Lecture 19: Physiology of Liver and Pancreas Flashcards
Be familiar with each of the following.
Wasn’t a slide on these - refer to figure 70-1
- central vein
- hepatic veins
- liver cell plates
- bile canaliculi
- sinusoids
- space of Disse
- portal vein
- hepatic artery
- lymphatic duct
What is the blood flow through the liver lobule?
Portal vein -> sinusoids -> central vein -> hepatic veins
Hepatic artery -> sinusoids -> central vein -> hepatic veins
Liver cell plates are composed of how many layers of hepatocytes?
Two layers of hepatocytes.
Liver cell plates are composed of two layers of hepatocytes. What is found between the two layers of hepatocytes in each cell plate?
bile canaliculi
What type of cells line sinusoids in the liver?
- endothelial cells
- Kupffer cells (hepatic macrophages)
What space is found between endothelial cells and hepatocytes?
Space of Disse
part of the lymphatic system
Know figure 71-1 well for the exam!
Hepatic Lobule Figure
True or False:
The liver has high blood flow and high vascular resistance.
False - liver has high blood flow and low vascular resistance.
- 1050 ml from portal vein + 300 ml from hepatic artery flows into sinusoids each minute.
- 27% of resting cardiac output.
What is the portal pressure into the liver?
9 mm Hg
What is the pressure from the liver to vena cava?
0 mm Hg
What effect does cirrhosis have on blood flow?
Cirrhosis increases blood resistance to blood flow.
What is the effect of a clot blocking the portal vein or a major branch?
> Blockage of return blood from spleen and intestines.
> Increase in capillary pressure in intestinal wall –> loss of fluid –> death.
What is the normal volume of blood in the liver?
450 ml
(10% of body’s blood volume)
What happens to blood flow in the liver if there is high pressure in the right atrium?
High pressure in right atrium -> backpressure on liver -> increased blood volume in liver up to 1.5 L.
may occur during cardiac failure with peripheral congestion
Therefore: the liver can store blood in times of excess and supply blood in times of diminished volume
True or False:
Hepatic sinusoids are highly permeable to proteins.
True
efferent lymph has a protein concentration of 6 g/dl (almost equivalent to plasma concentration)
What happens if you have a higher than normal pressure in hepatic veins?
> Back pressure causes fluid to transude into lymph.
> Fluid leaks through liver capsule into abdominal cavity.
> Fluid is almost pure plasma.
> Large amount of fluid in abdominal cavity = ascites.
What are ascites?
Large amount of fluid in abdominal cavity.
What are the 7 major functions of the liver?
- Carbohydrate metabolism
- Fat metabolism
- Protein metabolism
- Vitamin storage
- Immune function
- Formation of coagulation factors
- Removal or excretion of drugs, hormones, and other substances
List the specific happenings of carbohydrate metabolism in the liver.
> Stores glucose as glycogen.
> Converts galactose and fructose to glucose.
> Gluconeogenesis
> Forms many intermediate products of carbohydrate metabolism.
> Releases stored glucose into the circulation.
List the specific happenings of fat metabolism in the liver.
> Oxidation of fatty acids for energy.
> Synthesis of cholesterol, phospholipids, lipoproteins.
> Synthesis of fats from proteins and carbohydrates.
List the specific happenings of protein metabolism in the liver.
> Deamination of amino acids.
> Formation of urea.
> Formation of plasma proteins.
> Interconversion of various amino acids and synthesis of other compounds from amino acids.
Which vitamins are stored in the liver?
Vitamin A
Vitamin D
Vitamin B12
What coagulation factors are formed in the liver?
> fibrinogen
prothrombin
accelerator globulin
factors VII, IX, X
List the specific happenings in the removal or excretion of drugs, hormones, and other substances in the liver.
> Detoxifies or excretes into the bile:
- sulfonamides
- penicillin
- ampicillin
- erythromycin
potentially toxic substances are presented to the liver via the portal system. phase I reactions are catalyzed by P-450 enzymes. phase II reactions conjugate products from phase I reactions
> Excretes excess calcium into the bile.
> Detoxification and removal of ammonia and ethanol.
Hepatic bile is produced and secreted by what?
Liver
What is bile from the gallbladder?
Bile from the gallbladder is hepatic bile that has been stored and concentrated.
What are the components of bile?
> Bile Acids
- cholic and chenodeoxycholic acids (synthesized by hepatocytes)
- deoxycholic acid and lithocholic acid (converted by bacteria)
> Water and Electrolytes
> Cholesterol and Phospholipids (especially lecithin)
> Pigments and Organic Molecules (major pigment is bilirubin)
What is cholic and chenodeoxycholic acids synthesized by?
hepatocytes
What converts deoxycholic acid and lithocholic acid?
Bacteria
Bilirubin Formation
> Hemoglobin is released from damaged RBCs.
> Reticuloendothelial System
- hemoglobin is phagocytized by macrophages
- split into globin and heme
- heme ring is opened to free iron
- heme is transported in the blood by transferrin
- straight chain of pyrrole nuclei is formed
- heme is converted by heme oxygenase into biliverdin
- biliverdin is converted to free (unconjugated bilirubin
> Free bilirubin is transported in the blood stream attached to plasma albumin to liver hepatocytes.
> Liver
-Free bilirubin is released from plasma albumin within the liver cells and conjugated.
*with glucoronic acid -> bilirubin glucuronids (80%)
(enzyme = UDP glucoronyl transferase)
- with sulfate -> bilirubin sulfate (10%)
- with a variety of other substances (10%)
> Conjugated bilirubin is:
- secreted (active transport) into the intestine OR excreted into the urine.
How is free bilirubin transported in the blood stream?
Attached to plasma albumin to liver hepatocytes.
What are the fates of conjugated bilirubin?
> secreted (active transport) into the intestine
> excreted into the urine
Practice drawing out bilirubin formation cascade.
Slide 21 - bilirubin formation.
What is Jaundice?
Refers to a yellowish tint to the body tissues.
What is Jaundice usually caused by?
Quantities of bilirubin in the extracellular fluids:
> increased hemolysis
> obstruction of bile ducts or damage to liver
What are increased hemolysis and obstruction of bile ducts or damage to the liver common causes of?
Jaundice
What are the 3 major types of islet cells?
> Alpha
Beta
Delta
What do alpha cells secrete?
glucagon
What do beta cells secrete?
insulin and amylin
What do delta cells secrete?
somatostatin
What percentage of alpha cells make up the pancreatic islet?
25% of total cells
What percentage of beta cells make up the pancreatic islet?
60% of total cells
What percentage of delta cells make up the pancreatic islet?
15% of total cells
What inhibits glucagon secretion?
Insulin - which is secreted by beta cells.
What inhibits insulin secretion?
Amylin - which is secreted by beta cells.
What inhibits insulin, glucagon, and gastrin secretion?
Somatostatin - which is secreted by delta cells.
What does somatostatin do?
Inhibits insulin, glucagon, and gastrin secretion.
What does insulin inhibit the secretion of?
glucagon
What does amylin inhibit the secretion of?
insulin
What islet cells communicate via gap junctions?
> beta cells to beta cells
alpha cells to alpha cells
beta cells to alpha cells
What islet cells communicate via islet portal blood supply?
> beta cells to alpha and delta cells
Via what does beta cells communicate to alpha and delta cells in the pancreatic islet?
Via islet portal blood supply.
True or False:
Insulin circulates in unbound form in blood with half-life of 6 minutes.
True
What happens to insulin not bound to receptors?
Destroyed in Liver
What happens when insulin binds to its receptor?
> Increased uptake of glucose (decrease blood glucose)
> Increased permeability to amino acids, potassium, and phosphate ions (decrease blood amino acids and potassium)
> Increased uptake of fatty acids (decrease blood fatty acids)
> Increased activity levels for many enzymes.
> Changes in rates of translation and transcription.
Review in the text - was not included in the lecture Powerpoint.
> Secretion process of insulin.
> Structure or insulin receptor.
What is the structure of the insulin receptor?
Tetramer with two alpha (extracellular) and two beta (transmembrane) subunits.
intrinsic tyrosine kinase activity autophosphorylates the beta subunits, which then phosphorylate intracellular proteins
True or False:
Insulin down-regulates its own receptors.
True
- increased in starvation
- decreased in obesity
What is the effect of removing the pancreas on blood glucose, FFA, and acetoacetic acid levels?
> Blood Glucose - increases.
> Free fatty acids - sudden increase and then stays the same level.
> Acetoacetic acid - slowly starts to rise and then quickly increases by day 3 to 4.
What is most of the glucose absorbed after a meal stored as?
Glycogen in the Liver
What are glucose uptake mechanisms for the liver?
> Insulin inactivates liver phosphorylase.
> Insulin activates glucokinase and enhances uptake of glucose from blood.
> Insulin increases activities of enzymes needed for glycogenesis.
What is one of the most important functional roles of insulin in the body?
Control from moment to moment whether fat (reduced insulin) or carbohydrate (increased insulin) will be used by cells for energy.
List events that cause liver to release glucose into the blood.
> Decreased blood glucose resulting in decreased insulin secretion.
> Lack of insulin reverses glycogen synthesis pathway.
> Lack of insulin activates phosphorylase which splits glycogen into glucose phosphate.
> Glucose phosphatase removes phosphate from glucose and allows it to diffuse back into blood.
> Insulin inhibits gluconeogenesis.
True or False:
Insulin promotes conversion of excess glucose into fatty acids and decreases utilization of fat.
True
List the effects of insulin on fat storage.
> Increases transport of glucose into liver creating excess.
> Excess glucose is converted to acetyl-CoA
> Fatty acid synthesis is initiated.
> Newly synthesized fatty acids are converted into triglycerides and transported from liver as lipoproteins.
> Triglycerides are split into fatty acids in capillaries and taken up into fat cells.
> Insulin promotes uptake of glycerol by fat cells.
What is the effect of the lack of insulin on fat storage?
> Large amounts of acetoacetic acids are formed in the liver.
> Carnitine transport mechanism in the liver is activated.
> Beta-oxidation results in excess of acetyl-CoA.
> Excess acetoacetic acids cause acidosis.
> Increase of ketone bodies in the blood.
What are the two major effects of glucagon?
> Break down of liver glycogen.
> Increased gluconeogenesis.
Recall: released by alpha cells.
What type of tissue does glucagon act on?
- liver tissue
- adipose tissue
List the glucagon cascade of events that lead to the increase in blood glucose.
> Activated adenyl cyclase in hepatic cell membrane.
> Which cuases formation of cAMP.
> Which activates protein kinase.
> Which activates phosphorylase B kinase.
> Which converts phosphorylase B into phosphorylase A.
> Which promotes degradation of glycogen to glucose-1-phosphate.
Besides causing the break down of liver glycogen and increased gluconeogenesis, what else does glucagon increase?
> Increases lipolysis
> Increases urea production (due to deamination of amino acids used for gluconeogenesis)
What is the major factor that regulates glucagon secretion?
blood glucose concentration
What does increased blood amino acids stimulate?
glucagon secretion
Increased blood amino acids stimulate glucagon secretion. What does this prevent?
Prevents hypoglycemia due to unopposed insulin in response to a high protein meal.
What cell type secretes somatostatin?
delta cells
What major effects does somatostatin cause?
> inhibits secretion of insulin, glucagon, and gastrin
> decreases motility of stomach, duodenum, and gallbladder
> decreases secretion and absorption of GI tract
List negative effects of having an increased blood glucose level.
> increased osmotic pressure in extracellular fluid
> loss of glucose in urine
> osmotic diuresis (dehydration and loss of electrolyts)
> damage to tissues and blood vessels
Diabetes Mellitus Type I (IDDM)
> Due to lack of insulin secretion.
> Injury to Beta cells:
- viral infections
- autoimmune disorders
Diabetes Mellitus Type II (NIDDM)
> Due to insulin resistance.
> Obesity is major risk factor.
> Preceded by metabolic syndrome.
List the conditions that a patient with metabolic syndrome would present with.
> obesity (esp. abdominal fat) > insulin resistance > fasting hyperglycemia > increased lipid triglycerides > decreased HDL levels > hypertension
