Water-soluble vitamin deficiency and toxicity: B1-B7: Pathology review

Definitions & Key takeaways

Water-soluble vitamin deficiencies are mainly caused by insufficient dietary intake and chronic alcohol abuse. Their toxicities or hypervitaminosis can be caused by excess intake of supplements, fortified foods, or vitamin derivative-containing medications, but this is rare. Various types of vitamin B deficiencies can result in distinct health issues. Vitamin B1, or thiamine deficiency can cause Wernicke encephalopathy and beriberi. Vitamin B2, or riboflavin, deficiency can lead to angular cheilosis, glossitis, and corneal neovascularization.

Vitamin B3, or niacin, deficiency can cause pellagra, which presents with diarrhea, dementia, and dermatitis. Vitamin B5, or pantothenic acid deficiency can cause enteritis, adrenal insufficiency, dermatitis, alopecia, and burning feet syndrome. � Vitamin B6, or pyridoxine deficiency can lead to peripheral neuropathy and sideroblastic anemia. Vitamin B7, or biotin, deficiency can cause alopecia, dermatitis, and enteritis.

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Case study0:00–0:50

82 year old Henry presents to the clinic with his daughter who is really worried that he is not eating proper meals, but he refuses any help.
She mentions that Henry has been living alone since his wife died about two years ago. Upon physical examination, you notice that Henry is severely underweight.
In addition, his tongue is swollen and he has some scaling and painful lesions on his lips and at the corners of his mouth next to him.
60 year old Beth is brought to the clinic by her son because she's had several episodes of diarrhea for the past few weeks.
Her son also mentions that Beth has started forgetting things and that she has a history of chronic alcohol abuse on physical examination.
You notice multiple rough and scaly skin lesions on Beth's face, neck and limbs. Based on the initial presentation.

Water-soluble vitamin deficiency 0:50–1:23

Both Henry and Beth seem to have some form of water soluble vitamin deficiency or toxicity. Water soluble vitamins include the B complex vitamins and Vitamin C and just like all vitamins, they need to be derived from food and inadequate dietary consumption can result in deficiency.
So in a test question, look for individuals who come from lower income countries are at an advanced age, engage in chronic alcohol abuse or have an eating disorder like anorexia nervosa.

Water-soluble vitamin toxicity1:23–1:54

Ok. Now, another high yield fact is that water soluble vitamins get easily excreted in the urine.
On the other hand, fat soluble vitamins get stored in fat cells. And that's why the water soluble vitamin toxicity also known as hypervitaminosis is much less common than that of fat soluble vitamins.
Keep in mind that hypervitaminosis can indeed occur when there's excess intake of vitamin supplements, highly fortified foods or medications containing a vitamin derivative.

Vitamin B1 (thiamine) 1:54–3:29

Ok. Now, in this video, we're gonna be focusing on the water soluble vitamins B1 through B7.
Let's start with vitamin B1, also known as thiamine which is mainly found in whole grain cereals and legumes. The active form of B1 is thiamine pyrophosphate or TPP, which acts as a cofactor for four important enzymes.
These include pyruvate dehydrogenase which converts pyruvate coming from glycolysis into acetyl coa which can then be used in the Krebs cycle, also known as the tricarboxylic acid or TCA cycle.
Then there's alpha ketoglutarate dehydrogenase, which is an enzyme of the Krebs cycle that converts alpha ketoglutarate to succinyl coa.
The third enzyme is branched chain, alpha ketoacid dehydrogenase, which is involved in the breakdown of branched chain amino acids.
And finally, there's trans cylase, that's part of the pentose phosphate pathway. Also known as the hexose monophosphate or hmp shunt, which provides an alternative pathway to glycolysis.
As a result, thiamine deficiency impairs carbohydrate and amino acid metabolism, which is essential for the production of energy in the form of ATP four year exams.
Remember that this mainly affects tissues with high energy requirements such as the brain and the heart. And for your exams.
Remember that the main causes of thiamine deficiency are inadequate dietary intake or chronic alcohol abuse. Now, a very high yield manifestation of thiamine deficiency is Wernicke encephalopathy, which is an acute and reversible neurologic condition characterized by a classic triad of symptoms, including ophthalmoplegia, ataxia, and altered mental status.

Wernicke encephalopathy3:29–4:26

Now, ophthalmoplegia means weakness or paralysis of the eye muscles and it occurs when there's damage to the brainstem. Next ataxia or unsteady gait occurs when there's damage to the cerebellum, which is responsible for coordination of our movements.
Finally, altered mental status occurs when there's damage to the mammillary bodies which are part of the limbic system. So, this can manifest as confusion, apathy, difficulty concentrating and disorientation.
If not promptly treated. Wernicke encephalopathy can lead to coma and death.

Korsakoff syndrome4:26–5:16

Now, severe thiamine deficiency can lead to Korsakoff Syndrome, which instead is chronic and irreversible for your exams.
It's important to know that the damage usually occurs in the thalamus and more specifically in the anterior and dorsomedial nuclei.
Now, the hallmark of Korsakoff Syndrome is severe and permanent memory impairment, which includes anterograde amnesia, meaning the inability to create new memories as well as retrograde amnesia, which is the inability to recall previous memories.
And another characteristic finding is confabulation, which is when the person creates stories to fill in the gaps in their memory, which they believe to be true.
Finally, individuals with Korsakoff syndrome may also experience personality changes like apathy or indifference four year exams note that there's also Wernicke Korsakoff syndrome, which presents as a combination of Wernicke encephalopathy and Korsakoff Syndrome and occurs due to damage to the mammillary bodies and the dorsomedial nuclei of the thalamus.

Wernicke-Korsakoff syndrome5:16–5:34

Moving on. Another high yield manifestation of thiamine deficiency is Beriberi, which can occur in two forms dry and wet, dry.

Beriberi5:34–6:28

Beriberi is characterized by peripheral neuropathy which may manifest as burning, tingling, prickling and pain in the hands and feet as well as symmetrical muscle wasting, especially involving the lower limbs.
On the other hand, wet Beriberi typically affects the cardiovascular system resulting in high output heart failure, meaning that the body has an unusually high demand for blood that can't be met even though the heart is pumping a high volume of blood.
This can manifest as dyspnea, tachycardia and most importantly, peripheral edema or swelling of the lower legs. Ultimately wet beriberi can lead to dilated cardiomyopathy where the heart becomes enlarged and weak.
Now, diagnosis of thiamine deficiency involves a thiamine loading test in which we measure the activity of transketolase in red blood cells twice once before and once after giving a thiamine load diagnosis is confirmed when the preload test shows a reduced activity of transketolase in red blood cells.

Diagnosis of thiamine deficiency6:28–6:55

While the postload test shows increased transketolase activity. Treatment of thiamine deficiency involves thiamine supplementation.

Treatment of thiamine deficiency6:55–7:24

In addition, individuals with malnutrition or chronic alcoholism may also require glucose infusion. But what's extremely important to remember is that glucose should not be administered before thiamine levels normalize.
That's because it will increase thiamine demand by its four dependent enzymes. Further exacerbating the deficiency and ultimately precipitating Wernicke encephalopathy.
Ok. Next up is vitamin b2 or riboflavin, which is found mainly in leafy, green vegetables, nuts, cheese, milk and eggs.

Vitamin B2 (riboflavin)7:24–9:02

Riboflavin is the precursor of flavin mononucleotide or FMN and flavin adenine dinucleotide or F AD which act as coenzymes in several reduction oxidation or redox reactions in which electrons are transferred from one molecule to another.
An important example that you have to know for the exams is the succinate dehydrogenase reaction in the Krebs cycle where the enzyme succinate, dehydrogenase converts succinate to fumarate using F ad as coenzyme.
Finally, riboflavin is also required to synthesize vitamin B3 or niacin in the liver causes of riboflavin deficiency. Once again, include inadequate dietary intake and chronic alcohol abuse for your tests.
It's important to know that riboflavin deficiency manifests as glossitis or a swollen and inflamed tongue as well as angular chilosis.
Meaning there's inflammation of the lips with scaling and painful fissures, affecting the corners of the mouth. Another characteristic finding is corneal neovascularization, which is the formation of abnormal blood vessels in the cornea.
Finally, some individuals may develop seborrheic dermatitis which presents with inflamed scaly skin lesions in areas rich in sebaceous or oil producing glands such as the face, scalp and chest.
Ok. Now let's move on to vitamin B3, also called niacin or nicotinic acid, which is found mainly in cereals, seeds and legumes as well as animal liver products.

Vitamin B3 (niacin) 9:02–10:05

Niacin can also be synthesized in the liver from the amino acid tryptophan and its synthesis requires two other B vitamins B2 and B6.
Now, niacin is the precursor of nicotinamide adenine, dinucleotide or N AD and nicotinamide adenine dinucleotide phosphate or NA ADP that similarly to FMN and F AD are important cofactors for many redox reactions.
Another high yield concept about niacin is that it decreases the production of bad cholesterol VLDL and LDL and increases the levels of good cholesterol HDL.
Because of that niacin can be used as a lipid lowering agent to treat dyslipidemia, which refers to abnormal blood levels of lipids like cholesterol.
Now causes of niacin deficiency once again, include inadequate dietary intake and chronic alcohol abuse. But what's unique here is that it can also be caused by Hartnup disease, which is an autosomal recessive disorder characterized by deficiency of transporters of neutral amino acids like tryptophan in the gastrointestinal tract and the proximal convoluted tubule as a result, there's a decreased tryptophan absorption in the gastrointestinal tract and an increased excretion in the urine.

Niacin deficiency 10:05–11:59

This means that there's not enough tryptophan left in the body to synthesize niacin and ultimately leads to niacin deficiency.
Hartnup disease can be treated with a high protein diet that contains tryptophan as well as daily supplementation with niacin.
Another cause of niacin deficiency is Carcinoid syndrome, where cancerous neuroendocrine cells start producing a variety of hormones including serotonin.
Now, just like niacin serotonin is produced from tryptophan. So in Carcinoid syndrome, tryptophan gets used up and there's not enough to produce niacin.
Finally isoniazid, an antimycobacterial agent can also lead to niacin deficiency by indirectly decreasing the levels of vitamin b6, which is required for niacin synthesis.
Now, in all cases, niacin deficiency leads to what's known as pellagra. And this manifests with a classic triad of the three Ds.
So, diarrhea, dementia and dermatitis, keep in mind that this dermatitis presents with rough scaly and sometimes hyperpigmented skin lesions.
These typically appear in the cervical or C three and C four dermatomes and take a characteristic broad collar shape, also known as the kal necklace, sometimes the sun exposed areas and especially the limbs can also be affected.
Ok. Now, let's switch gears and talk about niacin toxicity.

Niacin toxicity11:59–12:44

Now, niacin stimulates Langerhans cells which are dendritic cells of the skin immune system to release prostaglandins which cause vasodilation.
So, the most classic symptom of niacin toxicity is facial flushing and remember that this can be prevented by taking medications that reduce the production of prostaglandins like aspirin or other nonsteroidal anti inflammatory medications or nsaids.
Other high yield findings of niacin toxicity are hyperglycemia or high blood glucose and hyperuricemia or high uric acid in blood.
Although the mechanisms are poorly understood next up is vitamin b5, also known as pantothenic acid, which is found mostly in animal liver and kidney products as well as egg yolk and dairy products.

Vitamin B5 (pantothenic acid) 12:44–14:29

Now, pantothenic acid is a fundamental component of acetyl coenzyme A or acetyl coa which is an essential cofactor for the transfer of acyl groups.
Acetyl coa can participate in acetylation reactions where enzymes transfer acetyl groups from one molecule to another. What's high yield to know is that acetyl coa is important for the first reaction of the Krebs cycle where acetyl coa donates its acetyl group to oxaloacetate to form citrate, releasing a coenzyme A molecule.
And then at the fourth reaction where alpha ketoglutarate replaces one carbon dioxide molecule for coenzyme A forming succinyl coa.
Now keep in mind that pantothenic acid is also required by the enzyme fatty acid synthase, which is involved in the synthesis of fatty acids.
Now, pantothenic acid deficiency is quite rare and mostly occurs due to inadequate dietary intake. It typically presents with enteritis or intestinal inflammation, often with diarrhea.
In addition, individuals may develop symptoms of adrenal insufficiency like anorexia or decreased appetite, weight loss, abdominal pain, fatigue weakness, and muscle and joint pain.
Other characteristic findings include dermatitis or a red and scaly skin rash and alopecia or abnormal hair loss. Finally, some individuals may present with burning feet syndrome, which is characterized by a burning sensation and pain of the feet.
All right, let's move on to vitamin b6 or pyridoxine. Its main sources are nuts, whole grains, vegetables and poultry.

Vitamin B6 (pyridoxine) 14:29–16:30

Now, our body tissues convert pyridoxine into its active form, pyridoxal phosphate or PLP, which works as a cofactor for various enzymatic reactions including transamination where an aminogroup is transferred from one molecule to another as well as deamination or removal of an aminogroup and decarboxylation or removal of a carboxyl group.
In addition, remember that PLP is required for the synthesis of neurotransmitters such as Gabaa serotonin, epinephrine, norepinephrine and dopamine.
PLP is also the cofactor for delta aminolevulinic acid or delta ala synthase, which is involved in the heme synthesis pathway.
Finally, PLP is also the cofactor for the synthesis of glutathione cystathionine histamine. And don't forget, niacin pyridoxine deficiency can occur in people with inadequate dietary intake and chronic alcohol abuse as well as those with liver and kidney dysfunction.
But what's really important here is that pyridoxine deficiency can also be induced by medications like isoniazid and oral contraceptives since they can increase the excretion of pyridoxine into the urine.
In terms of symptoms. Pyridoxine deficiency is typically associated with neurological problems such as seizures, hyperirritability and peripheral neuropathy, which may manifest as burning, tingling, prickling and pain, typically affecting the hands and feet.
Another high yield manifestation is sideroblastic anemia which is when the body is unable to use iron for heme synthesis.
And instead it builds up in the mitochondria of red blood cells. Finally, there's vitamin b7 or biotin, which is mainly found in soy products and nuts as well as animal liver products, egg yolk and dairy products.

Vitamin B7 (biotin) 16:30–18:13

In addition, biotin is produced by the bacteria that make up our normal intestinal flora. Now, biotin acts as a carbon dioxide carrier for several carboxylation enzymes which add a carboxyl group to molecules.
Some important examples for your exams are pyruvate carboxylase which converts pyruvate to oxo acetate in gluconeogenesis, acetyl coa carboxylase that converts acetyl coa to malonyl coa during fatty acid synthesis and propionyl coa carboxylase which converts propionyl coa to methylmalonyl coa during protein metabolism.
Now, biotin deficiency is relatively rare but may occur if there's inadequate dietary intake. Another frequently tested cause of biotin deficiency is the excessive consumption of raw egg whites.
That's because egg whites contain a protein called avidin that binds to biotin and prevents its absorption. Keep in mind that this doesn't happen with cooked eggs as the heat destroys avidin.
Finally, biotin deficiency can be caused by long term use of antibiotics which may alter the intestinal flora. Symptoms of biotin deficiency include alopecia and dermatitis which presents as a red and scaly skin rash around the body openings such as the eyes, nose mouth and anus.
In addition, some individuals may develop enteritis. All right, as a quick recap.

Review18:13–20:56

Most water soluble vitamin deficiencies are caused by inadequate dietary intake and chronic alcohol abuse. On the other hand, their toxicity or hypervitaminosis can rarely occur when there's excess intake supplements highly fortified foods or medications containing a vitamin derivative vitamin b1 or thiamine is a cofactor for enzymes like pyruvate dehydrogenase and transketolase deficiency may lead to Wernicke encephalopathy with its classic triad of ophthalmoplegia ataxia and altered mental status.
Korsakoff syndrome with memory impairment or Wernicke Korsakoff syndrome with a combination of the two as well as dry beriberi with peripheral neuropathy and wet beriberi with high output heart failure and peripheral edema.
Vitamin B2 or riboflavin is the precursor of FMN and FAD that participates in redox reactions. Deficiency can present with angular kosis glossitis and corneal neovascularization.
Vitamin B3 or niacin is produced from tryptophan with the help of vitamins B2 and B6. And it's the precursor of NA D and NDP, which are cofactors for redox reactions.
Additional causes of niacin deficiency include harm up disease, carcinoid syndrome and taking isoniazid niacin deficiency causes Pella which presents with diarrhea, dementia and dermatitis.
On the other hand, niacin toxicity presents with facial flushing hyperglycemia and hyperuricemia. Vitamin B5 or pantothenic acid is an essential component of acetyl coa.
A cofactor for acetylation reactions, deficiency causes enteritis, adrenal insufficiency, dermatitis, alopecia, and burning feet syndrome.
Vitamin B6 or pyridoxine is converted to its active form pyridoxal phosphate or PLP, which is involved in the synthesis of neurotransmitters, heme glutathione, cystathionine, histamine and niacin deficiency can be caused by taking isoniazid or oral contraceptives and mainly leads to peripheral neuropathy and sideroblastic anemia.
Vitamin B7 or biotin acts as a carbon dioxide carrier for carboxylation reactions. Deficiency can be due to excessive consumption of raw egg whites or long term antibiotic use.
And symptoms include alopecia, dermatitis and enteritis. Going back to our cases.

Summary20:56–21:54

Henry is an 82 year old male who has glossitis as well as scaling and painful lesions on his lips and at the corners of his mouth, which are characteristic for angular chilosis.
These two findings should make you think of vitamin b2 or riboflavin deficiency. And this combined with the fact that he seems severely malnourished indicates that Henry's deficiency is due to inadequate dietary intake.
On the other hand, Beth is a 60 year old female that has a history of chronic alcohol abuse, which is another frequent cause of water soluble vitamin deficiency.
Now, two highly suggestive clues here include the fact that she's presenting with diarrhea and has started to experience dementia, which are two of the three Ds for pellagra due to vitamin b3 or niacin deficiency.
The final clue that confirms your suspicion is her dermatitis involving sun exposed skin areas, which is the third D for pellagra