Physiology of Liver and Pancreas (Lecture 19)

Question 1

Describe/diagram the overall lobular structure of the liver with emphasis on the lobule

Answer 1

• Basic functional unit of the liver is the liver lobule, which is a cylindrical structure. The human liver contains 50,000 to 100,000 individual lobules

Question 2

Describe the vascular supply to the liver. What is the impact of cirrhosis on the vascular supply

Answer 2

• Liver has high blood flow and low vascular resistance:
  
  • 1050 mL from portal vein + 300 mL from hepatic artery flows into sinusoids each minute
  • That represents about 27% fo the resting cardiac output
• Portal pressure into liver= 9mmHg
• Pressure form liver to vena cava= 0mmHg
• Cirrhosis
  
  • increases blood resistance to blood flow
• Effect of clot blocking 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
    *

Question 3

Explain how the liver can store blood in times of excess blood and supply extra blood in times of diminished volume

Answer 3

• Normal volume of blood in the liver = 450mL (10% of body’s blood volume)
• High pressure in right atrium → backpressure on liver → increased blood volume in liver up to 1.5 liters.
  
  • May occure during cardiac failure with peripheral congestion
• Therefore: liver can store blood in times of excess and supply blood in times of diminished volume

Question 4

Relate the formation of ascites to the vascular supply to the liver

Answer 4

• Higher than normal pressure in hepatic veins
  
  • back pressure causes fluid to transduce into lymph
  • fluid leaks through liver capsule into abdominal cavity
  • Fluid is almost pure plasma
  • Large amount of fluid in abdominal cavity = ascites

Question 5

Describe the roles(s) of the Kupffer cells in the liver and describe their location

Answer 5

• Line Hepatic venous sinuses
• fxn: macrophages that act as particulate filtration system so that almost none of the bacteria form the GI tract pass from the portal bloood into the general systemic circulation.

Question 6

List the functions of the liver

Answer 6

• Carbohydrate metabolism
• Fat metabolism
• Protein metabolism
• Vitamin storage
  
  • Vitamin A, D, and B₁₂
• Immune function
• Formation fo coagulation factors
• Removal of excretion of drugs, hormones, and other substances

Question 7

• Incorporate the following terms into your description of bilirubin formation and excretion:
  
  • Heme ring
  • transferrin
  • pyrrole nuclei
  • biliverdin
  • free (unconjugated) bilirubin
  • bilirubin glucuronids
  • urobilinogen
  • urobilin
  • stercobilin

Answer 7

*

Question 8

Define “jaundice” and list common causes

Answer 8

• Referes to a yellowish tint to the body tissues
• usually caused by quantities of bilirubin in the extracellular fluids
• Common causes
  
  • Increased hemolysis
  • Obstruction of bile ducts or damage to liver

Question 9

Review the overall structure of the pancreatic islets and know which cells in the islets secrete which specific hormones

Answer 9

• Major types of islet cells
  
  • Alpha:
    
    • Secrete glucagon
    • 25% of total cells
  • Beta
    
    • Secrete insulin and amylin
      
      • insulin inhibits glucagon secretion
      • Amylin inhibits insulin secretion
    • 60% of total cells
  • Delta
    
    • Secrete Somatostatin
      
      • Inhibits insulin, glucagon, and gastrin secretion

Question 10

Describe the effects of insulin on muscle tissue

Question 11

Describe the effects of insulin on the liver

Answer 11

• Most of the glucose absorbed after a meal is stored as glycogen in the liver
• Glucose uptake mechanism 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

Question 12

List events which cause the liver to release glucose back into the blood

Answer 12

• 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 into blood
• Insulin inhibits gluconeogenesis

Question 13

Describe the effects of insulin leading to fat storage in adipose tissue

Answer 13

• Insulin promotes conversion of excess glucose into fatty acids and decreases utilization of fat
  
  • 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

Question 14

Explain why lack of insulin results in excessive amounts of acetoacetic acid to be formed in the liver

Answer 14

• The liver uses only a small proportion of fatty acids for its own intrinsic metabolic processes. Instead, when the fatty acid chains have been split into acetyl-CoA, to molcuels of Acetyl-CoA condencse to form one molecule of acetoacetic acid, which is then transported in the blood to the other cells throughout the body, where it is used for energy

Question 15

Define “ketone bodies”

Answer 15

• Acetoacetic acid
• Beta-hydroxybutyric acid
• acetone

Question 16

Describe the effects of insulin on protein metabolism and growth

Answer 16

insulin promotes transport of amino acids into tissue cells, as well as the intracellular formation of protein.

Question 17

Describe the major effects of glucagon

Answer 17

• Acts on liver and adipose tissue
  
  • break down of liver glycogen
  • increased gluconeogenesis

Question 18

List the events of the glucagon cascade leading to major effects

Answer 18

• Glucagon cascade of events leading to increase blood glucose:
  
  • Activates adenyl cyclase in hepatic cell membrane
  • which causes 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

Question 19

Explain how glucagon is regulated

Answer 19

• Blood glucose concentration is the most potent factor for controling glucagon secretion
• increased blood amino acids stimulate secretion of glucagon

Question 20

List the effects of somatostatin secretion

Answer 20

• Secreted by delta cells
• Major effects
  
  • inhibits secetion of insulin, glucagon, and gastrin
  • Decreases motility of stomach, duodenum, and gallbladder
  • decreases secretion and absorption of GI tract

Question 21

Explain why high blood glucose levels are problematic

Answer 21

• Increased osmotic pressure in extracellular fluid
• loss of glucose in urine
• osmotic diuresis (dehydration and loss of electrolytes)
• Damage to tissues and blood vessels

Question 22

Compare Type I and Type II diabetes mellitus and list causes and symtpoms of each

Answer 22

• Type I (IDDM)
  
  • Due to lack of insulin secretion
  • Injury to Beta cells:
    
    • Viral infections
    • Autoimmune disorder
• Type II (NIDDM)
  
  • Due to insulin resistance
  • Obesity is major risk factor
  • Preceded by metabolic syndrome

Question 23

Describe the most important risk factor for diabetes II in children and adults

Answer 23

Obesity

Question 24

List and describe features of the metabolic syndrome

Answer 24

• Obesity (esp. abdominal fat)
• Insulin resistance
• Fasting hyperglycemia
• Increased lipid triglycerides
• Decreased HDL levels
• Hypertension