Liver (Dr. Sharkady): Pt. 1 Diagnostic Enzymes and Iron, Copper and Alcohol Metabolism

What are the general function of the liver in terms of digestion?

bile production and secretion

What are the general function of the liver in terms of carbohydrate metabolism?

gluconeogenesis and storage of glycogen

How does the liver metabolize fats?

exogenous pathway (chylomicrons) & endogenous pathway (VDL to LDL)

Which fat soluble vitamins does the liver store?

A, D, E, K, B12

Which minerals does the liver store?

copper and iron

T/F: The liver is responsible for detoxification and biotransformation and excretion of lipophilic molecules and metals.

True

How is the liver involved in protein synthesis?

urea cycle

List the plasma proteins synthesized and secreted by the liver

albumin

immunoglobins & their complement proteins

protease inhibitors

coagulation factors

What are acute-phase proteins?

proteins released by the liver when the body is under stress

What is the role of alpha1-Antitrypsin?

Protease inhibitor that helps prevent further damage of tissues by proteases released from dead tissues

What is the role of alpha2-Macroglobulin?

Indirect anti-protease that fixes proteases and allows macrophages to engulf them.

What is C-Reactive Protein (CRP)?

produced during inflammation and binds to phosphocholine released by dying cells

What is ceruloplasmin?

Copper-carrying protein, and anti-oxidant.

What are complement proteins?

inflammatory mediators

What is ferritin?

iron-protein carrier

What is fibrinogen?

clotting factor

What is haptoglobin?

bind free hemoglobin released from lysed RBCs and to prevent the iron within hemoglobin from reacting with molecular oxygen to produce the free radicals (superoxide)

Where does heme synthesis occur in the body?

liver & bone marrow

What is the starting compound of heme?

succinyl CoA (from TCA cycle)

Where does bile salt conjugation to taurine and choline occur?

peroxisome

T/F: Bile is the major excretory route for potentially harmful exogenous lipophilic substances (e.g. xenobiotics) and cholesterol

True

Bile contains ____ and inflammatory cytokines that modulate innate immune system of the gut

IgA

T/F: Bile is not essential for enterohepatic circulation.

False

Why does vitamin B6 (pyridoxine) deficiencies cause microcytic anemia?

aminolevulinic acid synthase requires vitamin for 1st step of making porphyrin ring

Why does vitamin B12 and B9 (folic acid) deficiencies cause megaloblastic anemia?

RBCs require vitamins for DNA replication. Deficiency causes cells to be stuck in S phase and reduce oxygen transport

Hemoglobin becomes heme then biliverdin then unconjugated bilirubin. What colors are biliverdin and bilirubin, respectively?

green, yellow

Free/unconjugated bilirubin is hydrophobic so it has to be transported by which plasma protein in order to enter the liver from the blood?

albumin

Which compounds are conjugated to free bilirubin to make it soluble?

2 sugars (bilirubin diglucuronide)

Conjugated bilirubin enters the bile then the intestines. How does bacteria modify conjugated bilirubin?

converts it to urobilinogen (colorless) which then becomes stercobilin (brown, feces)

Some urobilinogen enters enterohepatic cycling while some is excreted in the urine. What compound is urobilinogen converted to in the kidneys?

urobilin (yellow)

Define jaundice

yellowing of the sclera, the mucous membranes, and skin due to excess bilirubin

Define prehepatic jaundice

caused by conditions that present an excessive bilirubin load to the liver (hemolysis).

Define hepatic jaundice

results from an inability to take up, metabolize, or excrete bilirubin

Define post-hepatic jaundice

caused by an obstruction to the biliary tract

Define obstructive jaundice

occurs with a malignant tumor of the head of the pancreas, results in suppression of hepatic bile flow and reabsorption of conjugated bile into the circulation.

Define cholestasis

condition of impaired bile production or obstruction of bile flow due to intrahepatic or extrahepatic causes

What plasma bilirubin concentration (unconjugated or conjugated) is indicative of jaundice?

> 2 mg/dL

How is unconjugated bilirubin measured?

total bilirubin - conjugated bilirubin

What is total bilirubin?

waste product of hemoglobin breakdown

In excessive RBC breakdown, such as hemolytic anemia, or impaired liver function or some sort of obstruction, such as a tumor or gallstone, total bilirubin is increased or decreased?

increased total bilirubin