Exam 3 – Dr. Sullivant Hepatic Physiology Flashcards
What is ascites?
Fluid accumulation in peritoneal cavity
What are the different types of ascites?
Transudate
Modified transudate
Exudate
What is icterus?
Elevated bilirubin levels
What is cirrhosis?
Condition in which normal cells are replaced by scar tissue
What is portal hypertension?
Hypertension in the portal vein and its branches
What is metabolism?
Sum of all anabolic and catabolic reactions as it related to use of all nutrients
What are the functions of the liver?
Filtering and storage of blood Metabolism of CHOs, proteins, and fats Metabolism of hormones, drugs, and toxins Formation of cholesterol and bile Storages of vitamins and iron Production of coagulation factors Production of plasma proteins Lymph formation
What is the liver lobule?
Basic functional unit of the liver
Where do most of the liver functions occur?
In the lobules
Where does the liver make lymph?
In the sinusoids
Where does the major supply to the liver come from?
Portal vein
What do hepatocytes do?
Clean and detoxify blood to make sure it does not go into systemic circulation
What happens once everything that goes to the liver gets cleaned up?
It moves to the central vein where it is released to the jugular vein, the heart, and then goes through it all again
Look at liver anatomy
Look at liver anatomy
Describe the liver anatomy
Largest internal organ
2-5% total body weight
Receives 30% of cardiac output
How many lobes does the liver consist of? What are they?
6 Right and left medial Right and left lateral Quadrate Caudate
What are venous sinusoids lined by?
Endothelial cells with large pores to allow movement of plasma proteins
Large Kupffer cells
What are Kupffer cells?
Macrophages
Describe Kupffer cells
Keeps less than 1% of GI bacteria from entering systemic circulation
Defense mechanism
What percentage of lymph in the body is made in the liver?
50%
What do sinusoidal endothelial cells do in the lymph formation the liver?
Leak fluids and proteins into “space of Disse”
What happens if lymph leaks out into the body?
There is a protein concentration of 6g/dl (slightly less than plasma protein)
What does increased sinusoidal pressure cause?
Increase in lymph production
What happens if the liver is losing a lot of lymph?
Any disease of the liver can occur, especially chronic disease such as fibrosis and cirrhosis
What happens once sinusoidal pressure rises enough?
The liver sweats lymph which leads to ascites
What does the liver have a high capacitance for?
Lymph
What can lymph cause the liver volume to do?
Increase by 1 liter or more
What can the liver perform for blood?
Vast storage
Extramedullary hematopoiesis
What is extramedullary hematopoiesis?
Making blood cells outside of the bone marrow
When can the liver make blood cells?
Cytokine stimulation
Hypoxia
What is the blood flow break down of the liver?
20% from hepatic artery
80% from portal vein
What is the oxygen supply breakdown of the liver?
50% from hepatic artery
50% from portal vein
What do portosystemic shunts do?
Shunting of blood from portal circulation to systemic circulation without passing through the liver
What are the types of portosystemic shunts?
Congenital
Acquired
What does an extrahepatic shunt do?
Goes around the liver
What does an intrahepatic shunt do?
Go through the liver, but it is not the correct path
What makes up the portal vein?
Spleen
Pancreas
GI tract
Look at blood flow picture
Look at blood flow picture
What are congenital shunts?
Intrahepatic or extrahepatic anomalous vessels that does not allow the blood to take a normal course through the liver
What is an examples of a congenital shunt?
Portocaval shunt: portal vein empties directly into caudal vena cava
What are consequences of congenital shunts?
Impaired liver development
Liver dysfunction
Liver failure
End stage cirrhosis without repair
What does impaired liver development cause?
Stunted growth
What does liver dysfunction cause?
Build up of toxins, especially ammonia
Poor ability to metabolize anesthetics/sedatives
What is the pressure in portal vein?
9 mmHg
What is the pressure in the hepatic vein leading to the vena cava?
0 mmHg
Why is the 0 mmHg pressure in the hepatic vein good?
It is the perfect low pressure gradient to get blood from the intestines and spleen, throughout the liver, into vena cava and back into the right atrium
What can ascites do?
It can leak from the portal vessels or from the liver tissue itself
What are causes of portal hypertension?
Cirrhosis
Severe infection
Chronic biliary tract obstructions
Portal vein thrombosis
What are the consequences of portal hypertension?
Gastrointestinal edema/ulceration
Severe GI signs and protein loss
Ascites
Acquired portosystemic shunts
What does cirrhosis cause?
Fibrous tissue to contract around blood vessels
Describe acquired shunts
Multiple tortuous vessels outside of the liver develop due to high pressure in the liver (acts as a relief valve for portal vasculature)
All throughout abdomen
Often near the kidney
Worsens liver function
What are causes of congestion?
Right sided congestive heart failure
Heartworm disease
Congenital diseases
Cor pulmonale
What are the consequences of congestion?
Gastrointestinal edema/ulceration
Severe GI signs and protein loss
Ascites
How can ascites happen in liver disease?
Obstruction of lymph flow/congestion (right sided heart failure)
Portal hypertension (increases resistance to blood flow through the liver)
Increased sinusoidal pressure in the liver
Hypoalbuminemia
How is the liver forgiving?
There are insults and then there is a repair process
Great ability to repair and regenerate
Transforming growth factor B can stop liver cell proliferation
When the liver does not repair, what happens?
Insults turn into fibrosis which turns into cirrhosis
What does the liver store?
Vitamins (A, D, B12)
Iron
What is iron stored as?
Ferritin in hepatic cells by combining with the protein “apoferritin”
It is released from storage in times of need
What is the livers role in coagulation?
Makes most of proteins needed in the process–fibrinogen, prothrombin, and clotting factors 2, 7,9, and 10
Describe clotting factors 2, 7, 9, and 10
Vitamin K dependent
The liver activates vitamin K so that it can be used to make these factors
What is the role of the liver in drug, hormone, and toxin metabolism?
Detoxify/activate antibiotics Excrete antibiotics into bile Chemical alteration of hormones Excrete hormones Calcium excretion
What is bilirubin?
Greenish, yellow pigment that is the major end product of hemoglobin degradation
Where does bilirubin come from?
Old, sick, and tired RBCs that get phagocytosed by macrophages
Hgb is split into globin and heme which releases free iron and a substrate from which bilirubin will be formed
What is biliverdin?
Free bilirubin released from macrophages into circulation
What is the formation of bilirubin?
Senescent RBCs have Hgb which splits into iron and biliverdin by heme oxygenase. Biliverdin becomes bilirubin by biliverdin reductase
What does free bilirubin do?
Joins albumin and is transported throughout the body
What happens when the bilirubin/albumin combo reaches the liver?
They are absorbed through the hepatocyte membrane
What happens to bilirubin inside the hepatocyte?
Conjugation with glucuronide, sulfate, and others (conjugated bilirubin)
It is excreted into bile canaliculi and then into intestines
What is the fate of bilirubin?
Converted via bacteria to urobilinogen
What happens to urobilinogen?
It is reabsorbed through intestinal mucosa back into blood
Most goes back to liver for re-excretion into gut and is oxidized to stercobilin
5% is excreted by kidneys and is oxidized to the urobilin
Where is stercobilin excreted?
Feces
Where is urobilin excreted?
Urine
Look at bilirubin metabolism
Look at bilirubin metabolism
What is increased bilirubin known as?
Hyperbilirubinemia, icertus, or jaundice
What is the yellowish tint to body tissues due to?
Excessive build up of conjugated or unconjugated bilirubin
What is the normal range of bilirubin? What is the range of bilirubin with jaundice?
0.2-0.6 mg/dl
2 mg/dl
What occurs with hyperbilirubinemia?
Bilirubinuria, which is often the first sign of liver disease
What can cause hyperbilirubinemia?
Hemolytic anemia
Liver failure/dysfunction
Obstruction of biliary tracts in the lover
Obstruction of posthepatic biliary system
What happens with liver failure/dysfuction?
Bilirubin is not processed/conjugated properly by sick liver cells
What happens with obstruction of biliary tracts in the liver?
Bilirubin can’t get out of the liver due to obstructed bile flow
Where does obstruction of postheptaic biliary system?
Gallbladder
Common bile duct
Pancreas
Describe hepatic metabolism
High rate of metabolism
Shares substrates with other organs
Processing and transportation to other organs
What are manifestations of liver disease?
Decreased albumin Decreased glucose Increased bilirubin Decreased protein metabolism Increases ammonia
What does decreased albumin cause?
Decreased colloidal osmotic pressure which leads to effusions and edema
What does decreased protein metabolism cause?
Decreased urea
What does increased ammonia cause?
Hepatic encephalopathy
What are coagulopathies involved in the manifestations of liver disease?
Increased prothrombin time Increased partial thromboplastin Platelet dysfunction Decreased fibrinolysis Excessive fibrinolysis
What is alanine aminotransferase (ALT)?
Leakage enzyme made inside hepatocytes
Indicators of hepatic injury
What is aspartate aminotransferase (AST)
Leakage enzyme made inside hepatocytes mitochondria
Indicators of hepatic injury
What is alkaline phosphorase (ALP)?
Induced enzyme made in lining of bile caniliculi
Elevated with cholestasis
What is gamma glutamyltranspeptidase (GGT)?
Induced enzymes made in lining of bile caniliculi
Excellent marker for hepatobiliary disease especially biliary tract disease
Elevated with cholestasis
What do you look for on bloodwork?
Increased bilirubin Decreased albumin Decreased cholesterol Decreased glucose Decreased BUN Increased ALT/AST Increased ALP/GGT
What can be done to test liver function?
Bile acid assay
Ammonia tolerance test
What are the pros of bile acid assay?
Can do in practice
What are the cons of bile acid assay?
Have to feed patient
Cannot rely on results if bilirubin is elevated
What are the pros of ammonia tolerance test?
Can do if bilirubin is elevated
What are the cons of ammonia tolerance test?
Not able to do in practice
Can cause hepatic encephalopathy/coma
