How much bile is produced by the hepatocytes per day?
What are the main organic components of bile secreted by the hepatocytes?
Bile salts Bile pigments Lecithin Cholesterol
Where is the aqueous component of bile produced? What does is contain?
The bile ducts NaHCO3
Where is bile mixture secreted into?
The bile canaliculi to the common hepatic bile duct and then is stored an concentrated in the gall bladder
What is the capacity of the gall bladder?
NaHCO3 secretion is increased by the action of what?
How is bile concentrated in the gall bladder?
The absorption of H20 which is mediated by active transport of Na+ and Cl- across the gall bladder mucosa
What induces gall bladder contration?
The presence of fatty acids in the duodenum after a meal stimulates CCK release from I cells, stimulating gall bladder contraction, relaxation of the sphincter of Oddi and emptying of bile into the intestine via the common bile duct
What are bile salts produced by?
What are bile salts produced from?
What rate are bile salts produced at and what percentage of the bile do they constitute?
approx 6g/day approx 65% bile
Describe the chemical makeup of bile salts
They have a steroid nucleus which is usually conjugated with an amino acid, making them AMPHIPATHIC (part water, part fat soluble) which allows stabilisation of fatty emulsions in aqueous conditions.
What are the most abundant bile salts?
Taurocholic and Glycocholic Acid (80% hepatic secretion)
What would occur with fats in the absence of bile salts?
Fats would form an oily later on the surface of the liquid chyme.
What is the function of bile salts?
Act as a deterrent to decrease surface tension and promote emulsification of fat particles, creating a large SA for the action of lipases. They then combine with lipid digestion products (monoglycerides, free fatty acids) to form MICELLES.
How are MICELLES arranges?
With their fat soluble side towards the LIPID CORE, and water soluble aspect in contact with the external solution.
Why is micelles formation necessary for efficient fat absorption?
It maintains a LARGE SA for lipd diffusion across the mucosal epithelium
How are bile salts reabsorbed?
Approx 94% is reabsorbed in the small intestine by ENTEROHEPATIC RECIRCULATION (on average bile salts recirculate 17 times before they are excreted) By PASSIVE DIFFUSION through the mucosa in the duodenum and by ACTIVE TRANSPORT in the TERMINAL ILEUM
Where are bile salts absorbed after being reabsorbed into the small intestine?
Into the LIVER before resecretion in the bile This process minimises the rate of DE NOVO bile salt synthesis which is controlled by enterohepatic availability and can be increased 10-fold by secretin
What is the main bile pigment?
Bilirubin, responsible for the yellow/green colour
What is bilirubin?
Main bile pigment, A breakdown product of the porphyrin subunit released from haemoglobin following lysis of ageing for damaged red blood cells.
How is bilirubin transported in the blood? Why?
Bound to albumin. Poorly soluble in water
What is bilirubin conjugated with in the LIVER?
Glucuronic acid in the liver to form water-soluble BILIRUBIN GLUCOURONID which is excreted into the bile canaliculi and ducts.
What to INTESTINAL BACTERIA convert the conjugated bilirubin into?
UROBILINOGEN, some of which is absorbed and either recirculated in the bile or excreted in the urine.
What is the majority of urobilinogen concerted into in the intestines before excretion in the faeces?
Why does jaundice occur?
Elevated levels of plasma bilirubin leading to yellow discolouration of the eyes, skin and mucous membranes
What are the three types of Jaundice?
Pre-hepatic Hepatic Post-Hepatic
What is PRE-HEPATIC Jaundice?
Due to haemolysis and excess bilirubin production leading to increased levels of circulating free bilirubin.
What is HEPATIC jaundice?
Occurs due to an inability of the liver to conjugate or excrete bilirubin and is common in hepatitis and alcoholic liver disease.
What is POST-HEPATIC jaundice?
Occurs due to OBSTRUCTION of the bile duct and is typically caused by gallstones formed due to increased cholesterol precipitation in the gall bladder.
What is the toxicity of bilirubin in adults?
Fat-soluble and accumulated in lipid rich material, such as the sclera of the eyes, but has minimal toxicity in the adult.
Why is a bilirubin build up dangerous in neonates?
It can cross the immature Blood Brain Barrier causing permanent mental retardation (kernicterus).
How is neonatal jaundice typically treated?
What is the majority of digestion dependant on>
Enzymes secreted from the stomach and pancreas
What does the mucosa secrete? In response to what?
approx 1500ml/day of mucous and electrolytes from BRUNNER'S GLANDS and the CRYPTS OF LIEBERKUHN In response to tactile/chemical irritation, vagal stimulation and secretin.
What do mucosa secretions function to do?
Lubricate and protect the intestine and provide a water vehicle for nutrient absorption.
What role do the cells of the intestinal mucosa have in digestion?
Carbohydrate digestion Oligosaccharides and polypeptides are present in the small intestine as a result of carb digestion by pancreatic alpha-amylase and protein digestion by pepsin/protease. Investine can't absorb these, so further digestion is mediated by OLIGOSACCHARIDASES and PEPTIDASES which are bound to electrolytes in the Crypts of Lieberkuhn covering the epithelium of the intestinal brush border with their active sites exposed to the luminal contents.
What types of absorption are important to consider in the body?
Carbohydrate Protein Lipid Sodium and Water Vitamins Minerals
What is digestion?
The enzymatic degradation of nutrient molecules into simpler component molecules
What is absorption?
The transfer of digestion products along with vitamins, minerals and water from the intestinal lumen into the circulation
Where does absorption mainly occur?
The small intestine approx 7L of the 9L of fluid that is ingested and secreted per day
How is the luminal surface of the small intestine adapted for absorption?
Possesing specific transport mechanisms and a large surface area. -Macroscopic folds in mucosa (project up to 8mm into the lumen, ^ SA by x3) -Folding of the epithelial membrane producing MICROVILLI, giving rise to the EPITHELIAL BRUSH BORDER (^SA by x20) Together these adaptations give an increase in absorptive surface area of the small intestine 1000-fold (tennis court)
What are dietary carbohydrates absorbed as?
Which is the predominant form?
Monosaccharides (glucose, galactose, fructose) following digestion by intestinal enzymes.
Glucose (80% total carb absorption)
Generally, how does absorption of carbohydrates across the epithlial membrane occur?
Either by secondary active transport (which can carry sugars against a concentration gradient) or facilitated diffusion (which cannot)
How does absorption of GLUCOSE and GALACTOSE take place?
What is the energy for this provided by?
Via Secondary Active Transport
The Na+/K+ ATPase on the basolateral membrane
This process is Na+ Dependent and relies upon a Na+ cotransporter carrier molecule in the luminal epithelial membrane to move monosaccharides against the concentration gradient
How does FRUCTOSE absorption across the epithelial membrane take place?
Via facilitated diffusion.
This requires a diffusion gradient from the intestinal lumen into the epithelium, the carrier molecule (GLUT5) simply acting to decrease the diffusion barrier created by the fatty cell membrane.
How do the carbohydrates then diffuse across the basolateral membrane?
The high intracellular concentrations of monosaccharides generated during absorption generate the concentration gradients required for these nutrients to diffuse across the basolateral membrane into the mucosal capillaries.
For all monosaccharides, this process occurs via facilitated diffusion linked to a carrier protein (GLUT2) to increase the rate of transport through the lipid membrane.
In what form are proteins absorbed?
Short peptides and amino acids
How are proteins absorbed?
The short proteins and amino acids are absorbed via secondary active transport using an H+ co-transport system.
In protein absorption, how is the H+ gradient across the apical membrane created? (for the secondary active transport)
What is the energy for the process provided?
How is H+ movement linked to transport of different pepides and AAs?
Created by a luminal Na+/H+ exchanger
Na+/K+ ATPase on the basolateral membrane.
Several specific carrier molecules are required, due to their diverse binding properties.
How are the di and tripeptides transported across the basolateral membrane?
Absorbed short peptides are degraded by intracellular peptidases before transport of amino acids across the basolateral membrane into the mucosal capillaries occurs via facilitated diffusion.
In what form are lipids absorbed?
Free fatty acids and monoglycerides
(after action of pancreatic lipases on emulsified dietary fat)
These are then packaged into micelles and transported to the luminal epithelial membrane where their lipid contents are released and diffuse into the cell.
What happens after the lipid contents of micelles diffuse across the luminal epithelial membrane?
MonoGs and Free FAs are then reconsituted into triglycerides by intracellular enzymes before being taken up by the endoplasmic reticulum and packaged within a lipoprotein coat to form chylomicrons.
How do the lipoprotein particles leave the mucosal epithelium?
Through the basolateral membrane by EXOCYTOSIS
but as they are too large to enter the mucosal capillaries they pass into the intravillous lymphatics (lacteals) instead before being returned to the blood via the lymphatic system.
What happens to bile salts from the micelles?
They are recycled to the liver by enterohepatic recirculation before being re-released to ferry more lipid to the mucosal epithelium for absorption.
How much water enters the small intestine per day?
9L (1.5L ingested, 7.5L secreted) and >80% is absorbed
<2L progresses into the large intestine, where a further 1.8L is absorbed
How does absorption of water occur?
Entirely by diffusion via an osmotic gradient across the intestinal wall, occurring largely secondary to absorption of NaCl
When H2O enters the intestine, it dilutes the chyme and reduces its osmolarity, thus favouring osmotic absorption of H2O.
How much Na+ must an adult abosrb from the diet per day in order to balance that lost via intestinal secretions?
How are even isotonic solutions absorbed in the small intestine?
Primary active transport of Na+ out of the epithelial cells (via a Na+/K+ ATPase on the basolateral membrane) into the paracellular space between adjacent cells is followed by electrostatic diffusion of Cl- and osmotic movement of H2O.
Epithelial cell Na+ is then replaced by facilitated diffusion from the intestinal lumen. This requires a carrier protein, meaning that Na+ diffusion usually occurs in association with nutrient absorption using one of the co-transport systems.
What does movement of Na+ and H2O into the paracellular space result in?
Elevated hydrostatic pressure - fluid is forced out into the interstitium (since this offers a low-resistance escape route), before being absorbed by the mucosal capillaries.
What is very important in the oral treatment of dehydration?
The mutual dependence of Na+ and nutrient absorption
e.g. in cases of childhood diarrhoea and vomiting. Both Na+ and H2O must be replaced, but Na+ absorption is poor unless some nutrients are available for co-transport. Feeding appropriate mixtures of NaCl and sucrose dissolved in sterilised water can achieve life-saving results, and is greatly superior to using an isotonic solution of salt alone.
Why does Na+ diffusion into the epithelial cell usually occur in association with nutrient absorption?
(Epithelial cell Na+ is then replaced by facilitated diffusion from the intestinal lumen)
This requires a carrier protein, and occurs in association with nutrient absorption using one of the co-transport systems.
What are the fat-soluble vitamins?
A, D, E, K
How are the fat-soluble vitamins absorbed?
With the fats in which they are dissolved
How are water-soluble vitamins absorbed?
Water soluble vitamins generally diffuse across the intestinal mucosa if they are taken at sufficiently high doses. This process is dependent on Na+ co-transport.
How is Vitamin B12 absorbed?
Requires a special complexing protein (intrinsic factor) which is secreted in parallel with HCl by the parietal cells of the gastric glands.
Intrinsic factor binds to vitamin B12 in the intestine forming a dimer which is both protective against digestion and allows binding to the epithelial cell membrane receptor. Vitamin B12 then dissociates from intrinsic factor within the cell and is carried in the blood bound to transcobalamin II.
What does Vitamin B12 most commonly result in?
This is an autoimmune disease in which antibodies are produced against parietal cells leading to intrinsic factor deficiency and malabsorption of vitamin B12.
Generally, how are most minerals absorbed?
In proportion to dietary intake, but absorption of iron and calcium may be regulated depending on physiological requirements --> This is achieved through increases in the availability of carrier sites on specific transport molecules within the mucosa.
What does absorption of dietary Ca2+ require?
Vitamin D (cholecalicferol)
What is the availibility of cholecalciferol regulated by?
Parathyroid hormone promotes renal activation of vitamin D, which increases levels of Ca2+ binding protein in the mucosal epithelium and the activity of the Ca2+ ATPase in the basolateral membrane, thereby increasing intestinal Ca2+ absorption.
What is the activity of parathyroid hormone inhibited by?
Elevated plasma Ca2+ levels (thereby providing negative feedback regulation of intestinal Ca2+ absorption)
How much iron is absorbed each day?
About 1 mg of iron, which is necessary for haemoglobin synthesis, (although 15-20 mg is normally ingested)
Where does iron absorption occur?
duodenum and jejunum
In terms of iron absorption, what type of ions are absorbed?
ferrous (Fe2+), rather than ferric (Fe3+), ions are absorbed
How are iron ions absorbed?
Intestinal absorption relies on binding to a transport protein, known as transferrin. The Fe2+-transferrin complex then binds to an epithelial membrane receptor before passing into the cell by endocytosis. Once inside the mucosal epithelium, the Fe2+ is released from transferrin as is absorbed into the circulation, where it becomes bound to plasma transferrin.
What occurs in iron deficiency?
(e.g. following blood loss) the ability to absorb iron is increased, with an increased density of membrane receptors for the iron-transferrin complex.