5.2.2-5.2.4 - Mammalian Liver

• Liver


  Carries out several important roles in the body, including the breakdown of unwanted or toxic substances and the production of excretory waste
• Liver


  • Requires a constant blood supply
  • Supplied with oxygenated blood from the heart via the hepatic artery
  • Supplied with deoxygenated blood from the digestive system via the hepatic portal vein
  • Allows the liver to absorb and metabolise many of the nutrients that are absorbed into the blood in the small intestine
  • Deoxygenated blood leaves the liver in the hepatic vein and flows back to the heart
  • Connected directly to the gall bladder
  • Bile salts and bile pigments are stored in the gall bladder as part of the bile
  • Bile is released into the duodenum via the bile duct
• Liver lobules


  The functional unit of the liver, where all the functions of the liver occur
• Internal structure of the liver


  1. Divided into many lobules

  2. Separated from each other by connective tissue

  3. Branches of the hepatic artery and hepatic portal vein supply each lobule with blood

  4. Blood is carried in wide capillaries known as sinusoids

  5. Sinusoids are lined with an incomplete layer of endothelial cells

  6. Allows blood to reach the hepatocytes

  7. Each hepatocyte has a large surface area in contact with the blood to maximise the exchange of substances

  8. Each lobule is connected to a branch of the hepatic vein that drains blood away from the lobule
• The liver is mainly made up of cells known as hepatocytes that carry out almost all the functions required
• Which blood vessel brings oxygenated blood from the heart (aorta) to the liver?

  
  

  
  

  Why does the liver need this blood??

  hepatic artery

  (heart --> aorta --> hepatic artery --> liver)

  
  

  - hepatocytes v. active, bc they carry out many metabolic processes, which require energy in form of ATP

  - so it's important that liver has good supply of O2 for aerobic resp.
• Which blood vessel takes deoxygenated blood from the liver to the heart?

  hepatic vein
• What type of blood does the liver receive from the small intestine, and by which artery does it receive this?

  - deoxygentated blood which is high in nutrients/rich in products of digestion

  - blood may also contain toxic compounds absorbed from intestine

  
  

  hepatic portal vein
• What is the role of the hepatic portal vein?


  carries products of digestion from intestine to liver
• How can the hepatic portal vein and hepatic artery be differentiated?


  - Hepatic artery is narrow

  - Hepatic portal vein separates into many branched vessels
• Why does the hepatic portal vein have a larger diameter than the hepatic artery?

  - (lower BP)

  - slower blood flow

  - allows more time for exchange
• How will the composition of blood travelling in HPV differ from HA and why?


  HPV has

  - more CO2/less O2

  (intestine cells produce more CO2 from respiration/intestine cells use O2)

  
  

  - more monosaccharides, amino acids, vitamins, minerals and lipids (transported as lipoproteins) than blood in HA
• What are hepatocytes?


  liver cells
• How are hepatocytes adapted for their function?

  - metabolically active cells

  - constantly dividing by mitosis rapidly (liver regeneration)

  - large nuclei --> active DNA transcription

  - lots of Golgi apparatus --> high level of protein packaging + modification

  - lots of mitochondria --> produce ATP for cell reactions

  - (lots of rough and smooth endoplasmic reticulum)
• What are the roles of hepatocytes?

  - absorb products of digestion, oxygen + toxins from blood

  - break down toxins

  - convert glucose to glycogen

  - deaminate amino acids

  - break down RBCs to produce bile

  - secrete bile into canaliculi
• What are canaliculi and how are they related to bile?


  - spaces in the liver (narrow tubes)

  - hepatocytes secrete bile into canaliculi, which the drains into bile ductules then to gall bladder
• Outline the role of Kupffer cells


  - line sinusoids

  - act as macrophages

  - ingest foreign particles/pathogens (protect against disease)

  - breakdown + recycle old RBCs (one product is the bile pigment bilirubin, excreted as part of bile)
• Explain how the structure of the liver is adapted for its functions in the body


  - Blood from HPV brings products of digestion and cell metabolism to liver

  - Blood from HA brings oxygenated blood to liver

  - Blood from HPV and HA combine in the sinusoids --> provides raw materials + O2 for hepatocytes

  - Hepatocytes line sinusoids + absorb digested food, toxins + O2 from blood --> also break down toxins, convert glucose to glycogen, deaminate amino acids

  - Kupffer cells act as macrophages --> engulf + digest foreign cells and debris

  - Bile secreted into canaliculi as haemoglobin broken down in (/by?) hepatocytes

  - Hepatic vein removes deoxygenated blood carrying products of detoxification --> e.g. urea away from the liver
• What does bile contain?

  
  

  What are bile salts made of and what is their function?

  
  

  What are bile pigments and give 2 e.g.s?

  water, bile salts, bile pigments, cholesterol, electrolytes, hydrogen carbonate ions

  
  

  bile salts made from cholesterol - only they have a digestive function:

  * emulsify lipids - emulsification is physical breakdown of a large oil drop into smaller oil droplets - increases SA - more lipase action - faster/easier lipid digestion + easier absorption into the lymphatic capillaries in the villi.

  * aid in the absorption of fatty acids, cholesterol, certain vitamins.

  
  

  bile pigments are breakdown products from RBCs (e.g. bilirubin + biliverdin)
• How does the liver store sugar?


  - in the form of glycogen

  - the glycogen forms granules in cytoplasm of hepatocytes
• Hepatocytes respond to _____ to convert glucose into glycogen

  insulin
• Hepatocytes respond to ______ to convert glycogen back into glucose + release it into the b________

  glucagon

  
  

  bloodstream
• Give 6 functions of the liver

  - control of blood glucose, amino acid + lipid levels

  - synthesis of RBCs in the fetus, bile, plasma proteins, cholesterol

  - storage of iron, glycogen, vit A, D, B12

  - detoxification of alcohol, drugs

  - breakdown of hormones

  - destruction of RBCs
• Give 2 e.g.s of enzymes hepatocytes use to render toxic molecules less toxic and explain how they're used/their function

  catalase

  - hydrolyses hydrogen peroxide to O2 + H2O

  - has a high turnover number (no. of molecules of H2O2 that 1 mol of catalase can render harmless in 1 second) of 5 million

  
  

  cytochrome P450

  - group of enzymes that breakdown drugs inc cocaine + medicinal drugs

  - cytochromes are also used in other metabolic reactions like electron transport during resp

  - their role in metabolising drugs can interfere w other metabolic roles + cause the unwanted side effects of some medicinal drugs
• Why is catalase important?


  - H2O2 produced naturally in body

  - H2O2 is toxic

  - catalase converts H2O2 into non-toxic H2O and O2
• What does alcohol (ethanol) do?

  
  

  Where is ethanol found?

  
  

  What does alcohol contain?

  a drug that depresses nerve activity

  
  

  ethanol found in alcoholic drinks

  
  

  contains chemical potential energy, which can be used for respiration
• Describe how alcohol (ethanol) is detoxified by hepatocytes


  - ETHANOL broken down in hepatocytes into ETHANAL by ETHANOL dehydrogenase

  - dehydrogenated further into ETHANOIC ACID by ETHANAL dehydrogenase

  - this is then broken down into ETHANOATE (acetate)

  - acetate combines w coenzyme A to make ACETYL COENZYME A --> used in aerobic resp
• How is reduced NAD formed in process of alcohol detoxification?

  
  

  What is NAD also required for?

  - during the first 2 conversions, H atoms released from alcohol combine w NAD to form reduced NAD

  
  

  - NAD required to oxidise + break down fatty acids for use in resp.
• What happens to the liver when too much alcohol is drunk?

  - too much NAD is used by liver in breaking the alcohol down

  - has insufficient NAD left to oxidise + break down fatty acids

  - fatty acids then converted back to lipids + stored as fat in hepatocytes

  - this causes liver to become enlarged - this is called FATTY LIVER, which can lead to HEPATITIS or CIRRHOSIS
• Why can't excess amino acids be stored?

  
  

  Why would it be wasteful to excrete the whole of an amino acid?

  
  

  Which 2 processes do excess amino acids undergo to remove and excrete their amino groups? Give a word equation to illustrate all of this (the formation of urea)

  because the amine groups make them toxic

  
  

  amino acid molecules contain a lot of energy - almost as much energy as carbohydrates

  
  

  deamination followed by ornithine cycle

  
  

  amino acid --[deaminiation]--> ammonia (+ keto acid) --[ornithine cycle]--> UREA
• What is the ornithine cycle?


  a series of biochemical reactions that convert ammonia to urea
• Define transamination


  - conversion of one amino acid to another

  - carried out by hepatocytes

  - necessary as diet may not contain correct balance of amino acids
• Define deamination

  
  

  Give the word equation for deamination

  the removal of an amine group (NH2) from an amino acid

  - produces keto acid + ammonia

  
  

  amino acid + oxygen --> keto acid + ammonia
• Ammonia is v. soluble + toxic. So what must happen to it?


  - must not be allowed to accumulate

  - must be converted to a less toxic form v. quickly
• What is the removed amine group converted to and where is it converted?

  amine group --> ammonia --> urea

  - ammonia converted to urea in ornithine cycle
• Why is it necessary for deamination to occur in the liver?

  - body cannot store excess proteins or amino acids

  - excess protein would be egested

  - hepatocytes process excess protein to produce organic compounds (keto acid?) --> that can be used in resp or converted into lipids

  - toxic urea also produced --> excreted in urine
• Why would a high intake of protein likely result in a high concentration of urea in urine?


  - high intake of protein leads to a large amount of amino acids

  - excess amino acids cannot be stored

  - amino acids deaminated --> NH2 group converted to NH3 (ammonia)

  - large amount of ammonia enters ornithine cycle --> converted to urea

  - increased blood conc of urea leads to more urea in urine
• Describe how ammonia is converted into urea in the orthinine cycle


  - ammonia + CO2 combine w the amino acid orthinine to produce citruline (+ H2O mol)

  - addition of further ammonia converts citruline to arginine (+H2O mol produced)

  - arginine re-converted to orthinine by removal of urea (uses up H2O mol)
• Give the word and chemical equations for the formation of urea (summarising the ornithine cycle)


  ammonia + carbon dioxide --> urea + water

  
  

  2NH3 + CO₂ --> CO(NH₂)₂ + H₂O
• Draw a diagram of the orthinine cycle

  
  

  Where does this occur?

  in hepatocytes in liver