Lecture 21: Digestion and Absorption in the GI tract Flashcards
Lactose intolerance:
Classic presentation and findings
AP, bloating, diarrhea after eating dairy.
Positive Hydrogen breath test
What is the pathophysiology of lactose intolerance
lack of brush border enzyme lactase that metabolizes lactose > unabsorbed lactose becomes SCFAs & H2 > acetate, butyrate and proprionate ferments to methane and H2 > effect is to keep water in lumen of intestine (not reabsorbed) > osmotic diarrhea
What are the major sugars in the human diet?
Primary sugars include sucrose, lactose, starch
Everything else is secondary sugars
Cellulose is indigestible
Where are carbs digested and what are the main players?
What are the major products of carbohydrate breakdown in these locations?
Mouth: starch breakdown begins, main enzyme is salivary amylase
Small intestine:
most starch broken down here, main enzyme is pancreatic amylase
Major product:
Starch > maltose + 3-9 polymers of glucose
How do these disaccharides break down (include enzymes) Maltose Trehalose Lactose Sucrose
- glucose + glucose (maltase)
- glucose + glucose (trehalase)
- glucose + galactose (lactase)
- glucose + fructose (sucrase)
How are the monosaccharides transported from the SI lumen to the blood (include type of transport)?
From lumen to SI cell:
- SGLT carries glucose and galactose with Na+ in (secondary active transport)
- GLUT5 carries fructose in (facilitated diffusion)
From SI cell to blood:
- Na/K ATPase maintains Na/K balance (primary active)
- GLUT2 carries glucose, galactose and fructose into bloodstream (facilitated diffusion)
How would you clinically test for carb absorption issues?
-D-xylose test, methane, 13CO2, sucrose breath tests
How do you perform a D-xylose test?
- Patient ingests 25 g of D-xylose which is absorbed but not utilized by human body
- if <4g of D-xylose is excreted by urine = CHO malabsorption is present
What are the major causes of protein assimilation disorders?
-pancreatic enzyme or SI transporter deficiency
Chronic pancreatitis
Congenital trypsin absence
- lack of proteases (e.g. trypsinogen)
- lack of trypsin, no pancreatic enzymes (since trypsin activates a lot of other pancreatic enzymes)
Cystinuria
Cause
Clinical
- SLC3A1/SLC7A49 defect causes deficient COAL AA transporter > not reabsorbed by kidney
- COAL AAs form stones or are excreted in feces
Hartnup disease
Cause
Clinical
- can’t absorb neutral AAs due to SLC6A19/B(0)AT1 mutation
- pellegra like (diarrhea, dermatitis, dementia), increased neutral AAs in urine
Cystic fibrosis (GI manifestation)
Cause
Clinical
- CTFR mutation, HCO3- can’t be released into duct = acidic duct = digestive enzymes digest the pancreas
- pancreatitis
Where are proteins digested and what are the main players?
What are the major products?
Stomach:
Pepsin activated at pH 2-3, breaks down a small amount of protein
Pancreas releases these enzymes:
Trypsinogen, chymotrypsinogen, procarboxypeptidase, proelastase (all these activated by trypsin)
- turns protein to small polypeptides
Small intestine enterocytes release these enzymes:
aminopolypeptidase, dipeptidases - broken down into AAs
Explain the activation cascade of gastric pancreatic enzymes
Gastric:
Pepsinogen > pepsin (activated by low pH)
Pancreatic:
pancreas releases enzymes to duodenum > enterokinase/trypsin activates trypsinogen > more trypsin > activates the other pancreatic enzymes
How are the peptides transported from the SI lumen to the blood?
Lumen to SI:
- different types of AAs (basic, acidic, neutral, imino) have their specific transporters into the enterocyte
- carried with H-dipeptides and H-tripeptides
SI to blood:
- Na/K ATPase maintains balance
- different types of AAs have their specific transporters into the blood stream (facilitated diffusion)
- dipeptides and tripeptides also diffuse
Celiac Sprue/Celiac Disease
classic presentation and findings
-greasy, pale and foul smelling diarrhea/steatorrhea, AP, weight loss
Positive for anti-transgluatminase (tTG-IgA) antibodies
What is the pathophysiology of Celiac Disease?
-presence of Abs against gliadin (found in gluten) > small intestinal villi atrophy and crypt hyperplasia > malabsorption of lipids (e.g. Vit. A, B9, B12, D, Fe and Ca2+)
Be sure to look at the histo images of damaged villi on the slides
Tropical Sprue
Cause
Clinical
- possible intestinal infection causes decreased number of intestinal epithelial cells decreasing microvilli surface area > lipid malabsorption
- diarrhea (major sign), treat with abx
What characteristics of the intestinal mucosa make it ideal for absorption?
-intestinal mucosa brush border made of folds of Kerckring with lots of villi and microvilli > increased surface area for absorption
What types of cells are in the intestinal mucosa that aid with digestion?
Enterocytes
Goblet cells - secrete mucus
Paneth cells - immune defense
What mechanisms are used to transport molecules into enterocytes?
-Pinocytosis, passive and facilitated diffusion, active transport
What is an important step in lipid absorption?
emulsification by bile salts and lecithin > induces micelle formation
What are the major players of lipid digestion in the stomach?
- lingual and gastric lipase break down TAGs
- CCK - inhibits gastric emptying and increases gallbladder secretion (mixes the bolus)
What are the major players of lipid digestion in the small intestine?
*most of the digestion occurs here
Pancreas releases these enzymes ….
- pancreatic lipase - secreted as active, trypsin activates partner colipase
- cholesterol ester hydrolase - secreted as active, generation of free cholesterol, turns TAGs into glycerol
- Phospholipase A2 - secreted as inactive, trypsin activates it, generates FAs
Outline the mechanism of lipid absorption into the bloodstream
- Bile salts “separate” the lipids for lipase breakdown, products absorbed by enterocyte
- lipids re-esterified in enterocyte (by adding FFA)
- lipids packaged into chylomicron (with the help of ApoB)
- Chylomicron released to lymphatics first > thoracic duct > bloodstream release
ApoB deficiency leads to…
-lipid absorption problems (abetalipoproteinemia)
How does pancreatic secretion problems cause disease?
- ) Pancreas not releasing HCO3- to neutralize acids > > duodenum is acidic causing disease
- ) Pancreas not releasing the needed enzymes = no breakdown
Pancreatic insufficiency
Zollinger Ellison syndrome
Pancreatitis
- pancreas not releasing enough enzymes
- gastrnoma > increased gastrin > increased H+ secretion
- acidic pancreatic duct > enzymes self digest the pancreas
What conditions can cause bile salt deficiency and why?
Ileal resection - ileum reabsorbs most bile salts, lack of recyclable bile salts
SIBO - pH not low enough to kill pathogenic bacteria > bacteria deconjugate bile salts in duodenum > defective bile salts = impaired micelle formation
How is SIBO diagnosed?
methane and hydrogen breath test
What are the fat soluble vitamins and how are they absorbed?
What are the water soluble vitamins and how are they absorbed?
- Vit. A,D,E,K > absorbed like lipids (micelle strategy)
- Vit, B (except B12), C > absorbed via Na+ dependent cotransport
How is B12 absorbed (very briefly)?
B12 + R proteins (stomach) > B12 + IF (SI) > B12 + transcobalamin II (to bloodstream)
Why is B12 important?
- serves as hydrogen acceptor coenzyme
- gene replication
- folate recycling, myelination, RBC synthesis
Pernicious anemia
Major cause
Pathophysiology
- main reason is IF deficiency
- low B12 > RBC maturation impaired > pernicious/macrocytic megaloblastic anemia
Why is Vitamin D important for Ca2+ absorption?
Lack of vitamin D leads to…
- having enough Vit. D since calbindin depends on Vit. D to bind the Ca2+ and transport into the enterocyte
- rickets (kids), osteomalacia (adults)
Draw the pathway of Vitamin D absorption
Ok
Draw the pathway of iron absorption
Ok
Describe electrolyte absorption in the GI tract
- SI and colon both absorb and secrete electrolytes
- solute absorbed first, water follows (same proportions of both are reabsorbed > isoosmotic)
What electrolytes are absorbed/secreted in the .... Duodenum Jejunum Ileum Colon
- small amount of Na in exchange for H+ into SI lumen
- lots of Na
- Na,Cl, HCO3- secreted to neutralize H+ buildup in lumen
- Na, water absorption, K+ secreted (modulated by aldosterone like in kidneys
Pathophysiology of cholera
Vibrio cholerae (cholera toxin) > increased cAMP > Cl- flows out of enterocyte, Na+ and H2O follow > too much flow into lumen than the colon can reabsorb > secretory diarrhea (lost both water and NaCl)
