Lecture 6: liver, bile & jaundice Flashcards
What is the liver?
an organ in the body that is situated in the upper right quadrant of the abdominal cavity
Describe are the functions of the liver?
- synthesis and secretion of** bile **
- carbohydrate metabolism - liver contains glycogen, it can form glucose through gluconeogenesis
- fat metabolism - facilitated by bile salts
-
detoxification- inactivation of hormones, removal and detox of drugs through first pass metabolism etc
*** iron storage ** - synthesises and secretes IGF-1 & IGF-2 in response to secretion of growth hormone
what is the liver’s accessory organ & and what is it’s function?
- gall bladder
- stores bile synthesised by liver
what are the **structural units **of the liver called?
- hepatic lobules
- roughly hexagonal in shape
Describe the components of hepatic lobules
- they contain a central vein that lies at the centre of each lobule
- portal triads - branch of the hepatic artery, branch of the portal vein & a** bile duct**
- the hepatocytes radiate from the central vein - arranged like a spongle like structure
- sinusoids - branching blood vessels around hepatocytes
- bile cannaliculus - space between hepatocytes that communicates with bile duct
What are the hepatic acinus?
- this is the functional unit of the liver
- it is situated around the afferent vascular system of liver
What are the different types of cells in the liver?
- hepatocytes - most abundant
- Kupffer cells - macrophages of the liver
- endothelial cells (fenestrated)
- hepatic stellate cells
- cholangiocytes- bile secretion & motility
what is the** space between the hepatocytes & the sinusoidal wall** called?
- space of Disse
- contains a system of supoporting collagen fibres & drained by terminal lymphatic vessels
Describe the hepatic circulation
- the liver receives 25% of the cardiac output at rest
- hepatic artery carries oxygenated blood from the aorta to liver
- portal vein delivers nutrient rich but deoxygenated blood from the stomach, intestines and spleen
- **small portal venules **lying in the septa between the lobules receive blood from portal veins
- small hepatic arterioles in septa receive blood from hepatic artery
- from the venules and arterioles , blood flows into the** sinusoids **
- blood returns from liver to systemic ciruclation via hepatic vein
what does the blood in the portal vein contain?
- it conatins breakdown products of haemoglobin from the spleen & digested nutrients from the GIT
what do the sinusoids form?
- they essentially form a** leaky capillary network** from which blood flows from the portal vein and hepatic artery to the central vein of the lobules
where does the deoxygenated blood that has flowed into the central veins go to?
empties into the hepatic veins, which join the inferior vena cava
what are the** 2 types of cells** that line sinusoids?
- endothelial cells
- phagocytic kupffer cells (macrophages) - they remove debris and pathogens from the ciruclation by phagocytosis
Describe hepatocytes
- large polyhedral cells that have rough and smooth ER, mitochondria and lysosomes
- microvilli are present on their plasma membrane which provides a large surface area for exchanges of substances with the blood
What are the 3 zones of the hepatic acinus?
- zone 1- most oxygenated zone - carries out gluconeogenesis & oxidation of fatty acids
- zone 2 - intermediate zone
- zone 3 -least well oxygenated - glycolosis (anaerobic process - glucose to pyruvic acid), lipogenesis
Where does the liver gets its oxygen from?
-
hepatic artery - 15ml of oxygen per min
* portal vein - 36ml of oxygen per min (still delivering a substantial amount of oxygen to liver, but o2 delivery can decrease due to increase in GIT activity and oxyegn demand)
what fluid do the hepatocytes secrete?
- they secrete a fluid called hepatic bile into the bile canaliculi
what does hepatic bile contain?
- hepatic bile contains bile salts, bile pigments, cholesterol, mucus & lecithin
what happens to the hepatic bile after it passes through the bile ducts?
- the ductal epithelial cells (line bile duct)** modify **this primary secretion by secreting a watery, bicarbonate rich fluid that increases the volume of bile
- ductal epithelial cells add the aqueous component
What** hormone** stimulates the ductal epithelial cells that line the bile duct?
secretin
What are the functions of bile?
- emulsification of lipids
- hormonal action
- elimination of waste products eg bilirubin
what are the precursors for bile salts?
the bile acids
2 types - primary and secondary bile acids
what are the primary bile acids?
- cholic acid and chenodeoxycholic acid are synthesised from cholesterol in the hepatocytes
what are** secondary bile acids**?
- deoxycholic acid & lithocholic acid
- they are formed in the intestine by the dehydroxylating action of bacteria on the primary acids
what happens to the primary bile acids before their secretion as bile salts into the bile?
- they are conjugated (reversibly combined) with amino acids such as glycine & taurine to form water soluable bile salts
how does** bile emulsify lipids**?
note emulsify means - mixing 2 liquids that are normally not mixable
- bile salts have both hydrophobic and hydrophillic regions (they are amphipathic)
- they aggregate to form micelles when they reach a certain conc in the bile
- the hydrophillic group face the aqueous medium while the hydrophobic groups face eachother to form a core
How does bile act as hormones?
ie signalling molecules, where is the receptor expressed etc
- bile acids can also function as signalling molecules
- GPBA (G protein coupled receptor for bile acids) is expressed on several cells
1. These include enterochromaffin cells (neuroendocrine cells in GIT) & enteric neurons ** to control perastalisis
2. also on brown fat and skeletal muscle** for energy homeostasis
3. also expressed on **monocytes and macrophages ** - anti - infalmmatory effect
how are bile salts recycled?
- bile salts that enter the intestine via the bile duct are reabsorbed into the portal circulation via the portal vein in the terminal ileum via specific transporters
what** transporter** allows bile acids to return to the liver?
- they return to the hepatocytes via Na+ dependent organic anion transporter
What is bile acid solubility altered by?
- hydroxylation
- conjugation - this increases the water solubility of bile salts, which makes them relatively impermeable in the duodenum - which causes accumulation in the lumen
what is the role of the gall bladder?
- it stores the bile that isnt required immediately for digestion
- it also concentrates the bile by absorbing Na+, Cl-, bicarbonate and water
Explain the phases of gall bladder contraction
- cephalic phase - thought and taste of food - GB emptying
- **gastric phase **- vagus stimulated by gastric distension- GB emptying
-
intestinal phase
* presence of acid in duodenum causes a release of hormone secretin which causes the ductal epithelail cells to produce bicarb rich secretion
* presence of fat in duodenum causes CCK secretion which stimulates contraction of GB
how does bile remove waste products eg bilirubin?
- bilirubin is a component of bile
- bilirubin is formed when old red blood cells are broken down in the spleen
- in hepatocytes, the bilirubin becomes conjugated
what occurs if there is an accumulation of bilirubin in the blood?
- jaundice occurs if bilirubin is not being removed in bilary secretions
- yellow colour of the skin, the sclera of the eyes
what are gallstones?
- any excess cholesterol that cannot be dispersed into micelles may form crystals in the bile and contribute to the formation of gall stones
