Exocrine Function GI Flashcards

1
Q

What is gastrinoma?

A

Tumor of G cells → excessive production of Gastrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are a common treatmnt for peptic ulcer disease?
what are common causes for ulcers?

A

Omeprazole → H2 blocker
- Blocks the Histamine receptor → blocks the increased activation of H+ secretion from parietal cells

Causes of Uclers:
High acid content or Weak barrier of the stomach/duodenum
- High acid
- Irritation
- Poor blood supply (lack of cell turnover or mucus secretion)
- Poor secretion of mucus
- Infection (ex: H. pylori)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the effect of Gastrin in the stomach?
What is Omeprazole?

A

Gastrin is produced by G cells sensing lumen contents in the stomach (secretagogues) → Blood stream →
1. Binds CCK-B R on ECL cells → Histamine release → binds to H2 R on parietal cells
2. Binds to CCK-B R on Parietal cells → increase activation + proliferation

*Activation = depolarization

Omeprazole → H2 R blocker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are different effects of increased gastrin production?

A

1- Increased basal acid secretion in parietal cells
2- Increased pepsinogen release + breakdown to pepsin (due to higher H+)
3- Hypertrophy of the mucosa (increase in foldings in the stomach du to increase proliferation of parietal cells

All of these lead to multiple ulcers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are general effects of having too much acid present in the duodenum in the context of Gastrinoma?

A
  1. Overwhelms absorptive capacity of SI
    - Not able to produce enough alkaline secretions to neutralize the chyme
  2. Impairs digestion
    - Intestinal enzymes need neutral pH to operate
  3. Increased GI motility
    - Due to distension of the duodenum

*Gastrin increases secretions at multiple levels → Stomach, pancreas, liver, SI
*Leads to to diarrhea and steatorrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the physiological consequences on the SI of excess gastrin and acid production?

A
  1. Acid-base balance → pronouced alkaline tide must be neutralized by pancrease & liver
    - HCO3-&raquo_space; H+ blood (every time bincarbonate is pumped into the gastric lumen, H+ is pumped into the blood)
  2. Digestion & Absorption (steatorrhea)
    - Low pH inactivates pancreatic lipase and other digestive enzymes
    - Micelle formation is impaired by low pH → fatty acids, A, D, E, K vitamin absorption is impaired (micells allow lipases to act for absorption of fats)
    - High acid → D cell activation → increase somatostatin secretion
    *This normally should downregulate acid secretion, but gastrinoma patients don’t have negative regulation on acid secretion in tumor cells
  3. Vitamin B12
    - Low pH impairs Vit B12 absorption in the Ileum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are different treatment for stomach/SI ulcers?

A
  • Antibiotics → target H. pylori and fight other infections
  • Protons pump inhibitors → main target if too much acid = H+/K+ pump
  • H2 antagonist (block histamine binding)
  • Muscarinic receptor antagonist (secretory cells have muscarini receptors on their surfaces)
  • Antacids → lower stomach pH

Common combination = Omeprazole + Antibiotic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the 2 main functions of secretory glands of the GI tract?

A
  1. Secrete digestive enzymes
  2. Secrete mucus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are all the different glands if the exocrine GI tract?

A
  • Single-cells distributed in mucosa → mucus
  • Crypts of Lieberkühn cells (SI)
  • Tubular glands (stomach)
  • Complex glands → salivary glands, pancreas, liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the basic structure of glands?

A
  1. Ductal region → alkaline secretions
  2. Acinar region → enzyme secretions
  3. Capillaries in close contact with the acinar region → provide energy and raw materials for secretions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the different components of saliva production/secretion?
What is the pH of saliva?

A

1) Saliva = ultrafiltrate of plasma to which is added alpha−amylase and mucins
2) Other secretions from acinar cells lysozyme, amylase, lipases, etc.
3) Immunoglobulin entry (from plasma)
4) Ductal region: alkaline secretion (Na+, K+, Cl-, HCO3-, Mg2+, PO4-) → Saliva is Hypotonic with plasma
*With HCO3- secretion in the duct comes H+ secretion into the blood stream (carbonic anhydrase: CO2 + H2O → H2CO3 → H+ + HCO3-)

pH: 6.8 - 8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some major differences in cell types and structure between Salivary glands, pancreatic Secretory glands and Liver glands?

A

Salivary glands → saliva

Pancreatic secretory glands → Acinar region (enzymes: proteases, lipases), Centroacinar region (bicarbonate), Ductal region (bicarbonate/Cl- exchange)

liver gland → Bile secretion, Secretory cell = hepatocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are different mechanisms of gland stimulation?

A

1) Contact of the epithelium with food

2) Enteric Nervous stimuli
→ tactile stimulation, chemical irritation, gut wall distension (leading to increased glandular secretion)

3) Parasympathetic stimulation
→ increases secretion (and blood flow), excitatory drive

4) Hormones (ex: gastrin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are important organelles of glandular cells?

A

Large ER + Golgi → for production/secretion of zymogenic granules
- Nutrients + ATP are used for synthesis in the ER and Golgi Complex (GC)
- In the GC materials are modified and discharged into the cytoplasm (zymogen granules)
- Zymogen granules are stored at the apical end of the cells & released by exocytosis in response to signals (depolarization of cell)

  • Good amount of mitochondria to support these functions
  • Basal side = close contact with blood as supply for nutrients
  • Apical side = site of secretion

Zymogen = secreted as INACTIVE components

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is it important thet glandular cells are activated during cephalic phase?

A

Transport through the ER and GC takes ~ 20 minutes, so need stimulate cells before the contents before the food gets there

*Enzymes have to be packaged into granules unlike H+/HCO2-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is Water and Electrolytes secreted from ductal cells?

A
  1. Nerve stimulation
  2. Influx of Na+ → depolarizes the cells
  3. Increase in osmolarity
  4. H2o flows in from basal side to neutralize this high osmolarity → which also increases pressure in the cells
  5. Due to this pressure, biacrbonate and H2O flow out on the apical into the duct (via aquaporins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which hormones are important for regulation of secretions?

A
  1. Gastrin
  2. Cholecystokinin (CCK)
  3. Secretin
  4. Gastric Inhibitory peptide
  5. Motilin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does Gastrin (as a hormone) regulate secretion?

A
  • Secreted by G cells in stomach, duodenum and pancreas
  • Stimulates acid secretion (by Parietal Cell)
  • Stimulates growth of the gastric mucosa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does Cholecystokinin (as a hormone) regulate secretion?

A
  • Secreted by I cells in duodenum and jejunum (open APUD cells)
  • Stimulated by fat in duodenum
  • Acts on CCK-A receptors in smooth muscle & gallbladder → CCK is the most potent stimulus for gallbladder contraction
  • Relaxes the Spincter of Oddi (common bile duct → duodenum) → for secretion of bile acids and pancreatic enzymes
  • Competes with gastrin for CCK-B receptor-binding sites in the stomach → to inhibit acid and histamine secretion in stomach
  • Stimulates pancreatic enzyme secretion by acinar cells, contracts gallbladder for release of bile salts

**CCK secretion is inhibited by bile acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does Secretin (as a hormone) regulate secretion?

A
  • Secreted by S cells in duodenum (open APUD cells)
  • Stimulated by acid in duodenum
  • Inhibits H+/gastric juice secretion by Oxyntic/parietal cells
  • Promotes pancreatic secretion of bicarbonate
  • Secretin (with CCK) affects smooth muscles → slows the movements of contents into duodenum

**Secretin is used to test pancreatic function (measuring bicarbonate secretion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does Gastric Inhibitor peptide (GIP) (as a hormone) regulate secretion?

A
  • Secreted by mucosa of upper intestine
  • Decreases motor activity of stomach
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does Motilin (as a hormone) regulate secretion?

A
  • Secreted by upper duodenum during fasting
  • Stimulates motility of GI tract (in absence of a meal)
  • Stimulates interdigestive Myoelectric Motor Complex (helps move contents through GIT in absence of a meal)
23
Q

What are APUD cells? (What does each letter mean?)

A

Amine → high amine content in the gut lumen
Precursor Uptake → high uptake of (amine) precursor
Decarboxylase → high content of the enzyme AA decarboxylase converts precursor to amines

Open → luminal surface with contact in the lumen to sense contents (secretagogues)
Closed → no contact withh GIT lumen

**neuroendocrine cells that share the ability to take up amine precursors, decarboxylate them, and produce peptide hormones, playing a role in regulating various physiological processes

24
Q

What inhibits secretion of CCK?

A

Bile acids in the lumen of the duodenum

25
Q

What are features/roles of mucus?

A

1) Thick secretion → composed mainly of water electrolytes and glycoproteins

2) Adheres tightly to food or other particles → spreads a thin film over surfaces

3) Convers the gut wall → limits direct contact of particles with the mucosa

4) Resistant to GI enzymes → long durability because not broken down by GI enzymes

5) Causes fecal particles to adhere → forming the feces

6) Has amphoteric properties → can buffer small amounts of acids or alkalis

26
Q

What is the structure an main functions of the pancreas?
What hormone is important in its regulation?

A

Major organ for digestion → releases pancreatic juices & enzymes

  • pancreatic juices enter with bile from liver/gall bladder
  • regulated entry into GIT at spincter of Oddi → Spincter is relaxed by CCK + CCK promotes secretion of pancreatic enzymes by acinar cells + contract gall bladder
27
Q

What are the Exocrine vs Endocrine functions of the Pancreas?

A

Exocrine: (Head/Body)
- Tubuloacinar glands → similar to salivary glands
- Individual ducts flow into main collecting duct that leads to duodenum

Endocrine: (Tail)
- “Islet of Langerhans”
- Adjacent to and surround Acinar cells
- Produce hormones → blood
- D cells → secrete Somatostatin

*Somatostatin decreases Gastrin production (activated by H+) // Decreases enzyme release by acinar cells

28
Q

What features of the Alkaline pancreatic juice?
Which cells secrete it?
What stimulates its secretion?
What is its composition?
What are its functions?

A
  • Ductal region of the pancreas
  • Stimulated by Secretin

Composition = Na+, K+, HCO3-, Mg2+, Ca2+ → similar to plasma - isotonic

Functions:
- Neutralizes chyme
- Protects mucosa form acid
- pH necessary for enzyme function

29
Q

In the ductal region of the pancreas, what is the mechanism of HCO3- secretion of the alkaline pancreatic juice?

A
  1. Secretion of Cl- via CFTR channels into the lumen
  2. Secretion of HCO3- in exchange for Cl- at the lumenal membrane
  3. Secretion of H+ via the pumps on the basolateral membrane
    **Balances “alkaline tide”
  • No net Cl- secretion
  • CO2 entry from the basolateral side → H+ + HCO3-
30
Q

What is essential for activation of pancreatic Enzyme?

A
  1. Enterokinase is secreted by cells in the duodenum → cleaves Trypsinogen → Trypsin

Pancreatic enzymes are released as Zymogen granules by exocytosis → inactive components because they are so powerful they could dammage the pancreas if already active
- Activated by proteolytic cleavage with enterokinase from SI

  1. Trypsin acts in a positive feedback loop on itself and further cleaves Trypsinogen → trypsin
  2. Trypsin cleaves all other pancreatic enzymes into their active form in the SI
    Chymotrypsinogen → chymotrypsin + peptide
    Proelastase → Elastase + peptide
    Procarboxypeptidase → carboxypeptidase + peptide
    Prophospholipase a → phospholipase A + peptide
31
Q

What are 2 mechanisms of protection of the pancreas against the action of pancreatic enzymes?

A
  1. Enzymes are secreted as Zymogens (inactive form) and are activated by enterokinase which is produced in the SI, not in the intestine
  2. The pancreas produces a Trypsin inhibitor to prevent proteolytic cleavage and activation of the enzymes

*In the case of blockage of the pancreatic duct, there can be activation of the enzyme that are stuck and this can be very dammaging for the pancreas

32
Q

At each phases of digestion, what mechanisms regulate pancreatic secretions?

A

Pancreatic cells have Muscarini receptors (activated by ACh) + CCK-A receptor (CCK/Gastrin) + VIP receptor (Secretin/VIP)

Cephalic phase → Nervous control (Vagus ACh)

Gastric phase → Nervous (stretch) + hormonal (Gastrin)

Intestinal phase → APUD cells sense contents of the SI lumen
- H+ → Secretin → inhibits parietal cells, stimulates duct cells to secrete HCO3-
- Fat → CCK → stimulate acinar cells to secrete enzymes
- Somatostatin from D cells in islet of Langerhans → inhibits gastrin release + inhibits pancreatic acinar cells (decrease enzyme secretion)

33
Q

When would a doctor give somatostatin analogues to a patient?

A

If the case of pancreatic duct blockage, somatostatin analogues would inhibit pancreatic enzyme secretion → prevent risks of dammaging the pancreas

34
Q

How are the endocrine and exocrine functions of the pancreas impaired in chronic pancreatitis?
*Pancreatitis = inflammation at the level of the pancreas

A
  1. Blockage of secretory ducts + loss of acinar tissue
  2. Decrease alkaline secretion (ductal cells) + decrease enzyme secretion (acinar cells)

Has 3 possible major effects:
- Decreased enzyme activity → reduced digestion, poor absorption and weight loss
- Decreased micelle formation (change in pH and loss of lipases) → steatorrhea
- Increase acidity → ulcers, fiborsis of pancreas (not always the case, but can be)

35
Q

In Chronic pancreatitis, what would a Secretin test and a Glucose tolerance test show? (In our case there is ductal blockage of the pancreas)

A

Secretin test (stimulates bicarbonate secretion from ductal cells) showed loss of bicarbonate output

Glucose Tolerance test showed loss of blood sugar control
- pancreas is involved in regulation of blood sugar through release of Glucagon by a-cells and release of insulin through b-cells (in Islet of Langerhans)

*One could also detect higher CCK secretion to try to stimulate enzyme secretion from acinar cells, but this can be dangerous because enzymes are being produced, but are stuck in the pancreas → can be damaging
→ Give a Somatostatin analogue to inhibit enzyme secretion from acinar cells

36
Q

What are different functions of the Liver?

A
  1. Production of alkaline juices → to neutralize chyme
  2. Production of Bile acids → for fat digestion and absorption
  3. Degrade products of metabolism
  4. Detoxify poisonous and harmful subtances (ex: breakdown product of Heme)
  5. Excrete waste materials in bile
37
Q

What are 2 important effect of CCK on the liver/gall bladder?

A
  1. Opens the sphincter of Oddi (allows entry of contents in the duodenum)
  2. Contraction of the gall bladder
38
Q

What are some anatomic features of the Liver + Vessels?

A
  • 2 lobes
  • Largest gland in the body
  • Can remove ~3/4 and still have adequate function

Right and left hepatic ducts → join into the common bile duct
- In the absence of a meal, the sphincter of Oddi is closed, the bile goes into the gall bladder and is concentrated
- Cystic duct connected Gall bladder to Common bile duct

39
Q

How much bile is produced by the liver/day?

A

~ 500 mL
much less than pancreas (1500 mL/day)

40
Q

What are 2 types of hepatocytes?

A

Periportal hepatocytes:
- closer to the portal vein
- handle glucose (Gluconeogenesis + Glycogen deposition)
- oxidize metabolites
- produce bil salts (new + recycling/conjugation) → common bile duct and duodenum

Perivenous hepatocytes:
- closer to the other end (common bile duct?)
- transform toxins to excrete in the bile and enter the feces (Biotransformation)
- Glycolysis/ketogenesis/fat deposition
- Toxic metabolites → Commone bile duct and duodenum

41
Q

what are main features of bile salts?
What are primary vs secondary bile acids?

A
  • Made from cholesterol
  • Essential for digestion and absorption of fats

Primary Bile Acids:
- Made by hepatocytes
- Soluble in water → can be reabsorbed (at ileum)
- Conjugation of Glycine or Taurine residues to Cholesterol → increases water solubility

Secondary Bile Acids:
- Modified by bacteria in intestines
- Decarboxylation of bile salts
- Insoluble in water (unconjugated) → excreted in feces

42
Q

What explains steatorrhea?

A

Lack of absorption of fats → fats in feces
Due to:
- Lack micelle formation
- Lack of bile acid production

43
Q

What some Oxidized wastes products that can be found in the bile ?

A
  1. Detoxification of drugs in perivenous hepatocytes (Ethanol)
  2. Breakdown of Heme in perivenous hepatocytes (Conjugated bilirubin)
44
Q

How is ethanol detoxified in perivenous hepatocytes?

A

Ethanol → {Aldehyde} → Acetaldehyde → Acetic Acid → Acetyl-CoA (used for energy in cells)

45
Q

What are the steps of Heme breakdown in perivenous hepatocytes?

A

Heme comes from RBC destruction or myoglobin from a meal of meat

Heme → Biliverdin (green bile) → Bilirubin (red-orange)

Bilirubin ~ Bile pigments (gives color to feces) *Not soluble → conjugated in perivenous hepatocytes *Water soluble

Bilirubin diglucuronide = conjugated bilirubin which can move into the bile

46
Q

what does epigastric mean?

A

The right upper quadrant of the abdomen

47
Q

Why is the gallbladder important for digestion?

A
  1. Stores and concentrates bile
  2. Delivers bile to the SI during a meal

Concentration of hepatic bile = 26.0 mM vs Gallbladder bile = 145.0 mM

Gallbladder contraction is stimulated by CCK and Gastrin

48
Q

What is the composition of gallstones (both types)? What causes them to form?

A

Cholesterol Gallstones (80%):
- Caused by too much cholesterol in the liver due to high fat/sugar diet → can’t be fully processed into soluble bile acids or held into micelles → precipitates
- Decrease concentration of bile acids and phospholipids → cholesterol is not held within icelles and precipitates as crystals

Pigment Gallstones (20%):
- Overload of unconjugated bilirubin (hemolysis, burns)
- Bile becomes supersaturated and precipitates
- Free bilirubin combines with Ca++
- Burn patients → high hemolysis → lots of heme to breakdown

49
Q

How do gallstones cause pain?

A

meal → Gallbladder contraction (due to CCK secretion) → Bile flows through cystic duct, but presence of gallstones causes distension and pain

50
Q

In a patient with gallstones, what can explain the pale and greasy appearance of stools?

A

Pale color: absence of bile pigment
Greasy and floating: presence of abnormally large quantities of unabsorbed fat

*Bile is not properly secreted?

51
Q

How can Gallstones explain the yellowing of the sclera (eyes) and darkening of urine?

A

Gallstones can cause jaundice, leading to yellowing of the sclera (whites of the eyes) and darkening of urine, because a gallstone can block the bile duct, preventing bile, which contains bilirubin, from flowing into the intestines, causing (conjugated) bilirubin to build up in the bloodstream and be excreted in the urine

  • Bilirubin is not very water soluble
  • Hepatocytes conjugate bilirubin secreted into intestines → most will be secreted in feces
  • Intestinal bacteria modify bilirubin → deconjugated bilirubin can re-enter circulation (very small amounts) → converted to Urobilinogen (colourless)
52
Q

What is jaundice?

A

jaundice = yellowing of skin, sclera and mucous membranes

Plasma bilirubin > 34 uM/L
*Bilirubin is not very water soluble

53
Q

What is Stercobilinogen?

A

Last form of bilirubin modified by bacteria in the SI → ready to go into the feces

54
Q

Is the gallbladder essential for digestion?

A

The gallbladder concentrates the bile, but does not produce it → no problem as long as the patient does not have a very fatty meal in 1 sitting because the body will not be able to process all the fat