Liver Physiology Flashcards
What is the basic cellular structure of the liver?
Lobules
What are lobules made of?
Ramifying columns of hepatic cells
Where do portal vein and hepatic artery drain into?
Sinusoids
What do sinusoids open into?
Central vein
What are sinusoids? What is their function?
Special liver capillaries, blood flow regulation
What is the dual blood supply to the liver?
Hepatic portal system
Hepatic artery
Where does the hepatic portal system receive blood from?
Spleen
Intestines
Pancreas
Stomach
Where does the hepatic portal system empty into?
Inferior vena cava
What does the hepatic portal system supply?
Nutrient rich blood form the GI
What % of blood to the liver does the hepatic portal system supply?
70 to 80%
Why does the hepatic portal system store some blood?
It stores 450ml that can be shifted in times of stress
What is the blood in the hepatic portal system like?
Incompletely saturated
What kind of branch is the hepatic artery?
Primary branch from celiac artery which is one of the three main visceral branches of the aorta
What % of blood does the hepatic artery supply to the liver?
20 to 30%
What kind of blood does the hepatic artery bring to the liver?
Oxygen-rich blood
What are the functions of the liver?
Metabolism
Detoxification
Bile Production
Storage
Hematologic Functions
Synthesis
Conversion
Cholesterol Production
Enterohepatic Circulation
What kind of metabolic processes is the liver involved in?
Carbohydrate metabolism
Fat metabolism
Protein metabolism
What is the carbohydrate metabolism like?
Converts glucose to glycogen for storage and vice versa
What is the fat metabolism like?
Synthesis of fatty acids from glucose, breaks down fatty acids for energy and produces cholesterol
What is the protein metabolism like?
Deaminates amino acids, forms urea from ammonia and synthesis plasma proteins
What are the hematologic functions of the liver?
Synthesis of clotting factors
Hematopoiesis in the fetus
Recycling of haemoglobin
What is the conversion process like?
Converts ammonia to urea, which is excreted in the urine
What is cholesterol production like?
Produces cholesterol and excretes it in the bile
What are hepatocytes responsible for?
Synthesis of most of the plasma proteins
What is albumin?
The major plasma protein and is almost exclusively synthesised by the liver
What other substances does the liver synthesise?
Non-essential amino acids
What is one of the benefits of the liver regarding the fat metabolism?
Extremely active in oxidising triglycerides to produce energy
Where does the liver get fatty acids from and what does it do with them?
Gathers fatty acids from the diet and breaks them down to acetyl-coA
Where does the liver export large quantities of acetoacerate into?
The blood
What does it convert insoluble lipids into?
Soluble forms (lipoproteins)
What % of cholesterol is produced by the liver?
85%
What is interesting about synthesis and degradation of fats?
Both synthesis and break down of fats take place in the liver
Where is acetoacetate produced? And from what?
In the mitochondria of the liver from acetyl-coA
What are the functions of cholesterol?
It makes cell membrane, sex hormones, bile acids and vitamin D
What does “endogenous” mean, and how does it relate to cholesterol?
Manufactured by our own cells, 85% of cholesterol is endogenous
Where does the rest of cholesterol come from (the remaining 15%)?
From the food we eat
What is the function of the liver in regards of detoxification?
Serves as a gatekeeper between the circulation and the absorbed substances
What is the First Pass?
Every substance absorbed in GIT passes through the liver
What does detoxification include?
Drugs, poison and metabolic products like ammonia, alcohol and bilirubin
What are the two mechanisms of detoxification?
Binds materials reversible to inactivate and chemically modify compound for excretion
What are the principles of detoxification?
Elimination of hydrophobic compounds from the body
Formation of polar/soluble products
What is bile?
A yellow-green liquid that is continuously secreted by hepatocytes
What is the bile secretion pathway?
Bile from hepatocytes enters bile canaliculi which empty into small bile ducts
Hepatic ducts join the cystic duct from the gallbladder to form common bile duct
What is the daily secretion of bile?
500ml
What is bile composed of?
Bile salts including bile acids (50%)
Phospholipids, Lecithin (40%)
Bile pigments, bilirubin (2%)
Cholesterol (4%)
Electrolytes & Water
What is the function of bile?
Emulsifying fats; aids in fat digestion and absorption
What are bile salts?
Amphipathic molecules
Ampipathic = hydrophobic and hydrophilic parts
What do hepatocytes secrete?
Organic components (bile acids, cholesterol and bilirubin)
What do bile ducts secrete?
Watery solution, sodium, bicarbonate
What are organic constituents like?
Highly concentrated
What happens to watery components?
Reabsorbed by the gallbladder mucosa
What is the function of the gallbladder?
Stores bile
Concentrates bile
Empties bile
What happens to most of the bile?
Most of the bile is recycled, 2 to 3 times during the digestion of a single meal –> Enterohepatic circulation
Which kinds of agents increase the formation of bile?
Cholerectic agents
Which is the rate limiting enzyme in the bile formation process?
Cholesterol 7-a-hydroxylase
When is cholesterol 7-a hydroxylase inhibited?
By high levels of bile acids
What are the bile formation processes?
Primary bile acids formation
Secondary bile acids formation
Where are primary bile acids formed?
Hepatocytes
How are secondary bile acids formed?
In the large intestine, bacteria convert a portion of each primary bile acid to a secondary one
What are the primary bile acids?
Cholic acid and Chenodeoxycholic acid
What are the secondary bile acids?
Deoxycholic acid and lithocholic acid
What are the two pathways used for bile acid synthesis?
Classic and alternative pathways
Explain the classic pathway of the bile acid synthesis process
Cholesterol –> 7a hydroxylate –> Sterol 12-a hydroxylate OR CYP27A1 –> Cholic acid OR Chenodeoxycholic acid
What do gut microbiota do?
15% of conjugated bile acids are deconjugated by intestinal bacteria
What are the enzymes used by gut microbiota to deconjugate the bile acids?
Bacterial bile salt hydrolase
Bacterial 7 a dehydroxylase
What is the alternative pathway process?
Cholesterol –> 27 hydroxylase –> Oxysterol 7a hydroxylase –> Chenodexycholic acid
What is the final step of bile acids synthesis?
It goes into the terminal ileum and colon and it becomes DCA, LCA and UDCA
What is the process of formation of canicular bile?
Bile salts and bile acids are formed by hepatocytes
Bile pigments are picked up from blood sinusoids
Conjugation of bilirubin occurs in hepatocytes
What is bilirubin?
A metabolite of heme that is potentially toxic to the body
What is one of the key characteristics of bilirubin?
It is capable of crossing the BBB
Where does most of the bilirubin come from?
RBCs
Where does the minority of bilirubin come from?
Heme-containing proteins in other tissues (skeletal muscle and liver)
What does bilirubin provide colour to?
Bile, feaces, and to a lesser extent urine
What are the three fates of bilirubin in the intestines?
- Reabsorption into the blood
- Excretion in feaces
- Conversion by intestinal flora to urobilinogen
How does bilirubin relate to jaundice?
Bilirubin accumulation in the blood stream, often due to liver diseases, leads to jaundice which manifests as the yellow discolouration of the skin and the conjunctiva
How does jaundice develop in newborn babies?
Red blood cells die in large numbers after birth,
A lot of bilirubin is created,
The liver is not mature yet so it processes bilirubin very slowly,
Very little bilirubin actually leaves the body,
The excess, unprocessed bilirubin builds up everywhere in the body –> yellow discolouration in skin and eyes
What are the functions of the gallbladder?
Storage of bile
Release of bile
Regulation of bile flow
Bile pH regulation
How is storage of bile in the gallbladder important?
Bile is stored and concentrated in the gallbladder, aids in digesting fats
What happens during the release of bile in the gallbladder?
After consuming fatty meals, the gallbladder releases bile into the small intestine to emulsify fats –> Aids absorption
How is the bile flow regulated in the gallbladder?
Gallbladder controls bile flow into the small intestine by contracting and relaxing its muscles, ensuring bile is released in a controlled manner
What happens if bile becomes too acidic?
It can lead to gallstones
What is the neurohormonal control of gallbladder contraction and biliary secretion?
Bile is released in response to signals that simultaneously relax the sphincter of Oddi and contract the smooth muscle that encircles the gallbladder epithelium
What is hormonal control mechanism of biliary secretion?
CCK
What are the neural control mechanisms of biliary secretion?
Parasympathetic (vagal nerve)
Sympathetic
What is the effect of the parasympathetic neural control on biliary secretion?
Contraction of gallbladder
Relaxation of sphincter of Oddi
Increased bile formation
What is the effect of the sympathetic neural control on biliary secretion?
Reduced bile secretion
Relaxation of gallbladder smooth muscle
What is the enterohepatic circulation?
The recirculation of bile salts
Where are specialised cells contained and what are their function regarding bile salts?
The terminal ileum contains specialised cells that are responsible for the absorption of primary and secondary bile salts by active transport
Why is enterohepatic circulation important?
It is necessary because of the limited pool of bile salts
What does resection of the ileum lead to?
Prevents absorption of bile salts which leads to steatorhea
How could fats and bile salts increase water content of feaces?
By promoting the influx of water into the lumen of the colon
How is ammonia primarily produced?
Through the breakdown of amino acids during protein metabolism
Where is ammonia derived from?
The colon by bacterial creases (50%)
The kidney (40%
Deamination of amino acids (liver and metabolic processes in muscle cells) (10%)
What is the only tissue in the body that can convert ammonia to urea?
The liver
What does ammonia do to CNS?
It is toxic
What is the purpose of converting ammonia to urea in the liver?
To prevent toxic accumulation of ammonia in the bloodstream
What are the key enzymes in the urea cycle?
Carbamoyl phosphate synthase I
Ornithine Transcarbamylase
What is the toxic effect of urea oil comparison to ammonia?
Urea is much less toxic than ammonia so it is released into the bloodstream and transported to the kidney
Where is urea excreted?
In the urine
How does liver disfunction lead to hyperammonemia?
Liver disease impairs the liver’s ability to function properly leading to increased ammonia levels in the blood
What kind of liver disease can lead to hyperammonemia?
Cirrhosis or hepatitis
What can hyperammonemia lead to?
Encephalopathy, CNS impairment (confusion and disorientation)
