the pancreas and small bowel Flashcards
what do liver buds become
the liver lol
what forms when the join between the liver and foregut narrows
becomes the bile duct
what does the bile duct give rise to
the gallbladder and cystic duct
what happens by 11 weeks
the proximal duodenum rotates clockwise and all organs are in place
what happens when the ventral and pancreatic ducts and bud have rotated clockwise
fuses with dorsal duct
what does part of the dorsal and ventral duct become
becomes the main pancreatic duct
what do the bile and pancreatic ducts join to drain together at
at the major papilla
where pancreatic duct emerges at the major papilla - joins up with distal common bile duct to form papilla/ampulla
what duct emerges at the minor papilla and what is it known as
dorsal duct
known as accessory pancreatic duct (can degenerate or is absent as adult)
what kind of an organ is the pancreas
retroperitoneal organ - behind the posterior peritoneum of the abdomen
and doesn’t exist within abdomen
what is in front of the pancreas
transverse colon and stomach (both are anterior to pancreas)
where does the head of the pancreas fit
into duodenum (C shaped and is labelled D1/2/3/4)
what is the superior edge of the pancreas called
coeliac axis
are the main pancreatic duct and the ventral duct fused together
n o
both ducts are separated = pancreas divisum
why do patients get recurrent episodes of pancreatitis
as a large flow has to go through minor duct
what is angiography used for
used for interventional purposes
patients that are bleeding
accessing femoral artery in groin under local anaesthetic to aorta by inserting wire - dye
what does endocrine mean
secretion into the bloodstream to have an effect on distant target organ (autocrine/paracrine) - ductless glands
what does exocrine mean
secretion into a duct to have a direct local effect
what is insulin and what does it do
an anabolic hormone
promotes glucose transport into cells and storage as glycogen
decreases blood glucose
promotes protein synthesis and lipogenesis
what does glucagon do
increases gluconeogenesis and glycogenolysis
increases blood glucose
what does somatostatin do
endocrine cyanide
inhibits almost everything
what is endocrine % and function relative to pancreas
2% of a gland
islets of langerhans
secrete hormones into blood - insulin and glucagon (also somatostatin and pancreatic polypeptide)
regulation of blood glucose, metabolism and growth effects
what is exocrine % and functions
98% of a gland
secretes pancreatic juices into duodenum via MPD (main pancreatic duct)/sphincter of Oddi/ampulla
digestive function
what is pancreatic cell differentiation
formation of acini and islets from ducts in various stages of development
what are acini
attach to ducts
grape like clusters of secretory units
acinar cells secrete pro enzymes into ducts
what are islets
derived from the branching duct system
lose contact with ducts - become islets
differentiate into alpha and beta cells secreting into blood
number of islets is higher in the tail than in the head
what is around a duct (of pancreas)
pancreatic acinus
what does the pancreatic acinus consist of
consists of pancreatic acinar cells
between cells = intercellular canaliculi
draining into pancreatic ducts > intercalated duct > intralobular duct - joins main pancreatic duct
does the islet have connections to ducts and how many capillaries
many capillaries
no connection to duct
how much % do alpha cells form of islet tissue and what do they secrete
15-20%
secrete glucagon
how much % do beta cells form of islet tissue and what do they secrete
60-70%
secrete insulin
how much % do delta cells form of islet tissue and what do they secrete
5-10%
secrete stomatostatin
are the islets highy vascularised
yes
ensuring that all endocrine cells have close access to a site of secretion
what do exocrine pancreatic units (acini) show
secretory acinar cells - large with apical secretion granules
duct cells - small and pale
what are the 2 components of pancreatic juice
produced by acinar cells - low vol and viscous and enzyme rich
produced by the duct and centroacinar cells - high in volume, watery HCO3- rich
where is bicarbonate produced
produced by duct and centroacinar cells
what juice is high in bicarbonate
pancreatic juice
~120 mM (mmol/L) - (plasma ~ 25 mM)
pH 7.5-8
what does bicarbonate do
neutralises acid chyme from stomach
prevents damage to duodenal mucosa
raises pH to optimum range for pancreatic enzymes to work
washes low volume enzyme secretion out of pancreas into duodenum that is produced by acini
what happens when duodenal pH <5
- linear increase in pancreatic HCO3- secretion up to pH3
what happens when duodenal pH <3
- not much more increase in HCO3- secretion
what does bile also contain and what does it do
bile also contains HCO3- and helps neutralise acid chyme (liver functions)
what do Brunner’s glands secrete
alkaline fluid
how is pancreatic HCO3- secreted
CO2 enters pancreatic cell
catalysed by carbonic anhydrase
separation of H+ and HCO3-
NA+ moves down gradient via paracellular (tight) junctions
H2O follows
CL-/HCO3- exchange at lumen (anion exchanger)
NA+/H+ exchange at basolateral membrane into bloodstream (sodium-hydrogen exchanger antiporter) type 1
exchange driven by electrochemical gradients
high EC (blood) Na+ compared to IC (duct cell)
high Cl- in lumen compared to IC (duct cell)
Na+ gradient into cell from blood maintained by Na+/K+ exchange pump
uses ATP - primary active transport
K+ returns to blood via K+ channel
Cl- returns to lumen via Cl- channel (cystic fibrosis transmembrane conductance regulator)
what is the equation for H2O and CO2 and where does this happen
H2O + CO2 ←→ H2CO3 ←→ H+ + HCO3-
same reaction in gastric parietal cells (acid) and pancreatic duct cells (alkaline)
what happens in the stomach in terms of HCO3- and H+
H+ secreted into gastric juice
HCO3- secreted into blood
gastric venous blood is alkaline
what happens in the pancreas - in terms of HCO3- and H+
HCO3- secreted into pancreatic juice
H+ secreted into blood
pancreatic venous blood is acidic
what enzymes break down fats
lipases
what enzymes break down proteins
proteases
what enzymes break down carbohydrates
amylases
where are lipases/amylases/proteases synthesised and stored
in zymogen granules of acinar cells
what are zymogens
pro enzymes - inactive forms of subsequent enzymes
why are proteases released as inactive proenzymes
to protect the acini and ducts from autodigestion
what prevents trypsin activation in the pancreas
trypsin inhibitor
where are enzymes activated
duodenum
what might blockage of the main pancreatic duct cause
overload protection > auto digestion
acute pancreatitis
what does duodenal mucosa secrete
enzyme called enterokinase (enteropeptidase)
what does enterokinase/enteopeptidase do
converts trypsinogen to trypsin (active form)
what does trypsin do
converts all other proteolytic and some lipolytic enzymes
trypsinogen > trypsin
chymotrypsinogen > chymotrypsin
proelastase > elastase
procarboxypeptidase A > carboxypeptidase A
procarboxypeptidase B > carboxypeptidase B
how is lipase secreted and what does it require
it is secreted in its active form but requires colipase (ie secreted as a precursor)
what do lipases require for effective action
presence of bile salts
what can a lack of pancreatic enzymes (+bile) cause
malnutrition even if dietary input is reasonable
what does the anti obesity drug orlistat do and side effects
inhibits pancreatic lipases
side effects:
increased faecal fat
occurs when pancreatic lipase secretion decreased
cystic fibrosis, chronic pancreatitis, orlistat (decreases intestinal fat absorption)
steatorrhoea
what happens in the cephalic phase (control of pancreatic juice secretion)
reflex response to sight/smell/taste of food
enzyme rich component only
low volume - mobilises enzymes
what happens in the gastric phase (control of pancreatic juice secretion)
stimulation of pancreatic secretion originating from food arriving in the stomach
same mechanisms involved as for cephalic phase
what happens in the intestinal phase (control of pancreatic juice secretion)
(70-80% of pancreatic secretion)
hormonally mediated when gastric chyme enters duodenum
both components of pancreatic juice stimulated
enzymes and HCO3- juice flows into duodenum
what is pancreatic juice enzyme secretion controlled by in acini
1) vagus nerve (cholinergic and vagal stimulation of enzyme secretion - and communicates info from gut to brain) acetylcholine
2) cholecystokinin (CCK) (Ca2+/PLC)
pancreatic juice bicarbonate secretion controlled in duct and centroacinar cells by:
secretin (cAMP)
what are some mechanisms responsible for controlling release of CCK from duodenum cells
protein > amino acids > CCK releasing peptide (stimulatory)
fatty acids > CCK releasing peptide (stimulatory)
ACh and gastrin releasing peptide stimulate trypsin which inhibits release of CCK
CCK in bloodstream stimulates pancreas - negative feedback
is acinar fluid isotonic
yes
how does acinar fluid resemble plasma
resembles plasma in its concs of Na+, K+, Cl-, HCO3-
what is secretion of acinar fluid and the proteins inside the fluid stimulated primarily by
CCK (cholecystokinin)
what does secretin do
secretin stimulates secretion of H2O and HCO3- from cells lining extralobular ducts
secretin stimulated secretion is richer in HCO3- cf acinar secretion because of Cl-/HCO3- exchange
what does a decrease in pH in the duodenum do
stimulates S cells to release secretin
secretin stimulates pancreatic/ductal HCO3- secretion (alkaline - increases pH)
CCK alone has no effect on HCO3- secretion but what can it do
can increase HCO3- secretion that has been stimulated by secretin
what has a similar effect to CCK
vagus nerve
what has no effect on enzyme secretion from acinis
secretin
summarise the steps after having a meal
food mixed and digested in stomach pH2
chyme squirted into duodenum
H+ ions in duodenum > increases secretin > increases pancreatic juice
and bile and Brunner’s gland secretions
the two above increases pH to neutral/alkaline
peptides and fat in duodenum causes sharp increase in CCK and vagal nerve stimulation
stimulation pancreatic enzyme release
peaks by 30 mins continues until stomach is empty
CCK potentiates effects of secretin on aq component
necessary as most of duodenum not at low pH
what is the function of the small bowel
absorb nutrients, salt and water
how long is the small bowel
approx 6m
what is the diameter of the small bowel
3.5cm
how long is the duodenum
25cm
how long is the jejunum
2.5m
how long is the ileum
3.75m
is there a sudden transition between the small bowel, duodenum, jejunum and ileum
no
they all have the same basic histological organisation
what is the mesentery
its is a fold of membrane
suspends the small and large bowel from posterior abdominal wall
anchoring them in place whilst still allowing some movement
provides a conduit for blood vessels, nerves and lymphatic vessels
where does the superior mesenteric artery come from and what does it supply
comes out of the inferior border of the pancreas - supplies the jejunum and the ileal via jejunal and ileal arteries
what does the ileocolic artery supply
supplies the terminal ileum and the ascending colon and the caecum
what does the right colic artery supply
the ascending colon
what does the middle colic artery supply
supplies the hepatic flexure, transverse colon and splenic flexure
sends blood vessels down the descending colon
what is the outer covering of the small bowel called
serosa
what is underneath the serosa
longitudinal muscle and circular muscle - important for motility
describe the layers of the digestive epithelium of the small bowel
serosa circular and longitudinal muscle submucosa mucosa lumen
what does the apex of the villus have
microvilli
at the centre = arteries, veins and lymphatic vessels
what do crypts of Lieberkuhn contain
paneth cells
stem cells
what are some properties of villi
they only occur in the small intestine
they are motile
rich blood supply and lymph drainage for absorption of digested nutrients
good innervation from submucosal plexus
have simple epithelium
one cell thick
dominated by enterocytes (columnar absorptive cells)
what is the villi (mucosa) lined with
simple columnar epithelium consisting of
primarily enterocytes (absorptive cells)
scattered goblet cells
enteroendocrine cells
what is the most abundant cell type in the small bowel
enterocytes
what are enterocytes
tall columnar cells with microvilli and a basal nucleus
specialised for absorption and transport of substances
short life span 1-6 days
what do microvilli make up
0.5-1.5 micrometres high
make up brush border
what is the surface of microvilli covered with
glycocalyx
what is glycocalyx
rich carb layer on apical membrane
protection from digestional lumen
but allows absorption
traps a layer of water and mucous = unstirred layer
regulates rate of absorption from intestinal lumen
what are goblet cells
2nd most abundant epithelial cell type
mucous containing granules accumulate at apical end - goblet shape
increase abundance of goblet cells along entire length of bowel
less in duodenum and more in colon
what is mucous
large glycoprotein that facilitates passage of material through bowel
what are enteroendocrine cells
columnar epithelial cells
scattered among enterocytes
most often found in lower parts of crypts
hormone secreting
to influence gut motility
can be referred to as chromaffin cells - affinity for chromium/silver salts
what are paneth cells
found only in bases of crypts
contain large, acidophilic granules
what do the granules in paneth cells contain
antibacterial enzyme - lysozyme (protects stem cells)
glycoproteins and zinc (essential trace metal for a number of enzymes)
also engulf some bacteria and protozoa
may have a role in regulating intestinal flora
what are stem cells
undifferentiated cells which remain capable of cell division to replace cells which die
what are epithelial stem cells for and what do they do
essential in the GI tract to continually replenish the surface epithelium
continually divide by mitosis
migrate up to the tip of the villus - replace older cells that die by apoptosis > digested and absorbed
differentiate into various cell types (pluripotent)
what cells have a rapid turnover rate
enterocytes and goblet cells
due to short lifespan
how are enterocytes related to pathogens
enterocytes are first line of defence against GI pathogens and may be directly be affected by toxic substances in the diet
effects of agents which interfere with cell function, metabolic rate etc will be diminished
describe the duodenum and its functions
distinguished by Brunner’s glands
submucosal coiled tubular mucous glands secreting alkaline fluid
open into the base of the crypts
alkaline secretions of Brunner’s glands
neutralise acidic chyme from stomach - protecting proximal small bowel
help optimise pH for action of pancreatic digestive enzymes
what is more proximal
the jejunum or duodenum
jejunum is most proximal
duodenum > jejunum
which is thicker
jejunum or ileum
and why
jejunum is wider and thicker walled than ileum due to plicae circulares - are larger and more numerous and closely set
where is the jejunal mesentery
- above and to the left of the aorta
where is the ileum mesentery
right and below to the aorta
how many arcades do the jejunal mesentery vessels form
form only one or two arcades - long infrequent branches to intestinal wall
how many arcades does the ileum have
numerous short terminal - about ¾ arcades
what is only found in the lower ileum
Peyer’s patches
what are the functions of small bowel motility (3)
to mix ingested food with digestive secretions and enzymes
to facilitate contact between contents of intestine and the intestinal mucosa
to propel intestinal contents along alimentary tract
what is the process of segmentation (mixing)
mixes contents of lumen
occurs by stationary contraction of circular muscles at intervals
more freq contractions in duodenum cf. ileum
allow pancreatic enzymes and bile to mix with chyme
although chyme moves in both directions, net effect is movement > colon
what is the process of peristalsis (propelling)
involves sequential contraction of adjacent rings of smooth muscles
propels chyme towards colon
most waves of peristalsis only travel about 10cm
segmentation and peristalsis result in chyme being segmented, mixed and propelled > colon
what is the process of migrating motor complex
cycles of smooth muscles contractions sweeping through gut
begin in stomach > small intestine > colon > next wave starts in duodenum
prevents migration of colonic bacteria back into ileum
in what kind of environment does digestion in small bowel occur
alkaline
where do pancreatic enzymes come from and go to
come from MPD and CBD
go to duodenum
what does duodenal epithelium also produce
own digestive enzymes
does digestion occur in lumen and in contact with the membrane
yes
where does digestion begin
digestion begins in mouth by salivary alpha-amylase (destroyed in stomach (acid pH))
where does most of digestion of carbohydrates occur
small intestine
what are 2 examples of simple carbohydrates
monosaccharides - glucose and fructose
what are 2 examples of disaccharides
sucrose and maltose
what are some complex carbohydrates
starch, cellulose, pectins
> sugars bonded together to form a chain
what is secreted into duodenum in response to a meal
pancreatic alpha-amylase
what does pancreatic alpha-amylase do
continues digestion of starch and glycogen in small bowel (started by salivary amylase)
what does pancreatic alpha amylase require
needs Cl- for optimum activity and neutral/slightly alkaline pH
where does pancreatic alpha amylase work
acts mainly in lumen (some also absorbs to brush border)
digestion of amylase products and simple carbohydrates occurs at the brush border
what transport does absorption of glucose and galactose happen by
secondary active transport
what are the 2 carrier proteins on apical membranes
SGLT-1
GLUT-5
what happens at SGLT-1
absorption of fructose is by facilitated diffusion
what happens at GLUT-5
GLUT-2 facilitates exit at basolateral membrane
STEPS for digestion of proteins
protein digestion begins in lumen of stomach by pepsin
pepsin is then inactivated in alkaline duodenum
5x pancreatic proteases secreted as precursors > lumen of small bowel (eg trypsinogen)
trypsin activated by enterokinase - an enzyme located on duodenal brush border
trypsin > activates other proteases
hydrolyse proteins > single amino acids and oligopeptides
what do a variety of peptidases at brush borders of enterocytes do
progressively hydrolyse multi amino acids > single amino acids
what do enterocytes do
directly absorb some of small oligopeptides via action of H+/oligopeptide cotransporter PepT1
STEPS for digestion of lipids
lipids are poorly soluble in water - more complicated to digest
4 stages process in small bowel
1) secretion of bile salts and pancreatic lipases
2) emulsification (increases SA for digestion)
3) enzymatic hydrolysis of ester linkages - colipase complexes with lipase - prevents bile
salts displacing lipase from fat droplet
4) solubilization of lipolytic products in bile salt micelles
unlike amino acids and simple sugars what happens to lipids at enterocytes
they are transformed as absorbed via enterocytes
STEPS for absorption of lipids
1) FAs and MG (monoglycerides) leave micelles and enter enterocytes
2) FAs and MG resynthesized into TGs by 2x pathways :
- monoglyceride acylation (major)
- phosphatidic acid pathway (minor)
3) after resynthesis into chylomicrons - lipoprotein particles synthesised as an emulsion
(80-90% TGs and 8-9% phospholipids, 2% cholesterol, trace carbohydrates) in Golgi
apparatus
4) chylomicrons secreted across basement membrane by exocytosis
5) chylomicrons enter a lacteal (lymph capillary) > lymph transports them away from
bowel
how is the ileum and colon separated
ileum is separated from the colon by the ileocaecal valve
what does the illeocaecal valve do
relaxation and contraction controls passage of material into the colon
also prevents backflow of bacteria into ileum
