Biochem step 1

Question 1

A 30-year-old man of African heritage presents to his primary care physician complaining of dizziness and lethargy. About a week ago he completed a course of antibiotics for sinusitis. On physical examination he appears pale and uncomfortable, with icteric sclerae?
Which of the following is the most likely cause of this patient’s condition?

Answer 1

This patient has symptoms of anemia, including lethargy and dizziness. Pallor and icteric sclerae suggest a hemolytic anemia. Lab findings are significant for a normocytic anemia and Heinz bodies on peripheral smear. This presentation after recent antibiotic use is consistent with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Question 2

Heinz bodies are a hallmark of ?

Answer 2

G6PD deficiency is an X-linked recessive disorder that results in decreased levels of NADPH, which is needed to keep glutathione in the reduced state. Decreased glutathione leaves RBCs susceptible to hemolysis when exposed to oxidants like fava beans, sulfa drugs, and primaquine. Heinz bodies are a hallmark of G6PD and represent accumulations of denatured hemoglobin.

Question 3

β-Thalassemia, which is caused by ?

Answer 3

a defect in one or more of the four β-globin chains of hemoglobin, is a chronic hemolytic anemia that is not precipitated by infection or medication

Question 4

Intrinsic factor deficiency is seen in pernicious anemia, which is characterized by?

Answer 4

chronic atrophic gastritis and autoantibodies directed against gastric parietal cells. It causes a megaloblastic, macrocytic anemia (MCV > 100 fL)

Question 5

Malaria manifests with an acute cyclic fever in a patient with?

Answer 5

recent travel to an area where Plasmodium is endemic. Interestingly, G6PD deficiency decreases one’s risk for malaria.

Question 6

Vitamin deficiency (folate or vitamin B12) can lead to?

Answer 6

a megaloblastic, macrocytic anemia with an MCV >100 fL.

Question 7

A 6-year-old boy with recurrent otitis media has been treated with multiple courses of antibiotics, including ceftriaxone. His father now brings him to the pediatrician’s office, saying that the child has been bruising easily on his legs and bleeding heavily when he brushes his teeth

Answer 7

This patient presents with signs of coagulopathy, including bleeding from mucosal surfaces and easy bruising. His lab results suggest impairment of both the intrinsic (PTT) and extrinsic (PT/INR) coagulation pathways. Given his history of recent antibiotic use, you should suspect vitamin K deficiency.

Question 8

Vitamin K-dependent γ-glutamyl carboxylase converts ?

Answer 8

glutamic acid residues to γ-carboxyglutamic acid (GLA) residues on clotting factors II, VII, IX, and X, as well as proteins C and S. GLA residues bind calcium, which is required to activate the factors. Therefore, vitamin K deficiency may lead to dysfunctional clotting factors in both arms of the coagulation cascade (see image). Dysfunction can manifest with elevations of both PTT and PT; clinically, patients may present with easy bruisability, melena, hematuria, and subungual hemorrhages.

Question 9

the mushrooms Amanita phalloides, a poisonous mushroom that contains the toxin α-Amanitin inhibits?

Answer 9

RNA polymerase II, which is responsible for the production of mRNA. RNA polymerase I is responsible for the synthesis of rRNA, while RNA polymerase III synthesizes tRNA.

Question 10

Angiotensin-converting enzyme inhibitors disrupt the conversion of angiotensin I to angiotensin II, thereby causing decreased activation of Gq and decreased activity of?

Answer 10

phospholipase C in vascular smooth muscle cells in the efferent renal arteriole.

Question 11

This patient, with a medical history notable for hypertension and T2DM, presents with worsening dyspnea and crackles in the lungs. His chest x-ray is notable for air space opacifications, enlarged cardiac silhouette, perihilar infiltrates and air bronchograms, which are consistent with?

2. Angiotensin-converting enzyme inhibitors ( ACE such as lisinopril) disrupt the conversion of angiotensin I to angiotensin II, thereby causing?

Answer 11

pulmonary edema in the setting of congestive heart failure (HF).

2. decreased activation of Gq and decreased activity of phospholipase C in vascular smooth muscle cells in the efferent renal arteriole

Question 12

This middle-aged woman presents with joint pain, morning joint stiffness that lasts for >30 minutes, and swollen PIP and MCP joints. Additionally, she is positive for anti-CCP antibodies. This clinical picture is the classic presentation of ?
2. Which drug acts at the same point in the cell cycle as the drug this woman is initiating?

Answer 12

rheumatoid arthritis. The first-line medication for RA is methotrexate. Methotrexate is a disease-modifying antirheumatic drug (DMARD) known to cause neural tube defects. As a folic acid analog, it binds to and inactivates dihydrofolate reductase, thereby inhibiting nucleotide synthesis. Remember that DNA replication occurs during the S phase of the cell cycle. Thus, any drug that interferes with DNA synthesis will primarily affect a cell during the S phase.
2. Of the medications listed, only 6-mercaptopurine (6-MP) also disrupts the S phase of the cell cycle. 6-MP is a purine analog that is taken up into DNA during the S phase, halting DNA synthesis and leading to cell death. Its adverse effects include bone marrow, GI, and liver toxicities.

Question 13

Bleomycin and doxorubicin are antitumor antibiotics; bleomycin has the greatest affect on the?

Answer 13

G2 phase, whereas doxorubicin’s actions are not specific to a particular cell cycle phase.

Question 14

Paclitaxel and vincristine are microtubule inhibitors and both act in the ?
2. Methotrexate is a folic acid analog that inhibits nucleotide synthesis, and thus affects ?

Answer 14

M phase of the cell cycle.

2. the S phase of the cell cycle, during which DNA replication occurs. 6-Mercaptopurine, a purine analog? also acts during the S phase.

Question 15

The patient is 2-year-old and her father reports that she has become clumsy in recent weeks, running into furniture and hitting her head on door frames. The fundoscopy image in this case shows an amelanotic large endophytic mass in the inferior pole of the retina of the right eye, which is most consistent with ?

Answer 15

retinoblastoma.

Question 16

Retinoblastoma is inherited in 40% of cases. A point mutation inactivates the RB tumor-suppressor gene on chromosome 13, which encodes a protein that binds to and regulates the E2F transcription factors. When both alleles are lost, the E2F transcription factors are uninhibited and cause the cell to move from a quiescent stage into the synthesis phase. As a result of the mutation she carries in her functioning RB tumor-suppressor gene?

Answer 16

the patient is at increased risk of developing osteosarcomas later in life.

Question 17

A mutation in the WT1 tumor-suppressor gene on chromosome 11 leads to?

Answer 17

Wilms tumor of the kidney in children.

Question 18

Chronic myelogenous leukemia is caused by chromosomal translocation resulting in the fusion of the ?

Answer 18

BCR gene on chromosome 22 with the ABL gene on chromosome 9. This fusion proto-oncogene product is a tyrosine kinase that inhibits DNA repair.

Question 19

Colon cancer is associated with?

Answer 19

mutations in the APC and DCC genes. The APC tumor-suppressor gene on chromosome 5 codes for a protein that prevents nuclear transcription. Its inactivation is responsible for familial adenomatous polyposis

Question 20

RET gene is a proto-oncogene on chromosome 10 that encodes a receptor tyrosine kinase. Activating point mutations of this gene can lead to constitutive activation of the receptor tyrosine kinase and can give rise to?

Answer 20

multiple endocrine neoplasia type 2, which includes medullary thyroid cancers.

Question 21

This is a young patient who presents with lethargy, vomiting, abdominal pain, and decreased skin turgor. This presentation is suggestive of ?
2. Histologic examination of the pancreas would reveal a reduction in the number and size of islets, as well as leukocytic infiltration of the islets, representing? i

Answer 21

diabetic ketoacidosis (DKA), an emergency caused by insulin deficiency in patients with type 1 diabetes mellitus.
2. Insulitis involving T lymphocytes.

Question 22

Type 1 diabetes mellitus (DM) is an autoimmune disease often diagnosed at an early age. A common clinical scenario is one in which a young patient presents with symptoms of diabetic ketoacidosis: vomiting and diffuse abdominal pain, an elevated serum ketone level, and a high serum glucose level. Histologically, type 1 DM is characterized by ?

Answer 22

lymphocyte-mediated insulitis, fibrosis, and islet degeneration.

Question 23

The patient initially presented with increased weakness, increased abdominal adipose tissue, and decreased muscle mass and bone density. Although this clinical picture is similar to normal aging, a growth hormone-releasing hormone-arginine (GHRH-arginine) stimulation test demonstrated a subnormal increase of growth hormone, indicating the most likely etiology is?

2. The most important point to gather from this question is that GH is diabetogenic, meaning that increased levels of GH cause increased lipolysis and gluconeogenesis, contributing to a state of elevated glucose and free fatty acids in the blood. One of the side effects of GH therapy is worsening of?

Answer 23

adult growth hormone deficiency. In this case, the patient’s treatment was with biosynthetic growth hormone (GH), which resolved his symptoms.

2. a patient’s glucose tolerance and increased insulin resistance, as seen in this patient, who has an elevated fasting blood glucose during his return visit to the clinic.

Question 24

This patient presents with an unknown vaccination history and a recent infection consisting of cough, coryza (leading to runny nose), and conjunctivitis (red eyes). Since this prodrome is followed by a rash, it is most likely that the child had an ?

2. . Vitamin A is absorbed via ?

Answer 24

infection with measles. Furthermore, the findings on eye exam demonstrate an edematous and thickened cornea, otherwise known as keratomalacia. Keratomalacia is an associated complication of vitamin A deficiency. which can also lead to night blindness, dry eyes and conjunctivae (keratoconjunctivitis sicca, which may lead to stinging, burning, and blurry vision), and gray plaques

2 . micelle-mediated transport in the gastrointestinal system.

Question 25

This patient presents with vague symptoms of fatigue and weight loss. Without any other information, the differential for his presentation would be broad and include depression, thyroid problems, and liver disease. The physical findings of splenomegaly, gingival bleeding, and easy bruising point to a different cause, however, which the results of his CBC and blood smear reinforce. This patient’s low hemoglobin and low platelet counts indicate ?

Answer 25

anemia and thrombocytopenia, respectively. His lab results also reveal a dramatically elevated WBC count, high monocytes, and high basophils, whereas the blood smear shows an overabundance of granulocytes in various stages of maturation. Together with this patient’s experience of mild fatigue and weight loss in recent months, the lab results and physical findings point to a diagnosis of chronic myeloid leukemia (CML)

Question 26

CML typically occurs in older patients and follows a chronic progressive course that can accelerate into a blast crisis. The disease is caused by a t(9;22) chromosomal translocation (Philadelphia chromosome) that produces a deregulated, constitutively active enzyme? ,

2. Treatment for CML is ?

Answer 26

tyrosine kinase (BCR-ABL). Increased levels of BCR-ABL lead to the clonal overproduction of hematopoietic myeloid stem cells that is a hallmark of CML, which in turn leads to increased numbers of both mature and immature granulocytes
2. with imatinib, a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein

Question 27

This patient has extreme abdominal pain and a “surgical abdomen” (rebound tenderness with free air and fluid on a CT scan) and is later found to have intestinal rupture during an exploratory laparotomy. In addition, on examination, he is found to have nearly translucent skin with prominent veins, varicosities, and bruises. Given these findings, the physician should be very concerned about?

Answer 27

Ehlers-Danlos syndrome (EDS), particularly the vascular type. Vascular EDS is less common and more severe than the other EDS types. It can manifest milder skin and joint manifestations but is associated with vascular (aneurysmal) and organ rupture. The vascular type is due to a type III collagen defect. Type III collagen (reticulin) makes up the skin, blood vessels, uterus, fetal tissue, and granulation tissue.

Question 28

This patient with a history of chronic rheumatoid arthritis refractory to hydroxychloroquine is started on a new medication that increases plasma homocysteine levels. The most likely new medication is methotrexate. Methotrexate is a reversible competitive inhibitor of dihydrofolate reductase (DHFR), so methotrexate will ?

Answer 28

increase the Km of DHFR without affecting the enzyme’s Vmax as shown in the graphs

The Michaelis-Menten constant (Km) of an enzyme reflects the enzyme’s affinity for a particular substrate [S] in an inverse fashion. Therefore, if the Km is high, the enzyme will have low affinity for the substrate

Question 29

This patient presented with palpitations, weight loss, and increased appetite and subsequently underwent thyroidectomy as a treatment for?

2. Thyroid receptors are located on bones and in both the central and autonomic nervous systems. Thyroid hormone stimulates glycogenolysis, gluconeogenesis, and lipolysis. Because she has undergone thyroidectomy, this patient is at risk for?

Answer 29

hyperthyroidism. Patients who undergo thyroidectomies are treated postoperatively with levothyroxine for thyroid hormone replacement
2. a decrease in all these processes if she does not take levothyroxine.

Question 30

Decreased serum calcium is a feature of hypoparathyroidism, which can be caused by ?

Answer 30

damage to the parathyroid. Because there is no indication that the parathyroid was injured during surgery, decreased serum calcium is unlikely to occur if the patient stops taking levothyroxine.