What are the functions of the stomach?
- Store and mix food
- Dissolve + continue digestion
- Regulate emptying into duodenum
- Kill microbes
- Secrete intrinsic factor
- Activate proteases
- Mucosal protection
- Produces chyme
Mucous cells, parietal cells, chief cells, enterochromaffin (ECL)-like cells, G cells and D cells. What do these cells secrete? What is the function do these cells?
When gastric acid (HCl) is formed, H+ ions have to enter the lumen of the stomach. Is this passive or active?
This is an active process. H+ ions are pumped into the lumen of the stomach from parietal cells via a H+/K+ proton pump. It is important that H+ and K+ have the same charge.
Picture of mucous cells, parietal cells, chief cells and enteroendocrine cells.
What are the two phases responsible for turning gastric acid secretion on?
- Cephalic phase
- Gastric phase
- Also protein in stomach. Proteins in the lumen cause pH to rise by mopping up H+ ions. This decreases somastatin secretion, which increases parietal cell activity (as somastatin inhibits parietal cells)
What happens in the cephalic phase of turning on gastric acid secretion?
- Parasympathetic nervous system stimulated by sight, smell + taste of food
- Acetylcholine released. This acts directly on parietal cells + triggers release of gastrin + histamine. The net effect is increased acid production
What happens in the gastric phase of turning on gastric acid secretion?
- Gastric distension, presence of amino acids + peptides
- Gastrin release. This acts directly on ECF-like + triggers the release of histamine. Histamine acts directly on parietal cells. Net effect = increased acid production
What are the two phases involved with turning off gastric acid secretion?
- Gastric phase
- Intestinial phase
What happens in the gastric phase when turning gastric acid secretion off?
- Low luminal pH (high H+)
- This directly inhibits gastrin secretion from G cells. This indirectly inhibits histamine secretion (via gastrin).
- This low pH stimulates stomastatin release which inhibits parietal cell activity
What happens in the intestinial phase of turning off gastric acid secretion?
- In the duodenum there is:
- Low luminal pH
- Hypertonic luminal contents
- Amino acids + fatty acids
- These factors all decrease HCl secretion via:
- Parasympathetic nerve inhibition (less ACh = less gastrin + histamine release)
- Triggering the release of enterogastrones, e.g. secretion + CKK. These inhibit gastrin release + promote somastatin release
As a summary of gastric acid regulation, what is it regulated by?
- Controlled by the brain, stomach + duodenum
- 1 parasympathetic neurotransmitter (ACh)
- 1 hormone (gastrin)
- 2 paracrine factors (histamine, somatostatin)
- 2 key enterogastrones (secretin, CCK)
What are the protective mechanisms of gastric mucosa?
- Alkaline mucus on luminal surface
- Tight junctions between epithelial cells
- Rapid cell replacement of damaged cells by stem cells present in base of pits
- Feedback loops for regulation of gastric acid secretion
What is the consequence of insufficient gastric mucosa defense? What are the causes of this condition?
- Consequence of insufficient defense = peptic ulcers
- Causes of peptic ulcers:
- Helicobacted pylori infection (damages gastric epithelium, can be treated by 1 proton pump inhibitor + 2 antibiotics, e.g. amoxicillin)
- NSAIDs (non-steroidal anti-inflammatory drugs, inhibit cyclo-oxygenase 1 which causes reduced mucosal defense. Treated by prostaglandin analogues, e.g. misoprotol, reduced acid secretion with proton pump inhibitors or H2-receptor antagonists
- Chemical irritants, e.g. alcohol, bile salts
- Gastrinoma (tumours of G cells, secret gastrin in an unregulated way). Worth noting that G cells are enterochromaffin-like cells
How is pepsin made? What is its role?
- Pepsinogen, an inactive zymogen is secreted by chief cells. This secretion is stimulated by ACh (parasympathetic)
- Pepsinogen's secretion parallel HCl secretion from parietal cells
- Pepsinogen --> pepsin. Converted by HCl and pepsin (pepsin catalyses the reaction as it is a positive feedback loop)
- Most efficient conversion when pH < 2 (as HCl needed)
- Pepsin accounts for ~20% of protein digestion
- Pepsin increases surface area for later digestion
What is receptive relaxation in gastric motility? What is it mediated by?
- Empty stomach volume = 50ml, maximum volume after eating = 1.5L. This is achieved by receptive relaxation of muscles in body + fundus of stomach
- Mediated by:
- ACh (parasympathetic - Vagus nerve)
- Nitric oxide + serotonin (releases by enteric nerves)
What is peristalsis? How does it work?
- Peristalsis is a series of wave-like muscle contractions that moves food. It is produced in response to arriving food
- Ripple movement begins in body
- More powerful contraction wave in antrum
- Pyloric sphincter closes (little chyme can enter duodenum)
- Antral contents forced back to body - mixing
What is the basic electrical rhythm for peristalsis? What cells determine the frequency of the contractions?
- Frequency of peristaltic waves determined by pacemaker cells called the interstitial cells of Cajal and is constant (3x per minute)
- Depolarisation waves transmitted through gap junctions to adjacent smooth muscle cells
- The strength of peristaltic waves varies (excitatory hormones + neurotransmitters further depolarise membranes, action potential generated when threshold reached)
What increases the strength of gastric contractions?
- Gastric distension (mediated by mechanoreceptors)
What decreases the strength of gastric contractions?
- Duodenal distension
- Increase in duodenal fat
- Increase in duodenal osmolarity
- Decrease in duodenal pH
- Increased sympathetic NS stimulation
- Decreased parasympathetic NS stimulation
Diagram of gastric emptying.
What is gastroparesis? What drugs can it be caused by?
- Gastroparesis = delayed gastric emptying, makes people feel nauseous etc.
- Caused by:
- Gastrointestinal agents, e.g. H2 receptor antagonists, proton pump inhibitors
- Anticholinergic medications, e.g. diphenhydramine (Benadryl)
- Miscellanous, e.g. calcium channel blockers
What are the main functions of the liver?
- Detoxification = filters + cleans blood of waste products
- Immune functions = fights infections + diseases
- Involved in synthesis of clotting factors, proteins, enzymes, glycogen + fats
- Production of bile + breakdown of bilirubin
- Energy storage (glycogen + fats)
- Regulation of fat metabolism
- Ability to regenerate
The liver maintains a continuous supply of energy for the body by controlling the metabolism of what? What is the liver regulated by?
- Carbohydrates and fats
- Regulated by endocrine glands, e.g. pancreas. Also regulated by nerves
What are lipids? What are triglycerides? Where can fat be stored?
- Lipds are esters of fatty acids + glycerol or other compounds, e.g. cholesterol. Insoluble in water and variety of structures and functions
- 90% of lipids are triglycerides, others phospholipids etc. Triglycerides = 1 glycerol molecule esterified to 3 fatty acids
- Storage areas of fat include adipocytes and hepatocytes
What are the two types of fatty acids?
- Saturated = line up
- Unsaturated = one or more kink
What are the functions of lipids?
- Energy reserve, almost all energy required is provided through oxidation or lipids, carbohydrates + proteins (liver is main storage place for glycogen)
- Part of cell membranes
- Hormone metabolism
Through which vessels are lipids transported to the liver?
- Portal vein
- Hepatic artery
In what form are lipids transported?
- Lipids are often transported as triglycerides or fatty acids bound to albumin, within lipoproteins or as chylomicron remnants
How are the lipids taken up into the adipocytes? What happens to the fatty acids in the adipocytes?
- Triglycerides can't diffuse through cell membranes, so lipoprotein lipase breaks down triglycerides to release free fatty acids which can diffuse through bilayer
- They can be stored + the fatty acids are re-esterified to triglycerides. Adipocytes are the main store of lipids, but hepatocytes also store some
How are lipids transported from adipocytes to hepatocytes?
- Hormone sensitive lipase releases free fatty acids
- Hepatic lipase enables the uptake of free fatty acids into hepatocytes