A 23-year-old woman presents to her physician with a nevus on her arm that is asymmetrical with irregular borders. She has noticed a change in the color of this nevus in recent weeks. The nevus is removed and sent to the pathologist. On examination of the specimen, the pathologist determines that it is a melanoma. Which of the following features of this lesion is the greatest indicator of a poor prognosis for this patient?
Depth within the dermis of >2 mm
In the vertical growth phase of melanoma, neoplastic cells grow deeply into the dermis. Considering that invasion of lymphatics or blood vessels (deep structures) is necessary for distant metastasis of any cancer, it can easily be understood why the depth of invasion is so important in highly labile melanoma. The depth of invasion into the dermis is an established prognostic factor for the patient, since most melanoma patients die due to complications of metastatic melanoma involvement of other organs (lung or brain). Patients with a tumor depth 6 mm, and Elevation/Evolution
A 57-year-old smoker presents to her primary care physician with a lump in the upper outer quadrant of her right breast. Mammography confi rms a 2.5-cm lesion and core needle biopsy yields invasive ductal carcinoma. The patient undergoes lumpectomy with axillary lymph node dissection, and is referred to an oncologist to begin chemotherapy. Which of the following should be coadministered with the chemotherapy that this patient will most likely receive?
The patient has invasive ductal carcinoma, which must be resected and then treated with chemotherapy. There are many chemotherapy combinations used to treat breast cancer, two of the most common being (1) cyclophosphamide, methotrexate, and 5-fl uorouracil (5-FU) and (2) cyclophosphamide, doxorubicin, and 5-FU. Almost all of the regimens use the drug cyclophosphamide, an alkylating agent, which is commonly also used to treat non-Hodgkin’s lymphoma and ovarian cancer. The most important toxicity of this drug is hemorrhagic cystitis, which can lead to transitional cell carcinoma. Hemorrhagic cystitis is prevented by coadministration of mesna. This is especially important in thispatient because she is a smoker, which is independently a signifi cant risk factor for transitional cell carcinoma.
A 43-year-old man comes to the physician because of increasing epigastric pain, heartburn, and weight loss over the past 4 months. When asked about bowel habits, the patient recalls a few occasions on which he had black, tarry stools. On physical examination, the physician notes that the patient is thin and pale and has diffuse tenderness over the epigastric area. Serum levels of which of the following substances are likely to be elevated in this patient?
The question stem describes a case of a pancreatic gastrinoma leading to Zollinger-Ellison syndrome. This syndrome results from hypergastrinemia. Gastrin is normally produced by the G cells of the antrum and duodenum. For example, ectopic and unregulated production of gastrin by malignant pancreatic islet cells stimulates excess secretion of acid by parietal cells of the stomach. Gastrin also promotes hypertrophy of the stomach. Increased stomach acid leads to symptoms of gastroesophageal reflux disease and to ulceration and gastric bleeding, as evidenced by the patient’s pallor and melena. Elevated serum gastrin would be diagnostic of gastrinoma.
A 65-year-old man presents with a 2-month history of a cough. He also complains of a droopy right eyelid and dry facial skin. On a head and neck examination, the physician fi nds the right pupil is more constricted than the left one. CT scan reveals a 3-cm nodule in one lung. Based on these symptoms, which of the following is the most likely location of the tumor found on CT scan?
Apex of right upper lobe
The question stem describes a case of Pancoast’s tumor, in which a lung neoplasm of any type located in the apex impinges on the cervical sympathetic plexus. This impingement results in Horner’s syndrome of ptosis, miosis, and anhidrosis, as described in this patient. The symptoms are ipsilateral to the damaged plexus, so the tumor must be located in the apex of the right upper lobe.
A 58-year-old woman presented to her physician after discovering a lump in her left breast. The physician examines the lump and fi nds it to be hard, nontender, and moveable. Which of the following increases this woman’s risk of breast cancer?
Having gone through menopause 2 years ago
Late menopause (>50 years old) is associated with an increased risk of breast cancer. Other risk factors include being female, older age, early fi rst menarche (30 years old), and family history of a fi rst-degree relative with breast cancer at a young age.
Low-molecular-weight heparins (LMWH) are distinct from unfractionated heparin in several ways. Which of the following is the primary target of LMWH?
LMWHs act predominantly on Xa, whereas unfractionated heparin targets both Xa and IIa. A major advantage of using LMWHs over unfractionated heparin is that there is no need for monitoring of APTT
A 4-year-old girl is brought to the emergency department with an 8-hour history of projectilevomiting and headache. Her parents say that the patient was well until 2 months ago, when they noted that she was becoming increasingly clumsy. Physical examination shows nystagmus in all directions of gaze, as well as truncal ataxia. Laboratory studies of blood show a WBC count of 7200/mm³, a hemoglobin level of 12.3 g/dL, and a platelet count of 225,000/ mm³. A CT scan shows a lesion in the cerebellar vermis with associated dilation of the third and lateral ventricles. Which of the following is most likely to be evident on histopathologic examination of the lesion?
Deeply staining nuclei with scant cytoplasm arranged in pseudorosettes
The diagnosis is medulloblastoma, which occurs predominantly in children and is found exclusively in the cerebellum, accounting for 20% of brain tumors in children. On microscopic examination the tumor is very cellular with sheets of anaplastic cells. Each tumor cell is small with little cytoplasm and crescent-shaped, deeply staining nuclei (due to high mitotic activity) arranged in pseudorosettes. These tumors are frequently radiosensitive.
A 17-year-old boy presents to the emergency department with severe abdominal pain. Laboratory tests show a defi cit in uroporphyrinogen I synthetase and excess δ-aminolevulinate and porphobilinogen in the urine. Which of the following symptoms would most likely also be present in this patient?
This patient suffers from acute intermittent porphyria (AIP), an autosomal dominant disorder caused by a lack of uroporphyrinogen I synthetase. The buildup of toxic levels of δ-aminolevulinate (ALA) and porphobilinogen lead to the associated symptoms of abdominal pain (more than 90% of cases), neuropathy, high sympathetic tone, and neuropsychiatric disturbances, including anxiety, depression, seizures, and paranoia. AIP almost never presents before puberty, and it can be hard to diagnose because of its acute nature. Untreated, it can lead to paralysis and death.
A 35-year-old woman visits her primary care physician after feeling a hard lump in her neck. Her physician notes that she has a single, hard, nontender nodule in the left lobe of her thyroid that moves when she swallows. There is no cervical lymphadenopathy. The patient denies any changes in her recent health. The patient does not have tremor, restlessness, heat intolerance, or an increased level of anxiety. Blood tests show normal thyroid hormone and calcitonin levels. A scintiscan shows a cold nodule in the left lobe of her thyroid. Tissue is obtained and a histological section is shown in the image. This patient most likely has which of the following?
This patient has papillary carcinoma, the most common form of thyroid cancer. Patients are frequently in their 20s–40s and many have a history of exposure to ionizing radiation. Most papillary carcinomas are cold masses on scintiscan. On histologic exam, papillary carcinomas show branching papillae with a fi brovascular stalk. Thesepapillae are lined by epithelial cells with empty-looking, ground-glass nuclei often called “Orphan Annie eye” nuclei. Also characteristic of papillary carcinoma is the concentrically calcifi ed psammoma bodies shown in the image above. Psammoma bodies are almost never seen in follicular or medullary carcinomas. The prognosis of papillary carcinoma is excellent. The overall 10-year survival rate is about 98%, especially in patients without lymph node metastases.
A 7-year-old African-American boy is brought to see his pediatrician. His father says he has noticed that the boy has been complaining of right knee pain for the past week. On physical exam, multiple ecchymoses are noted on both upper and lower extremities. His father claims that the boy has always bruised easily, and he has recently learned how to ride a bicycle. Which of the following elements of the coagulation cascade is most likely to be missing in this child?
This patient has hemophilia A, an X-linked disorder caused by factor VIII defi ciency. Bleeding frequently occurs in joints and the retroperitoneal space. It is the most common inherited coagulopathy, as 1:10,000 males has a defi ciency or dysfunction of factor VIII.
A 16-year-old boy is brought to the emergency department because of the acute onset of fever, chills, and a productive cough. X-ray of the chest shows an infi ltrate restricted to the left lower lobe. Samples taken of the sputum show α-hemolytic gram-positive cocci in pairs. The patient says that he has had similar infections over the past year. A peripheral blood smear is done, and results show several sickle-shaped RBCs. Which of the following explains why this patient is susceptible to this particular type of infection?
Microvascular infarcts resulting in splenic dysfunction
This patient has sickle cell disease, as evidenced by the erythrocyte sickling in the peripheral blood smear. Patients with this disease are prone to microvascular infarcts in several vascular beds in the body. Over time, multiple micro-infarcts in the spleen result in functional asplenia, making patients particularly susceptible to infections with encapsulated organisms. This patient presents with pneumonia caused by Streptococcus pneumoniae. This is an encapsulated bacterium, which can be confi rmed by a positive quellung reaction.
A 55-year-old man presents to his physician with easy bruising, splenomegaly, and fatigue. A peripheral blood smear is shown in the image. Which of the following is the most likely diagnosis?
Acute myeloid leukemia
The cytoplasmic inclusions seen in the myelocytic precursors in the image are fused lysosomal granules known as Auer rods. Release of these fused granules may cause acute disseminated intravascular coagulation (DIC) and fatal hemorrhage. Auer rods defi ne a cell as being of myelocytic lineage as opposed to lymphocytic and are seen in acute myeloid leukemia (AML), especially in the subgroup of acute promyelocytic leukemia, also known as M3 in the French American British system (FAB). AML is the most common form of leukemia in adults and constitutes approximately one-fi fth of acute leukemia cases in children. Symptoms of AML are related to complications of pancytopenia (i.e., anemia, neutropenia, and thrombocytopenia) and include weakness and easy fatigue, infections, and hemorrhagic fi ndings such as gingival bleeding, ecchymoses, epistaxis, or menorrhagia. The prognosis for patients with AML is poor; many patients die within a few years of diagnosis.
During autopsy of a 65-year-old woman, the liver is examined, revealing multiple tumors of various sizes throughout both lobes. This pattern, along with the fact that most tumors found in the liver are metastases, leads the pathologist to suspect that a primary tumor exists in another organ. Which of the following is the most likely location of the primary tumor?
The liver and lung are the most common sites of metastasis (after lymph nodes) due to the high blood fl ow through these organs. Therefore, primary tumors in any of the locations listed may metastasize to the liver. However, given that the blood vessels from the gastrointestinal tract drain into the hepatic circulation, the most likely primary tumor that metastasizes to the liver would be from a gastrointestinal source such as the colon.
A child is brought to the pediatrician because her parents are concerned about lead poisoning since their house is known to contain leadbased paint. A complete blood cell count reveals anemia. Lead poisoning causes anemia because it does which of the following?
Disrupts heme synthesis by inhibiting ferrochelatase
Lead inhibits δ-aminolevulinate (ALA) dehydratase and ferrochelatase, preventing both porphobilinogen formation and the incorporation of iron into protoporphyrin IX, the fi nal step in heme synthesis. Inhibition of both of these steps results in ineffective heme synthesis and subsequent microcytic (hemoglobin-poor) anemia
A 10-year-old boy with jaundice, splenomegaly, and chronic normocytic, normochromic anemia with an abnormal osmotic fragility test and increased mean corpuscular hemoglobin concentration presents to the clinic for a consult. He has had these symptoms for most of his life, and his parents are requesting a defi nitive cure. Which of the following confers a defi nitive cure for this patient’s disease?
The patient is exhibiting symptoms of a hemolytic anemia because he is anemic and has jaundice, which results from the breakdown of RBCs leading to the formation of excess bilirubin. Moreover, his anemia is normochromic and normocytic with an abnormal osmotic fragility test and increased mean corpuscular hemoglobin concentration (MCHC). These are all characteristics of hereditary spherocytosis, an intrinsic, extravascular hemolysis due to spectrin or ankyrin defect. RBCs are small and round with no central pallor. The osmotic fragility test detects hemolysis by measuring the fraction of hemoglobin released from RBCs at progressively more dilute salt concentrations. It detects hemolysis in spherocytes at salt concentrations that do not affect normal RBCs. The MCHC measures the concentration of hemoglobin in a given volume of packed RBCs and is elevated only in hereditary spherocytosis. The defi nitive treatment of hereditary spherocytosis is splenectomy because the spleen is responsible for the breakdown of the defective RBCs in this disease. Once eliminated, the spleen no longer hemolyzes the RBCs, and thus, the anemia improves
A 60-year-old woman presents to her physician with findings of decreased proprioception in her lower extremities and gait instability consistent with subacute combined degeneration secondary to cobalamin defi ciency. However, blood tests show normal hematocrit and nearnormal mean cell volume. The physician orders additional tests. Which of the following laboratory results would support a diagnosis of cobalamin deficiency?
Elevated methylmalonic acid
In a minority of patients with cobalamin (vitamin B12) defi ciency, hematocrit and mean corpuscular volume can be normal. In these cases, laboratory testing for elevated homocysteine and methylmalonic acid can be used to make the diagnosis
A 73-year-old woman is brought to the emergency department after passing out on the subway. The patient has a 3-month history of burning epigastric pain that is worse after eating, along with dark stool. Physical examination shows a blood pressure of 95/52 mm Hg, a pulse of 97/min, epigastric tenderness, and guaiac-positive stool. Laboratory tests show a hemoglobin level of 9.5 g/dL, a hematocrit of 28%, and a mean corpuscular volume of 75 μm3. Which of the following is the most likely diagnosis?
Iron deficiency anemia secondary to blood loss
This patient is suffering from iron defi ciency anemia secondary to blood loss from the gastrointestinal tract. Since the body possesses a limited ability to absorb iron from the gut (which occurs mainly in the duodenum), occult blood loss can quickly lead to a depletion of existing iron stores and hence to an iron defi ciency anemia. The burning epigastric pain that worsens after eating is consistent with a gastric ulcer. The black stool is melena, which occurs with blood loss in the upper gastrointestinal tract (bleeding in the lower gastrointestinal tract causes visibly bloody red stools). Iron defi - ciency anemia is shown by the low hematocrit level and mean corpuscular volume. The most common cause of iron defi ciency anemia in postmenopausal women is occult blood loss, often from a gastrointestinal source.
Breast cancer is the leading cause of cancer in women in the United States and the second leading cause of cancer deaths in women. Age, a family history of breast cancer, and mutations in the BRCA1 and BRCA2 genes are important risk factors for the development of breast cancer. Which of the following drugs is used as prophylaxis in women at high risk for developing breast cancer?
Tamoxifen and raloxifene
Use of tamoxifen and raloxifene as prophylaxis in women at high risk for breast cancer has been shown to reduce the incidence of breast cancer by 50%–80% in this population. It is thought that selective estrogen receptor modulators have a selective benefi t in reducing the incidence of estrogen receptorpositive cancers for BRCA2-positive women. The decision to begin tamoxifen and raloxifene, however, is not one that should be taken lightly. These drugs have many adverse effects that impact quality of life, such as hot sweats and amenorrhea associated with early menopause and increased risk of stroke and pulmonary embolism. Women who have previously been diagnosed with breast cancer are also often put on tamoxifen as prophylaxis against a second cancer.
A 47-year-old woman from the Middle East presents to the clinic with fever, general malaise, and weight loss. Physical examination reveals hepatomegaly and massive splenomegaly, along with edema. Laboratory tests show moderate anemia and a peripheral WBC count <4000/mm3. Macrophages containing amastigotes are seen on histologic analysis. Which of the following parasites does the woman most likely harbor?
Leishmania donovani infection presents with hepatomegaly and splenomegaly, malaise, anemia, leukopenia, and weight loss. L. donovani is transmitted via the sandfl y. Microscopically, macrophages containing amastigotes are observed. Sodium stibogluconate is used to treat L. donovani infection.
A type of lymphoma is characterized by onset in middle age and by neoplastic cells that resemble normal germinal center B lymphocytes. Additionally, it is the most common type of non-Hodgkin’s lymphoma in the United States. What is the characteristic chromosomal translocation and protein that is produced by this translocation?
The question stem describes follicular lymphoma, the most common type of non-Hodgkin’s lymphoma in the United States. The characteristic chromosomal translocation is t(14:18), which juxtaposes the IgH locus on chromosome 14 next to the BCL2 locus on chromosome 18. This causes overproduction of the bcl-2 protein, an antiapoptotic factor, facilitating the survival of the cancer. An important simplifying fact to help remember the different chromosomal translocations is that those involving the immunoglobulin loci on chromosome 14 tend to be cells that normally produce antibodies (e.g., B lymphocytes). Thus, these translocations are common in B-lymphocyte lymphomas.
A 52-year-old heart transplant patient on chronic immunosuppressive therapy that includes cyclosporine develops bacterial sinusitis. The patient’s physician decides to start him on antibiotic therapy but is having diffi culty choosing between amoxicillin and erythromycin to treat the infection. Concurrent use of erythromycin and cyclosporine would most likely lead to which of the following serum drug levels?
Increased cyclosporine serum concentrations
Cyclosporine is an immunosuppressant that binds to cyclophilins, thereby blocking the differentiation and activation of T lymphocytes by inhibiting the production of interleukin-2 (IL-2). Erythromycin is a macrolide antibiotic that binds to the 50S ribosomal subunit and inhibits protein synthesis. Amoxicillin is a β-lactam antibiotic that inhibits bacterial cell wall synthesis. Studies have shown similar results with amoxicillin and erythromycin in the treatment of bacterial sinusitis. Concurrent use of erythromycin and cyclosporine could lead to elevated cyclosporine serum concentrations because erythromycin inhibits the cytochrome P-450 enzyme system in the liver. The cytochrome P-450 enzyme superfamily is a major site of drug metabolism and is responsible for the oxidation, reduction, and hydrolysis of drug compounds, including cyclosporine.
A 56-year-old man is diagnosed with transitional cell carcinoma and treated with excision and chemotherapy. Which of the following risk factors most likely led to this patient’s cancer?
Exposure to aniline dyes
Transitional cell carcinoma (TCC) is a malignant tumor that arises from the transitional epithelium of the renal pelvis. It can spread to adjacent tissues and often recurs after removal. It is the most common tumor of the urinary tract system. While it can occur in renal calyces, the renal pelvis, and the ureters, the most common site for TCC is in the bladder. There is signifi cant association of TCC with phenacetin (a common painkiller), smoking, aniline dyes, and cyclophosphamide (a chemotherapeutic drug); remember the mnemonic “associated problems in your Pee SAC.” Painless hematuria is the most common presenting sign of TCC. The presence of otherwise unexplained hematuria denotes cancer in the urinary tract in individuals over the age of 40 years until proven otherwise. Commonly, TCC is treated surgically. Other treatment modalities include radiation and chemotherapy as either adjuvant or primary treatment, depending on the case.
A 70-year-old man with no prior surgical history presents with a tingling sensation of the extremities, weakness, and an enlarged tongue that is sore and smooth. Preliminary laboratory studies are negative for antinuclear antibodies and antimitochondrial antibodies, and peripheral blood smear reveals a macrocytic megaloblastic anemia. When the patient is given an oral dose of radiolabeled cyanocobalamin, none of that compound is detected in his urine. What is the function of the protein that is most likely defi cient and/or affected in this disease process?
Complex with free vitamin B12 in the small intestine and then binds to receptors on the wall of the ileum
The clinical and laboratory fi ndings are consistent with pernicious anemia. This chronic progressive anemia is caused by a defi ciency of intrinsic factor, a protein produced by gastric parietal cells. Once vitamin B12 is released from food, it binds R-proteins upon which it travels to the duodenum. In the duodenum, vitamin B12 is released from R-proteins and then complexes with intrinsic factor. The intrinsic factor-B12 complex binds to receptors in the ileum, where it is endocytosed by enterocytes. Pernicious anemia is believed to be caused by immune-mediated destruction of gastric mucosa, leading to a loss of parietal cells. A Schilling test (as described in the stem) will reveal whether the labeled vitamin B12 is being absorbed and eliminated in the urine (as in normal individuals), or whether a lack of intrinsic factor or malabsorption is preventing the radiolabeled compound from appearing in the urine
A 2-year-old boy is brought to a clinic because his mother noticed a large, unilateral, painless abdominal mass while she was bathing him. While performing an ultrasound-guided biopsy, the technician notes that the kidney calyces are highly distorted by the mass. Which of the following is most likely the origin of this lesion?
Embryonic renal cells from the embryonic kidney
Wilms’ tumor arises from neoplastic embryonal renal cells of the metanephros. Wilms’ tumor is the most common solid tumor of childhood (most commonly occurring between the ages of 2 and 4 years) and is rarely seen in adults. It commonly presents with a huge palpable flank mass and is seen with hemihypertrophy (abnormal enlargement of one side of the body). It is associated with the deletion of tumor suppressor gene WT1 on chromosome 11. Since it arises from the kidney parenchyma, it distorts the kidney calyces as it grows.
An 8-year-old boy is brought to the pediatrician after his parents noticed very dark urine in the toilet earlier that morning. Initial laboratory studies show intravascular hemolysis; further testing shows that his RBCs are susceptible to complement-mediated lysis. This patient most likely has which of the following conditions?
Paroxysmal nocturnal hemoglobinuria
This patient suffers from paroxysmal nocturnal hemoglobinuria, an acquired disease caused by RBC susceptibility to complement-mediated cell lysis. This is due to insuffi cient synthesis of GPI anchors, which anchor proteins that protect RBCs from this process. Clinical manifestations include intravascular hemolysis with hemoglobin release into the blood and subsequent hemoglobinuria, thrombotic complications (such as Budd-Chiari syndrome), and aplastic anemia.
A 58-year-old man has a past medical history signifi cant for chronic renal insuffi ciency. He was recently diagnosed with transitional cell carcinoma of the bladder and will be started on chemotherapy. Which of the following chemotherapeutic agents should be avoided in this patient?
Cisplatin has been shown to cause nephrotoxicity and acoustic nerve damage. Use of cisplatin requires that the patient be vigorously hydrated in order to prevent kidney damage. In patients with documented kidney dysfunction, cisplatin should be avoided altogether due to these patients’ greater susceptibility to dose-related nephrotoxicity
A 3-year-old girl was in her usual state of good health 1 month ago when she developed an acute viral upper respiratory infection. She now presents to the emergency department with nonblanching purple skin lesions. The rest of her physical examination is unremarkable. The complete blood count demonstrates a low platelet count, while the peripheral blood smear is notable only for large platelets. Which of the following laboratory fi ndings would most likely be present in this patient?
This patient presents with clinical features of idiopathic thrombocytopenic purpura (ITP), the most common cause of thrombocytopenia in childhood. ITP is an autoimmune disease and is most commonly instigated by a viral illness. Bleeding disorders due to platelet defects or defi ciencies will present with microhemorrhage of the mucous membranes and of the skin, like the nonblanching purple skin lesions (purpura) seen in this patient. ITP is a diagnosis of exclusion but classically presents with thrombocytopenia, antiplatelet antibodies, as well as signs of a compensatory increase in platelet production,including large platelets on peripheral blood smear and increased megakaryocytes on bone marrow biopsy. As ITP only affects platelets, patients will have normal prothrombin time and normal partial thromboplastin time.
A 57-year-old woman is diagnosed with smallcell lung carcinoma. She has gained weight, and she says that her face has recently “ballooned.” Which of the following symptoms is this patient likely to be experiencing in addition to the ones mentioned?
Poor wound healing and hirsutism
Although her symptoms may be somewhat nonspecifi c, the fact that this patient has small-cell lung carcinoma (SCLC) should be a clue that her symptoms may be part of a paraneoplastic syndrome. SCLC is notorious for production of ACTH and ADH. In this case, excessive ACTH pro-duction has lead to increased glucocorticoids. Weight gain and redistribution of body fat (in contrast to the cachexia typical of cancers alone) and moon facies are classic signs of Cushing’s syndrome. Poor wound healing (due to inhibition of collagen synthesis by glucocorticoids) and hirsutism (stimulation of androgen production by ACTH) are also part of Cushing’s syndrome.
A 45-year-old woman arrives in the emergency department complaining of intense pain in her upper abdomen for the past 4 hours. She had a similar episode in the past, but it went away within an hour. Her history is signifi cant for a recent fl u-like infection and a prolonged feeling of fatigue and general exhaustion. Physical examination reveals that her sclerae are icteric, her palate is abnormally pigmented, and her skin has a yellow hue. Ultrasound shows radiopaque gallstones. A Coombs’ test is negative. A peripheral blood smear shows small RBCs, several of which have no central pallor. Which of the following is the most likely cause of this patient’s condition?
A mutation in the gene encoding ankyrin
This woman suffers from hereditary spherocytosis (HS), typically caused by mutations in the genes that code for either ankyrin or spectrin. Both of these proteins contribute to the erythrocyte cytoskeleton. When the erythrocytes with abnormal membranes pass through the spleen, the reticuloendothelial cells remove pieces of the membrane, causing a decreased membrane-to-cytoplasm ratio. This results in spherocyte formation. HS is often associated with hemolytic crisis resulting in jaundice and pigmented gallstones.
A research group is studying sickle cell disease in a small community of 6000 people in central Africa and performs a genetic analysis on every community member. At the beginning of the year, it is determined that 10% are homozygous for hemoglobin S and therefore have sickle cell disease. Thirty percent of the community is heterozygous for the mutant allele. Over the course of the year, 100 infants are born, six of whom are diagnosed with sickle cell disease. Of the 80 people who die during the year, three had sickle cell disease. Which of the following describes the current prevalence of homozygous sickle cell disease in this population?
Prevalence is the total number of cases in a population divided by the total population; that is, the proportion of the total population with the disease. The total number of cases at the beginning of the study can be calculated by multiplying the initial population (6000) by the initial prevalence (10%), yielding 600 cases. Over the course of the year, there was a net gain of 3 patients with sickle cell disease (6 births – 3 deaths), bringing the new total to 603. Likewise, the new total population is 6020, a net gain of 20 people. Therefore, the current prevalence of sickle cell disease is 603/6020