65 - GI Digestion and Absorption Flashcards
Describe the general pathway of carbohydrate digestion
- Carbohydrate digestion is initiated in the mouth by salivary amylase
- Subsequently, pancreatic amylase continues digestion in the lumen of
the intestines. - Further digestion of oligosaccharides by specific enzymes at the intestinal brush border yields monosaccharides
Describe the basics of carbohydrate absorption
- Following digestion, glucose and galactose are transported into the intestinal enterocyte by the sodium-glucose transporter (SGLT-1) and fructose via the glucose transporter, GLUT-5
What are the three main transporters of carbohydrates and what do they transport?
- SGLT-1: sodium-glucose transporter
- GLUT-5: fructose via the glucose transporter
- GLUT-2: responsible for the transport of all three monosaccharides across the basolateral membrane
Where does most carbohydrate absorption occur?
Carbohydrates are absorbed throughout the small intestines; however the greatest uptake occurs in the duodenum
Describe the basic pathway of protein digestion
- Gastric peptidases (pepsin) initiate protein digestion in the stomach
- Once chyme enters the duodenum, pancreatic peptidases (trypsin, etc.) continue to digest proteins to oligopeptides
- When these peptides reach the intestinal brush border, they can be absorbed by enterocytes or be completely digested to amino acids and subsequently absorbed
Describe the basic pathway of protein absorption
- There a multiple transporters that mediate oligopeptide and amino acid uptake in the small intestine
- For example, the oligopeptide transporter (PEPT1) and the amino acid transporter B mediated uptake across the apical membrane of intestinal enterocytes
- Like the carbohydrates, proteins are absorbed throughout the small intestine; however the greatest uptake occurs in the duodenum
Describe lipid digestion
- Initiated in the stomach
- Lingual lipase and gastric lipase digest lipids in the stomach
- Both are enzymatically active at the relatively low pH in the stomach and are resistant to pepsin digestion
- Once in the lumen of the duodenum, the lipases will be degraded by pancreatic proteases (trypsin)
- Pancreatic lipases then digest the lipids further, releasing more free fatty acids
Describe lipid emulsification
- Gastric churning also helps with emulsifying the lipid droplets in the stomach
- In the duodenum, bile is mixed with the emulsified lipid droplets forming micelles
- Micelles: bile salt, cholesterol, other lipids
- Micells increase solubility of lipids by forming a spherical droplet with a hydrophilic border and hydrophobic core
- This dramatically increases delivery of lipids through mucus/water layer to the brush border for absorption
Describe lipid absorption
- Once the micelle reaches the mucosal surface, the lipid content of the micelle can be absorbed and the bile salts are recycled
- Absorption of many lipids is mediated by simple diffusion through the lipid bilayer whereas cholesterol can be taken up by a specific transporter
What is the cholesterol-specific transporter?
Neimann Pick C1 Like1 (NPC1L1)
What else is taken up similarly to lipids?
In addition to dietary lipids, it should be noted that fat soluble vitamins such as Vitamin A, D, E, and K partition into the micelle for delivery to the absorptive enterocytes
What happens once lipids have been taken up?
- Following cellular uptake of dietary lipids, the lipids are packaged with a family of proteins known as lipoproteins
- These lipoproteins along with the lipids form a chylomicron
- Chylomicrons eventually make their way into the circulation
- The chylomicrons will then be taken up by the liver
Where does the greatest amount of lipid absorption occur?
Lipids are also absorbed throughout the small intestines; however the greatest uptake occurs in the duodenum
Where is folic acid absorbed?
Primarily in the duodenum
How is folic acid absorbed?
The uptake of folic acid is mediated by an exchange protein expressed on the surface of enterocytes
Where is vitamin B12 absorbed?
In the ileum
Describe the mechanism for vitamin B12 absorption
- Intrinsic factor (IF) secreted by the parietal cells of the stomach is required for the absorption of Vitamin B12
- Once IF and Vitamin B12 pass from the stomach into the duodenum they form a complex
- The IF-Vitamin B12 complex is then taken up by receptor-mediated process in the ileum
- Once the Vitamin B12 is inside the cell it binds to the carrier protein transcolbalmin II
- The transcolbalmin II-Vitamin B12 complex is secreted into the blood and taken up by the liver for storage
Where is calcium absorbed?
Calcium absorption occurs primarily in the duodenum
Describe the mechanism for vitamin B12 absorption
- The uptake of calcium by the absorptive enterocyte requires the expression of a calcium channel
- The presence of this channel is regulated at the level of transcription by the fat soluble vitamin, Vitamin D
What happens when there is a vitamin D deficiency in relation to Ca++?
Nutritional deficits resulting in impaired Vitamin D uptake or synthesis will also result in impair calcium channel expression in the duodenum and a resulting hypocalcaemia.
Where is iron absorbed?
Small intestine
Iron is available in two forms. What are they?
Iron is available in two forms, ferrous iron (Fe+2) and ferric iron (Fe+3).
Why is calcium needed for iron absorption?
- The ferric form of
iron precipitates at pHs greater than 3. - Therefore, in the neutral environment in the small intestines ferric iron will precipitate and is unabsorbable
- Vitamin C-dependent reduction of ferric iron to ferrous iron will render the iron soluble
How is soluble iron taken up?
- Similar to Vitamin B12 absorption, ferrous iron uptake in the small intestines is mediated by a receptor that binds and internalizes the soluble transferrrin-Fe+2 complex
- Ferrous iron can also be taken up by the divalent cation transporter 1 (DCT1)
- Iron is transferred into the blood where it complexes with plasma transferrin and is carried to the liver
What is lactose intolerance?
- The inability to digest lactose (lactose intolerance) results in an increased liquidity of the stool or diarrhea
How does lactose intolerance cause diarrhea?
- Accumulation of luminal lactose from dairy products results in changes in osmotic pressure that cause water to remain in lumen of the intestine
- Additionally, intestinal bacteria will breakdown lactose liberating gas which causes pain and discomfort for the patient.
What is celiac sprue?
Celiac sprue (Gluten-sensitive enteropathy) is a loss of mature villi of the duodenal and jejunal epithelium following ingestion of gluten (protein component of cereal grains)
Describe the pathophysiology of celiac sprue
- The damage to the intestinal mucosa is due to a hyperactive immune response stimulated by gluten.
- Ultimately this response causes significant cell death to the intestinal epithelial cells.
- As a result of the intestinal cell death the villi shorten.
- Consequently, the surface area of the small intestines is greatly reduced which ultimately decreases the absorptive capacity of the small intestine
What is pernicious anemia?
Pernicious anemia is a Vitamin B12 deficiency often caused by atrophy of gastric mucosa and parietal cells resulting in a loss of intrinsic factor production
Descibe the pathophysiology of celiac sprue
- Vitamin B12 and folic acid (FA) are important for DNA synthesis, impaired absorption of these nutrients results in a decrease in cell growth.
- This has a significant effect on hematopoiesis.
- The result is a decrease in the quantity of blood cells; however the blood cell actually increases in size but does not divide resulting in a megaloblastic anemia.
Onto case #7…
Go read case #7
What does the diagnostic information indicate?
Absorption problem
Given the information from the diagnostic tests, what is the impact on digestive processes (gastric, pancreatic, intestinal)?
Histological examination
- Showed a flattening of the villi (indicates Celiac sprue)
- This explains all of the other symptoms
- Symptoms include slow growth is a result of the malabsorption
X-ray of hand
- The bones are thin (vitamin D problem)
Family history
- Rickets fits in with a celiac diagnosis
- He couldn’t absorb B12 so he got shots, which may have put cell replication into overdrive and resulted in B cell lymphoma
- What is the cause of diarrhea (osmotic vs. secretory)?
Diarrhea is osmotic because he isn’t absorbing much of the material eaten. This shifts the osmotic gradient causing water retention in the lumen.
