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Flashcards in GI VIII Deck (71):
1

Define digestion. In what juices are digestive enzymes secreted? Where are these enzymes present (What part of membrane of intestinal epithelial cells?)

The process by which ingested food is broken down chemically into absorbable molecules.

Digestive enzymes are secreted in salivary, gastric, pancreatic juices.

These enzymes are also present in the apical membrane of intestinal epithelial cells.

2

Define absorption.

What are the two paths? Define each.

Where is absorption of carbohydrates, proteins, and lipids highest?

Calcium, phosphate and iron?

Bile acids?

Is the movement of nutrients, water and electrolytes from the lumen of the intestine into blood.

There are two paths: Cellular and paracellular.

Cellular path- the substances enter the intestinal epithelial cells via the apical (luminal membrane) and are extruded via basolateral membrane to enter blood.

Paracellular path -substances move across the tight junctions, through the lateral interspaces into blood.


Where is absorption of carbohydrates, proteins, and lipids highest? - duodenum

Calcium, phosphate and iron? -duodenum

Bile acids? -ilieum

3

Describe the types of ingested carbohydrates.

Carbohydrates ingested are polysaccharides, disaccharides and very little amount of monosaccharides.

4

Which are the absorbed through intestinal epithelial cells?

polysaccharides, disaccharides, or monosaccharides?

monosaccharides

Thus all ingested carbohydrates must be digested to monosaccharides to be absorbed through the intestine.

5

Describe starch.

Major dietary carbohydrate is starch – is a mixture of both straight and branched-chain polymers of glucose.

Amylose – are the straight chain polymers.

Amylopectin - are the branched-chain polymers.

6

What are the disaccharides in food? What do they consist of?

The disaccharides in food are – trehalose, sucrose and lactose.

Trehalose – consists of two molecules of glucose.

Sucrose – consists of glucose and fructose.

Lactose – consists of glucose and galactose.

7

What are the monosaccharides?

Monosaccharides are – glucose, fructose and galactose.

8

Describe cellulose.

Cellulose (β1,4-linkage) no enzymes available to hydrolyze this linkage – cellulose is excreted.

9

Which sugar is excreted? Why?

Cellulose (β1,4-linkage) no enzymes available to hydrolyze this linkage – cellulose is excreted.

10

Which linkage is hydrolysed in alpha amylase?

hydrolysis of α 1,4 linkage only

11

What does digestion of a starch begin with?

Digestion of starch begins with alpha amylase.

Salivary amylase starts the process , but plays an insignificant role in a healthy individual, since amylases are inactivated by low gastric pH.

12

Which amylase is most significant? What bonds does it digest? What results?

Pancreatic amylase (most significant) digests internal alpha-1,4-bonds in starch – yielding a mixture of disaccharides, trisaccharides and oligosaccharides.

alpha-limit dextrins (oligosaccharide), maltose (disaccharides)and maltotriose (trisaccharide).

13

How are disaccharides further digested to monosaccharides? What is the product?

These disaccharides are further digested to monosaccharides by intestinal brush border enzymes:

alpha-dextrinase (isomaltase), maltase and sucrase.

The product of each of these is glucose (monosaccharide) – absorbed by the epithelial cells.

14

Draw a flow chart of carbohydrate digestion.

Slide 9

15

The three disaccharides in food are – trehalose, sucrose and lactose. How is each digested? What is the end product?


These don’t require amylase digestion.

Trehalose – digested by trehalase – two molecules of glucose.

Lactose - digested by lactase – glucose and galactose.

Sucrose - digested by sucrase – glucose and fructose.

Glucose, galactose and fructose - the three end-products of carbohydrate digestion – are absorbed by intestinal epithelial cells.

16

Describe how glucose and galactose is transported in the cell on both apical and basolateral membranes . What transporter?

The symporter sodium/glucose transporter I (SGLT1) transports glucose and galactose against their concentration gradients by coupling their transport to that of Na+ (active process).

Glucose and galactose - extruded across basolateral membrane by facilitated diffusion by a transporter called GLUT2.

Fructose - transported across apical & basolateral membranes by facilitated diffusion
GLUT5 (apical) - fructose specific
GLUT2 (basolateral).

picture slide 12

17

What is lactose intolerance? What is lacking?

What happens if lactose is ingested?

Lack or deficiency of lactase in the brush border- lactose is not digested to glucose and galactose.

This reflects a normal developmental decline in the expression of lactase by enterocytes.

Present in 50% of adult and higher in some populations (Asians).

If lactose is ingested (in milk or milk products), lactose remains undigested and unabsorbed in the intestinal lumen – and retains water causing osmotic diarrhea.

Some patients benefit from taking bacterially derived lactase enzyme in a tablet form.

18

Describe congenital lactose intolerance. What is lacking?

(lack of jejunal lactase)– rare and very serious.
Replace lactose with a sucrose or fructose diet to avoid diarrhea and its consequences.

19

What causes glucose-galactose mal-absorption?

This is due to mutation of SGLT1 – very rare.

Can result in severe diarrhea and its consequences.

Fructose diet is recommended.

20

Describe protein digestion. Which aa are essential? (What does that mean?)

Of the 20 amino acids (AAs), some are called essential amino acids (in boxes)- which cannot be synthesized by the body - must be obtained from diet.

21

Where does protein digestion start and by what action? Where is it completed? How?

Protein digestion starts in the stomach with the action of pepsin.

It is completed in the small intestine with pancreatic and brush-border proteases.

22

Describe the two classes of proteases.

Endopeptidases – hydrolyze the interior peptide bonds of proteins- Example – pepsin, trypsin, chymotrypsin, elastase.

Exopeptidases – hydrolyze one amino acid at a time from the C-terminal ends of proteins and peptides - Example - carboxypeptidases A&B.

23

Describe pepsin. How is it derived? When is it active and inactive? (What places)

Can pepsin digest proteins?

Protein digestion starts in the stomach.

Pepsinogen (inactive precursor of pepsin) is released in response to a meal by gastric chief cells.

At low gastric pH, pepsinogen is activated to pepsin.

Pepsin is active at low pH and inactivated in the duodenum due to pancreatic HCO3-.

Pepsin cannot digest protein fully and yields a mixture of intact protein, large peptides and very little free amino acids.

24

Is pepsin necessary for normal protein digestion?

Pepsin is not essential for normal protein digestion, since in people whose stomach has been removed or who do-not secrete gastric H+, have normal protein digestion and absorption.

25

Protein digestion continues in the small intestine with combined actions of pancreatic and brush border proteases.

What are the five major pancreatic proteases that are secreted as inactive precursors?

trypsinogen
chymotrypsinogen
proelastase
procarboxypeptidase A
procarboxypeptidase B

26

What is the first step in intestinal protein digestion? By what enzyme?

First step in intestinal protein digestion is the activation of inactive trypsinogen to active trypsin – by brush border enzyme enterokinase.

27

What cleaves trypsinogen to yield active trypsin?

What does trypsin do?

Enterokinase cleaves trypsinogen to yield active trypsin.

Trypsin then catalyzes the conversion of all the other inactive precursors to their active enzymes.

It even autocatalyzes the remaining trypsinogen – to active trypsin.

Slide 20

28

What enzymes does active trypsin yield?

What do they do?

trypsin
chymotrypsin
elastase
carboxypeptidase A
carboxypeptidase B

These pancreatic proteases digest dietary protein into amino acids, di- and tri-peptides and larger peptides called oligo-peptides.

29

Trypsin activation yields five active enzymes:
trypsin
chymotrypsin
elastase
carboxypeptidase A
carboxypeptidase B

These pancreatic proteases digest dietary protein into amino acids, di- and tri-peptides and larger peptides called oligo-peptides.

Which are absorbable? Which are not? What happens to those that are not?

Only amino acids, di- and tri-peptides are absorbable.

Oligo-peptides are not absorbable. They are further hydrolyzed by brush-border proteases – to smaller absorbable molecules.

30

Describe protein absorption. Describe the transporters.

What happens to most peptides inside the cell?

How do amino acids exit the cell?

Wide number of amino acid transporters (neutral, acidic, basic and imino amino acids).

Some of those transporters (not all) symport amino acids and Na+.

Peptide transporters work in a symport mode with H+.

Peptide transporters uptake some drugs (clinically relevant).

Inside the cell, most of the peptides are hydrolyzed to amino acids by cytosolic peptidases.

Amino acids exit the cell by facilitated diffusion.

31

How can rare diseases related to single AA absorption be partially or totally compensated?

That defect can be partially or completely compensated by the absorption of di- and tri-peptides that will have their AAs hydrolyzed by enzymes in the cytoplasm of epithelial cells and released into the blood.

32

Describe the two rare diseases related to single AA absorption.

Trypsinogen deficiency – rare and serious. Diet of partially hydrolyzed proteins.

Cystinuria – transporter for dibasic amino acids (cystine, lysine, arginine, ornithine) is absent in small intestine and kidney - low or no absorption of these in intestine or kidney. The intestinal defect results in failure to absorb amino acids – excreted in feces. The renal defect results in increased excretion – thus called cystinuria.

33

What are the major categories of lipid in diet?

How do they interact with water?

Major categories of lipid in the diet:
Triglycerides (major pool) – most of these have long-chain fatty acids (> 12 carbons) esterified to glycerol backbone.
Phospholipids
Cholesterol
Vitamins A, D, E and K (not lipids but fat soluble)


These are insoluble in water – requires special processing to be digested and absorbed in the GI tract.

34

What happens to a lipid fatty meal amongst gatric contents? What is the effect?

How does the body respond? By what process?

Lipid in a fatty meal floats on the surface of gastric contents.

This limits the area of interface between aqueous and lipid phases – thus access to lipolytic enzymes are restricted (enzymes are soluble in aqueous phase).

Emulsification – the mixing action of the stomach churns the dietary lipids into a suspension of fine droplets – this greatly increases the surface area for digestive enzymes.

35

How are lipid droplets emulsified in stomach vs small intestine? By what agents?

In the stomach, lipid droplets are emulsified by dietary proteins.

In the small intestine, the primary emulsifying agents are bile acids.

36

Lipid digestion starts in the stomach.

What does gastric lipase do?

Does lipolysis complete in the stomach?

What is the major contribution of stomach in lipid digestion?

When is CCK released? What is the effect?

Lipid digestion starts in the stomach.

Gastric lipase released by gastric chief cells – hydrolyzes approx 10% of the dietary triglycerides to glycerol and free fatty acids.

Lipolysis is incomplete in the stomach and dispensable in healthy individuals.

Major contribution of stomach in lipid digestion – it empties chyme slowly in the small intestine – allows adequate time for pancreatic enzyme action.

CCK is released when dietary lipids enter small intestine- reduces gastric emptying.

37

In the small intestine what emulsify dietary lipids?

Bile acids together with lysolecithin and products of lipid digestion surround and emulsify dietary lipids.

38

What does emulsification produce in the intestinal lumen?

Emulsification produces small lipid droplets dispersed in the aqueous solution of intestinal lumen – provides a large surface area for pancreatic enzymes.

39

Pancreatic juice contains three important lipolytic enzymes that can work at what kind of pH? Name the 3 enzymes.

Pancreatic lipase
Phospholipase A2
Cholesterol ester hydrolase

40

Describe pancreatic lipase. What does it hydrolyze? How is it inactivated?

What does colipase do?

Hydrolyzes triglycerides to monoglycerides and fatty acids.

Bile acids inactivate pancreatic lipase- which is overcome by an important cofactor colipase.

Colipase binds to both bile acids and lipase – anchors lipase to the fat droplet even in the presence of bile acids.

41

Describe Phospholipase A2

How is secreted/activated?
What does it hydrolyze?

Secreted as a proenzyme (inactive)– activated by trypsin.

Hydrolyzes phospholipids such as those present in cell membranes to lysolecithin and fatty acids.

42

Describe Cholesterol ester hydrolase.

What does it hydrolyze?

Hydrolyzes cholesterol ester to free cholesterol and fatty acids - also hydrolyzes ester linkages of triglycerides, producing glycerol.

43

Summarize the digestion of lipids in a flow chart.

Slide 30

44

The products of lipid digestion - monoglycerides, fatty acids, cholesterol, lysolecithin) – how are they solubilized in the intestinal lumen?

mixed micelles

This excludes glycerol, which is water soluble.

45

Is glycerol water soluble?

yes

46

What is contained within the core of a micelle. What lines the exterior?

Core of a micelle contains the products of lipid digestion – the exterior is lined with amphipathic (has both hydrophilic and hydrophobic face) bile salts.

47

Describe what the hydrophilic and hydrophobic portions of bile salts do in aqueous solution of intestinal lumen.

The hydrophilic portion of the bile salts dissolves in the aqueous solution of intestinal lumen - shields the hydrophobic regions of lipolytic products – solubilizes the lipids in micellar core.

48

Describe lipid absorption into cells. What happens inside the cells?

The micelles then diffuse to the apical membrane of brush border epithelium.

Lipids are released from micelles at the apical membrane – they diffuse down their concentration gradient into the cells.

The micelles do not enter the cells.

The bile salts are left in the intestinal lumen – reabsorbed in the ileum.

Inside the cells- lipid digestion products are re-esterified with free fatty acids on the smooth endoplasmic reticulum – to form triglycerides, cholesterol ester and phospholipids.

49

What happens to re-esterified lipids in the cell?

Describe size, core, outside.

How are the packaged?

Can they enter blood vessels? If so, how? If not, what do they enter instead?

How are they transported?

The re-esterified lipids are packaged with apoproteins to form chylomicrons.

Chylomicrons have an average diameter of 1000 A0 – have triglycerides and cholesterol at the core, phospholipids and apoproteins on the outside.

The chylomicrons are packaged in secretory vehicles – migrate to the basolateral membranes - undergoes exocytosis.

Due to the large size they cannot enter blood vessels and enters the lymphatic capillaries.

Chylomicrons are transported by lymphatic circulation to the thoracic duct – that empties into bloodstream.

50

Describe pancreatic insufficiency diseases, result.

What does abnormality of lipid digestion/absorption result in?

Results in defects of pancreatic enzyme secretion
Abnormality of lipid digestion/absorption – results in steatorrhea.

51

Pancreatic enzymes cannot function optimally at acidic pH.
Provide 2 reasons why.

Gastric parietal cells secrete excessive H+ (Zollinger-Ellison syndrome)

Pancreas doesn’t secrete enough HCO3- to neutralize acidic chyme.

52

Describe the deficiency of bile salts.

No micelle formation – interferes with lipid digestion/absorption.
In Ileal resection (removal of ileum) enterohepatic circulation of bile is interrupted – bile is lost in feces

53

What is Abetalipoproteinemia?

Failure to synthesize Apo B – chylomicrons are either not formed or are unable to be transported into lymph.

54

How do ingested and secreted fluids compare to absorbed fluids?

Slide 36.

55

Fluidity of intestinal content (especially small intestine) is essential.

How much fluid a day comes from oral intake? How much passed onto colon for reabsorption?

What can disturbance of absorptive mechanisms lead to?

1-2L fluid/day comes from oral intake. Additional 8L is supplied by stomach, small intestine and the associated organs.

About 2L of fluid is passed to colon for reabsorption - only 100-200 ml excreted in stool.

Thus a majority of the fluid is absorbed back in the intestine.

Disturbance of absorptive mechanisms can lead to excessive fluid loss from GI tract – diarrhea.

56

The mechanisms of fluid and electrolyte absorption and secretion in the intestine involve transcellular and paracellular routes.

Describe each.
What determines which route will take place?

Paracellular = passage of salts and water between intercellular spaces including through the tight junctions.

Transcellular = passage through the epithelial cells.

The permeability of the tight junctions determines paracellular or transcellular movement:
The tight junctions of small intestine are leaky and permit significant paracellular movement.
The tight junctions of the colon are tight and do-not permit paracellular movement.

The movement of water follows the absorption/secretion of ions and other substances (osmotic flow).

57

What is the major site of Na+ absorption in the small intestine?

The jejunum is the major site of Na+ absorption in the small intestine.

58

How does Na+ enters the jejunal epithelial cells on the apical side?
(3 ways)

What happens on the basolateral side?

Na+ -monosaccharide cotransporters
Na+ -amino acid cotransporter
Na+ -H+ exchanger

Na+ is then extruded across basolateral membrane via Na+ - K+ ATPase.

H+ is derived from intracellular CO2 and H2O which are converted to H+ and HCO3- by carbonic anhydrase.

H+ is secreted into the lumen on the Na+ -H+ exchanger

HCO3- is absorbed into blood.

59

Describe the ilium apical and basolateral membranes. What does this mean for H+ and HCO3-?

Describe the net results of these movements. How does this compare with the jejunum?

The ileum contains the same transport mechanisms as jejunum.

It also has a Cl- - HCO3- exchange mechanism in the apical membrane.

It has a Cl- transporter (instead of HCO3- transporter) in the basolateral membrane.

Thus on the apical side, both H+ and HCO3- are secreted.

Thus on the apical side there is net movement of NaCl into the cell, which is then absorbed.

So in ileum, there is net absorption of NaCl and in the jejunum there is net absorption of NaHCO3.

Slide 40

60

What do epithelial cells of intestinal crypts secrete? How does this compare with the villi?

What transporters are on the apical/basolateral sides?

The epithelial cells of intestinal crypts secrete fluid and electrolytes vs. the those lining the villi which mostly absorb fluid and electrolytes.

The apical membrane has Cl- channels.

The basolateral membrane has Na+-K+ ATPase and Na+ -K+ -2Cl- cotransporter.

This three-ion cotransporter brings Na+, K+ and Cl- into the cells from blood.

Cl- diffuses into the lumen through the Cl- channels.

Na+ diffuses passively through tight junctions.

Water is secreted into lumen following secretion of NaCl.

61

Are the Cl- channels in apical membrane usually open or closed?

The Cl- channels of the apical membrane are usually closed.

62

The Cl- channels of the apical membrane are usually closed.

How are these channels activated?

But these channels are activated by hormones, neurotransmitters such as Ach, VIP.

These bind to the basolateral receptors and activate adenylyl cyclase – generates cAMP in the crypt cells.

cAMP opens the Cl- channels and causes Cl- secretion.

63

What happens in Cholera? How does this differ from the norm in regards to crypt and villi cells?

Normally electrolytes and water secreted by crypt cells are absorbed by villus cells.

In diseases like Cholera, adenylyl cyclase is highly activated - fluid secretion by the crypt overwhelms the absorptive capacity of villus cells causing life-threatening diarrhea.

64

What causes osmotic diarrhea. Give an example.

Caused by the presence of non-absorbable solutes in the intestinal lumen.

Example – in lactase deficiency, lactose is not digested to glucose and galactose. Undigested lactose in the lumen is osmotically active -retains water and causes osmotic diarrhea. Intestinal bacteria may degrade lactose to more osmotically active forms aggravating the condition further.

65

What causes secretory diarrhea?


Secretory diarrhea (example in Cholera) is caused by excessive secretion of fluid by crypt cells.

The major cause of secretory diarrhea is overgrowth of enterohepatic bacteria – e.g. Vibrio cholerae or Escherichia coli.

66

Describe calcium absorption in small intestine.

What factor must be present for absorption?

What induced its synthesis?

How does Ca get into cell?

What does inadequate Ca absorption result in children and adults?

Actively absorbed in small intestine and depends on the presence of the active form of vitamin D, 1,25-dihydroxycholecalciferol.

1,25-dihydroxycholecalciferol induces synthesis of vitamin D-dependent Ca2+ -binding protein calbindin D-28K.

Ca2+ diffuses into the cells (luminal side) down its electrochemical gradient – is bound to calbindin D-28K inside – pumped across basolateral membrane by a Ca2+ -ATPase.

Inadequate Ca2+ absorption causes rickets (in children) and osteomalacia (in adults).

67

Absorption of Vitamin B12 (Cobalamin)

How is Vit. B12 released from food? What does it bind to?
What happens in duodenum?

What happens in a gastroectomy? What can prevent this?

Vitamin B12 is released from food by pepsin in the stomach – binds to R proteins.
In the duodenum, pancreatic proteases degrade R proteins – vitamin B12 transferred to intrinsic factor (IF), secreted by gastric parietal cells.
vitamin B12 -IF complex absorbed by a specific transport mechanism in the ileum.

68

What happens in a gastroectomy? What can prevent this?

In gastrectomy, parietal cells are lost - IF is not released – no vitamin B12 absorption – can lead to pernicious anemia - vitamin B12 injection can prevent this.

69

What is key enzyme that initiates protein digestion?
From where is it released?

This is enterokinase (NOT released by pancreas, released by brush border epithelium) THIS is trigger to activate trypsinogen to trypsin

70

What opens Cl- channels in pancreas and intestine?

pancreas- secretin stimulates cAMP and opens CFTR into lumen

intestine- VIP or Ach, adenylate cyclase, cAMP to open Cl- channels in apical membrane to secrete Cl-

71

How is parathyroid hormone involved in Ca absorption?

req. for converting 25 hydroxycholecalciferol to 1-25 dihydroxy… need PTH. so deficiency of PTH see effect of Ca absorption.