Pathophysiology of jaundice Flashcards
What is the liver?
It is the largest and most important organ
- It contains 50K-100K lobules
What are the functions of the liver?
1) Blood reservoir
2) Blood cleansing
3) Metabolic functions
4) Storage of vitamins
5) Bile synthesis
6) Detoxification and excretion
7) Synthesis of substances used in coagulation
8) Iron buffering and storage
9) Storage of vitamins
Describe the blood supply of the liver
- It has a dual blood supply
- Supplied by the hepatic artery
- It has the portal vein
- It receives 27% of the cardiac output
- In case of cirrhosis, the blood flow will face an increased resistance
- Normally holds 450ml of blood in the hepatic veins and sinuses which can go up to 0.5-1 liter in case of right heart failure
What happens to the liver in a case of cirrhosis?
It is when the liver parenchyma cells are replaced by fibrous tissue that contracts around the blood vessels, impeding the flow of the portal blood through the liver
- It could be caused by alcoholism and excess fat accumulation in the liver which greatly increases the resistance to blood flow
What happens in the case of portal hypertension?
When a large clot for example develops in the portal vein the blood returned from the intestine, and spleen through the liver portal blood flow system is impeded which results in portal hypertension
How is the blood cleansed of debris in the liver?
The hepatic macrophage system includes:
1) Kupffer cells which line the hepatic venous sinuses, are very efficient phagocytic macrophages that digest the bacteria in less than 0.01 seconds
What are the metabolic functions of the liver?
- The liver has a chemically reactant pool of cells with high rates of metabolism including:
1) Carbohydrates:
- Stores glycogen
- Converts galactose and fructose to glucose
- Gluconeogenesis to maintain a normal blood glucose concentration
2) Fat metabolism:
- Oxidates fatty acids for energy
- Synthesizes cholesterol/phospholipids and lipoproteins
- It synthesizes fats from proteins and carbohydrates
3) Protein metabolism
- Deamination of amino acids for them to be used as a energy source or converted to carbohydrates or fats
- Formation of urea (removing ammonia from the body fluids)
- Formation of plasma proteins)
- Interconversion of amino acids
Describe the glucose buffer function
- In case of increased blood glucose:
1) The pancreas will release insulin
2) Insulin will induce the conversion of glucose to glycogen by the liver
3) Insulin will also induce ti the uptake of glucose by the cells
- This will lower the glucose levels in the blood
- In case of low blood glucose:
1) Pancreas releases glucagon
2) The liver will then break glycogen into glucose and release it to the blood returning it to normal levels
What are the vitamins that are stored in the liver?
1) The highest quantities of vitamin A (which is important for vision, growth, cell division, reproduction and immunity)
- In vitamin A deficiency the amount of light available at night is very minimal due to the depression in the formation of the rhodopsin and retinal
2) 3-4months store of Vitamin D
3) Vitamin B12
Describe the iron buffer function (apoferritin-ferritin system) of the liver
- The largest quantities of iron are stored as ferritin (Tranferrin releases ferrous which binds with apoferritin to be stored as ferritin)
1) A mixture of ferrous and ferric is ingested where the stomach acid converts the ferric into ferrous
2) Ferrous binds to gastroferritin which is transported into the small intestine and released for absorption
3) In the plasma the ferrous binds to the transferrin
4) Extra iron binds to apoferritin which binds reversibly and stores iron in the liver as ferritin
5) Other transferrin is distributed to other organs to use (for synthesizing hemoglobin or myoglobin for example)
What is the function of the gastroferritin?
It converts the ferrous iron into an absorbable form for the S.I
What are the substances synthesized by the liver for coagulation?
1) Fibrinogen
2) Prothrombin (Requires vitamin K)
3) Accelerator globulin
4) Factor 7 (Requires vitamin K)
What are the different causes of vitamin K deficiency?
1) Poor absorption of FAT from the GIT
2) Failure of the liver to secrete bile
Describe the detoxification and excretion function of the liver
1) Drugs like sulfonamides, penicillin, ampicillin, and erythromycin are excreted in bile
2) It eliminates ammonia by transferring it into urea
3) Degrades the Hemoglobin, eliminating the bilirubin (yellow pigment)
4) Excretes calcium (secreted by the liver in bile “feces”)
5) Excretes hormones (estrogen, progesterone, thyroxine, cortisol, aldosterone), in case of liver damage excess accumulation of these hormones can occur, and thus overactivity
How does the liver handle ammonia?
- Sources of ammonia include the colon, kidneys, RBCs, metabolism of muscles
- Ammonia is toxic to the brain as it can cross the BBB
- The urea cycle in the liver can convert ammonia to urea, and in case of liver disease ammonia can accumulate in the blood reaching the brain which can lead to brain-hepatic coma -death
What is the main function of the liver?
Secretion of bile
What is the function of bile?
- Fat digestion and absorption
- Bile emulsifiers large fat particles into minute particles so that it is easy for the lipase to attack it and aids in the absorption of the digested fat by the intestinal mucosal membrane
- Bile also helps in excreting waste products from blood like bilirubin and excess cholesterol
How is bile formed and secreted?
- Two stages:
1) Stage 1:
- The initial portion is secreted by the hepatocytes containing:
1) Bile acid
2) Cholesterol
3) Lecithin
4) Bilirubin
5) Ions
- Which are secreted into the bile canaliculi originating in between the hepatic cells
2) Stage 2:
- A second secretion of a watery solution of Na+ and HCO3- is secreted by the epithelial cells lining the ducts into the bile, which is stimulated by secretin
- The bile flows in the canaliculi towards the interlobular ducts which join forming larger ducts, finally reaching the hepatic duct and the common bile duct
- The bile then is either emptied into the second part of the duodenum or diverted towards the cystic duct into the gallbladder
What stimulates the second secretion of the bile?
Secretin
The final bile is composed of what?
1) Bile acids
2) Cholesterol
3) Lecithin
4) Bilirubin
5) Ions
6) Water
7) Na+
8) HCO3-
How is bile stored and concentrated?
- Bile that is continuously secreted by the liver is stored in the gallbladder
1) 450 ml of bile can be stored as a concentrated 30-60ml in the gallbladder as the water, sodium, chloride and most other small electrolytes are being absorbed through the gallbladder mucosa (concentrating constituents like the bile salts, cholesterol, lecithin and bilirubin)
What concentrates the bile?
The Gallbladder mucosa, which removes the water, sodium, chloride, and most other electrolytes
What are the final constituents of the concentrated bile?
1) Bile salts
2) Cholesterol
3) Lecithin
4) Bilirubin
What are the different control mechanisms of bile secretion?
- All under the intestinal phase
1) Chemical mechanism
2) Hormonal mechanism
3) Neural mechanism
What is the chemical mechanism of bile secretion control?
- Controlled by:
1) Bile salts
2) Fat digestion after a meal
What is the hormonal control mechanism of biliary secretion?
1) Secretin (stimulates aqueous alkaline secretion)
2) CCK (mediates the contraction of the gallbladder and the relaxation of the sphincter of Oddi
What is the neural control mechanism of bile secretion?
Vagal stimulation and intestinal enteric nervous system (minor role)
How is the gallbladder emptied?
- CCK is the most important hormone for gallbladder contraction
- As we digest food in the upper GIT the gallbladder begins to empty especially (fatty foods), rhythmically contracting the gallbladder and relaxing the sphincter of oddi
- CCK also activates the vagal afferents, triggering the vasovagal reflex which reinforces the gallbladder contraction (via ACh) and relaxes the sphincter of Oddi (via NO and VIP)
What is the reflex of the vagus that helps in emptying the gallbladder?
The VAGOVAGAL REFLEX TRIGGERED BY CCK
What is the electrolytes that is not absorbed when concentrating the bile?
Calcium
How is RBC recycled?
1) When the fragile RBC membrane is ruptured or the spleen self-destructs the RBC (if the spleen is removed old RBC is increased)
2) Hb is then released and phagocytosed by the kupffer cells in the liver and macrophages in the bone marrow and spleen
3) The breakage of Hb will produce globin which is recycled by the blood and heme, heme is broken down into iron which is stored, and bilirubin
4) The bilirubin gets picked from the blood by the liver and secreted into the intestine in the bile, it is then metabolized into stercobilin by the bacteria and excreted in feces
What and where is Hb phagocytosed?
1) Liver (by the kupffer cells)
2) Bone marrow and spleen (by the macrophages)
What is bilirubin toxicity?
- Normally bilirubin should be low (<1.2 mg/dl)
1) Free bilirubin can cross the BBB and bind to the phospholipid (gangliosides of the neuronal plasma membrane) causing irreversible brain damage
