swallowing or high resting LES pressure. It is usually idiopathic in origin but can be secondary to cancer or Chagas disease (parasitic infection)

- it's treated through dilatation of LES with a bougie and GERD prophylaxis. If this doesn't work, it's treated with a myotomy.

Diffuse esophageal spasm

How far is it from the teeth to the LES? How about from the UES to the LES?

- Teeth to LES = 40 cm

- UES to LES = 20 cm

Describe the muscles of the esophagus.

- striated it in the upper part, smooth on the bottom part

- circular layer is on the inside, longitudinal layer is on the outside.

What are the 3 muscles that work as a unit to make up the upper esophageal sphinter?

- inferior constrictor

- cricophayngeus

- proximal esophagus

What is esophageal monometry?

- when they have pressure sensors at different spots on the esophagus

- as soon as you swallow, the LES should lower it's pressure (so a down spike) until it gets the bolus.

- when the bolus passes the area you see a spike up which is peristalsis.

What's the nerve most responsible for swallowing? What are the 2 types of dysphagia?

- vagus!

- oropharyngeal dysphagia (nasal regurg, coughing, aspiration)

- esophageal dysphagia (sensation of obstruction below the sternal notch, drinking fluids may help)

How can you tell the difference between motor and structural dysphasia? Describe structural dysphagia.

- in motor you have problems swallowing regardless of texture (so solid and liquid are both difficult, wheras with structural the liquid gets by the blockage much more easily).

- structural can progress to problems with liquid though.

- food impaction and weight loss can happen in both.

- Examples of structural: invasive carcinoma, esophageal webs (too much mucosa), muscular or mucosal rings.

- can be secondary to acid injury.

- tx is disruption and acid suppressive therapy if necessary

Describe motor dysphagia

- usually slow onset, both solid and liquid problem, may rely on gravity and upper body movement to help

- could be due to: degeneration of dorsal motor nucleus, vagal fibres or ganglion cells in the mucle.

- Achalasia is pretty much LES hypertension. This one is degeneration of vagal fibres innervating the distal esophagus (the ganglion cells of the LES). There is then loss of vasoactive intersinal peptide (VIP) which is a local neurohormone allowing LES relaxation. 

- Strategy is to take a bunch of fluid to flush it. Here you see the bird's beak sign when you do barium swallow. Looks like a humingbird.

What causes achalasia? How do you treat it?

- Primary: autoimmune vagal fibre destruction

- Secondary: tumor of GE junction, Chagas disease (Trypanosoma cruzi).

*A tumor could distort how the muscles work. Chagas is a parasitic infection. In that case look for Abs.

- Treat with: Ca2+ channel blockers, nitrates, pneumatic LES dilatation, Botulin toxin injection into LES, myotomy of LES.

What are the symptoms of scleroderma?

C - Calcinosis (gross nodules of Ca2+)

R - Raynauds

E - Esophageal motility problems

S - Sclerodactily (thinning and tightening of skin on finger and toes)

T - telangectasia (face and tongue) - these are small dilated blood vessels near the surface of skin or mucosal membranes.

* Scleroderma is an autoimmune disorder and that causes smooth muscle injury to the esophagus (so that would be the bottom part!). They get problems with acid clearance too.

*the other 2 motor disorders are nutcracker esophagus and esophageal spasm

What's the triad of symptoms associated with GERD?

- heartburn, regurgitation and/or epigastric discomfort attributable to gastric acid injury of the esophageal epithelium.

- may be associated with waterbrush (overflow of spit to dilute the acid), odynophagia (pain when swallowing), dysphagia and aspiration.

- they mostly diagnose this historically

How should you diagnose GERD?

- mostly historical diagnosis.

- take a history asking for the triad (epigastric pain, regurgitation, heartburn)

- do a treatment trial (PPI)

- if that doesn't help them fully, then do a gastroscopy to see if there's esophagitis is a hiatus hernia

- do a biopsy which may show typical changes

- do a pH test (gold standard)

What could cause GERD?

What causes heartburn in pregnancy?

- well up to half of pregnant women get it

- hormonal: high estrogen and progesterone can cause LES dysfunction

- mechanical: enlarging uterus will increase intra-abdominal pressure

- treat with antacids, sucralfate, H2 blockers

What is the therapy for GERD? (drug and sx)

- Antacids: Mylanta, Gaviscon

- Histamine blockers: Ranitidine (Zantac) and Famotidine (Pepsid AC)

* PPIs are gold standard treatment. (omeprazole, etc.) they also have good SE profile.

- sx: when meds don't work. Fundoplication (wrapping the fundus around the esophagus and sticking the two sides together. They may also tighten the hiatus.

What is Barrett's esophagus?

- it's replacement of squamous mucosa with intestinal type mucosa (intesinal metaplasia)

- risk factor for ADENOCARCINOMA but most ppl with this will not get cancer (however ca always starts like this). 

What is a functional esophageal disorder?

- pt presents with complaints referable to the esophagus (heartburn, regurg, epigastric pain, dysphagia)

- incomplete or no response to acid suppression, normal gastroscopy, normal biopsy, myometry, and pH testing.

- most common problem we'll see.

- can't lead to anything serious.

What's a good ddx for GERD?

- Angina (look for ST elevation, BBB, ST depression, T inversion) 

- Pneumonia

- ACE inhibitor side effect

- cancer

How should you work up someone with GERD? (or, eating associated chest pain)

- good history and P obviously

- do an EKG right away, remember that angina can be brought on by eating too

- do a CXR

- urea breath testing, H. pylori serology, stool antigen test.

- endoscopy and biopsy (in our "case" he didn't get this for 6 months after his initial complaint, not sure if that's cause they don't do it until you do a ppi trail or just cause that's how long he had to wait...) 

What are the two types of esophageal carcinoma?

Squamous cell carcinoma: cervical and mid-esophagus (declining incidence in North America

Adenocarcinoma: distal esophagus and GE junciton. In the past this was way way more rare but now it's very common (about 50% of esophageal cancers).

What are the risk factors for squamous cell carcinoma of the esophagus?

- low SES

- smoking and alcohol

- Diet (low fruits and veggies, N-nitroso compounds)

- Underlying esophageal disease

- HPV

- Tylosis (a congenital skin condition of the palms and soles)

- upper aerodigestive tract ca

What are the risk factors for adenocarcinoma of the esophagus?

- GERD, particularly Barrett's metaplasia

- smoking

- obesity

What is Barrett's esophagus and what's it's chance of turning into cancer?

- aquired condition from longstanding GERD

- metaplastic change from squamous epithelium to columnar epithelium

- risk of cancer transformation is 0.5% per year, which is 30-125 times higher risk then general population

- you have ot follow these pts well, and screening recommendations now exist.

How would someone with esophageal adenocarcinoma present?

- Dysphagia

- Weight loss (due to dysphagia, change in diet, tumor anorexia)

- Odynophagia

- dull retrosternal pain

- cough, hoarseness (laryngeal nerve involvement), chronic GI bleeding (Fe deficient anemia)

- uncommon: transesophageal fistula, pneumonia, exsanguinating bleed due to erosion of tumor into aorta.

How do you treat esophageal cancer?

Surgery: standary primary curative treatment in small local lesions. It's a morbid operation, surgical technique varies by center.

- about half of pts present with locally advanced or metastatic disease, so sx for sure is not possible.

Chemo

Radiation

*best if chemo and radiation are combined. Can also be done pre-op or post-op (or instead of surgery)

What's the prognosis for esophageal adenocarcinoma and what is their palliative protocol?

- overall 5 year survival about 10%. (5-30 if it's resectable)

- stage 4 disease medial survival is 6-12 mo

- treat the dysphagia/obstruction and weight loss. You can do endoscopy with dilatation and stents. You can also do external beam or intraluminal brachytherapy (super local) radiation. Chemo has little proven benefit in widespread disease.

How common is gastric cancer? What's the most common histological type of gastroma?

- there are super duper high rates in Japan where it's #1 ca in men and women.

- 60% occur in developing countries, lower rates in western canada, Europe and US

- 90-95% are adenocarcinomas (fungating, ulcerating, superficial or diffusely spreading, signet ring- which is not the same is those stricture rings, it's a microscopic description thing)

- squamous are rare

- gastric lymphomas (treatment is radically different so this histology has to be r/o by biopsy.

What are the risk factors for gastric ca?

- Diet (nitroso compounds in processed meats, food additives, high salt which damages gastric mucosa, low intake of citrus fruits and veggies)

- smoking

-alcohol

- SES (lower class get lower ca, higher class get higher - like proximal)

- gastric surgery

- Epstein-Barr virus

- Helicobacter pylori.

- blood group A (higher rate of pernicious anemia and 20% more gastric ca), familial predisposition (Hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, and Peutz Jeghers syndrome), genetic polymorphisms, gastric polyps, pernicious anemia.

How would a pt with gastric ca present?

- early symptoms are vague and non-specific

- weight loss, anorexia, fatigue, epigastric discomfort

- dysphagia with proximal and GE junciton tumors

- nausea and early satiety

- persistent vomiting if there's pyloric obstruction

- Fe deficient anemia from bleeding (although thats uncommon)

- most will present with symptoms due to advanced disease.

How should we treat gastric ca? What's their prognosis like?

- peri-operative chemotherapy and surgery.

- palliative chemo improves quality of life and survival, combination chemo (5-FU based)

- about 80% survival at 5 years for non advanced disease, but only up to 20% of pts present at an early stage.

- with mets, median survival is around 6 mo.