UWorld Pathology 1

Question 1

Patient with fatigue, nausea, pruritus, and scleral icterus has characteristic biopsy findings associated with ——–, a chronic disorder characterized by inflammation, fibrosis, and stricture of the intrahepatic and extrahepatic bile ducts. Histologic features include fibrous obliteration of the bile ducts and concentric periductal deposition of connective tissue, which resembles an onion skin–like pattern. PSC affects men disproportionately and has a strong association with ulcerative colitis, likely explaining this patient’s bloody stools.

Answer 1

primary sclerosing cholangitis (PSC)

Question 2

——sided colon cancers (ascending colon) usually grow as exophytic masses and present with occult bleeding and symptoms of iron deficiency anemia. ——sided colon cancers tend to infiltrate the intestinal wall and encircle the lumen, causing constipation and symptoms of intestinal obstruction.

Answer 2

Right

Left

Question 3

Korsakoff syndrome is associated with damage to the —– nuclei. This results in memory loss and a psychological phenomenon called “confabulation.” Usually perminent

Answer 3

anterior and dorsomedial thalamic

Question 4

One of the most dangerous effects of SHS exposure (pre- and postnatal) is the increased risk of ——

SHS also increases the risk of recurrent otitis media, asthma, and other respiratory tract illnesses (eg, pneumonia) in children.

Answer 4

sudden infant death syndrome (SIDS)

Question 5

Left atrial myxomas frequently obstruct blood flow from the left atrium to the left ventricle, leading to a murmur mimicking that of —– (ie, mid-diastolic rumble at the apex). The obstruction can also lead to a decrease in cardiac output that manifests as dyspnea, lightheadedness, or syncope. Because the mass is typically mobile, obstructive symptoms may be transient and influenced by position (ie, upright posture exacerbates mitral obstruction, whereas lying down alleviates it). In some patients, fragments of the mass may embolize into the systemic circulation (eg, resulting in stroke or acute limb ischemia). In addition, some myxomas can produce cytokines (eg, interleukin-6) that lead to constitutional symptoms including fever and weight loss.

Histologically, these tumors demonstrate scattered myxoma cells within a mucopolysaccharide stroma and blood vessels, which may be encircled by myxoma cells. Myxomas produce a large amount of vascular endothelial growth factor, which contributes to the angiogenesis, hemorrhaging (seen as brown hemosiderin deposits), and friability characterizing these tumors.

Answer 5

mitral stenosis

Question 6

—- ingestion causes acute tubular necrosis with vacuolar degeneration and ballooning of the proximal tubular cells. Typical clinical findings include altered mentation, renal failure, high anion gap metabolic acidosis, increased osmolar gap, and calcium oxalate crystals in the urine

Answer 6

Ethylene glycol (anti freeze)

Question 7

Acute —– is an acute inflammation of the gallbladder in the absence of gallstones. It typically occurs in critically ill patients (eg, those with sepsis, severe burns, trauma, immunosuppression) due to gallbladder stasis and ischemia. Clinical findings may be subtle and include fever, right upper quadrant pain, and leukocytosis.

Answer 7

acalculous cholecystitis

Question 8

—– disease, is an inherited peripheral nervous system tumor syndrome. Patients develop neurofibromas, optic nerve gliomas, Lisch nodules (pigmented nodules of the iris), and café au lait spots (hyperpigmented cutaneous macules)

Answer 8

Von Recklinghausen’s/or neurofibromatosis type 1 (NF1)

Question 9

—- syndrome (encephalotrigeminal angiomatosis) is a rare congenital neurocutaneous disorder characterized by the presence of cutaneous facial angiomas as well as leptomeningeal angiomas. This condition is associated with mental retardation, seizures, hemiplegia, and skull radiopacities. Skull radiographs may show characteristic “tram-track” calcifications.

Answer 9

Sturge-Weber

Question 10

—- syndrome (hereditary hemorrhagic telangiectasia) is an autosomal dominant condition marked by the presence of telangiectasias in the skin as well as the mucous membranes of the lips, oronasopharynx, respiratory tract, gastrointestinal tract, and urinary tract. Rupture of these telangiectasias may cause epistaxis, gastrointestinal bleeding, or hematuria.

Answer 10

Osler-Weber-Rendu

Question 11

Barrett esophagus is a metaplastic condition in which the normal squamous epithelium of the distal esophagus is replaced by intestinal-type columnar epithelium. It occurs most often in longstanding acid reflux and is associated with an increased risk of —-

Answer 11

adenocarcinoma

Question 12

Craniopharyngiomas are tumors arising from —– remnants in the anterior pituitary. They characteristically have three components: solid, cystic, and calcified. They present during childhood, usually, with mass effect and visual deficits.

symptoms include headaches, visual field defects, and hypopituitarism, evidenced by the growth retardation of this child. Ultimately, compression of the pituitary stalk by craniopharyngioma leads to hyperprolactinemia by loss of dopaminergic inhibition. Craniopharyngiomas are usually tumors of childhood, being most frequently discovered between the ages of 5 and 10 years of age.

Answer 12

Rathke’s pouch

Question 13

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. B-cell ALL is responsible for approximately 70-80% of all cases of ALL, whereas –cell ALL accounts for 15-17% of all cases of ALL. T-cell ALL often presents as a mediastinal mass that can cause respiratory symptoms, dysphagia, or superior vena cava syndrome.

Answer 13

T

Question 14

Follicular neoplasms typically present as slowly enlarging, painless thyroid nodules. Differentiation between a follicular adenoma and follicular thyroid carcinoma is not possible using only fine-needle aspiration results. Histologic evidence of invasion of the —— is needed to diagnose follicular thyroid carcinoma.

Answer 14

tumor capsule and/or surrounding blood vessels

Question 15

—- thyroid carcinoma (the most common type of thyroid malignancy) has distinct cytologic and histologic features. These include laminar calcifications (psammoma bodies), large cells with pale, empty-appearing nuclei (Orphan Annie–eye or ground-glass nuclei) with nuclear inclusion bodies and nuclear grooves

Answer 15

Papillary

Question 16

The —–is the area of the brain demonstrating the greatest degree of atrophy in Alzheimer’s disease.

Answer 16

hippocampus

Question 17

Thinning of the glomerular basement membrane is seen in —- syndrome. Associated with microscopic hematuria. Alport syndrome is caused by an inherited defect in the formation of type IV collagen; patients have hearing loss, ocular abnormalities, hematuria, and progressive renal insufficiency

Answer 17

Alport

Question 18

von Willebrand disease (vWD) will cause both a prolonged — and bleeding time. von Willebrand factor (vWF) is produced by endothelial cells and megakaryocytes and functions as a carrier protein for factor VIII and as a mediator of platelet adhesion to the endothelium. Absence of vWF leads to impaired platelet function and coagulation pathway abnormalities

Answer 18

PTT

Question 19

—–, a precursor of calcitonin produced by monocytes and the C cells of the thyroid, is a unique APR that has positive and negative properties. Levels rise in response to bacterial toxins and fall in response to viral infections

Answer 19

Procalcitonin

Question 20

In —– syndrome, there is an absence of GnRH secretory neurons in the hypothalamus due to defective migration from the olfactory placode. These patients have central hypogonadism and anosmia, and often present with delayed puberty.

Most often, the cause is a mutation in the KAL-1 gene or the fibroblast growth factor receptor-1 gene, which code for proteins required in this migration

Answer 20

Kallmann

Question 21

Sickle cell disease is characterized by repeated splenic infarctions that ultimately result in splenic ——

Answer 21

atrophy and fibrosis

Question 22

Severe macrocytosis (MCV >110 µm3) is usually due to megaloblastic anemia, a subtype of macrocytic anemia caused by impaired DNA synthesis.

Patients with sickle cell disease (SCD) or other hemolytic anemias have increased folic acid requirements due to increased erythrocyte turnover. As such, they are prone to developing relative —- deficiency and megaloblastic anemia

Answer 22

folic acid

Question 23

Colon adenocarcinoma is the most common gastrointestinal malignancy. Right-sided lesions (location: )are more likely to bleed and cause iron deficiency anemia;

left-sided lesions tend to present with obstructing symptoms (eg, altered bowel habits, constipation, abdominal distension, nausea and vomiting).

Answer 23

ascending colon is right side

rectosigmoid colon is left side

Question 24

Alzheimer disease is characterized by decreased levels of acetylcholine in the nucleus basalis of Meynert and the hippocampus, caused by defeciency of —-

Answer 24

choline acetyltransferase.

Question 25

**Pulmonary arterial hypertension** is a common complication of **systemic ---**, likely resulting from proliferation of **T cells with release of cytokines** (eg, TGF-beta) and consequent **progressive thickening and occlusion of the small and medium-sized pulmonary arteries/arterioles.** Patients typically have **progressive dyspnea and a loud pulmonic component of S2** and may develop signs of right-sided heart failure (eg, **hepatomegaly, peripheral edema**).

Answer 25

**sclerosis**

Question 26

**Myxomatous** changes, with **pooling of mucopolysaccharides in the media layer of large arteries**, are found in **cystic medial degeneration**, which predisposes affected patients to the development of **-----.** Medial degeneration in younger individuals is frequently due to **Marfan syndrome**

Answer 26

**aortic aneurysms**

Question 27

**Acute tubular necrosis** is caused by **renal ischemia** and is characterized by **oliguria, increased serum creatinine, and _muddy brown casts_.** Ischemic injury predominantly affects the **renal medulla**, which has a relatively low blood supply. The terminal (straight) portion of the ----- **_& ------_**of the loop of Henle are the most commonly involved portions of the nephron due to their high metabolic rate and location within the medulla

Answer 27

**_proximal tubules and the thick ascending limb_**

Question 28

The most common cause of **liver metastases is colorectal cancer**, which spreads directly from the colon or superior rectum through the **----** **system to the liver**. This patient, who has not received recommended cancer screening (eg, colonoscopy), likely developed hepatic metastases from colorectal cancer.

Answer 28

**portal venous**

Question 29

Patient, an **elderly woman with headaches, muscular pain, and a rapid response to glucocorticoids**, has typical features of **giant cell arteritis (GCA).** Giant cell arteritis is characterized by **---- inflammation of the media with intimal thickening** and predominantly involves branches of the **carotid artery, especially the temporal artery**. It is strongly associated with **polymyalgia rheumatica.**

Answer 29

**granulomatous**

Question 30

**Myotonic dystrophy** is an **autosomal-dominant** disorder. It is caused by an **increased number of ----** on myotonia-protein kinase gene. **Sustained muscle contraction** (myotonia), along with **weakness and atrophy**, is common. Classic symptoms are **difficulty loosening one's grip after a handshake or inability to release the doorknob.** **Cataracts** are seen in almost all patients. F**rontal balding and gonadal atrophy** are other common features. Type 1 fibers are more affected.

Answer 30

**trinucleotide repeats**

Question 31

**Osteosarcoma** is the most common primary bone malignancy in children and young adults. It occurs most frequently at the **metaphyses of long bones** and presents with local pain and swelling. Most cases are associated with sporadic or inherited mutations in---- and **TP53 (Li-Fraumeni syndrome).**

Answer 31

RB1 (hereditary retinoblastoma)

Question 32

Activating mutations of ---- are responsible for most cases of **hairy cell leukemia,** a B-cell neoplasm that typically presents in older patients with p**ancytopenia, splenomegaly**, and systemic symptoms (eg, fatigue, recurrent infections). It is also present in many cases of **malignant melanoma**

Answer 32

BRAF

Question 33

The key growth factors that promote **angiogenesis** in **neoplastic and granulation tissue** are vascular endothelial growth factor **(VEGF)** and **-----**

Answer 33

fibroblast growth factor.

Question 34

**hereditary nonpolyposis colon cancer (HNPCC), or Lynch syndrome**, an autosomal dominant genetic predisposition to **colon cancer.** In patients with HNPCC, colon cancer occurs at a **young age (age \<50).** Family history reveals a high incidence of colon cancer and, occasionally, extraintestinal (eg, **endometrial) cancers in first-degree relatives.** With HNPCC, there is an inherited mutation in one of the genes responsible for **DNA mismatch repair** (eg, ----).

Answer 34

MSH2, MLH1

Question 35

Inactivation of **retinoblastoma** protein activity by **human papillomavirus** can lead to the formation of ---- **squamous cell carcinoma**.

Answer 35

head and neck

Question 36

**_-------_** are zinc-containing enzymes that **degrade components of the extracellular matrix** (ECM) and **basement membrane,** which are composed primarily of **_laminin and collagens IV and VII._** These enzymes participate in many physiologic processes, such as tissue remodeling and embryogenesis. They also f**acilitate basement membrane penetration, which distinguishes an invasive tumor** from carcinoma in situ

Answer 36

**_Metalloproteinases_**

Question 37

When the humidity and temperature are favorable, specific strains of the fungi **Aspergillus flavus and Aspergillus parasiticus grow on foods such as corn, soybeans, and peanuts,** producing **_aflatoxins_** as a byproduct. High levels of dietary **aflatoxin exposure** is associated with a **G:C → T:A transversion** in codon 249 of the **_p53 gene_**, a mutation thought to greatly increase the risk of developing ----- carcinoma.

Answer 37

hepatocellular

Question 38

Activating **mutations** of the **--- gene** lead to constitutive **activation of the epidermal growth factor receptor (EGFR) pathway**, promoting increased cell proliferation and growth. Tumors harboring these mutations are **resistant to treatment with anti-EGFR drugs (eg, cetuximab, panitumumab).**

Answer 38

KRAS

Question 39

---- protooncogene mutation facilitates the **growth of adenomas** by causing uncontrolled cell proliferation.

Answer 39

KRAS

Question 40

FAP is caused by a **_germline mutation in the tumor suppressor gene adenomatous polyposis coli (APC)._** Although it is an **autosomal dominant disorder**, a spontaneous mutation to the other (wild-type) APC gene is required for expression (which usually occurs in the patient's teens or twenties). **APC encodes for a protein that degrades ----** Loss of function of the APC protein increases cellular concentrations of beta-catenin, which activates transcriptional proteins that lead to **intestinal crypt hyperproliferation**; accumulation of subsequent mutations leads to development of polyps.

Answer 40

**beta-catenin**.

Question 41

**medullary thyroid cancer (MTC)** presenting with a palpable nodule and **elevated serum calcitonin.** MTC is a **neuroendocrine** tumor that arises from **calcitonin-secreting C (parafollicular) cells**. Microscopy shows **_nests or sheets of ---- cells_**, often with **extracellular amyloid deposition** (consisting of full-length calcitonin). MTC is often seen in the context of **multiple endocrine neoplasia type 2 (A and B)**, although the majority of cases are sporadic. Paraneoplastic symptoms (eg, **diarrhea, flushing**) can occur due to elevated calcitonin levels

Answer 41

**_polygonal or spindle-shaped_**

Question 42

**Vimentin** is an intermediate filament present in **mesenchymal tissue** and can be used to detect ---

Answer 42

sarcomas.

Question 43

**Chromogranin A** and **synaptophysin** are markers used for ---- tumors.

Answer 43

neuroendocrine

Question 44

The **HER2 oncogene** encodes for a **transmembrane glycoprotein** with intrinsic **---- activity** and is a member of the family of **epidermal growth factor receptors**. Overexpression of this protein is associated with a worse prognosis and increased risk of disease recurrence.

Answer 44

tyrosine kinase

Question 45

An essential step in the activation of the **cellular immune response to a virus** is the **breakdown of intracellular viral proteins by** the **--- pathway**. This pathway is initiated by **ubiquitin ligase**s, which recognize specific protein substrates and attach a **ubiquitin tag**. The target proteins are then **degraded by a proteasome into peptide fragments**, which are coupled with major histocompatibility complex **class I proteins** and presented on the cell surface for surveillance by **cytotoxic CD8+ lymphocytes**

Answer 45

ubiquitin proteasome

Question 46

**BRCA1 and BRCA2** are tumor supressor genes, involved in repair of **--- breaks.**

Answer 46

**double-stranded DNA**

Question 47

A history of **sarcoma, leukemia, adrenal, and breast** **cancer** is suggestive of **_Li-Fraumeni syndrome._** Cancers of the **brain** are also common. The syndrome is the result of an **autosomal dominant** mutation in ---

Answer 47

TP53

Question 48

**Nuclear factor-kappa B (NF-κB)** is a **transcription factor** with a critical role in the **immune response to infection.** NF-κB is normally present in the cytoplasm in a **latent, inactive state** bound to its **inhibitor protein, ---.** Extracellular substances such as **lipopolysaccharide** can initiate a signal cascade that results in the **destruction of IκB** and translocation of **free NF-κB to the nucleus.**

Answer 48

**IκB**

Question 49

**Heparin-induced thrombocytopenia and thrombosis** results from the production of **IgG antibodies** against complexes of **heparin** and platelet **factor -**. The Fc component of these antibodies binds to platelets, resulting in widespread platelet activation and a prothrombotic state. Ex) patient with a **significant drop in platelet count and acute venous thromboembolism following recent exposure to low molecular weight heparin** likely has heparin-induced thrombocytopenia and thrombosis (HITT)

Answer 49

**4**

Question 50

**Acquired protein C deficienc**y occurs early in the course of **warfarin therapy**, as the inhibition of protein C by warfarin occurs more rapidly than the inhibition of other factors (ie, **factors II, VII, IX, X)**. **If not bridged with --- when starting therapy,** patients may develop **warfarin-induced skin necrosis** due to localized cutaneous thrombus formation.

Answer 50

**heparin**

Question 51

**Thrombotic thrombocytopenic purpura (TTP)** results from **decreased levels** of the **von Willebrand factor-cleaving protease ----.** The classic presentation of TTP is the **pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, renal insufficiency, and neurologic dysfunction.**

Answer 51

**ADAMTS13**

Question 52

**Idiopathic thrombocytopenic purpura (ITP)** results from splenic destruction of platelets labeled by **IgG antibodies** to **---- receptors**. ITP often causes **very low platelet levels** and is associated with **bleeding** complications

Answer 52

**glycoprotein IIb/IIIa**

Question 53

**_Disseminated intravascular coagulation (DIC)_** can occur with **abruptio placentae** due to release of ----- a **procoagulant that activates the coagulation cascade,** from the damaged decidua into the maternal circulation. DIC classically presents with **thrombocytopenia** and **bleeding from mucosal surfaces (eg, gums) and intravenous line sites.**

Answer 53

tissue factor,

Question 54

**Amniotic fluid embolism (AFE**) introduces **fetal antigens and tissue factor** from the **amniotic fluid into the maternal circulation**, triggering a massive immune response and i**ncreased release of procoagulant factors** that can lead to --- However, AFE typically causes maternal circulatory collapse with **_severe hypotension_**

Answer 54

DIC.

Question 55

An **anterior mediastinal mas**s with elevated serum levels of **alpha fetoprotein and β-hCG** is classic for a **nonseminomatous ---- tumor.**

Answer 55

**germ cell**

Question 56

**Saddle pulmonary embolism** straddles the bifurcation of the main pulmonary artery. Venous thromboembolism (ie, pulmonary embolism or deep vein thrombosis) arises due to the **Virchow triad of endothelial injury, venous stasis, and a hypercoagulable state.** ---- causes a hypercoagulable state and is a strong risk factor for venous thromboembolism

Answer 56

Malignancy

Question 57

**------** classically presents with the pentad of severe **thrombocytopenia, microangiopathic hemolytic anemia** (eg, schistocytes on peripheral smear), **renal insufficiency, neurologic symptoms, and fever.** However, all these signs and symptoms are rarely present. Diagnosis is often made by identifying **_severe deficiency of ADAMTS-13_**, a protease that cleaves large **von Willebrand factor** multimers off the endothelium. ## Footnote Labs: **elevated indirect bilirubin level** and an **undetectable haptoglobin** level Thrombocytopenia (↑ bleeding time, **normal PT/PTT)**

Answer 57

**Thrombotic thrombocytopenic purpura**

Question 58

**Inherited deficiency of ------** typically causes **hemolytic anemia** during times of oxidative stress (eg, i**nfection, medication exposure, certain foods**). **High bilirubin and low haptoglobin** are often present due to hemolytic anemia; however, thrombocytopenia is not seen, and peripheral smear would show **_bite cells and Heinz bodies_**

Answer 58

glucose-6-phosphate dehydrogenase

Question 59

patient with m**ultiple injuries following a severe motor vehicle accident** developed **respiratory distress, reduced renal output, and oozing from the catheter and venipuncture sites.** This presentation raises strong suspicion for disseminated intravascular coagulation **_(DIC)_**, a consumptive coagulopathy associated with **trauma, sepsis, malignancy, and obstetrical complications.** Will **protein c & s, fibrinogen factor 7, antithrombin** be increased or decreased?

Answer 59

decreased

Question 60

Patient has **recurrent epistaxis, ecchymoses, and marked thrombocytopenia** (normal 150,000-400,000/mm3). She has a **normal hematocrit, leukocyte count and differential, fibrinogen level, and prothrombin time/International Normalized Ratio**. She takes no medications, and there is no obvious hepatosplenomegaly on physical examination. **---- platelet destruction** is a common cause of thrombocytopenia and should be suspected in patients with ecchymoses, petechiae, mucosal bleeding, and no other obvious causes of thrombocytopenia (eg, medications, bone marrow failure).

Answer 60

**Autoimmune**

Question 61

**Excessive bleeding** (ex bleeding around the catheter) is common in patients with significant renal dysfunction due in part to the accumulation of **--- toxins** in the circulation. These toxins impair platelet aggregation and adhesion, resulting in a **qualitative platelet disorder** characterized by **_prolonged bleeding time_** with **normal platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT).** Uremic bleeding can be **improved with dialysis** as it removes the toxins and partially reverses the bleeding abnormality.

Answer 61

uremic

Question 62

The major clinical manifestations of **_factor V Leiden_** include deep vein thrombosis (**_DVT_**), cerebral vein thrombosis, and **recurrent pregnancy loss**. One to nine percent of **Caucasians** worldwide are heterozygote carriers of factor V Leiden, which is modified to **resist activated protein C.** Pt with "**a single amino acid substitution (glutamine for ----) near the protein C cleavage** site in her coagulation factor **V gene product**."

Answer 62

**arginine**

Question 63

Up to 30% of patients with **SLE** have **antiphospholipid antibodies,** which can cause paradoxical **_aPTT prolongation_** and a **false-positive RPR/VDRL.** Patients with antiphospholipid antibodies are **at risk for venous and arterial thromboembolism** and unexplained, **recurrent ---**

Answer 63

**pregnancy loss.**

Question 64

Vitamin C (ascorbic acid) is a ---- vitamin Cutaneous signs of **_scurvy_** include phrynoderma (**perifollicular hyperkeratosis), coiled hair, and poor wound healing**. Mucosal findings include **bleeding gums and loose teeth**. Hemorrhagic complications include **ecchymoses and petechiae, hemarthrosis, intramuscular bleeding**, and bleeding within the central nervous system, gastrointestinal tract, and genitourinary system. **Normocytic, normochromic anemia i**s typical, while coagulation studies (including **PT and PTT) are normal.**

Answer 64

water soluble

Question 65

**Nephrotic syndrome** is a **_hypercoagulable state_**. Sudden-onset **abdominal or flank pain, hematuria, and left-sided varicoceles** suggest **_renal vein thrombosis_**, a well-known complication of nephrotic syndrome. Loss of anticoagulant factors, especially ------- is responsible for the **thrombotic and thromboembolic** complications of nephrotic syndrome.

Answer 65

antithrombin III,

Question 66

Serum ---- is **decreased in Wilson disease** (hepatolenticular degeneration), which is clinically characterized by **liver disease, motor abnormalities, and psychiatric symptoms**

Answer 66

ceruloplasmin

Question 67

patient's **severe thrombocytopenia and schistocytes on peripheral blood smear indicate microangiopathic hemolytic anemia (MAHA).** The presence of **normal coagulation studies** indicate that there is no systemic activation of the coagulation cascade, which makes disseminated intravascular coagulation unlikely. Therefore, a **platelet-activated thrombotic microangiopathy such as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome is most likely.** In this case, the patient has 4 of the 5 classic findings of acquired TTP: **Severe thrombocytopenia**, which may cause bruising or bleeding MAHA, which may cause symptomatic **anemia** (eg, fatigue, dyspnea on exertion) **Renal damage,** which may cause renal insufficiency (eg, elevated creatinine) and mild proteinuria **Neurologic damage**, which may cause confusion, headache, and transient focal findings (eg, numbness, weakness) Fever (not present) **Acquired TTP** occurs due to the formation of an autoantibody inhibitor against **ADAMTS-13**, a ----–cleaving protease.

Answer 67

von Willebrand factor (vWF)

Question 68

**Reactive ----** is the most common cause of **_elevated platelet count_** in all age groups. It is generally caused by **_high levels of inflammatory cytokines (eg, IL-6)_**, which prompt the liver to release **thrombopoietin,** which **triggers megakaryocyte proliferation and maturation** in the bone marrow.**.** Reactive thrombocytosis is seen in **chronic infection, rheumatologic disease, and burns**; it can also occur with hemolysis and iron deficiency anemia. **Elevated circulating levels of inflammatory cytokines** also trigger the liver to generate **hepcidin**, which down-regulates iron absorption in the gut and iron release by the reticuloendothelial system; this frequently leads to concurrent **_anemia of chronic disease (normocytic anemia)_** due to reduced iron availability for reticulocytosis.

Answer 68

**thrombocytosis**

Question 69

---- bodies are **round, dark, purple/red inclusions within erythrocytes**. These represent nuclear fragments that are typically removed by the spleen; they can be seen in patients with **splenectomy or reduced splenic function (eg, sickle cell)**

Answer 69

Howell-Jolly

Question 70

**Hemolytic uremic syndrome (HUS)** manifests with **acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia**. Characteristic laboratory abnormalities include increased or decreased **hemoglobin, haptoglobin and platelet count** and **increased bleeding time, lactate dehydrogenase**, **indirect bilirubin, blood urea nitrogen, and creatinine**.

Answer 70

**decreased hemoglobin, haptoglobin and platelet count** **increased bleeding time, lactate dehydrogenase**, **indirect bilirubin, blood urea nitrogen, and creatinine**