GIT secretions 2 Flashcards
What are functions of pancreatic secretions?
– Digestion
– Protection
• Neutralizes the acidity of the contents leaving the stomach
• Optimal pH for enzyme activity
What is the composition of pancreatic secretions?
• Composition:
– Same Na+ and K+ as plasma - isotonic
– high HCO3- concentrations (alkaline)
– low Cl-
– Enzymes: lipase, amylase and proteases
– Composition depends on flow rate:
• Low flow rates: isotonic – mostly Na+ and Cl-
• High flow rates: isotonic – mostly Na+ and HCO3-
Describe pancreatic secretions
• Acinar cells: low volume, NaCl, enzymes
• Ductal cells: modifies; absorbing Cl-, secreting HCO3-
via Cl HCO3- exchanger
• Pancreatic ductal cells are permeable to water
Describe the secretion of Secretin
Secreted from S cells of the dupdenum
Inresponse to protons in duodenal lumen
Cquses increases bicarbonate secretion
Describe the secretion of CCK
Secreted from I cells of duodenum
In response to small peptides, amino acids, fatty acids in duodenal lumen
Causes increased enzyme secretion and potentiates bicarbonate secretion
Describe the secretion of ACh
Secreted from vagus terminalis
In response to protons, small peptides, amino acids, fatty acids
Causes increased enzyme secretion and potentiates bicarbonate secretiom
What are the modulators of pancreatic acinar secretion?
- increases Cl secretion = -ve lumen
- increases Na and H2O follow passively into the lumen
- increases Exocytosis - release of zymogen granules into SI lumen
A rise in calcium conc. Triggers Acinar cell secretion
Describe ion transporter naming conventions
• final letter:
– C – co-transporter/symporter • moves ions in same direction
– E – exchanger/antiporter
• exchanges ions, i.e. moves them in opposite directions
• preceding letters: – N – sodium (Na+)
– H – proton (H+)
– B – bicarbonate (HCO3-) – K – potassium (K+)
– C – chloride (Cl-)
• e.g. NKCC is the sodium (N) potassium (K) chloride (C) co-transporter (C)
Describe bicarbonate secretion by ductal cells
HCO3-
– produced by carbonic anhydrase
– secretion via HCO3- Cl exchanger
Describe bicarbonate secretion by ductal cells
HCO3-
– produced by carbonic anhydrase
– secretion via HCO3- Cl exchanger
Describe Cl- secretion by ductal cells of the pancreas
– cellular Cl- can diffuse passively back into lumen through CFTR channel
– NKCC transporter also provides cellular Cl-
Describe Na+ and H2O secretion in ductal cells of the pancreas
follow passively para-cellularly down electrochemical gradient
Describe H+ secretion in pancreatic ductal cells
– formed with HCO in the cell
– exits across basolateral membrane via Na-H exchanger, entering bloodstream and neutralizing the alkaline tide
What is the pancreatic two component model?
Low Flow
- mainly NaCl
- from acinar cells
High Flow
- mainly NaHCO3
- from ductal cells
Describe the cystic fibrosis
• Defective CFTR (Cl- channel and eNaC regulator) • Consequences: Decreases Cl- secretion Decreases Lumen negativity Decreases Na+ and H2O movement Decreases Ductal secretion Decreases Enzyme action→ Malabsorption
Describe the pancreatic secretion time course
Interdigestive (fasting) phase- basal secretion rate
- Cephalic —> increased secretion rate (25%)
- Gastric—> increased secretion rate (10%)
- Intestinal —> increased (50-80%)
Late digestive —> decreased
Summarize pancreatic secretions of the cephalic phase
Cephalic phase—> increased vagal activity —> stimulates ductal and acinar cell
Ductal cells increase secretions of bicarbonate
Acinar cells—> increased secretion (enzym3s)
Describe pancreatic secretions of gastric phase
Food in stomach—>
Gastric distension increases vagal response (ACh) + gastrin release
Protein in food stimulates CCK
ACh, Gastrin, CCK stimulates acinar cells enzyme release
What is the rlevance of CCK to acinar cells?
• CCK release depends on content of meal – Fatty acids: large CCK response
– Amino Acids: intermediate CCK response
– Carbohydrates: minimal CCK response
- Exocrine pancreas has large reserves of digestive enzymes for carbohydrates and protein, less for lipid digestion
- Even lipid digestion is not affected until 80-90% of the pancreas is destroyed
Describe the relevance of secretin to the pancreas
• acts on pancreatic duct cells to increase cAMP levels, activating HCO3- and fluid secretion
• food buffers gastric acidity
– pH drop in duodenum may not be enough to produce high secretin levels
• CCK and ACh potentiate the effect of secretin on ductal HCO3- and fluid secretion
What are the functions of small intestines secretions?
Functions
– Protection
• Mucus prevents acid and protease damage to intestine
• Alkaline solutions neutralize chyme
– Digestion • Enzymes break down all major foodstuff • Alkaline solutions neutralizes chyme • Trypsin activates chymotrypsin and procarboxypeptidase • Bile emulsifies fat
– Control
• CCK and Secretin inhibit gastric motility and secretion
• CCK stimulates contraction of the gall bladder and relaxation of the hepatopancreatic sphincter
• Secretin stimulates secretion of bicarbonat
What are the functions of intestinal fluid secretions?
- Aids lubrication and motility (secretion failure = gut obstruction)
- Provides a source of Na+ to absorb nutrients if a meal has low Na+ content
- Vehicle for gut antibodies secreted from crypts
- General response to irritation/infection to “wash out” the problem
What are the steps in NaCl secretion in the small intestines?
- Na+-K+ pump in basolateral in membrane
- Low intracellular [Na+]
- Provides the energy for uptake of Cl- into the cell via the NKCC transporter in basolateral membrane
- [Cl-] increase so that Cl can exit passively through Cl channels in the apical me,brane
- Lumen becomes more negative
- Attracts Na+into the lumen down an electrical gradient
- H2O follows passively by osmosis
Describe large Intestinal secretions
– Alkaline mucus solution containing bicarbonate and K+
What are the functions of large intestinal secretions?
– Protection
• Resident bacteria release acid
• Mechanical damage by passage of feces
What stimulates large intestinal secretions?
Stimulation:
– Acid and mechanical
– Mediated by long and short reflexes
Describe distal colon NaCl Reabsorption
Na+ influx→ Lumen becomes more –ve. Cl- is absorbed paracellularly.
When body Na+ is low, aldosterone stimulates the ENaC pump to promote Na+ retention (similar in the kidney)
Summarize secretion of K+ in the distal colon
Passive K+ secretion driven by –ve luminal potential
Summarize K+ movement
- Intestines can absorb or secrete K+
- GIT plays a minor role in regulating K+ in the ECF.
- The kidney is the major regulator of K+ levels.
- K+ is absorbed in proximal segments of the GIT
- K+ is secreted in distal segments of the GIT
- Salivary, Gastric, Pancreatic and Biliary secretions: rich in K+
- High K+ load is presented to the small intestine
- Stool contains high levels of K+ (partly due to colonic secretion)
What is the effect of aldosterone?
Active K+ secretion in the distal colon
Summarize intestinal secretion & absorption
Small Intestine • Net absorption • H2O • Na+ • Cl- • K+• • Net secretion • HCO3
Large intestine Net absorption H2O Na+ Cl- Net secretion HCO3 K+
Describe intestinal solute abd H2O balance
- Secretory mechanisms are located in crypts
- Absorption mechanisms are located in the villi
- Cl- is the primary ion secreted
- Transported through a chloride channel regulated by cAMP
- Na+ secretion passively follows Cl-
- H2O follows osmotically
What is diarrhea?
(an increase in the volume or frequency of defecation) • Osmotic – Ingestion of poorly absorbed substrate – Malabsorption – carbohydrates
• Secretory
– Bacterial toxins
– Tumors, hormones
What is secretory diarrhea?
Increased endogenous secretions of fluid and electrolytes from GIT
Enterotoxin, V. Cholera
E. Choli
Enterotoxin e.g., Clostridium Difficile
VIP., histamine, prostaglandins
ACh, 5-HT, Bradykinin
What are the factors affecting Cl- secretion in SI?
Apical Cl- channels open in response to: ↑ cAMP ↑ Ca2+
Secretagogues induce apical Cl channel opening
Secretagogues: Hormones and neurotransmitters (ENS, VIP)
Products of immune cells (e.g. histamine)
Bacterial exotoxins (“enterotoxins”) Laxatives
Either by ↑cAMP
or ↑ Ca2+
Induction (recruitment and activation) of apical Cl- channels plays a major role in the pathophysiology of secretory diarrheas
Describe diarrhea and ootassium balance
Bacterial exotoxins (“enterotoxins”) Laxatives
What are the consequences of secretory diarrhea?
Loss of ECF type fluid from the GIT: up to 9L/day
1. ↓ Intravascular volume
↓ Arterial pressure
Circulatory collapse
- Loss of bicarbonate—> metabolic acidosis
- Loss of K+ - ->hypokalemia—> cardiac arryhthmias
