SYTM 5503 Week 1 Practice Questions

[1M] A research is studying the different types of hemoglobin present in patients with the homozygous sickle cell disorder. The findings are confusing due to heterozygous sickle cell disease, presence of other hemoglobinopathies, and treatment with blood transfusions. Based on knowledge of globin protein chains, which one of the following hemoglobin combinations would be typically seen in a patient with sickle cell anemia presenting for the first time to the hospital? A. 80% HbS, 16% HbF, 4% HbA2 B. 90% HbS, 10% HbA1 C. 75% HbS, 20% HbF, 5% HbA1 D. 95% HbS, 5% HbA1 E. 50% HbS, 30% HbA1, 20% HbF

A. 80% HbS, 16% HbF, 4% HbA2 In sickle cell disease, metabisulfite screen is used to identify patients w/ sickle cell disease or trait. This test causes cells w/ any amount of HbS to sickle & is therefore positive in both disease & trait. On different note, HbC is autosomal recessive mutation similar to HbS. It presents w/ mild anemia due to extravascular hemolysis. In blood smear, characteristic HbC crystals are seen in RBCs (see figure).

[1J] A 43-year-old man is transported to the ER. In the last few days, he collapsed multiple times after feeling extremely weak. He has a history of alcohol, schizophrenia, and hypertension. On examination, he appears pale and agitated. He is tachycardic and tachypneic. Complete blood count shows a macrocytic anemia. Hemoglobin is 7.2 g/dL. BUN is moderately elevated, but creatinine is normal. EKG shows increased heart rate. What is the likely etiology of this patient's problem? A. Alcohol abuse B. Antipsychotic drug side effects C. Mental abnormality D. Hemolysis caused by alcohol E. Chronic blood loss

A. Alcohol abuse

[1K] A 13-year-old girl undergoing hematologic evaluation is found to have a hemoglobin abnormality that decreases the partial pressure of oxygen at which Hemoglobin is 50% saturated from 26 to 20 mm Hg. Which of the following sequelae is this patient most likely to develop? A. Erythrocytosis B. Hypoxia-induced hemolysis C. Increased erythrocyte osmotic fragility D. Megaloblastic erythrocyte changes E. Oxidant-induced hemolysis

A. Erythrocytosis

[1I] A researcher in investigating iron deficiency anemia for which he carries out and studies a series of laboratory tests for their diagnostic importance. Which of the following tests is the most diagnostic (i.e., most specific) for iron deficiency? A. No stainable bone marrow iron B. Low serum ferritin C. High serum transferrin D. Low serum iron E. Microcytic anemia

A. No stainable bone marrow iron "Gold standard" of iron-deficiency anemia is lack of stainable iron in bone marrow. Other lab values one would expect is as follows: decreased Hb (no iron = no heme), decreased MCV (microcytic anemia b/c erythroblasts undergo extra division), decreased MCHC, decreased serum Fe, decreased serum ferritin (no iron = no ferritin needed to store it), & increased transferrin & TIBC (no iron = more carrier proteins to scavenge it).

[1B] A 6-year-old girl is undergoing tonsillectomy. During the operation, the surgeon has to secure bleeding from the tonsillar bed between the 2 arches surrounding the palatine tonsils. One of these 2 arches is the palatoglossal arch. What is the name of the second arch? A. Palatopharyngeal B. Salpingoglossal C. Stylopharyngeal D. Pharyngeotympanic E. Glossopharyngeal

A. Palatopharyngeal Waldeyer's ring is circle of 6 lymphatics in back of throat. Pharyngeal tonsil is found in pharyngeal recess, i.e. depression at back of throat. Palatine tonsils (one on each side) are located b/w two folds of mucous membrane called palatopharyngeal arch & palatoglossal arch. These tonsils are most often ones that become inflamed in children & are removed during tonsillectomy. Source of bleeding during tonsillectomy is external palatine vein & tonsillar branch of facial artery. Tubal tonsils (one on each side) are near Eustachian tympanic tube. Adenoids is where enlarged pharyngeal or tubal tonsils causes difficulty in nasal breathing or hearing (if auditory tube is obstructed). Lingual tonsil is found under tongue.

[1B] A 65-year-old cancer patient underwent radical neck dissections to remove the deep cervical lymph nodes and the surrounding tissues along the internal jugular vein. This vein forms the venous angle with which of the following veins? A. Subclavian B. Brachiocephalic C. Facial D. Superficial temporal E. Posterior auricular

A. Subclavian Venous angle b/w subclavian & internal jugular veins (on right & left sides) is ultimate destination for all lymph.

[1M] A 9-year-old African-American male complains of sudden difficulty in walking starting a few hours ago. The child has a past medical history of a blood disorder and has been hospitalized several times since infancy. He has had several episodes of swelling in his hands and arms and a few episodes of hematuria. The child has been adopted, and the family history is unknown. Blood pressure, pulse rate, respiratory rate, and temperature are normal. Physical examination reveals right arm weakness. CT scan of head without contrast shows no evidence of bleeding. Which of the following is the most likely cause of the development of the patient's condition? A. Vaso-occlusion by abnormal cells B. Thrombosis C. Vasculitis D. Arterial dissection E. Blood pooling in spleen

A. Vaso-occlusion by abnormal cells Dactylitis is result of vaso-occlusion in capillaries of hands. Sickle cell disease patients have greater chance of sickling under hypoxemia, dehydration, or acidosis. Having sickle cell disease leads to massive erythroid hyperplasia, where hematopoiesis expands to skull bones (crewcut appearance on X-ray) & facial bones (chipmunk facies). Extramedullary hematopoiesis also takes place, causing hepatomegaly. This puts patient at risk of aplastic crisis w/ parvovirus B19 infection.

[1M] A 15-year-old African American boy presents with painful swollen fingers. The patient says that he has sickle cell anemia. On physical exam, there is pallor. After prescribing opioid analgesics, a complete blood count is done. What type of anemia does a patient with sickle cell disorder initially present with? A: Normocytic, normochromic B: Normocytic, hypochromic C: Microcytic, hyperchromic D: Microcytic, normochromic E: Normocytic, hyperchromic

A: Normocytic, normochromic Destruction of RBCs leads to excess iron deposition (hemosiderosis) in liver, lung, kidneys, & adrenals. It also causes jaundice w/ unconjugated hyperbilirubinemia & increased risk for bilirubin gallstones. Patients will also have AVN & priapism.

[1E] Which one of the following about hemoglobin A (Hb-A) is the most influenced by low concentration of 2,3 bisphosphoglycerate (BPG)? A) Heme iron becomes more oxidized. B) Affinity of Hb-A to oxygen increases. C) Ratio of T state to R state of HbA increases. D) RBCs become hypochromic. E) Porphyrins accumulate in RBC.

B) Affinity of Hb-A to oxygen increases. 2,3-BPG binds to large pocket in T (tense) state & stabilizes it, thus encouraging O2 release. In R (relaxed) state, narrow pocket is instead occupied by His HC3, thus encouraging O2 binding.

[1A] Which of the following lymph nodes develop from the jugular lymph sac? A. Retroperitoneal B. Axillary C. Lumbar D. Inguinal E. Common iliac

B. Axillary 6 primary lymph sacs develop as local dilatations of lymphatic channels. 2 jugular lymph sacs pop up near junction subclavian veins; 2 iliac lymph sacs near junction of iliac veins; 1 retroperitoneal lymph sac in root of dorsal mesentery; & 1 cisterna chyli dorsal to peritoneum. 2 jugular lymph sacs will become deep cervical, axillary, parasternal, & mediastinal lymph nodes. Cisterna chyli will become cisternal chyli, retroperitoneal, lumbar, & inguinal lymph nodes.

[1A] Which of the following is the most common cause of small sized thymus in adults? A. DiGeorge deletion syndrome B. Chronic thymic involution C. Lack of migration from neck to the chest D. First arch syndrome E. Asplenia syndrome

B. Chronic thymic involution Thymic involution is part of normal aging. Thymus continues to grow & develop until puberty. In young child, thymus occupies large space in thorax. However, past teenage years, it starts to involute & is replaced by fatty tissues.

[1G] Which one of the following enhances iron absorption? A. Phytates B. Citrate C. Tea D. Oxalate E. Calcium

B. Citrate Organic acids like Vit. C, citrate, & fructose reduce Fe3+ to Fe2+ & form iron complexes that enhance uptake. Alcohol also enhances iron absorption somehow. However, phytates (found in high-fiber cereals & legumes), polyphenols (found in high-fiber foods, tea, & coffee), & oxalate (found in spinach, nuts, & chocolate) form insoluble iron complexes that inhibit iron absorption. In addition, divalent cations like Ca2+, Mg2+, & Zn2+ compete for transport into enterocyte, thereby hindering iron absorption.

[1A] Which one of the following ligaments develops from the dorsal mesogastrium? A. Lesser omentum B. Gastrolienal C. Gastrocolic D. Falciform E. Hepatogastric

B. Gastrolienal Spleen is supported by two ligaments, both of which develop from dorsal mesogastrium. Lienorenal ligament connects spleen to body wall, while gastrolienal ligament connects spleen to stomach.

[1F] Patients with chronic hypoxia due to decreased lung function may adapt by increasing BPG levels of the RBCs to above normal levels. Predict which of the following statements regarding hemoglobin A (HbA) of these patients will be true. A. HbA's P50 for O2 decreases. B. HbA's P50 for O2 increases. C. R-state of Hb A increases. D. HbA's affinity to O2 increases. E. Heme will be more oxidized.

B. HbA's P50 for O2 increases. Factors that increase Hb O2 affinity left shift O2 saturation curve, while factors that decrease Hb O2 affinity right shift it. 2,3-BPG stabilizes T state, so it causes right shift. H+ also causes right shift (aka Bohr effect). This is b/c H+ attaches to His-146, which forms salt bridge w/ Asp-94 to stabilize T state. This works b/c metabolism produces protons, so tissues are more acidic than lungs. In addition, most CO2 produced is dissolved in blood as bicarbonate by carbonic anhydrase, process that produces proton. Remaining 15-20% of CO2 binds to amino terminal of Hb globin subunits to form carbamate, process that also produces proton. Hyperthermia also produces right shift.

[1K] A 23-year-old African-American female with a history of sickle cell anemia is admitted with severe diffuse body pains. She has already had five similar episodes this year. Her physician considers adding hydroxyurea to her treatment regimen. Which best describes the mechanism of action of hydroxyurea? A. Increases HbA2 synthesis B. Increases HbF synthesis C. Decreases cellular dehydration D. Directly inhibits polymerization E. Stimulates red cell production

B. Increases HbF synthesis As previously mentioned, HbF is produced in residual amounts in all adults. However, profound erythroid stresses, e.g. severe hemolytic anemias, bone marrow transplantation, or cancer chemotherapy, cause more F-potent BFU-e to be recruited. HbF levels tend to rise in some patients w/ sickle cell anemia or thalassemia. Hydroxyurea facilitates this phenomenon, as do other agents like butyrate & histone deacetylase inhibitors.

[1B] Ultrasound is used to evaluate the size of the spleen in a 17-year-old man who has recently recovered from infectious mononucleosis. In its normal location, the spleen is most likely directly related to which of the following structures? A. Ascending colon B. Left kidney C. Duodenum D. Head of the pancreas E. Inferior vena cava

B. Left kidney Spleen is located in left hypochondrium nearby ribs 9-11. It is related to left kidney, left cholic flexure of large colon, & tail of pancreas. Left cholic flexure is junction b/w transverse colon & descending colon.

[1CD] At a seminar, a histopathologist announces that he has managed to experimentally "knock-out" the granulocyte-monocyte precursor (GMP or CFU-GM) cells in mice. This means that the mature blood cells that would fail to appear in peripheral blood in these mice include one of the following? A. Erythrocytes B. Macrophages C. Lymphocytes D. Plasma cells E. Platelets

B. Macrophages If granulocyte-monocyte precursor is knocked out, then no granulocytes (neutrophils, eosinophils, etc.) or monocytes aka macrophages would be seen in peripheral blood.

[1E] Circulating erythrocytes often contain enzymes that are known to participate in heme synthesis. Despite this, they are still unable to synthesize heme because they lack which of the following cellular structures? A. Nucleus B. Mitochondria C. Endoplasmic reticulum D. Golgi apparatus E. Proteasomes F. Peroxisomes

B. Mitochondria

[1L] A mother brings her little daughter in to the clinic because she does not seem her usual energetic self. She also noticed her daughter's eyes had turned yellow. Physical exam reveals a pale girl with icteric sclera and splenomegaly. Her complete blood count shows a decrease in hematocrit. Blood smear shows small round RBCs. Which of the following tests would be most beneficial in confirming the diagnosis? A. Hemoglobin electrophoresis B. Osmotic fragility test C. Direct Coombs test D. Indirect Coombs test E. Total bilirubin

B. Osmotic fragility test Patient has hereditary spherocytosis, autosomal dominant disorder involving mutations in spectrin, ankryn (50% of all cases), or Band 3 protein. Mutations can cause reduced synthesis, stability, or function of spectrin/ankryn or reduced membrane incorporation, direct loss, or loss of assoc. lipids of Band 3 protein. Ultimately, RBCs have abnormal cytoskeleton that causes membrane blebbing & loss. As result, central concavity is lost & round spherocytes w/ decreased deformability are formed. Blood smear will show round RBCs w/ loss of central pallor. There will be increased reticulocytes, LDH, & bilirubin. Osmotic fragility test will show hemolysis starting at higher saline concentration, i.e. increased fragility in hypotonic solution. RDW will be high since older RBCs will have lost more membrane & be smaller compared to newer RBCs. MCHC will also be increased since presence of smaller RBCs means Hb is more concentrated. Patient presents w/ splenomegaly, jaundice due to unconjugated bilirubin, increased risk for bilirubin gallstones, & increased risk for aplastic crisis w/ parvovirus B19 infection. Splenectomy resolves anemia but Howell-Jolly bodies (containing fragments of nuclear material that would normally be removed by spleen) will appear on blood smears thereafter.

[1K] A 24-year-old African American female presents for prenatal counseling. She has a 4-year-old with sickle cell anemia from a previous marriage. She remarried 2 years ago and now she is pregnant and concerned that her next child will be affected as well. She does not have the disease. Which of the following is the best initial test that can be offered to this woman? A. Maternal hemoglobin electrophoresis B. Paternal hemoglobin electrophoresis C. Paternal karyotype analysis D. Western blot analysis of paternal blood sample E. X-ray based 3D analysis of the parents' hemoglobin

B. Paternal hemoglobin electrophoresis Since we know patient is sickle cell carrier, only possible option is testing father for sickle cell disease. If father is normal, then their children will be fine. If father is carrier or has disease, then there may be issues.

[1A] Which of the following structures is the embryonic precursor of the thymus? A. Pouch of the 1st pharyngeal arch B. Pouch of 4th pharyngeal arch C. Cleft of 2nd pharyngeal arch D. Pouch of 2nd arch E. Cleft of 3rd pharyngeal arch

B. Pouch of 4th pharyngeal arch Thymus starts developing during 5th week. It develops as two halves, each from epithelium of 3rd and/or 4th pharyngeal pouches on each side of body. Gland primordia eventually lose their connection w/ pharyngeal wall in neck region & migrate in caudal & medial direction. 2 glands meet in thoracic region & fuse to develop single thymic gland in thorax.

[1E] A 6-year-old male who lives in an old house suffers from irritability, constipation and anemia. His high blood level of δ- aminolevulinic acid is maintained secondary to the presence of which of the following cofactors? A. Thiamine pyrophosphate (TPP) B. Pyridoxal phosphate (B6) C. Lipoic acid D. Retinoic acid (RA) E. Biotin (B7)

B. Pyridoxal phosphate (B6)

[1CD] A 16-year-old high school girl with sickle cell anemia is brought into the emergency room complaining of bone pain. Examination of the abdomen reveals an enlarged spleen. This enlargement is best explained by activity in which lymphoid tissue in this patient? A. White pulp of the spleen B. Red pulp of the spleen C. Reticulocytes of the thymus D. Subcapsular sinuses of the lymph nodes E. Lymphoid tissue of the tonsil

B. Red pulp of the spleen ???

[1B] A 30-year-old woman has an abscess on the skin on the side of her jaw. Lymphatics from this area initially collect into which of the following groups of lymph nodes? A. Deep cervical B. Submandibular C. Submental D. Superior cervical E. Superficial cervical

B. Submandibular Submandibular nodes are located on either side of chin below mandibles. They drain sides of tongue & teeth on either side. Submental nodes are located directly below chin; they drain tip of tongue & front teeth. Superficial cervical nodes are found atop sternocleidomastoid muscle. Jugulodigastric (superior deep cervical) nodes are found at intersection b/w digastric muscle & internal jugular vein, while juguloomohyoid (inferior deep cervical) nodes are found at intersection b/w two muscles.

[1B] A 30-year-old woman complained of a swollen left leg. Examination revealed obstruction in the lymph vessels on the left leg by a parasitic infestation. The obstructed lymph vessel should eventually convey lymph to which of the following vessels? A. Right lymphatic duct B. Thoracic duct E. Portal vein D. Pulmonary vein E. Hepatic vein

B. Thoracic duct

[1E] The two major conformations of the quaternary structure of hemoglobin are the "Relaxed" (R) and "Tense" (T) conformations. What is the effect that oxygen binding has on hemoglobin's conformation? A. Stabilizes the T state B. Triggers the T to R state transition C. Triggers the R to T state transition D. Triggers covalent modifications to hemoglobin tetramers E. Triggers expansion of the pocket between the β-subunits

B. Triggers the T to R state transition T (tense) state has lower O2 affinity & has open pocket that binds 2,3-BPG. T state also has greater number of ion pairs in pocket b/w subunits. R (relaxed) state has higher O2 affinity & has narrow pocket that contains His HC3, which displaces 2,3-BPG.

[1A] Which of the following embryonic structures are precursors of adult thymus gland capsule? A. endoderm of 3rd and 4th pharyngeal pouch B. neural crest derived mesenchyme of 3rd Pharyngeal pouch C. ectoderm of 6th Pharyngeal Cleft D. neuroectoderm from the neural tube

B. neural crest derived mesenchyme of 3rd Pharyngeal pouch Thymic capsule develops from neural crest cells. They enter mesenchyme of thymus & will influence development of mature thymic gland. DiGeorge syndrome is caused by 22q11.2 deletion where thymus & PTH glands fail to develop from 3rd & 4th pharyngeal pouches, & there is abnormal neural crest cell migration. Affected individuals have immunodeficiency & hypocalcemia. They present w/ facial anomalies too, including micrognathia, low-set ears, etc.

[1E] A 2-day-old infant born to a 22-year-old female demonstrates a good appetite despite some weight loss. Physical examination is within normal limits. Which of the following hemoglobin compositions most likely dominates in this newborn girl? A. α2β2 B. α2γ2 C. α2δ2 D. ζ2ε2 E. γ4

B. α2γ2 There are 6 types of Hb that each person has throughout their lifetimes. Gower 1, Gower 2, & Portland Hb are embryonic. They appear at about 6 wks after conception & are replaced at 10-11 weeks by HbF. Fetal Hb is made of α2γ2 & persists until 38 weeks, upon which HbA is almost exclusively synthesized. Adult Hb is made of α2β2. HbA2 is minor adult Hb & made of α2δ2.

[1E] A 5-year-old male is being evaluated for cognitive impairment, behavioral problems and mild anemia. He lives in an 80-year-old house with toxic metals-based paint. Which of the following enzymes would be most sensitive to environmental toxic exposure in this patient? A. δ-Aminolevulinate synthase 1 (ALAS1) B. δ-Aminolevulinate dehydratase C. Uroporphyrinogen I synthase D. Uroporphyrinogen decarboxylase E. δ-Aminolevulinate synthase 2 (ALAS2)

B. δ-Aminolevulinate dehydratase (1) δ-Aminolevulinate (ALA) synthase combines succinyl-CoA & Gly to form ALA. Requires Vit. B6. Takes place in mitochondria (2) ALA dehydratase converts ALA to porphobilinogen. Requires Zn & is targeted by lead poisoning. Takes place in cytoplasm (3) Hydroxymethylbilane (HMB) synthase converts prophobilinogen to HMB. Takes place in cytoplasm (4) Uroporphyrinogen III synthase converts HMB to uroporphyrinogen III. Takes place in cytoplasm (5) Uroporphyrinogen decarboxylase converts uroporphyrinogen III to coproporphyrinogen III (COPRO). Takes place in cytoplasm (6) COPRO oxidase converts COPRO to protoporphyrinogen IX (PROTO). Takes place in cytoplasm (7) PROTO-oxidase converts PROTO to protoporphyrin IX. Requires Vit. B2 (riboflavin). Takes place in mitochondria (8) Ferrochelatase adds Fe2+ to protoporphyrin IX to form heme. Targeted by lead poisoning. Takes place in mitochondria.

[1J] A 48-year-old man is getting more tired than usual. Laboratory studies show the following: Hemoglobin 8 (range, 14- 16 g/dL) Hematocrit 22.0% (range, 41%- 50%) Mean cell volume 129 (range, 80-100 fL) Hypersegmented neutrophils are seen on the blood smear. The serum lactate dehydrogenase is elevated, and the reticulocyte count is low. Which one of the following laboratory tests should be ordered next in the work-up of this patient? A: Schilling test B: Serum folate C: Serum iron D: Serum ferritin E: Bone marrow biopsy

B: Serum folate Megaloblastic anemia is characterized by macrocytosis (increased MCV since erythrocytes undergo one fewer division) & hypersegmented neutrophils (5+ lobes of nucleus). Since initial lab findings point to macrocytic anemia, next step would be differentiating b/w folate & Vit. B12 deficiencies. Bone marrow biopsy would show giant metamyelocytes & large RBC precursors w/ peppery nuclei. However, biopsy would fail to differentiate b/w two deficiencies. Serum folate should be taken since folate deficiency is far more common that Vit. B12 deficiency. Schilling test for Vit. B12 is outdated.

[1CD] A 7-year old boy develops an intestinal infestation of worms. This is confirmed by a change in blood cell counts from lab tests. Following antihelminthic treatment, the infestation clears and a repeat blood test is performed. For which cell type in peripheral blood would you expect to find a change in cell count between the 2 blood tests in the boy? A. Neutrophils B. Platelets C. Eosinophils D. Basophils E. Monocytes

C. Eosinophils Eosinophils are mainstays of fighting parasitic infections.

[1M] An 8-year-old boy has severe chest pain, non-productive cough, and fever. On examination, his temperature is 39°C, pulse 110/min, respiratory rate 22/min, and BP of 80/50 mm Hg. He has no organomegaly in the abdomen. Laboratory studies show hematocrit of 18% (range 41-50%). Hemoglobin electrophoresis shows 70% Hemoglobin S. A diagnosis of sickle cell anemia is made. A chest x-ray shows bilateral pulmonary infiltrates. Which of the following is the mechanism for pulmonary problems in sickle cell anemia? A. Chronic hypoxia of pulmonary parenchyma B. Defects in alternate pathway of complement activation C. Extensive RBC adhesion to endothelium D. Formation of autoantibodies E. Intravascular antibody induced hemolysis

C. Extensive RBC adhesion to endothelium Thromboemboli can form in lungs, usually precipitated by pneumonia (promotes vasodilation & slowing blood flow in lungs). This will present w/ shortness of breath & lung infiltrates. It is most common cause of death in adults w/ sickle cell disease (acute chest syndrome).

[1A] Which of the following is the sequence of events in the development of lymph nodes? A. Neural crest cells -> lymph channels -> lymph sac -> lymph nodes B. Lymph sacs -> lymph channels -> lymph nodes C. Mesenchyme -> lymph channels -> lymph sac -> lymph nodes D. Lymph vessels -> lymph channels -> lymph sacs -> lymph nodes

C. Mesenchyme -> lymph channels -> lymph sac -> lymph nodes Development of lymph system starts during 6th week. It has two origins: diverticulae of endothelium of veins & clefts in embryonic mesenchyme. Cells lining these clefts become endothelial cells & channels that secondarily connect w/ venous system.

[1K] A 4-year-old patient is presented in the pediatric clinic with microcytic anemia. An analysis of his blood by nondenaturing electrophoresis reveals the following composition of hemoglobin isoforms: HbF = 75%, HbA = 23%, HbA2 = 2%, and HbS = 0%. The child is most likely homozygous for which of the following? A. Complete deletion of the alpha-globin locus B. Complete deletion of the beta-globin locus C. Mutation in the promoter of the beta-globin genes D. Nonsense mutation in the alpha-globin genes E. Nonsense mutation in the beta-globin genes

C. Mutation in the promoter of the beta-globin genes Patient has hereditary persistence of fetal hemoglobin (HPFH), as demonstrated by his Hb electrophoresis. This is possible b/c some red cell clones called F cells are progeny of small pool of immature committed erythroid precursors (BFU-e) that retain ability to produce HbF. Residual amounts of HbF are produced in all adults. However, since people w/ HPFH have mutation in promoter of beta-globin genes, HbF is produced to compensate.

[1J] A clinical study looks at patients who have macrocytic anemia due to Vitamin B12 or folate deficiency. A comparison of laboratory testing strategy is shows that the best strategy includes testing for serum homocysteine, methylmalonic acid, vitamin B12, and folate. Which of the following is the most important reason for ordering these tests simultaneously? A. Anemia can result from lack of either B. Both nutrients are absorbed similarly C. Neurologic injury must be prevented D. Life threatening thrombocytopenia can occur in both E. Therapy for one deficiency also treats the other

C. Neurologic injury must be prevented Homocysteine & MMA are used to differentiate Vit. B12 from Vit. B9 deficiency since metabolism of both involves B12 but only metabolism of homocysteine requires B9 too. Therefore, homocysteine would accumulate in deficiency of either but MMA would only accumulate in Vit. B12 deficiency. Diagnosing Vit. B12 deficiency ASAP is esp. important b/c of its neurological symptoms, which are irreversible in later stages. Vit. B12 deficiency causes inadequate myelin synthesis; these neurological symptoms are non-existent in folate deficiency.

[1F] A 34-year-old male who is accidentally exposed to nitrites at work presents to the ER with anxiety, weakness, dyspnea, and headaches. Physical examination reveals cyanosis that is not corrected by oxygen supplementation. Which of the following is most likely to be normal in this patient? A. Oxygen content of the arterial blood B. Oxygen carrying capacity of the arterial blood C. Partial pressure of oxygen in the arterial blood D. Bound fraction of oxygen in the arterial blood E. Oxygen delivery to peripheral tissues

C. Partial pressure of oxygen in the arterial blood MetHb is Hb w/ Fe3+ instead of Fe2+. It has higher affinity to oxygen & therefore enacts left shift in oxygen binding curve. < 1% of normal blood is metHb due to spontaneous oxidation of Hb-Fe2+. Exposure to nitrites causes methemoglobinemia by increasing metHb & causing cyanosis, esp. in infants since their metHb reducing/repairing capacity is not yet fully developed.

[1E] A 34-year-old man is brought to the ER after a motor vehicle accident. Examination showed a large bruise over his anterior chest. Several days later, the bruise has a greenish color that is best explained by A. The activity of ferrochelatase B. The formation of protoporphyrin IX C. The activity of heme oxygenase D. Localized iron accumulates due to bleeding E. Excess methemoglobin in the bruised area

C. The activity of heme oxygenase Old RBCs are degraded in reticuloendothelial system (liver & spleen). Heme oxygenase (HO) cleaves heme into Fe3+, CO, & biliverdin. This requires O2 & NADPH. Biliverdin is then reduced to bilirubin by biliverdin reductase & NADPH. Iron is recycled.

[1B] A pediatric heart surgeon has just divided the sternum in a child to repair a cardiac malformation. A lobulated gland-like structure is seen immediately obscuring the heart. This is most likely which of the following? A. Lung B. Thyroid gland C. Thymus D. Lymph nodes E. Liver

C. Thymus

[1J] A 48-year-old woman complains of anorexia, numbness and tingling of the feet, dyspepsia, and weakness of the legs. On exam, she has a smooth sore tongue, numbness, and anemia. She most likely has a deficiency of which of the following? A. Niacin B. Riboflavin C. Vitamin B12 D. Iron E. Pantothenic acid

C. Vitamin B12 Patients w/ megaloblastic anemia present w/ glossitis since their tongue cells are not turning over. Vit. B12 deficiency additionally involves neurological symptoms, which patient has. Most common cause of Vit. B12 deficiency is pernicious anemia, where autoimmune destruction of parietal cells leads to intrinsic factor deficiency & inability to absorb Vit. B12. Other causes of Vit. B12 deficiency include pancreatic insufficiency (inability to produce proteases that cleave R-binder from Vit. B12), damage to terminal ileum due to Crohn's disease or fish tapeworm, & dietary deficiency, esp. in vegans.

[1E] An infant born to a Greek immigrants appears healthy at birth but develops transfusion-dependent hemolytic anemia by the age of 6 months. His erythrocytes contain insoluble aggregates of hemoglobin subunits. The child developed normally in utero because at that time he produced high quantities of: A. α-globin B. β-globin C. γ-globin D. δ-globin E. ζ-globin

C. γ-globin

[1K] HbC disease is due to mutation that substitutes Glutamate to Lysine at position 6 in the beta-globin chain of the hemoglobin molecule. Patients homozygous for HbC have a mild chronic hemolytic anemia. HbS disease generally causes a more severe hemolytic anemia compared to HbC. Which of the following explains why the hemolytic anemia of HbS is more severe than HbC? A: HbS impairs oxygen binding to the heme moiety B: HbS impairs proper folding of the alpha-helix in the beta-globin chain C: HbS allows hydrophobic interaction among hemoglobin molecules D: HbS impairs beta-globin interaction with 2,3-biphosphoglycerate E: HbS stabilizes iron moiety at ferric state (Fe3+)

C: HbS allows hydrophobic interaction among hemoglobin molecules Since Lys that replaces Glu in HbC is still hydrophilic, there is no aggregation.

[1M] An African American woman brings in her 14-year-old daughter with right upper quadrant pain. The mother mentions that her daughter has just recently recovered from a Salmonella osteomyelitis infection; her father has sickle cell disease. The ultrasound shows cholelithiasis. The spleen is not visible. What would be most likely seen on a blood smear? A: Hypersegmented neutrophils B: Macrocytosis C: Reticulocytosis D: Atypical lymphocytes E: Megaloblasts

C: Reticulocytosis Lab results will show persistent reticulocytosis (5-20%) & increased bilirubin & LDH. Haptoglobin is decreased due to limited intravascular hemolysis. Target cells also show up on blood smear due to progressive membrane damage leading to dehydration & decreased cytoplasm.

[1F] A 46-year-old male is brought to the emergency department by EMS. He has attempted suicide twice in the past, once by cutting his wrists and another time by taking an overdose of amitriptyline to treat depression. He has no known drug allergies. This evening a neighbor found him in a closed garage with the car running. As you examine him, he loses consciousness and begins to seize. The toxic substance causing this patient's condition affects hemoglobin by: A. Oxidation of the iron moiety B. Oxidation of the porphyrin ring C. Covalent linking to heme D. Competitive binding to heme E. Altering the partial pressure of oxygen

D. Competitive binding to heme Carbon monoxide has higher affinity for Hb & outcompetes oxygen. It depresses oxygen dissociation curve by half rather than shifting it left or right.

[1F] A 21-year-old laboratory worker experiences rapid-onset breathing difficulty, palpitations, and flushed skin. He has no significant past medical history and takes only loratadine for seasonal allergies. The patient is suspected to have accidental poisoning. Amyl nitrite from a laboratory safety kit is immediately administered via inhalation. Amyl nitrite affects the affinity of hemoglobin for which of the following? A. Carbon dioxide. B. 2,3-biphosphoglycerate. C. Carbon monoxide. D. Cyanide. E. Lead.

D. Cyanide. Cyanide ion binds tightly to hemoglobin to produce cyanohemoglobin, which causes severe hypoxia since it can no longer bind oxygen. Although the body can transform cyanide into relatively non-toxic thiocyanate, this process is too slow prevent fatal poisoning. Cyanide poisoning is treated w/ inhalation of amyl nitrate & administration of sodium thiosulfate, sodium nitrate, ferrous sulfate, dicobalt edentate, or hydroxocobalamin. Oxygen therapy is also useful.

[1L] A 48-year-old African American man with a past medical history of asthma and hypertension presents with a 5-day history of progressive fatigue, anorexia, and exertional dyspnea. He has recently been treated for a urinary tract infection with a 1-week course of nitrofurantoin. Examination reveals pallor and tachycardia. Labs reveal Hemoglobin 7.9 g/dL, MCV 108 fL, and total bilirubin 5.5 mg/dL. A peripheral smear shows bite/helmet cells. What is the most likely cause of anemia in this patient? A. Iron deficiency B. Anemia of chronic disease C. Sickle cell disease D. Glucose-6-phosphate dehydrogenase deficiency E. Beta-thalassemia

D. Glucose-6-phosphate dehydrogenase deficiency Clinical presentation of G6PD deficiency is often precipitated by exposure to certain foods or medications (or medical conditions). Patients will have jaundice, red urine due to hemoglobinuria, & back pain since Hb is nephrotoxic. Blood smear shows bite & blister cells as well as Heinz bodies, which are formed by intracellular precipitation of Hb.

[1F] A single amino acid residue replacement (serine instead of histidine) in the hemoglobin β-subunit results in poor ionic interaction with 2,3-biphosphoglycerate. The resultant hemoglobin has the properties of which of the following? A. HbA B. HbS C. HbC D. HbF E. HbA2

D. HbF HbF has low affinity to 2,3-BPG, giving it higher O2 affinity; this is because it must compete for oxygen w/ mom's Hb. However, this also means that oxygen release from HbF is slower, hence why HbA replaces it & is more useful in postnatal life. Increasing BPG, proton, & CO2 concentrations all shift oxygen binding curve right, as does heat & HbS. Conversely, decreasing BPG, proton, & CO2 concentrations all shift oxygen binding curve right, as does cold & HbF.

[1H] Which of the following folate concentrations correlate closely with liver stores of the folate? A. Urine B. Sweat C. Fecal D. RBC E. Serum

D. RBC RBC folate correlates w/ liver folate levels & is decent measure of past folate intake. It may also be low in Vit. B12 deficiency or high in reticulocytosis & iron deficiency. Serum folate doesn't correlate w/ liver stores b/c it only reflects very recent intake.

[1G] Which of the following can provide a good estimate of the amount of iron stored in the body? A. Serum transferrin B. Serum hemosiderin C. Ferroportin D. Serum ferritin E. Divalent metal iron transporter (DMT1)

D. Serum ferritin Ferritin is huge, soluble protein that sequesters 2/3 of iron stored in body. Hemosiderin is insoluble modified aggregate of protein-iron complexes that stores remaining 1/3. Both are found in liver, bone marrow, & spleen. When serum ferritin is b/w 20-200 mcg/L, there is close correlation b/w serum ferritin & iron stores. Multiple serum ferritin by 10 for rough estimate of stored iron in mg. Below 12 μg/L, person has iron deficiency; above 200 μg/L for women & 400 μg/L for men, person has iron overload. Serum ferritin can be affected (regardless of iron status) by inflammation, infection, malignancy, or liver disease.

[1F] A group of investigators is studying the effect of various factors on the shape of the oxygen-dissociation curve for hemoglobin. A left shift would most likely be caused by which of the following? A. Strenuous exercise B. Adaptation to high altitude C. Hypoventilation D. Severe hypothermia E. Chronic anemia

D. Severe hypothermia

[1B] A 45-year-old woman is admitted to the hospital after her automobile left the highway in a rainstorm and hit a tree. She had been wearing a seatbelt. On radiographic examination, it is observed that she has suffered fractures of the ninth and tenth rib on her left side and that she has intraabdominal bleeding. Physical examination reveals hypovolemic shock and progressive hypotension. Which of the following organs is most likely injured to result in these clinical signs? A. Liver B. Pancreas C. Left kidney D. Spleen E. Ileum

D. Spleen

[1E] A 22-year-old Caucasian male develops recurrent skin blistering and prefers to work as nocturnist. Laboratory evaluation shows elevated total plasma porphyrins due to PCT. Which of the following enzymes is most likely deficient in this patient? A. δ-Aminolevulinatesynthase 1 (ALAS1) B. δ-Aminolevulinatedehydratase C. Hydroxymethylbilane synthase D. Uroporphyrinogen decarboxylase E. δ-Aminolevulinatesynthase 2 (ALAS2)

D. Uroporphyrinogen decarboxylase Porphyria cutanea tarda (PCT) is hepatic porphyria caused by uroporphyrinogen decarboxylase deficiency. Symptoms include photosensitivity. Another clinically relevant porphyria is acute intermittent porphyria (AIP) which affects porphobilinogen deaminase aka hydroxymethylbilane synthase. It is another hepatic porphyria w/ neurological symptoms. Porphobilinogen that accumulates is excreted in urine, which is initially clear but will turn dark red after exposure to air. Hepatic porphyrias are symptomatic primarily in adults & generally involve neurological symptoms (PCT is exception); erythropoietic porphyrias usually present at birth or early childhood & generally involve photosensitivity.

[1K] A 12-year-old African American male is brought to the emergency room with high fever, chest pains, and dyspnea. His past medical history is significant for two prior hospitalizations for abdominal pain, which resolved with analgesics and hydration. Evaluation reveals hematocrit of 23% and reticulocyte count of 9%. Several hours after being admitted, the patient dies in the hospital. At autopsy, the patient's spleen is enlarged, firm, and brown. This finding is most likely related to... A. Work hypertrophy B. Hyperplasia C. Dysplasia D. Vascular occlusion E. Lipid accumulation

D. Vascular occlusion Spleens should not be brown; that color indicates that it's ischemic due to occlusion.

[1J] A 42-year-old man has been chronically fatigued for the past six months. A physical examination yields no abnormal findings. A complete blood count shows the following: Hemoglobin 11.0 g/dL (range, 14-16) Hematocrit 33.0% (range, 41%-50%) MCV 104 fL (range, 80-100) His peripheral blood smear shows normal WBC and RBCs morphology. His serum vitamin B12 is within the reference range. His serum haptoglobin is not decreased and hemolysis as a cause of anemia is ruled out. Which one of the following conditions could explain the macrocytosis? A: Beta thalassemia B: Hereditary spherocytosis C: Lead poisoning D: Chronic alcoholism E: Iron deficiency

D: Chronic alcoholism While folate or Vit. B12 deficiency can cause megaloblastic macrocytic anemia, other things cause non-megaloblastic macrocytic anemia. This means that they do not involve deficient DNA synthesis & therefore no hypersegmented neutrophils or megaloblastic changes in other cells are seen. Non-megaloblastic macrocytic anemia can be caused by alcoholism, liver disease, or drugs like 5-FU.

[1K] A 6-year-old boy presents to your office accompanied by his parents. He has been hospitalized multiple times for painful episodes in his hands and legs over the last several years. He takes hydroxyurea to help him with his medical problems. You suspect that he has a valine for glutamic acid substitution at position 6 of the beta-globin chain of the hemoglobin molecule. This patient's hemoglobin would most likely aggregate upon: A: Beta-chain folding B: Interaction with HbF C: Proton release D: Deoxygenation E: Depletion of 2,3-bisphosphoglycerate

D: Deoxygenation Patient has sickle cell disease, where Glu is replaced w/ Val at 6th position in beta-globin. This creates lipophilic patch on surface of HbS, which also has 2 fewer negative charges than HbA at physiological pH. Lipophilic patch becomes more prominent in deoxygenated HbS & stick together to stay away from water, thus forming long fibrous aggregates. These can lead to painful vaso-occlusive crises, which cause ischemia of connective & MSK tissues.

[1M] A 24-year-old African American woman with sickle cell anemia (SS genotype) presents to the hospital for severe pain in her lower extremities and back. She has had four hospitalizations for vaso-occlusive crisis in last 15 months. Her current symptoms are similar to her previous episodes. What is associated with sickle cell anemia? A: Autosomal dominant inheritance B: Hepatomegaly C: Hemoglobinuria D: Howell Jolly bodies on blood smear E: Antibodies to alveolar basement membrane

D: Howell Jolly bodies on blood smear Sickle cell disease causes autosplenectomy, where spleen shrinks & fibroses due to vaso-occlusion & overwork. Without spleen, Howell-Jolly bodies are not removed from blood. Absence of spleen also places patients at greater risk of infection, esp. w/ Salmonella paratyphi osteomyelitis. Infection is most common cause of death in kids w/ sickle cell disease.

[1E] What is sideroblastic anemia? A) This is an additional type of porphyria. B) It is RBC hemolysis caused by excess heme in RBC C) The membrane of RBC rupture causing hemolysis due to low ATP D) Hemolysis caused by excess porphyrins which lead to rupture of the RBC membrane E) Insufficient heme synthesis with iron accumulation in the mitochondria.

E) Insufficient heme synthesis with iron accumulation in the mitochondria. Sideroblastic anemia is caused by defective protoporphyrin synthesis, so iron, which is in sufficient supply, accumulates. This can be congenital (most commonly due to defective ALAS) or acquired (alcoholism, lead poisoning, or Vit. B6 deficiency).

[1E] The genes for globin monomers are clustered in an α-like and β-like groups on chromosomes 16 and 11, respectively. Expression of which one of the following globin genes predominates only after birth? A) ε B) α C) ζ D) γ E) β

E) β

[1H] Which of the following statement best describes the sign and symptoms associated with vitamin B12 deficiency? A. All patients with neurological symptoms of B12 deficiency eventually become anemic. B. Vitamin B12 deficiency has specific symptoms that occur in every patient. C. A low intake of plant based foods will increase the risk of B12 deficiency. D. A high intake of animal based food will increase the risk of B12 deficiency. E. Inadequate myelin synthesis causes neurological symptoms of B12 deficiency.

E. Inadequate myelin synthesis causes neurological symptoms of B12 deficiency. Early peripheral symptoms of Vit. B12 deficiency may be reversible but later symptoms aren't. Neurological symptoms also occur independently of anemia (25-50% of neurologically affected patients have normal HCTs and/or MCVs). Symptoms include bilateral vision loss, symmetric abnormal sensations in feet or hands, loss of coordination & postural sense, loss of vibration sense in feet, & blunting of pain, temp, & tactile sensations. Older patients may also have enlarged spleen & liver & CHF. Psychiatric symptoms include apathy, depression, irritability, confusion, & dementia. Non-neurological symptoms of Vit. B12 deficiency include indigestion & episodic diarrhea.

[1F] A 56-year-old male smoker presents to your office complaining of a chronic cough. He has been hospitalized several times in the past for respiratory infections requiring parenteral antibiotics. He has smoked cigarettes for the past 30 years despite multiple attempts to quit. Today, his oxygen saturation is 90% at rest and decreases to 84% with moderate exertion. Which of the following additional findings is most likely in this patient? A. Decrease in 2,3-Bisphosphoglycerate. B. Mutations in his β-globin genes. C. Increased blood level of porphyrins. D. Left shift in his purified hemoglobin saturation curve. E. Increased erythropoietin production.

E. Increased erythropoietin production. Hypoxia-induced factor (HIF) promotes gene transcription of EPO under anemic/hypoxic conditions. HIF also promotes absorption & transport of iron. EPO is produced in kidneys & promotes production of mature RBCs in bone marrow.

[1K] Beta-thalassemias are genetic disorders in the synthesis of the beta-globin chains in hemoglobin. Affected individuals usually begin to exhibit some degree of anemia at about 6 months of age. Therapy for severe anemia involves multiple transfusions. What is the most serious complication of transfusion therapy? A. Methemoglobinemia B. Copper overload C. Alpha-globin overload D. Increased blood hematocrit E. Iron overload

E. Iron overload

[1I] A 29-year-old woman visits her general practitioner with a 6-week history of feeling tired after routine tasks. On physical examination, she is pale, and her blood pressure is borderline low. The physician suspects severe iron deficiency anemia. He orders many laboratory investigations to confirm the diagnosis. Which of the following combination of laboratory results would be a typical for the diagnosis of iron deficiency anemia? A. Low serum hemosiderin, increased serum transferrin and increased serum ferritin B. Low serum iron, decreased total iron binding capacity and decreased serum ferritin C. Normal bone marrow stainable iron, decreased serum transferrin and decreased serum ferritin D. Low serum iron, increased total iron binding capacity and normal serum ferritin E. Low serum iron, increased serum transferrin and decreased serum ferritin

E. Low serum iron, increased serum transferrin and decreased serum ferritin Since you don't have iron, serum iron will be low. Having less iron means you don't need as much ferritin to store it, so you have decreased serum ferritin. There is increased serum transferrin since you want to bind as much iron as possible.

[1F] A patient is found to have a rare hemoglobin abnormality that decreases P50 of hemoglobin from 26.7 mmHg to 16 mmHg. This patient is most likely to develop which of the following? A. Hyperoxia-induced hemolysis B. Oxidative stress induced hemolysis C. Increased osmotic susceptibility of RBC D. Iron deficiency E. Polycythemia

E. Polycythemia

[1K] A patient is found to have a rare hemoglobin abnormality that decreases P50 of hemoglobin from 26.7 mm Hg to 16 mm Hg. This patient is most likely to develop which of the following? A. Hyperoxia-induced hemolysis B. Oxidative stress induced hemolysis C. Increased osmotic susceptibility of RBCs D. Iron deficiency E. Polycythemia

E. Polycythemia Polycythemia is condition where there is increase in RBC volume in response to mild tissue hypoxia. This is aka compensatory erythrocytosis & can be seen in people living at higher elevations. Tumors can also cause polycythemia by releasing EPO. In extreme cases of polycythemia, increased blood viscosity causes headache, somnolence, or dizziness. Treat w/ phlebotomy.

[1B] Drainage of a pleural effusion following surgical removal of an esophageal tumor confirms the presence of chyle. What is the most likely source of the fluid? A. Azygos vein B. Accessory hemiazygos vein C. Hemiazygos vein D. Thoracic aorta E. Thoracic duct

E. Thoracic duct Lymph from upper right quadrant of body, i.e. upper right head, neck, & chest as well as right arm, drains into right lymphatic duct. Lymph from rest of body drains into thoracic duct (aka left lymphatic duct), which originates from cisterna chyli in abdomen. It ascends thru aortic hiatus in diaphragm & has beaded appearance due to presence of valves.

[1L] What is an example of red blood cell (RBC) hemolysis which occurs intravascularly and caused by an intra-corpuscular defect? A: Autoimmune hemolytic anemia B: Sickle cell anemia C: Beta-thalassemia D: Hereditary spherocytosis E: Glucose-6-phosphate dehydrogenase deficiency

E: Glucose-6-phosphate dehydrogenase deficiency G6PD deficiency is most common human enzyme defect worldwide; it is X-linked & therefore more common in men. According to Lyon hypothesis, heterozygous females are clinically normal but have dimorphic population of RBCs due to random inactivation of X chromosome. Heterozygous carriers are also resistant to P. falciparum, so gene has distribution similar to that of malaria. There are two types: Type A is milder & found in African patients, while Type B is more severe & found in Mediterranean patients.

[1F] If hemoglobin A was dismantled to form the free monomeric β-subunits and α-subunits, then the β-subunits were separated from the α-subunits. The oxygen-dissociation curve of these β-subunits will most likely resemble what kind of curve?

Individual globin subunits & myoglobin have rectangular hyperbolic binding curve (labeled #1). Its P50 is 0.26 kPa, so it binds O2 well & doesn't let it go. Hb tetramer has sigmoidal cooperative binding curve (labeled #2). Its P50 is 3.5 kPa, so it has high-affinity in lungs & low-affinity in tissues.

[1F] What is the difference between partial arterial pressure of O2 (PaO2), arterial blood O2 content, and SaO2?

PaO2 is dissolved O2 in atrial blood. This is mediated by adequate ventilation & is unrelated to Hb concentration. This is also different from PvO2, which is partial venous pressure of O2. Arterial blood O2 content refers to total quantity of O2 in blood, equal to dissolved O2 plus O2 bound to Hb.

[1F] How can someone be anemic and have arterial saturation of O2 (SaO2) of 99%?

SaO2, measured by pulse oximeter, is ratio of oxygenated Hb to deoxygenated Hb. It doesn't measure amount of oxygenated O2. Anemic person may have small amount of Hb, but it will be normally saturated if their ventilation is normal.