Pathology Flashcards
(183 cards)
1
Q
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.
A
EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase).
This results in a constitutive active tyrosine kinase that causes malignancy.
2
Q
__ __ 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.
A
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.
3
Q
Patients with __ __ have a t(14;18) translocation that causes overexpression of the __ __ gene product.
A
Patients with follicular lymphoma have a t(14;18) translocation that causes overexpression of the antiapoptotic BCL2 gene product.
4
Q
__-__ 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, __
A
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.
5
Q
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.
A
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.
6
Q
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
A
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
7
Q
Ischemia causes a __ __ __ within cardiac myocytes. Elevated concentrations of __ and __ draw free water into the cells, causing edema.
A
- net solute gain*
- Na+ and Ca2+*
8
Q
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).
A
late-peaking systolic ejection murmur
left ventricular blood volume
aortic stenosis
calcific aortic valve disease
9
Q
__ 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
A
Cardiomyocyte hypertrophy and disarray
crescendo-decrescendo systolic murmurleft ventricular
10
Q
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
A
calcific aortic valve disease
arterial atherosclerosis
fibroblasts
osteoblast-like cells
valvular calcification
11
Q
patient has altered mental status and acute renal failure. In conjunction with the oxalate crystals noted on renal biopsy, this presentation is consistent with __ __
A
ethylene glycol poisoning.
12
Q
__ __ 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.
A
Ehtylene glycol
Ethanol intoxication
Oliguria, flank pain
24-72 hrs
13
Q
Ethylene glycol itself is relatively nontoxic; however, it is metabolized to __ __and __ __, resulting in its various toxicities.
A
glycolic acid and
oxalic acid
14
Q
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.
A
glycolic acid
direct tubular cytotoxicity
crystalizes
acute tubular necrosis (ATN)
cell ballooning
vascular degeneration
15
Q
__ __can cause light-chain cast nephropathy due to obstruction of the proximal tubules.
A
Multiple myeloma
16
Q
___ 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
A
Hyperparathyroidism
calcium stone
postobstructive nephropathy
blunting of calyces
17
Q
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.
A
acute tubular necrosis
vacuolar degeneration
ballooning
high anion gap metabolic acidosis
osmolar gap calcium oxalate
18
Q
Glomerulonephritis can cause __, __ and __ __ but is not associated with cyst formation. Casts are typically visible on urinalysis.
A
hematuria, hypertension, and renal failure
19
Q
Hydronephrosis can cause __ and __, particularly if associated with an __ __. However, dilation of the ureters and calyces would be __ __ imaging.
A
hematuria and pain
obstructing stone
expected on imaging
20
Q
__ (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.
A
Nephroblastoma (ex: Wilms tumor)
abdominal mass, hematuria, and hypertension
heterogenous renal mass
21
Q
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 __ __.
A
polycystin genes (PKD1, PKD2)
cystic enlargement of the kidney
renal dysfunction
hypertension, abdominal/flank, gross hematuria,intracranial aneurysms
22
Q
patient’s pale red reflex and well-circumscribed white mass within the retina are indicative of ___
A
retinoblastoma.
23
Q
Retinoblastoma is an intraocular tumor caused by inactivating mutations affecting the __ __ __ with subsequent dysregulation of the cell cycle.
A
RB1 tumor suppressor gene
24
Q
Checkpoints occur at the __ and __ transitions, allowing the cell cycle to be stopped if damaged DNA is detected by __ and __-__ __.
A
G1/S and G2/M transitions
cyclins and cyclin-dependent kinases.
25
The ***RB1 gene*** encodes the __ \_\_ that regulates the ____ checkpoint. In its\_\_ form, ***Rb protein __ and __ \_\_*** transcription factors, thereby halting the cell cycle.
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.
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.*
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.
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.
Retinoblastoma
G1/S checkpoint
unrestricted progression
G1/S
28
overexpression of __ and __ are associated with non–small cell lung cancer, and __ is associated with breast cancer.
EGFR and MET
HER2
29
overexpression of EGFR and MET are associated with \_\_-\_\_ \_\_cancer, and HER2 is associated with\_\_ \_\_
non–small cell lung
Breast Cancer
30
Abnormal ***\_\_ \_\_***function due to a ***KRAS mutatio***n prevents the conversion of __ to \_\_, which results in constant activation of the ___ pathway and ***uncontrolled cellular proliferatio***n.
\_\_ __ are associated with lung and colorectal cancers, not retinoblastoma.
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***
31
***KRAS mutations*** are associated with __ and __ \_\_ , not retinoblastoma.
***lung and colorectal cancers***
32
Tumor suppressor __ \_\_ arrests the cell cycle at the \_\_***checkpoint*** if *DNA damage is detected* and __ \_\_ \_\_if DNA repair fails.
***Protein P53*** arrests the cell cycle at the ***G1/S checkpoint*** if DNA damage is detected and ***initiates cell apoptosis*** if DNA repair fails.
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.
***Li-Fraumeni syndrome*** (sarcoma, breast, leukemia, and adrenal cancers).
## Footnote
***Rb and p53 proteins***
34
***Li-Fraumeni syndrome***
Definition and Ex's
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
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.***
***BRCA1 and BRCA2***
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 __ \_\_ \_\_
***generalized atherosclerosis***
***achronic mesenteric ischemia***
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.***
***atherosclerosis***
***within an hour after meals***
***intestinal angina***
***stable cardiac angina***
***duplex ultrasonography*** or ***angiography***
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.
aortic intimal tear
renal, splanchnic, spinal, lower limb
acute end-organ damage
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.***
***gastrointestinal erosions*** and ***ulcerations***
***Helicobacter pylori***
nonsteroidal anti-inflammatory
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 __ \_\_.
*Chronic mesenteric ischemia*
intestinal angina
angina pectoris
41
\_\_ __ \_\_ typically presents with gross hematuria and flank pain.
renal papillary necrosis
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.*
Acute tubular necrosis
oliguria, serum creatinine, muddy brown casts
renal medulla
***proximal tubule***s and ***thick ascending*** *limb of loop of Henley*
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.
colon cancer
prostate and lung
IDA
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.
Right-sided colon ( eg.ascending colon)
colonic lumen
bleed
IDA
positive fecal occult blood test
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 \_\_
left-sided tumors (rectosigmoid colon)
wall of the colon
narrowing the lumen
obstruction
abdominal distension, and nausea and vomiting
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).***
ruptured aneurysm
fibromuscular webs
internal elastic lamina
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* __ \_\_.
* fibromuscular webs alternating*
* aneurysmal dilation*
fibromuscular dysplasia (FMD).
48
***FMD*** is a __ *disease* characterized by __ \_\_ __ within *arterial wall*s, 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.*
nonatherosclerotic
abnormal tissue growth
(arterial stenosis, tortuosity, aneurysms, or dissections)
age \<55
string-of-beads
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.
renal, cerebral (eg, carotid, vertebral), and visceral
renal artery stenosis
renin-angiotensin-aldosterone system.
50
*Adrenal tumors* that can present with *severe hypertension include* (name 3)
pheochromocytoma
aldosterone- or cortisol-secreting adrenocortical adenomas.
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.
Hypertrophic cardiomyopathy
hypertrophied myocytes
***interstitial fibrosis***
hypertrophic cardiomyopathy
52
\_\_ __ \_\_ can cause ***hyperthyroidism*** (eg, \_\_,\_\_ \_\_). This commonly causes \_\_,\_\_,\_\_but would ***not cause aneurysm formation.***
Thyroid follicular hyperplasia
(Graves disease, thyroid adenoma)
tachycardia, tremor, and palpitations
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.***
Fibromuscular dysplasia
stenotic and tortuous arteries
54
Pathology of *Fibromuscular Displasia* typically demonstrates ***alternating\_\_ __ and __ dilation with absent __ \_\_ \_\_***(string-of-beads appearance).
fibromuscular webs
aneurysmal dilation
***internal elastic lamina***
55
***Renovascular hypertension*** occurs due to\_\_ __ \_\_ and *activation of* the\_\_-\_\_-\_\_ system.
renal artery stenosis
renin-angiotensin-aldosterone
56
***Petechiae*** and ***ecchymoses*** are more consistent with qualitative or quantitative __ \_\_
platelet abnormalities
57
Recurrent ***hemarthroses (bleeding into a joint cavity)*** *are* suggestive of __ (factor __ or \_\_).
***hemophilia*** (factor ***VIII or IX deficiency***)
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._***
***atherosclerosis*** and ***fibromuscular disease***
***factor V Leiden***
59
Major causes of ***splenic infarction include*** (name 3)
Moreover, the __ \_\_ \_\_mutation is associated with ***deep venous (not arterial) thrombosis.***
***sickle cell anemia, infectious endocarditis, myel******oproliferative disorders***
## Footnote
*factor V Leiden*
60
*One to nine percent* of *Caucasians worldwide* are ***heterozygote carriers of factor V Leiden***, *which is modified to resist* __ \_\_ \_\_.
The *resultin*g ***hypercoagulable state*** predisposes to __ \_\_ ***thromboses***, which are the source of ***most __ emboli.***
activated protein C
deep vein thromboses
***pulmonary emboli***
61
***Gastrointestinal blood loss*** results in \_\_, __ \_\_due to *iron deficiency*
hypochromic, microcytic anemia
62
***Red blood cell fragments, burr cells***, and ***helmet cells*** are associated with either (name 2)
In patients with ***prosthetic valve***s, __ \_\_ __ are exposed to *excessive shear* and *turbulence in the circulation*, causing damage from __ trauma.
***microangiopathic hemolytic anemia or mechanical red cell destruction.***
red blood cells
mechanical trauma
63
This patient with an ***aggressive lung cancer*** (SCLC) has symptomatic ***\_\_***(eg, confusion, lethargy) despite appearing ***euvolemic*** (\_ __ \_\_).
This presentation suggests __ \_\_ __ \_\_complicated by _ \_ _ \_\_ \_.
***hyponatremia***
***euvolemic*** (moist mucous membranes)
***small cell carcinoma of the lung***
***paraneoplastic syndrome of inappropriate antidiuretic hormone secretion (SIADH).***
64
***Small cell carcinomas*** show evidence of ***\_\_ \_\_.***. These tumors stain for ***neuroendocrine marker***s, such as (name 4).
***neuroendocrine differentiation***
neural cell adhesion molecule (CD56),
neuron-specific enolase,
chromogranin,
synaptophysin.
65
\_\_ __ can be identified in the *cytoplasm of the tumor cells on electron microscopy.*
Neurosecretory granules
66
\_\_ __ \_\_ show evidence of ***neuroendocrine differentiation.*** These tumors stain for __ \_\_, such as __ \_\_ \_***\_ molecule (CD56)***
Small cell carcinomas
neuroendocrine markers
***neural cell adhesion molecule (CD56)***
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.***
Small cell carcinoma
paraneoplastic syndromes
(SIADH, Cushing syndrome)
***neuroendocrine origin***
(eg, neural cell adhesion molecule, chromogranin, synaptophysin)
68
What does pyruvate kinase deficiency mean?
Pyruvate kinase deficiency is an ***inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells.***
69
\_\_ __ is the *enzyme responsible for the final step of glycolysis*, in which ___ is *converted to* _ with the production o***f ATP***. __ \_\_***catalyzes*** the ***last step of glycolysis*** which is important for ***generating adenosine triphosphate (ATP).***
Pyruvate kinase (PK)
phosphoenolpyruvate
pyruvate
Pyruvate kinase catalyzes
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 \_\_.
cations
insufficient ATP
water and potassium loss
Hemolysis
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 ***hyperplasi***a, resulting in\_\_.
reticuloendothelial cells
pyruvate kinase deficiency
***splenomegaly.***
72
***Passive congestion of the spleen*** with ***blood occurs in the setting of (name 3).*** Resultant __ \_\_ \_\_can lead to splenomegaly.
***portal hypertension, splenic vein thrombosis, or congestive heart failure***
splenic sinusoid dilation
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*
Pyruvate kinase deficiency
***glycolysis, ATP***
splenic hyperplasia
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 \_- \_\_).
constrictive pericarditis
chest radiation
ventricular filling
low cardiac output
hepatomegaly and peripheral edema
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.
**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***
76
*A **loud pulmonic component** of the **second heart sound (P2)** is heard in patients with __ \_\_*
*pulmonary hypertension.*
77
\_\_ __ occurs when *cardiac pathology* (eg ***name 2***) delays closure of the ***aortic valv***e, causing __ to occur noticeably later than \_\_.
***Paradoxical splitting***
(aortic stenosis, left bundle branch block)
A2 to occur, than P2
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)*
***S3 gallop***
*dilated cardiomyopathy or severe mitral regurgitation.*
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
left parasternal lift
chronic right ventricular pressure overload
volume overload
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)
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).
81
*Monoclonal immunoglobulin spikes* are found in __ \_\_.
\_\_ cells suppress ***osteoblasts*** and would cause ___ lesions. Patients commonly have what symptoms: name 3
multiple myeloma.
Myeloma cells
osteolytic lesions
***symptoms:*** bone pain, recurrent infections, and symptoms of anemia.
82
***Hematuria*** and ***polycythemia*** (due to __ \_\_) are suggestive of *renal cell cancer*. Renal cell cancer bone metastases are commonly\_\_\_.
(due to erythropoietin release)
osteolytic
83
\_\_ and __ (due to *erythropoietin release*) are suggestive of __ \_\_ cancer. __ \_\_ __ bone metastases are commonly ***osteolytic.***
Hematuria and polycythemia
renal cell cancer
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.
non-small cell lung cancer (NSCLC)
***hypercalcemia***
Osteolytic bone lesions
85
\_\_ and ___ overexpression are found in lymphomas.
Lymphadenopathy and BCL-2
86
\_\_\_ is an *anti-apoptosis factor*, and overexpression plays a role in *resistance to chemotherapy.*
Common manifestations of lymphoma also include: Name 3
BCL-2
night sweats, weight loss, and fatigue.
87
A *rapidly enlarging irregular mole* is *suggestive of a \_\_\_\_.* The \_\_, __ , __ are the *most common metastatic sites.*
\_\_\_ causes ***lytic bone lesions.***
*melanoma*.
liver, bone, and brain
Melanoma
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* __ \_\_.
Bone metastases
prostate cancer.
89
Proto-oncogenes
1-hit GAIN of function
## Footnote
***RAS
(GTP binding protein)***
Cholangiocarcinoma
Pancreatic adenocarcinoma
90
Proto-oncogenes
1-hit GAIN of function
## Footnote
***MYC
(Transcription factor)***
Burkitt lymphoma
91
Proto-oncogenes
1-hit GAIN of function
## Footnote
***ERBB1 (EGFR)
(Receptor tyrosine kinase)***
Lung adenocarcinoma
92
Proto-oncogenes
1-hit GAIN of function
## Footnote
***ERBB2 (HER2)
(Receptor tyrosine kinase)***
Breast cancer
93
Proto-oncogenes
1-hit GAIN of function
## Footnote
***ABL
(Nonreceptor tyrosine kinase)***
Chronic myelogenous leukemia
94
Proto-oncogenes
1-hit GAIN of function
## Footnote
***BRAF
(Ras signal transduction)***
Hairy cell leukemia
Melanoma
95
Tumor suppressor genes
2-hit LOSS of function
## Footnote
***BRCA1/2
(DNA repair genes)***
Breast & ovarian cancer
96
Tumor suppressor genes
2-hit LOSS of function
## Footnote
***APC/β-catenin (Wnt signaling pathway)***
Colon, gastric & pancreatic cancer
Familial adenomatous polyposis
97
Tumor suppressor genes
2-hit LOSS of function
## Footnote
***TP53
(Genomic stability)***
Most cancers
Li-Fraumeni syndrome
98
Tumor suppressor genes
2-hit LOSS of function
## Footnote
***RB
(G1/S transition inhibitor)gtpv***
Retinoblastoma
Osteosarcoma
99
Tumor suppressor genes
2-hit LOSS of function
## Footnote
***WT1
(Urogenital differentiation***
Wilms tumor
100
Tumor suppressor genes
2-hit LOSS of function
## Footnote
***VHL
(Ubiquitin ligase component)***
Renal cell carcinoma
Von Hippel-Lindau syndrome
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.***
osteosarcoma
metaphysis of long bones
102
Osteosarcomas typically form when a __ \_***\_ cell*** develops mutations in the following genes: Name 2
* mesenchymal stem cell*
* 1. RB1 Tumor suppressor gene*
* 2. TP53 tumor suppressor gene*
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:
RB1 tumor suppressor gene
RB1
***osteosarcoma, retinoblastoma, melanoma, and soft-tissue sarcomas***
104
\_\_ __ suppressor gene, which encodes for ***P53***, a protein that *regulates \_\_-\_\_ \_\_* and *maintains\_\_ __ by **activating DNA repair*** following damage.
TP53 tumor suppressor gene
## Footnote
* regulates cell-cycle progression*
* and*
* maintains genomic integrity*
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)*.
***Li-Fraumeni syndrome***
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.***
hairy cell leukemia
pancytopenia, splenomegaly, and systemic symptoms
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.*
KRAS proto-oncogene
KRAS encodes for a GTPase
108
*Germ-line mutations* of the __ proto-oncogene cause ***multiple endocrine neoplasia type 2,*** which is associated with NAME: 4 conditions
RET proto-oncogene
pheochromocytoma, medullary thyroid cancer, parathyroid hyperplasia, and/or mucosal neuromas.
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:;
Osteosarcoma
metaphyses of long bones
***RB1*** (hereditary retinoblastoma)
and
***TP53*** (Li-Fraumeni syndrome).
110
BRCA1 and BRCA2 are involved in repair of \_\_-\_\_ ___ breaks.
double-stranded DNA breaks
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.***
autosomal dominant
70%-80% lifetime risk
40%
BRCA2 gene
112
Unlike BRCA1 and BRCA2, ***HER2 mutations*** are __ and not \_\_\_.
***HER2 mutations*** are ***acquired, not inherited.***
113
***Hereditary breast cancer*** is most commonly associated with mutations in __ and \_\_. These ***tumor suppressor genes*** are involved in ***DNA repai***r, and their mutations increase the risk of developing *breast and ovarian cancer.*
BRCA1 and BRCA2 tumor suppressor genes
114
***Liquefactive necrosis***
Etiology and Morphology
**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
115
***Fibrinoid necrosis***
*Etiology and Morphology*
**E:** Hypertension
Vasculitis
**M:** Damaged vessels leak fibrin/immune complexes Eosinophilic layer of proteinaceous material in vessel walls
116
*Etiology and Morphology*
***Fat necrosis***
**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)
117
*Etiology and Morphology*
***Caseous necrosis***
***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)
118
*Etiology and Morphology*
***Coagulative necrosis***
**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
119
***Membranous Nephropathy (MN)***
define:
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.
120
***Nephrotic syndrome***
***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).
121
Membranous Nephropathy (MN)
Caused by:
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.
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 ***aflatoxin***s are categorized as \_\_,\_\_,\_\_ and __ with aflatoxin __ the most common and most toxic.
When the humidity and temperature are favorable, specific strains of the fungi ***Aspergillus flavu***s 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.
123
High levels of dietary aflatoxin intake have been strongly associated with __ \_\_.
High levels of dietary aflatoxin intake have been strongly associated with ***hepatocellular carcinoma.***
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.***
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.*
125
***Two types of genes*** can be altered to increase malignant potential:
***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.
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:
***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:
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.*
*HPV viral protein* ***E6*** *binds t*o ***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.*
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.
*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.
129
***E2F***
*E2F*
## Footnote
***(a transcription factor that induces cell cycle activation),***
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***
***BRAF*** encodes for a serine/threonine–specific protein kinase involved in regulating the mitogen-activated protein kinase signaling pathway.
## Footnote
*It is often mutated in:*
***melanoma***
***non-Hodgkin lymphoma***
***papillary thyroid cancer***
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).
***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).
132
***BRCA1*** and ***BRCA2*** (associated with \_\_,\_\_,\_\_cancers) encode a ***DNA repair protein***
BRCA1 and BRCA2 ***(****associated with* ***breast, ovarian, and pancreatic cancers***) encode a DNA repair protein
133
Both ***BRCA1/2 and MEN1*** are __ \_\_ genes, meaning that their *inactivation* (rather than overexpression) ***leads to tumor development.***
Both BRCA1/2 and MEN1 are ***tumor suppressor genes,*** meaning that their ***inactivation*** (rather than overexpression) ***leads to tumor development.***
134
*Inactivation* of\_\_ protein activity by ***human papillomavirus*** can lead to the formation of ***head and neck squamous cell carcinoma.***
*Inactivation* of ***retinoblastoma protein*** activity by *_human papillomavirus_* can lead to the formation o***f head and neck squamous cell carcinoma.***
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.*
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.
136
***Retinoblastoma (Rb) protein*** is a regulator of the\_/\_ phase transition.
The *Rb protein has two forms*, ***active*** (\_\_) or ***inactive*** (\_\_).
R*etinoblastoma (Rb) protein* is a regulator of the ***G1/S*** *phase transition.*
The *Rb protein has two forms, active* (***dephosphorylated)*** or *inactive **(phosphorylated).***
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.
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 throug*h 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.
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.
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.
139
\_\_ are cysteine proteases, enzymes essential for apoptosis.\_\_ are not associated with the G1/S transition in the cell cycle.
***Caspases*** are cysteine proteases, enzymes essential for apoptosis. ***Caspases*** are not associated with the G1/S transition in the cell cycle.
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.*
***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.*
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.***
*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.***
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.
The ***p27 protein*** is a cell c*ycle 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.
143
***P53***
*Tummor suppressor gene*
which i***nhibits replication*** and ***induces apoptosis*** of the affected cell.
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.
***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.
145
*Other cells that are highly sensitive to the effects of ionizing radiation include the following:*
***Bone marrow:*** hematopoietic progenitors (pancytopenia)
***Gonads:*** spermatogonia (infertility)
***Skin:*** basal keratinocytes, hair follicle stem cells (desquamation, hair loss)
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.*
***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.***
147
anti-apoptotic proteins __ and \_\_
anti-apoptotic proteins ***Bcl-2 and Bcl-x***
148
pro-apoptotic proteins such as \_\_,\_\_, and \_\_
pro-apoptotic proteins such as ***Bak, Bax, and Bim***
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 __ \_\_.
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.***
150
***Hemosiderin accumulation*** is common in patients who have __ \_\_ or who undergo frequent blood transfusions.
***Hemosiderin accumulation*** is common in patients who have ***hemolytic anemia*** or who undergo frequent blood transfusions.
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.*
The ***extrinsic pathway*** r*equires 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.*
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.
***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.
153
***Superoxide dismutase*** *catalyzes the reduction of* __ \_\_ to __ \_\_.
This enzyme is not involved in apoptosis.
*Superoxide dismutase* catalyzes the reduction of ***superoxide anions*** to ***hydrogen peroxide***.
This enzyme is not involved in apoptosis.
154
\_\_ plays a key role in the ***synthesis of leukotrienes,*** a *class of inflammatory mediators.*
***Lipoxygenase*** plays a key role in the ***synthesis of leukotrienes***, a *class of inflammatory mediators.*
155
***Cytochrome c*** is a *mitochondrial enzyme t*hat activates __ and indirectly brings about cell death through __ *pathway apoptosis.*
***Cytochrome c*** is a *mitochondrial enzyme* that *activates **caspases*** and indirectly brings about cell death through ***intrinsic*** pathway apoptosis.
156
The ***esophagus*** is normally lined by __ \_\_ __ epithelium.
The *esophagus* is normally lined by ***nonkeratinized, stratified squamous epithelium.***
157
The substitution of one differentiated epithelial cell type for another in response to adverse environmental conditions is called \_\_\_\_\_.
The substitution of one differentiated epithelial cell type for another in response to adverse environmental conditions is called ***metaplasia.***
158
the *metaplasia seen in the distal esophagus* in response to *chronic acid exposure* ***\_\_ \_\_*** is associated with a high risk of malignant transformation into __ \_\_
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.***
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 ("\_\_ \_\_").
***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").***
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.
*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.
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.
***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.
162
This patient who has ***recurrent abdominal pain*** and ***bloody diarrhe***a with ***CT evidence of bowel wall thickening*** in the ***distal colon and rectum***
likely has __ \_\_
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.***
163
***Chronic inflammatory condition**s* are *characterized by the persistent stimulation of* __ and \_\_, leading to *long-term elevation of circulating* pro-inflammatory cytokines such as: Name 4
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:*
## Footnote
**IL-1, _IL-6_**
**tumor necrosis factor-alpha**
**interferon-gamma.**
164
The ***liver*** *respond*s 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***
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***
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.***
*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.***
166
*Bradykinin* is a component of the kinin system. It is a short-lived peptide that causes \_\_\_
***and*** increases
Name: 3
*vasodilation.*
***vascular permeability***
***stimulates endothelial smooth muscle dilation***
***mediates pain.***
167
\_\_\_ is a growth factor for erythrocyte precursors in the bone marrow. It is produced by \_\_\_cells of the __ in response to hypoxia.
***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.
168
\_\_ __ is a ***metabolite of arachidonic acid.*** Its main function is to stimulate neutrophil migration to the site of inflammation.
***Leukotriene B4*** is a *metabolite of arachidonic acid. Its main function is to stimulate neutrophil migration to the site of inflammation.*
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
*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
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.
***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.
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
***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
172
Acute wounds
This process involves activation and recruitment of different cell types during ***4 sequential (but overlapping) phases:***
***hemostasis, inflammation, proliferation, and maturation.***
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.
***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
174
\_\_\_ usually starts within hours of injury. During this phase, __ \_\_ ***degranulate,*** releasing ***histamin***e 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.
* Inflammation* usually starts within hours of injury. During this phase, ***mast cells degranulat*****e,**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.
175
***\_\_\_***, which begins during the inflammatory phase and continues for weeks afterward, leads to replacement of injured or missing tissue via the following:
***Proliferation***,
## Footnote
***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.
176
\_\_\_\_ the final phase of wound healing, results in ___ \_\_ and \_\_-\_\_ , which are the primary mechanisms by which the t*ensile strength of the wound increases.*
***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.
177
Wounds typically heal according to an organized sequence of 4 phases:
***hemostasis*** (fibrin clot formation)
***inflammation*** (cellular infiltration)
***proliferation*** (reepithelization, fibroplasia, and angiogenesis)
***maturation*** (collagen remodeling).
178
\_\_ \_\_-\_\_ _ is part of a family of transcription factors that perform a critical role in the immune response to infection and inflammation.
***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.
179
\_\_ \_\_-\_\_ __ (G-CSF) is the principal protein that stimulates the production and release of ***neutrophils from the bone marrow.***
*Granulocyte colony-stimulating factor (G-CSF)* is the principal protein that ***stimulates the production and release of neutrophils from the bone marrow.***
180
\_\_ __ \_\_-\_ (\_\_-\_) plays a major role in the response to infection by ***increasing neutrophil chemotaxis*** and stimulating ***macrophage phagocytosis.***
***Tumor necrosis factor-α (TNF-α)*** plays a major role in the response to infection by *increasing neutrophil chemotaxis* and *stimulating macrophage phagocytosis.*
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
***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
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\_\_ \_\_-\_\_ __ 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 ***lipopolysaccharid***e can *initiate a signal cascade that results in the destruction of* \_\_and *translocation of free* \_\_-\_\_ to the nucleus
.***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 o*f ***IκB*** and translocation of free ***NF-κB*** to the nucleus
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