Hepatic Physiology: ABCs of the Liver

Question 1

What are some important functions of the liver?

Answer 1

Protein metabolism
Transformation of carbohydrates
Synthesis of cholesterol, bile salts, and phospholipids
Detoxification!
…

Question 2

Most important protein produced by liver

Answer 2

Albumin (plasma protein)

Plasma albumin levels are reflective of liver function

Question 3

Define gluconeogenesis
Define glycogenlysis

Question 4

Main minerals stored by liver (2)

Answer 4

copper, iron

Question 5

Main vitamins stored by liver (5)

Answer 5

Fat soluble vitamins A, D, E, K, B12

Question 6

What is hematochromatosis?

Answer 6

Iron overload from an inherited condition (involving HFE gene mutation).

Affects and causes pain in liver, pancreas, heart and joints.

Question 7

What is Wilson’s disease?

Answer 7

Genetic disorder inability to excrete copper (leads to deposition in liver, eyes, brain, which causes vascular degeneration).

Question 8

What substance does the liver secrete?

Answer 8

Bile

Question 9

Describe bile and its functions

Answer 9

Alkaline, yellow coloured fluid secreted by hepatocytes.
….

Question 10

Explain the cytochrome p450 pathway of detoxification (liver)

Question 11

Name the 2 detox functions of the liver

Answer 11

1. Destruction of endogenous (proteins) and exogenous (toxins, alcohol) substances
2. Conversion of ammonia to urea

Question 12

What is bilirubin? What 2 sources is it derived from?

Answer 12

Yellow pigment made from the breakdown of RBCs

Question 13

Heme is converted to unconjugated bilirubin, which binds albumin (becoming indirect bilirubin).
Once it gets into the liver, it gets converted to direct bilirubin.
Direct bilirubin is excreted through the bile duct into the SI.
Gut bacteria convert it to urobilinogen.

Question 14

How does our body get rid of urobilinogen?

Answer 14

80% excreted in feces
….

Question 15

Name the 3 liver function tests

Answer 15

Bilirubin
INR (?)
Albumin

Question 16

Name the liver enzymes tests

Answer 16

ALT
AST
ALP
GGT

Question 17

Define direct vs indirect bilirubin

Answer 17

Indirect: Bound to albumin
…

Question 18

In what cases would we have an elevated level of direct (conjugated) bilirubin?

Question 19

In what cases would we have an elevated level of indirect (unconjugated) bilirubin?

Answer 19

Elevated due to pre-hepatic causes like hemolysis, sepsis.

Question 20

I missed the discussion about alanine aminotransferase

Question 21

Normal range of aspartate aminotransferase (AST)

Answer 21

8-20 IU/L

Question 22

Biliary/liver related causes of high ALP (>2-3 x ULN)

Answer 22

• GALLSTONES!
• Cholangiocarcinoma
• Pancreatic head carcinoma
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Certain cases of drug-induced liver injury

Question 23

Causes of high GGT

Answer 23

• Any cause of biliary obstruction (marker of cholestasis)
• Acute pancreatitis
• Drug-induced liver injury (anti-epileptics, rifampin, antidepressants, alcohol)
• Hypothyroidism

Question 24

Cholestatic liver injury can be divided into 2 categories

Answer 24

Intra-hepatic
Extra-hepatic

Question 25

Most common intra-hepatic cause of cholestasis

Answer 25

Malignancy

Question 26

3 subcategories of intra-hepatic cholestatic liver injury

Answer 26

Obstructive * Malignancy * PBC/PSC * Infiltrative disease Toxic * Medication * Pregnancy * Alcohol * TPN Infectious * Sepsis * Tuberculosis

Question 27

2 subcategories of extra-hepatic cholestasis liver injury

Answer 27

Biliary * CBD stone * Strictures * Malignancy * Choledocal cyst Pancreatic * Acute/chronic pancreatitis * Pseudocyst * Pancreatic cancer

Question 28

When we get mixed liver enzyme results, how do we determine whether we are dealing with cholestatic or hepatocellular disease?

Question 29

Common causes of mixed liver enzyme results (2)

Answer 29

Drug-induced liver injury Alcohol

Question 30

Define jaundice

Answer 30

* Also known as hyperbilirubinemia (elevation of conjugated bilirubin). * Causes yellow discoloration of skin, sclera and body tissue. * ...

Question 31

Causes of jaundice

Question 32

Some signs/suggestions of jaundice (on patient history)

Answer 32

* Abdominal pain * Nausea, vomiting * Dark urine, pale stools * Fever, chills * Recent substance use or alcohol * Recent travel

Question 33

Some symptoms of jaundice (on physical exam)

Answer 33

* Yellowing of skin/sclera * Diaphoretic/cachectic * Abdominal tenderness/distension * Slow or slurred speech ...

Question 34

Fetor hepaticus

Answer 34

Sweet smell of breath suggesting liver failure and jaundice.

Question 35

Most important stigmata of chronic liver disease

Answer 35

Ascites!

Question 36

First modality of choice for liver imaging

Answer 36

Ultrasound of abdomen or liver to... * assess biliary structures * assess hepatic vascular structures * check for splenomegaly

Question 37

Define fulminant hepatic failure

Answer 37

Acute liver failure with impaired synthetic function (not making albumin, clotting factors, etc)

Question 38

3 main consequences of fulminant hepatic failure

Answer 38

* acute liver injury * hepatic encephalopathy (confusion, slurred speech or coma) * coagulopathy

Question 39

Common causes of fulminant hepatic failure (2)

Answer 39

Viral hepatitis Drug-induced hepatitis

Question 40

What is the prognosis for fulminant hepatic failure? How is it dealt with?

Answer 40

BAD prognosis: extremely high morbidity and mortality Requires early transplant evaluation and referral to transplant center

Question 41

Define chronic liver failure (important to remember)!

Answer 41

Progressive deterioration of liver function of more than six months.

Question 42

End stage of chronic liver failure

Answer 42

cirrhosis

Question 43

Most common etiologies of chronic liver failure

Question 44

True or false: Cirrhosis of the liver is a precancerous condition

Answer 44

TRUE! IMPORTANT! We need to ultrasound the liver and measure tumour markers every 6-12 months for patients with cirrhosed livers!

Question 45

4 complications of cirrhosis

Answer 45

1. Varices 2. Ascites 3. Hepatic encephalopathy 4. Portal vein thrombosis

Question 46

Define the following: 1. Varices 2. Ascites 3. Hepatic encephalopathy 4. Portal vein thrombosis

Answer 46

1. Varices: dilated veins (esophageal, gastric, sometimes duodenal) 2.

Question 47

What is ascites?

Answer 47

Pathological accumulation of fluid in the peritoneal cavity, most commonly observed in cirrhosis.

Question 48

What is the pathophysiology of ascites in each of the following etiologies: a) cirrhosis b) low albumin c) activation of RAAS

Answer 48

a) Cirrhosis: Portal HTN b) Low albumin: Change in oncotic pressure c)

Question 49

Cardiac causes of ascites (2)

Answer 49

Congestive heart failure Constrictive pericarditis (due to congested state)

Question 50

Malignancies that can cause ascites (4)

Answer 50

Liver Ovarian Peritoneal disease Pancreatic

Question 53

What is the SAAG value? How is it used?

Answer 53

Serum ascites albumin gradient value. If this value is greater than 1.1, it is secondary to portal hypertension.

Question 54

Other than SAAG, how else can we determine ascites (labs)?

Answer 54

* Measuring serum protein levels *

Question 55

SAAG greater than 1.1: What is the cause of ascites?

Question 56

SAAG greater than 2.5: What is the cause of ascites?

Question 57

SAAG greater than 1.1 but less than 2.5: What is the cause of ascites?

Question 58

SAAG less than 1.1: What is the cause of ascites?