Murdoch - Gastrointestinal Flashcards
Transient lower oesophageal sphincter relaxation has been implicated as a factor in gastro-oesophageal reflux disease. What is the major stimulus for transient lower-oesophageal sphincter relaxation?
= a. Stimulation of mechanoreceptors by proximal gastric distension
Transient lower oesophageal relaxation does not directly follow a swallow, and is independent of primary peristalsis in the body of the oesophagus. The major stimulus is gastric distension, acting on mechanoreceptors, with an afferent (and efferent) pathway via the vagus (X). It allows venting of gas from the stomach, and is a factor in gastro-oesophageal reflux disease.
- Prolonged (>10sec)
- LES relaxation independent of swallowing
- Contraction of distal oesophageal longitudinal muscle (oesophageal shortening)
- Absence of synchronised peristalsis
- Crural diaphragm inhibition
In addition to histamine, and acetylcholine neurotransmission, what is the third major substance which stimulates gastric acid secretion?
The three major secretagogues for acid secretion in the stomach are histamine, acetylcholine-mediated neurotransmission via the muscarinic M3 receptor, and gastrin.
A patient complains of ‘heartburn’, present for several months. This is a photomicrograph of an oesophageal biopsy from the patient. It has been stained routinely with haematoxylin and eosin. What is your interpretation?
The correct answer is: Normal oesophageal epithelium
Although heartburn is a symptom of gastro-oesophageal reflux, which can lead to a metaplastic change from stratified squamous epithelium to intestinal-type columnar epithelium, the image shows normal oesophageal epithelium.
Barrett’s oesophagus is illustrated below. Metaplasia is a potentially reversible change from one mature epithelial type to another. Barrett’s oesophagus carries an increased risk for cancer (adenocarcinoma).
The correct answer is: middle constrictor.
The dissection shows the middle constrictor muscle of the pharynx. It arises from the lesser and the greater horn of the hyoid bone. It is innervated by the vagus nerve (X) and, along with theother constrictors, pushes the bolus into the oesophagus (it has been implicated in hyoid bone syndrome).
The superior and inferior constrictor muscles are shown here for comparison.
During development of the foregut name (a) the two peritoneal folds (suspensions) which support the developing stomach and (b) the organs which develop within these suspensory folds. Explain (c) how the stomach rotates during development.
a) The developing stomach is suspended by the dorsal and ventral mesogastrium.
b) The liver develops within the ventral mesogastrium, and the spleen develops within the dorsal mesogastrium.
c) During development, the stomach rotates clockwise when viewed from the superior aspect (the ventral mesogastrium carrying the liver, rotates to the right of the body, with the spleen moving over to the left. Additionally, the stomach rotates clockwise when viewed from the anterior (ventral) aspect, carrying the proximal portion to the left of the body, and the distal portion (carrying the duodenum) to the right of the body.
(Also, the stomach elongates asymmetrically, developing a greater curvature and a lesser curvature).
Viewed from below, the spleen (arrowed) develops in the dorsal mesogastrium, and the liver in the ventral mesogastrium. the stomach rotates in two different axes, to bring the greater curvature (from dorsal mesogastrium) to the left of the body, and then rotating to bring the duodenum over to the right of the body.
This photomicrograph of the small intestine show normal histological features. Describe what changes you would expect in a biopsy from someone affected with coeliac disease.
There is blunting and then effacement of villi. The crypts or Lieberkuhn become hyperplastic. There is chronic inflammation with increased numbers of intraepithelial lymphocytes.
Coeliac disease is gluten-sensitive enteropathy, causing malabsorption. There is a genetic predisposition in individuals with a specific HLA-DQ (MHC-II antigen receptor) variant, which binds gliadin peptides more strongly.
Note the loss of villi, increased density of cells in lamina propria (inflammation), and the elongated, hyperplastic crypts.
In the diagram below, showing an enterocyte from the small intestine, luminal digestion of starch has yielded glucose molecules, which are transported into the enterocyte. What membrane molecule is shown by [A] in the diagram below?
A = GLUT2
Lumenal digestion of the polysaccharides starch or glycogen by amylase, followed by brush border digestion by enzymes such as glucoamylase and sucrase, yields the monosaccharide glucose. The Na+ coupled transporter SGLT-1 carries glucose (or galactose) into the enterocyte. GLUT2 facilitates movement out of the enterocyte into the interstitial fluid.
Describe the Brush Border and Carbohydrate Digestion
In the upper small intestine, how is water absorbed?
- a.Water is absorbed mostly by the paracellular route, following osmotic gradients.
- b.Water is actively absorbed across the apical membrane in a sodium-coupled water transporter molecule, which exchanges one sodium leaving the cell for one water molecule entering the cell.
- c.Water is absorbed by an active protein transporter molecule in the apical membrane, driven by ATP and adenyl cyclase.
- d.Very little water is absorbed in the small intestine. Most of it is absorbed in the colon.
- e.Very little water is absorbed in the small intestine. Most of it is absorbed in the stomach.
= a. Water is absorbed mostly by the paracellular route, following osmotic gradients.
Water is absorbed in a passive process, with much travelling via the paracellular route, following an osmotic gradient generated by sodium ion pumps and other solute transport.
Match the missing substances A-D on the diagram of B12 (cobalamin) absorption with the relevant molecule from the options available.
- A - binds to cobalamin, protecting it in the stomach
- B - secreted in the stomach, binds to cobalamin in the small intestine.
- C - the type of gastric cell which secretes B
- D - binds to cobalamin in the blood, during transport to the liver.
- A - binds to cobalamin, protecting it in the stomach → haptocorrin
- B - secreted in the stomach, binds to cobalamin in the small intestine. → intrinsic factor
- C - the type of gastric cell which secretes B → parietal
- D - binds to cobalamin in the blood, during transport to the liver. → transcobalamin II
Give four causes of vitamin B12 (cobalamin) deficiency.
Causes of vitamin B12 (cobalamin) deficiency
- Strict vegetarian diet
- Pernicious anaemia - Absence of gastric parietal cells (e.g. from immune-mediated or other chronic gastritis, or gastric resection, or effectively by gastric bypass surgery, or an antibody that binds to intrinsic factor) results in absence of gastric acid and intrinsic factor secretion, reduced cobalamin absorption and thus deficiency (causing anaemia)
- Small intestinal bacterial overgrowth can cause destruction of cobalamin
- Cobalamin receptors (cubilin receptors) in ileum may be lost with ileal resection or inflammatory diseases such as Crohn’s disease
What effect do opioids have on intestinal function, and how is this effect mediated?
The opioids (loperamide, diphenoxylate, codeine) act as μ (MU) receptor agonists, causing hyperpolarisation of the myenteric neurones and consequently inhibiting acetylcholine release. This reduces bowel peristalsis, and opioids may be used for the symptomatic relief of mild to moderate forms of acute diarrhoea. Opioid also increase sphincter tone, and reduce secretions.
(Loperamide has the least CNS effects, and minimal potential for abuse, therefore).
(Note of course that antimotility agents do not necessarily address the primary cause of the diarrhoea.)
(Constipation is a symptom of opioid abuse.)
Which bacterium causes acute onset food poisoning by producing pre-formed toxins within incorrectly handled and stored food?
- a. Staphylococcus aureus
- b. Helicobacter pylori
- c. ETEC - enterotoxigenic Escherichia coli
- d. EPEC - enteropathogenic Escherichia coli
- e. Vibrio cholerae
= a. Staphylococcus aureus
- Staphylococcus aureus* produces 8 distinct enterotoxins. The onset of illness is 1-6 hrs and with vomiting, abdominal pain and diarrhoea. Food handler contaminates food which is incorrectly stored so that the microbe multiplies and produces a heat stable toxin.There are other causes of food poisoning by ingestion of pre-formed toxins (these are toxaemias and so are distinct from food-borne infections, of course, because the toxin is already present in the ingested food):
- Bacillus cereus* is a gram positive sporing bacillus which produces 2 enterotoxins. Type 1 (heatstable) has IP of 0.5 –6 hrs and produces mainly vomiting. Type 2 has IP of 10-12 hrs and produces diarrhoea.
Type 1 typically associated with starchy foods such as rice. Spores survive cooking, and following improper storage germinate and produce toxin.
- Clostridium perfringens* : Anaerobic sporing gram positive rod. Toxin which is formed at sporulation disrupts ion transport in small bowel and this leads to diarrhoea. IP 8-24h, explosive diarrhoea and abdominal pain. Self limiting.
- Clostridium botulinum* IP 12-36h depending on dose and antigenic type of toxin (A-G). Potent neurotoxin (ingested preformed) binds to peripheral nerve endings and blocks neurotransmission. Blurred vision, abdominal pain and eventually flaccid paralysis and respiratory arrest. Requires treatment with antitoxin. C. botulinum spores are relatively heat resistant but the toxin is heat labile. Associated with low acidity and vegetable foods, but especially home bottling and canning. Some types associated with waterbirds and fish.
On the images shown, which arrow best indicates the left colic flexure?
The correct answer is: C
The left colic flexure is on the left side of the body, and is also called the splenic flexure. It is tucked up in a high position.
Match the images
- A → Transverse colon
- B → Ascending colon
- C → Hepatic flexure
- D → Gastrocolic ligament
- E → Transverse mesocolon
During development, how does the midgut rotate, as viewed from the front (anterior or ventral aspect)?
- a. 270 degrees anticlockwise
- b. 180 degrees anticlockwise.
- c. 180 degrees clockwise
- d. 360 degrees anticlockwise, followed by a 90 degree clockwise ‘unwinding’
- e. 90 degrees anticlockwise
= a. 270 degrees anticlockwise
There are three quarter-turns anticlockwise as viewed from the anterior (ventral) aspect.
Briefly describe the life cycle of hepatitis B virus, including the type of nucleic acid it has, and how this is replicated.
The virus particle binds to the host cell membrane, and the viral envelope fuses, releasing the uncoated virus core particle into the cytoplasm. Within the nucleus, viral DNA is transcribed to various RNAs, which encode viral proteins, and act as a template for reverse transcription to viral DNA (via virally-encoded reverse transcriptase). The core particle then leaves the cell by budding, becoming coated in the process. Note that viral DNA does not become integrated into the host genome as part of the life cycle.
Why is Hepatitis D virus considered to be defective?
- a. It cannot infect a human cell unless the cell is first infected with hepatitis B.
- b. It needs surface antigen from a hepatitis B infection to form its coat.
- c. It infects humans but has no clinical effects
- d. Hepatitis D infection cannot be prevented by vaccination
- e. It became an evolutionary dead-end, and is no longer present in the population.
= b. It needs surface antigen from a hepatitis B infection to form its coat.
Although the hepatitis D virus can infect liver cells, and replicate new virus cores, it needs the surface antigen (HBSAg) from a hepatitis B co-infection or superinfection in order to form its envelope. Because Hep D is essentially a Hep D virus in a Hep B coat, vaccination against Hep B will prevent Hep D infection.
Causes of portal hypertension can be categorised by their anatomic/microanatomic location. List the three categories for the origin of portal hypertension and, for each category, list one specific cause of portal hypertension that arises from a lesion at that location.
- Presinusoidal e.g. portal vein thrombus, or other obstruction (such as neoplasia).
- Sinusoidal e.g. hepatic cirrhosis or fibrosis, sinusoidal obstruction (from drugs, such as chemotherapeutics, or toxin-related endothelial damage)
- Postsinusoidal e.g. Hepatic vein or central vein thrombosis
