Pathology

Question 1

Some patients with non-small cell lung carcinoma (NSCLC) harbor a chromosomal rearrangement that creates a fusion gene between ___ and ___.

This results in a constitutive__ __ __ that causes malignancy.

Answer 1

EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase).

This results in a constitutive active tyrosine kinase that causes malignancy.

Question 2

__ __ is characterized by a translocation of the c-myc oncogene on the long arm of chromosome 8 to the Ig heavy chain region on chromosome 14.

This causes constitutive overproduction of __, a nuclear phosphoprotein that functions as a transcription activator.

Answer 2

Burkitt lymphoma is characterized by a translocation of the c-myc oncogene on the long arm of chromosome 8 to the Ig heavy chain region on chromosome 14. This causes constitutive overproduction of c-myc, a nuclear phosphoprotein that functions as a transcription activator.

Question 3

Patients with __ __ have a t(14;18) translocation that causes overexpression of the __ __ gene product.

Answer 3

Patients with follicular lymphoma have a t(14;18) translocation that causes overexpression of the antiapoptotic BCL2 gene product.

Question 4

__-__ syndrome is an autosomal dominant predisposition to a variety of cancers, particularly sarcomas and tumors of the breast, brain, and adrenal cortex.

This syndrome is associated with a mutation of the tumor suppressor gene, __

Answer 4

Li-Fraumeni syndrome is an autosomal dominant predisposition to a variety of cancers, particularly sarcomas and tumors of the breast, brain, and adrenal cortex.

This syndrome is associated with a mutation of the tumor suppressor gene, p53.

Question 5

Translocation between the cyclin D1 locus on chromosome 11 and the immunoglobulin heavy chain locus on chromosome 14 is characteristic of __ __ __.

This abnormality results in increased production of cyclin D1, a promoter of the _ to _-phase transition during the cell cycle.

Answer 5

Translocation between the cyclin D1 locus on chromosome 11 and the immunoglobulin heavy chain locus on chromosome 14 is characteristic of mantle cell lymphoma.

This abnormality results in increased production of cyclin D1, a promoter of the G1 to S-phase transition during the cell cycle.

Question 6

The pathophysiology of EML4-ALK NSCLC is most similar to the pathophysiology of chronic __ __ (__).

In __, the classic and most common cause is a translocation between chromosomes 9 and 22. The ABL proto-oncogene is transported from chromosome 9 to chromosome 22 where it is placed adjacent to the BCR gene. The resulting oncogene,__-__, codes for a fusion protein with constitutive tyrosine kinase activity

Answer 6

The pathophysiology of EML4-ALK NSCLC is most similar to the pathophysiology of chronic myelogenous leukemia (CML).

In CML, the classic and most common cause is a translocation between chromosomes 9 and 22. The ABL proto-oncogene is transported from chromosome 9 to chromosome 22 where it is placed adjacent to the BCR gene. The resulting oncogene, BCR-ABL, codes for a fusion protein with constitutive tyrosine kinase activity

Question 7

Ischemia causes a __ __ __ within cardiac myocytes. Elevated concentrations of __ and __ draw free water into the cells, causing edema.

Answer 7

• net solute gain*
• Na+ and Ca2+*

Question 8

This patient’s soft S2 and __ __ __ __
that decreases in intensity with maneuvers that decrease __ __ __ __ (eg, abrupt standing, Valsalva straining phase) are consistent with __ __, which most commonly occurs due to age-related __ __ __ __(CAVD).

Answer 8

late-peaking systolic ejection murmur

left ventricular blood volume

aortic stenosis

calcific aortic valve disease

Question 9

__ and __ with asymmetric septal thickening occurs in hypertrophic cardiomyopathy. As with aortic stenosis, patients have a harsh __-__ __ __; however, the murmur increases (rather than decreases) in intensity with maneuvers that reduce __ __ blood volume

Answer 9

Cardiomyocyte hypertrophy and disarray

crescendo-decrescendo systolic murmurleft ventricular

Question 10

Aortic stenosis most commonly results from age-related __ __ __ __(CAVD). The early pathogenesis of CAVD closely mimics that of __ __. In the later stages, __ differentiate into __-like cells and deposit bone matrix, leading to progressive __ __ and stenosis

Answer 10

calcific aortic valve disease

arterial atherosclerosis

fibroblasts

osteoblast-like cells

valvular calcification

Question 11

patient has altered mental status and acute renal failure. In conjunction with the oxalate crystals noted on renal biopsy, this presentation is consistent with __ __

Answer 11

ethylene glycol poisoning.

Question 12

__ __ is a toxic alcohol found in antifreeze, engine coolants, and brake fluids and may be accidentally or intentionally ingested (used as a substitute for alcohol). Patients initially have symptoms of __ __; signs of acute renal failure (__, __) develop approximately __-__hours after ingestion.

Answer 12

Ehtylene glycol

Ethanol intoxication

Oliguria, flank pain

24-72 hrs

Question 13

Ethylene glycol itself is relatively nontoxic; however, it is metabolized to __ __and __ __, resulting in its various toxicities.

Answer 13

glycolic acid and

oxalic acid

Question 14

Acute kidney injury occurs due to both __ __, which causes direct _ _, and oxalic acid, which ___and causes tubular obstruction. This results in __ __ __, demonstrated histologically by proximal tubular __ __ and vacuolar __with morphologically normal glomeruli.

Answer 14

glycolic acid

direct tubular cytotoxicity

crystalizes

acute tubular necrosis (ATN)

cell ballooning

vascular degeneration

Question 15

__ __can cause light-chain cast nephropathy due to obstruction of the proximal tubules.

Answer 15

Multiple myeloma

Question 16

___ causes hypercalcemia, which predisposes patients to __ __(eg, calcium oxalate) formation. However, kidney stones typically cause __ __ with cortical atrophy and __ of __; (ATN) acute tubular necrosis would be unexpected

Answer 16

Hyperparathyroidism

calcium stone

postobstructive nephropathy

blunting of calyces

Question 17

Ethylene glycol ingestion causes __ __ __ with __ degeneration and __of the proximal tubular cells. Typical clinical findings include altered mentation, renal failure, high anion gap __ __, increased __ gap, and __ __crystals in the urine.

Answer 17

acute tubular necrosis

vacuolar degeneration

ballooning

high anion gap metabolic acidosis

osmolar gap calcium oxalate

Question 18

Glomerulonephritis can cause __, __ and __ __ but is not associated with cyst formation. Casts are typically visible on urinalysis.

Answer 18

hematuria, hypertension, and renal failure

Question 19

Hydronephrosis can cause __ and __, particularly if associated with an __ __. However, dilation of the ureters and calyces would be __ __ imaging.

Answer 19

hematuria and pain

obstructing stone

expected on imaging

Question 20

__ (ex:__) is the most common pediatric renal malignancy but is rare in adults. It typically presents with a painful __ __, ___ and __. CT scan demonstrates a solid, __ __ __ with patchy enhancement.

Answer 20

Nephroblastoma (ex: Wilms tumor)

abdominal mass, hematuria, and hypertension

heterogenous renal mass

Question 21

Autosomal dominant (adult) polycystic kidney disease is caused by mutations in the__ __ (__,__) , which result in __ __of the kidneys and progressive __ __. Clinical features include __, __/__pain, and gross __; extrarenal manifestations include liver cysts and __ __.

Answer 21

polycystin genes (PKD1, PKD2)

cystic enlargement of the kidney

renal dysfunction

hypertension, abdominal/flank, gross hematuria,intracranial aneurysms

Question 22

patient’s pale red reflex and well-circumscribed white mass within the retina are indicative of ___

Answer 22

retinoblastoma.

Question 23

Retinoblastoma is an intraocular tumor caused by inactivating mutations affecting the __ __ __ with subsequent dysregulation of the cell cycle.

Answer 23

RB1 tumor suppressor gene

Question 24

Checkpoints occur at the __ and __ transitions, allowing the cell cycle to be stopped if damaged DNA is detected by __ and __-__ __.

Answer 24

G1/S and G2/M transitions

cyclins and cyclin-dependent kinases.

Question 25

The RB1 gene encodes the __ __ that regulates the ____ checkpoint. In its__ form, Rb protein __ and __ __ transcription factors, thereby halting the cell cycle.

Answer 25

The RB1 gene encodes the Rb protein that regulates the G1/S checkpoint. In its active form, Rb protein binds and inhibits E2F transcription factors, thereby halting the cell cycle.

Question 26

The ___ ___encodes the Rb protein that regulates the G1/S checkpoint. In its active form, __ __ binds and inhibits __ __ factors, thereby halting the cell cycle.

Answer 26

The RB1 gene encodes the Rb protein that regulates the G1/S checkpoint. In its active form, Rb protein binds and inhibits E2F transcription factors, thereby halting the cell cycle.

Question 27

__is associated with inactivating mutations of the RB1 tumor suppressor gene, which normally restricts cells from passing the __ __ until the cell is ready to divide.

Impaired function of the Rb protein allows __ __ through the __ checkpoint, leading to uncontrolled cell division.

Answer 27

Retinoblastoma

G1/S checkpoint

unrestricted progression

G1/S

Question 28

overexpression of __ and __ are associated with non–small cell lung cancer, and __ is associated with breast cancer.

Answer 28

EGFR and MET

HER2

Question 29

overexpression of EGFR and MET are associated with __-__ __cancer, and HER2 is associated with__ __

Answer 29

non–small cell lung

Breast Cancer

Question 30

Abnormal __ __function due to a KRAS mutation prevents the conversion of __ to __, which results in constant activation of the ___ pathway and uncontrolled cellular proliferation.

__ __ are associated with lung and colorectal cancers, not retinoblastoma.

Answer 30

Abnormal K-Ras GTPase function due to a KRAS mutation prevents the conversion of GTP to GDP, which results in constant activation of the MAPK pathway and uncontrolled cellular proliferation.

KRAS mutations

Question 31

KRAS mutations are associated with __ and __ __ , not retinoblastoma.

Answer 31

lung and colorectal cancers

Question 32

Tumor suppressor __ __ arrests the cell cycle at the __checkpoint if DNA damage is detected and __ __ __if DNA repair fails.

Answer 32

Protein P53 arrests the cell cycle at the G1/S checkpoint if DNA damage is detected and initiates cell apoptosis if DNA repair fails.

Question 33

Mutations of p53 are associated with most cancers, particularly __ -__ __ (sarcoma, breast, leukemia, and adrenal cancers).

__ and__ proteins are both critical components of tumor suppression pathways, and their normal function complements one another to prevent cancer progression.

Answer 33

Li-Fraumeni syndrome (sarcoma, breast, leukemia, and adrenal cancers).

Rb and p53 proteins

Question 34

Li-Fraumeni syndrome

Definition and Ex’s

Answer 34

a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults:

sarcoma

breast

leukemia

adrenal cancers

Question 35

__ and __ are two of many DNA repair genes that have been identified. When mutated, these genes are associated with an increased risk of breast and ovarian cancer.

Answer 35

BRCA1 and BRCA2

Question 36

This patient’s postprandial epigastric pain and associated food aversion/weight loss in the setting of __ __ (eg, coronary and carotid artery disease) is consistent with __ __ __

Answer 36

generalized atherosclerosis

achronic mesenteric ischemia

Question 37

When ___involves the mesenteric arteries, the bowel can suffer from diminished blood supply. Intestinal hypoperfusion, which can be very painful, is especially pronounced within an__ __ __ when more blood is needed for the digestion/absorption of nutrients (__ __a).

This is analogous to __ __ __, chest pain that occurs with physical exertion due to increased myocardial oxygen demand.

The diagnosis can be made with __ ultrasonography or __ showing high-grade stenosis in the celiac and mesenteric arteries.

Answer 37

atherosclerosis

within an hour after meals

intestinal angin​a

stable cardiac angina

duplex ultrasonography or angiography

Question 38

Aortic dissection results from an __ __ __ with formation of a false lumen that can propagate and obstruct the vessels branching off the aorta (eg; __,__,__,__) similar process would be more likely to cause __ __-__ __(eg, cerebral infarction) rather than chronic, episodic ischemia.

Answer 38

aortic intimal tear

renal, splanchnic, spinal, lower limb

acute end-organ damage

Question 39

Peptic ulcer disease is characterized by __ __ and__and is typically due to __ __ infection or __ __ -__drug use. This patient’s pain did not respond to antacids and his upper endoscopy is normal, so he is unlikely to have a condition associated with peptic ulcers.

Answer 39

gastrointestinal erosions and ulcerations

Helicobacter pylori

nonsteroidal anti-inflammatory

Question 40

__ __ __is characterized by atherosclerosis of the mesenteric arteries, resulting in diminished blood flow to the intestine after meals.

This causes postprandial epigastric pain (__ __) with associated food aversion/weight loss. Its pathogenesis is similar to __ __.

Answer 40

Chronic mesenteric ischemia

intestinal angina

angina pectoris

Question 41

__ __ __ typically presents with gross hematuria and flank pain.

Answer 41

renal papillary necrosis

Question 42

__ __ __ can be caused by renal ischemia and is characterized by __, increased __ __, and __ __ casts.

Ischemic injury predominantly affects the__ __, which has a relatively low blood supply.

The __ __and the __ __ limb of the loop of Henle are the most commonly involved portions of the nephron.

Answer 42

Acute tubular necrosis

oliguria, serum creatinine, muddy brown casts

renal medulla

proximal tubules and thick ascending limb of loop of Henley

Question 43

elderly patient with weight loss, anorexia, and iron deficiency anemia (IDA) likely has __ __, the third most common cancer among men (after __ and __). It is the most common gastrointestinal malignancy and one of the most common causes of __ in the elderly.

Answer 43

colon cancer

prostate and lung

IDA

Question 44

__-__ __cancers (eg, __ __) tend to grow as large, bulky masses that protrude into the __ __ due to the relatively large caliber of the ascending colon.

They are more likely to __and therefore more likely to cause__ . The bleeding is usually occult and detected by __ __ __ blood testing.

Answer 44

Right-sided colon ( eg.ascending colon)

colonic lumen

bleed

IDA

positive fecal occult blood test

Question 45

__ __ tumors (eg, __ colon) tend to be smaller.

They often infiltrate the __ __colon, encircling it and __ __lumen. Therefore, they are more likely to cause __ , and patients generally have altered bowel habits, __ __ and __ and __

Answer 45

left-sided tumors (rectosigmoid colon)

wall of the colon

narrowing the lumen

obstruction

abdominal distension, and nausea and vomiting

Question 46

This young woman with recent-onset hypertension died of an intracranial hemorrhage, likely from a__ __. This, in conjunction with the characteristic pathology findings of __ _alternating with aneurysmal dilation and loss of the __ __ __, is consistent with fibromuscular dysplasia (FMD).

Answer 46

ruptured aneurysm

fibromuscular webs

internal elastic lamina

Question 47

This young woman with recent-onset hypertension died of an intracranial hemorrhage, likely from a ruptured aneurysm. This, in conjunction with the characteristic pathology findings of __ __ alternating with __ __ and loss of the internal elastic lamina, is consistent with __ __.

Answer 47

• fibromuscular webs alternating*
• aneurysmal dilation*

fibromuscular dysplasia (FMD).

Question 48

FMD is a __ disease characterized by __ __ __ within arterial walls, leading to (name 4).

FMD typically occurs in women age __.

Angiography (ie, percutaneous, CT, MRI) is diagnostic and typically demonstrates a __-__-__appearance in multifocal disease.

Answer 48

nonatherosclerotic

abnormal tissue growth

(arterial stenosis, tortuosity, aneurysms, or dissections)

age <55

string-of-beads

Question 49

FMD can involve any artery but most commonly the (name 3) arteries.

Up to 80% of patients develop __ __ __, which limits renal perfusion and leads to activation of the __ -__ -__ system.

Answer 49

renal, cerebral (eg, carotid, vertebral), and visceral

renal artery stenosis

renin-angiotensin-aldosterone system.

Question 50

Adrenal tumors that can present with severe hypertension include (name 3)

Answer 50

pheochromocytoma

aldosterone- or cortisol-secreting adrenocortical adenomas.

Question 51

__ __ may present with sudden death in young patients due to left ventricular outflow obstruction; histology demonstrates __ __and __ fibrosis. However, __ __ is not associated with aneurysm formation.

Answer 51

Hypertrophic cardiomyopathy

hypertrophied myocytes

interstitial fibrosis

hypertrophic cardiomyopathy

Question 52

__ __ __ can cause hyperthyroidism (eg, __,__ __). This commonly causes __,__,__but would not cause aneurysm formation.

Answer 52

Thyroid follicular hyperplasia

(Graves disease, thyroid adenoma)

tachycardia, tremor, and palpitations

Question 53

__ ___is characterized by abnormal tissue growth within arterial walls, resulting in __ and __arteries that can cause tissue ischemia and are prone to aneurysm formation.

Answer 53

Fibromuscular dysplasia

stenotic and tortuous arteries

Question 54

Pathology of Fibromuscular Displasia typically demonstrates alternating__ __ and __ dilation with absent __ __ __(string-of-beads appearance).

Answer 54

fibromuscular webs

aneurysmal dilation

internal elastic lamina

Question 55

Renovascular hypertension occurs due to__ __ __ and activation of the__-__-__ system.

Answer 55

renal artery stenosis

renin-angiotensin-aldosterone

Question 56

Petechiae and ecchymoses are more consistent with qualitative or quantitative __ __

Answer 56

platelet abnormalities

Question 57

Recurrent hemarthroses (bleeding into a joint cavity) are suggestive of __ (factor __ or __).

Answer 57

hemophilia (factor VIII or IX deficiency)

Question 58

Renal artery stenosis is primarily caused by atherosclerosis and fibromuscular disease, not thrombosis.

Moreover, __ __ is associated with an _increased risk of deep venous_ (not arterial) thrombosis.

Answer 58

atherosclerosis and fibromuscular disease

factor V Leiden

Question 59

Major causes of splenic infarction include (name 3)

Moreover, the __ __ __mutation is associated with deep venous (not arterial) thrombosis.

Answer 59

sickle cell anemia, infectious endocarditis, myeloproliferative disorders

factor V Leiden

Question 60

One to nine percent of Caucasians worldwide are heterozygote carriers of factor V Leiden, which is modified to resist __ __ __.

The resulting hypercoagulable state predisposes to __ __ thromboses, which are the source of most __ emboli.

Answer 60

activated protein C

deep vein thromboses

pulmonary emboli

Question 61

Gastrointestinal blood loss results in __, __ __due to iron deficiency

Answer 61

hypochromic, microcytic anemia

Question 62

Red blood cell fragments, burr cells, and helmet cells are associated with either (name 2)

In patients with prosthetic valves, __ __ __ are exposed to excessive shear and turbulence in the circulation, causing damage from __ trauma.

Answer 62

microangiopathic hemolytic anemia or mechanical red cell destruction.

red blood cells

mechanical trauma

Question 63

This patient with an aggressive lung cancer (SCLC) has symptomatic __(eg, confusion, lethargy) despite appearing euvolemic (_ __ __).

This presentation suggests __ __ __ __complicated by _ _ _ __ _.

Answer 63

hyponatremia

euvolemic (moist mucous membranes)

small cell carcinoma of the lung

paraneoplastic syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Question 64

Small cell carcinomas show evidence of __ __.. These tumors stain for neuroendocrine markers, such as (name 4).

Answer 64

neuroendocrine differentiation

neural cell adhesion molecule (CD56),

neuron-specific enolase,

chromogranin,

synaptophysin.

Question 65

__ __ can be identified in the cytoplasm of the tumor cells on electron microscopy.

Answer 65

Neurosecretory granules

Question 66

__ __ __ show evidence of neuroendocrine differentiation. These tumors stain for __ __, such as __ __ __ molecule (CD56)

Answer 66

Small cell carcinomas

neuroendocrine markers

neural cell adhesion molecule (CD56)

Question 67

__ __ __ of the lung is the most aggressive type of lung cancer and is commonly associated with __ __ (eg, SIADH, __ _).

It is thought to have a __ origin; tumor cells express neuroendocrine markers (eg,name 3) and contain neurosecretory granules in the cytoplasm.

Answer 67

Small cell carcinoma

paraneoplastic syndromes

(SIADH, Cushing syndrome)

neuroendocrine origin

(eg, neural cell adhesion molecule, chromogranin, synaptophysin)

Question 68

What does pyruvate kinase deficiency mean?

Answer 68

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells.

Question 69

__ __ is the enzyme responsible for the final step of glycolysis, in which ___ is converted to _ with the production of ATP. __ __catalyzes the last step of glycolysis which is important for generating adenosine triphosphate (ATP).

Answer 69

Pyruvate kinase (PK)

phosphoenolpyruvate

pyruvate

Pyruvate kinase catalyzes

Question 70

Most of the ATP produced is used for transport of __ against a concentration gradient in the RBC membrane. Therefore, pyruvate kinase deficiency, which results in __ __production, disrupts this gradient, leading to __ and __ loss, defective maintenance of membrane architecture (echinocyte formation), and __.

Answer 70

cations

insufficient ATP

water and potassium loss

Hemolysis

Question 71

As __ __ in the splenic red pulp are involved in removal of damaged RBCs, their increased activity in the setting of __ __ __ causes them to undergo hyperplasia, resulting in__.

Answer 71

reticuloendothelial cells

pyruvate kinase deficiency

splenomegaly.

Question 72

Passive congestion of the spleen with blood occurs in the setting of (name 3). Resultant __ __ __can lead to splenomegaly.

Answer 72

portal hypertension, splenic vein thrombosis, or congestive heart failure

splenic sinusoid dilation

Question 73

__ __ deficiency causes hemolytic anemia due to failure of __ and resultant failure to generate sufficient __ to maintain erythrocyte structure.

In this case, __ __results from increased work of the splenic parenchyma, which must remove these deformed erythrocytes from the circulation

Answer 73

Pyruvate kinase deficiency

glycolysis, ATP

splenic hyperplasia

Question 74

The autopsy finding of thick, fibrous tissue in the pericardial space is consistent with __ __, a potential complication of __ __ therapy for non-Hodgkin lymphoma.

This dense, rigid pericardial tissue encases the heart and restricts __ __ , causing __ __ __(manifesting with fatigue and dyspnea on exertion) and progressive right-sided heart failure (manifesting with __ and _- __).

Answer 74

constrictive pericarditis

chest radiation

ventricular filling

low cardiac output

hepatomegaly and peripheral edema

Question 75

Physical examination in constrictive pericarditis typically shows elevated __ __ __with prominent x and y descents and a __ __(early diastolic sound that occurs before S3) and may also demonstrate __ __ (___mm Hg drop in __ __ __during inspiration). In addition, __ sign may be present.

Answer 75

elevated jugular venous pressure (JVP)

pericardial knock (early diastolic sound that occurs before S3)

pulsus paradoxus (>10 mm Hg drop in systolic blood pressure during inspiration)

Kussmaul Sign

Question 76

A loud pulmonic component of the second heart sound (P2) is heard in patients with __ __

Answer 76

pulmonary hypertension.

Question 77

__ __ occurs when cardiac pathology (eg name 2) delays closure of the aortic valve, causing __ to occur noticeably later than __.

Answer 77

Paradoxical splitting

(aortic stenosis, left bundle branch block)

A2 to occur, than P2

Question 78

An __ __ occurs due to the sudden deceleration of blood as it enters a dilated ventricle; it is typically heard in patients with (name 2)

Answer 78

S3 gallop

dilated cardiomyopathy or severe mitral regurgitation.

Question 79

A sustained __ __ is most commonly a sign of right ventricular hypertrophy, such as occurs with __ __ __ __ __ (eg, pulmonary hypertension, pulmonic stenosis) or __ __(eg, tricuspid regurgitation

Answer 79

left parasternal lift

chronic right ventricular pressure overload

volume overload

Question 80

In __ __, normal pericardium is replaced by dense, rigid pericardial tissue that restricts __ __, leading to __ __ output and progressive__-__ __ failure.

Physical examination findings in such patients include (name 4)

Answer 80

constrictive pericarditis

ventricular filling

low cardiac

right-sided heart failure

elevated jugular venous pressure (JVP), pericardial knock, pulsus paradoxus, and a paradoxical rise in JVP with inspiration (Kussmaul sign).

Question 81

Monoclonal immunoglobulin spikes are found in __ __.

__ cells suppress osteoblasts and would cause ___ lesions. Patients commonly have what symptoms: name 3

Answer 81

multiple myeloma.

Myeloma cells

osteolytic lesions

symptoms: bone pain, recurrent infections, and symptoms of anemia.

Question 82

Hematuria and polycythemia (due to __ __) are suggestive of renal cell cancer. Renal cell cancer bone metastases are commonly___.

Answer 82

(due to erythropoietin release)

osteolytic

Question 83

__ and __ (due to erythropoietin release) are suggestive of __ __ cancer. __ __ __ bone metastases are commonly osteolytic.

Answer 83

Hematuria and polycythemia

renal cell cancer

Question 84

Elevated parathyroid hormone-related peptide (PTH-rP) levels can occur with __-__ __ cancer (___) and are associated with symptoms of ___ (confusion, abdominal pain, bony pain). __ __ lesions would be seen in NSCLC.

Answer 84

non-small cell lung cancer (NSCLC)

hypercalcemia

Osteolytic bone lesions

Question 85

__ and ___ overexpression are found in lymphomas.

Answer 85

Lymphadenopathy and BCL-2

Question 86

___ is an anti-apoptosis factor, and overexpression plays a role in resistance to chemotherapy.

Common manifestations of lymphoma also include: Name 3

Answer 86

BCL-2

night sweats, weight loss, and fatigue.

Question 87

A rapidly enlarging irregular mole is suggestive of a ____. The __, __ , __ are the most common metastatic sites.

___ causes lytic bone lesions.

Answer 87

melanoma.

liver, bone, and brain

Melanoma

Question 88

Imaging of bone metastases assists in cancer diagnosis.

__ __ are characterized as osteolytic or osteoblastic. Bony pain in an older man with osteoblastic lesions on imaging is highly suspicious for __ __.

Answer 88

Bone metastases

prostate cancer.

Question 89

Proto-oncogenes
1-hit GAIN of function

RAS
(GTP binding protein)

Answer 89

Cholangiocarcinoma

Pancreatic adenocarcinoma

Question 90

Proto-oncogenes
1-hit GAIN of function

MYC
(Transcription factor)

Answer 90

Burkitt lymphoma

Question 91

Proto-oncogenes
1-hit GAIN of function

ERBB1 (EGFR)
(Receptor tyrosine kinase)

Answer 91

Lung adenocarcinoma

Question 92

Proto-oncogenes
1-hit GAIN of function

ERBB2 (HER2)
(Receptor tyrosine kinase)

Answer 92

Breast cancer

Question 93

Proto-oncogenes
1-hit GAIN of function

ABL
(Nonreceptor tyrosine kinase)

Answer 93

Chronic myelogenous leukemia

Question 94

Proto-oncogenes
1-hit GAIN of function

BRAF
(Ras signal transduction)

Answer 94

Hairy cell leukemia

Melanoma

Question 95

Tumor suppressor genes
2-hit LOSS of function

BRCA1/2
(DNA repair genes)

Answer 95

Breast & ovarian cancer

Question 96

Tumor suppressor genes
2-hit LOSS of function

APC/β-catenin (Wnt signaling pathway)

Answer 96

Colon, gastric & pancreatic cancer

Familial adenomatous polyposis

Question 97

Tumor suppressor genes
2-hit LOSS of function

TP53
(Genomic stability)

Answer 97

Most cancers

Li-Fraumeni syndrome

Question 98

Tumor suppressor genes
2-hit LOSS of function

RB
(G1/S transition inhibitor)gtpv

Answer 98

Retinoblastoma

Osteosarcoma

Question 99

Tumor suppressor genes
2-hit LOSS of function

WT1
(Urogenital differentiation

Answer 99

Wilms tumor

Question 100

Tumor suppressor genes
2-hit LOSS of function

VHL
(Ubiquitin ligase component)

Answer 100

Renal cell carcinoma

Von Hippel-Lindau syndrome

Question 101

patient’s expansile tumor in the distal femur likely indicates___ , the most common primary bone tumor affecting children and young adults.

Most cases arise at the __ of __ bones and present with progressive pain and swelling.

Answer 101

osteosarcoma

metaphysis of long bones

Question 102

Osteosarcomas typically form when a __ __ cell develops mutations in the following genes: Name 2

Answer 102

• mesenchymal stem cell*
• 1. RB1 Tumor suppressor gene*
• 2. TP53 tumor suppressor gene*

Question 103

__ __ gene, which encodes for RB, a protein that regulates cell-cycle progression.

Inactivating mutations to__ promote unchecked and unregulated cellular replication and are associated with

Name 4:

Answer 103

RB1 tumor suppressor gene

RB1

osteosarcoma, retinoblastoma, melanoma, and soft-tissue sarcomas

Question 104

__ __ suppressor gene, which encodes for P53, a protein that regulates __-__ __ and maintains__ __ by activating DNA repair following damage.

Answer 104

TP53 tumor suppressor gene

• regulates cell-cycle progression*
• and*
• maintains genomic integrity*

Question 105

Germ-line mutations to TP53 are associated with __-__ syndrome, which increases the risk for multiple tumors (eg, osteosarcoma, other bone and soft-tissue sarcomas, breast cancer, brain tumors, adrenal carcinomas).

Answer 105

Li-Fraumeni syndrome

Question 106

Activating mutations of BRAF are responsible for most cases of __ __ __, a B-cell neoplasm that typically presents in older patients with __, __ and __ (eg, fatigue, recurrent infections). It is also present in many cases of malignant melanoma.

Answer 106

hairy cell leukemia

pancytopenia, splenomegaly, and systemic symptoms

Question 107

Activating mutations in the ___ proto-oncogene are common in colorectal cancer and non-small cell lung cancer. __ encodes for a ___ that relays cellular growth and proliferation signals from outside the cell.

Answer 107

KRAS proto-oncogene

KRAS encodes for a GTPase

Question 108

Germ-line mutations of the __ proto-oncogene cause multiple endocrine neoplasia type 2, which is associated with NAME: 4 conditions

Answer 108

RET proto-oncogene

pheochromocytoma, medullary thyroid cancer, parathyroid hyperplasia, and/or mucosal neuromas.

Question 109

___ is the most common primary bone malignancy in children and young adults. It occurs most frequently at the _____ of long bones and presents with local pain and swelling. Most cases are associated with sporadic or inherited mutations in NAME 2 genes:;

Answer 109

Osteosarcoma

metaphyses of long bones

RB1 (hereditary retinoblastoma)

and

TP53 (Li-Fraumeni syndrome).

Question 110

BRCA1 and BRCA2 are involved in repair of __-__ ___ breaks.

Answer 110

double-stranded DNA breaks

Question 111

Both BRCA mutations are inherited in an __ dominant manner with variable penetrance.

Affected women have a __ to __% __ risk for developing breast cancer. Moreover, their lifetime risk of developing ovarian cancer is also increased by up to __ %, although the __ __ is less likely to lead to ovarian cancer.

Answer 111

autosomal dominant

70%-80% lifetime risk

40%

BRCA2 gene

Question 112

Unlike BRCA1 and BRCA2, HER2 mutations are __ and not ___.

Answer 112

HER2 mutations are acquired, not inherited.

Question 113

Hereditary breast cancer is most commonly associated with mutations in __ and __. These tumor suppressor genes are involved in DNA repair, and their mutations increase the risk of developing breast and ovarian cancer.

Answer 113

BRCA1 and BRCA2 tumor suppressor genes

Question 114

Liquefactive necrosis

Etiology and Morphology

Answer 114

E: Severe bacterial infections (eg, gangrene)

CNS infarcts

M: Necrotic tissue is digested by hydrolytic enzymes into a viscous fluid: Infected abscess fluid is creamy yellow due to dead leukocytes (pus) Brain infarcts resolve into CSF-filled spaces

Question 115

Fibrinoid necrosis

Etiology and Morphology

Answer 115

E: Hypertension

Vasculitis

M: Damaged vessels leak fibrin/immune complexes Eosinophilic layer of proteinaceous material in vessel walls

Question 116

Etiology and Morphology

Fat necrosis

Answer 116

E: Acute pancreatitis Trauma (subcutaneous adipose tissue)

M:

Free fatty acids released by active enzymes (eg, lipases) or mechanical damage

Fatty acids combine with calcium, forming chalky-white deposits (saponification)

Question 117

Etiology and Morphology

Caseous necrosis

Answer 117

E:

Mycobacterial infections

Fungal infections (eg, Histoplasma, Cryptococcus, Coccidioides)

M:

Friable, cheeselike material composed of cell fragments & amorphous proteinaceous debris

Surrounded by epithelioid macrophages & giant cells (granuloma)

Question 118

Etiology and Morphology

Coagulative necrosis

Answer 118

E: Irreversible ischemic injury outside CNS

M: Tissue architecture is preserved due to denaturation of lytic enzymes: Cells are anucleate with eosinophilic cytoplasm Leukocytes eventually infiltrate & digest necrotic tissue

Question 119

Membranous Nephropathy (MN)

define:

Answer 119

a kidney disease that affects the filters (glomeruli) of the kidney and can cause protein in the urine, as well as decreased kidney function and swelling. It can sometimes be called membranous glomerulopathy as well.

Membranous nephropathy is one of the most common causes of the nephrotic syndrome in adults.

Membranous nephropathy is considered an autoimmune disease.

Question 120

Nephrotic syndrome

Answer 120

Nephrotic syndrome includes significant amounts of protein in the urine (at least 3.5 grams per day), low blood protein (albumin) levels, and swelling (edema).

Question 121

Membranous Nephropathy (MN)

Caused by:

Answer 121

MN is caused by the build-up of immune complexes within the filters (glomeruli) of the kidney itself.

The immune system normally creates antibodies to recognize and attach to something (called an antigen). When an antibody attaches to an antigen, this is called an immune complex.

Antigens are normally foreign to the body, like a virus or bacteria.

Question 122

When the humidity and temperature are favorable, specific strains of the fungi __ __ and ___ parasiticus grow on foods such as corn, soybeans, and peanuts, producing aflatoxins as a byproduct.

These aflatoxins are categorized as __,__,__ and __ with aflatoxin __ the most common and most toxic.

Answer 122

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.

These aflatoxins are categorized as A1, B2, G1, and G2, with aflatoxin B1 the most common and most toxic.

Question 123

High levels of dietary aflatoxin intake have been strongly associated with __ __.

Answer 123

High levels of dietary aflatoxin intake have been strongly associated with hepatocellular carcinoma.

Question 124

High levels of dietary aflatoxin exposure is associated with a _ → _transversion in codon 249 of the __ gene, a mutation thought to greatly increase the risk of developing hepatocellular carcinoma.

Answer 124

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 hepatocellular carcinoma.

Question 125

Two types of genes can be altered to increase malignant potential:

Answer 125

Protooncogenes (eg, RET), which require gain-of-function mutations to convert to oncogenes. They typically encode proteins that promote cell division (eg, growth factors, receptors, signal transduction factors). Only one allele must be damaged to increase the risk of cancer formation.

Tumor suppressor genes (eg, TP53, RB), in which loss of function results in unregulated growth. They typically encode proteins involved in apoptosis or inhibition of cell cycle progression; both alleles must be inactivated to increase the risk of malignancy.

Question 126

__ __ __ (__) is implicated in several types of cancer, including head and neck, cervical, anal, and penile cancer.

__ produces viral oncoproteins E6 and E7, both of which affect tumor suppressors:

Answer 126

Human papillomavirus (HPV) is implicated in several types of cancer, including head and neck, cervical, anal, and penile cancer.

HPV produces viral oncoproteins E6 and E7, both of which affect tumor suppressors:

Question 127

HPV viral protein __ binds to __, a tumor suppressor protein that normally inhibits the proliferation of cells with genetic abnormalities.

___ of the __-__complex induces degradation of p53, leading to unregulated cellular growth.

Answer 127

HPV viral protein E6 binds to p53, a tumor suppressor protein that normally inhibits the proliferation of cells with genetic abnormalities.

Ubiquitination of the E6-p53 complex induces degradation of p53, leading to unregulated cellular growth.

Question 128

HPV viral protein E7 binds to __ (__) protein, which results in the displacement of __ (a transcription factor that induces cell cycle activation), promoting unregulated DNA replication and cyclin-mediated cell cycling.

Answer 128

HPV viral protein E7 binds to retinoblastoma (Rb) protein, which results in the displacement of E2F (a transcription factor that induces cell cycle activation), promoting unregulated DNA replication and cyclin-mediated cell cycling.

Question 129

E2F

Answer 129

E2F

(a transcription factor that induces cell cycle activation),

Question 130

__ encodes for a serine/threonine–specific protein kinase involved in regulating the mitogen-activated protein kinase signaling pathway.

It is often mutated in : Name 3

Answer 130

BRAF encodes for a serine/threonine–specific protein kinase involved in regulating the mitogen-activated protein kinase signaling pathway.

It is often mutated in:

melanoma

non-Hodgkin lymphoma

papillary thyroid cancer

Question 131

RET encodes for a receptor tyrosine kinase and is associated with NAME 3…

Both__ and ___ are protooncogenes that require gain-of-function mutations to become oncogenes.

Decreased activity can protect against uncontrolled proliferation (eg, BRAF inhibitors used in melanoma).

Answer 131

RET encodes for a receptor tyrosine kinase and is associated with multiple endocrine neoplasia (MEN) 2A, MEN 2B, and papillary thyroid cancer.

Both RET and BRAF are protooncogenes that require gain-of-function mutations to become oncogenes.

Decreased activity can protect against uncontrolled proliferation (eg, BRAF inhibitors used in melanoma).

Question 132

BRCA1 and BRCA2 (associated with __,__,__cancers) encode a DNA repair protein

Answer 132

BRCA1 and BRCA2 (associated with breast, ovarian, and pancreatic cancers) encode a DNA repair protein

Question 133

Both BRCA1/2 and MEN1 are __ __ genes, meaning that their inactivation (rather than overexpression) leads to tumor development.

Answer 133

Both BRCA1/2 and MEN1 are tumor suppressor genes, meaning that their inactivation (rather than overexpression) leads to tumor development.

Question 134

Inactivation of__ protein activity by human papillomavirus can lead to the formation of head and neck squamous cell carcinoma.

Answer 134

Inactivation of retinoblastoma protein activity by human papillomavirus can lead to the formation of head and neck squamous cell carcinoma.

Question 135

An increase in the activity of enzymes responsible for DNA synthesis (eg, __,__) signifies that the cell is in the S phase of the cell cycle.

Answer 135

An increase in the activity of enzymes responsible for DNA synthesis (eg, dihydrofolate reductase, DNA polymerase) signifies that the cell is in the S phase of the cell cycle.

Question 136

Retinoblastoma (Rb) protein is a regulator of the_/_ phase transition.

The Rb protein has two forms, active (__) or inactive (__).

Answer 136

Retinoblastoma (Rb) protein is a regulator of the G1/S phase transition.

The Rb protein has two forms, active (dephosphorylated) or inactive (phosphorylated).

Question 137

When the cell is stimulated by growth factors, activation of cyclin __, cyclin __, and the corresponding cyclin ____ (CDK 4 and 2) occurs and the Rb protein is ___ (rendering it inactive).

Phosphorylated Rb releases the __ __ factor, which allows progression through the__/__checkpoint.

After the cell divides, Rb protein is __ (active) and remains so until the cell is ready to enter S phase again.

Answer 137

When the cell is stimulated by growth factors, activation of cyclin D, cyclin E, and the corresponding cyclin kinases (CDK 4 and 2) occurs and the Rb protein is phosphorylated (rendering it inactive).

Phosphorylated Rb releases the E2F transcription factor, which allows progression through the G1/S checkpoint. After the cell divides, Rb protein is dephosphorylated (active) and remains so until the cell is ready to enter S phase again.

Question 138

In terminally differentiated cells, the Rb protein stays in the__ (active) state bound to __transcription factors, resulting in inhibited transcription of genes necessary for__ transition.

Therefore, active Rb protein stops the cell from dividing and allows the cell to enter a quiescent (G0) phase.

Answer 138

In terminally differentiated cells, the Rb protein stays in the dephosphorylated (active) state bound to E2F transcription factors, resulting in inhibited transcription of genes necessary for G1/S transition.

Therefore, active Rb protein stops the cell from dividing and allows the cell to enter a quiescent (G0) phase.

Question 139

__ are cysteine proteases, enzymes essential for apoptosis.__ are not associated with the G1/S transition in the cell cycle.

Answer 139

Caspases are cysteine proteases, enzymes essential for apoptosis. Caspases are not associated with the G1/S transition in the cell cycle.

Question 140

__ and __ polymerase are enzymes involved in DNA synthesis, which occurs during the S phase of the cell cycle.

The Rb protein, in its active (dephosphorylated) form, regulates cell cycle progression by preventing the transition from the __ phase to the __ phase.

__ of the Rb protein inactivates it, allowing cells to progress through the G1/S checkpoint and proliferate.

Answer 140

Dihydrofolate reductase and DNA polymerase are enzymes involved in DNA synthesis, which occurs during the S phase of the cell cycle.

The Rb protein, in its active (dephosphorylated) form, regulates cell cycle progression by preventing the transition from the G1 phase to the S phase.

Phosphorylation of the Rb protein inactivates it, allowing cells to progress through the G1/S checkpoint and proliferate.

Question 141

Ras protein is a component of the __-__signal transduction system.

It transmits growth signals from cell surface receptors into the nucleus, leading to the transcription of cyclin_ complexes.

Although involved in cell cycle progression, Ras protein signaling would occur before phosphorylation of __ __and would not immediately precede the S phase.

Answer 141

Ras protein is a component of the MAP-kinase signal transduction system.

It transmits growth signals from cell surface receptors into the nucleus, leading to the transcription of cyclin D complexes.

Although involved in cell cycle progression, Ras protein signaling would occur before phosphorylation of RB protein and would not immediately precede the S phase.

Question 142

The__ protein is a cell cycle inhibitor.

It acts during the G1 phase by inhibiting__-__ kinases. Normal tissues (composed primarily of differentiated cells) contain high levels of __, and malignant tissues contain very low levels of p__. Upregulation of__ would stop the cell cycle.

Answer 142

The p27 protein is a cell cycle inhibitor.

It acts during the G1 phase by inhibiting cyclin-dependent kinases. Normal tissues (composed primarily of differentiated cells) contain high levels of p27, and malignant tissues contain very low levels of p27. Upregulation of p27 would stop the cell cycle.

Question 143

P53

Answer 143

Tummor suppressor gene

which inhibits replication and induces apoptosis of the affected cell.

Question 144

__ __ cells divide continuously to produce new intestinal epithelial cells, which have a short life span and are completely renewed every __-__ days.

Rapid denudation of the gastrointestinal mucosa can occur if the radiation dose is significant, resulting in nausea/vomiting, diarrhea, and gastrointestinal bleeding.

Answer 144

Intestinal crypt stem cells divide continuously to produce new intestinal epithelial cells, which have a short life span and are completely renewed every 3-5 days.

Rapid denudation of the gastrointestinal mucosa can occur if the radiation dose is significant, resulting in nausea/vomiting, diarrhea, and gastrointestinal bleeding.

Question 145

Other cells that are highly sensitive to the effects of ionizing radiation include the following:

Answer 145

Bone marrow: hematopoietic progenitors (pancytopenia)

Gonads: spermatogonia (infertility)

Skin: basal keratinocytes, hair follicle stem cells (desquamation, hair loss)

Question 146

Ionizing radiation induces DNA damage (eg, double-strand breakage, free radical generation) that predominantly affects highly proliferative cells (eg,__ __, __ __,__ __ __).

These rapidly dividing cells are the first to be lost following significant radiation exposure, resulting in hair loss, pancytopenia, diarrhea, and nausea/vomiting.

Answer 146

Ionizing radiation induces DNA damage (eg, double-strand breakage, free radical generation) that predominantly affects highly proliferative cells:

(eg, skin stem cells, hematogenous progenitors, intestinal crypt cells).

These rapidly dividing cells are the first to be lost following significant radiation exposure, resulting in hair loss, pancytopenia, diarrhea, and nausea/vomiting.

Question 147

anti-apoptotic proteins __ and __

Answer 147

anti-apoptotic proteins Bcl-2 and Bcl-x

Question 148

pro-apoptotic proteins such as __,__, and __

Answer 148

pro-apoptotic proteins such as Bak, Bax, and Bim

Question 149

The pro-apoptotic proteins (name 3) allow for the increased permeability of the mitochondria, which results in the release of caspase-activating substances like __ __.

Answer 149

The pro-apoptotic proteins (eg: Bak, Bax, and Bim) allow for the increased permeability of the mitochondria, which results in the release of caspase-activating substances like cytochrome c.

Question 150

Hemosiderin accumulation is common in patients who have __ __ or who undergo frequent blood transfusions.

Answer 150

Hemosiderin accumulation is common in patients who have hemolytic anemia or who undergo frequent blood transfusions.

Question 151

The __ __ requires engagement of death receptors on the cell surface. These death receptors are in the tumor necrosis factor receptor family, with the type _ __ __(_ _ _ _ _) and a related protein named ___ (CD_) the two best known members of this family.

After cross-linkage of __ with its ligand, multiple molecules of __ come together to form a binding site for a death-domain containing adapter protein called __ __ __ __. __ __ __ __ then binds an inactive form of a caspase, again bringing multiple caspase proteins together that through a cascade effect eventually induce caspase activation.

Answer 151

The extrinsic pathway requires engagement of death receptors on the cell surface. These death receptors are in the tumor necrosis factor receptor family, with the type 1 TNF receptor (TNFR1) and a related protein named Fas (CD95) the two best known members of this family.

After cross-linkage of Fas with its ligand, multiple molecules of Fas come together to form a binding site for a death-domain containing adapter protein called FADD. FADD then binds an inactive form of a caspase, again bringing multiple caspase proteins together that through a cascade effect eventually induce caspase activation.

Question 152

__ __ is a mitochondrial enzyme in the electron transport chain that acts by oxidizing succinate into fumarate and reducing _ __ __ to __ __ __ __ __ . This enzyme is not involved in apoptosis.

Answer 152

Succinate dehydrogenase is a mitochondrial enzyme in the electron transport chain that acts by oxidizing succinate into fumarate and reducing FAD to FADH2. This enzyme is not involved in apoptosis.

Question 153

Superoxide dismutase catalyzes the reduction of __ __ to __ __.

This enzyme is not involved in apoptosis.

Answer 153

Superoxide dismutase catalyzes the reduction of superoxide anions to hydrogen peroxide.

This enzyme is not involved in apoptosis.

Question 154

__ plays a key role in the synthesis of leukotrienes, a class of inflammatory mediators.

Answer 154

Lipoxygenase plays a key role in the synthesis of leukotrienes, a class of inflammatory mediators.

Question 155

Cytochrome c is a mitochondrial enzyme that activates __ and indirectly brings about cell death through __ pathway apoptosis.

Answer 155

Cytochrome c is a mitochondrial enzyme that activates caspases and indirectly brings about cell death through intrinsic pathway apoptosis.

Question 156

The esophagus is normally lined by __ __ __ epithelium.

Answer 156

The esophagus is normally lined by nonkeratinized, stratified squamous epithelium.

Question 157

The substitution of one differentiated epithelial cell type for another in response to adverse environmental conditions is called _____.

Answer 157

The substitution of one differentiated epithelial cell type for another in response to adverse environmental conditions is called metaplasia.

Question 158

the metaplasia seen in the distal esophagus in response to chronic acid exposure __ __ is associated with a high risk of malignant transformation into __ __

Answer 158

the metaplasia seen in the distal esophagus in response to chronic acid exposure (Barrett esophagus) is associated with a high risk of malignant transformation into esophageal adenocarcinoma.

Question 159

__is characterized by hyperplasia, an increase in the number of cells within a tissue due to hormones or growth factors.

Histology will show hyperproliferation of the dermis with epidermal thickening (__) and prolonged downward thickenings between dermal papillae (“__ __”).

Answer 159

Psoriasis is characterized by hyperplasia, an increase in the number of cells within a tissue due to hormones or growth factors.

Histology will show hyperproliferation of the dermis with epidermal thickening (acanthosis) and prolonged downward thickenings between dermal papillae (“rete ridges”).

Question 160

Irregular moles (eg, __, __ __) are likely to contain dysplastic cells.

__ is characterized by abnormal epithelial cellular architecture and irregular cellular growth.

In __a, one mature, differentiated cell type is replaced by another.

Answer 160

Irregular moles (eg, melanoma, atypical mole) are likely to contain dysplastic cells.

Dysplasia is characterized by abnormal epithelial cellular architecture and irregular cellular growth.

In metaplasia, one mature, differentiated cell type is replaced by another.

Question 161

___ is often seen in the bronchi of chronic cigarette smokers (substitution of ciliated columnar epithelium with stratified squamous cells) and the distal esophagus of patients with chronic gastroesophageal reflux (substitution of stratified squamous epithelium with intestinal columnar cells).

Metaplasia can lead to subsequent __and malignant transformation.

Answer 161

Metaplasia is often seen in the bronchi of chronic cigarette smokers (substitution of ciliated columnar epithelium with stratified squamous cells) and the distal esophagus of patients with chronic gastroesophageal reflux (substitution of stratified squamous epithelium with intestinal columnar cells).

Metaplasia can lead to subsequent dysplasia and malignant transformation.

Question 162

This patient who has recurrent abdominal pain and bloody diarrhea with CT evidence of bowel wall thickening in the distal colon and rectum

likely has __ __

Answer 162

This patient who has recurrent abdominal pain and bloody diarrhea with CT evidence of bowel wall thickening in the distal colon and rectum likely has ulcerative colitis.

Question 163

Chronic inflammatory conditions are characterized by the persistent stimulation of __ and __, leading to long-term elevation of circulating pro-inflammatory cytokines such as: Name 4

Answer 163

Chronic inflammatory conditions are characterized by the persistent stimulation of neutrophils and macrophages, leading to long-term elevation of circulating pro-inflammatory cytokines such as:

IL-1, IL-6

tumor necrosis factor-alpha

interferon-gamma.

Question 164

The liver responds to these circulating cytokines (particularly __ by generating __ __ __ , proteins that modulate and influence the inflammatory response and play some role in innate immunity.

Testing for acute phase reactants can help diagnose and track conditions associated with NAME: 4

Answer 164

The liver responds to these circulating cytokines (particularly IL-6) by generating acute phase reactants, proteins that modulate and influence the inflammatory response and play some role in innate immunity.

Testing for acute phase reactants can help diagnose and track conditions associated with:

inflammation, infections,

autoimmune diseases, malignancies

Question 165

___ is a component of the kinin system. It is a short-lived peptide that causes vasodilation, increases vascular permeability, stimulates endothelial smooth muscle dilation, and mediates pain.

Answer 165

Bradykinin is a component of the kinin system. It is a short-lived peptide that causes vasodilation, increases vascular permeability, stimulates endothelial smooth muscle dilation, and mediates pain.

Question 166

Bradykinin is a component of the kinin system. It is a short-lived peptide that causes ___

and increases

Name: 3

Answer 166

vasodilation.

vascular permeability

stimulates endothelial smooth muscle dilation

mediates pain.

Question 167

___ is a growth factor for erythrocyte precursors in the bone marrow. It is produced by ___cells of the __ in response to hypoxia.

Answer 167

Erythropoietin is a growth factor for erythrocyte precursors in the bone marrow. It is produced by peritubular cells of the kidneys in response to hypoxia.

Question 168

__ __ is a metabolite of arachidonic acid. Its main function is to stimulate neutrophil migration to the site of inflammation.

Answer 168

Leukotriene B4 is a metabolite of arachidonic acid. Its main function is to stimulate neutrophil migration to the site of inflammation.

Question 169

Platelet-activating factor is released by __, __, and __ __ and is involved in leukocyte function (eg, endothelium attachment, phagocytosis, degranulation), platelet stimulation, and changes to vascular tone and permeability

Answer 169

Platelet-activating factor is released by endothelium, platelets, and immune cells, and is involved in leukocyte function (eg, endothelium attachment, phagocytosis, degranulation), platelet stimulation, and changes to vascular tone and permeability

Question 170

__ __ is one of the products of the cyclooxygenase pathway. It is synthesized by __ and causes platelet activation and aggregation. It does not cause erythrocyte aggregation or rouleaux formation.

Answer 170

Thromboxane A2 is one of the products of the cyclooxygenase pathway. It is synthesized by platelets and causes platelet activation and aggregation. It does not cause erythrocyte aggregation or rouleaux formation.

Question 171

Chronic inflammation is associated with increased circulating __-__ __ (eg, IL-1, IL-6, tumor necrosis factor-alpha), which stimulates the liver to release acute-phase reactants (eg, _-__ __, __).

The presence of acute-phase reactants increases the __ __ rate, a nonspecific marker for inflammation

Answer 171

Chronic inflammation is associated with increased circulating pro-inflammatory cytokines (eg, IL-1, IL-6, tumor necrosis factor-alpha), which stimulates the liver to release acute-phase reactants (eg, C-reactive protein, fibrinogen).

The presence of acute-phase reactants increases the erythrocyte sedimentation rate, a nonspecific marker for inflammation

Question 172

Acute wounds

This process involves activation and recruitment of different cell types during 4 sequential (but overlapping) phases:

Answer 172

hemostasis, inflammation, proliferation, and maturation.

Question 173

____ which occurs immediately after tissue injury, involves small vessel constriction, platelet aggregation, and clotting cascade activation that leads to platelet plugging, fibrin clot formation, and cessation of bleeding.

Answer 173

Hemostasis, which occurs immediately after tissue injury, involves small vessel constriction, platelet aggregation, and clotting cascade activation that leads to platelet plugging, fibrin clot formation, and cessation of bleeding. For relatively minor injuries, hemostasis is often accomplished within minutes.

The fibrin clot that is formed during this phase provides a scaffold for subsequent wound healing

Question 174

___ usually starts within hours of injury. During this phase, __ __ degranulate, releasing histamine and other chemical mediators that increase vascular permeability and promote cellular infiltration (eg,__,__).

Neutrophils digest __, __tissue, and__ debris.

Monocytes are transformed into __, which secrete growth factors (eg, NAME 2) that promote the next phase of healing.

Answer 174

• Inflammation* usually starts within hours of injury. During this phase, mast cells degranulate,releasing histamine and other chemical mediators that increase vascular permeability and promote cellular infiltration (eg,neutrophils, monocytes).
• Neutrophils* digest bacteria, necrotic tissue, and foreign debris.
• Monocytes* are transformed into macrophages, which secrete growth factors (eg, transforming growth factor-beta, vascular endothelial growth factor) that promote the next phase of healing.

Question 175

___, which begins during the inflammatory phase and continues for weeks afterward, leads to replacement of injured or missing tissue via the following:

Answer 175

Proliferation,

Epithelization: Basal keratinocyte proliferation and migration of new epithelial cells form a new superficial epithelial layer that acts as a barrier to bacteria.

Fibroplasia: Fibroblasts proliferate and synthesize ground substance and collagen, forming a matrix into which capillaries can grow. Simultaneous contraction of myofibroblasts (ie, differentiated fibroblasts that produce contractile proteins) helps decrease the wound size.

Angiogenesis: Proliferation and migration of endothelial cells from nearby blood vessels lead to ingrowth of new capillaries into the collagen matrix.

Question 176

____ the final phase of wound healing, results in ___ __ and __-__ , which are the primary mechanisms by which the tensile strength of the wound increases.

Answer 176

Maturation, the final phase of wound healing, results in collagen remodeling and cross-linking, which are the primary mechanisms by which the tensile strength of the wound increases.

Question 177

Wounds typically heal according to an organized sequence of 4 phases:

Answer 177

hemostasis (fibrin clot formation)

inflammation (cellular infiltration)

proliferation (reepithelization, fibroplasia, and angiogenesis)

maturation (collagen remodeling).

Question 178

__ __-__ _ is part of a family of transcription factors that perform a critical role in the immune response to infection and inflammation.

Answer 178

Nuclear factor-kappa B (NF-κB) is part of a family of transcription factors that perform a critical role in the immune response to infection and inflammation.

Question 179

__ __-__ __ (G-CSF) is the principal protein that stimulates the production and release of neutrophils from the bone marrow.

Answer 179

Granulocyte colony-stimulating factor (G-CSF) is the principal protein that stimulates the production and release of neutrophils from the bone marrow.

Question 180

__ __ __-_ (__-_) plays a major role in the response to infection by increasing neutrophil chemotaxis and stimulating macrophage phagocytosis.

Answer 180

Tumor necrosis factor-α (TNF-α) plays a major role in the response to infection by increasing neutrophil chemotaxis and stimulating macrophage phagocytosis.

Question 181

__ __ _ is a tyrosine kinase involved in the signaling pathway for myeloproliferation. Constituent activation of ___ is associated with polycythemia vera, essential thrombocytosis, and myelofibrosis.

It does not play a major role in the immune response to infection

Answer 181

Janus kinase 2 (JAK2) is a tyrosine kinase involved in the signaling pathway for myeloproliferation. Constituent activation of JAK2 is associated with polycythemia vera, essential thrombocytosis, and myelofibrosis. It does not play a major role in the immune response to infection

Question 182

__ __-__ __ is a transcription factor with a critical role in the immune response to infection. ___ 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 __and translocation of free __-__ to the nucleus

Answer 182

.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, IκB.

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