Lecture 29 Flashcards
Where is the main area of absorption?
Duodenum
Where is the main area of watery absorption?
Colon
Anatomy of Small Intestine
Water, Sodium Chloride and Nutrient absorption
Secretors of bicarbonate
-done by increase SA
Surface of small intestine is amplified (folded) at 3 levels
Folds of Kerchring
Microvilli and Crypts of Lieberkuhn
Submicroscopic microvilli (facing lumen)
Anatomy of Large Intestine
Reabsorption of Water
Active secretion of Potassium and Bicarbonate
Surface of Large intestine is amplifies (folded) at 3 levels
-Semilunar folds
-Crypts, but no villi
-Microvilli
What is the daily volume of secretions into the GI tract?
Food 2.0 L/day Saliva 1.5 L/day Gastric Secretion 2.0L/day Pancreatic secretion 1.5L/day =8.5 L of secretions into GI tract daily
How much water is Reabsorbed and Secreted by the Small Intestine?
Reabsorbed= 6.5 L (of the daily 8.5L secreted-presentations of secretions to the small intestine is 8.5L/day
-main, along with nutrient, NaCl
Secreted= 1L daily
How much water is Reabsorbed by the Large Intestine?
Reabsorbed= 1.9L/day
-presentation of 2.0L of fluid/day
-primary secretion of K and Bicarbonates
(99% reabsorbed, and 0.1L lost as feces)
Increased Fluid loss in Feces
Change in (increase) secretion or (decreased) absorption
- will increase in fluid loss in feces
- diarrohea
Features of Small Intestine
6m Length ~200 m2 Area of apical Plasma Membrane Present: Folds, Villi, Crypts or glands, Microvilli -Yes Nutrient absorption -Yes Active Na+ absorption Absent Active K+ secretion
Features of Large Intestine
2.4m Length
~25 m2 area of apical plasma membrane
Present: Folds, Crypts or glands, Microvilli
No: Villi or Nutrient Absorption
-Yes Active Na+ absorption
-Yes Active K+ secretion (main functional difference, alongside bicarbonate and water reabsorption)
Comparing Structural and Functional Differences between the small and large intestine
Absorption of non-electrolyte nutrients occurs mainly in small intestine. where as both the small and large intestine absorb water and electrolytes (Na+, Cl- etc)
The small intestine absorbs net amounts of water, Na+, Cl- and K+ secretions and secretes HCO3-
Whereas the Large intestine absorbs net amounts of Water, Na+, Cl- and secretes both K+ and HCO3-
Intestinal Epithelial cells
Intestinal epithelial cells are Polar
Basolateral and Apical surface
Basal surface:
1. NaK ATPases- have alpha and beta units, remove 3x Na+ out of cell in exchange for 2x K+ = always have a deficiency of Na+ inside of the cell. (maintains low intracellular Na+) Channel has to work against Na+ gradient therefore active. always need deficiency of Na+ in the cell, therefore diffusive conc gradient for Na lumen –> cell through Apical 2Na+ glucose channel (co-transporter/symporter) (on submicroscopic villi)
-driven be high extracellular (Na+)
Therefore: -If you block, then no absorption of Na+ and glucose into the cell
Lastly: Glucose uniporter GluT2 facilitates downhill efflux (into blood stream)
Transepithelial movement of water and solutes
Either absorptive or secretory
Transcellular or paracellular
Transcellular= must move across 2 membranes (apical and basal) in series. Solutes involved, across at-least one membrane is active
Paracellular= movement passive via tight junctions
Absorption of water
Entirely of osmosis
Coupled by solute movement
Occurs via transcellular or paracellular routes
Paracellular predominates mode of absorption
Primarily in the jejunum
“solvent drag” responsible for considerable Na+ and urea absorption in jejunum
Na+ absorption
Occurs in villus epithelial cells of the small intestine and surface epithelial cells of the large intestine
All transcellular Na absorption mediated by Na-K pump (Na-K ATPase) on basolateral membrane
Maintains a low intracellular Na concentration
Provides force for Na movement from diffusion from lumen across apical membrane
Apical transport mediated by Na+ coupled transporters (e.g. Na/glucose transporters) or Na+ channels …. dependant on fasting/postprandial state and GI region (amount of glucose in GI tract)
-postprandial: Na-glucose co-transporters
-fasting: Na+ channels
4x types of Na+ reabsorption
- Na glucose co-transporters. Primarily on Jejunum (high) and (small a) Ileum, where most glucose reabsorption occurs.
-occurs due to activity of Na+K+ATPase maintaining low sodium in cell, concentration gradient - Na+H+ exchangers. Primarily in Duodenum and Jejunum (high a). Apical surface. Amiluroide drug blocks H+ ions and Na+H+ channel, NHe3
- Parallel Na+H+ x Cl-HCO3- exchangers. Ileum and Proximal Colon
ensure electrical charge balance, Cl- enters cell. HCO3- and H+ combine to form H2O and CO2 - Epithelial Na+ channel. Distal Colon(High a). Apical surface specific sodium channels which reabsorb Na+ in large colon
3x types of Cl- reabsorption
- Cl- channels. Jejunum(high), Ileum and Distal Colon(high)
- due Na+K+ ATPase - Cl-HCO3- exchanger
- Ileum, Proximal colon(high a), Distal colon - Parallel Na-H and Cl-HCO3- exchanges. Ileum and Proximal Colon.
Cl secretion
mainly absorb Cl- in GI tract
Some areas (Illeum and Prox colon) channels actively secrete Cl- ions.
These secretions still less than absorption (Net Cl- absorption)
1. Na+K+ ATPases, obtiquous channels present everywhere is nerves, muscles, cardiac, kidneys. Always deficiency of Na+ intracellularly
2. NaKCl2 channel- brings 2x Cl- into cell.
3. CFTR: Cystic Fibrosis Transmembrane Regulatory: Prox colon and distal colon contain CFTR. Receptor actively secreting Cl- (Active)
-activated when increase in cAMP in cell, or increased Ca2+ ions
-caMP and Ca2+ increase levels= Ecoli, serotonin, vibriocollora= seratigogs
4. Na+ moves Extracellular compartment –> into lumen via Paracellular pathway
5. NaCl (salt) conc increased in lumen. Osmotic gradient of Water (Extracellular –> Lumen)
=fluid loss
Histology Intestine
Goblet cell
-Large intestine colon
K+ absorption and secretion
- Passive Paracellular absorption of K+.
- Jejunum and Ileum. due to NaKATPase. With H2O - Passive secretion of K+
- Prox and Distal colon. due to NaKATPase (the lumen potential is -25mV) - Active secretion of K+.
- Prox and Distal colon. Due to BK channels - Na+K+H+ exchangers.
- Distal colon. apical K+H+ ATPase (H+ into cell) then Na+K+ basolateral
- Moderated by Aldosterone.
- Aldosterone increases when
a) Decreased Blood Pressure
b) Decreased Renal perfusion
c) Renin and Angiotensin activity
- increases Aldosterone
- -> increased Na+ reabsorption in Distal colon
- -> Increased H2O absorption (increased secretions)
- -> Increased BP blood pressure
Control of Absorption and Secretion
- Enteric nervous system ENS- release of Ach, VIP (vaso-active peptides) and other Secretagogues
- Endocrine system- aldosterone (ensures NA+ and K+ levels are maintained in GI tract)
- Paracrine system- 5HT (serotonin) (modulates Na+ K+ and HCO3- absorption and secretion in GI)
- Any change in absorption or secretion –> will lead to increased fluid loss in feces = diarohea
Small intestine absorption and secretion
The small intestine is a net absorber of water, Na+, Cl- and K+, but it is a net secretor of bicarbonates
Colon/Large intestine absorption and secretion
The human colon carrier out net absorption of water, Na+ and Cl- with few exceptions, but it carrier out net secretion of K+ an bicarbonate
Fluid movement
Fluid movement is always coupled to active solute movement
Solute movement
Solute movement may be coupled to fluid movement by solvent drag, a phenomenon in which the dissolved solute (e.g. Na+ or glucose) is swept along by bulk movement of the solvent (i.e. water)
Dysfunction of fluid absorption in the GI-diarrhoea
diarrhoea = Greek for “a flowing through”
>200g/day or 0.2L/day faecal water
3 or more liquid bowel movements per day (WHO)
2009:
-1.1 million deaths in people aged 5 and over
-1.5 million deaths in children under the age of 5
-2nd most common cause of infant death worldwide
Small intestine origin- voluminous
Large intestine origin- small volume diarrhoea
Osmotic diarrhoea: results from disturbances of absorption
Secretory diarrhoea: results from disturbances in secretion
Origins of Diarrhoea
Small intestine origin- voluminous
Large intestine origin- small volume diarrhoea
Functional Types of Diarrhoea
Osmotic diarrhoea: results from disturbances of absorption
Secretory diarrhoea: results from disturbances in secretion
Osmotic Diarrhoea
Interference with absorption
Generally caused by macronutrients malabsorption retaining osmotic pressure in the lumen and therefore water is retained
Examples include:
a) pancreatic disease (proteases, lipase and amylase)
b) large intakes of sugar alcohols (sorbitol, fructose intolerance, lactose intolerance, coeliac disease)
c) Lactose intolerance (carbs not broken down due to failing enzyme, increased osmotic load)
d) Coeliac disease
Lactose intolerance
Lack of the enzyme lactase in adulthood
75% of the world population show some intolerance
5% incidence rate in Northern Europe to >90% in part of Africa and Asia
-osmotic diarrohea
Coeliac Disease
Also called non-tropical spruce, or gluten enteropathy
(antibodies against own villi, villi destruction, less villi, decreased absorption, large osmotic load, diarrhoes + nutrient malabsorption)
Autoimmune reaction to gluten
Results in destruction of the epithelial cells
If severe results in blunting of the Villi
Nutrient malabsorption
-osmotic diarrhea
Secretory diarrhoea
An increase in the active secretion (Cl or Na+)
The most common cause of this type of diarrhoea is a exposure to the E. coli or cholera toxin
Enterotoxins produced by the bacterial micro-organisms raise intracellular [cAMP], [cGMP] or [Ca2+] -second messengers
–> (increased cytosolic Ca, increased activity of CFTR, increased Cl- movement into lumen, Na+ and H2O follows, diarrhoea)
Leads to stimulation of anion secretion, especially Cl- . To maintain a charge balance in the lumen Na+ is carried with it, along with water
Also congenital absence of Cl-HCO2 exchanger
- not just infection but congential
***Does not impact on nutrient coupled Na absorption (cotransporters), ORS containing glucose and Na+ is an affective treatment for secretory diarrhoea
Secreotry diarrhoea Bacterial Enterotoxins
Secretagogue+ 2nd messenger:
- Cholera toxin cAMP
- E coli: heat labile cAMP
- E coli: heat stabile cGMP
- Yersinia toxin cGMP
Secretory diarrhoea Hormones and
Secretagogue+ 2nd messenger:
- VIP cAMP
- ACh cGMP
- Serotonin Ca2+
Secretory diarrhoea Immune cell products
Secretagogue+ 2nd messenger:
- Histamine cAMP
- Prostaglandins cAMP
Secretory diarrhoea Laxatives
Secretagogue+ 2nd messenger::
1. Bile acids Ca2+
Sandy
CFTR activity increase
BP 60/40mm of Hg (normal 120/80 mmHg)
HR 120 Beats/min (normal 70 beats/min)
-decreased fluid, decreased Bv, decreased BP. Body tries to maintain homeostasis, baroreceptor reflex, HR increase (MAP= CO x TPR) (CP=SV x HR)
-Microscopic examination of the patient’s stool reveals the presence of a large number of Vibrio cholera bacteria (which increase cAMP activity, increased Ca2+ conc., increased CFTR activity, increase active secretion Cl-, Na+ paracellular movement, H2O flows paracellularily = increased Na+, Cl and H2O secretion into lumen=diarrhoea)
-watch diagram
Which compartments of the body are the fluids lost from?
BP low and HR high
Answer: ECF
-CFTR is active, removing Cl- into lumen, Na+ moves from ECF and equal amount if being lost from ECF
-(ECF –>ICF requires change in osmolarity)
No change in ICF, therefore no change in osmolarity, = ISOosmotic fluid loss (same osmolarity as within cell)
-no net change in osmolarity
-ECF is decreasing by the hour
-hence why BP is very low
Based on the new evidence what is your diagnosis of the patient?
Secretory diarrhoea
-increased CFTR activity, due to Vibrio cholera bacteria
Treatment:
1. Give IV fluids (isotonic fluid to expand shrinking ECF)
-Vib cholera infested cells (due to flow diarrhoea) get removed from body
-therefore dont need antibiotics.
-simply need to hydrate patient
-once ECF expanded well enough, patient can return home with ORS Oral Rehydration Solution
Principle behind Oral Rehydration Solution
- Na/Glucose or Na Amino Acid Co-transporters (Jejunum-high and Ileum)
-solution contains large Na and gluose, to facilitate the SGLT1 co-transporters = glucose drage Na+ into cell with it = Cl- moves with it = effectively H2O reabsorbed
-Na/glucose absorption effective - Cl-HCO3 exchanger (Proximal Colon-high, Ileum and Distal Colon)
- Parallel Na-H and Cl-HCO3- exchangers (ileum and Proximal colon)
-Cl absorption and secretion effective
** ORS contains Na+, glucose, Bicarbonates, Cl-
=to maintain ionic loss
- correct acidosis (that can result after acute or chronic diarrhoea)
Additional Result of Chronic or Acute diarrhoea
Acidosis
- Hence ORS Oral Rehydration Solution contains Bicarbonates
- to ensure acidosis is corrected
What is the purpose of Oral rehydration solution?
- To correct the loss of electrolytes from the body
- To restore fluid loss from the body
- To restore Na+ balance across the brush border to maintain the transport mechanism
- To aid osmotic reabsorption in the lumen
