Exam 2 Copy Flashcards
1
Q
Patient has a cancer with slow growth. Would they be a good candidate for chemotherapy? Why/why not? Explain.
A
- Cancers with slow growth have inhibited activity and are therefore resistant to chemotherapy. - Cancers with rapid growth have high proliferative activity and are highly susceptible to chemotherapy
1
Q
Which cancers are more typical to spread via lymphatics
A
- Carcinomas more likely than sarcomas
1
Q
What is the cytological marker(s) used to determine ALL?
A
- CD10 (CALLA)
2
Q
Describe the action of platelets after endothelial injury – include action of their granule contents
A
Adhesion:
After injury, vWF (subendothelium) binds to platelets (via glycoprotein Ib receptor) firmly
Secretion/activation
Above binding activates platelets = release of granules containing Ca, ADP, platelet 4, serotonin
Ca: functions in coagulation cascade
ADP/thromboxane (TxA2): mediates aggregation of more platelets
Platelet 4: binds to heparin = heparin inactivation = AT cannot function, favor coagulation
Serotonin: vasoconstriction
Expression of phospholipid complex = promotion of coagulation by binding coagulation factors/calcium
Aggregation
ADP/Thromboxane (released from platelets) stimulates further platelet aggregation
Fibrinogen (I) links platelets via their GpIIb-IIIa receptors.
Thrombin (IIa) under activation of coagulation cascade, binds to platelet surface and converts fibrinogen to fibrin (Ia) monomer when coagulation cascade is activated
2
Q
Thrombus vs embolus
A
- Thrombus: clot with firm attachment to vessel wall - Embolus: detached intravascular solid, liquid or gaseous mass carried by blood to distant site of origin. Majority of these originate from clot detached from vessel wall known as thromboembolus.
2
Q
Suffix to benign tumors
A
- -oma
2
Q
At what molecular levels do miRNAs function?
A
- Regulate mRNA at post-transcriptional and translational level
3
Q
Function of apixaban
A
- Direct Xa inhibitor
3
Q
True / False. Hypotension is a requirement for shock.
A
- False.
3
Q
What is Peutz-Jeghers syndrome?
A
- Aka hereditary intestinal polyposis syndrome - AD disease characterized by development of benign hamartomatous (haphazard/disorganized tissue) polyps in GI tract + hyperpigmented macules on lips and oral mucosa
3
Q
What does loss of polarity/polarization refer to?
A
- Anaplastic cells show this feature are markedly disturbed / disorganized when compared to normal. One is unable to tell difference between up and down in the specimen.
3
Q
Examples of cancers that seed into peritoneal cavity
A
- Surface epithelial tumors of ovary - Serous papillary cystadenoCA - Mucinous cystadenoCA - Colorectal CA - Pancreatic CA
3
Q
4 classes of regulatory genes altered in cancer cells. Describe each.
A
1.) Proto-oncogenes: regulate growth/differentiation. Mutations result in overproduction of normal protein or mutation of protein with aberrant function. - When activated become oncogene = oncogenic proteins = protein kinases = induction of cyclins = cell cycle induction (into S-phase). 2.) Tumor suppressor genes: regulate inhibition of growth. Homozygous loss is necessary for loss of function. 3.) Apoptotic genes 4.) DNA repair genes
3
Q
Cancers associated with anabolic steroid use?
A
- Benign/malignant liver tumors
3
Q
What are the para-neoplastic syndromes associated with some lung cancers?
A
- ACTH producing = Cushing syndrome = DM, weight loss, HTN, hyperpigmentation (MSH) - Small cell carcinoma in lung = ADH producing = hyponatremia (SIADH), HoTNh
3
Q
Tumor marker associated with hepatocellular CA and germ cell tumors of testes or ovary
A
- AFP (alpha-fetoprotein)
4
Q
What is von Willebrand’s disease?
A
- Bleeding disorder with deficiency of VWF, prevalence 1 in 100 (most common).
5
Q
True/False. Non-neoplastic proliferations are monoclonal
A
- False. These are polyclonal – this is a hyperplasia, derived from multiple cells. - Neoplasms are monoclonal.
7
Q
What is the cytological marker(s) used to determine tumor of neuronal origin?
A
- NSE (neuron-specific enolase) - Chromogranin - Synaptophysin
8
Q
What is an infarction? Causes? Factors that determine the development of infarct? Morphology – red vs white? Type of healing in infarcted tissue? Septic infarct?
A
- Infarction: death of tissue (ischemic necrosis) d/t interruption in blood supply - Causes: vasospasm, hemorrhage within atherosclerotic plaque, compression of vessels, torsion of vessel - Factors: collateral circulation, single venous outflow, end flow (spleen, kidney), cell type’s vulnerability to hypoxia (neuron > myocardium > fibroblast) Morphology: - Wedge-shaped: occluded vessel at apex, periphery at base, over time the infarct becomes delineated by rim of hyperemia reflecting inflammation at edge of lesion. - Red infarct: aka hemorrhagic infarct. Where? Venous occlusions, loose tissues, tissues with dual circulation (lung, bowel), tissue previously congested, re-established blood flow to a site of previous occlusion/necrosis - White infarct: aka anemic infarct. Where? Arterial occlusions in solid organ with limitation of blood flow, ie. kidney, heart, spleen. - Healing: dominant = ischemic coagulative necrosis except in brain = liquefactive necrosis. Inflammation along margin (ring of hyperemia). Repair after inflammation, mostly = granulation tissue followed by scar tissue (fibrous tissue). - Septic infarct: when origin of embolus is infected tissue (bacterial or otherwise)
8
Q
Does dysplasia progress to cancer?
A
- Is precursor to cancer, but does not always progress
9
Q
Define edema
A
- Increased fluid in interstitial tissue space, ie. when greater movement of fluid out of vasculature than is returned by venous absorption or lymphatic drainage.
9
Q
What is a leukemia?
A
- cancer derived from bone marrow stem cells
9
Q
Most common childhood cancer?
A
- ALL: acute lymphoblastic leukemia
9
What cancers account for \>50% of cancer deaths in US? Top 3 males vs females cancer deaths? Top 3 males vs females cancer incidences?
- \> 50% cancers deaths due to: lung, breast (female), prostate, colorectal - Cancer deaths males: lung \> prostate \> colorectal - Cancer deaths females: lung \> breast \> colorectal - Cancer incidences males: prostate \> lungs \> colorectal - Cancer incidences females: breast \> lungs \> colorectal
9
Cancers associated with hep B, C. Describe mechanism used.
- DNA virus - Hepatocellular CA - Hep B: injury = regeneration hyperplasia & Hbx protein inhibits p53 (tumor suppressor) and activates I-like GF (growth promoting) - Hep C: injury = regeneration hyperplasia
9
Tumor marker associated with trophoblastic tumors (chorioCA)
- beta-HCG
10
Describe mechanism for HPV association with cervical CA
- HPV has proteins E6 and E7 - E6 inhibits p53 preventing apoptosis - E7 inhibits p53, p21 (which acts on cyclinD/CDK4), RB-E2F (another tumor suppressor gene) = prevention of growth arrest
11
How are the management and prognoses of cancers determined? Explain.
- Grading: microscopic findings a.) Degree of differentiation: I-IV (well differentiated, moderately, poorly, nearly anaplastic) b.) Mitotic index (higher = higher grade) OR BrdU uptake - Staging (more important usually): a.) T: size (in situ = 0; 1-4) b.) N: nodal involvement (no nodes = 0, 1-3) c.) M: distant metastases (0 = none, 1-2) OR Dukes (colorectal), Ann Arbor (lymphomas)
13
What is the cytological marker(s) used to determine vascular neoplasms?
- vWF, CD31
14
Pre-cancerous lesions associated with oral cavity, esophagus, stomach, colon, liver, endometrium, skin. State the pre-cancerous and cancerous forms.
1.) Oral cavity = oral leukoplakia to SCC (squamous cell CA) 2.) Esophagus = Barrett’s esophagus metaplasia to adenoCA 3.) Stomach = chronic atrophic gastritis of pernicious anemia to adenoCA 4.) Colon = UC to adenoCA 5.) Liver = hep B/C infection to hepatocellularCA 6.) Endometrium = simple/complex hyperplasia to EIN (endometrial intraepitheal neoplasia) to endometrial adenoCA 7.) Skin = solar keratosis to SCC (usually)
14
Hepatoblastoma, hepatocellular CA. What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Signal transduction = beta-catenin - Point mutation/over-expression
14
Categories of carcinogenic agents
1.) chemical carcinogens: account for 80-90% of cancers a.) direct acting: chlorambucil, busulfan, melphalon b.) indirect acting: require metabolism by P450 – PAH (polycyclic aromatic hydrocarbons) 2.) radiation 3.) viruses and other microbes
15
What hormone do some small cell carcinomas in lung produce? What signs?
- ADH = hyponatremia, HoTN
16
What is CIS (carcinoma in situ)/dysplasia?
- Pre-invasive tumor with cells that show features of malignancy
17
What is PT INR?
- International normalized ratio is measure of time coagulation takes for patient in comparison to large group of individuals/standard compensating for differences in tissue factor.
17
Cancers associated with beta-naphthylamine, aniline dyes and rubber industries?
- Bladder
17
What is a tumor marker?
- Substance found in blood, urine, or body tissues elevated in cancer
19
Which coagulation factors are vit K dependent?
- 1972. 10, 9, 7, 2
21
Composition of thrombus
- Platelets, fibrin, RBCs, leukocytes
21
What is a polyp? Is it cancerous?
- Name for morphology of club-shaped growth in colon. Can be benign epithelial tumor or hyperplasia.
21
Cytologic features of anaplasia/poorly differentiated tumors
1.) nuclear and cellular pleomorphism (size/shape changes) 2.) hyperchromatic nucleus 3.) increase N:C ratio 4.) prominent nucleoli 5.) abundant and atypical mitoses (figures) 6.) tumor giant cells = anaplasia = single huge polymorphic nucleus (-ei) that are hyperchromatic 7.) loss of architecture/function = more aggressive
21
Function/mechanism of telomerase normally and in cancer cells
- Telomere shortens in absence of telomerase = p53 activation = cell cycle arrest, apoptosis - Telomerase upregulation = maintenance of telomere strength = no activation of p53 = prevention of cell cycle arrest, apoptosis
23
What is aplastic anemia?
- Bleeding disorder with pancytopenia d/t issue in bone marrow
24
What are Lines of Zahn?
- Refer to organization of thrombus – alternating layers of platelets, fibrin and RBCs
25
Compare and contrast active hyperemia and congestion. Define and provide mechanisms. Color of tissue? Provide clinically important examples.
1.) Hyperemia: active process where arterioles dilate resulting in increased blood flow to tissue. a.) Color: erythematous with oxygenated blood b.) Examples: exercised skeletal muscle, inflammation (eg. conjunctivitis), blushing 2.) Congestion: passive process due to impaired blood flow to tissue – can occur on an acute or chronic basis. a.) Color: blue-red with accumulation of deoxygenated blood b.) Examples: CHF (systemic), local venous obstruction
25
Cancers associated with hypercalcemia? Why, what factor(s)?
- Squamous cell CA, renal cell CA, breast CA - PTH-related peptide by SCC, RCC - Breast CA when bone metastases with release of osteolytic factors (PGE2, IL-1). Note this cancer can also be associated with osteoblastic metastases too.
26
Describe gross/microscopic findings of hepatic congestion
- Gross: nutmeg liver – central regions of lobules red/brown, depressed (d/t cell loss) surrounded by unaffected areas - Microscopic: centrilobular necrosis accompanying hemorrhage with hemosiderin laden macrophages; hepatic fibrosis if longstanding
26
What is cellular atypia? 3 features?
- Features seen in pre-malignant and malignant tumors only 1.) Cellular pleomorphism: cells vary in size/shape 2.) Nuclear changes: a.) nuclear pleomorphism (size/shape vary) b.) dense/irregular nuclear outline c.) hyperchromatic nuclear material (represent higher content of DNA, darker staining) d.) nucleolar pleomorphism 3.) increase N:C (nucleus:cytoplasm) ratio (greater than 1:5 normal)
27
How does anaplasia reflect prognosis?
- Anaplasia reflects aggressiveness = poorer prognosis
27
Pancreas, colon and lung cancer. What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Signal transduction = KRAS (mnemonic = panKReAS) - Point mutation
29
Cancers associated with hypocalcemia? Why, what factor(s)?
- Medullar CA of thyroid - Calcitonin
30
Signs of warfarin overdosage? Complication?
- Signs: blood in stools/urine, menorrhagia, bruising, excessive epistaxis, bleeding gums, oozing from injuries, bleeding from tumor/ulcer/other lesion - Complication: warfarin necrosis – mostly in patients with low protein C levels given high dose of warfarin in absence of heparin. In presence of warfarin, protein C fall more rapidly causing a transient hypercoagulable state = local thrombosis of dermal vessels. Require initial anticoagulation with heparin.
31
Do all carcinomas spread via lymphatics? Explain.
- No. - Follicular, renal cell and hepatocellular CAs do not - Follicular: local invasion - Renal: hematogenous (renal vein to IVC) - Hepatocellular: hematogenous
32
Function of WNT signaling pathway
- Embryonic development (cell fate, adhesion, polarity) - HSC self-renewal
33
Cancer(s) associated with arsenic
- Skin cancer
33
Tumor marker associated with CA of GI and breast
- CEA (carcino-embryonic antigen) - GI (colon, pancreas): CA-19-9
34
Which tumor listed below is a benign tumor? A. melanoma B. hepatoma C. seminoma D. lymphoma E. astrocytoma F. fibroma
- F. Fibroma
36
Can heparin cause prolonged time to extrinsic pathway?
- Yes at high dose - Also, warfarin at high dose can cause prolonged intrinsic (PTT) pathway time
37
Factors involved in vascular dissemination of cancer cells
- Most importantly: expression of CD44 on tumor cells favors metastasis - NK cells kills cells in circulation - Protection of cancer cells when in clumps - Clump with platelets
38
What is dependent edema?
- Edema in an area of the body lower than the heart (eg. legs, arms etc.) d/t increased hydrostatic pressure.
38
What is carcinoid syndrome? Symptoms? Cancers that cause this?
- This is associated with carcinoid tumors (neuro-endocrine tumors) located in appendix or small intestine. Carcinoid syndrome has clinical features of flushing, diarrhea, bronchospasm, tachycardia – attacks provoked by abdominal metastases or by alcohol ingestion. - This is caused by the secretion of serotonin. Diagnosis by urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid), a metabolite of serotonin.
39
Compensatory mechanisms to hemorrhage??
Compensatory mechanisms to hemorrhage??
40
Are all –omas benign?
- No, does not indicate benign. Not all –omas are tumors or are benign.
41
Virchow's triad. What does this predict?
1.) hypercoagulable state 2.) endothelial injury 3.) circulatory stasis - All lead to thrombosis/hypercoagulable state
41
Clinical features in a cancer patient?
1.) Local effects: related to location of tumor 2.) Cancer cachexia: d/t TNF-alpha (primarily) produced by tumor and stroma (macrophages) = loss of body fat, wasting, profound weakness 3.) Para-neoplastic syndromes: tumor produces particular hormones therefore pt experiences hormone-induced symptoms
43
Most dangerous sites for edema
a.) Brain b.) Lung
43
Describe stages of shock
1.) Non-progressive: reflexive compensation where mechanisms maintain tissue perfusion - reflexes maintain BP and CO - reflexes = baroreceptor, catecholamine release, RAAS, ADH, SNS stimulation 2.) Progressive: decompensating stage with worsening circulatory status, metabolic imbalance and acidosis - Widespread tissue hypoxia, lactic acidosis = decrease in vasomotor responses leading to arteriole dilation= decrease CO = anoxic endothelial cell injury - Decreased urinary output - Confusion 3.) Irreversible stage: irreversible tissue damage/organ failure has occured - Lysosomal enzyme leakage - Decreased myocardial contraction - Renal failure
43
A 63 yo male presents with cough and increasing weight loss for 3 months. CT scan shows a 3 cm mass in his right lung. A biopsy is performed and the cells are positive for NSE (neuron-specific enolase). Which of the following is the most likely pathological diagnosis shown in the report? A.) Neuroblastoma B.) AdenoCA C.) Squamous cell CA D.) Small cell CA E.) RhabdomyoSA
- D. Small cell CA
43
Cancers associated with H. pylori? Mechanism?
- Gastric lymphoma (MALT lymphoma), gastric carcinoma - CagA stimulates growth factor
44
Staining used to detect fat embolus in tissue
- Oil red O
45
Which country has highest skin cancer rate?
- New Zealand
46
Function of TFPI
- inhibitor of VIIa+TF (III) complex
48
Clinically detectable mass of cancer cells
- 1 gm, ie. 30 doublings
48
Why do malignant tumors show central necrosis/umbilication?
- Neoplasms outgrow blood supply. Limited diffusion into central area = ischemic necrosis.
48
Individuals with xeroderma pigmentosum are more likely to get what cancers? Why?
- Skin cancers, defect in NER pathway enzymes
49
Primary and secondary hypercoagulable states/risk factors
- Primary (genetic): factor V Leiden, prothrombin mutation, increased levels of factors VIII, IX, XI or fibrinogen; antithrombin III deficiency, protein C/S deficiency - Secondary: immobilization, MI, afib, tissue injury, CA, cardiac valves, DIC, antiphospholipid antibody syndrome
50
What is the cytological marker expressed on small cell carcinomas of lung and carcinoids?
- NSE (neuron-specific enolase)
51
What are paradoxical emboli?
- Rare condition in which an embolus from venous circulation passes through ASD/VSD to gain access to systemic circulation
52
List (7) essential alterations for malignant transformation.
1.) Self-sufficiency of growth signals: produced by cancer cells themselves 2.) Insensitivity to growth inhibitory signals 3.) Evasion of apoptosis 4.) Limitless replicative potential 5.) Sustained angiogenesis 6.) Ability to invade and metastasize 7.) Defects in DNA repair
53
Causes of turbulence leading to hypercoagulable/thrombosis
- Ulcerated atherosclerotic plaque - Aneurysms - MIs - Mitral valve stenosis - Afib - Polycythemia - Sickle cell anemia
53
Criteria used to differentiate between a benign and malignant neoplasm? Generally: appearance of tumor, behavior of tumor, but specifically:
1. Rate of growth 2. Differentiation (resembles tissue of origin) and anaplasia (lack of differentiation – don’t resemble their tissue of origin) 3. Local invasion 4. Metastasis
53
Maximum tumor size/mass compatible with life
- 1 kg, single cell undergone 30 doublings then 10 further
54
Cancers associated with HTLV-1? Mechanism?
- RNA virus - T-cell leukemias, lymphomas (virus endemic in Caribbean and Japan) - Tax gene activates c-Fos, IL-2, GM-CSF = proliferation - Tax gene inhibits p16INK4a (anti-proliferation) = proliferation
55
What is a hydrothorax?
- Fluid accumulation in the pleural space
56
Fates of thrombus
1.) Resolve 2.) Propagate 3.) Embolize 4.) Organize and incorporate into wall of vessel 5.) Organize and recanalize
56
Cancers associated with contraceptive hormone use?
- Breast cancer - Benign/malignant liver tumors
58
Burkitt lymphoma. What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Nuclear reg protein = C-myc - translocation
59
Mechanism of action of ASA and NSAIDs on hemostasis
- These are PG inhibitors. Overall these drugs have anticoagulation effects through inhibiting the action of TxA2 (thromboxane A2), which = prevention of platelet aggregation. PGI2 should also be inhibited, which counters the above effect, so I’m not sure which and why one is more powerful?
60
Tumor marker associated with breast CA
- CA-15-3
61
Factors that activation endothelium creating pro-coagulant state
- Infectious agents - Hemodynamic forces - Cytokines - Plasma mediators
61
Function of PAI
- inhibits tPA
61
Pro-Angiogenic factors (TAFs = tumor angiogenic factors)
- VEGF, FGF, HIF
62
What is Factor V Leiden?
- Genetic disorder in factor V that is resistance to degradation by protein C = increased probability of thrombosis
63
How can one distinguish between a factor deficiency or use of inhibitor (drug) causing anticoagulation/delay in coagulation from a patient’s sample?
- Mix the patient’s sample with normal plasma - If factor deficiency: will get clotting - If inhibitor/drug use: no clotting
64
Pt presents to ER with tachypnea, dyspnea, tachycardia and restlessness 2 days after fracturing his femur and sustaining burns to his leg. Patient also has diffuse petechial rash with thrombocytopenia. Embolus is suspected. What type?
- Given fracture of long bone with soft tissue burns, fat embolus should be highly suspected.
65
Cancers associated with estrogen?
- Breast cancer - Squamous cell carcinoma of cervix - Leiomyoma of uterus
66
CML. Describe molecular/genetic basis. Treatment?
- Translocation of c-abl from c/s 9 to bcr on c/s 22 = bcr-abl fusion gene (Philadelphia c/s) = high tyrosine kinase activity = proliferation of granulocytic precursors = CML - Tx = Gleevec (imatinib mesylate) = tyrosine kinase inhibitor
67
Match A: stroma and B: parenchyma to the following descriptions 1. ( ) determines the biological behavior of a tumor 2. ( ) determines the growth and evolution of a tumor 3. ( ) is composed of clonal neoplastic cells 4. ( ) is composed of CT, blood vessels and immune cells 5. Tumor derives its name based on ( )
- 1.) B: parenchyma - 2.) A: stroma - 3.) B: parenchyma - 4.) A: stroma - 5.) B: parenchyma
67
Through what mechanism does ionizing radiation cause cancer?
- Direct effect / indirect (via free radicals) causes chromosome breakage (mostly), translocation, point mutation
69
What is a sentinel lymph node?
- 1st lymph node that receives lymph flow from primary tumor
70
Two types of retinoblastoma. Explain mechanisms.
1.) Familial: inherit germline mutation + acquisition of somatic mutation = dz 2.) Sporadic: born with two normal genes + acquisition of somatic mutations through life = dz
71
Cancers associated with x-rays
- Radiation dermatitis - Skin cancers
72
Cancers associated with radium
- Osteosarcoma
74
Draw/Describe the process of normal hemostasis (coagulation, anticoagulation and fibrinolytic systems including the following: a.) intrinsic pathway b.) extrinsic pathway c.) final common pathway d.) fibrin, stable clot formation e.) fibrinolytic pathway (plasminogen, TPA, PAI, alpha-2 antiplasmin) f.) anticoagulation pathway (TFPI, antithrombin III, protein C/S) g.) anticoagulation drugs (warfarin/coumadin, heparin, dabigatran, rivaroxaban, apixaban)
see picture
74
What is the function of plasmin? How is its action inhibited?
- Plasminogen activated to plasmin by tPA (tissue plasminogen activator) and uro/streptokinase. Plasmin degrades fibrin into fibrin degradatory products. - Plasmin inactivated by circulating alpha-2 antiplasmin. Also tPA is inactivated by PAI (plasminogen activator inhibitor)
74
What are the chemical mediators of septic shock? Explain the pathogenesis.
- Inflammatory mediators such as TNF, IL-1, which lead to activation of coagulation cascade, PG/LT release, activation of complement. This leads to ARDS, DIC, endothelial damage = low CO, low peripheral resistance = ultimately multi-organ failure.
75
3 factors that play a role in uncontrolled growth rate of neoplasms?
- Evasion of host control: inhibition of apoptosis - Limitless replicative potential: remain in cell cycle - Loss of contact inhibition
76
Morphologic methods used to diagnose cancer
- Biopsy - Frozen section - Cytology: FNAC (fine needle aspiration cytology), exfoliative cytology/Pap - IHC: when diagnosing undifferentiated tumor (origin not known)
78
Gross / microscopic (on acute and chronic) tissue findings of pulmonary edema/congestion
- Gross: exaggerated lobular structures, frothy fluid - Microscopic: a.) Acute: alveolar capillaries engorged with blood, alveolar septal edema, focal intra-alveolar hemorrhage b.) Chronic: thickened/fibrotic septa, heart failure cells (hemosiderin in macrophages) in alveolar spaces
78
What is desmoplasia? What staining picks this up? What does it show? How does gross specimen of this appear? Cancers associated with desmoplasia?
- Hyperplasia of activated fibroblasts leading to abundant collagenous stroma - Trichrome stain shows blue collagen in stroma - Stony, hard (scirrhous) gross feel/appearance - Cancers: female breast cancers, cholangiocarcinoma
79
Well-differentiated tumors is a hallmark of a high grade malignant tumor. True/False
- False. Anaplasia is the hallmark of this.
80
Most lymphomas are non-Hodgkin’s or Hodgkin’s?
- non-Hodgkin’s
82
Etiological classification of shock
- Mnemonic = SSHHOCCKE - S: sepsis - S: spinal (neurogenic) - H: hypovolemic - H: hemorrhagic - O: obstructive (PE, pneumo, hydrothorax…) - C: cardiogenic - C: cellular toxins - K: anaphylaK(c)tic - E: endocrine/adrenal crisis
83
Cancer(s) associated with asbestos?
- Mesotheliomas - GI cancers
84
What is antiphospholipid antibody syndrome? Clinical presentation?
- Disorder where antibodies are directed against phospholipids causing hypercoagulable state in vivo. In vitro experiments shows less clotting. - Occurs in pts with/without autoimmune dz, is associated with SLE - Presentation: recurrent thrombi, repeated miscarriages, cardiac valve vegetations, thrombocytopenia
85
What is anasarca?
- Severe generalized edema usually d/t lack of oncotic pressure with earliest sign being periorbital edema
86
List and describe the laboratory diagnostic procedures used to approach patients with bleeding disorders and thrombotic disorders.
Order the following: - PT - PTT - Bleeding time - Platelet count: thrombocytopenia = decrease seen in ITP, TTP, DIC, end-stage liver failure
87
Name of adenomas with cysts?
- Cystadenomas
89
What cancers/disorders are associated with mutations to the VHL gene? Function of this gene product?
- Cancers: hereditary renal cell carcinomas, pheochromocytomas, hemangioblastomas of CNS, retinal angiomas, renal cysts - Function: (on c/s 3p) part of ubiquitin ligase complex that regulates nuclear txn of HIF-1alpha
90
Molecular methods used to diagnose cancer
- Flow cytometry - DNA probe analysis
91
What is idiopathic thrombocytopenic purpura (ITP)?
- Bleeding, immune disorder with autoimmunity against platelets
92
Criteria for hemorrhagic shock
- 4/6 Rosen’s
93
Tumor suppressor gene mutation associated with FAP (familial polyposis coli) and non-familial colorectal adenoCA / sporadic adenomas. Function/mechanism?
- APC gene - Function = prevents nuclear txn via beta-catenin/WNT pathway. APC binds beta-catenin leading to its degradation and inability to translocate to nucleus to cause proliferation. - When mutated, continuous WNT signaling occurs via increased beta-catenin = increased proliferation
94
Define neoplasia. Define neoplasm.
- Neoplasia: process of uncontrolled growth and accumulation of cells d/t proliferation and/or evasion of apoptosis - Neoplasm: (aka tumor), abnormal mass of tissue
95
If culturing normal tissue, benign neoplasms and malignant neoplasms, what is the % of cells from each that would be found to be in s-phase?
- Normal: 1% - Benign: 10-20% - Neoplasms: 20-80%
96
Compare and contrast carcinomas/sarcomas vs benign tumors in terms of capsule, growth, invasion, mitosis, degree of differentiation
- Carcinomas/sarcoma: capsule absent generally, rapid growth, invasion present, atypical mitosis, well/poorly (aka anaplastic if poorly) differentiated - Benign tumors: capsule generally present, slow growth, invasion absent, no atypical mitosis, well differentiated
98
List steps of metastatic cascade
1.) Invasion (detachment, attachment, degradation, migration through ECM) 2.) Vascular dissemination (directly or via lymphatics) 3.) Homing
100
What is phlebothrombosis?
- Venous thrombosis
101
Growth of CA cells would be enhanced by downregulation of the gene for which of the following proteins? a.) VEGF b.) bFGF c.) thrombospondin-1 d.) Ki-67 e.) PCNA
- C. Thrombospondin-1 is an anti-angiogenic factor
103
Cancers associated with gynecomastia? Why, what factor(s)?
- ChrorioCA of testis - Beta-HCG
104
Cancers associated with nitrosamines?
- GI tract (mostly stomach) cancers
106
Melanoma. What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Signal transduction = BRAF - Point mutation
108
Steps of chemical carcinogenesis
1.) initiation a.) chemical carcinogens (directly or indirectly) are electrophiles that remove electrons from DNA/RNA/proteins = production of alteration / permanent DNA rapidly b.) irreversible step 2.) promotion a.) induction of tumors in cells that have undergone initiation, does not affect DNA b.) reversible step
110
34 year old female gives birth to a healthy baby boy after a 4 hour labor. 1 hour after delivery, she becomes dyspneic, cyanotic, hypotensive and begins to have a seizure, falls into a coma and dies. What has likely occurred? What will the pathology report show?
Amniotic fluid embolism occurred
Emboli consisted of epithelial cells (from fetal skin), Lanugo hair, fat from vernix caseosa, mucin from fetal respiratory and GI tract.
111
Function of heparin
- Heparin\* binds and activates antithrombin III and works by inhibiting IIa (thrombin), IXa and Xa - It prolongs intrinsic pathway time - Given IV or Subq
112
Microscopic appearance of edema
a.) Clearing/separation of ECM elements b.) Pink-staining if protein significant
114
What is septic shock?
- Septic shock = sepsis + hypotension (refractory to volume resuscitation and requiring pressors) = SIRS + documented infection + hypotension (refractory to volume resuscitation and requiring pressors) - SIRS = Fever, HR \> 90, RR \> 20 (or Paco2 \< 32), leukocytosis/leukopenia (or 10% bands)
116
What type of cancer does estrogen promote?
- Liver tumors
117
What is the cytological marker(s) used to determine tumor of leukocyte origin?
- LCA: leukocyte common antigen
119
Tumor suppressor genes related to cancer
- APC, BRCA-1/2, RB, TGF-beta, WT-1/2, p53, VHL
120
Steps of ECM invasion by cancer cells
1.) Detachment from other cells: E-cadherin down-regulated or shut off 2.) Attachment to ECM: laminin receptor (by cancer) binds to laminin in ECM 3.) Degradation of ECM: tumor cells release MMPs (collagenases) to degrade type IV BM collagen or induce other cells (fibroblasts/inflammatory cells) to release these 4.) Migration: mediated fibronectin to receptor (on tumor cell), other motility factors for locomotion
122
What is a lymphoma?
- cancer derived from lymph nodes or lymphoid tissue
123
Examples of cancers that seed into subarachnoid space
- glioma - GBM: glioblastoma multiforme
125
Role of endothelium in hemostasis
a.) Procoagulant (injury/activation) - vWF (Von Willebrand Factor): binds platelets to subendothelium - Tissue factor: induced by endotoxin and cytokines - PAI (Plasminogen activator inhibitor): inhibits tPA b.) Anticoagulant (normal conditions) - Inhibition of platelet aggregation: binds thrombin and then secretes prostacyclin (PGI2) and NO, which inhibit platelet aggregation. Secretes adenosine diphosphatase (degrades ADP) - Heparin-like molecules: cofactor for antithrombin, which inactivates thrombin, Xa and IXa - Thrombomodulin: binds thrombin = activates protein C, which proteolyzes factors Va and VIIIa - Fibrinolytic: makes tPA (tissue plasminogen activator)
126
Cancer(s) associated with Cr and Ni?
- Lung cancer
128
HPV is associated with what cancer? What subtypes specifically? Mechanism?
- DNA virus - Associated with cervical cancer - Subtypes = 16, 18, 31 - Mechanism: a.) E6 protein: inhibits p53 (tumor suppressor) b.) E7 protein: inhibits RB-E2F (mostly), p53, p21
129
Function of tPA
- Converts plasminogen to plasmin for it to cleave fibrin into FDPs
131
What is rhabdomyosarcoma?
- Malignant, Striated muscle cancer
131
Typical spread of rhabdomyosarcoma
- Spreads beneath sub-mucosal layer and locally invades rather than blood
132
What cancers are most common in young adults?
- Leukemias, lymphomas, CNS and soft tissue tumors
133
4 categories of tumor differentiation
1.) Well-differentiated 2.) Moderately differentiated 3.) Poorly differentiated 4.) Anaplastic (undifferentiated)
135
Contraindications to warfarin
- Pregnancy - Situation where risk of hemorrhage greater than clinical benefits (drug/alcohol use or dementia/psychosis)
135
Tumor marker associated with ovarian carcinoma
- CA-125
137
What is a teratoma? Is it benign or malignant?
- Tumor composed of more than one parenchymal cell type, derived from more than one germ layer – totipotent cells (in gonads) - Either benign or malignant - Benign: mature teratoma (aka dermoid cyst) - Malignant: immature teratoma (teratocarcinoma)
138
What is a transitional cell carcinoma?
- Malignant cancer of from transitional epithelium in urinary system
140
Anti-Angiogenic factors
- Thrombospondin-I, angiostatin, endostatin, tumstatin
142
MEN2a/b, familial medullary thyroid CA. What oncogene (and category) can be involved in this cancer? What DNA change occurred? Hyperplasia or neoplasia? Organs involved
- Growth factor = RET - Point mutation - Can be hyperplasia or neoplasia - Involves many endocrine organs
143
What is thrombotic thrombocytopenic purpura (TTP)?
- Bleeding disorder, autoimmune disease where antibodies are directed against von Willebrand factor cleaving protease ADAMTS-13. ADAMTS-13 normally disrupts platelet: vWF interaction.
144
What type of cancer does DES (diethylstilbestrol) promote?
- Post-menopausal endometrial cancer - Vaginal cancer in offspring exposed in utero
146
Categories of oncogenes
1.) Growth factor (GF): PDGF-beta (SIS), FGF, TGF-alpha, HGF 2.) GF receptor: ERBB1/2 (Her-2/NEU), RET, PDGFR-beta, KIT 3.) Signal transduction: KRAS, ABL, BRAF, beta-catenin 4.) Nuclear txn: C-myc, N-myc 5.) Cell cycle regulators: cyclin-D/E, CDK4
147
Cancers associated with UV radiation? Mechanism?
- Skin cancers: melanoma, basal cell carcinoma, squamous cell carcinoma - Mechanism: pyrimidine dimer formation (escape NER pathway)
148
Components of a tumor. What does each component determine about the cancer?
a.) parenchyma: clonal neoplastic cells; determines biologic behavior, name is derived from this component b.) stroma: CT, BVs, macrophages, lymphocytes; determines growth/evolution of tumor
150
What is shock? Sequela?
- Cardiovascular collapse: inability of circulatory system to adequately supply tissues with nutrients and remove toxic waste = organ failure - Sequela: hypotension = impaired tissue perfusion = cellular hypoxia
151
What is Bernard-Soulier dz?
- Bleeding disorder, defect of platelet adhesion d/t defect in glycoprotein Ib
152
Thrombi from which veins are more likely to embolize?
- From deep veins
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What is an intermediate tumor?
- Locally malignant tumor without tendency for metastasis
154
Factors from endothelium that inhibit platelet aggregation
- Prostacyclin (PGI2), NO – stimulated by cytokines and thrombin - NO, adenosine diphosphatase (degrades ADP)
155
Cancers associated with p53. Function of gene product / mechanism?
- Lung, colon, breast CA, Li-Fraumeni syndrome, cervical CA (with HPV E6/7) - Function/mechanism of gene product = a.) anti-proliferative: arrests cell-cycle at G1/S by acting on p21 to inhibit cyclinD/CDK4 b.) pro-apoptotic: induces BAX (member of Bcl-2), which is pro-apoptotic c.) induction of DNA repair: activates DNA repair enzymes
156
Rosen’s empiric criteria for diagnosis of shock. How many are needed to make the diagnosis?
- 4 out of 6 needed a.) ill-appearing / LOC b.) HR \> 100 c.) RR \> 22 or Pco2 \< 32 d.) Base deficit (amount of base required to neutralize pH) \< -5 or lactate \> 4 e.) Urine output \< 0.5 ml/kg/hr f.) Hypotension \> 20 mins
158
Factors that contribute to endothelial injury
- DM, HTN, smoking, uraemic factors, oxidative stress, LDL cholesterol, homocysteine ADMA, inflammation
159
What is Glanzmann’s thrombasthenia?
- Bleeding disorder, defect of platelet aggregation d/t defect in glycoprotein IIb/IIIa
160
Compare and contrast the following types of emboli with emphasis on the composition, (etiology) source, organs destinations of emboli.
a.) Systemic - Composition: thrombus/clot - Etiology: afib, mitral stenosis, endocarditis, mural thrombi, ulcerated plaque, aortic aneurysm, valvular vegetation - Sources: arterial source/mural source primarily, rarely paradoxical (venous circulation via ASD/VSD) - Destination: 75% lower extremities, brain, other (intestine, kidney, spleen, UE) b.) Pulmonary - Composition: thrombus/clot - Sources: ~95% arise from deep leg vein above knee - Destination: lung (pulmonary emboli): majority to peripheral vessels, then to medium-sized, then to major arteries (pulmonary artery as saddle emboli causing sudden death) c.) Fat - Composition: fat - Sources: fracture of long bone, soft tissue trauma, burn - Destination: lungs, brain d.) Air - Composition: air - Sources: obstetric procedure, chest wall injury, sudden atmospheric pressure changes (decompression sickness) - Destination: brain, lung (chokes: edema, hemorrhage atelectasis, emphysema), skeletal muscles (bends) e.) Amniotic fluid - Composition: amniotic fluid - Sources: breach in placental membrane and uterine veins causes infusion of amniotic fluid into maternal circulation - Destination:
161
Patient presents with black, verrucoid appearing skin lesion on axilla. This patient has cancer. What type of cancer most likely? What other skin lesion is associated with such cancer?
- Stomach CA - Lesion is called acanthosis nigricans - Leser-Trelat sign: multiple, outcroppings of pigmented seborrheic keratosis
162
Causes of cardiogenic and non-cardiogenic pulmonary edema
a.) Cardiogenic: left ventricular failure, MI, systemic HTN, PE b.) Non-Cardiogenic: anything that increases capillary permeability – alveolar hypoxia, ARDS, inhalation of toxic agent, pulmonary infection, radiation of lungs, head injury, renal failure, hypersensitivity rxn
162
What is the Warburg effect? Clinical implication?
- Warburg effect: in presence of ample o2, cancer cells have characteristic metabolism: high uptake of glucose, increased glucose to lactose via glycolytic pathway - Clinically: detect this by PET by infusing patient with non-metabolically active, but readily up-takeable glucose, most tumors = PET positive, rapidly growing = markedly PET positive
163
Which country has highest gastric cancer mortality rate?
- Japan
165
Discuss thrombocytopenia in terms of differential diagnosis, clinical features, bone marrow morphology, and laboratory findings.
- Thrombocytopenia = low platelet - Differential: heparin-induced, TTP, ITP, aplastic anemia, DIC, end-stage liver failure, maybe Bernard-Soulier syndrome (can be normal platelet count) - Labs: a.) heparin-induced: ? b.) TTP/ITP: nml PT/PTT, prolonged bleeding time c.) aplastic anemia: ? d.) DIC: prolonged PT/PTT, prolonged bleeding time e.) end-stage liver failure: as DIC f.) Bernard-Soulier: nml PT/PTT, prolonged bleeding time - Bone marrow morphology: ?
166
Mantle cell lymphoma, breast/esophageal cancers. What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Cell cycle reg = cyclin D - Translocation in mantle cell lymphoma - Amplification in breast / esophageal cancers
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Risk factors for venous thrombus formation
\* Anything that promotes stasis - CHF - Trauma - Surgery - Pregnancy - CA - Trousseau syndrome (migratory thrombophlebitis: some tumor cells release procoagulant factors such as tissue factor and protease that activates factor 10)
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What drugs prolong PTT/PT?
- PTT prolonged by heparin - PT prolonged by warfarin/coumadin
169
Names and actions of endogenous anticoagulants
a.) antithrombin III: inactivates motley IIa (thrombin)and Xa (also: IXa, Xia and XIIa) b.) protein C: inhibits Va and VIIIa c.) protein S: enhances activity of protein C d.) thrombomodulin: activated by thrombin = activates protein C e.) TFPI (tissue factor pathway inhibitor): inhibits VIIa-TF(III)
170
Types of shock, causes?
a.) Cardiogenic: infarction, arrhythmia, tamponade, PE = decreased CO b.) Hypovolemic/hemorrhagic: trauma, fluid loss, burns c.) Septic: septicemia, endotoxic shock, systemic microbial infection d.) Neurogenic: trauma, loss of vascular tone/peripheral pooling of blood e.) Anaphylactic: IgE hypersensitivity rxn
172
What is the cytological marker(s) used to determine tumor of mesenchymal origin?
- Vimentin, desmin, muscle-specific actin (muscle)
173
Cancers associated with aromatic amines and azo dyes?
- Liver (hepatocellular CA)
175
What is a leiomyoma?
- Tumor of smooth muscle origin
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Bone metastases. Most common site? Symptoms? Types?
- Site: vertebral column (Batson’s paravertebral venous plexus connects vena cava and vertebral bodies directly - Symptom: most commonly pain (which is typically at stage 4) - 2 types: a.) osteolytic (bone lysing/reabsorbing): tumors produce PGE2, osteoclast activating factor (IL-1), hypercalcemia can be present b.) osteoblastic (bone forming): high serum alk phos, most commonly from prostate cancer
178
Breast/ovarian cancer. What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Growth factor = ERBB2 (Her-2/NEU) - Amplification
179
What cancers does exposure to the following substances predispose one to? a.) Arsenic b.) Asbestos c.) Benzene d.) Berrylium e.) Chromium f.) Nickel g.) Radon h.) Vinyl chloride i.) Aniline dyes j.) Cigarettes
- Arsenic: lung, skin, hemangiosarcoma - Asbestos: lung, mesothelioma, GI - Benzene: leukemia, Hodgkin lymphoma - Berrylium: lung - Chromium: lung - Nickel: nose, lung - Radon: lung - Vinyl chloride: angiosarcoma - Aniline dyes: bladder - Cigarettes: CA of oropharynx and lungs
180
Cancers associated with tobacco, smoked meats and fish?
- Lung, bladder
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60 yo man presents with cough, SOB and increasing weight loss for 2 months. CT scan shows 5 cm mass in left lung. Biopsy performed and diagnosis of lung SCC is made. Compared to normal cells in right lung, which protein listed below is MOST likely to be upregulated? a.) tumstatin b.) telomerase c.) thrombospondin-1 d.) endostatin e.) angiostatin
- B. Telomerase. All others are anti-angiogenic.
182
Malignant mesenchymal tissue names
- -sarcoma
183
What is a leiomyosarcoma?
- Malignant, Smooth muscle cancer
185
Describe the molecular basis of cancer
1.) Acquired DNA damage (chemicals, radiation, viruses) / inheritance of mutations of via point mutation, translocation or amplification a.) proto-oncogenes promoting growth b.) tumor suppressor genes inhibiting growth c.) genes regulating apoptosis d.) genes regulating DNA repair 2.) Unregulated cell proliferation or/and decreased apoptosis 3.) Clonal expansion 4.) Angiogenesis, immune system escape, additional mutations etc. 5.) Tumor progression 6.) Malignant neoplasm 7.) Invasion/metastasis
187
Meaning of differentiation when it comes to cancers? Anaplasia definition?
- Differentiation refers to cells/tissues resembling their progenitors on both morphological and functional basis - Anaplasia = undifferentiation/complete lack of differentiation
189
What is ascites?
- Fluid accumulation in the peritoneal space
190
Why doesn’t venous thrombosis usually result in congestion?
- Collateral circulation/alternate pathways for venous return. - In organs with single outflow, infarct more likely
191
What type of cancer does high dietary fats promote? How?
- Colon CA via high bile acids d/t high fat intake
193
Clinical signs/symptoms of pulmonary edema
- Dyspnea, orthopnea, cyanosis, tachypnea, air hunger, productive cough (copious, frothy, blood-tinged), tachycardia/bounding pulse, crackles, JVD - CXR a.) interstitial: pan-haziness b.) alveolar: perihilar consolidations c.) enlarged heart, pleural effusion
194
What cancers are most common in infancy/childhood?
- Blastomas - ALL - Rhabdoymyosarcoma
195
Define dysplasia. What are the tissue features?
- Defined as disordered growth in epithelial cells - Features: loss in uniformity of individual cells, loss in architectural orientation, pleomorphism (size/shape changes), mitoses more prominent
196
Criteria for cardiogenic shock
- Cardiogenic shock: decreased CO and evidence of tissue hypoxia in presence of adequate volume - Criteria: 4/6 Rosen’s OR: a.) hypotension for 30 minutes b.) 30 mmHg below baseline c.) Cardiac index \< 2.2 L/min/m2 d.) PCWP (pulmonary capillary wedge pressure) \> 15 mmHg
197
Pt arrives to ER with acute swelling and severe pain to left leg after a 20-hour plane trip back from Australia. While being worked up, patient suffers acute respiratory distress, codes and dies minute later. What is the likely finding on autopsy that caused this patient’s death?
- DVT that embolized to lung. It was likely a saddle emboli that resulted in sudden death and acute right heart failure.
199
Function of warfarin
- Interferes with vit K metabolism, preventing synthesis of 1927 (10, 9, 7, 2) - Prolongs extrinsic pathway time
201
Outline the processes for stepwise evaluations of bleeding patients, patients with suspected platelet disorder, and patients with suspected hypercoagulability.
- Order PT, PTT, bleeding time and platelet count - If hypercoagulable d/t drug/inhibitor, mixing with normal pts/pooled serum will inhibit coagulation in that serum too. If deficiency, coagulation will occur.
202
Function of rivaroxaban
- Direct Xa inhibitor
204
Most common childhood leukemia?
- ALL: acute lymphoblastic leukemia
205
Discuss disseminated intravascular coagulopathy (DIC) in terms of etiology, pathogenesis, morphologic features, clinical presentation and course, laboratory diagnosis, and complications and prognosis.
- Etiology/Pathogenesis: underlying disorder (infections, malignancy, obstetrical complication such as amniotic fluid embolus, hypersensitivity rxn, trauma/surgery, etc.) result in systemic activation of coagulation cascade = fibrin thrombi form through the body primarily in capillaries and small vessels = organ failure/infarcts & consumption/depletion of platelets and coagulation factors resulting in bleeding - Morphologic features: ? - Clinical presentation/course: bleeding/organ failure - Lab diagnosis: PT/PTT/bleeding time prolonged, thrombocytopenia, blood smear shows schistocytes/sheared RBCs, D-Dimer (measurement of plasmin-cleaved insoluble cross-linked fibrin) indirectly measures plasmin/thrombin activity - Complications: organ failure - Prognosis: high chance of death
206
Describe CIN grading and transformation
- CIN = cervical intraepithelial neoplasia 1.) Mild dysplasia = CIN1: up to 1/3rd of squamous cells have undergone dysplasia above BM 2.) Moderate dysplasia = CIN2: up to 2/3rd of squamous cells have undergone dysplasia above BM 3.) Severe dysplasia = CIN3: over 2/3rds of squamous cells have undergone dysplasia above BM. When full thickness (100%), called CIS (carcinoma in situ). 4.) Invasive carcinoma = breach of basement membrane by cells • CIN1 also referred to has low-grade SIL (squamous intraepithelial lesions) • CIN2/3/CIS also referred to has high-grade SIL
207
Cancers associated with HHV-8?
- RNA virus - Kaposi’s sarcoma
208
Define the following: Are these neoplasms? a.) Granuloma b.) Hematoma c.) Hamartoma d.) Choristoma
- a.) granuloma: collection of macrophages following immune reaction - b.) hematoma: collection of blood - c.) hamartoma: disorganized / haphazard tissue – eg. pulmonary hamartoma (firm, sharply delineated and discreet lesion with calcifications) in lung OR Peutz-Jeghers polyp (aka hereditary intestinal polyposis syndrome) in GI system - d.) choristoma: normal tissue located at a different site – eg. adrenal cells in kidney capsule, lung, ovaries; pancreatic tissue in stomach mucosa/SI \* all the above are normal, non-neoplastic lesions
209
Tumor marker associated with prostate cancer
- PSA (prostate-specific antigen)
210
Causes of localized vs generalized cerebral edema
a.) Localized: abscess, neoplasm, trauma b.) Generalized: encephalitis (infection), HTN-crisis, obstruction of venous outflow, trauma
211
Most common overall leukemia?
- CLL: chronic lymphoblastic leukemia
212
Compare and contrast bleeding disorders due to the following, in terms of etiology, genetics, pathogenesis, clinical presentation, laboratory diagnosis, and clinical course: a. hemophilia A b. hemophilia B c. hemophilia C d. von Willebrand disease e. vitamin K deficiency f. liver disease
a.) Hemophilia A (most common): XR, factor VIII (Aight) deficiency, bleeding disorder (see below); labs: unaffected PT, prolonged PTT, unaffected bleeding time, unaffected platelet count b.) Hemophilia B: XR, factor IX deficiency, bleeding disorder (see below); labs: unaffected PT, prolonged PTT, unaffected bleeding time, unaffected platelet count c.) Hemophilia C (least common): AR, factor XI deficiency, bleeding disorder (see below); labs: unaffected PT, prolonged PTT, unaffected bleeding time, unaffected platelet count - Signs/symptoms hemophilia: deep internal bleeding, joint damage, transfusion infection, adverse rxn to clotting factor tx, intracranial hemorrhage d.) vW disease: deficiency of vWF, bleeding disorder, presentation: easily bruised, epistaxis, gingival bleeding menorrhagia; labs: unaffected PT, prolonged PTT, prolonged bleeding time, unaffected platelet count e.) Vit K deficiency (or warfarin use): bleeding disorder; labs: prolonged PT, normal/mildly prolonged PTT, unaffected bleeding time, unaffected platelet count f.) Liver disease (end-stage): inability to produce coagulation factors d/t destruction of liver; bleeding disorder; labs: prolonged PT, prolonged PTT, prolonged bleeding time; decreased platelets
213
Cancers associated with HIV?
- RNA virus - Lymphoma
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Typical sites of hematogenous spread of cancers
- Sites of high blood perfusion – liver, lungs, brain, adrenals, kidneys, bones
216
Classification of neoplasms. Describe in terms of invasion, metastasis, treatment, clonality of precursor cell, differentiation, proliferating activity
- Benign: neoplasm that grows without invading adjacent tissue or metastasizing, well-circumscribed, amenable to treatment, monoclonal (derived from single precursor cell), always differentiated, low proliferating activity - Malignant: neoplasm that grows with invasion into adjacent tissue and usually metastasizes, may be treated successfully or follows deadly course, monoclonal, may or may not be differentiated, lower to higher degree of proliferating activity (higher than benign though)
217
Routes of metastasis of cancers? What route is more common?
1.) Seeding of body cavities (peritoneal, pleural, sub-arachnoid space) 2.) Lymphatic spread: most common 3.) Hematogenous spread: veins \>\> arteries d/t mural thickness
218
What are cellular indicators of proliferation used in lab?
- Molecules: Ki-67 or PCNA - Mitotic figures, especially when atypical are indicative of malignant neoplasms
219
Neuroblastoma, small-cell CA of lung. What oncogene (and category) can be involved in this cancer? What DNA change occurred? What can be seen on karyotype?
- Nuclear reg protein = N-myc - Amplification - Karyotype: a.) HSR (homologous staining region) = chromosome with large area of amplification b.) Multiple double minutes, each representing “tiny chromosomes”
220
What clinical findings are of concern for malignant cancer during physical exam of lymph node?
- Enlarged, hard and NON-TENDER (key)
221
What does it mean if a tumor feels soft/fleshy vs stony/hard?
- Soft/fleshy: stroma is scant in comparison to parenchyma - Stony/hard (scirrhous): stroma composed of abundant collagenous (desmoplasia)
222
What is SIRS?
- Systemic inflammatory response syndrome - Fever, HR \> 90, RR \> 20 (or Paco2 \< 32), leukocytosis/leukopenia (or 10% bands)
223
Cancers associated with aflatoxin b1? What is the source?
- Source = mycotoxin produced by aspergillus flavus fungus – improperly stored corn, rice and peanuts - High incidence in China and Gambia - Cancer = hepatocellular (via p53 mutation)
224
What are the etiologies/pathogeneses of edema? Include diseases/disorders that cause each. Discern what etiologies lead to systemic vs localized.
1. elevated hydrostatic pressure: systemic - CHF, constrictive pericarditis, liver cirrhosis (leads to ascites), venous obstruction/compression 2. decreased plasma oncotic pressure: systemic - low protein in plasma d/t reduced synthesis or loss: - nephrotic syndrome, end stage liver dz, malnutrition, protein losing gastroenteropathy 3. lymphatic obstruction: localized - impaired drainage = increase tissue hydrostatic pressure - inflammation, neoplasm, surgery (lymph node resection), post-irradiation 4. sodium retention: systemic - shift of fluid to intravascular space/plasma = increased hydrostatic pressure = decreased oncotic pressure (dilution of protein) - RAAS activation, renal insufficiency/failure 5. inflammation: localized or systemic - increased passage of fluid into extracellular space (vasodilation/endothelial contraction) - infection, angiogenesis, allergy
225
What is a hemorrhage? Predisposition to hemorrhage? Causes? Clinical manifestations?
- Definition: extravasation of blood d/t ruptured vessels - Predisposition: fragile vessels, platelet dysfunction, coagulation defect, iron deficiency - Causes: trauma, atherosclerosis, aneurysm, neoplasia, inflammation, chronic congestion (capillary bleeding) - Manifestation: a.) Hematoma: collection of blood - petechiae (tiny pin sized, not palpable): 1-2 mm - purpura (in between): \>= 3 mm - ecchymoses (large bruise): \> 1-2 cm
226
How to tell microscopically the difference between venous and arterial thrombi?
- Arterial: Lines of Zahn – organizational layers of platelets, fibrin and RBCs - Venous: more RBCs, more red, typically not organized as above
227
What is sepsis?
- Sepsis = SIRS + documented infection - SIRS = Fever, HR \> 90, RR \> 20 (or Paco2 \< 32), leukocytosis/leukopenia (or 10% bands)
229
What is the cytological marker(s) used to determine thyroid cancer?
- Thyroglobulin
230
Pathophysiological features of shock
FIVE features that lead to cell injury 1.) intracellular calcium overload 2.) intracellular hydrogen ion abundance 3.) cellular / interstitial edema 4.) catabolic metabolism 5.) inflammation
231
What is heparin-induced thrombocytopenia?
- Patient’s that develop this develop heparin-induced platelet antibodies, but without thrombocytopenia. These patients develop arterial and venous thrombosis, can lead to venous limb gangrene and secondary skin ulceration.
232
What is the most common extra-nodal site for primary malignant lymphoma?
- Stomach
233
Of the following cancers, provide the most common metastatic sites: a.) Stomach adenoCA b.) Breast cancer c.) Colorectal cancer d.) Renal adenoCA e.) Lung f.) Melanoma g.) Prostate h.) Testicular tumor
- Stomach adenoCA: Virchow’s left supraclavicular node - Breast cancer: lung, bone - Colorectal cancer: liver - Renal adenoCA: lung - Lung: adrenal, liver - Melanoma: liver, lung - Prostate: bone - Testicular tumor: para-aortic nodes
234
Function of dabigatran
- Direct thrombin (IIa) inhibitor)
235
What is the cytological marker(s) used to determine seminoma?
- placental alkaline phosphatase
236
What cancers is the tumor suppressor gene Rb associated with? What is the function of this gene product? Describe mechanism.
- Retinoblastoma, osteogenic sarcoma, soft tissue sarcoma - Function: inhibits G1 to S phase induction
237
Epithelial tissue tumor names
- Benign: adenoma (glandular origin), papilloma (non-glandular with finger-like/warty projections from epithelial surfaces) - Malignant: carcinoma (non-gland), adenocarcinoma (glandular)
238
Cancers associated with Eaton-Lambert syndrome/Myasthenia gravis-like syndrome?
- Small cell CA of lung
239
43 yo female presents with an abnormal cervical Pap in her yearly health check. Colposcopy reveals a suspicious lesion on ectocervix and biopsy is performed. Path examination reveals full thickness dysplasia from the basement membrane to the surface epithelium. No cells have crossed the BM. Which of the following is the most likely diagnosis? a.) cervicitis b.) mild dysplasia (CIN1) c.) severe dysplasia (CIN3) d.) carcinoma in situ (CIS) e.) invasive carcinoma
- D. CIS, which is specific type of CIN3 when dysplasia in 100% (full thickness) of cells.
240
What cancers increase in frequency with age?
- Carcinomas
241
Compare and contrast carcinomas vs sarcomas in terms of incidence, initial mode of spread, nomenclature, examples, prognosis, metastasis time presentation
a.) Carcinoma (epithelial origin) - CA - more common incidence, lymphatic spread, named: tissue of origin+carcinoma, better prognosis, metastasis presents later - examples: squamous cell CA, transitional cell CA, adenoCA b.) Sarcoma (mesenchymal origin) – SA - less common incidence, hematogenous spread, tissue of origin+sarcoma, poor prognosis, metastasis presents early - examples: leiomyoSA, rhabdomyoSA
243
Cancers associated with atomic bomb
- Leukemias (except CLL) - Thyroid cancer (papillary type) - Less commonly breast, lung, skin, bone, gut
244
Examples of cancers that seed into pleural cavity
- primary lung cancer - metastatic lung cancer - adenocarcinoma (at periphery of lung)
245
Tumor suppressor gene mutation associated with breast and ovarian cancers. Function?
- BRCA-1 (both), BRCA-2 (mostly ovarian) - Functions to regulate DNA repair normally. - Also p53 associated with breast cancer
246
B cell follicular lymphoma. Describe the molecular/genetic basis.
- Translocation of Bcl-2 anti-apoptotic genes between c/s 14 and 18 = over-expression of genes = evasion of apoptosis in B lymphocytes
247
Mutation to single copy of tumor suppressor gene is not sufficient to cause loss of function. True / False.
- True. Requires homozygous mutation to = loss of function. - Knudson’s two-hit hypothesis
248
The metastatic potential of cancer cells would be enhanced by upregulation of the gene for which of the following proteins? a.) CD2 b.) CD4 c.) CD8 d.) CD22 e.) CD44
- CD44
249
What is the cytological marker(s) used to determine tumor of epithelial origin?
- CK (cytokeratin) or EMA (epithelial membrane antigen)
250
Describe epigenetic changes that leads to changes in DNA expression
- DNA methylation of histones = formation of heterochromatin = compaction of DNA = reduction in expression - If reduction in tumor suppression gene expression = potential for cancer development
251
Burkitt lymphoma. Describe molecular/genetic basis. Types of disease?
- Translocation of C-myc from c/s 8 to adjacent Ig HC site on c/s 14 = over-expression of c-myc - Types: endemic/African, sporadic, HIV-associated
252
What is a hydropericardium?
- Fluid accumulation in the space between the heart and pericardium
253
What is severe sepsis?
- Severe sepsis = sepsis + MODS (multi-organ dysfunction) = SIRS + documented infection + MODS - SIRS = Fever, HR \> 90, RR \> 20 (or Paco2 \< 32), leukocytosis/leukopenia (or 10% bands)
254
Describe morphological changes that occur in the following organs with shock: brain, heart, kidneys, lungs, adrenal gland, GI tract, liver
- Brain: ischemic encephalopathy - Heart: coagulation necrosis, subendothelial hemorrhage, contraction band necrosis - Kidneys: acute tubular necrosis - Lungs: diffuse alveolar damage - Adrenals: cortical cell lipid depletion - GI tract: mucosal hemorrhage / necrosis - Liver: fatty change, central hemorrhagic necrosis
255
Most common adult leukemia?
- CLL: chronic lymphoblastic leukemia
256
What is growth fraction? How does this relate to rate of cancer growth? To benign vs malignant neoplasms? Well-differentiated vs poorly differentiated tumors?
- Growth fraction refers to the percentage of cells in s-phase - Benign: typically has low growth fraction, generally grow slowly and are well-differentiated - Malignant: typically has high growth fraction, generally grows fast and are poorly-differentiated
257
Laboratory measurement of extrinsic/intrinsic coagulation time
- Intrinsic: PTT (partial thromboplastin time) - Extrinsic: PT (prothrombin time)
258
CML (chronic myeloid leukemia) and ALL (acute lymphoblastic leukemia). What oncogene (and category) can be involved in this cancer? What DNA change occurred?
- Signal transduction = ABL - Translocation
259
Epidemiological parameters for cancer studies
- SAREE - Sex, age, race, ethnicity, environmental
260
Define spinal vs neurogenic shock
- Spinal: initial loss of spinal cord function following injury including motor, sensory and SNS function - Neurogenic: loss of SNS ANS function d/t spinal cord injury. Result = unopposed PSNS (vagal) tone = systemic vasodilation, bradycardia. Occurs with lesion at or above T6.
261
What type of situation normal leads to arterial thrombi vs venous thrombi? Locations?
- Arterial thrombi is usually occlusive results from endothelial injury – coronary \> cerebral \> femoral arteries - Venous thrombi usually results from stasis – mostly in lower extremity deep veins
262
Cancers associated with EBV
- DNA virus - Burkitt lymphoma - Hodgkin lymphoma - B-cell lymphoma in immunosuppressed - Nasopharyngeal CA
263
What does generation of heterogeneity in tumor progression refer to?
- Normal cell becomes tumor cell (monoclonal origin) - All daughter cells in tumor mass are variants, ie.: a.) Some cells require fewer growth factors b.) Some cells are non-antigenic c.) Some cells are invasive d.) Some cells are metastatic
