lecture 5 The liver Flashcards
Hepatic artery
supplies the majority of oxygen to the liver
Portal vein
drains most of the gut, nutrients absorbed from the gut reach the liver
Hepatic veins
blood leaves from the liver and drain to the vena cava
Liver Functions
- Carbohydrate metabolism
➢Gluconeogenesis
➢Glycogen synthesis and breakdown - Fat metabolism
➢Fatty acid synthesis
➢Cholesterol synthesis/excretion
➢Lipoprotein synthesis - Protein metabolism
➢Synthesis of plasma proteins (albumin, coagulation factors, NOT immunoglobulins) - Metabolism and excretion
➢Bilirubin metabolism
➢Steroid hormones
➢Drugs/foreign compounds - Storage
➢Glycogen
➢Vitamin A, B12, E, D, K
➢Iron
Functional anatomy of the Liver
- The lobules are the functional unit of the liver
lobules
- Lobules are exagonal in shape
- At each corner: artery, vein, bile
duct (PORTAL TRIAD) - Central vein in the middle of the
lobule. This vein receives blood from
the sinusoids and drains into the
hepatic vein.
SINUSOIDS
- where the oxygenated blood
from the hepatic artery and the
deoxygenated, but full of nutrients, blood
from the portal vein mix - have endothelial cells with big gaps
that allow proteins to move out (NOT WBC or
RBC)
Kupffer cells
interspersed among
hepatocytes. They are macrophages which
get rid of bacteria that can be absorbed with
the nutrients (from the digestive tract).
Hepatocytes
receive fluid containing oxygen,
nutrients. They store most of the nutrients,
detoxify, and produce proteins (i.e. albumin).
Hepatocytes also produce bile (carries away
waste and breaks down fat)
Bilirubin Metabolism
- Bilirubin is derived from haem moiety of haemoglobin molecules
- RBC degradation releases
➢Haem
➢Iron
➢Protein - Haem is converted to bilirubin
read over slide 10 part a
Functional assessment of the liver
- Plasma bilirubin
- Plasma proteins concentration
Biochemical assessment of the liver
Plasma bilirubin concentration (3-20 μmol/L)
Hyperbilirubinemia can be due to either an excess of conjugated
bilirubin, an excess of unconjugated bilirubin, or both
An increase in plasma bilirubin concentration can induce jaundice
Jaundice
When excessive amounts of bilirubin circulate in the blood stream, they dissolve in the subcutaneous fat (the layer of fat
just beneath the skin), causing a yellowish appearance of the skin and eyes.
Albumin
➢Synthesized in the liver
➢A good indicator of liver’s functional capacity
* Has a long half life (about 21 days) so a reduction tells us that liver damage has
been ongoing for a while
➢It is reduced in chronic liver disease
➢It can also be reduced in malabsorption/malnutrition (reduces the nutrients in the
hepatocytes and they can’t synthesize albumin)
Coagulation factors
➢Liver synthesizes clotting factors
➢Significant liver damage can reduce the levels of circulating clotting factors→
increased coagulation time (also known as PT, prothrombin time)
General considerations on assessing liver function
- Plasma bilirubin concentration helps to assess the excretive function
of the liver - Plasma protein concentration helps us assess the synthetic function
of the liver - Liver function markers are not very sensitive to identify liver
damage → liver biopsy is the gold standard
Markers of liver damage
AST and ALT: Enzymes involved in amino acid metabolism
Aspartate (AST)/Alanine aminotransferase (ALT) ratio
an alteration of
this ratio can reflect cell damage
- AST/ALT ratio can be useful in assessing liver health
➢Ratio around 1.15 in healthy adults
Markers of liver damage
Alkaline Phosphatase (ALP):
➢Can indicate obstructive, viral, or drug-induced liver damage
γ-glutamyltransferase (GGT):
➢Can increase in ethanol abuse, certain drugs
Acute liver disease (acute hepatitis)
- Acute injury to the hepatocytes
- Causes:
➢Viral/immunological
➢Ischemic
➢Toxic (drug-induced-Tylenol, ethanol, herbal or dietary supplements)
All forms of acute hepatitis are associated with irreversible damage to
the hepatocytes and subsequent release of biomarkers in the plasma
AST over 200 IU/L
ALT over 300 IU/L
Are a FEATURE OF ACUTE VIRAL
HEPATITIS
Typically, 5-8X the upper reference
limit (URL), sometimes can reach 10-
50X!!!
AST/ALT ratio is <1 in viral hepatitis
how to tell if Acute hepatitis: viral-induced
Viral-induced
AST over 200 IU/L
ALT over 300 IU/L
Increase 5-50X URL
AST/ALT <1
ALP can be mildly elevated
Bilirubin increased
PT, Albumin within range
ex. Plasma findings
AST 230 (8-33 IU/L)
ALT 305 (10-50 IU/L)
ALP 150 (44-147 IU/L)
GGT 25 (5-40 IU/L)
Bilirubin 29 (3-20 μmol/L)
how to tell if Acute hepatitis: Alcohol-induced
Alcohol-induced
AST about 2-fold increase compared to ALT
Increase <10X URL
AST/ALT>2
ALP and GGT are elevated
Bilirubin increased
PT, Albumin within range
ex. plasma findings
AST 197 (8-33 IU/L)
ALT 95 (10-50 IU/L)
ALP 178 (44-147 IU/L)
GGT 75 (5-40 IU/L)
Bilirubin 22 (3-20 μmol/L)
Toxic and ischemic hepatitis
- Increase in AST and ALT is observed 24-48 hours post
ingestion/ischemic event - AST and ALT can increase of 100X the URL
- Bilirubin increase is minimal
Chronic liver disease (chronic hepatitis)
Prolonged inflammation/damage to the hepatocytes lasting over 6
months
→ can induce liver scarring (fibrosis) which may progress to cirrhosis (end
stage of liver dysfunction)
* Asymptomatic or non-specific symptoms, jaundice is a late finding (and
rare)
All liver functions are impacted by the progressive & permanent damage
Chronic liver disease: biochemical features
- Mildly elevated AST and ALT (around 2X URL) for over 6 months
- ALP, GGT, bilirubin are within range
Liver biopsy is the gold standard in the diagnosis and evaluation of
the progression of this disease
