GI and Liver Flashcards
How is swallowing initiated?
Initiated when pressure receptors in the walls of the pharynx are stimulated by food or drink, forced into the rear of the mouth by the tongue
What is the innervation of the nasopharynx, oropharynx, and laryngopharyx?
- Nasopharynx: Maxillary nerve (V2 (second branch of trigeminal nerve (V))
- Oropharynx: Glossopharyngeal nerve (IX)
- Laryngopharynx: Vagus nerve (X)
What is step 1 of the process of swallowing?
Voluntary:
- Food is compressed against the roof of the mouth and pushed towards the oropharynx by the action of the tongue
- The buccinator & supra hyoid muscles manipulate food during chewing. They also elevate the hyoid bone and flatten the floor of the mouth
What is step 2 of the process of swallowing?
Involuntary:
- The nasopharynx is closed off by the soft palate via the action of the muscles of
the palate which tense & elevate it - helping to form the bolus of food
- The pharynx is also shortened & widened (using longitudinal muscles) by the
elevation of the hyoid bone via the actions of the muscles of the floor of the palate
which depress (lower) the mandible if the hyoid bone is fixed or elevate (raise) the
hyoid bone & larynx if the mandibles is fixed - Impulses from the swallowing centre inhibit respiration, raise the larynx (as
mentioned above) and close the glottis (the area around the vocal cords and the space
between them) - keeping food from entering the trachea - As the tongue forces the food farther back into the pharynx the food tilts the epiglottis
backward to cover the closed glottis - this prevents aspiration of food - a
dangerous situation where food travels down the trachea and can cause choking or
regurgitated stomach contents are allowed into the lungs causing damage
What is step 3 of swallowing?
Involuntary:
- Pharyngeal constrictor muscles - 3 overlapping muscles that form the posterior & lateral sides of the pharynx - innervated by vagus (X). They contract sequentially from above down to drive the bolus into the oesophagus
- Depression of the hyoid bone and pharynx is carried out by the infra hyoid muscle of the neck - they fix the hyoid bone enabling the opening of the mouth.
What is the fourth and final step of swallowing?
The next stage of swallowing occurs in the oesophagus:
- Skeletal muscle surrounds the upper third of the oesophagus
- Smooth muscle surround the lower two-thirds of the oesophagus
- The luminal pressure in the pharynx at the opening to the oesophagus is equal to the atmospheric pressure and the pressure at the opposite end of the oesophagus in the stomach is slightly greater than atmospheric pressure. Thus these pressure differences tend to force both air from above and gastric contents from below into the oesophagus - however this does not occur due to the presence of sphincter muscles at both ends of the oesophagus.
- A ring of skeletal muscle surround the oesophagus just below the pharynx - called the upper
oesophageal sphincter
- A ring of smooth muscle surround the oesophagus in the last portion of the oesophagus - called the lower oesophageal sphincter
- Before food can enter the oesophagus the upper oesophageal sphincter relaxes - immediately after the food has passed through the sphincter closes, the glottis opens and breathing resumes
- Once in the oesophagus, the food moves towards the stomach by a progressive wave of muscle contractions that proceed along the oesophagus, compressing the lumen and forcing the food ahead - these are peristaltic waves
- One oesophageal peristaltic wave takes 9 seconds to reach the stomach
- The lower oesophageal sphincter opens and remains relaxed throughout the process of swallowing, allowing the arriving food to enter the stomach
Explain the gag reflex?
• The reflex elevation of the pharynx - often followed by vomiting cause by irritation
of the oropharynx - the back of the tongue
• Reflex arc between the glossopharyngeal (IX) and the vagus (X) nerves
What are the functions and features of saliva?
Functions:
- Lubricant for mastication
- Maintaining oral pH: needs to be maintained at about pH 7.4 (slightly alkaline) this is
achieved by the bicarbonate/carbonate buffer system for the rapid neutralisation of
acid
- Release digestive enzyme - salivary alpha amylase is released from the parotid gland for starch digestion
Features:
• Daily secretion = 800 -1500ml in adults
• pH ranges from 6.2 to 7.4
Serous secretion = alpha amylase for starch
digestion
• Mucous secretion = mucins for lubrication of
mucosal surfaces
What are the three main salivary glands and what percentage of salivary flow do they contribute?
Submandibular gland, Parotid gland, Sublingual Gland.
They contribute 80% of salivary flow
What are minor salivary glands?
Minor salivary glands contribute to 20% of salivary flow - they are found in the submucosa or the oral mucosa of the lips, cheeks, hard & soft plate and the tongue
Which glands have mucous secretions and which have serous secretions?
Parotid: Serous
Submandibular: Mucous and Serous
Sublingual: Mucous and Serous (mainly mucous)
Minor glands: Predominantly mucous (but some are serous)
What are the Factors affecting the composition & amount of saliva produced?
Flow Rate Circadian Rhythm (Sleep Cycle) Type and Size of Gland Duration and type of stimulus that causes saliva to be produced Diet Drugs Age Gender Time of Day
Defences of the oral cavity are provided by?
The Mucosa: Physical barrier
Salivary glands: Saliva washes away food particles
which bacteria or viruses may use as metabolic support
Palatine tonsils: act as the “surveillance system” for the immune system
Salivary glands are surrounded by lymphatic system(linked to thoracic duct and
blood): which contains a broad range of functional immune cells
Which glands are continously active and which require stimulation?
Submandibular: Continuously Active (Unstimulated components of the salivary system are dominated by submandibular components)
Sublingual: Continuously Active
Parotid: Requires stimulation to become main source of saliva
Minor Glands: Continuously Active
What is the structure of salivary glands?
Composed of two morphologically and distinct epithelial tissues:
Acinar Cells
(functional unit of a salivary gland)
There are two types of acini:
- Serous acinus:
- Dark staining nucleus
- Nucleus in basal third
- Small central duct
- Secrete: water & alpha amylase
- Found mainly in the parotid gland - Mucous acinus:
- Pale staining “foamy”
- Nucleus at base
- Large central duct
- Secrete: mucous (water & glycoproteins)
- Found in submandibular & sublingual glands
Ducts (surrounded by acinar cells)
collect to form the large cut entering the mouth. Equipped with channels and transporters in the apical and basolateral membranes enabling transport of fluid and electrolytes
- Intralobular ducts are divided into intercalated & striated
- Intercalated:
• Short narrow
duct segments with cuboidal cells that
connect acini to larger striated ducts - Striated:
• Striated like a thick lawn
• Major site for reabsorption of NaCl
• Appear striated at basal end
• Basal membrane is highly folded into microvilli (giving the duct its striated appearance) for active transport of HCO3 against concentration gradient, the
microvilli are filed with mitochondria for energy to facilitate the active transport
The epithelium of the ducts reabsorbs water so final saliva is hypotonic (has less water in it so have a higher concentration of solutes (K+ & HCO3-)
What is the Structure and location, Structures passing through, and Innervation of the Parotid gland?
Structure and location: Superficial triangular outline between: - Zygomatic arch - Sternocleidomastoid - Ramus of mandible •Parotid duct: -Also called Stenson’s duct - crosses masseter muscle and pierces through the buccinator muscle where it enters the oral cavity near the second upper molar - Can be palpated a fingers breadth below the zygomatic arch
Structures passing through:
- External carotid artery
- Retromandibular vein
- Facial nerve (VII - exits skull through the
stylomastoid foramen) - supplies the muscles of facial expression
- Thus the parotid capsule is very tough
• The parotid glands are entirely made up of serous acini with ducts interspersed
Innervation:
- Sympathetic sensory innervation (inhibits/minimises secretion) is provided by the auriculo-temporal nerve which is a branch of the mandibular nerve (V3 - this
division of the trigeminal nerve exits the skull through the foramen ovale)
- Parasympathetic innervation is supplied by glossopharyngeal nerve (IX) - stimulates secretion
• Horizontally it has a triangular outline with the apex on the carotid sheath
What is the Structure and location and Innervation of the submandibular gland?
Structure and location:
Two lobes separated by mylohyoid muscle - larger superficial lobe and a smaller
deep lobe in the floor of the mouth
• The submandibular duct (Whartons duct) begins in the superficial lobe, wraps around the free posterior border of the mylohyoid, then runs along the floor of the mouth and empties into the oral cavity at the sublingual papillae - located more posteriorly than the sublingual gland
Innervation:
Parasympathetic innervation is supplied by the chorda tympani branch of the facial nerve (VII)
- Sympathetic innervation is supplied via the lingual nerve which is derived from the facial nerve (VII)
What is the Structure and location and Innervation of the sublingual gland?
Structure and location:
located more anteriorly than the submandibular glands
Located in the floor of the mouth between mylohyoid muscles and oral mucosa of
floor of mouth
• Very close to the submandibular gland
• Saliva is transmitted via the submandibular/
whartons duct as well or small ducts that pierce oral
mucosa floor of mouth
• Much smaller than submandibular - but size is variable
Innervation:
- Similar to submandibular gland
- Parasympathetic innervation is supplied by the chorda tympani branch of the
facial nerve (VII)
- Sympathetic innervation is supplied via the lingual nerve which is derived from the facial nerve (VII)
What is the Structure and location and Innervation of the minor salivary glands?
Structure and location:
Concentrated in the; buccal labial, palatal & lingual regions
• Also found at; superior pole of tonsils (Weber’s glands), tonsillar pillars & at the base
of the tongue (von Ebner’s glands - underlying circumvallate papillae)
• All minor salivary glands are mucous EXCEPT for the serous glands of von Ebner
• They lack a branching network of draining ducts so each salivary unit has its own simple duct
Innervation:
• PARASYMPATHETIC = stimulates salivary secretion
• SYMPATHETIC = inhibits salivary secretion (but some baseline secretion)
What is Xerostomia?
Dry Mouth, classified by If salivary output falls to
less than 50% of normal flow
What are the causes of xerostomia?
• medication and irradiation for head and neck cancers
• Obstruction:
- Saliva contains calcium & phosphate ions that can from salivary calculi (stones)
- Most common in submandibular gland (80% incidence) - they block the duct at the
bend around the round mylohyoid or at exit at the sublingual papillae
• Inflammation:
- Caused by infection secondary to obstruction
- Infections caused by; mumps (viral infection) - results in fever, malaise, swelling of the glands
• Degeneration:
- Complication of radiotherapy to head and neck for cancer treatment
- May be a consequence of cystic fibrosis or Sjorgren’s syndrome (autoimmune
condition where immune cells attack glands resulting in little or no saliva produced -
affects mainly women)
What are the consequences of xerostomia?
• Low lubrication - oral function becomes difficult
• Low natural oral hygiene -poor pH control =accumulation of plaque =dental caries or increases
incidence of opportunistic infections especially fungal
e.g candida - thrush
What is the name for an oral cancer?
Squamous cancer, Squamous tumours respond well to radiotherapy and chemotherapy
What epithelium is present in salivary glands?
Secretory Glandular epithelium
What are the is the foregut?
Foregut starts from the mouth to the common
bile duct
- Blood supply: Celiac artery
- Components: • Pharynx • Oesophagus • Stomach • Proximal half of duodenum and the derivative (liver, biliary apparatus & the pancreas)
What is the midgut?
Midgut starts from the common bile duct to
2/3rds of the transverse colon
- Blood supply: Superior mesenteric artery
- Components: • Distal half of the duodenum • Jejunum • Ileum • Caecum • Appendix • Ascending colon • Right 2/3rds of the transverse colon
What is the hindgut?
Hindgut starts from 2/3rds of the transverse colon
to the anal canal
- Blood supply: Inferior mesenteric artery
- Components: • Left 1/3 of the transverse colon • Descending colon • Sigmoid colon • Rectum • Anal canal
What is step 1 of the GI embyronic folding?
Folding occurs in two planes, the horizontal & medial
Planes
Folding occurs in two planes due to the differing rates of growth of the embryonic
structures
- Folding in the horizontal plane results in the formation of the two lateral body folds
What is step 2 of the GI embryonic folding?
Folding in the medial plane results in the formation of the cranial & caudal folds
- Folding in both planes takes place simultaneously
What is step 3 of the GI embryonic folding?
The endoderm is mainly responsible for the development of the GI tract
- As embryonic folding continues, the endoderm moves towards the midline and
fuses - incorporating the dorsal part of the yolk sac to form the primitive gut tube
- The primitive gut is derived from the endoderm and the visceral mesoderm
What is step 4 of the GI embryonic folding?
The foregut is on the cranial end of the embryo and is temporarily closed by the oropharyngeal membrane which at the end of the 4th week of development ruptures to form the mouth
- The midgut lies between the fore and hindgut and remains connected to the yolk sac until the 5th week of development
- As embryonic folding continues, the connection to the yolk sac narrows into a stalk called the vitelline duct
- The hindgut lies at the caudal end of the embryo, it is temporarily closed by the cloacal membrane, which
during the 7th week of development, ruptures to form the anus
What GI structures are formed from the endoderm?
- Epithelial lining of digestive tract
- Hepatocytes of the liver
- Endocrine and exocrine cells of the pancreas
What GI structures are formed from the visceral mesoderm?
- Muscle, connective tissue & peritoneal components of the wall of the gut
- Connective tissue for the glands
- The primitive gut tube, differentiates into three distinct parts; the foregut, midgut &
hindgut
Describe the development of the pharyngeal arches?
Part of the foregut
Extends from the oropharyngeal membrane to the respiratory diverticulum
In the 4th & 5th week of fetal life, the pharyngeal arches develop:
• There are five arches; 1,2,3,4 & 6 (there is no 5th in humans - sort of combines into
the 4th)
• They contribute greatly to the external appearance of the embryo.
• Formed of masses of mesenchymal tissue (connective tissue derived from
mesoderm) which are invaded by cranial neural crest cells.
Each pharyngeal arch is covered externally by endoderm (forming the pharyngeal
clefts)
- Each pharyngeal arch is covered internally by ectoderm (forming the pharyngeal
pouches)
Each arch has its own; nerve supply, arterial supply & venous supply
• Each arch gives rise to various structure of the pharynx & larynx
What is the innervation, the muscles and bone of the 1st pharyngeal arch?
Innervation: Mandibular nerve (V3 - i.e third branch of trigeminal (V)
Muscles: mastication, tensor tympani, digastric, myolohyoid
Bone:maxilla, mandible, incus, malleus
What is the innervation, the muscles and bone of the 2nd pharyngeal arch?
Innervation: Facial nerve (VII)
Muscles: facial expression, stapedius, stylohyoid
Bone: stapes, styloid and lesser horn of hyoid cartilage
What is the innervation, the muscles and bone of the 3rd pharyngeal arch?
Innervation: Glossopharyngeal nerve (IX)
Muscles: stylopharyngeus of the pharynx
Bone: body & greater horn of hyoid cartilage
What is the innervation, the muscles and bone of the 4th pharyngeal arch?
Innervation: Superior laryngeal nerve of Vagus nerve (X)
Muscles: Cricothyroid
Bone: thyroid cartilage & epiglottic cartilage
What is the innervation, the muscles, and bone of the 6th pharyngeal arch?
Innervation: Recurrent laryngeal nerve of Vagus nerve (X)
Muscles: All muscles of the larynx except the cricothyroid
Bone: cricoid cartilage, arytenoid cartilages, corniculate & cuneiform cartilage
What is the process of the development of the oesophagus?
Step 1: At the 4th week, at the end of the pharynx and the beginning of the oesophagus, at
the ventral wall of the foregut - respiratory diverticulum (lung buds) appear
Step 2: The trancheoesophageal septum develops and separates the respiratory diverticulum from the dorsal part of the foregut - in this way the foregut is divided
into the ventral respiratory primordium & the dorsal oesophagus
Step 3: Initially the oesophagus is short but it lengthens rapidly with the descent of the heart and lungs
What are mesenteries?
Parts of the gut tube are suspended from the dorsal & ventral body walls by mesenteries
Mesenteries are double layers or peritoneum that surround an organ and connect
it to the body wall, such an organ is called intraperitoneal
When an organ is sitting directly on the posterior abdominal wall and covered by peritoneum on its anterior surface only, it is known as a retroperitoneal organ
Ligaments: are double layers of peritoneum which pass from one organ to another or from one organ to the body wall
Mesenteries & ligaments provide pathways for blood vessels, lymphatics & nerves
to go to and come from the abdominal viscera
By the 5th week the lower part of the foregut, midgut & major part of the hindgut are suspended from the posterior abdominal wall by DORSAL MESENTERY - which extends from the lower part of the oesophagus to the cloacal region
What is the vental mesentery?
Present only in the region of the foregut - terminal part of the oesophagus, the stomach and the upper part of the duodenum
Thus the foregut has both ventral & dorsal mesenteries
is derived from the septum transversum
Its free lower margin contains; the hepatic artery, portal vein and bile duct
The liver develop IN the ventral mesentery and divides IT into the lesser omentum & the falciform ligament
What is the first step of stomach development?
Appears as a fusiform (spiral-shaped) dilation in the foregut in the 4th week
•Its appearance and position changes greatly as a result of the different rate of growth in various
regions of its wall
•The developing stomach is attached to the body walls by the dorsal & ventral mesenteries
•The left & right vagus nerves flank the left and right side of the developing stomach respectively
•The dorsal wall of the stomach grows faster than the ventral wall, this differential growth
forms the greater & lesser curvatures of the stomach
What is the second step of stomach development?
During the 7th week, the stomach rotates 90 degrees CLOCKWISE about a longitudinal axis - this rotate
produces a space behind the stomach called the lesser sac
The greater curvature (on the embryonic dorsal side) now faces the left of the body & the lesser curvature (on the embryonic ventral side) faces the right
• The left vagus is now on the anterior side of the stomach and the right vagus is located on the posterior side - thus they are now
called the anterior & posterior vagal trunks
What is the third step of stomach development?
In the 8th week the stomach and duodenum ROTATE about a ventrodorsal axis, pulling the end of the stomach upwards, they
pull the duodenum into a C-shape
•These rotations result in the thinning of the dorsal mesentery, which now hangs from the greater
curvature of the stomach - it is now called the greater omentum
•The ventral mesentery is now attached to the developing liver and has formed the lesser
omentum
•The development of the omen and the rotations of foregut structures produce distinct spaces of
the peritoneal cavity
•The space posterior to the stomach is called the lesser sac
•The space anterior to the stomach is called the greater sac
•The greater and lesser sacs communicate via a small opening (located near the hilum of the liver) called the epiploic foramen
What is the fourth step of stomach development?
During the foetal period, the anterior & posterior folds of the greater omentum FUSE to form one THICK sheet formed from 4 layers of peritoneum
What are the functions of the stomach?
Store and mix food Dissolve and continue digestion Regulate emptying into the duodenum Kill microbes Secrete protease Secrete intrinsic factor Activate proteases Lubrication Mucosal Protection
What are the key cell types and what are their functions?
Mucous Cells: produce mucous, at entrance to gland
G Cells: Produce Gastrin
Parietal Cells: produce gastric acid and intrinsic factor
D Cells: Release somatostatin
Chief Cells: Secrete pepsinogen
Enterochromaffin-like (ECL) cell: releases histamine
What are the features of gastric acid secretion?
Occurs from parietal cells
Hydrochloric acid: very strong, pH 2, [H+] > 150mM, approximately 2 litres/day
Energy Dependent
Neurohormonal regulation
H20 in the parietal cell breaks down into Oh- and H+
What is the process of gastric acid secretion?
1: The origin of the H+ ions is CO2
2: CO2 & H2O from respiration are converted into bicarbonate (H2CO3) via the enzyme carbonic anhydrase
3: H2CO3 rapidly disassociates into HCO3- and H+
4: The H+ ions produced can then react with the OH- ions from the breakdown of H2O to regenerate H2O
5: The H+ ions from the break down of H2O are then pumped into the stomach lumen via H+/K+ ATPase pumps in the luminal membrane of parietal cells, they pump 1 K+ ion into the parietal cell for every 1 H+ ion they pump out into the stomach (so as to ensure there is no change in polarity of the cell) - these pumps require ATP to function
6: The K+ ions pumped in can then diffuse back out into the stomach via K+ channels on
the plasma membrane of parietal cells
7: The HCO3- from the breakdown of H2CO3 is secreted into the capillary for the
exchange of Cl- ions
8:Cl- ions can then enter the stomach by diffusing through Cl- channels in the plasma
membrane of the parietal cell
9:Then in the stomach, the H+ ions and Cl- ions can react to form HCl
10:Removal of the end products of this reaction enhance the forward rate of reaction -
in this way production and secretion of H+ are coupled
11: Increased acid secretion stimulated by the factors mentioned in section on regulating gastric acid secretion, results from the migration of H+/K+ - ATPase protein in the membranes of intracellular vesicles in the parietal cell to the plasma membrane by fusion of these vesicles with the membrane thereby increasing the number of pump protein in the plasma
membrane meaning more H+ can be pumped in = more acid
What is the process of the Cephalic Phase (during a meal) of regulating gastric acid secretion?
• Parasympathetic nervous system
• Initiated by the sight, smell, taste of food and chewing
• Acetyl choline is released
• ACh acts indirectly on parietal cells, triggering the release of GASTRIN (from G
cells in the pyloric antrum of stomach) & HISTAMINE (from enterochromaffin-like
(ECL) cells)
• Both gastrin & histamine increase the number of H+/K+-ATPase pumps on the
plasma membrane of the parietal cell
• Net effect = increased acid production
What is the process of the gastric phase (after the meal) of turning on gastric acid secretion?
• Initiated by; gastric distension from the volume of ingested material & the presence
of peptides and amino acids (released by the digestion of luminal proteins)
• Gastrin is released which acts directly on parietal cells
• Gastrin also triggers the release of histamine which also acts directly on the parietal cells
• Both gastrin & histamine increase the number of H+/K+-ATPase pumps on the
plasma membrane of the parietal cell
• Net effect = increased acid production
• NOTE: it can be deduced that histamine is really important since it mediates the effects of gastrin and acetylcholine - thus can be a good therapeutic target for e.g. acid overproduction etc.
- Protein in the stomach:
• Direct stimulus for gastrin release (as seen above)
• Proteins of foods in the lumen, act as a buffer thereby reducing the amount of H+ ions = increase in pH : resulting in the decreased secretion of somatostatin (see below) which results in more parietal cell activity resulting in more acid production
What is the process of the gastric phase (after the meal) of turning off gastric acid secretion?
• Low luminal pH (high [H+]) directly inhibits gastrin secretion thereby indirectly
inhibiting histamine release
• Low pH also stimulates SOMATOSTATIN release which inhibits parietal cell activity
- Intestinal phase - in the duodenum:
• Initiated by; duodenal distension, low pH, hypertonic solutions, the presence of amino acids & fatty acids
• These all trigger the release of a locally produced chemical messengers called
enterogastrones such as SECRETIN (inhibits gastrin release & promotes somatostatin release) & CHOLECYSTOKININ (CKK)
• They also trigger short & long neural pathways which reduce ACh release
• Net effect = reduced acid secretion
What is the summary of the molecules involved in gastric acid secretion?
Regulation of gastric acid secretion is controlled by the brain, stomach &
duodenum
• 1 parasympathetic neurotransmitter -ACh (+)
• 1 hormone - gastrin (+)
• 2 paracrine (produced in stomach) -histamine (+) & somatostatin (-)
• 2 key enterogastrones - secretin (-) & CCK (-)
What is a peptic ulcer?
An ulcer is a breach in a mucosal surface
What are the causes of peptic ulcers?
Helicobacter pylori infection - most common
Drugs - NSAIDS e.g. aspirin and ibuprofen
Chemical irritants: alcohol, bile salts (secreted into duodenum but can reflux into
stomach and wash way protective mucous lining)
Explain how Helicobacter Pylori infection leads to peptic ulcer formation and explain the treatment?
Explanation:
• Lives in gastric mucus
• Secretes urease, splitting urea into CO2 and ammonia
• Ammonia + H+ = ammonium
• Ammonium is toxic to gastric mucosa resulting in less mucous produced
• Secreted proteases, phospholipase & vacuolating cytotoxin A can then begin
attacking the gastric epithelium further reducing mucous production
• Results in an inflammatory response and less mucosal defence
Treatment:
eradicate organism using triple therapy; proton pump inhibitor (inhibits pump pumping H+ ions into stomach lumen thereby increasing gastric pH making
conditions inhospitable for helicobacter pylori) & antibiotics (clarithromycin, amoxicillin, tetracycline & metronidazole)
Explain how NSAIDs may lead to peptic ulcer formation and explain the treatment?
Explanation:
NSAIDS - non-steroidal anti-inflammatory drugs
• Mucous secretion is stimulated by prostaglandins (in inflamed tissue, prostaglandin
triggers inflammatory response thus inhibition = less inflammation)
• Cyclo-oxygenase 1 is needed for prostaglandin synthesis
• NSAIDS inhibit cylclo-oxygenase 1
• Thus reduced mucosal defence
Treatment:
use prostaglandin analogues (mimic effect of prostaglandins) e.g.
misoprostol and reduce acid secretion
Explain how chemical irritants may lead to peptic ulcer formation?
Duodenal-gastric reflux causes bile to enter stomach, alkaline bile strips away
gastric mucous layer of stomach resulting in reduced mucosal defence
- Gastrinoma - rare tumours of parietal cells = excessive gastrin release = increase in gastric acid = increased attack on gastric mucosa = ulcer
List and explain the synthetic ways to regulate gastric acid secretion?
Proton Pump Inhibitor: inhibit pumps pumping H+ into stomach lumen, they only
block pumps NOT the activators e.g. gastrin, examples include; omeprazole, lansoprazole & esomeprazole (all have varied side effects)
H2 receptor agonist: block receptors for histamine thereby reducing acid
secretion, examples include; cimetidine & ranitidine
What is the process of protease secretion?
1: Chief cells produce pepsinogen
2:Pepsin is secreted as an inactive zymogen (pepsinogen) - it is stored this way to
prevent it digesting the chief cells and the rest of the body
3: Pepsinogen is mediated by input from the enteric nervous system via neurotransmitter ACh
(parasympathetic)
4: Secretion parallels HCl secretion
5: When pepsinogen is released into the stomach lumen, the low pH (generated by HCL) of the stomach activates a rapid autocatalytic process
in which pepsin is produce from pepsinogen ((Most efficient conversion when pH < 2)
6: Once some pepsin is produced, it can be used to produce more since it can aid in
the cleavage of pepsinogen - positive feedback
7:HCO3- released in the duodenum irreversibly inactivates pepsin
What is the role of pepsin in protein digestion?
Not essential - protein digestion can occur if the stomach is removed, HOWEVER if
removed then no vitamin B-12 absorption can occur in the small intestine since the
stomach parietal cells produce intrinsic factor - essential for vitamin B-12
absorption in the small intestine
Accelerates protein digestion
Normally accounts for 20% of total protein digestion
Breaks down collagen in meat thereby helping shred meat resulting in smaller pieces with greater surface area for digestion
What is gastric motility?
- Empty stomach has volume of around 50ml
- When eating it can accommodate roughly 1.5L with little increase in luminal
pressure - It does this by the smooth muscles in the body & fundus receptive relaxation
What is receptive relaxation?
Mediated by parasympathetic nervous system acting on the enteric nerve plexuses with coordination provided by afferent input from the stomach via the vagus nerve and by the swallowing centre in the brain
Nitric oxide and serotonin released by the enteric nerves mediate relaxation
Acetyl choline activates parietal & chief cells & initiates receptive relaxation
What is the process of peristalsis?
1
1: As in the oesophagus the stomach produces peristaltic waves in response to the arriving food
2: Each wave begins in the body of the stomach producing a ripple as it proceeds towards the antrum
3: The initial contraction in the body is too weak to produce much mixing of luminal contents with acid and pepsin
4: There are more powerful contractions in the antrum which enables better mixing of the luminal contents
5: The pyloric sphincter (a ring of smooth muscle and connective tissue between the atrium and duodenum) closes as peristaltic waves reach it
6:This contraction, every time a wave reaches it means little chyme (smooth, somewhat orange coloured liquid = the end result of stomach digestion and peristalsis) enters the duodenum
It also means that the antral contents are forced back towards the body meaning there is more mixing and thus digestion
- The frequency of peristaltic waves are determined by pacemaker cells (INTERSTITIAL CELLS OF CAJAL) in the muscular propria (longitudinal smooth
muscle layer) and is constant (3 every minute)
- Pacemaker cells undergo slow depolarisation-repolarisation cycles
- The depolarisation waves are transmitted through gap junctions to adjacent smooth muscle cells
- These cells do not cause significant contraction in the empty stomach
The strength of the peristaltic contraction varies
• Excitatory neurotransmitters and hormones further depolarise membranes
• Action potentials are generated when the threshold is reached
• The interstitial cells of cajal are active all the time, but the action potential threshold for muscle contraction can be altered by the enteric nervous system
What is the effect of gastrin secretion on the strength of contraction?
Increases the strength
What is the effect of gastric distension (mediated by mechanoreceptors) on the strength of contraction?
Increases the strength
What is the effect of Duodenal distension, Increase in duodenal fat, Increase in duodenal osmolarity, Decrease in duodenal pH,Increase in sympathetic nervous system stimulation, Decrease in parasympathetic nervous system stimulation on the strength of contraction?
Decreases the strength
What is the result of overfilling of the duodenum?
The capacity of the stomach is greater than that of the duodenum, the overfilling of the duodenum by a hypertonic solution results in dumping syndrome; vomiting, bloating, cramps, diarrhoea, dizziness, fatigue, weakness, sweating & electrolyte
Imbalances
What are the natural mechanisms to delay gastric emptying?
- As gastric contents enter duodenum, duodenal pH falls
- Gastric emptying is regulated by the same things that regulates parietal & chief cells
What is gastroparesis?
Delayed gastric emptying
What are the causes and symptoms of gastroparesis?
Causes:
- Idiopathic (cause unknown)
- Autonomic neuropathies e.g. diabetes mellitus
- Abdominal surgery
- Parkinsons disease
- Multiple sclerosis
- Scleroderma (connective tissue disorder)
- Amyloidosis
- Female gender (more common in women)
Drugs can cause gastroparesis: - H2 receptor antagonists
- Proton pump inhibitors
- Opiod analgesics
- Diphenhydramine (Benadryl)
- Beta-adrenergic receptor agonists
- Calcium channel blockers
- Levodopa (Parkinson’s drug)
Symptoms:
• Gastroparesis can cause matter in the stomach to rot and smell and become a similar
appearance to faeces
- Nausea
- Early satiety (feeling full early)
- Vomiting undigested food
- GORD (gastro-oesophageal reflux disease - can be caused by; PREGNANCY,
HIATUS HERNIA (when stomach goes above oesophagus), OBESITY & SMOKING)
- NOTE: a sedentary lifestyle does not increase the risk of acid reflux
- Abdominal pain/bloating
- Anorexia (loss of appetite)
How much water enters the small intestine per day?
Approx 8000ml
What percentage of water is reabsorbed in the small intestine?
Approx 80%
Of the remaining water that passes to the large intestine, what percentage is reabsorbed? What happens to the remaining water?
Approx 98%, the final 2% is excreted in the stool as about 200ml
Which part of the small intestine absorbs the most water?
Jejunum
Why are such small amounts of water absorbed in the stomach?
Small amounts of water are reabsorbed in the stomach, but the stomach has a much smaller surface area available for diffusion and lacks the solute-absorbing
mechanisms that create the osmotic-gradient necessary for absorbing water
Describe the mechanism of the absorption of the water in the small intestine?
- The epithelial membranes of the small intestine are very permeable to water, and net water diffusion occur across the epithelium whenever a water concentration
difference is established by the active absorption of solutes - Na+ accounts for most of the actively transported solutes because it constitutes the
most abundant solute in chyme - it is actively transported from the lumen in the
cell membranes of the ileum & jejunum - Luminal membrane transport is variably coupled glucose, amino acids or other
substances
Describe the mechanism of the absorption of the water in the colon?
- The contents are iso-osmotic (concentration in lumen of colon = that of blood) in the
colon so Na+ is actively pumped from the lumen and water follows - Potassium reabsorption: In general K+ reabsorption is by passive diffusion, the
net movement begin determined by the potential difference between the lumen and
intestinal capillaries. Note: Diarrhoea can result in severe hypokalaemia (loss of K+) - Chloride reabsorption: Cl- is actively reabsorbed in exchange for bicarbonate -
resulting in the intestinal contents becoming more alkaline
Describe the absorptive state?
- During which ingested nutrients enter the blood from the GI tract
- During this state, some of the ingested nutrients provide the energy requirements of the body and the remainder is added to the body’s energy stores to be called upon during the next postabsorptive state
Describe the postabsorptive state?
- During which the GI tract is empty of nutrients and the body’s own stores must supply energy
Where are vitamin B and C absorbed and what is the process?
absorbed by diffusion or mediated transport in the JEJUNUM
Where is Vitamin B12 absorbed and what is the process?
vitamin B-12, which is a very large and charged vitamin. To be absorbed B-12 must first bind to the protein intrinsic factor (secreted by
parietal cells of the stomach) - intrinsic factor whit bound B-12 then binds to specific sites on the epithelial cells in the LOWER PORTION OF THE ILEUM
where vitamin B-12 is absorbed via endocytosis.
• Vitamin B-12 is needed for erythrocyte formation and a deficient in B-12 can lead to pernicious
anaemia and is usually caused due to a deficiency in intrinsic factor
How long will the energy stores of glycogen, lipid, and tissue protein last?
Glycogen: 12 hours
Lipids: sufficient to last 3 months
Tissue Protein: Only becomes significant in times of prolonged starvation
What fuel can be used by the brain?
Glucose, ketone bodies
What fuel can be used by muscle?
glucose, ketone bodies (in starvation), triacyglycerol & branched-chain amino acids
What fuel can be used by the liver?
amino acids, fatty acids (including short chain acids), glucose & alcohol.
NOTE: ketone bodies are not used by the liver, although they are produced here
they are then sent to extrahepatic tissue to buy used there, the liver cannot use ketone bodies for fuel due to the fact they do not have the enzyme thiolase
What fuel can be used by the kidney?
glucose & ketone bodies (cortex), only glucose (medulla)
What fuel can be used by the small intestine?
ketone bodies (mainly in starvation), glutamine (amino acid)
What fuel can be used by the large intestine?
short-chain fatty acids, glutamine
What is the Basal Metabolic Rate?
Minimum amount of energy required to keep the body alive
• Usually measured by O2 consumption in a person who is awake, restful and faster
for 12 hours
• BMR decrease with age
• Measure in kcal expended/hr/m2
Equations used across the UK:
• Harris Benedict Equations (1919)
• Schofield Equations (1985)
• Henry equations (2005)
Rough estimate: ~1kcal/kg body mass/hour
What are the conditions essential for measuring BMR?
What must be stated if these conditions are not met?
Post-absorptive (12 hour fast) Lying still at physical and mental rest Thermo-neutral environment (27 – 29oC) No tea/coffee/nicotine/alcohol in previous 12 hours No heavy physical activity previous day Establish steady-state (~ 30 minutes)
If any of the above conditions are not met, we may refer to Resting Energy Expenditure (REE) or Resting Metabolic rate (RMR)
What factors cause BMR to decrease?
Age- Increasing
Gender- Females have lower rate
Dieting/Starvation
Hypothyroidism
Decreased Muscle mass
What factors cause BMR to increase?
Increasing Body Weight
Fever/infection/chronic disease
Low ambient temperature
Hyperthyroidism
What is the storage, function, source, and effect of deficiency of Vitamin A?
Storage:
Fat Soluble
Store in ito cells in the space of Disse of the liver
Functions: • Cellular growth & differentiation • Process of vision (retinal pigments) • Healthy skin • Reproduction • Embryonic development • Maintenance of bodies mucus membranes • Used in lymphocyte production - immune system
Sources: • Liver • Dairy products • Oily fish • Margarine
Deficiency: • Night blindness • Xerophthalmia (eye fails to produce tears) • Growth retardation • Keratinisation of epithelia • Impaired hearing, taste & smell • Increased susceptibility to infection
What is the storage, function, source, and effect of deficiency of Vitamin C?
Storage:
Water Soluble
Function:
• Synthesis of; collagen, neurotransmitters & carnitine (used in beta-oxidation)
• Antioxidant ability - can donate electrons to radical O2 compounds
• Absorption of non-haem (plant based) iron
Source: • Citrus fruits • Green leafy vegetables • Potatoes • Kidney
Deficiency:
• Initial signs are non-specific
• Weakness
• Bleeding gums
• Hyperkeratosis (thickening of outer layer of skin)
• 50 - 100 days without Vitamin C = signs of scurvy
What is the storage, function, source, and effect of deficiency of B Vitamins?
Storage:
Water soluble
Function:
Important in cell metabolism & energy production
- Main one is B-12 For absorption, intrinsic factor is required which is produced by the parietal cells of
the stomach
Source:
found in fish, poultry, meat & eggs
Deficiency:
Deficiency results in less erythrocyte formation - pernicious anaemia
- B-12 is absorbed in the terminal ileum
What is the storage, function, source, and effect of deficiency of Vitamin D?
Storage:
Fat Soluble
Function:
- Vitamin D3 (cholecalciferol) is formed by the action of ultra-violet (UV) radiation from sunlight on a cholesterol derivative in the skin
- Vitamin D2 is derived from plants
- Both these are collectively referred to as Vitamin D
- Its metabolised by the addition of hydroxyl groups, first in the liver and then in certain kidney cells, the end result of these changes is 1,25-dihydroxyvitamin D
(1,25-(OH)2D) - the active hormonal form of vitamin D
- Functions of 1,25-(OH)2D:
• Its major action is to stimulate intestinal absorption of Ca 2+ and phosphate
Source:
Sunlight and plants
Deficiency:
• Major consequence is decreased intestinal Ca2+ absorption resulting in a
decreased plasma Ca2+
• This decrease in detected via a plasma membrane Ca2+ receptor in the
parathyroid glands (embedded in the posterior surface of the thyroid gland)
• Resulting in the parathyroid glands releasing PARATHYROID HORMONE (PTH)
which exerts multiple actions that increase extracellular Ca2+ concentration:
1. It directly increases the resorption of BONE by osteoclasts, which causes
Ca2+ & phosphate ions to move from bone into the extracellular fluid - this
can lead to a decrease in bone mass - osteoporosis (higher incidence of
bone fractures etc.)
2. It directly stimulates the formation of 1,25-dihydroxyvitamin D which then
increases intestinal absorption of Ca2+ & phosphate ions, thus the effect of
PTH on the intestines is indirect
3. It directly increases Ca2+ reabsorption in the kidneys, thereby decreasing
urinary Ca2+ excretion
4. It directly decreases the reabsorption of phosphate ions in the kidneys
thereby increasing its excretion in the urine - this keeps plasma phosphate
ions from increasing when PTH causes an increased release of both Ca2+ &
phosphate ions from the bone and an increased production of 1,25-
dihydroxyvitamin D leading to calcium & phosphate ion absorption in the
intestine
Liver storage prevent deficiency for 3-4 months
What is the storage, function, sources, and effect of deficiency of vitamin E?
Storage:
Fat Soluble
Function:
Main function is as an antioxidant
Source:
plant oils – such as rapeseed (vegetable oil), sunflower, soya, corn and olive oil.
nuts and seeds.
wheatgerm – found in cereals and cereal product
Deficiency:
Vitamin E deficiency can cause nerve and muscle damage that results in loss of feeling in the arms and legs, loss of body movement control, muscle weakness, and vision problems. Another sign of deficiency is a weakened immune system
What is storage, function, source, and effect of deficiency of Vitamin K?
Storage:
Fat Soluble
Function:
Main function is that is is essential for the production of clotting factors (10,9,7 & 2) in the liver
Source:
green leafy vegetables – such as broccoli and spinach. vegetable oils. cereal grains.
Deficiency:
Vitamin K deficiency results from extremely inadequate intake, fat malabsorption, or use of coumarin anticoagulants. Deficiency is particularly common among breastfed infants. It impairs clotting.
What is malabsorption?
The inadequate absorption of nutrients from the intestines
• Failure to absorb certain vitamins, minerals, carbohydrate, proteins or fats
• Chiefly caused by disease of the small bowel
What is Giardiasis?
infection which causes the villi to atrophy thus reducing absorption capacity
