PBL 3 Flashcards
What is pancreatic juice composed of?
Pancreatic digestive enzymes
Sodium bicarbonate solution
Water
What are the different types of pancreatic enzymes?
Pancreatic alpha amylase
Pancreatic lipase
Nucleases
Proteolytic enzymes
What are the proteolytic proenzymes secreted in pancreatic juice?
What are they converted to in the small intestine?
Trypsinogen - trypsin
Chymotrypsinogen - chymotrypsin
Procarboxypeptidase - carboxypeptidase
Proelastate - elastase
What causes proteolytic enzymes to be converted to their active form in the small intestine?
Enterokinase - causes activation of trypsin
Trypsin - causes activation of all other proteolytic enzymes
Where is trypsin inhibitor found and what is its purpose?
Produced in the cytoplasm of glandular cells and released from the same pancreatic cells that secrete proteolytic enzymes into the acini
It prevents the activation of pancreatic proteolytic enzymes until they reach the intestine to ensure they do not self digest the pancreas
How are bicarbonate ions and water secreted into the pancreatic duct by ductular cells?
Carbon dioxide diffuses into duct cells and is converted into bicarbonate and hydrogen ions via carbonic anhydrase
Hydrogen ions are exchanged for sodium at basolateral membrane
Sodium and bicarbonate ions are actively transported into the duct lumen
Water moves across into the duct lumen via osmosis
Share are the 3 basic stimuli of pancreatic secretion
Ach from nerve endings
CCK from enteroendocrine cells in duodenum
Secretin from duodenum
What are the three phases of pancreatic secretion?
What percentage of enzyme secretion occurs in each stage?
Cephalic stage (20%) Gastric phase (5-10%) Intestinal phase (50-80%)
What phase of pancreatic secretion are secretin and CCK released in?
Intestinal phase
What effect does secretin have in the intestinal phase of pancreatic secretion
Released as prosecretin from S cells in the duodenum
Converted into secretin by acidic HCL
Secretin travels to the pancreas, causing high concentrations of bicarbonate ions to be secreted in acini
Why are bicarbonate ions secreted alongside digestive enzymes in pancreatic juice?
They provide an appropriate slightly alanine pH of 7-8 which is what pancreative enzymes work best at
What effect does CCK have in the intestinal phase of pancreatic secretion?
Food in the duodenum causes CCK to be released from I cells
CCK passes to the pancreas, binding to CCKA receptors causing secretion of pancreatic digestive enzymes by the acinar cells
What are the enzymes responsible for carbohydrate digestion in brush border of the small intestine?
Pancreatic alpha amylase - breaks up starch into maltose
Maltase - breaks up maltose into glucose monomers
Lactase - breaks up lactose into galactose and glucose
Sucrase - breaks up sucrose into fructose and glucose
How does emulsification of fat occur?
Bile secreted from the liver is soluble in fat and in water
The fat soluble portion of bile salts dissolve into the surface layer of the fat globules
Lecithin makes the fat globules readily fragmentable by agitation with the water
This increases the surface area of fatty droplets
What is the enzyme responsible for Fat Digestion in the small intestine?
Pancreatic lipase
What are triglycerides split into by pancreatic lipase?
Free fatty acids
2-monoglycerides
What is the role of bile salts in removing fat digestion products from the GI lumen?
Bile salts form Micelles due to sterol nucleus that is highly fat soluble and polar group which is water soluble
Bile salt micelles act as a transport medium to carry the fat digestion products to the brush border of intestinal epithelial cells
Bile salts are then released back into gut lumen to be used again and again
How much water is absorbed in the intestine each day?
Where does this take place
8.4L of water is absorbed each day
- 5L - small intestine
- 9L - large intestine
How much water is excreted in feces each day?
100mL roughly
How does water reabsorption occur?
Via osmosis - following nutrient reabsorption
Via junctional complexes between cells
Via SGLT1 & a.a. Transporters
How does absorption of glucose occur at the brush border membrane in the intestine?
Na/K+ ATPase pump, pumps out sodium on basolateral membrane, setting up a sodium gradient
Na+ is brought into enterocyte, by SGLT1, which brings glucose in with it via secondary active transport at the apical membrane
Glucose diffuses out of the basolateral membrane into the blood stream via GLUT2 transporter
How is galactose absorbed by the epithelial cells of the small intestine?
Na/K+ ATPase pump, pumps out sodium on basolateral membrane, setting up a sodium gradient
Na+ is brought into enterocyte, by SGLT1, which brings galactose in with it via secondary active transport at the apical membrane
Galactose diffuses out of the basolateral membrane into the blood stream via GLUT2 transporter
How is fructose absorbed in the epithelium of the small intestine
Facilitated diffusion through:
GLUT 5 on apical membrane
GLU2 2 on basolateral membrane
Which transporter is mutated in glucose-galactose malabsorption syndrome?
SGLT1
How are fats absorbed into the blood stream once they reach intestinal epithelial cells
Once fatty acids and monosaccharides are absorbed they are resynthesised into TCAs and packaged into chylomicrons
Chylomicrons are transported in lateals to the liver
What are short chain fatty acids and where are they produced?
How are they absorbed?
SCFAs are butyrate, propionate, acetate
They are produced by bacterial fermentation in the colon
They are absorbed in the colon by SMCT1 transporter
What are the two proteolytic brush border membrane enzymes?
Dipeptidase
Aminopolypeptidase
How are di and tripeptides absorbed by the enterocytes?
Co transport with H+
How are most amino acids absorbed by enterocytes?
Co transport (secondary active transport) with sodium
Different amino acids have different transporter classes
How does sodium absorption occur in the intestines?
Na/K+ gradient is set up on basolateral membrane
Na+ moves into intestinal epithelium down the concentration gradient
How are chloride ions absorbed by the small intestine?
Absorption of Na+ sets up an electrochemical gradient
Cl- ions follow and are passively dragged by the positive electrical charges of the sodium ions
How does aldosterone effect sodium absorption?
Aldosterone enhances sodium absorption by increasing the activity of the enzymes and transport mechanisms for all aspects of sodium absorption by the intestinal epithelium
How does bicarbonate ion Reabsorption in the intestine occur?
Bicarbonate ion absorption occurs in an indirect way
H+ ions are secreted into the lumen in exchange for sodium
H+ combine with bicarbonate to form carbon dioxide + water
Carbon dioxide is then readily absorbed into blood
What are the two routes for calcium absorption?
Paracellular - between epithelial cells
Transceullar - enters through TRPV6, binds to calbindin and moved to the basolateral membrane where it is removed by calcium pump ATPase
How does iron absorption occur in the duodenum?
Fe3+ is reduced to Fe2+ by Dcytb
DMT co transports Fe2+ into cells with H+
Fe2+ transfers to mobilferrin
Fe2+ leaves cell at basolateral membrane via ferroportin (FP1)
How is iron absorption regulated by hepcidin?
Hepcidin is produced by the liver in response to high iron levels
Hepcidin binds to ferroportin and blocks iron absorption at the basolateral membrane
How much is in 1 unit of alcohol?
10mL or 8g pure ethanol
What is the recommend safe limit of drinking per week for men and women?
14 units
Spread over 3-4 days, with 2-3 alcohol free days
Where is alcohol metabolised and by which enzymes?
In the stomach - by alcohol dehydrogenase
In the liver - by cytochrome p4502E1
Both these convert ethanol into Acetaldehyde
Acetaldehyde is further metabolised to acetate in mictochondria by aldehyde dehydrogenase
What are the positive effects of alcohol? (At low levels)
CNS stimulant - binds to GABA receptors and causes sedation
Protective against atheroma
Reduced cardiovascular risk
What are the two screening approaches used to detect alcoholism?
CAGE
AUDIT
What are the 3 main causes of acute pancreatitis?
Idiopathic
Gallstones
Alcohol
How can alcohol lead to acute pancreatitis?
Causes secretion of pancreatic enzymes without bicarbonate and water - so pancreatic juice becomes thick and forms plugs which block the ducts
Activation of pancreatic enzymes leads to auto Digestion
Alcohol also causes inflammation of the pancreas
How do gallstones lead to acute pancreatitis?
Block the ampulla of vater, occluding pancreatic drainage
What are the clinical signs of acute pancreatitis?
Severe epigastric pain that radiates to the back
Increased serum amylase or serum lipase (3x upper limit of normal)
How is acute pancreatitis managed?
Pain management
Fluid resuscitation
Feeding
Prophylactic antibiotics
How can pancreatitis lead to psudocysts
Inflammatory response causes rupture of blood vessels
Digestion and bleeding can liquefy the pancreatic tissue
When fibrous tissue surrounds this liquefactive necrotic tissue it forms a cavity that fills up with pancreatic juice
This is known as a pseudocyst
What are the complications of acute pancreatitis?
Haemorrhage
Shock
Respiratory distress
What is acute pancreatitis?
Sudden inflammation caused by destruction of itself by its own digestive enzymes
What is the difference between acute and chronic pancreatitis?
Acute is autodigestion and is reversible
Chronic is caused by changes to structure which is irreversible
What is the leading cause of chronic pancreatitis in children?
Cystic fibrosis
What is the pathophysiology of chronic pancreatis
Repeat attacks of acute pancreatitis lead to the healthy pancreatic tissue being replaced by:
- misshaped ducts
- fibrosis
- calcium deposits
How does alcohol contribute to chronic pancreatitis?
Alcohol metabolism is by CYP450 enzymes which produce reactive oxygen species as a by product
These can damage acinar cells, ductal cells and stellate cells of pancreas
Damage leads to cell death, calcification and fibrosis
What are the clinical features of chronic pancreatitis?
Pain - beginning in the epigastric region and radiating to the back
Malabsorption
Weight loss
Steatorrhoea
Diabetes - in severe chronic pancreatitis
How is chronic pancreatitis diagnosed?
Faecel elastase stool test - will be lowered in patients
CT/MRI - imaging the pancreas
Endoscopic ultrasound - when CT/MRI is unsuccessful
How is chronic pancreatitis managed?
Treat pain - using opiates/NSAIDs
Pancreatic enzyme supplements - pancreatin
What kind of cancer can chronic pancreatitis lead to?
Pancreatic adenocarcinoma
How does alcohol metabolism lead to fatty acid synthesis?
Alcohol is metabolised by alcohol dehydrogenase
Alcohol dehydrogenase uses NAD+ as a co factor
Alcohol metabolism therefore increases the NADH/NAD ratio
Increased NADH results in increased fatty acid synthesis
How does alcohol cause toxicity?
Broken down into acetaldehyde which is a toxic metabolite
Alcohol metabolism results the production of ROS
What is steatosis?
Acute fatty liver change due to alcohol
Accumulation of fat leads to holes in the liver tissue
What are the three enzymes which metabolise alcohol into Acetaldehyde?
Alcohol dehydrogenase
Cytochrome P450 2E1
Catalase
How can alcohol lead to alcoholic hepatitis?
Alcohol metabolism leads to over production of Acetaldehyde
Acetaldehyde forms Acetaldehyde adducts
These are recognised as foreign by the body
Infiltration of immune cells leads to hepatic necrosis resulting in hepatitis
What histological changes can be seen in alcohol hepatitis?
Mallory bodies - bundles of proteins which are damaged intermediate filaments located in the cytoplasm of hepatocytes
How does alcoholic hepatitis lead to hepatic fibrosis?
As cells begin to become damaged ad die, scar tissue can begin to form around the veins of the liver
This is called perivenular fibrosis
What biochemical markers can be seen with alcohol hepatitis?
Raised levels of:
ALT, AST, ALP, GGT
This is because they leak out of the damaged liver
What is the HARK questionnaire used for?
To assess for domestic violence
What are the cells found in the liver that result in fibrosis?
Stellate cells
What is acites?
Excess fluid in the peritoneal cavity
What is the difference between an endopeptidase and an exopeptidase?
Endopeptidase - proteolytic peptidases that break down peptide bonds of amino acids within the protein
Exopeptidase - proteolytic enzymes which break peptide bonds from end pieces of terminal amino acids
What is the only exopeptidase secreted from the pancreas?
Carboxypolypeptidase
