Test of Liver Function Flashcards
Functions of liver
- Excretion & detoxification
- Extracts endogenous & exogenous compounds from blood.
- Chemical transformation to aid urinary/faecal excretion (e.g. bilirubin conjugation)
and/or reduce toxicity (e.g. ammonia → urea)
- Excretion via bile - Digestion
- Synthesises bile acids required for fat digestion. - Lipid & lipoprotein homeostasis:
- Synthesises and stores lipids and fat‐soluble vitamins (A/D/E/K).
- Assembles lipoproteins to transport lipids to other tissues.
- Breaks down and recycles lipoproteins. - Protein synthesis:
- Major source of plasma proteins (e.g. albumin, fibrinogen & many clotting factors).
- Synthesises & metabolises amino acids. - Carbohydrate metabolism:
- Major site for gluconeogenesis.
- Stores glycogen to later release as glucose for systemic use.
other:
* Ketogenesis
* Storage of copper & iron.
* Immunologic ‘sieve’ for blood from lower GI tract
* Deactivates some hormones and medications.
* Activates other hormones and medications (e.g. angiotensinogen, vitamin D, codeine)
Label the Liver
Lecture Slide
Label the hepatocyte, lobule, portal tract (3 elements in it), central vein
Lecture Slide
Purpose of Hepatic artery, portal vein, biliary canaliculus
Hepatic artery:
Nutrients, wastes and toxins delievered by artery for processing and exported via hepatic vein
Portal vein: Delievers micorbial antigens and ingested toxins for clearance
biliary canaliculus: Bile is formed and shipped to canaliculus
What are the main LFT enzymes and other ones
ALT – alanine aminotransferase.
AST – aspartate aminotransferase.
GGT – gamma glutamyltransferase
ALP - alkaline phosphatase
Bilirubin and Albumin
ALT:
Location
Cause for rise in ALT
Marker for
Specific/sensitive?
Present in cytoplasm of many cells, highest concentration in liver.
Any disturbance to cell membrane & apoptosis allow ALT into circulation
- Sensitive marker of liver cell injury/inflammation etc
Quite specific to liver tissue, ALT may be elevated in non liver but large ALT elevations = liver disease
Lacks specificity fr type of injury
AST
Location
Cause for rise in AST
Specific/sensitive?
Highest conc in mitochondria. So mitochondrial leakage suggests lethal, uncontrolled cell damage
Lacks specificity for tissue source – High levels may be from: * Heart, e.g. myocardial infarction.
* Muscle, e.g. trauma, myositis.
* RBCs, e.g. intravascular haemolysis, in vitro haemolysis.
ALT and AST
- purpose of running both?
-Ratio of AST:ALT above 2 means what
-lower ratio means?
Avoid ratio if?
- Each provides an incomplete picture of site and severity of injury.
- ALT is quite sensitive and specific for liver, OK as a screening test alone.
- Together ALT & AST give a good picture of hepatocellular injury:
- AST/ALT ratio (aka De Ritis ratio) > 2 → liver necrosis ?ischaemia, ?toxic ?acute viral
- Lower ratio → ?recovery phase ?low‐grade viral disease
- Avoid if ALT is not notably elevated
GGT
-location
-marker for
- Found in? causes for elevation?
Non-specific (found in other tissues, and marker for alcohol intake and binge drinking)
- Bile is a detergent, disrupts hepatocyte membrane, releasing GGT.
- Very sensitive marker of cholestasis (↓bile drainage)
Found in many different tissues, sometimes also be elevated with:
* Non‐obstructive liver diseases, e.g. drug reactions, inflammation, MAFLD
* An alcohol binge can induce GGT (limited sensitivity/specificity).
* Renal transplantation.
* Hyperthyroidism.
ALP
- 4 ALP genes
- Placental (pregnancy, tumours).
- Germ‐line (tumours).
- Intestinal (benign or tumours).
- Tissue non‐specific ALP – Modified after synthesis to give 5 total isoenzymes:
a) Liver ALP (also on hepatocyte membranes).
b) Bone ALP.
BEcause the Bone and liver ALP makes up the most, if it is elevated, its lilely ot be a liver or Bone issue but use GGT to aid in confirmation
* When we measure ALP, we measure all 5 isoenzymes together
- usually bone and liver are the biggest parts
- Can’t differentiate cholestasis from bone disease without GGT and/or negative bone marker(s).
GGT and ALP
-useful for
-why have them as a combo?
- One elevated, both, neither what does it mean
- Useful screen for cholestasis.
- Neither enzyme is highly specific but in combination they have good sensitivity and specificity.
Both elevated: Pretty good sign of choleostasis
One elevated - probably not
neither - choleostasis unlikely
Bilirubin
- what is it
It is a breakdown of heme
When an erythrocyte (RBC) dies, haemoglobin is released and degraded, freeing haem. Haemoglobin = haem molecules + protein (globin)
Haem is degraded to bilirubin for excretion. Haem → Biliverdin → Unconjugated Bilirubin.
Bilirubin conjugated vs uncongated how are they excreted
Unconjugated bilirubin is not very water‐soluble, so hepatocytes conjugate bilirubin to glucuronide (easier to excrete in bile).
onjugated bilirubin is then mostly excreted via the biliary tract into
faeces, responsible for characteristic faecal colour.
Tests for Bilirubin
and how to calculate indirect bilirubin
- Direct bilirubin:
* A chemical reaction without the use of a detergent/accelerant. Only reacts with the water‐soluble conjugated bilirubin.
Direct bilirubin = the conjugated fraction. - Total bilirubin:
The same reaction with the use of the detergent/accelerant. The detergent
makes the insoluble unconjugated bilirubin soluble enough to react. Measures all forms of bilirubin.
- Unconjugated is not measured, it is calculated as “indirect” bilirubin:
- Indirect bilirubin = total bilirubin – direct bilirubin.
- (Total bilirubin ≈ conjugated + unconjugated)
What is Jaundice
Accumulation of bilirubin, visible in the skin and mucous membranes, esp. the sclera.
Cause of jaundice at different stages in regard to liver
Pre hepatic
- overproduction of bilirubin
Intra heaptic
- Problem with liver
post heaptic
- Obstruction stopping excreetion of bilirubin
Pre, intra and post heaptic
PHYSIOLOGY
ELEVATED TYPE OF BILIRUBIN
URINE COLOUR
STOOL COLOUR
PRURITUS
PRE:
PHYSIOLOGY: Excessive hemolysiss causing more biliruubin going to liver
ELEVATED TYPE OF BILIRUBIN: Unconjugated
URINE COLOUR: Normal
STOOL COLOUR: Normal
PRURITUS : No
INTRA:
PHYSIOLOGY: Defective conjugation, compaired cell uptake, absnormal secretion
ELEVATED TYPE OF BILIRUBIN: Conjugated and unconjugated possible
URINE COLOUR: Dark
STOOL COLOUR: Normal
PRURITUS : No
Post
PHYSIOLOGY: Mechanical obstruction of the bile flow causing build up
ELEVATED TYPE OF BILIRUBIN: Conjugated
URINE COLOUR: Dark
STOOL COLOUR: Acholic
PRURITUS : Yes
Pre heaptic Jaundice
-cause
- expected findings
Excessive production of bilirubin:
* Usually due to haemolysis or uncontrolled RBC production.
* Bilirubin produced more quickly than it can be conjugated and excreted.
Expected findings:
↑ total & unconjugated bilirubin.
↓ haptoglobin & total Hb
Possibly ↑ reticulocytes & RBC size
Intra‐Hepatic Jaundice
-causes
-expected results
↓ delivery of bilirubin to the liver – Sepsis, heart failure
↓ bilirubin uptake – Fever, competitive inhibition (e.g. rifamycin), fasting. >- inherited disorders
↓ conjugation – Gilbert syndrome, Crigler‐Najjar syndrome, liver prematurity, competitive inhibition (e.g. thyroid hormone), hepatocellular injury (e.g. viral hepatitis)
and/or ↓ cellular excretion of bilirubin – Sepsis, competitive inhibition (e.g.
anabolic steroids, oestrogens), various inherited conditions
- Expect ↑ unconjugated and/or conjugated bilirubin
Post‐Hepatic Jaundice
- Cause
-expected results
Mechanical obstruction of biliary tree
Obstruction may be:
* Inside the ducts, e.g. gallstones.
* In the duct walls, e.g. cholangiocarcinoma, strictures, biliary atresia.
* Outside the duct walls (compressing them), e.g. pancreatic cancer.
- Expect ↑ conjugated bilirubin and cholestatic LFT picture.
Albumin
Causes for hypoalbuminemia
- Hypoalbuminaemia is common in liver disease but very non‐specific:
- Malnutrition
- Sepsis and inflammation
- Protein loss (Nephrotic syndrome, protein‐losing enteropathy, burns)
Other markers for liver:
Glucose
- Liver is important for glucose storage (as glycogen), release and synthesis
SO
Spontaneous hypoglycaemia could indicate liver synthetic function is seriously impaired BUT VERY NO SPECIFIC.
