Lecture 21: Digestion and Absorption in the GI tract

Question 1

Lactose intolerance:

Classic presentation and findings

Answer 1

AP, bloating, diarrhea after eating dairy.

Positive Hydrogen breath test

Question 2

What is the pathophysiology of lactose intolerance

Answer 2

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

Question 3

What are the major sugars in the human diet?

Answer 3

Primary sugars include sucrose, lactose, starch

Everything else is secondary sugars
Cellulose is indigestible

Question 4

Where are carbs digested and what are the main players?

What are the major products of carbohydrate breakdown in these locations?

Answer 4

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

Question 5

How do these disaccharides break down (include enzymes)
Maltose
Trehalose
Lactose
Sucrose

Answer 5

• glucose + glucose (maltase)
• glucose + glucose (trehalase)
• glucose + galactose (lactase)
• glucose + fructose (sucrase)

Question 6

How are the monosaccharides transported from the SI lumen to the blood (include type of transport)?

Answer 6

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)

Question 7

How would you clinically test for carb absorption issues?

Answer 7

-D-xylose test, methane, 13CO2, sucrose breath tests

Question 8

How do you perform a D-xylose test?

Answer 8

• 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

Question 9

What are the major causes of protein assimilation disorders?

Answer 9

-pancreatic enzyme or SI transporter deficiency

Question 10

Chronic pancreatitis

Congenital trypsin absence

Answer 10

• lack of proteases (e.g. trypsinogen)

- lack of trypsin, no pancreatic enzymes (since trypsin activates a lot of other pancreatic enzymes)

Question 11

Cystinuria
Cause
Clinical

Answer 11

• SLC3A1/SLC7A49 defect causes deficient COAL AA transporter > not reabsorbed by kidney
• COAL AAs form stones or are excreted in feces

Question 12

Hartnup disease
Cause
Clinical

Answer 12

• can’t absorb neutral AAs due to SLC6A19/B(0)AT1 mutation

- pellegra like (diarrhea, dermatitis, dementia), increased neutral AAs in urine

Question 13

Cystic fibrosis (GI manifestation)
Cause
Clinical

Answer 13

• CTFR mutation, HCO3- can’t be released into duct = acidic duct = digestive enzymes digest the pancreas
• pancreatitis

Question 14

Where are proteins digested and what are the main players?

What are the major products?

Answer 14

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

Question 15

Explain the activation cascade of gastric pancreatic enzymes

Answer 15

Gastric:
Pepsinogen > pepsin (activated by low pH)

Pancreatic:
pancreas releases enzymes to duodenum > enterokinase/trypsin activates trypsinogen > more trypsin > activates the other pancreatic enzymes

Question 16

How are the peptides transported from the SI lumen to the blood?

Answer 16

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

Question 17

Celiac Sprue/Celiac Disease

classic presentation and findings

Answer 17

-greasy, pale and foul smelling diarrhea/steatorrhea, AP, weight loss
Positive for anti-transgluatminase (tTG-IgA) antibodies

Question 18

What is the pathophysiology of Celiac Disease?

Answer 18

-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

Question 19

Tropical Sprue
Cause
Clinical

Answer 19

• possible intestinal infection causes decreased number of intestinal epithelial cells decreasing microvilli surface area > lipid malabsorption
• diarrhea (major sign), treat with abx

Question 20

What characteristics of the intestinal mucosa make it ideal for absorption?

Answer 20

-intestinal mucosa brush border made of folds of Kerckring with lots of villi and microvilli > increased surface area for absorption

Question 21

What types of cells are in the intestinal mucosa that aid with digestion?

Answer 21

Enterocytes
Goblet cells - secrete mucus
Paneth cells - immune defense

Question 22

What mechanisms are used to transport molecules into enterocytes?

Answer 22

-Pinocytosis, passive and facilitated diffusion, active transport

Question 23

What is an important step in lipid absorption?

Answer 23

emulsification by bile salts and lecithin > induces micelle formation

Question 24

What are the major players of lipid digestion in the stomach?

Answer 24

• lingual and gastric lipase break down TAGs

- CCK - inhibits gastric emptying and increases gallbladder secretion (mixes the bolus)

Question 25

What are the major players of lipid digestion in the small intestine?

Answer 25

*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

Question 26

Outline the mechanism of lipid absorption into the bloodstream

Answer 26

1. Bile salts “separate” the lipids for lipase breakdown, products absorbed by enterocyte
2. lipids re-esterified in enterocyte (by adding FFA)
3. lipids packaged into chylomicron (with the help of ApoB)
4. Chylomicron released to lymphatics first > thoracic duct > bloodstream release

Question 27

ApoB deficiency leads to…

Answer 27

-lipid absorption problems (abetalipoproteinemia)

Question 28

How does pancreatic secretion problems cause disease?

Answer 28

1. ) Pancreas not releasing HCO3- to neutralize acids > > duodenum is acidic causing disease
2. ) Pancreas not releasing the needed enzymes = no breakdown

Question 29

Pancreatic insufficiency
Zollinger Ellison syndrome
Pancreatitis

Answer 29

• pancreas not releasing enough enzymes
• gastrnoma > increased gastrin > increased H+ secretion
• acidic pancreatic duct > enzymes self digest the pancreas

Question 30

What conditions can cause bile salt deficiency and why?

Answer 30

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

Question 31

How is SIBO diagnosed?

Answer 31

methane and hydrogen breath test

Question 32

What are the fat soluble vitamins and how are they absorbed?

What are the water soluble vitamins and how are they absorbed?

Answer 32

• Vit. A,D,E,K > absorbed like lipids (micelle strategy)

- Vit, B (except B12), C > absorbed via Na+ dependent cotransport

Question 33

How is B12 absorbed (very briefly)?

Answer 33

B12 + R proteins (stomach) > B12 + IF (SI) > B12 + transcobalamin II (to bloodstream)

Question 34

Why is B12 important?

Answer 34

• serves as hydrogen acceptor coenzyme
• gene replication
• folate recycling, myelination, RBC synthesis

Question 35

Pernicious anemia
Major cause
Pathophysiology

Answer 35

• main reason is IF deficiency

- low B12 > RBC maturation impaired > pernicious/macrocytic megaloblastic anemia

Question 36

Why is Vitamin D important for Ca2+ absorption?

Lack of vitamin D leads to…

Answer 36

• having enough Vit. D since calbindin depends on Vit. D to bind the Ca2+ and transport into the enterocyte
• rickets (kids), osteomalacia (adults)

Question 37

Draw the pathway of Vitamin D absorption

Answer 37

Ok

Question 38

Draw the pathway of iron absorption

Answer 38

Ok

Question 39

Describe electrolyte absorption in the GI tract

Answer 39

• SI and colon both absorb and secrete electrolytes

- solute absorbed first, water follows (same proportions of both are reabsorbed > isoosmotic)

Question 40

What electrolytes are absorbed/secreted in the ....
Duodenum
Jejunum
Ileum
Colon

Answer 40

• 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

Question 41

Pathophysiology of cholera

Answer 41

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)