Biochemistry Nutrition
(D) Pellagra Pellagra is caused by a deficiency of niacin. The classic presentation includes the "3 Ds" of diarrhea, dermatitis, and dementia.
A 55-year-old female has dementia worsening over the past year. She also has red, scaling skin in sun-exposed areas. A watery diarrhea has been present for the past month. Which nutritional deficiency is most likely present in this patient? (A) Beriberi (B) Macrocytic anemia (C) Microcytic anemia (D) Pellagra (E) Rickets
(D) Scurvy Scurvy can be subtle. A diet must contain a constant supply of vitamin C, because none is made endogenously. Older persons with a poor diet are just as much at risk as younger persons.
A 75-year-old female lives alone and eats sparingly because of her low fixed retirement income. She has pain in her legs. A radiograph reveals a right tibial subperiosteal hematoma. A cut on her right hand is healing poorly. She has a hyperkeratotic rash. The underlying condition that best explains these findings is (A) Kwashiorkor (B) Obesity (C) Anorexia Nervosa (D) Scurvy (E) Rickets
(E) Niacin Although niacin is a vitamin, it can be synthesized to a limited extent from tryptophan. None of the other vitamins indicated can be synthesized in humans to any extent.
A patient is on a very low calorie liquid diet and must take supplements to ensure that he has the essential vitamins and minerals to maintain his health. Under the appropriate conditions, which one of the following compounds can be synthesized in humans, and would not need to be supplemented to the extent that the others are? (A) Riboflavin (B) Linoleic acid (C) Leucine (D) Thiamine (E) Niacin
(B) Marasmus; histidine Proteins can be effective buffers of body and intracellular fluids, evidenced by frequent acidosis and edema with protein malnutrition. This child with emaciation is typical of marasmus that is more common with infantile protein deficiency. Kwashiorkor is more common in children over 1 or 2 years, showing edema of the feet, large and fatty liver, reddish hair, and skin depigmentation. Buffering capacity is dependent on presence of amino acids having ionizable side chains with pKas near physiologic pH. In the example given, only histidine has an ionizable imidazolium group that has a pK close to neutrality (pK = 6.0). Valine and leucine are amino acids with uncharged, branched side chains while lysine has a basic amino group and aspartic acid has a side chain carboxyl that is negative at pH 7.
A 1-year-old Caucasian girl presents to a pediatrician after being removed from her parents because of severe neglect. The pediatrician notes the child is undersized with tissue and muscle wasting, loss of adipose tissue, mild acidosis, and a hopeless, depressed look. Malnutrition is recognized and supported with laboratory studies that include a low serum protein concentration. The pediatrician institutes a gradual regimen of increased calories and nutrition, gradual because rapid feeding will produce diarrhea, worsening edema, and further protein loss. The extra tissue fluid (edema) acidosis demonstrate the importance of proteins in maintaining tissue hydration and pH. Indicate the child's disease and which protein amino acids would have the greatest buffering capacity at physiologic pH. (A) Kwashiorkor; lysine (B) Marasmus; histidine (C) Kwashiorkor; aspartic acid (D) Marasmus; valine (E) Kwashiorkor; leucine
(D) Milk and sunlight People with bowed legs and other bond malformations were quite common in the northeastern United States following the industrial revolution. This was caused by childhood diets lacking foods with vitamin D and by minimal exposure to sunlight due to the dawn-to-dusk working conditions of the textile mills. Vitamin D is essential for the metabolism of calcium and phosphorus. Soft and malformed bones result from its absence. Liver, fish oil, and egg yolks contain vitamin D, and milk is supplemented with vitamin D by law. Dark-skinned peoples are more susceptible to vitamin D deficiency (rickets).
A 15-month-old African American boy presents with prominent forehead, bowing of the limbs, broad and tender writs, swellings at the costochondral junctions of the ribs, and irritability. The head is deformable, able to be depressed like a ping-pong ball, while palpation of the joints is very painful. Which of the following treatments is recommended? (A) Lotions containing retinoic acid (B) Diet of baby food containing leafy vegetables (C) Diet of baby food containing liver and ground beef (D) Milk and sunlight (E) Removal of eggs from diet
(C) Vitamin D This patient likely has rickets due to exclusive breast feeding as well as lack of exposure to the sun. Breast milk does not contain vitamin D so children that are exclusively breast fed can develop vitamin D deficiency unless they are supplemented with vitamin D. In developing children, vitamin D is necessary for proper calcification of the bones. Patients can present with impaired closure of the fontanelles. When children begin walking, it can lead to lateral bowing of the legs.
A 2-year-old boy is brought to the office for a well-child visit. His mother says that he is doing well. She continues to breast feed exclusively to save money. He started walking 10 months ago and likes to play quietly inside. On examination he still has an anterior fontanelle that is 3 cm in diameter. The posterior fontanelle is very small but still palpable. He walks slowly with bowed legs. (A) Vitamin A (B) Vitamin B1 (C) Vitamin D (D) Vitamin E (E) Vitamin K
e. Calcitrol Vitamin D3 is hydroxylated to 25-OHD3 (calcifediol). Calcifediol is then hydroxylated in the kidney to the most active form of vitamin D, which is 1,25-dihydroxyvitamin D (calcitriol). Calcitriol has a rapid onset of action and a short half-life. The administration of calcitriol causes the elevation of serum Ca levels by enhancing the intestinal absorption of Ca. Calcitriol is indicated in vitamin D deficiency, particularly in patients with chronic renal failure or renal tubular disease, hypoparathyroidism, osteomalacia, and rickets. Serum phosphate levels usually increase with prolonged treatment.
A 25-year-old female suspected of having vitamin D-resistant rickets has decreased blood phosphate levels. Aside from high-dose vitamin D and oral phosphate, an alternative therapeutic approach might be the use of which of the following? a. Estrogen b. Pamidronate c. Hydrochlorothiazide d. Prednisone e. Calcitrol
(B) Phenylalanine Phenylalanine is the only amino acid listed as an answer choice that that does not have an ionizable sidechain. The symptoms of dermatitis (rash), diarrhea, and dementia arethe''3 Ds'' of pellagra. Pellagra is a congregate of symptoms resulting from vitamin B3 (niacin) deficiency. In Hartnup disease, the transport of neutral amino acids into intestinal epithelial cells is compromised, and this includes tryptophan. Because tryptophan is a precursor for niacin synthesis, if the patient has a low niacin uptake, the symptoms of pellagra can manifest.
A 28-year-old man complains of a rash on his sun-exposed skin, diarrhea, and loss of balance. His urinalysis results are significant for an increase in neutral amino acids, and he is diagnosed with Hartnup disease. Which one of the following amino acids would have been found in the urine sample? (A) Lysine (B) Phenylalanine (C) Arginine (D) Histidine (E) Glutamate
(A) Marasmus Body weight less than 60% of normal with muscle wasting is consistent with marasmus which results from a marked decrease in total caloric intake. In kwashiorkor, protein intake is reduced more than total caloric intake, and body weight is usually 60% to 80% of normal, with hypoalbuminemia a key laborat01y finding. Malignancies can promote wasting, but not to this degree. This child's problems are far more serious then a single vitamin deficiency: a lack of folate could account for the child's anemia, but not wasting. Bulimia is an eating disorder of adolescents and adults that is characterized by binge eating and self-induced vomiting.
A 36-month-old male appears chronically ill. He has had a succession of respiratory infections in the past 6 months. The child is underdeveloped, only 50% of ideal body weight, and exhibits marked muscle wasting. Laboratory findings include a normal serum albumin but a decreased hemoglobin. These findings are most characteristic for (A) Marasmus (B) Leukemia (C) Folate deficiency (D) Kwashiorkor (E) Bulimia
(B) Protein This child presents with kwashiorkor, which is due to severe protein malnutrituion. Patients may be of normal or near normal weight with ascites and edema. Other characteristics include dry, peeling skin, a round face, and hypopigmented hair. Patients usually have anorexia, which is in contrast with marasmus, a condition due to severe calorie deficiency, where patients will have a strong appetite once fed.
A 4-year-old boy is adopted from rural Haiti and is brought to the office to start his vaccination series. His adoptive parents do not know about the child's history prior to his presentation to the orphanage three months ago. He has not had a good appetite and would only eat about a third of his food at the orphanage. He has reached his milestones appropriately. On examination, the child is at the 40% for weight and height. He has a swollen abdomen and 1+ pitting edema in the ankles bilaterally. His liver is enlarged. This child's symptoms are due to the deficiency in which of the following? (A) Iron (B) Protein (C) Vitamin B3 (D) Vitamin C (E) Zinc
(E) Vitamin C Ascorbic acid (vitamin C) is found in fresh fruits (citrus, strawberries, and tomatoes) and vegetables (broccoli, potatoes, cabbage, and spinach). Pantothenic acid (vitamin B5) is found in most foods including meat and whole grains (incorrect answer d), as are niacin (vitamin B3 - not strictly a vitamin since it can be synthesized - incorrect answer b), thiamine (vitamin B1 - incorrect answer a), and cobalamin (vitamin B12 - found in meat, milk and eggs - incorrect answer c).
A 40 year-old African American male is concerned about weight gain acquired during his stressful schedule as a small business executive. He embarks on a low-carbohydrate diet consisting of packaged or dried meats that are convenient for travel and office meals. Which of the following vitamins would most likely become deficient on this diet? (A) Thiamine (B) Niacin (C) Cobalamin (D) Pantothenic acid (E) Vitamin C
(A) α-Ketoglutarate dehydrogenase The patient is exhibiting the symptoms of beriberi, due to a vitamin B1 deficiency. Thiamine (B1) is required for oxidative decarboxylation reactions, such as those catalyzed by pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. α-Ketoglutarate dehydrogenase requires thiamine (as thiamine pyrophosphate), lipoic acid, CoASH, FAD, and NAD+. Succinate dehydrogenase only requires FAD, fumarase has no cofactor requirement, malate dehydrogenase requires NAD+, and pyruvate carboxylase requires biotin.
A 40-year-old chronic alcoholic enters the hospital because of a variety of symptoms, including loss of feeling in his hands and feet, nystagmus, and difficulty with his balance when walking. This patient would have difficulty catalyzing which one of the following reactions? (A) α-Ketoglutarate dehydrogenase (B) Succinate dehydrogenase (C) Fumarase (D) Malate dehydrogenase (E) Pyruvate carboxylase
(C) Give injections of vitamin B12 The patient is displaying megaloblastic anemia due to a deficiency of vitamin B12. The use of omeprazole to reduce acid production in the stomach also reduces the ability of B12, bound to ingested proteins, to be released by the proteins to be bound by intrinsic factor for effective absorption into the blood. Providing injections of B12 will bypass the need for separation of B12 from its binding proteins and will allow B12 to circulate throughout the body and reach its intracellular targets and proteins. Oral B12 would also work under these conditions. The patient is unlikely to have an intrinsic factor problem (due to his age), and intrinsic factor cannot be given orally or via injection (since it needs to work in the intestine). For lack of intrinsic factor, injections of B12 are also required. The patient has normal folate levels, so giving more folate will not help the anemia, and vitamin B6 is not involved in these reactions.
A 42-year-old male has fatigue, pale skin, and shortness of breath with exercise. Blood work shows a macrocytic, hyperchromic anemia with hypersegmented neutrophils and normal folate levels. The patient has been taking omeprazole for over 3 years to treat gastric reflux disease. One method to treat this patient is to do which one of the following? (A) Give injections of vitamin B6 (B) Give injections of intrinsic factor (C) Give injections of vitamin B12 (D) Give oral folic acid (E) Give oral intrinsic factor
(B) Whole grains and meat While green, leafy vegetables are rich in other B vitamins, whole grains, meats, fish, and liver are the best sources of niacin. Citrus fruits are high in vitamin C. Orange and yellow vegetables are high in vitamin A. Chocolate cake is high in flavonoids, an antioxidant, fats, and carbohydrates.
A 43-year-old female has been on a "grapefruit and potatoes" diet for several months in an effort to lose weight. She now complains of a rash covering most of her body, a large, beefy tongue, nausea and diarrhea, and some confusion. To reverse these symptoms, a diet high in which one of the following should be recommended? (A) Green, leafy vegetables (B) Whole grains and meat (C) Citrus fruits (D) Orange and yellow vegetables (E) Chocolate cake
(A) The concentration of NAD+ This patient has the classic symptoms of pellegra, a vitamin B3 (niacin) deficiency. NAD+ is derived from niacin. Pellagra leads to the four Ds-dermatitis, dementia, diarrhea, and death. Riboflavin is the precursor for both FAD and FMN. Coenzyme Q is synthesized from acetyl-CoA, and its levels would not be affected as much as those of NAD+. Heme is synthesized from succinyl-CoA and glycine, and a reduction in heme levels would lead to an anemia and not the symptoms as described for this patient.
A 43-year-old female has been on a "grapefruit and potatoes" diet for several months in an effort to lose weight. She now complains of a rash covering most of her body, a large, beefy tongue, nausea and diarrhea, and some confusion. Which one of the following cofactors or enzyme complexes would be most affected by this condition? (A) The concentration of NAD+ (B) The concentration of FAD (C) The concentration of coenzyme Q (D) The functioning of the FMN components of complex I (E) The functioning of the cytochrome- containing components of complex III
(A) Thiamine Wernicke encephalopathy, with the classic triad of ataxia, confusion, and ophthalmoplegia (and nystagmus), is due to thiamine deficiency. Thiamine is an essential coenzyme in carbohydrate metabolism, including the pentose-phosphate pathway (transketolase) and the TCA cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase). Riboflavin deficiency is possible in malnourished alcoholics, causing cheilosis, glossitis, and corneal changes. Niacin deficiency causes diarrhea, dementia, and dermatitis.
A 45-year-old alcoholic man walks into the emergency room with a clumsy, wide-based gait and appears confused. He has pronounced nystagmus, and laboratory tests are significant for a metabolic acidosis and a serum blood alcohol level of 0.13. This patient should most probably be treated with IV fluids containing which of the following? (A) Thiamine (B) Riboflavin (C) Niacin (D) Pantothenic acid (E) Biotin
(B) Hartnup disease Hartnup disease is a transport defect, manifest in both the kidney and intestinal epithelial cells. The transporter is for large, neutral amino acids, and even though many amino acid transport systems have overlapping specificities, tryptophan uptake can be limiting with this disorder. Under such conditions, the body may not produce sufficient NAD for its needs (the nicotinamide ring can be produced from dietary niacin, as well as tryptophan), and a pellagra-like illness can develop. Giving the child niacin will allow the NAD to be regenerated, and a high-protein diet may increase tryptophan levels such that the transporter can transport tryptophan from the intestinal lumen into the bloodstream. Cystinuria is a different transport defect that will not allow cystine to be absorbed from the diet, or removed from the urine and returned to the blood in the kidney (which can give rise to kidney stones). Myasthenia gravis is due to autoantibodies directed against the acetylcholine receptor. Alkaptonuria is due to a defect in homogentisic acid oxidase, and jaundice results from an inability to add glucuronic acid residues to bilirubin in the liver.
A 5-year-old boy has had episodic periods during which areas of his skin would develop a rash, which would spontaneously resolve in a week to 10 days. An astute pediatrician told the boy's parents to give him niacin the next time this occurred and a high-protein diet, and when they did, the rash resolved in a day or two. A likely disorder that this child has is which one of the following? (A) Cystinuria (B) Hartnup disease (C) Myasthenia gravis (D) Alkaptonuria (E) Jaundice
(D) Vitamin C Scurvy develops when the body pool of vitamin C drops to <33 mg/d and the plasma levels drop to <11 mg/L. Vitamin C is a cofactor for many enzymes involved in connective tissue metabolism and cross-linking. Consequently, the symptoms of vitamin C deficiency reflect diminished formation of connective tissue components such as skin and gums. Impaired connective tissue formation presents with petechiae, ecchymoses, and perifollicular hemorrhages in the skin; bleeding gums; and bleeding into the joints, peritoneal cavity, pericardium, and adrenal glands. The symptoms of scurvy improve within a few days after administration of vitamin C. Whether or not vitamin C supplementation can prevent cancer due to its effect on the prevention of converting nitrate to carcinogenic nitrosamines is controversial.
A 50-year-old chronic alcoholic has bruising, inflamed and bleeding gums, and painful joints. The platelet count and prothrombin time are normal. The most likely cause for this clinical scenario is deficiency of which of the following vitamins? (A) Vitamin A (B) Vitamin B1 (C) Vitamin B12 (D) Vitamin C (E) Vitamin
(B) Thiamine Alcoholics are often deficient in thiamine and other nutrients (ethanol provides "empty calories"). Thiamine deficiency can lead to neuropathy, cardiomyopathy, and Wernicke disease. Alcoholics often have folate deficiency with macrocytic anemia. Pyridoxine or riboflavin deficiency can lead to neuropathy but not cerebral findings. Niacin deficiency leads to pellagra.
A 50-year-old male with a history of chronic alcoholism has had increasing congestive heart failure for the past year. For the past month, he has experienced increasing confusion and disorientation, with difficulty ambulating. He is found on physical examination to have nystagmus and ataxia of gait, along with decreased sensation in his lower extremities. TI1ese findings point to a dietary deficiency of (A) Folate (B) Thiamine (C) Pyridoxine (D) Niacin (E) Riboflavin
(A) Niacin The patient presents with the classic presentation of pellagra, or niacin deficiency, with diarrhea, dementia, and dermatitis. Niacin is synthesized from the essential amino acid tryptophan, which is particularly deficient in corn-based diets. However, niacin is still required in the diet because the amount of niacin derived from tryptophan is insufficient for daily needs. A cobalamin deficiency (vitamin B12) will lead to megaloblastic anemia along with methylmalonic acidemia. Folic acid deficiency often manifests with megaloblastic anemia. Vitamin C deficiency results in scurvy. Vitamin E deficiency is rare and can result in neurologic symptoms.
A 54-year-old Native American living on an Indian reservation in southwest Arizona is brought into the clinic by a family member. They are concerned because of impaired memory, diarrhea, and a rash on the face, neck, and dorsum of the hands. Which vitamin deficiency do these symptoms represent? (A) Niacin (B) Cobalamin (C) Folic acid (D) Vitamin C (E) Vitamin E
(E) Thiamine The patient is presenting with the signs and symptoms of Wernicke encephalopathy, which consists of the classic triad of ophthalmoplegia, ataxia, and global confusion. This syndrome is considered a medical emergency and necessitates immediate administration of thiamine, or vitamin B1.
A 57-year-old alcoholic man is brought to the emergency department in a state of global confusion, psychosis, and ataxia. On examination, ophthalmoplegia and polyneuropathy are also noted. Administration of which of the following would be the most appropriate treatment for this patient? (A) Biotin (B) Niacin (C) Pyridoxine (D) Riboflavin (E) Thiamine
(B) Marasmus This child likely has marasmus, which is a condition caused by severe calorie deprivation. This condition is extremely rare in developed nations but can be seen in children in developing nations where food is scarce. Symptoms include severe wasting of muscle and subcutaneous, leading to multiple skin folds, and significantly decreased height and weight. Edema may be seen, but ascites is uncommon. Children may also have hypotension, cool skin and bradycardia.
A 6-year-old boy is brought to a clinic in sub-Saharan Africa. His height and weight are less than the first percentile expected for his age. He has dry skin and coarse, brittle hair. He has numerous skin folds due to a decrease in subcutaneous tissues. No edema or ascites is noted on examination. What is the most likely diagnosis? (A) Kwashiorkor (B) Marasmus (C) Pellagra (D) Scurvy (E) Zince deficiency
(D) Injections of B12 The patient has a deficiency of B12, caused by inadequate intrinsic factor production for the absorption of dietary vitamin B12, which is required for the conversion of methylmalonyl-CoA to succinyl-CoA and of homocysteine to methionine. A vitamin B12 deficiency results in the excretion of methylmalonic acid in the urine and an increased dietary requirement for methionine. The methyl group transferred from vitamin B12 to homocysteine to form methionine comes from N5-methyl-FH4, which accumulates in a vitamin B12 deficiency, causing a decrease in free folate levels and symptoms of folate deficiency, including increased levels of FIGLU and decreased purine biosynthesis. Both B12 and folate deficiencies will lead to anemia, but only a B12 deficiency will give rise to the mental-status changes and tingling in the hands and feet. As individuals age, a variety of conditions can give rise to reduced intrinsic factor production by the stomach. Since intrinsic factor is low, B12 needs to be delivered by injection, not by the oral route of administration.
A 65-year-old man visits his primary physician because of tingling in his hands and feet, and a sense that he is forgetting things more than usual. A CBC indicates a mild anemia. The patient states that his diet has not changed, other than eating more red meat than before. This patient can be best treated by which one of the following? (A) Oral administration of vitamin B12 (B) Oral administration of folic acid (C) Oral administration of methionine (D) Injections of B12 (E) Injections of folic acid (F) Injections of methionine
(D) Vitamin C The patient described has scurvy, resulting from a deficiency of dietary vitamin C. Absence of vitamin C leads to impaired hydroxylation of proline residues in the nascent procollagen chains, leading to weakness of blood vessel walls. Clinically, the deficiency syndrome is characterized by perifollicular hemorrhages, fragmentation of hairs, purpura, ecchymoses, splinter hemorrhages, and hemorrhages into muscle. In patients with normal dentition, gum changes (swelling, bleeding, loosening of teeth) are also noted. Without vitamin C supplementation, death may eventually occur. Administration of factor VIII (choice A) would be indicated for factor VIII deficiency. This deficiency would also lead to a prolonged partial thromboplastin time (PTT), which was not noted. Administration of iron (choice B) would be of benefit in iron-deficiency anemia, but there is no indication of a hypochromic, microcytic anemia in this patient. The anemia of scurvy is typically normochromic and normocytic because of bleeding. Administration of vitamin B12 (choice C) would be indicated for a megaloblastic anemia. Although a macrocytic anemia may be observed in scurvy (because of concomitant dietary folate deficiency or perturbations in the folate pool), this patient did not show macrocytosis. Administration of vitamin K (choice E) would be appropriate in the setting of vitamin K deficiency, which would produce a prolonged prothrombin time (PT), followed eventually by a prolonged PIT as the vitamin K-dependent factors (II, VII, IX, X, protein C, and protein S) are depleted.
A 69 year-old edentulous alcoholic man, who lives alone, is admitted to the hospital for evaluation of a shoulder wound that is not healing well. On physical examination, numerous ecchymoses are noted on the posterior aspect of his legs and thighs. Careful examination of the man's skin revels minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds. Laboratory examination is remarkable for a hemoglobin of 10 g/dL; no other hematologic abnormalities are noted. Which of the following is the most appropriate therapy for this disorder? (A) Factor VIII (B) Iron (C) Vitamin B12 (D) Vitamin C (EJ Vitamin K
e. Vitamin C Vitamin C (ascorbic acid) is a water-soluble vitamin that is important in many body functions, such as the synthesis of collagen, osteoid, certain neurotransmitters, and carnitine. In the synthesis of collagen, vitamin C functions as a cofactor for the hydroxylation of proline and lysine and for the formation of the triple helix of tropocollagen. Patients with decreased vitamin C (scurvy) have abnormal synthesis of connective tissue due to abnormal synthesis of collagen along with abnormal synthesis of osteoid. The former leads to impaired wound healing. In addition, previous wounds may reopen. Because the synthesis of collagen is abnormal, the blood vessels are fragile, leading to bleeding gums, tooth loss, subperiosteal hemorrhage, and petechial perifollicular skin hemorrhages. Abnormal synthesis of osteoid (unmineralized bone) leads to decreased amounts of osteoid in the bone and increased calcification of the cartilage. Vitamin C also functions as an antioxidant and is important in neutrophil function and iron absorption in the gut. These functions are also decreased in patients with scurvy. This syndrome is common in elderly people living on a diet deficient in milk, fruits, and vegetables. In contrast to scurvy, which is caused by a deficiency of vitamin C, rickets is caused by a deficiency of vitamin D. Rickets is characterized by a lack of calcium. In this abnormality the osteoblasts in bone continue to
A 70-year-old female is brought to the emergency room by her granddaughter because she has developed ecchymosis covering many areas of her body. Her granddaughter states that her grandmother lives alone at home and has not been eating well. Her diet has consisted of mainly tea and toast, as she does not drink milk or eat fruits or vegetables. Your physical examination reveals small hemorrhages around hair follicles, some of these follicles having an unusual "corkscrew" appearance. You also notice swelling and hemorrhages of the gingiva. The signs and symptoms in this individual are most likely caused by a deficiency of a. Thiamine b. Pyridoxine c. Niacin d. Vitamin D e. Vitamin C
(A) Niacin The contestant has the symptoms of pellagra, which is characterized by the four Ds (i.e., diarrhea, dermatitis, dementia, and eventual death). Pellagra is due to a lack of niacin in the diet. A thiamine deficiency will lead to beriberi; a riboflavin deficiency to ariboflavinosis; a vitamin C deficiency to scurvy; and a vitamin D deficiency to rickets. Only pellagra would yield the symptoms observed by the patient.
A contestant on a TV reality show, in which the contestants had to survive off the land for an extended period of time, developed recurrent diarrhea, dermatitis, and had trouble remembering things. These symptoms could be brought about due to the lack of which one of the following in the contestant's diet? (A) Niacin (B) Thiamine (C) Riboflavin (D) Vitamin C (E) Vitamin D
(D) Kwashiorkor Protein deficiency (but not overall calorie deficiency), as in kwashiorkor, results in a deficiency of visceral proteins, including those in the blood that normally provide oncotic pressure to retain fluid within vessels. As such, patients with kwashiorkor have abdominal bloating secondary to edema. Marasmus is a deficiency of calories and protein; the children in this question are presumably receiving carbohydrate calories through the cornmeal. Anorexia nervosa and bulimia are disorders of self-induced weight loss that are found mostly in developed countries. Cachexia is weight loss associated with cancer.
A fourth-year medical student does an international rotation in Sub-Saharan Africa. While immunizing children against polio, he sees hundreds of malnourished children in refugee camps with bloated-appearing abdomens. He learns that they are severely protein deficient because they are fed a diet of cornmeal that is provided by international relief agencies. These children likely suffer from which of the following? (A) Marasmus (B) Anorexia nervosa (C) Bulimia (D) Kwashiorkor (E) Cachexia
(C) Reduced hydrogen-bond formation in collagen The homeless man has developed scurvy owing to a lack of vitamin C in his diet. Vitamin C is required cofactor for the hydroxylation of proline and lysine within the collagen molecule. The lack of hydroxyproline reduces the stability of the collagen because of reduced hydrogen-bonding capabilities within the collagen triple helix. The lack of vitamin C does not affect disulfide-bond formation, which is required to initiate triple-helix formation within the cell. Fibrillin is not altered by the lack of vitamin C; it is the protein mutated in Marfan's syndrome.
A homeless man was seen at a clinic because of bleeding gums and loosening teeth. His dietary history revealed that he has been consuming only chocolate milk and fast-food hamburgers for the past 6 months. The patient is exhibiting symptoms due to which one of the following? (A) Reduced synthesis of fibrillin (B) Reduced synthesis of collagen (C) Reduced hydrogen-bond formation in collagen (D) Increased hydrogen-bond formation in collagen (E) Reduced disulfide-bond formation in collagen (F) Increased disulfide-bond formation in collagen
d. Thiamine Chronic alcoholics are at risk for thiamine deficiency, which is thought to play a role in the incoordination (ataxia) and psychosis that can become chronic (Wernicke-Korsakoff syndrome). The thiamine deficiency produces relative deficiency of the pyruvate dehydrogenase complex. The administration of glucose without checking glucose levels can therefore be dangerous, since excess glucose is converted to pyruvate by glycolysis. The low rate of pyruvate dehydrogenase conversion of pyruvate to coenzyme A (and entry into the citric acid cycle) causes pyruvate to be converted to lactate (through lactate dehydrogenase). Lactic acidosis can be fatal. Chronic alcoholics can be deficient in the other vitamins mentioned, but thiamine is most likely to help the neurologic symptoms.
A homeless person is brought into the emergency room with psychotic imagery and alcohol on his breath. Which of the following compounds is most important to administer? a. Glucose b. Niacin c. Nicotinic acid d. Thiamine e. Riboflavin
(D) The functioning of the FMN components of complex I This patient has vitamin B2 (riboflavin) deficiency, ariboflavinosis, as indicated by the symptoms displayed by him. Both FAD and FMN require vitamin B2 to be produced. NAD+ and NADP+ are derived from niacin. Coenzyme Q is derived from acetyl-CoA, and vitamin B2 is not needed in the synthesis of the heme ring, which is derived from succinylCoA and glycine.
An alcoholic presents with swelling and fissuring of the lips, cracking at the angles of the mouth, red eyes, and an oily, scaly rash of his scrotum. Which one of the following cofactors of enzyme complexes would be most affected by this condition? (A) The concentration of NAD+ (B) The concentration of NADP+ (C) The concentration of coenzyme Q (D) The functioning of the FMN components of complex I (E) The functioning of the cytochrome- containing components of complex III
a. Decreased protein intake leads to decreased lipoproteins Protein-energy malnutrition (PEM) in underdeveloped countries leads to a spectrum of symptoms from kwashiorkor at one end to marasmus at the other. Marasmus, caused by a lack of caloric intake (i.e., starvation), leads to generalized wasting, stunted growth, atrophy of muscles, and loss of subcutaneous fat. There is no edema or hepatic enlargement. These children are alert, not apathetic, and are ravenous. In contrast, children with kwashiorkor, which is characterized by a lack of protein despite adequate caloric intake, have peripheral edema, a "moon" face, and an enlarged, fatty liver. The peripheral edema is caused by decreased albumin and sodium retention, while the fatty liver is caused by decreased synthesis of the lipoproteins necessary for the normal mobilization of lipids from liver cells. Additionally, these children have "flaky paint" areas of skin and abnormal pigmented streaks in their hair ("flag sign"). In children with marasmus, the skin is inelastic due to loss of subcutaneous fat. In either severe kwashiorkor or marasmus, thymic atrophy may result in the reduction in number and function of circulating T cells. B cell function (i.e., immunoglobulin production) is also depressed, so that these children are highly vulnerable to infections.
An apathetic male infant in an underdeveloped country is found to have peripheral edema, a "moon" face, and an enlarged, fatty liver. Which one of the listed mechanisms is involved in the pathogenesis of this child's abnormalities? a. Decreased protein intake leads to decreased lipoproteins b. Decreased caloric intake leads to hypoalbuminemia c. Decreased carbohydrate intake leads to hypoglycemia d. Decreased fluid intake leads to hypernatremia e. Decreased fat absorption leads to hypovitaminosis
b. Scurvy The signs and symptoms described are most consistent with scurvy (vitamin C deficiency). This syndrome can occur in older patients who are poorly nourished. Perifollicular papules develop when hairs become fragmented and buried in the follicle. Capillary fragility occurs, and bleeding into soft tissue is common. Pellagra (vitamin B3 deficiency) causes a dermatitis that is symmetrical and related to photosensitivity. Beriberi (vitamin B1 deficiency) does not typically cause a rash, but presents with high-output cardiac failure, peripheral neuropathy, and Wernicke's encephalopathy. The perifollicular nature of the bleeding described in this patient does not suggest a traumatic etiology.
An elderly homeless male is evaluated for anemia. On exam, he has purpura and ecchymoses of the legs. Perifollicular papules and perifollicular hemorrhages are also noted. There is swelling and bleeding of gums around the patient's teeth as well as tenderness around a hematoma of the calf. The most likely diagnosis is a. Elder abuse b. Scurvy c. Pellagra d. Beriberi
e. Hydroxyproline Hydroxyproline and hydroxylysine are not present in newly synthesized collagen. Proline and lysine residues are modified by hydroxylation in a reaction requiring the reducing agent ascorbic acid (vitamin C). The enzymes catalyzing the reactions are prolyl hydroxylase and lysyl hydroxylase. In scurvy, which results from a deficiency of vitamin C, insufficient hydroxylation of collagen causes abnormal collagen fibrils. The weakened collagen in teeth, bone, and blood vessels causes tooth loss, brittle bones with fractures, and bleeding tendencies with bruising and bleeding gums.
Certain amino acids are not part of the primary structure of proteins but are modified after translation. In scurvy, which amino acid that is normally part of collagen is not synthesized? a. Hydroxytryptophan b. Hydroxytyrosine c. Hydroxyhistidine d. Hydroxyalanine e. Hydroxyproline
(B) Peripheral neuropathy Thiamine (or vitamin B1), when metabolized to thiamine pyrophosphate, is the coenzyme required for proper energy-producing metabolism of branched-chain amino acids. Thiamine may also play a role in peripheral nerve conduction. Deficiency of this vitamin produces anorexia, irritability, apathy, generalized weakness, as well as pain and numbness in the extremities due to peripheral neuropathy. Vitamin B1 deficiency may also present with central nervous system problems, especially with the syndrome known as Wernicke's encephalopathy, which consists of horizontal nystagmus, ophthalmoplegia due to weakness of one or more extraocular muscles, cerebellar ataxia, and mental impairment. Thiamine should be given prophylactically to all chronic alcoholic patients in the emergency room to prevent precipitation of thiamine deficiency after administration of glucose-containing fluids. Unlike in vitamin B12 deficiency, joint position sense is usually maintained in patients with thiamine deficiency.
Dietary deficiency of thiamine produces which of the following clinical syndromes? (A) Loss of proprioception (B) Peripheral neuropathy (C) Color blindness (D) Osteoporosis (E) Bruising
(C) Hydroxylation Vitamin C (ascorbic acid) is an important cofactor for the enzymes prolyl hydroxylase and lysylhydroxylase. The hydroxylation of proline stabilizes the triple helix stricture of collagen. The hydroxyl group of lysine is often glycosylated with glucose and galactose. Cross-linkage of collagen results from the oxidation of lysine. C-peptide cleavage occurs in insulin processing.
In 1795, the British navy began to dispense limes during long sea voyages (hence the name ''limeys'' for British sailors), a measure that was largely successful in preventing scurvy. Scurvy is a condition characterized by general weakness, anemia, gum disease (gingivitis), and skin hemorrhages resulting from a lack of ascorbic acid (vitamin C) in the diet. Ascorbic acid plays a crucial role in which of the following processes in collagen synthesis? (A) Transcription (B) Glycosylation (C) Hydroxylation (D) Covalent cross-linkage (E) C-peptide cleavage
c. Thiamine In the Far East, rice is a staple of the diet. When rice is unsupplemented, beriberi can be manifest, since rice is low in vitamin B1 (thiamine). Thiamine pyrophosphate is the necessary prosthetic group of enzymes that transfers activated aldehyde units. Such enzymes include transketolase, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase. Beriberi is a wasting disease whose symptoms include pain in the limbs induced by peripheral neuropathy, weak musculature, and heart enlargement. Yeast products, whole grains, nuts, and pork are rich in thiamine. Choline, ethanolamine, and serine are polar head groups of phospholipids. Glycine is a common amino acid.
In the Far East, beriberi is a serious health problem. It is characterized by neurologic and cardiac symptoms. Beriberi is caused by a deficiency of a. Choline b. Ethanolamine c. Thiamine d. Serine e. Glycine
(C) Scurvy Because humans do not generate vitamin C endogenously, they must have a continuous dietary supply. The lack of fresh fruits and vegetables with vitamin C led to scurvy in many explorers in centuries past. Rickets is seen in children deficient in vitamin D. Beriberi leads to heart failure and results from thiamine deficiency. Kwashiorkor results from protein deficiency. Pellagra (with diarrhea, dermatitis, and dementia) is seen with niacin deficiency.
Sir Robert Falcon Scott reaches the South Pole on January 17, 1912, barely a month after Roald Amundsen achieved this goal with his more experienced and prepared expeditionary party. Scott's dejected party must now make the long trip back to their base, but they are weak and running low on supplies. They finally can go no further, ironically only a few kilometers from a cache of supplies. They are found by a rescue team, but too late. Scott and his men are observed to have a hyperkeratotic, papular rash, ecchymoses, and severe gingival swelling with hemorrhages. A contributing cause of death was most likely (A) Rickets (B) Beriberi (C) Scurvy (D) Kwashiorkor (E) Pellagra
a. Obtain platelet ascorbic acid level and give ascorbic Platelet ascorbic acid levels are the best approach to documenting this deficiency. Ascorbic acid 100 mg should be given three to five times per day until 4 g have been given. Scurvy is potentially fatal, and the patient should not be discharged until supplementation is guaranteed. Folic acid levels should be checked concomitantly to identify folate deficiency and folate should be given if necessary. Tryptophan levels are used in evaluating for pellagra.
The best approach to the management of a patient diagnosed with Scurvy is a. Obtain platelet ascorbic acid level and give ascorbic acid while in hospital b. Discharge with dietary consult c. Give folic acid d. Obtain plasma tryptophan
(B) Rickets This skeletal deformity with bowing of the legs results from vitamin D deficiency in children, known as rickets. Hyperkeratosis with follicular plugging from vitamin A deficiency leads to papular dermatosis marked by extensive papular excrescences on the skin. Pellagra from niacin deficiency can lead to dermatitis in sun-exposed areas; of skin. Beriberi from thiamine deficiency can result in heart failure with peripheral edema. A diet poor in protein can result in kwashiorkor, with areas of flaking, depigmented skin.
The child shown here is most likely to have (A) Papular dennatosis (B) Rickets (C) Pellagra (D) Beriberi (E) Kwashiorkor
e. Vitamin C Ascorbic acid (vitamin C) is found in fresh fruits and vegetables. Deficiency of ascorbic acid produces scurvy, the "sailor's disease." Ascorbic acid is necessary for the hydroxylation of proline to hydroxyproline in collagen, a process required in the formation and maintenance of connective tissue. The failure of mesenchymal cells to form collagen causes the skeletal, dental, and connective tissue deterioration seen in scurvy. Thiamine, niacin, cobalamin, and pantothenic acid can all be obtained from fish or meat products. The nomenclature of vitamins began by classifying fat-soluble vitamins as A (followed by subsequent letters of the alphabet such as D, E, and K) and water-soluble vitamins as B. Components of the B vitamin fraction were then given subscripts, e.g., thiamine (B1), riboflavin (B2), niacin [nicotinic acid (B3)], panthothenic acid (B5), pyridoxine (B6), and cobalamin (B12). The water-soluble vitamins C, biotin, and folic acid do not follow the B nomenclature.
Which of the following vitamins would most likely become deficient in a person who develops a completely carnivorous lifestyle? a. Thiamine b. Niacin c. Cobalamin d. Pantothenic acid e. Vitamin C
(D) Niacin deficiency The amino acid tryptophan is converted to the niacin derivatives nicotinic acid and nicotinamide, coenzymes required for numerous oxidative and reductive enzymes. Niacin deficiency causes pellagra, which is a complicated syndrome involving loss of appetite, weakness, irritability, abdominal pain, bright red tongue and stomatitis, and a skin rash characterized by pigmentation and scaling, particularly in areas exposed to sunlight. Pellagra can be seen in those whose diet consists primarily of corn in parts of China, Africa, and India; in chronic alcoholics; in those with congenital defects of tryptophan absorption; and in patients with carcinoid syndrome, in which there is an increased conversion of tryptophan into serotonin.
Why do patients with the carcinoid syndrome develop pellagra (loss of appetite, generalized weakness, abdominal pain, vomiting, stomatis and bright red glossitis, and a skin rash that is pigmented and scaling in sunlight exposed areas)? (A) Failure to elaborate serotonin (B) Vitamin B deficiency 12 (C) Thiamine deficiency (D) Niacin deficiency (E) Pyridoxine deficiency