small intestine pancreas Flashcards
Three main segments of the small intestine:
duodenum, jejunum and ileum
The surface area of the small intestine are covered by VILLI, the villi are covered by the intestinal epithelial cells which are called ___
enterocytes
The enterocytes further increase the surface area through the presence of ___ —- provides a great advantage for fast absorption of nutrients
microvilli
There are also invaginations called ___, which function as a nursery and they contain the stem cells which constantly divide and differentiate.
they then travel up to the tip of the villus before they undergo programmed cell death or apoptosis, and shed to the lumen to be replaced by the newly differentiated epithelial cells. This takes about __ days.
crypts
3
In the epithelial we have several cell types :
Absorptive epithelial cell
Enteroendocrine cells
Goblet cells
enterocytes which specialize to absorb the nutrients
Absorptive epithelial cell
this epithelial cell secrete various hormones into the blood
Enteroendocrine cell
produce mucous, which has very important protective functions.
Goblet cells
___ cells do not migrate up to the vilus but after differentiation they stay at the bottom of the crypt and it has been suggested that they function to protect the stem cells in the cypts against various bacterial toxins and viral factors
Paneth
Each vilus is supplied by a arteriole which in turn branches in the vilus pore into capillary network. And then capillaries join to form the venules, which is away from the vilus. In addition, in each vilus pore we have lymphatic vessels which is called the ___ ___
central lacteal
Most of the absorbed nutrients enter the capillary network and they enter blood circulation directly. However, the fats are too large to be absorbed directly into the capillary network, instead they first go into the ______ so the fats 1st enter the lymphatic circulation and then they join the venus circulation through the thoracic duct
lymphatic lacteal
____ cells produce a large amount of mucous. The mucous covers the intestinal epithelium and protects it against shear stress and microbial damage
goblet cells
one of the most important glycoproteins produced by the goblet cells is ____
Mucins MUC
____ can bind to the potential pathogenic bacteria and it prevents the colonization of the intestinal lumen by the dangerous bacteria.
Mucin MUC
____ ___ seal the space between epithelial cells and prevent the passage of substance via paracellular pathways between the cells
Most agents enter by crossing the epithelial cell membrane using the specialized membrane transporters
Tight junction
refers to the collection of disorders and conditions idiopathic associated with chronic gastrointestinal tract inflammation.
Inflammatory Bowel Disease (IBD)
The two major forms of inflammatory bowel disease are:
Ulcerative colitis
Crohn’s disease
___ is confined to the colon. The inflammation is diffused and only affects the mucosal layer
____ can affect any area of the digestive tract; inflammation is also discontinuous, so we can have skipped lesion where one area has inflammation and the next to it there isn’t any inflammation–
. Inflammation is also more severe bc it not only affects the mucosal layer but the sub-mucosal layer
Ulcerative colitis
Crohn’s disease
Common symptoms inflammatory bowel disease include:
abdominal pain, rectal bleeding, diarrhea, various nutritional deficiencies such as iron deficiency and weight loss
Patients can also have inflammation of the bile ducts (cholangitis) or arthritis or inflammatory conditions of the eyes
When tight junctions are leaky some bacteria products and dietary antigen in the lumen can pass through the tight junctions and enter the \_\_\_\_ \_\_\_. ---- which initiates an immune respnse The APC (antigen presenting cells)and dendritic cells can pick up various antigens which cause the differentiation of t cells and production of various pro-inflammatory \_\_\_
lamina propria
cytokines
are two pro-inflammatory cytokines which have been suggested to be involved in the pathogenesis of IBD
Interferon gamma and TNF-alpha
Signaling events triggered by IFNy and TNFa they cause further opening of the ___ ___, so they further compromise the tight junction barrier. As a result there’s more flux of the bacteria and various antigen from the lumen to the lamina propia which further amplifies the inflammatory response. (chronic inflammation is established)
tight junctions
the disruption of the gastrointestinal barrier leads to the over aggressive immune response of ___ —happens mostly in individuals that are genetically pre-dispose
Tcells
the combination of 3 factors are necessary for chronic inflammation in IBD
Genetic predisposition
Environmental triggers
Over aggressive immune response
therapeutic options for IBD
Aminosalicylates Corticoidsteroid Immunomodulator Biologic agents Antibiotics
1st line therapy for mild to moderate ulceraliphilits ; sometimes used to treat crohn’s disease; the exact mechanism of action is not well understood
Aminosalicylates
been used to treat patients with IBD, however, they are not used to maintain remission bc corticoidsteroids are associated with severe side effects.
Corticoidsteroid
were originally developed as immunosuppressant’s for organ transplant therapy, and has been used as cytotoxic agent in cancer therapy, but are also being used to manage IBD; mostly used with patients that don’t respond to aminosalicylates
Immunomodulator
specific pro-inflammatory cytokines which have been shown to be involved in IBD pathogenesis.
targets are TNFa agent and a4 integrins
Biologic agents
used for the manipulation of colonial bacteria seem to be beneficial for some patients.
are mostly used to treat crohn’s disease in patients with mild and moderate symptoms
Antibiotics
is the 1st line therapy for patients with mild to moderate ulcerative colitis as well as for management of patients with crohn’s disease.
Mesalamine (5ASA) (amino salicylate acid)
agent of 5ASA which showed improvements of the gastrointestinal symptoms in the patients who also had ulcerative colitis
Sulfasalazine
a good example oral administer drugs which is absorbed only in the distal gastrointestinal tract in the colon. it happens bc the chemical link between sulfapyridne and mesalamine prevents the absorption of ___ in the gastrointestinal tract, but then the colonic bacteria can breakdown this chemical link and then both components can be absorbed
Sulfasalazine
sulfasalazine
there are delayed released mesalamine capsules called ___ , which importantly, it is released and absorbed at the whole length of the digestive tract starting in the stomach.
PENTASA
There’s also the pH sensitive release tablet called _____, which is released and absorbed in the ileum
ASACOL / LIALDA
Mesalamine is a salicylate like aspirin, but its therapeutic effects are not related to ____ inhibition. In fact aspirin and NSAIDs can aggravate the symptoms of IBD. In addition NSAIDs are not recommended to individuals with active gastro intestinal inflammation
cyclooxygenase
____ seem to be the center of pro-inflamamtory cytokines, so when its released it further compromises the integrity of tight junction barrier , amplifying inflammation
TNFa
The inhibition of ___ is an effective approach to reduce the inflammation in IBD patients
TNFa
Current anti-TNFa available are:
—they are the monoclonal antibody against TNFa
infliximab, adalimumab, certolizumab
Inflammation in IBD is also amplified by trafficking of ___ from the blood circulation into the gastro intestinal tract
lymphocytes
____ are a family of signaling molecules which are located on the membrane of leukocytes and where it can bind to specific integrin receptors on the membrane of the endothelial cells of the blood vessels, and migrate from the blood circulation into the surrounding tissue to the site of inflammation
Integrins
inhibition of ___ signaling can prevent the migration of lympocytes
integrins
an anti-integrin monoclonal antibody, which targets several integrins on the lymphocyte membrane. However, during clinical trials patients taking this drug developed a severe disease called multilocal leukoencephalopathy
After further review, it was brought back, and its approved and used for the treatment of moderate to severe ___ disease
Natalizumab
crohn’s
multilocal leukoencephalopathy
fatal viral disease of the white matter of the brain
___ induces the differentiation of Tcells and initiation of the whole flammatory signaling
This is why suppresion and inhibition of ____ is an effective strategy to reduce inflammation in IBD patients
Interleuin12
interleukin12
Some anti-IL12 developed are
ustekinumab, briakinumab, apilimod
___ therapy remains the most effective biological therapy for management of IBD — however due to high risk of infection, -it is mainly used on patients that have no responds to other treatment
TNFa
After the meal, there are two major spasms of motility
segmentation contraction and peristalsis contraction
Between meals, “housekeeping” contractions, also called ____ propagate from the stomach through the entire small intestine, sweeping it clear of debris
migrating motor complex
the ___ has both endo and exocrine part-
pancreas
The endocrine part of the pancreas, which is the isle of langerhans produces
insulin and glucagon
The exocrine cells of pancreas are ___ cells connected to the system of the ducts and they eventually form the pancreatic duct and empty into the duodenum.
acinar
___ cells produces pancreatic juices which is rich in digestive enzymes. The pancreatic digestive enzymes they can breakdown and digest virtually all nutrients present in our food
acinar
pancreatic duct cells they secrete the ___ juice which is rich in bicarbonate. This ___ help neutralize the acid in the duodenum that s coming from the stomach
alkaline
alkaline
The main pancreatic duct joins the common bile duct to form a common excretory duct, which is guarded by the sphincter of ___.
Oddi
Exocrine pancreatic secretions and bile enter the __ when the sphincter of Oddi is relaxed.~1–2 L of pancreatic juice is secreted per day.
both pass through hepato-pancreatic ampula also known as ampula of vater before they enter the __
duodenum
duodenum
The enzymes produced by the acinar cells are synthesized in the inactive form as precursors and are called ___ which are stored in specific granules in the apical domain of the cell and they are just waiting for a specific signal to be released
zymogens
are secretagogues that stimulate exocytosis of zymogens into the acinar lumen (act by causing an increase in cytosolic Ca 2+).
Acetylcholine (ACh) and cholecystokinin (CCK)
a gastro intestinal hormones produced by the enteroendocrine cells of the small intestine
cholecystokinin CCK
One of the most important zymogens produced by the pancreatic asinar cell is
trypsinogen
is converted into its active form tyrpsin by brush border enteropeptidases
Once actived the trypsin can convert all other zymogens into their active form
Trypsinogen
the most important pancreatic enzymes are
trypsin, chymotrypsin carboxypeptidase lipase amylase ribonuclease deoxyribonuclease
regulates the function of many other zymogens
trypsin
are proteolytic enzyme so it digest the proteins, breaks the peptide bonds and converts the protein into a very small peptide to two or three amino acids
Trypsin and chymotrypsin
it digests the complex carbohydrate into disacharrides or monosacharrides
pancreatic amylase
Ribonuclease and deoxyribonuclease digest
RNA and DNA
its almost the only enzyme that is secreted through the digestive tract which is able to efficiently digest fat
Pancreatic Lipase
when ph in the duodenum falls due to the chyme, this acidic chyme stimulates specific entero endocrine cells which release the hormone ___
SECRETIN
The secretin released in the duodenum is released into the blood circulation and then it reaches the pancreatic ducts cells where it stimulates them to produce the high amount of ___ __ rich juices. When this juice is emptied into the duodenum, it helps to increase the pH
alkaline bicarbonate
Then the presence of the fatty and protein rich chyme stimulates another type of enteroendocrine cell to release the hormone ____
CCK cholecystokinin
CCK is released into circulation and then with the blood flow it reaches the pancreatic __ cells and it stimulates them to produce high amounts of juice in the digestive enzymes so that the fat and protein in the duodenum can be digested as soon as and as effectively as possible
acinar
common cause of pancreatitis is
gallstones
Both the bile and pancreatic juices, they pass through the common ___ ___ (ampoule) before they enter the duodenum. So if gallstones block this duct, it blocks not only the bile flow but also the flow of pancreatic juice.
The pancreatic juice can reflux back along with bile to the pancreas and causes the damage of pancreatic cells and the release of pancreatic enzymes which causes the ___ of the pancreatic and the surrounding tissue
secretory duct
auto-digestion
small amounts of pancreatic enzymes leave into the circulation due to blockage by gallstones
In ___ ___ the blood levels of pancreatic amylase and pancreatic lipase increase substantially, this is why increased plasma levels of pancreatic enzymes can be used to diagnose acute pancreatitis
acute pancreatitis
The release of pancreatic lipase in the surrounding fat tissue can cause __ __
fat necrosis
__ ___ can be very painful and is characterize by pain in the middle abdominal region which can radiate to the back. This pain can be alleviated by leaning forward
Acute pancreatitis
Two major causes of pancreatitis is ___ and __
gallstones
alcohol
can change the composition of the pancreatic juice and make it more viscous so the protein flux can form within the pancreatic ducts causing the rupture of the pancreatic ducts and subsequent development of pancreatitis
It also changes the normal motility of the sphincter of Oddi
Alcohol
Endocrine dysfunction can lead to the development of ___ ____
Exocrine dysfunction can lead to pancreatic exocrine insufficiency __ (deficiency in pancreatic digestive enzyme)
pancreatic diabetes
PEI
Nutrients are not absorbed and this leads to malnutrition, gradual weight loss, and steatorrhea (fat in stool) —- managed by lowfat diet as well as the pancreatic enzyme replacement therapy PERT
Exocrine dysfunction PEI
3 major pancreatic enzymes
amylase, lipase, proteases
Pancreatic __ is the most sensitive to acidic environment and degradation, this is why fat mal-absorption occurs earlier in patients with exocrine insufficiency
lipase
3 drugs associated with the highest risk of pancreatitis
Azathioprine
Mesalamine/Olsalazine
Simvastin (lowers cholesterol)
an immuno-modulating agent. Acts by inhibition of proliferation and activation of lymphocytes, so its used as an immunosuppresant in organ transplant therapy, also used in cancer patients, and manage patients with IBD
Azathioprine
Groups of patients at risk of drug induced pancreatitis
Pediatric Elderly Females HIV Patients with Inflammatory Bowel Disease
is the hormone that’s release by the entero-endocrine cells of the small intestine in response to a meal.
can stimulate the beta cells of the pancreas which secrete insulin and inhibits the function of alpha cells which secrete glucagon, therefore increasing the insulin production and accordingly decreases the blood glucose levels which is beneficial for patients with diabetes
Glucagon-Like Peptide-1 (therapy for type 2 diabetes)
GLP1 degraded by enzyme ____ enzymes
DPP4
enhance of β-cell proliferation, inhibit of β-cell apoptosis and promote differentiation of adult stem cells in the ductal pancreatic epithelium.
GLP-1–induced pathways
Chronic GLP-1 receptor activation induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic __ and chronic pancreatitis
lesions
