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Thiamine-dependent enzymes
For starters, you must know the four thiamine (vitamin B1)-dependent enzymes:
1) Pyruvate dehydrogenase (pyruvate → acetyl-CoA)
2) α-ketoglutarate dehydrogenase (α-KG → succinyl-CoA in the TCA cycle)
3) Branched-chain amino acid dehydrogenase (deficient in MSUD)
4) Transketolase (produced in HMP shunt)
| An ↑ in RBC transketolase activity >15% following B1 administration means B1 deficiency was severe; <5% ↑ indicates thiamine was not deficient.
If you ever get a question where they mention transketolase in relation to thiamine, increased RBC transketolase activity following thiamine administration means the patient was thiamine-deficient. |
There’s no hard and fast rule, but you can remember thiamine is generally a cofactor for dehydrogenase reactions.
Thiamine deficiency
Most often seen in the setting of chronic alcoholism. The mechanism is simply dietary deficiency. Alcohol doesn’t magically impede the absorption of thiamine.
Ethanol is 7 kcal/gram, so alcoholics tend to fill up on what they drink and don’t consume much else, putting them at risk for B vitamin deficiencies.
Dry beriberi (neuropathy) → classically numbness of the hands + feet, but can present with an array of non-specific features, including confusion.
Wet beriberi (dilated cardiomyopathy) → lateralized apex beat, S3 heart sound, bilateral pulmonary infiltrates, increased pulmonary capillary wedge pressure (PCWP), cephalization of the pulmonary vessels (pulmonary edema).
| Important point: Thiamine-deficiency and chronic alcoholism can BOTH cause dilated cardiomyopathy THAT ARE DISTINCT FROM EACH OTHER.
In other words, one of the causes of dilated cardiomyopathy is literally direct myocardial damage from chronic alcohol use, whereas a separate cause is thiamine deficiency. It is merely a coincidence that thiamine deficiency is seen in alcoholics. Alcohol can also damage skeletal muscle, increasing the risk of rhabdomyolysis, as well as the bone marrow, leading to non-megaloblastic macrocytic anemia. |
Wernicke encephalopathy is HY for B1 deficiency. There’s a triad you need to remember:
| A COW: Ataxia, Confusion and Ophthalmoplegia, Wernicke
That’s the classic triad. However if the USMLE asks you for what could occur by giving glucose to a patient without first giving thiamine, anterograde amnesia is sometimes the answer. |
If you administer glucose to an unconscious patient or in the setting of suspected alcohol use:
Never give glucose without thiamine.
If the patient is thiamine-deficient, excess pyruvate produced through glycolysis will be shunted to additional lactate. Wernicke encephalopathy will also be acutely worsened, exacerbating the patient’s confusion and anterograde amnesia.
Korsakoff psychosis, which occurs in even more advanced disease, is associated with retrograde amnesia + confabulations.
Confabulations are made up statements about the past / what the patient was doing earlier in the day to compensate for lack of memory.
The combination of the two pathologies is simply referred to as Wernicke-Korsakoff (W-K) syndrome.
| Extremely HY is knowing that the mammillary bodies are frequently damaged in W-K.
The medial dorsal nucleus of the thalamus is also thought to be damaged in W-K. |
For more on alcohol withdrawal, including delirium tremens and alcoholic hallucinosis, as well as alcohol metabolism and effects, I talk about all of that stuff in this post.
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