digestion and absorption 2 Flashcards
what are the lipids in food?
in our diet :
Triacylglcerides Tags
and cholesterol
cholesterol esters
phospholipids
unesterified free fatty acid FFA
what do lingual and gastric lipase break ?
Break triacylglcerides to 1,2 diacylgylcerides and free FFA
gastric lipase together with lingual lipase work in acidic PH
what secretes gastric lipase ?
Chief cells in the fundal mucosa in the stomach
it has PH optimum for 4-6
Acidic lipases are essential in neonate and patients with insufficient pancreatic function such as in cystic fibrosis
where are dietary fats absorbed ?
in the small intestine
in the duodenum : emulsification of the dietary lipids occurs
how does emulsification occur ?
Lipids are insoluble –> hydrolysis occurs
only at the interfaces —> emulsification increases surface area of lipid droplet
Pancreatic lipase, cholesterol esterase, phospholipases digest lipids
these enzymes are produced in pancreas
these enzymes only digest at the interfaces
to make the digestion more efficient we do Emulsification –> oil and water addition
occur by :
1- bile salts act as detergents , bile salt = bile acid ( steroid nucleus ) + glycin or taurine
2- mechanical mixing due to peristalsis –> forming micelles
how does emulsification occur ?
via conjugated bile salts and mechanical mixing by peristalsis
Bile salts are secreted by the liver to aid emulsification
Bile acids are AMPHIPHATIC
increase the surface area of hydrophobic lipids droplets so the enzymes can act effectively
Micelles facilitate digestion and absorption
how are bile salts synthesized?
From cholesterol then conjugated by amino acids to form bile salts
stored in the gallbladder
after helping in emulsitifaction they are reabsorbed again by hepatic portal vein
what is a cofactor of pancreatic lipase ?
colipase
crucial cofactor for pancreatic lipase
essential for efficient digestion of dietary fats
what is the function of colipase ?
Colipase facilitates the action of pancreatic lipase by anchoring the surface of lipid droplets in the small intestine
what activates colipase ?
Trypsin
Colipase is secreted by pancreas as PROcolipase and activated by trypsin
what is the function of pancreatic lipase?
Removes fatty acids from TAG at carbon 1 and 3 results in :
2 monoacylgycerol and free fatty acid
only 25% of ingested TAG is completely hydrolysed to glycerol and FFA before absorption
what is orlistat ?
Anti obesity drug that inhibit gastric and pancreatic lipase
thereby decreases fat absorption
what happens in cystic fibrosis ?
Pancreatic lipase deficiency —> significant malabsorption
what is phospholipase A2?
enzyme secreted by pancreas into the intestine
hydrolyzes the ester linkage between the fatty acid and hydroxyl on carbon 2 of PHOSPHOLIPIDS —> lysophospholipids
Snake and bee venoms contain phospholipase A2 –> when in blood produce lysophospholipids which disrupts cellular membranes and lyse blood cells
what is cholesterol esterase ?
Cholesteryl ester degradation are hydrolyzed by PANCREATIC CHOLESTERY ESTER HYDROLASE –> cholesterol esterase
Produce : Cholesterol plus and FFA
bile salts increases the activity of cholesterol esterase
describe the absorption of lipid by intestinal mucosal cells ?
Primary products of dietary lipid degradation with bile salts from mixed micelles
short and medium chain length fatty acids dont need MICELLES formation to be absorbed ( pass directly )
what happens to monoacylglycerols inside the cells?
reacylate to triglycerides via monoacylgycerol pathway
Glycerol fate : it is released in the intestinal lumen it goes to the hepatic portal vein ( only organ can synthesize glycerol is liver )
what happens to cholesterol inside the cell ?
some of the absorbed cholesterol is esterified to FATTY ACIDS , forming cholesteryl esters
what enzymes causes cholesterol esterified ?
ACAT :
Acyl coa cholesterol acyl transferase
describe resynthesis of triacylglycerol and cholesterly ester by intestinal mucosal cells ?
2 monoacylglycerol —-> triacylglycerol by ACYLTRANSFERASE
Cholesterol —> Cholesteryl ester BY ACYLTRANSFERASE
Fatty acid —> fatty acyl coa BY ACYLTRANSFERAE
Fatty acyl coa —> Cholesteryl BY ESTERIFICATION WITH CHOLESTEROL
Fatty acyl- coa —-> TRIACYLGLYCEROL by ESTERIFICATION WITH 2 MONOACYLGLYCEROL
Long fatty acid —-> Fatty acyl coa by THIOKINAS / fatty acyl synthetase
short and medium fatty acids are released into the portal circulation where they are carried by serum albumin to the liver
Phospholipids , cholesterol esters are resynthesized by family of acyl transferase
describe the secretion of lipids from intestinal mucosal cells ?
Newly synthesized triacylglycerol and cholesterol esters are packed as oily droplets surrounded by protein and phospholipids and unesterified cholesterol —-> CHYLMICRONS
this is to increase the solubility
describe lipoproteins ?
Lipid binding proteins found in the blood
responsible for transporting cholesterol ester , phospholipids and triacylglycerols between organs
Apolipoproteins –> free form without lipid
apolipoprotiens + lipids = lipoproteins
Spherical structures with hydrophobic core and hydrophilic surfaces
These aggregate have varies densities
Chylomicrons , very low density , lipoprotien , VLD, LDL, HDL , VHDL
describe the packing process?
One inside the enterocyte fatty acids and monoglyceride are transported into endoplasmic reticulum where they are used to synthesize triglyceride
In golgi , triglyceride is packed with cholesterol , other lipids into particles called CHYLOMICRONS
Chylomicrons are extruded from golgi into exocytotic vesicles which are transported through exocytosis
Chylomicrons are transported first into the lymphatic vessel that penetrates into each villus
Chylomicrons rich lymph then drains into the system lymphatic system which rapidly flow into bloods
Resterifications happens in ER
what enzyme degrade triacylglycerol from chylomicrons —> LIPOPROTEIN LIPASE
what happens to free fatty acids inside the cell?
Kept bound with the intestinal fatty acid binding protein —> I-FABP
free fatty acids are transported in the blood bound to albumin
describe cholesterol absorption ?
Niemann-pick C1 like 1 NPC1L1
protein will transport cholesterol from intestinal lumen into the enterocyte
Cholesterol is either esterified or remain non esterified
the drug ezetimibe blocks the NPC1L1 causing reduction in cholesterol absorption resulting in blood reduction between 15-20%
Polymorphic variation NPC1L1 gene could be associated with non response to ezetimibe treatment
what is definition of malabsorption ?
inability of intestine to absorb nutrients or specific nutrients
Suspected if patient present with :
1- history of chronic diarrhea of unknown origin
2- History of weight loss
3- clinical , radiological , hematological or biochemical finding suggestive of undernutrition with obvious cause
what are the causes of malabsorption?
Intraluminal / lumina :
Pancreatic insufficiency , decreased bile acid secretion, bacterial growth , lack of intrinsic factor
Mucosal :
Lactase or sucrase isomaltase deficiency
Hartnup disease
Poor absorbing surface celical disaeae , tropical sprue
whipple disease –> from infection
Gut infiltration of lymphoma
Post absorptive :
Lymphatic obstruction
Inflammation :
Crohn disease , chronic pancreatitis
Cystic fibrosis
Lactose intolerance
Disease of gall bladder , liver, bile acids deficiency
Radiation therapy
what are the symptoms of malabsorption ?
Hypovitaminosis symptoms
Steatorrhea
Weight loss
Weakness
on physical examination :
Edema –> excess fluid building up in the body resulting from hypoalbuminemia causing decreased oncotic pressure
Hepatomegaly
signs relate to vitamin deficiency , anemia
what are the tests of malabsorption ?
1- Quantitative stool fat test –> if more than 5g = steatorrhea
2- D-xylose absorption test : diagnostic test used to evaluate small intestine ability to absorb simple sugars helping differentiating between causes of malabsorption
D Xylose is a monosaccharide or simple sugar that doesnt require enzymes for digestion prior to absorption
its absorption require intact mucosa only
patient drinks water containing 25 grams of D xylose sugar
urine and blood are collected to measure D xylose
decreased urinary excretion of D xylose is seen in conditions involving the GI mucosa which shouldnt be decreased normally
3- Stool elastase activity to check for pancreatic insufficiency
other tests include blood tests
Checking for nutrients deficiency : B12, V D, iron , folate , etc
describe the investigation of steatorrhea :?
Steatorrhea —-> measure fecal fat :
IF normal = normal
IF abnormal do —-> Xylose absorption test
IF abnormal = upper small intestine mucosal disease –> confirm with biopsy
IF normal you have to do fecal elastase : —>
IF abnormal its pancreatic disease
IF normal its bacterial overgrowth
