Lecture 43 - Digestive System: Metabolism and the many roles of the liver

Question 1

What is the purpose of the liver?

Answer 1

Most absorbed substances pass through the liver before they reach the general circulation, making the liver a key hub for control of many aspects of metabolic functioning, particularly the delivery of nutrients to other tissues

Question 2

Where is the liver located?

Answer 2

It is anchored in the right superior portion of the abdominal cavity by the peritoneum and mesenteries

It is attached to the diaphragm by the peritoneum, and anchored to the stomach by mesentery. The mesentery also form the hepatic ligaments and divide the liver into lobes

Question 3

How much does a healthy adult liver weigh?

Answer 3

~1.5 kg

Question 4

What is the difference between a vessel and a duct?

Answer 4

Vessel - carries a fluid connective tissue

Duct - transports an exocrine secretion to a surface

Question 5

What is the function of the hepatic portal vein system?

Answer 5

It collects blood from many organs within the abdominal cavity. The blood from each of these organs travels through the hepatic portal veins to reach the liver before it goes to the rest of the circulatory system

Question 6

What does liver tissue consist of?

Answer 6

It’s highly vascularized and consists of hepatocytes (liver cells), which are organized into lobules

Question 7

Describe the structure of liver capillaries

Answer 7

Known as sinusoids - notable for their discontinuous endothelium. Sinusoids have large gaps between adjacent endothelial cells and the underlying basement membrane

Question 8

What resides inside liver sinusoids?

Answer 8

Stellate macrophages

Question 9

What is the primary function of the liver? Give 5 examples of the digestive and metabolic functions of the liver

Answer 9

The processing of nutrients (and vitamins) from ingestion through excretion. These are metabolic functions

1. Synthesizing and secreting bile
2. Glucose processing and storage in the absorptive state
3. Store for minerals and vitamins
4. Gluconeogenesis in the post-absorptive state
5. Detoxification (break-down) of alcohol

Question 10

Describe the “Synthesizing and secreting bile” function of the liver

Answer 10

The liver secretes bile, which is important for both digestion and excretion

Bile contains:
- Water and inorganic ions
- Bile salts - assist in fat digestion and absorption
- Bilirubin - a potentially toxic waste product from the breakdown of heme

Question 11

Describe the “Glucose processing and storage” function of the liver

Answer 11

When glucose levels are elevated after a meal, the absorptive state occurs and the liver:

1. Stores some glucose as glycogen
2. Uses the excess glucose to synthesize new triglycerides

Question 12

Describe the “Store for minerals and vitamins” function of the liver

Answer 12

The liver is the main store in the body for:

1. Several vitamins (especially A and B12)
2. Certain metal ions (especially Cu and Fe)

Homeostasis of these substances is helped by the liver stores acting as a buffer for the supply in blood

Question 13

Describe the “Gluconeogenesis in the post-absorptive state” function of the liver

Answer 13

When blood glucose levels drop below a set point, the post-absorptive state occurs and the liver:

1. Converts glycogen back to glucose (glycogenolysis)
2. Synthesizes new glucose from amino acids and glycerol (gluconeogenesis)

Question 14

Describe the “Detoxification (break-down) of alcohol” function of the liver

Answer 14

Hepatocytes contain many enzymes and enzyme co-factors, which allow them to process a wide variety of organic molecules

Ex. The liver is the main source of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the enzymes that break down alcohols into ATP-generating substrates

Question 15

How can different liver biochemistry process affect each other?

Answer 15

Liver biochemistry processes can compete - either because they require the same co-factors, or because they down regulate each other

Ex. Ethanol metabolism leads to biochemical signalling changes that enhances fatty acid synthesis, but inhibit gluconeogensis

Question 16

What is the function of the liver being able to store blood?

Answer 16

At rest, the liver receives 25% of cardiac output (between its arteries and the portal veins). Constriction in the liver vessels can increase venous return (and therefore inc. cardiac output) during exercise or in situations of reduced blood volume

Question 17

What are the 5 other functions of the liver that is not directly related to metabolism

Answer 17

A5/B: Detoxification of alcohol and many other drugs and toxins

C: Most soluble proteins found in plasma are synthesized within the liver

D: Liver macrophages play an important role in recycling RBCs

E: The liver is a secondary endocrine organ and secretes at least 4 hormones or pro-hormones

F: The liver contributes to the activation or inactivation of steroid hormones produced by other endocrine organs

Question 18

Describe the non-metabolic function of “the breakdown of other drugs and toxins” of the liver

Answer 18

The liver can inactivate and break down many drugs and toxins beyond alcohol, including ones that are excreted, rather than used to generate ATP

Ex. Hepatocytes are responsible for inactivating acetaminophen (Paracetamol/Tylenol) so it can be safely excreted

Question 19

Describe the non-metabolic function of “Most soluble proteins found in plasma are synthesized within the liver” of the liver

Answer 19

Most major extracellular protein components of blood plasma (except immunoglobulins) are synthesized in hepatocytes and join the bloodstream through liver sinusoids

Question 20

Describe the non-metabolic function of “Liver macrophages play an important role in recycling red blood cells” of the liver

Answer 20

Stellate macrophages (as well as macrophages in the spleen) phagocytose old RBCs and recycle their contents (especially iron)

Question 21

Describe the non-metabolic function of “The liver is a secondary endocrine organ and secretes at least 4 hormones or pro-hormones” of the liver

Answer 21

Four main hormones/pro-hormones secreted by the liver:

1. Somatomedins (especially IGF) are secreted in response to GH release from the anterior pituitary
2. Angiotensinogen is converted to the hormone angiotensin by renin when BP is low
3. Thrombopoietin stimulates platelet formation
4. Hepcidin is important for iron homeostasis

Question 22

Describe the non-metabolic function of “The liver contributes to the activation or inactivation of steroid hormones produced by other endocrine organs” of the liver

Answer 22

Class 3 (lipid derivatives) hormones are often broken down (inactivated) by enzymes within the liver

The liver (which is responsible for cholesterol synthesis) processes cholesterol derivatives, like steroids hormones

The liver also plays an essential intermediate step in the synthesis of the hormone calcitriol from vitamin D