Every liver panel answers two questions. One: is the injury in the cells (AST and ALT leak out) or in the bile ducts (alkaline phosphataseALP: made by liver canaliculi, osteoblasts, placenta, and intestine. Context determines origin → GGT is the referee. climbs)? Two: when alkaline phosphatase is high, did it come from liver or bone? GGTGGT: canalicular enzyme induced by alcohol and obstructive cholestasis. Bone osteoblasts cannot produce GGT → high GGT alongside ALP = hepatobiliary, not bone. settles it, because bone makes no GGT. Read the panel in that order and the diagnosis falls out.
Commit: A 48-year-old teacher has weeks of fatigue and a vague itch. Alkaline phosphatase is nearly twice the upper limit. AST and ALT are normal. No bone pain, no pregnancy. Alkaline phosphatase can come from liver or bone, and you need to know which. Which single lab tells you the source?
Repeat alkaline phosphatase weekly until it behaves
Serum calcium alone because bones hoard calcium stories
Gamma-glutamyl transpeptidase (GGT)
Urinary bilirubin dipstick as first referee
Alkaline phosphatase does not tell you where it came from. Bone osteoblasts make it, and so do the bile canaliculi in the liver. GGT is the tiebreaker: the liver makes GGT, bone does not. So if GGT is also high, the alkaline phosphatase is hepatobiliary. If GGT is normal, the source is bone. Calcium does not localize the enzyme. Repeating the same alkaline phosphatase adds no new information. Rule: isolated, unexplained alkaline phosphatase elevation → check GGT first to split liver from bone.
Lab Lineup ER
Five patients waiting. Each has a hidden lab panel. Tap a lab to reveal it. Make the call with as few reveals as possible.
ER Queue · 5 Patients
Each lab card shows the value when tapped. Pick the diagnosis below each patient when ready. Score tracks how many reveals you used per case.
0
solved
0
missed
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reveals used
From the Attending
Liver workup is a four-lab problem: AST / ALT / Alk Phos / GGT · add total + direct bilirubin and you've covered 90% of the differential. AST/ALT ratio > 2 with mild elevation = alcoholic (B6-dependent ALT drops). ALT > AST mild to moderate = NAFLD or chronic viral. Both > 1000 = acute viral, ischemic, acetaminophen. Alk Phos + GGT both up = cholestasis. Alk Phos up + GGT normal = bone source (Paget, fracture, growth). The lineup teaches by letting the pattern emerge one number at a time.
Ratios & Canalicular Labs
Flip between the two ratio patterns, then read the cholestasis lab panel below.
AST / ALT < 1
AST / ALT ≥ 1
ALT outruns AST
De Ritis ratioAST divided by ALT. Named after Fernando De Ritis who first described alcoholic liver disease patterns. >2:1 suggests alcoholic hepatitis; <1 suggests viral/NAFLD. below 1 means ALT is the bigger number.
Classic causesViral hepatitis and early fatty liver (NAFLD)
Still check alk phosBile-duct obstruction can shift enzymes too, so always read alkaline phosphatase alongside the ratio
Why ALT leadsCytosolic ALT leaks first in early hepatocyte injury, so ALT runs ahead of AST
TrapALT being high does not rule out bile-duct disease. Itch plus high alkaline phosphatase still means image the ducts.
AST catches ALT
AST climbs relative to ALT in alcohol, massive necrosis, advancing fibrosis, and from tissue outside the liver.
AlcoholAST tops ALT, ratio above 1.5, but AST stays under 400 IU/L. B6 depletion caps how high it can climb.
CirrhosisAs scar replaces hepatocytes, the ratio widens toward AST
Non-liver sourcesMassive necrosis, hepatocellular carcinoma, liver metastases, rhabdomyolysis, and MI all release AST
GGT clueGGT high while alkaline phosphatase stays normal points to chronic alcohol, not obstruction
The cholestasis lab pattern
When bile cannot drain (cholestasis), conjugated (direct) bilirubin backs up and alkaline phosphatase and GGT rise together.
Parameter
Board cheat sheet
Alkaline phosphatase
Made by liver bile canaliculi AND bone, plus placenta and intestine. A high value alone cannot name its source. Infiltrative liver disease and bone tumors both raise it.
GGT
Made in the bile canaliculi, not in bone. Rises fast with bile obstruction and with alcohol. A high GGT next to a high alkaline phosphatase confirms the liver is the source.
Indirect bilirubin
Unconjugated, fat-soluble pigment from heme breakdown. Rises when red cells break down faster than the liver can conjugate the pigment (hemolysis).
Direct bilirubin
Conjugated pigment. Spills back into the blood when bile cannot drain, as in obstruction or hepatocyte injury.
5 prime nucleotidase
Older liver-specific marker. Like GGT, it confirms that a high alkaline phosphatase came from the liver, not bone.
Splitting bilirubin into direct and indirect separates obstruction (direct rises) from overproduction like hemolysis (indirect rises). Trapped bile salts also injure hepatocytes, which leaks some AST and ALT later.
Decision Tree
Commit to a path before the answer reveals.
From the Attending
The AST/ALT ratio is a pattern, not a number to memorize blindly. AST > ALT (ratio > 2, "scotch and toast") · alcoholic liver disease. Mechanism: chronic alcohol depletes pyridoxal phosphate (B6), and ALT depends on B6 more than AST · so ALT drops out, AST rises relatively. ALT > AST · viral hepatitis, NAFLD, drug-induced (acetaminophen toxicity gives AST/ALT both >1000). Ratio >4 · think Wilson disease. Alk phos + GGT both up = hepatobiliary obstruction (cholestasis); alk phos up + GGT normal = bone source (Paget, fracture, growth). GGT is the bone-vs-liver splitter for alk phos.
1
A young office worker feels vaguely unwell. Alkaline phosphatase is high, but AST and ALT are normal. Which cheap serum test tells you whether the alkaline phosphatase is from liver or bone?
Gamma-glutamyl transpeptidase
Repeat every enzyme weekly without adding context
2
GGT is back. Which result points to the liver or bile ducts?
Both alkaline phosphatase and GGT are high together
Alkaline phosphatase is high but GGT is normal
The Lineup
Tap a card to flip it. Front: facts. Back: why it happens.
Blocked bile flow
Direct bilirubin and bile-duct enzymes rise; trapped bile salts then injure hepatocytes
DIRECT BILIRUBIN UP, WITH ALK PHOS AND GGT TOGETHER
tap to flip →
Why This Happens
Trace It
Bile cannot drain. Conjugated bilirubin backs up into the blood. Alkaline phosphatase and GGT rise from the stressed bile canaliculi. Trapped bile salts also damage hepatocyte membranes, so AST and ALT leak a little later.
Move
Image the bile ducts. Look for a stone, a stricture, or a mass. Trap: calling it viral hepatitis ignores the high direct bilirubin pointing to an obstruction.
Alcohol pattern
Alcohol switches on GGT and releases mitochondrial AST, so AST leads ALT
AST OVER ALT, GGT HIGH, ALK PHOS NORMAL
tap to flip →
Why This Happens
Trace It
Alcohol damages mitochondria, so mitochondrial AST pours out while ALT stays lower. Alcohol also switches on GGT production, so GGT can be high even when alkaline phosphatase is still normal.
Move
Get an honest drinking history. Trap: calling it acute viral hepatitis when the AST-over-ALT ratio and isolated GGT point to alcohol.
Memory Hooks
Tap to unblur. Test yourself before peeking.
🦴
Bone makes no GGT
Bone osteoblasts make alkaline phosphatase but not GGT. So a high alkaline phosphatase with a normal GGT means the bone, not the liver.
tap to reveal
🍺
GGT alone means alcohol
Alcohol switches on GGT production, so GGT can rise on its own, before any bile-duct blockage and before alkaline phosphatase moves.
tap to reveal
⚖️
De Ritis ratio
De Ritis ratio is AST divided by ALT. Below 1, ALT leads (viral, NAFLD). Above 2, AST leads (alcohol).
tap to reveal
The Enzyme Hunt
Watch the labs drop. Make the call. One patient, three clues.
ENZYME DETECTIVE · CASE 1
MARCUS
AGE 47
"Fatigue for six weeks. Noticed his eyes looked yellowish last Tuesday."
✓
LABS INCOMING
ALP248 IU/L HIGH
GGT186 IU/L HIGH
AST62 IU/L normal
ALT48 IU/L normal
Direct bili2.8 mg/dL HIGH
ALP and GGT are both high. Direct bilirubin is up too. What is the pattern?
Bone Wizardry is an independent educational resource for visual learning in the medical sciences. It is not affiliated with, endorsed by, or sponsored by any licensing or examination board, contains no real or recalled examination questions, and does not guarantee any educational or examination outcome.
