Alkaline Phosphatase

[Reperfused]

Can someone please explain to me the significance of increased/decreased Alkaline Phosphatase?

I understand that it's kinda non-specific serum marker. It's usually increased in cholestatic and obstructive hepatobiliary disease, HCC, infiltrative disorders and bone disease.

But exactly in which hepatic diseases can we expect it to rise? And what's the pathophysiology behind it? I know with injury to hepatocytes it's released by the cells.

Like I just had an RX qs, patient with hep C developed liver cirrhosis and now has hepatic encephalopathy. Alkaline Phosphatase was increased. Why?

Whereas in some other cases of liver injury I find it to be Normal.

Thanks in advance!

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[Reperfused]

Anyone?

@Phloston @Transposony

Thanks

 

[Transposony]

There are various isoenzyme of Alkaline Phosphatases: liver (ALP-1), bone (ALP-2), intestines (ALP-3), placenta, and the PCT of the kidney.
What is measured in blood is total ALP thereby making it non-specific. That's why an elevated ALP almost always requires other tests to determine the origin of the condition.

ALP is mainly produced by the cells lining the biliary system (including gallbladder) and therefore is a measure of their integrity. That's why it is raised in biliary obstruction. It is NOT an indicator of hepatocyte injury (aminotransferases are). It may be increased in cirrhosis due to the involvement of minor ducts and also in hepatitis as well as OCPs due to involvement of biliary canaliculi.
In the bone, it is an indicator of rapid bone formation as it is produced by osteoblasts (ALP splits off phosphate from pyrophosphate creating an alkaline pH). Therefore it is frequently (normally) raised in adolescents. So it will be increased in any osteoblastic bone condition e.g. Paget's Disease, Hyperparathyroidism,
It is also normally increased in pregnancy since the placenta produces ALP.
It is also increased in IBDs like Ulcerative colitis, Crohn’s etc. & Amyloidosis.

It is decreased in Zinc deficiency since ALP is a zinc containing metalloenzyme.
Therefore it will be decreased in malabsorptive states like celiac disease and also in any condition opposite of condition causing the increase i.e. hypoparathyroidism, hypophosphatemia, hypothyroidism etc.
Hope this helps.

 

[Phloston]

I think transposony has more than owned this with his excellent explanation.

Some things I'd note:

ALP tends to be up if PTH is up since PTH initially activates osteoBLASTS (which in turn activate -clasts via RANKL-RANK). So if you get a hyperparathyroidism question and they want up and down arrows, when PTH is up so is ALP. However ALP won't be down in hypoparathyroidism. There's no real significance to the idea of 'low ALP.'

This is really important: in an arrow question for Paget, calcium, phosphate and PTH are all normal, but ALP is high. That is, the answer is everything is normal except ALP is high. So many students get that wrong.

Placental alkaline phosphatase is one of the markers of seminoma. I remember that from questions. They'd make it obvious the diagnosis is seminoma (e.g., large cells with watery cytoplasm in young adult), but sometimes that detail is thrown in there. Seminoma is very responsive to radiotherapy.

USMLE likes high ALP for PSC 2 to UC. Patients may or may not be p-ANCA positive as well. But notably p-ANCA positivity in PSC is not accompanied by anti-myeloperoxidase antibodies (I remember reading that in Johns Hopkins IM board review).

And yeah, as transposony has said, overall, ALP is non-specific because it has many types, and is most certainly not an indicator of isolated intrahepatic damage.

 

[Reperfused]

Thank you so much both Transposony & Phloston!! Your explanations have definitely cleared my concepts about ALP. Thanks, Good luck!