Vitamin deficiency and toxicity

How long is B12 stored in the liver?

3-4 years

A 6-year-old boy is brought to the pediatrician by his father with easy bruising of his legs and heavy bleeding when he brushes his teeth. The patient has recurrent otitis media and has been treated with multiple courses of antibiotics, including ceftriaxone. Laboratory tests show prothrombin time of 22 seconds, international normalized ratio of 1.5, and activated partial thromboplastin time of 47 seconds. Which of the following mechanisms is most likely inhibited in this patient? A) Activation of antithrombin III B) Carboxylation of glutamic acid residues C) Cross-linking of fibrin polymers D) Hydrolysis of fibrinogen E) Hydroxylation of proline residues

B) Carboxylation of glutamic acid residues Vitamin K deficiency can occur after the prolonged use of broad-spectrum antibiotics, particularly cephalosporins. Vitamin K is required for the carboxylation of glutamic acid residues, a key event to support the function of factors within the clotting cascade. Vitamin K deficiency presents with easy bruising and a propensity for bleeding, along with an increased PT and PTT.

Vit D deficiency in children vs adults?

Children: - Rickets (bone deformity such as genu varum "bowlegs") Adults: - Osteomalacia (bone pain and muscle weakness)

Vitamin C deficiency causes scurvy due to defect in?

Collagen hydroxylation

The four most common vitamin deficiencies include?

D B6 (pyridoxine) B9 (folic acid) B12 (cobalamin)

Which vitamins aren't in breast milk?

D and K Neonates are given vitamin K injection at birth to prevent hemorrhagic disease of the newborn

Zinc deficiency symptoms

Delayed wound healing Suppressed immunity Male hypogonadism Decreased adult hair (axillary, facial, pubic) Dysgeusia Anosmia May predispose to alcoholic cirrhosis Figure: Associated with acrodermatitis enteropathica (Defect in intestinal zinc absorption).

Polyneuropathy with symmetric muscle wasting

Dry beriberi Thiamine (B1) deficiency

Autosomal recessive deficiency of neutral amino acid (eg, tryptophan) transporters in proximal renal tubular cells and on enterocytes Leads to neutral aminoaciduria, decreased absorption from the gut, and decreased tryptophan for conversion to niacin "pellagra-like symptoms"

Hartnup disease

High-dose supplementation of which vitamin may alter metabolism of vitamin K (such as enhanced anticoagulant effects of warfarin)

High dose Vit E (tocopherol, tocotrienol)

Why can Vitamin D excesses be seen with granulomatous diseases

Increased activation of vitamin D by epithelioid macrophages

Which vitamin A derivative needs a negative pregnancy test and two forms of contraception are required before is its prescribed

Isotretinoin Because it is Teratogenic (cleft palate, cardiac abnormalities)

Amnestic disorder due to chronic alcohol overuse that presents with confabulation, personality changes, and memory loss

Korsakoff syndrome - Thiamine (B1) deficiency Dont mix up with wrinkles encephalopathy which is also a Thiamine (B1) deficiency and presents with Confusion, Ophthalmoplegia, and Ataxia

Vitamin D deficiency can be due to?

Malabsorption and poor diet, Low sun exposure Chronic kidney disease (CKD) Advanced liver disease Darker skin

Which drug can cause a B12 (cobalamin) deficiency

Metformin

B9 (folate) deficiency can be caused by which drugs?

Phenytoin (Antiepileptic) Sulfonamides Methotrexate

Thiamine deficiency diagnosis is made by increase in ________activity following vitamin B1 administration

RBC transketolase activity

Cheilosis, "magenta" tongue, and Corneal vascularization

Riboflavin (B2) def Cheilosis = inflammation of lips, scaling, and fissures at the corners of the mouth

Swollen gums, easy bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, "corkscrew" hair

Scurvy Vit C (ascorbic acid) def

Symptoms of pellagra (B3 deficiency)?

The 3 D's - Diarrhea - Dementia (also hallucinations) - Dermatitis (C3/C4 dermatome circumferential "broad collar" or "Casal necklace" rash, and hyperpigmentation of sun-exposed limbs)

Impaired glucose breakdown which leads to ATP depletion worsened by glucose infusion; highly aerobic tissues (eg, brain, heart) are affected first

Thiamine (B1) deficiency

Vitamin K deficiency can be caused by prolonged use of which drug

broad-spectrum antibiotics

Malabsorption syndromes with steatorrhea (cystic fibrosis and celiac disease) can cause a deficiency in which vitamins

fat-soluble vitamin def

A 41-year-old woman reports months of worsening tingling in her feet. She has not traveled in the last 5 years and eats a balanced diet. She has no medical or surgical history. Physical examination reveals mild jaundice, and there is inflammation and a glazed, atrophic appearance of the tongue. Neurologic examination is significant for decreased vibration sense and decreased strength in the lower extremities. Blood smear shows megaloblastic anemia with hypersegmented neutrophils. Which of the following is the mechanism of this patient's most likely disorder? A) Autoantibodies against gastric epithelium B) Bacterial overgrowth C) Inadequate dietary vitamin intake D) Infection with Diphyllobothrium latum E) Pancreatic insufficiency

A) Autoantibodies against gastric epithelium. Vitamin B12 deficiency results in megaloblastic anemia, glossitis, and both motor and sensory symptoms (eg, paresthesia). Pernicious anemia because of autoantibodies against gastric epithelium is the most common cause of vitamin B12 deficiency in patients without other risk factors. - Bacterial overgrowth in an intestinal blind loop can lead to competition for nutrients. Typical symptoms associated include bloating, flatulence, abdominal pain, and diarrhea. - Dietary vitamin deficiency of vitamin B12 can rarely be seen in patients who have adhered to strict vegan diets over several years. - Infection with Diphyllobothrium latum can result in vitamin B12 deficiency. Risk factors include working in close proximity to livestock, poor hygiene, traveling to or living in endemic areas, and eating raw or undercooked meats. - Pancreatic insufficiency may present with diabetes and abdominal pain and involve bowel movements that are bulky, loose, and foul smelling.

A 14-year-old girl is brought to the physician by her parents because of a 1-month history of a rash that appears with sun exposure, Her parents tell the physician that she has been eating little food. Physical examination shows a pruritic rash on the exposed areas of the body. Her serum tryptophan concentration is decreased Urine studies show increased excretion of amino acids: predominantly alanine, isoleucine, leucine, phenylalanine: tryptophan, and valine. Production of which of the following vitamins is most likely impaired in this patient? A) Niacin B) Vitamin B (thiamine) C) Vitamin B2 (riboflavin) D) Vitamin B5 (pantothenic add) E) Vitamin C

A) Niacin Hartnup disease is an autosomal recessive disorder involving a defect in a kidney and intestinal neutral amino acid transporter protein. This defect leads to aminoaciduria and a decreased absorption of neutral amino acids from the gastrointestinal tract resulting in deficiencies of neutral amino acids. Neutral amino acids include tryptophan, phenylalanine, glycine, alanine, valine: isoleucine, leucine: methionine, and proline. Tryptophan is converted to niacin, so a deficiency in tryptophan can result in niacin deficiency. Niacin deficiency is characterized by rash, glossitis, diarrhea, and neuropsychological disturbances such as dementia and hallucinations.

A 71-year-old woman is brought to the emergency department by her daughter because of fatigue, dizziness, and palpitations. For the past few months, her diet has consisted of small quantities of coffee, rice crackers, and jelly. Laboratory studies show hemoglobin of 10.9 g/dL, mean corpuscular volume of 105.9 fL, elevated homocysteine, and normal methylmalonic acid. This patient has a deficiency in? A) Folate B) Cobalamin C) Pantothenic acid D) zinc

A) folate deficiency Megaloblastic anemia has two principal causes: vitamin B12 (cobalamin) deficiency and folate deficiency. This patient's diet over the last few months lacks fruit, vegetables, meat, fish, and dairy, so her megaloblastic anemia is most likely due to vitamin deficiency. Compared with vitamin B12, body stores of folate are minimal and can be depleted within a few months if intake is inadequate. Leafy green vegetables are a natural source of folate. In addition, vitamin B12 deficiency presents with neurologic symptoms such as weakness and peripheral neuropathy and increase in both methylmalonic acid and homocysteine

A 33-year-old woman comes to the office for a follow-up 6 months after a seizure. The underlying cause of her seizure was unclear, but she has not had any seizures since she began taking an antiseizure medication. However, she now complains of fatigue. On examination, the patient is pale. Laboratory studies from today's visit show a leukocyte count of 5600/mm3, hemoglobin of 10.9 g/dL, hematocrit of 35%, and platelet count of 199,000/mm3. Results of laboratory studies done just before starting the medication were normal. Peripheral blood smear shows MCV >115, anisocytosis, poikilocytosis, and hypersegmented neutrophil. Which of the following most likely explains both the fatigue and abnormality seen in this patient's peripheral blood smear? A) Folate deficiency B) Iron deficiency C) B12 deficiency D) B6 deficiency

A) folate deficiency This patient likely has megaloblastic anemia secondary to folate deficiency, given her medication history, history of fatigue, examination finding of pallor, and the findings of decreased hemoglobin and hematocrit with hypersegmented neutrophils on peripheral blood smear. Hypersegmented neutrophils have nuclei with greater than 5 lobes, which is seen in this patient's blood smear and common in patients with megaloblastic anemia. The most common causes of megaloblastic anemia are folate and vitamin B12 deficiencies. Folate stores deplete faster than vitamin B12 stores, lasting only around 4 months. Phenytoin, a common antiepileptic medication and likely what this patient was prescribed, blocks absorption of folate and increases the utilization of folate by the body, leading to folate deficiency - Iron deficiency results in a microcytic anemia with small, hypochromic RBCs on a peripheral blood smear. - Vitamin B12 deficiency may also cause hypersegmented neutrophils and megaloblastic anemia but is not associated with antiepileptic medication. - Vitamin B6 deficiency can cause dermatitis, glossitis, stomatitis, a microcytic anemia, and peripheral neuropathy in adolescents and adults.

A 7-year old girl is brought to a clinic because of fatigue and weight loss. She immigrated from a developing country with her family 1 week ago. The family has had very poor access to food for the past 2 years. The child says she feels itchiness all the time. She is at the 5th percentile for body weight, 50th percentile for height. On examination her abdomen is scaphoid. She has dry eyes, and further evaluation shows diminished lacrimal gland function. Which is most likely deficient in this patient? A) Vitamin B2 B) Vitamin A C) Vitamin B12 D) Vitamin C E) Vitamin D F) Vitamin K

B) Vitamin A The patient's overall appearance of malnutrition, history of limited food intake, impaired lacrimal gland function, and pruritus suggest vitamin A deficiency. Deficiency of vitamin A leads to impaired differentiation of specialized epithelia throughout the body, causing xerophthalmia, Bitot spots (see image) which are composed of epithelial debris on bulbar conjunctiva, metaplasia of specialized epithelia in pancreatic ducts, and metaplasia of epithelia in the respiratory and urinary tracts. This is most common in areas of the world with limited food and malnutrition. In resource-rich countries, it may occasionally be seen in children with malabsorption syndromes such as inflammatory bowel disease or pancreatic insufficiency. - Vitamin B12 deficiency include megaloblastic anemia and neurologic deficits secondary to subacute combined degeneration and/or reversible dementia. - vitamin C deficiency include weakness, gum disease, bleeding and petechial rash, poor wound healing, and hair changes. - vitamin D is associated with rickets in children and osteomalacia in adults. - riboflavin (vitamin B2) deficiency include glossitis, lesions of the lips, and anemia. - Vitamin K deficiency presents with prolonged bleeding due to an inability to create mature clotting factors

A deficiency in which vitamin can cause glossitis

B3 (niacin, nicotinic acid)

Malignant carcinoid syndrome (MCS) can be from a deficiency in which vitamin

B3 (niacin, nicotinic acid) def MCS - from increased tryptophan metabolism that causes more serotonin synthesis

Facial flushing (induced by prostaglandin, not histamine), hyperglycemia, hyperuricemia.

B3 (niacin, nicotinic acid) toxicity Facial flushing can be avoided by taking aspirin with niacin

Dermatitis, enteritis, alopecia, adrenal insufficiency may lead to burning sensation of feet ("burning feet syndrome"; distal paresthesias, dysesthesia)

B5 (pantothenic acid) deficiency

Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia (due to impaired hemoglobin synthesis and iron excess)

B6

Vitamin _____ deficiency can be inducible by isoniazid and oral contraceptives

B6 (pyridoxine)

Vitamin ____ deficiency can be caused by excessive ingestion of raw egg whites

B7 (biotin)

Dermatitis, enteritis, alopecia

B7 (biotin) def Dermatitis: itchy, dry skin, and or rash Enteritis: inflammation of the small intestine Alopecia: bald

Vitamin B9 vs B12 deficiency labs?

B9 - Increased homocysteine with normal methylmalonic acid B12 - Increased serum homocysteine and methylmalonic acid levels

Which vitamin deficiency can cause neural tube defects?

B9 (folate) Supplemental folic acid at least 1 month prior to conception and during early pregnancy to reduce risk of neural tube defects. Give vitamin B9 for the 9 months of pregnancy

Macrocytic megaloblastic anemia; hypersegmented polymorphonuclear cells (PMNs); glossitis; and no neurologic symptoms

B9 (folate) def (B12 def will show neurologic symptoms)

Increased homocysteine and Normal methylmalonic acid?

B9 (folate) def Can be Seen in chronic alcohol overuse, pregnancy, Drugs (Phenytoin, Sulfonamides, Methotrexate)

A 38-year-old male presents to the clinic with symptoms of hair loss, a rash, and a metallic taste in the mouth; the symptoms have worsened over the last 2 months. The patient has a history of Crohn disease, which has required multiple small bowel resections and for which he is not receiving regular medical care. Physical examination reveals an erythematous rash around his mouth and excoriations and erythema around the anus and buttocks. Patches of no hair are visible on his scalp. The patient suffers from a deficiency of which of the following? A) Copper B) Iron C) Selenium D) Zinc

This patient is likely suffering from zinc deficiency, as evidenced by symptoms of alopecia, perianal and perioral dermatitis, and dysgeusia and the history of severe Crohn disease, which can lead to malabsorption and zinc deficiency. Zinc plays a role in numerous processes through incorporation as a cofactor into the zinc-finger-domain structure of many transcription factors important in cellular growth, tissue repair, wound healing, metabolism, and immunity. Deficiency of zinc is rare but more common in patients with diseases involving the small bowel that may affect the absorption of zinc. Because it plays a diverse role in many biological processes, zinc deficiency presents with various symptoms in multiple body tissues. Dysfunctional wound healing, perioral and perianal dermatitis, dysgeusia (abnormal, unpleasant taste sensation), loss of smell, hypogonadism, alopecia, lowered immunity, and diarrhea are some potential symptoms

A 72-year-old woman comes to the clinic because of a 3-month history of fatigue. She lives alone and consumes a diet of mostly tea, bread, and cheese. She does not drink alcohol or take any medications. There is conjunctival pallor present, rest of the PE is normal. Results of the CBC are below: Hemoglobin: 8.7 g/dL Hematocrit: 26% Mean corpuscular volume: 113 Leukocytes: 7,000/mm3 Platelets: 140,000/mm3 Which of the following additional findings is most likely to be seen in this patient? A) Degeneration of posterior column of spinal cord B) Elevated serum levels of orotic acid C) Heinz bodies on peripheral blood smear D) Increased blood homocysteine E) Increased serum methylmalonic acid

This patient likely has folate deficiency, given her anemia (fatigue, pallor), high mean corpuscular volume (macrocytic anemia), and limited diet. This form of anemia can be due to folate or vitamin B12 deficiencies, liver disease, heavy alcohol use, hypothyroidism, and some antiretroviral drugs used for the treatment of HIV. In the absence of findings of liver disease (hepatomegaly, ascites, edema) or hypothyroidism (slow pulse, goiter) or the use of other medications, the most likely cause is a vitamin deficiency. This patient's limited diet includes cheese, which is rich in vitamin B12 but completely devoid of folate, suggesting folate deficiency as the most likely diagnosis. Unlike B12 deficiency, folate deficiency can present within months after removal of folate from the diet, whereas B12 deficiency takes years to develop. - Increased methylmalonic acid levels and degeneration of the posterior column and lateral corticospinal tract would be seen in vitamin B12 deficiency, which is much less common than folate deficiency and would also more likely present with neuropathy and glossitis. In addition, given the patient's diet, B12 deficiency would not be expected. - Glucose-6-phosphate dehydrogenase deficiency can cause Heinz bodies (ie, bite cells) on peripheral smear but would present with a normocytic anemia and jaundice. Additionally, this is X-linked recessive, so it is typically seen in men. - Increased serum orotic acid is associated with a defect in uridine monophosphate synthase, an important enzyme for de novo nucleotide synthesis. Although it may present with a macrocytic anemia, it typically presents in children as failure to thrive and/or developmental delay.

A 43-year-old man comes to the clinic because of a painful rash on his forearms and neck, muscle weakness, and loose stools. He has a history of alcohol use disorder. On physical examination, the patient is agitated and disoriented. His tongue is enlarged and erythematous, and the affected skin appears thickened and hyperpigmented. A deficiency in which of the following characterizes the most likely diagnosis in this patient? A) Biotin B) Pantothenic acid C) Thiamine D) Tryptophan E) Zinc

This patient most likely has niacin (vitamin B3) deficiency, also called "pellagra," based on his presentation with a painful upper extremity rash, diarrhea, muscle weakness, enlarged and erythematous tongue, mental status changes, and history of alcohol use disorder (AUD). Individuals who are homeless or affected by AUD are at risk for developing dietary vitamin deficiencies. The symptoms of pellagra are classically described as the 3 Ds: Diarrhea, Dementia, and Dermatitis. Glossitis is another important symptom. Pellagra is an Italian word meaning "thickened skin," which describes the hyperpigmentation on sun-exposed areas of the body (as seen in the image). The rash's circumferential distribution in the C3/C4 dermatome is known as the "Casal necklace." Niacin is derived from tryptophan, a decrease in tryptophan absorption or an increase in tryptophan metabolism results in pellagra. Niacin is an essential vitamin due to its roles as the building blocks in the production of NAD and NADP, which are cofactors that serve as oxidizing and reducing agents

How is Hartnup disease treated?

Treat with oral niacin (nicotinic acid) supplements and high protein diet

Corneal squamous metaplasia "Bitot spots" (keratin debris; foamy appearance on conjunctiva)

Vit A def

Night blindness (nyctalopia) Dry and scaly skin (xerosis cutis) Dry eyes (xerophthalmia) Corneal degeneration (keratomalacia) Immunosuppression

Vit A def

Chronic vit _____ toxicity = alopecia, dry skin (eg, scaliness), hepatic toxicity and enlargement, arthralgias, and idiopathic intracranial hypertension

Vit A toxicity

Acute vit _____ toxicity = nausea, vomiting, increased ICP

Vit A toxicity Increased ICP = vertigo and blurred vision

Which vitamin deficiency can cause degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts

Vit B12 (cobalamin)

Absence of terminal ileum (surgical resection for Crohn disease) can cause which deficiency

Vit B12 (cobalamin) def

Increased serum homocysteine and methylmalonic acid levels

Vit B12 (cobalamin) def

Lack of intrinsic factor (eg, pernicious anemia, gastric bypass surgery) can cause which deficiency?

Vit B12 (cobalamin) def

Macrocytic, megaloblastic anemia; hypersegmented PMNs; paresthesias and subacute combined degeneration due to abnormal myelin

Vit B12 (cobalamin) def

Veganism is at risk for which vitamin deficiency

Vit B12 (cobalamin) def

Which vitamin deficiency can be caused by malabsorption from sprue, enteritis, Diphyllobothrium latum, achlorhydria, or bacterial overgrowth

Vit B12 (cobalamin) def

Necessary for hydroxylation of proline and lysine in collagen synthesis

Vit C (ascorbic acid) side note: Also necessary for dopamine β-hydroxylase (converts dopamine to NE)

Which vitamin deficiency may be precipitated by tea and toast diet

Vit C (ascorbic acid) def

Can increase iron toxicity in predisposed individuals by increasing dietary iron absorption (ie, can worsen hemochromatosis or transfusion-related iron overload)

Vit C (ascorbic acid) excess

Nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis

Vit C (ascorbic acid) toxicity

Which vitamin helps to increase intestinal absorption of Ca2+ and PO4 3-

Vit D

An antioxidant that protects RBCs and membranes from free radical damage

Vit E (tocopherol, tocotrienol)

Neurologic presentation may appear similar to vitamin B12 deficiency, but without megaloblastic anemia, hypersegmented neutrophils, or increase in serum methylmalonic acid levels

Vit E def Demyelination of posterior columns (Decreased proprioception and vibration sensation) and spinocerebellar tract (ataxia).

Vitamin necessary for the maturation of clotting factors II, VII, IX, X, and proteins C and S

Vit K

Neonatal hemorrhage with increased PT and aPTT, but normal bleeding time

Vit K def Neonates have sterile intestines and are unable to synthesize vitamin K

A 6-year-old boy is evaluated at an urgent clinic for skin abnormalities and refusal to bear weight on the left leg. He has also had very slow wound healing after bumps and scrapes. The patient's family has suffered from inadequate food intake for the past year. Physical examination reveals bleeding, inflamed gums, abnormal coiled hairs, petechiae on the chest and back, and diffusely tender muscles. Laboratory studies show a hemoglobin level of 10.2 g/dL. Which Vitamin is most likely deficient given this patients condition?

Vitamin C deficiency may cause poor wound healing, petechiae, and gingivitis. Vitamin C is an essential cofactor in the hydroxylation of proline and lysine residues in collagen, and a deficiency of vitamin C disrupts collagen formation and function.

A 2-month-old male infant has jaundice and pale stools caused by congenital biliary atresia. Deficiency of which of the following is most likely in this patient? A ) Folic acid B) Vitamin B6 C ) Vitamin B2 D) Vitamin C E) Vitamin E

Vitamin E The absence of bile because of a congenital narrowing or complete obstruction of the common bile duct causes decreased intestinal absorption of fat. Without fat absorption the absorption of vitamins A: D, E: and K is also inhibited. Deficiency of these vitamins is a possible complication of congenital biliary atresia

Risk of enterocolitis in infants

Vitamin E excess

Acute, reversible, life-threatening neurologic condition. Symptoms: Confusion, Ophthalmoplegia/ Nystagmus, Ataxia

Wernicke encephalopathy Thiamine (B1) deficiency

Damage to medial dorsal nucleus of thalamus, mammillary bodies. Presentation is combination of Wernicke encephalopathy and Korsakoff syndrome

Wernicke-Korsakoff syndrome Thiamine (B1) deficiency

High-output cardiac failure and edema

Wet beriberi also called Dilated vitamin B1. cardiomyopathy

In patients with chronic alcohol overuse or malnutrition, give _____ before dextrose to lower risk of precipitating Wernicke encephalopathy.

thiamine (B1)