14 - Lab Interpretation of Liver Diseases

Hepatocytes face ___

Sinusoids on one side, and bile ducts on the other side

ALT and AST

• Full names and locations

• Alanine aminotransferase: Solely in the cytoplasm

• Aspartate aminotransferase: Found in the cytoplasm(ASTc) and the mitochondria(ASTm)

Which enzyme has more hepatic activity?

AST

What are other important enzymes inside the hepatocyte?

Canalicular enzymes

• Alkaline phosphatase(ALP)

• Gamma-glutamyl transferase(GGT)

What is the key feature about GGT?

It isn’t made in bone whereas ALP is

Half-lives of AST, ALT

ASTc: 1 day

ASTm: 3-4 days

ALT: 2 days

AST/ALT levels in acute and chronic hepatocyte injury

Because AST has higher hepatic activity, it’ll be higher than ALT, even though all of ALT is in the cytosol.

• Since ALT has a longer half-life than ASTc, it will later outnumber and be greater than AST

AST/ALT levels in alcoholism/fulminant liver

In these sorts of damages, since the damage is more severe, the ASTm in the mitochondria also come out, so AST > ALT

• Even when time passes, since ASTm has a longer half-life than ALT

  • Not only that, ALT requires vitamin B6, which heavy drinkers have little of

AST/ALT ratio in cirrhosis

• AST>ALT because ALT production decreases

• If long-standing cirrhosis, both enzymes production is affected, so the amount of both enzymes goes down

AST and ALT measure injuries that have a ___ pattern

Hepatocellular

ALP and GGT measure conditions that have a ___ pattern, and having 2 enzymes is useful because…?

Cholestatic

• Because ALP is found in bone too but GGT isn’t, so if ALP is high and GGT is normal, it could be from the bone

Why does cholestasis boost ALP and GGT?

1. Increased synthesis

2. Released from the membrane and freed into blood due to bile’s detergent-like quality

Bilirubin types and how they are given in lab results

Total bilirubin, unconjugated(indirect) bilirubin, conjugated(direct) bilirubin

In lab, we are given total bilirubin and direct bilirubin, so to get indirect bilirubin we have to do “Indirect = Total - direct”

Values required for conjugated/unconjugated hyperbilirubinemia

• Conjugated hyperbilirubinemia: Direct bilirubin > 50% of total

• Unconjugated hyperbilirubinemia: Indirect bilirubin > 80% of total

What does conjugated/unconjugated hyperbilirubinemia represent?

1. Unconjugated hyperbilirubinemia: Too much bilirubin being made(like hemolysis) or decreased UGT level or activity

2. Conjugated hyperbilirubinemia: Intrahepatic cholestasis, extrahepatic cholestasis

Globulin equation

Globulin = Total protein - albumin

Albumin half-life and implication

18-20 days, making it NOT a good indicator for acute/mild hepatic dysfunction

Why can we find a reverse A/G ratio in cirrhosis?

Because the damaged hepatocytes can’t properly make albumin, so globulin value rises above it

What factor has the shortest half-life, what does that mean for liver function and what test reflects that?

Factor VII(4-6 hr half-life), it means that it can be used as a fast marker of liver function since the liver makes factor VII, and a Prothrombin time test reflects that since it tests the extrinsic pathway(VII, X, V, II)

Hepatocellular pattern injuries include…

MASLD, alcoholic liver disease, viral hepatitis, drug-induced liver injury

Paracentesis meaning

Putting a needle into the abdominal wall to remove ascitic fluid, for diagnosis or for therapeutic purposes

When doing a cell count/differential test, what tube do we use?

EDTA

SAAG

• Stands for

• What it is

• Purpose

• Numerical value

• Serum-ascites albumin gradient

• Serum albumin - ascitic fluid albumin

• It reflects portal pressure. In portal hypertension (e.g., cirrhosis), high hydrostatic pressure forces water out of the vessels while most albumin stays in the blood, so the ascitic fluid is albumin-poor relative to serum and the gradient is large

• SAAG >= 1.1 g/dL = Portal hypertension

  • If SAAG < 1.1 g/dL, think nephrotic syndrome, pancreatitis, peritoneal carcinomatosis, tuberculous peritonitis

What do we do next after figuring out SAAG?

If SAAG is >= 1.1 g/dL, we look at ascitic protein

• If protein is < 2.5 g/dL = cirrhosis, because the sinusoids become capillarized (lose their pores and gain collagen), so water is forced out but most protein is held back

• If protein is ≥ 2.5 g/dL = post-sinusoidal obstruction, such as HF, constrictive pericarditis, Budd-Chiari syndrome, IVC obstruction, because the sinusoids are still normal and leaky, so back-pressure pushes protein-rich fluid into the peritoneal cavity

SBP

• Stands for

• Requirement

• Spontaneous bacterial peritonitis

• Ascitic neutrophil count of >= 250 cells mm³

  • The gold standard, culture can work too but often negative in true SBP

Another way bacteria gets into the peritoneum that isn’t SBP is ___

Secondary bacterial peritonitis

Secondary bacterial peritonitis

• Causes

• Difference from spontaneous

• Peptic ulcer, appendix, diverticulum

• Multiple organisms rather than one(due to spilling all at once), high ascitic total protein due to inflammation(spontaneous has low protein)

Do we give antibiotics first or take the bacterial sample first?

Take the sample first, the antibiotics might kill the bacteria and we won’t know what it was

HCC surveillance

• Demographic

• Tests done

• Anyone with cirrhosis, chronic HBV, and consider their age too

• U/S liver every 6 months, AFP optional(as a tumor marker)