Pharmacology Renal and Hepatic Disease Flashcards
Describe the basic anatomy of the liver:
Left and right lobe
8 segments made up of lobules
Describe the lobules of the liver:
Each lobule made of central vein, radiating sinusoids (type of blood capillary) bile ducts, hepatocytes and other cells
What are the functions of bile ducts in the liver?
Join to form common bile ducts which drains bile into the duodenum after storage and concentration in the gall bladder
What is the function of the hepatic vein?
Deoxygenated blood from liver to heart from inferior vena cava
What is the function of the hepatic portal vein?
Carrying nutrient rich blood, oxygen poor, coming from GIT so can then travel to the body
Describe the vascular structure of the liver:
25% of resting CO in the liver (25% of bodies blood in liver at a time)
25% of blood is coming from the hepatic artery to liver (oxygen rich)
75% of blood is coming from the hepatic portal vein to liver (nutrient rich)
Blood leaves by hepatic vein to inferior vena cava to the heart
Name the structures in the hepatic lobules:
Portal triad
Sinusoidal capillaries
Central vein
Bile canaliculi
Hepatocytes
Name the features of the portal triad:
Bile duct
Portal vein
Artery
Name immune cells in the hepatic lobule:
Hepatic stellate cells (HSC)
Kupffer cells (KC)
Fibrocytes
What is the function of the HSC in the hepatic lobule?
Supporting hepatocyte
Perisinusoidal- very close to the blood capillaries
Antigen presenting role
Responsible for liver fibrosis (scarring) in liver disease
Important physiologically but bad in disease
What is the function of the KCs in the hepatic lobule?
They are macrophages attached to the endothelium
Phagocytosis of any foreign substances/ bacteria carried from the GIT in the portal vein
During disease can become inflammatory cells
Important physiologically but bad in disease
What are the functions of the liver?
Metabolism
Immunity
Storage
Detoxification
Synthesis
Catabolism
Activation
Transport
Excretion
How does the liver metabolically process carbohydrates?
Stores glucose as glycogen:
-up to 24 hrs worth
-not as good as not as energy dense and need water in there so lots of space taken up
Glycogenolysis in fasting
Gluconeogenesis in fasting:
-made from F.A and a.a
How does the liver metabolically process lipids?
Synthesis of cholesterol in liver
Lipoproteins
How does the liver metabolically process proteins?
Non-essential a.a synthesis
Breakdown of a.a to ammonia to urea for excretion
What is the difference between essential and non-essential a.a?
Non- essential= means we can synthesise it ourselves in the body
Essential= comes from the diet
Why does detoxification take place in the liver?
Conversion of harmful ammonia to urea- major elimination route of nitrogenous waste
Name and describe the different phases of drug detoxification and degradation in the liver:
Phase I reactions- by cyp450 enzymes
Phase II reactions- conjugation with other compounds to become more hydrophilic e.g gluconosyltransferase
What factors can affect metabolism?
Age, nutrition and genetics
What endocrine activities for modification of some hormones does the liver do?
Vit D3 to 25-OH vit D3 then in kidney 1,2 (OH2)D3
Thyroid hormone-> conversion of T4 to more potent T3
Insulin like GFs produced by hepatocytes modify action of growth hormone
What endocrine activities for major organ degredation of hormones does the liver do?
Insulin and glucagon
Oestrogens, glucocorticoids, growth hormones, PTH
Gastrin and other GI hormones
What does the liver store?
Fats- can be a problem during obesity, fatty liver
Glycogen
Trace elements- copper, iron
Vitamins A,D,K, some water soluble B vitamins for shorter periods
What does the liver synthesise?
Hormones
Plasma proteins
Iron transport and metabolism proteins
Acute phase proteins
Bile acids
Describe hormones synthesised by the liver:
Insulin like GF
Thrombopoietin- stimulates platelets
Describe plasma proteins synthesised by the liver:
Coagulation factors
Transport for cholesterol (lipoproteins)
Transport for steroid and thyroid hormones
Angiotensinogen- important for salt conversion
Describe iron transport and metabolism proteins synthesised by the liver:
Transferrin- transports iron in the blood
Hepatoglobin- bind free Hb blood
Hemopexin- bind free heme in blood
Hepcidin- inhibits iron uptake by gut
How is hemopexin involved in inflammation?
Important as can’t have free iron in the blood as its a pro-oxidant
During infection bacteria is attracted to this
Describe bile acids synthesised by the liver:
Primary:
-cholic acid
-chenodeoxycholic acid
Secondary:
-deoxycholic acid
-lithocholic acid
Where is bile secreted and stored?
Actively secreted by liver and actively diverted to gall bladder between meals
After a meal it enters the duodenum
Stored and concentrated in gall bladder
What is the composition of bile acids?
Aqueous alkaline fluid containing:
-bile salts
-cholesterol
-lecithin
-bilirubin
Describe excretion in the liver:
Excretion of cholesterol and bilirubin through bile secretion
Secreted bile salts consist of 95% of old recycled bile salts and 5% newly synthesised bile salts
How are bile salts recycled?
Re-absorbed in terminal ileum into the hepatic portal vein and into liver