Hepatic Physiology: ABCs of the Liver Flashcards
What are some important functions of the liver?
Protein metabolism
Transformation of carbohydrates
Synthesis of cholesterol, bile salts, and phospholipids
Detoxification!
…
Most important protein produced by liver
Albumin (plasma protein)
Plasma albumin levels are reflective of liver function
Define gluconeogenesis
Define glycogenlysis
Main minerals stored by liver (2)
copper, iron
Main vitamins stored by liver (5)
Fat soluble vitamins A, D, E, K, B12
What is hematochromatosis?
Iron overload from an inherited condition (involving HFE gene mutation).
Affects and causes pain in liver, pancreas, heart and joints.
What is Wilson’s disease?
Genetic disorder inability to excrete copper (leads to deposition in liver, eyes, brain, which causes vascular degeneration).
What substance does the liver secrete?
Bile
Describe bile and its functions
Alkaline, yellow coloured fluid secreted by hepatocytes.
….
Explain the cytochrome p450 pathway of detoxification (liver)
Name the 2 detox functions of the liver
- Destruction of endogenous (proteins) and exogenous (toxins, alcohol) substances
- Conversion of ammonia to urea
What is bilirubin? What 2 sources is it derived from?
Yellow pigment made from the breakdown of RBCs
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.
How does our body get rid of urobilinogen?
80% excreted in feces
….
Name the 3 liver function tests
Bilirubin
INR (?)
Albumin
Name the liver enzymes tests
ALT
AST
ALP
GGT
Define direct vs indirect bilirubin
Indirect: Bound to albumin
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In what cases would we have an elevated level of direct (conjugated) bilirubin?
In what cases would we have an elevated level of indirect (unconjugated) bilirubin?
Elevated due to pre-hepatic causes like hemolysis, sepsis.
I missed the discussion about alanine aminotransferase
Normal range of aspartate aminotransferase (AST)
8-20 IU/L
Biliary/liver related causes of high ALP (>2-3 x ULN)
- GALLSTONES!
- Cholangiocarcinoma
- Pancreatic head carcinoma
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Certain cases of drug-induced liver injury
Causes of high GGT
- Any cause of biliary obstruction (marker of cholestasis)
- Acute pancreatitis
- Drug-induced liver injury (anti-epileptics, rifampin, antidepressants, alcohol)
- Hypothyroidism
Cholestatic liver injury can be divided into 2 categories
Intra-hepatic
Extra-hepatic
Most common intra-hepatic cause of cholestasis
Malignancy
3 subcategories of intra-hepatic cholestatic liver injury
Obstructive
* Malignancy
* PBC/PSC
* Infiltrative disease
Toxic
* Medication
* Pregnancy
* Alcohol
* TPN
Infectious
* Sepsis
* Tuberculosis
2 subcategories of extra-hepatic cholestasis liver injury
Biliary
* CBD stone
* Strictures
* Malignancy
* Choledocal cyst
Pancreatic
* Acute/chronic pancreatitis
* Pseudocyst
* Pancreatic cancer
When we get mixed liver enzyme results, how do we determine whether we are dealing with cholestatic or hepatocellular disease?
Common causes of mixed liver enzyme results (2)
Drug-induced liver injury
Alcohol
Define jaundice
- Also known as hyperbilirubinemia (elevation of conjugated bilirubin).
- Causes yellow discoloration of skin, sclera and body tissue.
- …
Causes of jaundice
Some signs/suggestions of jaundice (on patient history)
- Abdominal pain
- Nausea, vomiting
- Dark urine, pale stools
- Fever, chills
- Recent substance use or alcohol
- Recent travel
Some symptoms of jaundice (on physical exam)
- Yellowing of skin/sclera
- Diaphoretic/cachectic
- Abdominal tenderness/distension
- Slow or slurred speech
…
Fetor hepaticus
Sweet smell of breath suggesting liver failure and jaundice.
Most important stigmata of chronic liver disease
Ascites!
First modality of choice for liver imaging
Ultrasound of abdomen or liver to…
* assess biliary structures
* assess hepatic vascular structures
* check for splenomegaly
Define fulminant hepatic failure
Acute liver failure with impaired synthetic function (not making albumin, clotting factors, etc)
3 main consequences of fulminant hepatic failure
- acute liver injury
- hepatic encephalopathy (confusion, slurred speech or coma)
- coagulopathy
Common causes of fulminant hepatic failure (2)
Viral hepatitis
Drug-induced hepatitis
What is the prognosis for fulminant hepatic failure? How is it dealt with?
BAD prognosis: extremely high morbidity and mortality
Requires early transplant evaluation and referral to transplant center
Define chronic liver failure (important to remember)!
Progressive deterioration of liver function of more than six months.
End stage of chronic liver failure
cirrhosis
Most common etiologies of chronic liver failure
True or false: Cirrhosis of the liver is a precancerous condition
TRUE! IMPORTANT! We need to ultrasound the liver and measure tumour markers every 6-12 months for patients with cirrhosed livers!
4 complications of cirrhosis
- Varices
- Ascites
- Hepatic encephalopathy
- Portal vein thrombosis
Define the following:
1. Varices
2. Ascites
3. Hepatic encephalopathy
4. Portal vein thrombosis
- Varices: dilated veins (esophageal, gastric, sometimes duodenal)
2.
What is ascites?
Pathological accumulation of fluid in the peritoneal cavity, most commonly observed in cirrhosis.
What is the pathophysiology of ascites in each of the following etiologies:
a) cirrhosis
b) low albumin
c) activation of RAAS
a) Cirrhosis: Portal HTN
b) Low albumin: Change in oncotic pressure
c)
Cardiac causes of ascites (2)
Congestive heart failure
Constrictive pericarditis
(due to congested state)
Malignancies that can cause ascites (4)
Liver
Ovarian
Peritoneal disease
Pancreatic
What is the SAAG value? How is it used?
Serum ascites albumin gradient value.
If this value is greater than 1.1, it is secondary to portal hypertension.
Other than SAAG, how else can we determine ascites (labs)?
- Measuring serum protein levels
*
SAAG greater than 1.1: What is the cause of ascites?
SAAG greater than 2.5: What is the cause of ascites?
SAAG greater than 1.1 but less than 2.5: What is the cause of ascites?
SAAG less than 1.1: What is the cause of ascites?
