Are Drug toxicity, Infectious toxic disease, Hypoxia & Malignancy all Acquired Metabolic Diseases?

Question

Commonly when we talk about Acquired metabolic diseases, we refer to endocrine diseases (like Diabetic ketoacidosis, HONK, etc), electrolyte abnormalities (hyperkalemia, hyponatremia, etc), acid-base disorders (metabolic acidosis, respiratory alkalosis, etc), hyperammonemia (causing hepatic encephalopathy), hyperuricemia, nutritional deficiencies (vit def, etc), etc.

As for inherited metabolic disease, we have Inborn Errors of Metabolism (IEM).

I understand metabolic disease is any disease in which metabolic pathways inside a cell are affected. So I have questions as to whether some diseases are metabolic diseases or not.

1. Does drug toxicity/overdose or even drug side effect due to action at cell surface receptor come under this category? (for instance in belladonna/atropine poisoning, the toxin/drug acts at muscarinic receptors in various organs). Logic tells that action at a cell receptor affects obviously chemical reactions inside a cell. And so drug/food poisoning are acquired metabolic diseases. But I need second opinion.

2. Is Toxin disease due to infection (eg: clostridium difficile infection) a metabolic disease?

3. Is hypoxia a metabolic disease? (as in shock)

4. Is malignancy/cancer a metabolic disease? (because I know a lot of intracellular metabolic pathways are activated abnormally inside a cancer cell)

While logic tells me to include these disorders under metabolic disease, we don't commonly refer to them as metabolic diseases. Why is it so?

Is it true that inflammatory disease can not cause metabolic disease but metabolic disease can cause inflammatory disease (eg: hemochromatosis causing hepatitis & steatosis)?

Answer 1

When you classify diseases by causes, you put a disease in a certain group according to what happens first in that disease. For example, pheochromocytoma, a tumor of the adrenal medulla, releases excessive amounts of the hormone adrenaline, which can result in hyperglycemia. So, is pheochromocytoma a malignant, endocrine or metabolic disease? It's a malignant disease, because a tumor develops first.

Now, you can argue that pheochromocytoma is also an endocrine and metabolic disease at the same time. But an increased level of adrenaline and glucose in the blood are not diseases; they are just abnormalities that result from a disease.

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Metabolism is the term for a set of chemical reactions that occur in the cells of living organisms to sustain life.

Metabolic diseases are diseases that originate from errors in the molecules and enzymes involved in metabolism, most of which are genetic.

Drug toxicity, infections, hypoxia and malignancies can all affect metabolism as a result, but the problem does not start on the level of molecules or enzymes, so these are not metabolic diseases.

In most cases, "metabolic disease" refers to "inborn error of metabolism." But there seems to be no strict definition of metabolic disease, so you can find various very confusing lists of metabolic diseases, such as this one, which even includes dehydration...

If we agree that metabolic disease is an inborn error of metabolism, then inflammatory disease cannot result in metabolic disease, but a metabolic disease (hemochromatosis) can result in inflammation (hepatitis).

But you asked about acquired metabolic diseases. From your list, hypoxia can result from a metabolic disease, or, sometimes, causes further metabolic problems, so it is sometimes mentioned as a metabolic disorder. More examples from Oxfordmedicine.com:

...systemic acquired metabolic diseases that affect the central and/or peripheral nervous system: hypoxia, hypoglycemia, hyperthermia, disorders of serum electrolytes, vitamin deficiencies, and exogenous intoxications, particularly alcoholism and intoxications by drugs, methanol, and heavy metals.

You can think that the above conditions result in metabolic disorders, but they themselves are not metabolic disorders.