Liver Flashcards
Where is live Located?
Located in RUQ of abdomen
2 lobes made up of thousands of lobules
Lobules function:
centered on a branch of the hepatic vein (“central vein”)
interconnected by small ducts
contain hepatocytes, separated by sinusoids
“portal triads”at the corners of adjacent lobule–>branches of the bile duct , portal vein, hepatic artery
What is the heaptic duct?
Transports bile produced by liver cells to the gallbladder and duodenum
Unique function of liver cells
Liver cells can regenerate
About 70% of the liver tissue can be destroyed before the body is unable to eliminate drugs and toxins via the liver
Blood flow to liver
~25% of the cardiac output (~1500 mL of blood flow/minute)
Has a dual blood supply
Describe the blood supply flow to the liver
venous flow in from the portal vein*
venous blood from the small intestine (absorbed nutrients, drugs, toxins) directly to the liver
pancreatic venous drainage (pancreatic hormones)
spleen (bacteria, byproducts of blood-cell recycling)
arterial flow in from the hepatic artery
liver oxygenation
venous flow out through the hepatic vein
Blood from both portal vein and hepatic artery mixes together in sinusoids and exits the liver through the hepatic vein
Connected to the GI tract via portal veins and bile ducts
Major functions of the liver
Excretion
Bile* - produced by hepatocytes; metabolizes cholesterol and fat and detoxifies drugs and toxins
Metabolism
Bilirubin, drugs, nutrients, hormones
CHO, lipids, amino acids, hormones/steroids
Storage
Vitamins/minerals (B12, iron), CHO
Synthesis
Plasma proteins (albumin, coagulation proteins, other transport proteins)
Responsibility of gallbladder
Stores and concentrates bile (typically concentrated 5 fold in the gallbladder by absorption of water and electrolytes)
Bile Functions
Bile functions:
Emulsification: dietary fat, chol, vitamins
Elimination of waste: excess chol, xenobiotics, bilirubin
contraction of Gallbladder and bile duct is by…..
Stimulus (food in duodenum) Cholecytikinin
What is enetrohepatic recirculation?
enterohepatic recirculation (95% of bile acids reabsorbed) – some lost in feces, body makes up for it
What is Bilirubin? What is its metabolism?
End product of heme degradation
From breakdown of RBC in spleen/liver
Free bilirubin –> Insoluble-bound to albumin for transport to liver (measured as “indirect bilirubin”)
Bilirubin Metabolism:
Glucuronidated in liver (“direct bilirubin”)
Excreted in bile
Describe billirubin process
Liver Dx can be….
Can be acute or chronic, focal or diffuse, mild or severe, and reversible or irreversible…
Describe liver damage and the types? Is it reversible?
Acute damage to the functional cells of the liver without destruction of the liver’s capacity for regeneration is generally reversible (may be irreversible)
Fulminant liver failure/end-stage disease
insufficient residual hepatocytes to maintain minimal essential liver functionsirreversible
Descirbe the pattern of hepatocellular injury?
Etyiology of Hepatic Injury
Viruses (HAV, HBV, HCV, HDV, other Epstein bar virus as example )
Drugs (Rx, OTC, herbals)
Environmental toxins (chlorinated pesticides, insecticides, etc.)
Alcohol
What are the two types of hepatic injury?
CHOLESTASIS
HEPATOCELLULAR
Define cholestasis.Leads to?
A failure of normal amounts of bile to reach the duodenum’
Leads to accumulation of bile in liver cells and biliary passages (intra vs extrahepatic)
Causes of cholestasis
Cholelithiasis (gall stones) - most common
Tumor, viral hepatitis, alcohol-related liver disease, drugs
Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)
What is primary biliary cholangitis. Stat?
Caused by the slow, immune-mediated destruction of small bile ducts within the liver (impaired excretion of bile)
Leading cause of liver transplant in women in Canada
What is primary sclerosing cholangitis?What is it associated with?
Involves progressive inflammation and fibrosis affecting any part of the biliary tree
Leads to the progressive destruction of bile ducts
Commonly associated with inflammatory bowel disease
What is choletstaic syndrome? Sx?
Blockage of bile flow
Pruritis
Jaundice
Dark Urine
Light coloured stools (greenish)
Steatorrhea (fatty stools)
Xanthoma (growths under skin due to bile salts) and xanthelasma (little growths around the eyelids)
Hepatomegaly
Treatment of choleithiasis?
Ursodeoxycholic acid (ursodiol
MOA of Urosodiol
Naturally occurring bile acid (bile salt) – small amount endogenously
MOA unclear: decrease chol saturation
How are gall stones formeda nd removed?
Gall stones – super-saturation of cholesterol which causes precipitation
- Eliminated on their own, or they can be removed through laparoscopic surgery
Cholethialisis Urosodiol and Counselling
Stones often recur after drug d/c
Urosodiol Dose, A/E
Dose is often 250-500 mg BID – take until stones are gone or 1-3 months after
Genrally well tolerated; limited D.I. – may complain of some pruritis
Urosodiol can also be used in…. to…
Also used in chronic forms of cholestasis such as PBC or PSC
Improves serum biochemical tests
Limited efficacy in preventing disease progression in PSC
Alternative to ursodiol in PSC
Obeticholic acid (OCA) – may use as alternative in PBC
Semi-synthetic bile acid
Pruritis
Often associated wit long standing cholestasis
Rule out local cutaneous causes of pruritus such as eczema
Tx of Pruritis Algorithm
Cholestyramine (best drug – bile acid sequestrant)
will benefit about 90% of patients; must be continued as long as pruritus is present
Binds to bile salts and prevents reabsorption
Antihistamines
(e.g., hydroxyzine) are of no proven benefit, but their sedative properties may help
Naltrexone (opiod antagonist), rifampin (antibio) or sertraline (anti-depressant)
may be tried if refractory
Hepatiocellular damage definition
Direct damage to hepatocytes
Injury may be acute or chronic
Cuases of heaptocellular damage
Toxic agents: Alcohol, drugs, toxins
Infections: Hepatitis
Longstanding cholestasis (can lead to hepatocellular injury as well)
Ischemic injury: Thrombosis
Other Diseases (autoimmune, iron overload)
Course of Heaptocellular DamageDepends on n
Duration of assault (cells can regenerate)
Intensity of assault (massive: fulminant hepatic failure vs mild to moderate: hepatitis)
Tremendous reserve capacity of liver
When hepatocytes are destroyed, what happens?
contents of cells are released into the circulation
functional ability of the liver may be compromised (if enough damage has occurred)
Conditions that can lead to heaptocellular damage?
Autoimmune Hepatitis – autoimmune dx characterized by chronic inflammation of the liver with genetic component
Hemochromatosis – excessive absorption of iron; different types; think of inherited type; may be heterozygous and may not know they have; if homozygeous – will develop sx that may be severe – lead to accumulation of iron in liver, hearts, lungs, joints, ect. –> Could lead to liver transpant TX: Phlebotomy (removal of blood once over twice per month initially)
Evaluating liver function iclcudes:
Liver Enzyme measurement
Testing for enzymes residing inside hepatocytes (release from damaged hepatocytes)
Liver Function tests (LFTs) - abc’s
Evaluate synthetic capacity of liver
Albumin, Bilirubin, Clotting
Liver enzyme measurement includes:
Released into circulation after injury
ALP, AST, ALT, GGT
Liver enzymes measurements are what to liver cells? What do we use them for?
Relatively specific to liver cells
When look at pattern to them -Helps to distinguish type of injury.
Cholestatic
Hepatocellular
Other
Indicators of cholestatic injury
Liver Enzyme elevations in: ALP & GGT
What is ALp? Where is it found?
ALP (Alkaline phosphatase)
Present in bile duct > hepatocytes
High concentrations also found in bone
Marker of cholestatic issues
What is GGt?Also elevated in?
GGT (Gamma glutamyl transpeptidase) – non-specific liver enzyme
Elevated in all liver disorders
Confirms hepatic origin of ALP
Also: EtOH, pancreatitis, MI, COPD, renal
Pattern of ALP and GGT
Ifr ALP is elevated, but GGT is low –> May not be liver
If elevated with GGT, indicates liver involvement –> More conerned
ASTabd ALt are….
Aminotransferases (AST, ALT)
(aspartate aminotransferase, alanine aminotransferase)
Which is more specific, ALT or AST?
ALT more specific than AST
Aminotransferases Correlation and Severity
Poor correlation with severity, prognosis
May be minimally elevated in cholestatic syndromes (if long enough, may increase by direct toxic insult of hepatocytes)
LDH
LDH (LDH5)
very nonspecific
Benefit of liver enzymes.Disadvantage?
often go up before clinical sx goes up so allow for early detection of liver injury – poorly correlated with a severity or prognosis of liver injury
LFT’s measure what?
Test the synthetic capability of the liver
Albumin Normal Lifespan
20 days
Albumin in liver impairement.Sx?
Reduced after sustained assault
Sx: edema, ascites (because you can’t maintain oncotic pressure)
Effects on calcium, highly bound drugs (phenytoin).
When do see albumin decreasing?
- Delay before you see a change in serum albumin following liver injury
- Sustained assault to the liver – will not see this in acute hepatitis
Bilirubin does what in liver damage? Sx?
‘Bilirubin’ (Goes up)
Result of bilirubin retention
Deposits in skin and tissues
Dark urine, pale stools, yellow skin (jaundice)
Causes of Bilirubin increase?
Obstruction: Cholestasis
Impaired metabolism: Hepatocellular
Excessive production: e.g hemolytic anemia (increased breakdown of RBC, increase in unconjugated biliiribuin)
Unconjugated Bilirubin
Unconjugated bilirubin HIGH – bound to albumin and not soluble in water; measured as indirect
Conjugated by the liver
Conjugated bilirubinemia – conjugated by the liver, soluble in the liver, measured as direct
Clootting PT?
Liver synthesizes coagulation factors (I, II, V, VII, IX, and X) in excess. Increased bleeding times.
80% of capcity needs to be lost before see a change
- Acute: would not see this as well
Only seen after moderate to significant damage
Note: Vit K deficiency
Big 7 Lab Tests
Alcohol Related Enzymes
Modest incr <10x
AST>ALT – 2:1
Chronic if albumin low
Define Cirrhosis
A chronic diffuse disease characterized by fibrosis and nodular formation