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General Pathology Theory > misc first 10 Robbins chapters > Flashcards

misc first 10 Robbins chapters Flashcards

1
Q

List some AD inherited syndromes

A
  • Huntington disease - Marfan syndrome - Familial hypercholesterolemia - Achondroplasia
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2
Q

What does serum transferrin measure?

A
  • Iron absorption
  • transferrin saturation=serum iron x 100/total iron binding capacity
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3
Q

What type of organisms are Nocardia species?

A
  • Gram positive bacteria growing in bead-like chains - They cause skin, CNS, respiratory infections in immunocompromised patients
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4
Q

DIC depletes all factors except:

A
  • Fibrin split products
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5
Q

Which inheritable genetic condition exhibits anticipation?

A
  • Huntington disease
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6
Q

JAK2 mutations are associated with which condition?

A
  • Polycythemia vera 95% are associated with JAK2 mutations
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7
Q

Name an anti-apoptotic protein

A
  • BCL2, is anti-apoptotic and up-regulated in malignancies when compared to non-malignant conditions
  • Eg. follicular lymphoma vs reactive lymphoid follicle
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8
Q

In what condition would you expect to see cardiac rhabdomyomas in children?

A
  • Tuberous sclerosus, where cardiac rhabdomyomas are seen in 50% of neonates
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9
Q

Which cellular process is associated with cytochrome C release from the mitochondria?

A
  • Intrinsic pathway apoptosis
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10
Q

What are the conditions associated with trisomies 13, 18, 21?

A

13=Patau

18=Edward

21=Down syndrome

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11
Q

Name a disease associated to HLA-DR3

A
  • diabetes
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12
Q

Which disease is associated with an 8:14 translocation?

A
  • Burkitt lymphoma
  • c-myc/IGH translocation
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13
Q

Name 3 functions of p53

A
  • Induces cell cycle arrest
  • induces apoptosis
  • upregulates genes involved in DNA repair from radiation
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14
Q

What is the translocation involved in synovial sarcoma?

A
  • t (X;18), SYT-SSX
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15
Q

What are kimmelstein wilson bodies and what disease are they associated with?

A
  • Pink hyaline nodules forming in glomerular capilaries, seen in diabetes
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16
Q

What is the IF staining pattern associated with Lupus?

A

Full house: IgG, IgA, IgM and complement

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17
Q

Name a proto-oncogene

A

KRAS

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18
Q

What virus is implicated in Kaposi sarcoma

A

HHV8

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19
Q

Name a condition associated with abnormal imprinting

A
  • Prader-Willi, associated with 15q deletion in paternally derived chromosome
  • Angelman syndrome associated with 15q deletion in maternally derived chromosome
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20
Q

Describe the effects of whole body irradiation by sievert ranges

A

0-1 none

1-2 lymphocyte damage, moderate granulocytopenia

2-10 sv: bone marrow destruction (leucopenia infections, n/v, fatigue), skin burns and rash with mucosal desquamation

10-20sv: damage to mucosal surfaces within small bowel; severe diarrahea, fatigue, NV, permanent sterility

>50 sv: damage to brain, coma and convulsions

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21
Q

What is the function of the Langerhans cell? What are the ultrastructural features?

A
  • functions in antigen presenting in the skin
  • BIrbeck granules are present in the cytoplam
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22
Q

What is the Lyon law?

A
  • Lyon law refers to the random and fixed inactivation of one X chromosome in mammalian cells at an early stage of embryogenesis, leading to mosaicism of paternal and maternal X chromosomes in females
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23
Q

What are functions of mast cells?

A
  • Degranulation and release of allergic mediators from granules in response to allergens (immediate hypersensitivity)
  • Release of eicosanoids (thromboxane, PGD2, leukotrienes) for late phase allergic response
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24
Q

Describe the types of prostaglandins and their functions

A
  • PGI2: promotes vasodilation, inhibits platelet aggregtion
  • PGE2: decreases gastric acid, increases gastric mucin, promotes vasodilation and GI smooth muscle relaxation
  • PGD2: promotes vasodilation, increased vascular permeability
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25
Q

Describe the structure of an IgG molecule

A
  • Y-shaped structure with variable domain regions at the top of the Y arms and constant (FC) region at the base
  • 2 heavy chains and 2 light chains linked by disulfide bonds stabilize the structure
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26
Q

What is the most likely organism implicated in lung fungus balls?

A
  • Aspergillosis from mold Aspergillus fumigatus
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27
Q

What causes chronic granulomatous disease?

A
  • Cause: genetic defect in the phagocyte oxidase enzyme in neutrophils (NADPH oxidase), defect is x-linked or AR
  • NADPH required for respiratory burst in neutrophils activated by bacteria; generation of reactive oxygen species requires multiprotein NADPH oxidase complex that reduces oxygen to a superoxide anion and is able to form hydrogen peroxide. Hydrogen peroxide is further broken down into hypocholrite/halides to kill bacteria.
  • Reaction takes place in phagocytic vacuoles
  • Deficiency leaves pts prone to bacterial infections
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28
Q

Erythroblastosis is which type of hypersensitivity reaction?

A
  • Antibody mediated (type 2) hypersensitivity rxn
  • IgM/IgG binds to RBCs and triggers phagocytosis/lysis using membrane attack complex
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29
Q

Describe some types of brown pigmentation in tissue

A
  • BIle (green-brown): seen in bile canaliculi, intrahepatocytes. Stains with Hall’s bile stain.
  • Copper (yellow-brown): periportal hepatocytes, stains with orcein/rhodanine.
  • Iron (golden brown, refractile): in periportal hepatocytes, Kuppfer cells, iron overload. Perls Prussian blue.
  • Lipofuscin (brown): in centrolobular hepatocytes, maybe in Kuppfer cells. Acid fast stain + (FITE)
  • Melanin (black/brown, non refractile): melanoma, nevi, melanocytes.
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30
Q

What are some burn classifications and how do you estimate severity?

A
  • Can use 1st, 2nd, 3rd degree or superficial, partial thickness, full thickness
  • Superficial is epidermis only, erythema
  • Partial thickenss is epidermis/dermis, blistering
  • Full thickness is down to fascia/fat/muscle, painless, black
  • Estimating severity: rule of 9s (each arm=9%, each side of torso 18%, each leg 18%, head and neck 9%)
  • A burn requiring burn unit would be facial, perineal, cirumferential extremity burns, burns crossing joints, inhalational, any partial thickness >10% TBSA, any full thickness
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31
Q

What is the role of ATP in diffuse axonal injury?

A
  • Diffuse axonal injury is due to shear forces from rapid acceleration /deceleration leading to axonal disruption or separation in the brain stem, corpus callosum cerebral hemispheres, cerebral cortex, cerebral peduncles or basal ganglia
  • Is a biochemical cascade; initiating factor is disruption of microtubule skeleton. Axonal transport continues to the point of rupture where amyloid precursor protein is carried and accumulates via ATP-dependant proteins; this leads to retraction balls caused by axonal swellings
  • Further changes include opening of sodium channels, loss of calcium gradient, activation of phospholipases/caspases
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32
Q

What is Reye syndrome?

A
  • A sudden, potentially fatal disease of brain (encephalopathy) with degeneration of the liver
  • Occurs in children, 4-12 yrs
  • Post-viral (varicella, influenza)
  • associated with aspirin
  • presents with vomiting, lethargy, progressive neurologic dysfunction
  • histology: acute non-inflammatory encephalopathy and acute fatty liver changes
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33
Q

Define angiogenesis

A
  • Angiogenesis: the physiologic process of developing new blood vessels from pre-existing vessels that allows essential physiologic processes to take place: wound healing, revascularization after trauma, menstruation, granulation tissue
  • Pathologic angiogenesis occurs with tumor growth, diabetic retinopathy, chronic inflammation
  • Vasculogenesis is growth of new vessels from circulating stem cells during embryonic development
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34
Q

List 5 angiogenic growth factors

A
  • Vascular endothelial growth factor (VEGF)
  • Platelet derived growth factor (PDGF)
  • Transforming growth factor B (TGF-B)
  • Fibroblast growth factor (FGF)
  • Angiopoeitin 1/2
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35
Q

How does VEGF function?

A
  • VEGF is most important angiogenic factor
  • Binds to VEGF receptor, promotes the release of endothelial precursor cells from bone marrow
  • Stimulates endothelial cells to migrate and proliferate to new vessels from existing ones
  • Induced by hypoxia, TGF-B released from wounds, PDGF from platelets, TGF-a from inflammation
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36
Q

At what point after an injury does a wound reach 10%, 50% and 80% of its preinjury tensile strength?

A

1 week=10%

1 month=50%

3 months=80%

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37
Q

Describe the cells and factors involved in wound healing

A

Phase 1: homeostasis. Hours 0-24. Clot formation. Involves platelets, neutrophils. Factors: fibrin, growth factors, cytokines, clotting cascade.

Phase 2: inflammatory phase. 3-7 days. Formation of granulation tissue, macrophages remove bacteria and debris. Cells: fibroblasts, macrophages, endothelial stem cells. Factors: VEGF

Phase 3: proliferative phase. 1-3 weeks. Cells: fibroblasts deposit collagen, myofibroblasts contract wound, epithelial cells re-epithelialize. Factors: type 3 collagens, laminin, FGF, TGFB, chemokines

Phase 4: remodelling (3 weeks-months). Scar tissue formation at 4 weeks, collagen cross linking, replacement of type 3 collagen with type 1 collagen. Cells: fibroblasts, macrophages. Factors: MMPs, inhibitors of MMPS.

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38
Q

Describe the sequence of events in healing by primary intention

A
  • Occurs in small, clean incisions where edges line up
  • Standard 4 phases of wound healing: clot, inflammation, proliferation, maturaiton
  • either small lacerations/surgical wound, heals with minimal scarring
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39
Q

Describe the sequence of events in healing by secondary intention

A
  • Larger wounds heal with more granulation tissue, scar, wound remodeling and contraction
  • Broader scar formation, slow to heald if infected, requires wound care to prevent infection
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40
Q

What basic processes are involved in wound repair by connective tissue deposition?

A
  • Inflammation, angiogenesis, migration/fibroblast proliferation, scar formation, connective tissue remodelling
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41
Q

Name 4 local factors and 4 systemic factors retarding wound healing

A

Local: infection, mechanical (early motion), foreign bodies, size/location of wound

Systemic: nutrition (protein deficiency, vitamin C deficiency), metabolic status (DM), circulatory status, glucocorticoids

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42
Q

List 2 examples of abnormal wound healing

A
  • Keloid scar
  • Wound dehiscence
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43
Q

List vitamins affected by pancreatic insufficiency

A

ADEK (fat soluble)

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44
Q

List fat soluble vitamins, their physiologic functions, and diseases resulting from deficiencies

A

A: vision, embryogenesis, epithelium formation, infection resistance. Deficiency: night blindness, corneal dryness, infections, squamous metaplasia

D: calcium absorption from intestines, bone mineralization. Deficiency: bone defects, osteoporosis

E: antioxidant. Deficiency: spinocerebellar degeneration, immune response, retinopathies

K: cofactor for factors II, VII, IX, X in coagulation cascade. Deficiency: bleeding

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45
Q

List the fat insoluble vitamins, physiologic function and diseases from deficiency.

A

B1 (thiamine): coenzyme in decarboxylation. Wernicke-Korsakoff.

B2 (riboflavin): enzyme cofactor. Angular chelitis, stomatitis…etc.

B3 (niacin): NADH/NADPH formation. Pellagra: dermatitis/dementia/diarrhea

B6 (pyroxidine): Synthesis of serotonin/dopamine/norepi/epi. Peripheral neuropathy, depression, dermatitis

B12 (cobalamin): DNA/folate syntehsis. Megaloblastic anemai, posterior lateral spinal cord degeneration.

C: collagen hydroxylation. Scurvy (bleeding mucous membranes)

Folate: DNA synthesis. Neural tube defects, megaloblastic anemia.

Panthothenic acid: needed for coenzyme A. Numbness/burning in feet.

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46
Q

List the common causes of vitamin B12 deficiency

A
  • Autoimmune gastritis with pernicious anemia
  • Inadequate vitamin B12 intake
  • Terminal ileum damage/resection
  • Crohn disease
  • Intestinal bacterial overgrowt
  • Fish tapeworm infection
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47
Q

List the pathologic features of vitamin B12 deficiency

A
  • peripheral neuropathy: dgeneration of dorso-lateral spinal columns with ataxia, weakness
  • Macrocytic anemia: leukopenia with macro polymorphs, giant megakaryocytes
  • Atrophy and intestinal metaplasia of stomach (pernicious anemia)
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48
Q

Describe the synthesis of vitamin D

A
  • 7-dehydrocholesterol reacts with UVB in skin to form vitamin D3
  • D3 is processed in liver by 25-hydroxylase to 25-OH-D3
  • 25-OH-D3 processed in kidney by 1-alpha-hydroxylase to 1,25 dyhydroxy vitamin D
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49
Q

What are the biologic effects of vitamin D?

A
  • Increases calcium and phosphate absorption in gut
  • Induces bone mineralization
  • suppresses PTH secretion
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50
Q

What part of the complement system is responsible for lysing RBCs?

A
  • RBC lysis requires membrane attack complex formation (MAC) formed by classical pathway complement proteins
  • Classical pathway: IgM/IgG bind antigen and C1, C3 binds and activates C3 convertase=C3a and C3b. C3a forms C5 convertase=C5a. This leads to membrane attack complex formed of C6 and C9.
  • Alternate pathway: triggered by LPS on bacteria
  • Lectin pathway: binds sugars on bacteria
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51
Q

What type of toxicity does oxygen cause to cells?

A
  • Oxidative damage. Excess oxygen causes formation of free-radicals and reactive oxygen species, which can lead to direct damage to cell membranes, nuclear DNA, cellular organelles
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52
Q

UV causes what type of DNA damage?

A
  • UVB: cross-links between adjacent cytosine/thymidine forming pyrimidine dimers
  • UVA: free radical formation cuases indirect DNA damage or breaks
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53
Q

List 5 types of DNA damage

A
  • Oxidation of base pairs and DNA strand breaks from ROS
  • alkylation of bases (methylation)
  • Hydrolysis, including deamination, depurination, depyrimidation
  • Adduct formation (modification with benzopyrene rings)
  • DNA mismatch repair
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54
Q

List 3 biochemical mechanisms responsible for cell damage

A
  • ATP depletion (reults in loss of function of NA/K pumps)
  • pH drop from lactic acid accumulation and anerobic metabolism, denaturation of enzymes
  • Ca2+ entry into cells with activation of proteases, phospholipases, endonucleases
  • Osmotic changes (cell rupture)
  • Detachment of ribosomes from ER with decreased protein synthesis
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55
Q

Define apoptosis and describe pathogenesis

A
  • Apoptosis: programmed cell death pathway, regulated by enzyme cascade, leading to DNA fragmentation, apoptotic bodies and cytoplasm degeneration
  • Intrinsic pathway: release of mitochondrial proteins (cytochrome C) to activate caspase 9

pro-apoptotic: BAX, BAK

anti-apoptotic: BCL2, BCL-x, MCL1

  • Extrinsic pathway: plasma membrane receptors containing FADD/death domains bind ligands and activate caspases, resulting in apoptosis (FAS ligand/FAS receptor)
  • Common downstream effect is activation of executioner pathways (caspase 3,6) leading to DNAses to cleave DNA; results in fragmentation into DNA ladders of approximately 200 bp
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56
Q

Compare and contrast apoptosis and necrosis

A

Apoptosis: no inflammation in surrounding tissue, isolated cells in healthy tissue

cytology: pyknotic nuclei, condensed chromatin, chromatin fragmentation (karryorexkis), cell shrinkage, blebbing of plasma membrane, formation of apoptotic bodies
staining: cell membrane not permeable to staining agents

EM: dense nuclear crescents and apoptotic bodies

Necrosis: inflammatory reaction frequent, cells die together resulting in structural deformation

cytology: karyorrhexis, edema, chromatin fading
staining: cell membrane permeable to stains

EM: swollen mitochondria, vacuoles in cytoplasm, fragmented organelles, ruptured plasma membrane/nuclear membrane

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57
Q

List 4 physiologic instances where apoptosis occurs

A
  • Programmed destruction during embryogenesis
  • Involution of hormone dependant tissues (endometrium)
  • Cell loss in proliferating cell populations (immature lymphocytes in thymus)
  • Elimination of potentially harmful self-reactive lymphocytes
  • Death of host cells (eg. neutrophils) in acute inflammatory response
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58
Q

List 4 pathologic instances of aoptosis and list the gene involved in regulating it.

A
  • DNA damage (free radicals from radiation, chemotherapy, hypoxia)
  • Accumulation of misfolded proteins (neurodegenerative disease, alpha-1-antitrypsin)
  • Cell death in certain infections (acute hepatitis)
  • Atrophy in parenchymal organs after duct obstruction (pancreas, parotid, kidney)

BCL2 is regulator for apotosis.

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59
Q

List functions of p53 in normal cell cycle

A
  • p53 is guardian of the genome; thwarts neoplastic transformation by 3 mechanisms:
  • activation of temporary cell cycle arrest (for DNA repair)
  • induction of permanent cell cycle arrest (sensecence)
  • triggers programmed cell death (apoptosis)
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60
Q

What is the role of p53 in carcinogenesis?

A
  • Guardian of genome, functions at G1/S checkpoint in cell cycle
  • Senses DNA damage and induces DNA repair, p53 mutation leads to DNA damage accumulation
  • Indues senescence/apoptosis if damage sensed; mutation leads to immortalization via defective apoptosis
  • p53 mutation leads to aneuploidy via centrosome destabilization (multipolar spindle)
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61
Q

What are the clinical implications of p53 mutation testing

A
  • Confirming malignancy (in certain cases)
  • Identifying cancer subtypes (i.e. triple negative breast ca)
  • Suggesting mechanism of carcinogenesis (Li-Fraumeni is inherited, increased risk of sarcomas, gliomas, leukemias, carcinomas)
  • May predict response to chemotherapy/radiotherapy
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62
Q

What methods can be used to detect p53 mutations?

A
  • PCR assay
  • Direct sequencing
  • IHC
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63
Q

Describe the function of miR-34 with respect to p53

A
  • p53 activates transcription of miR-34
  • miR-34 is a microRNA, small RNA molecules targeteting messenger RNA for destruction. MiR-34 targets cyclins, BCL-2, myc, cyclin-dependant kinases, notch for degradation
  • once these are degraded, cell goes through apoptosis/quiescence/senescence
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64
Q

Define cell necrosis

A
  • Cell necrosis: morphologic changes indicative of cell death caused by progressive enzymatic degradation
  • May affect groups of cells, part of structure or entire organ
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65
Q

Describe some pathological processes involved in cell death

A
  • Factors external to cell: infections, hypoxia leading to irreversible cell injury
  • ATP depletion, pH change, osmotic formces leading to denaturation of cell proteins/loss of membrane integrity
  • Release of enzymes from lysozymes, leading to degradation
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66
Q

List 3 histologic types of cell necrosis and one example of each

A

Coagulative necrosis: infarcts (myocardial, splenic)

Liquefactive necrosis: abcess, stroke

Gangrenous necrosis: diabetic foot ulcer

Caseous necrosis: TB, histoplasma, other fungal infections

Fat necrosis: acute pancreatitis

Fibrinoid necrosis: vasculitis (leukocytoclastic, Wegeners’…)

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67
Q

Name 2 histologic features of reversible cell damage

A
  • Cellular swelling
  • Fatty change
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68
Q

List 4 vascular changes in acute inflammation

A
  • Vasodilation
  • endothelial permeability
  • neutrophil recruitement
  • blood flow stasis
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69
Q

List 4 endothelial leukocyte adhesion molecules

A
  • L-selection (CD34)
  • VCAM 1
  • P and L-selectins (sialyl-lewis modified proteins)
  • B2 integrins (CD18), which bind ICAM, fibrinogen, fibronectin
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70
Q

List 5 inflammatory mediators

A
  • Histamine
  • Serotonin
  • Cytokines
  • Tumor necrosis Factor
  • interleukins
  • chemokines
  • leukotrienes
  • complement factors
  • nitric oxide
  • ROS
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71
Q

List 5 gross morphologic features seen in diabetes

A
  • Blood vessels: atherosclerosis of aorta, peripheral vascular disease with ischemic foot ulcers, renal artery stenosis, stroke, coronary artery atherosclerosis
  • Kidneys: nephroscelrosis
  • Eyes: retinopathy, glaucoma, cataracts
  • Skin: cellulitis
  • Bladder: autonomic neuropathy, dysfunctional bladder
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72
Q

List 5 clinical features in untreated diabetes and 4 causes of death

A
  • Diabetic retinopathy, diabetic peripheral neuropathy, diabetic foot/amputation, diabetic nephropathy, atherosclerotic cardiovascular disease
  • causes of death: stroke, MI, infection/sepsis, renal failure
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73
Q

What invasive fungal infection occurs in DM and in immunocompromised patients?

A
  • Mucormycosis/zygomycosis: fungus has large, non-septate hyphae, 90 degree branching. Angioinvasive.
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74
Q

What are the 3 components of Virchow’s triad?

A
  • Hypercoagulability, hemodynamic change (stasis, turbulence), endothelial injury
  • Describes three overlapping categories of factors contributing to thrombosis
75
Q

List 2 types of infarcts and 6 types of emboli

A

Infarcts: red infarct (venous occlusion), white infarct (arterial occlusion)

Emboli: fat, air, amniotic, tumor, bacteria, thrombotic

76
Q

Define amyloid and amyloidosis

A

Amyloid: a pathologic proteinaceous substance, deposited in extracellular space in various organs in a wide variety of clinical settings

Ultrastructure: 7.5-10nm intermediate filaments, haphazardly arranged. B-pleated sheet on crystallography

Amyloidosis: accumulation of amyloid proteins, resistant to degradation, causing systemic disease

77
Q

List the types of amyloid and the associated disease conditions

A

Can be systemic, hereditary, localized.

Systemic:

  • Primary: AL. Associated with multiple myeloma/plasma cell dyscrasia, some chronic inflammatory conditions
  • Secondary: AA, transthyretin (ATTR), B2 microglobulin. Associated with systemic senile amyloidosis, hemodialysis

Hereditary:

  • Amyloid associated, ATTR. Associated with Familar mediterranean fever, familial amyloidotic neuropathies

Localized:

  • APP (Ab). Alzheimer
  • Calcitonin (Acal). Medullary carcinoma thyroid
  • Islet amyloid peptide (AIAPP, AANF)-type 2 diabetes
78
Q

What are the microscopic features of amyloidosis and special stains? How can it be diagnosed clinically?

A
  • Micro: eosinophilic, pink waxy accumulation in extracellular space
  • Special stains: congo red (apple green birefringence on polarization), thioflavin T-yellow
  • IHC: APP, others
  • Clinical diagnosis: abdominal fat pad biopsy/aspiration, biopsies from rectum/tongue, gingiva, serum/urine elctrophoresis, imaging
79
Q

What are ANCAs?

A
  • Antineutrophil cytoplasmic antibodies
  • Pathogenesis: molecular mimicry of bacteria, leading to ANCA formation. Neutrophils with defective apoptosis release cellular components–DNA, MPO, PR3, elastase- in response to microorganisms
80
Q

List ANCA types and related diseases

A
  • c-ANCA: anti-proteinase 3. Wegners
  • p-ANCA: anti-MPO. Churg-Strauss, microscopic polyangiitis, ulcerative colitis, PSC, rheumatoid, polyarteritis nodosa
81
Q

List types of calcium crystals including one that could be invisible on slides

A
  • Calcium oxylate: polarize as flat rhomboids, refractile pale yellow/clear. Found in apocrine cysts/giant cell reactions, but not malignant. Can show up on mammograms. MAY BE INVISIBLE ON SLIDES !
  • Calcium phosphate: purple granular material, doesn’t polarize well, commonly seen on mammogranms. Seen in chronic inflammation, heart valves, breast cysts, sclerosing adenossis, hyalinization, DCIS, etc.
  • Calcium pyrophosphate: blue-purple rhomboidal crystals found in pseudogout
82
Q

If you have a mammogram with calcs but none on slide, what do you do?

A
  • Polarize
  • Cut deepr
  • Xray block
  • Check fixation time (did they dissolve?)
  • Rule out specimen mix-up
83
Q

What causes hypercalcemia in sarcoidosis?

A
  • Serum angiotensin converting enzyme (ACE) elevated in 75% of sarcoidosis pts
  • leads to elevation in serum calcium, extrarenal production of calcitriol, increased absorption of calcium in gut with serum hypercalcemia/HYPER calciuria and NOT RELATED TO PTH
  • same can lead to hypercalcemia in other granulomatous disorders
84
Q

How is sarcoid diagnosed?

A
  • Imaging: CXR/CT/MRI, PET/radionucleotide
  • Biopsies: skin, lymph nodes, other involved organs such as liver
85
Q

GVHD: describe the pathophysiology

A
  • T-cells derived from bone marrow transplant recognize the recipient (host) as foreign, and mount an immune response typically targetting skin, mucosa, liver, GI tract
86
Q

Describe the characteristic histologic features of GVHD (acute and chronic) in the skin, colon, liver, esophagus, stomach

A

Skin:

  • acute: 0- no change. 1-vaculolar alteration at DEJ. 2-dyskeratotic keratinocytes. 3-partial separation of DEJ. 4-complete separation of DEJ
  • chronic: lichenoid GVHD or sclerodermoid GVHD

Colon:

  • acute: r/o CMV first. 1-increased epithelial cell apoptosis. 2-crypt abcesses. 3-necrosis of individual crypts. 4-complete destruction of mucosal lining
  • chronic: ischemic change from fibrosis, crypt loss

Liver:

  • acute: presents with portal/periportal inflammation with extension into parenchyma with hepatocyte necrosis, looking like chronic hepatitis
  • chronic: bile duct damage/loss, portal tract inflammation, fibrosis, endotheliasis with endothelial lifting

Esophagus: similar to skin

Stomach: glandular destruction, apoptotic debris similar to colon

87
Q

Describe the effects of corticosteroids and their mechanisms

A
  • Corticosteroids are produced in the adrenal cortex, affect stress reponse, immune response, carbohydrate metabolism, lipid and protein metabolism
  • Mechanisms:
  • Inflammation: bind to glucocorticoid receptor, enter nucleus, bind DNA and upregulate genes involved in anti-inflammation, downregulate pro-inflammatory
  • metabolisM: metaoblize glucose via stimulation of gluconeogensis in liver, mobilize amino acids from other tissue, inhibit glucose uptake by adipose, stimulate fatty acid release and fat breakdown
  • CNS: cross BBB and bind to receptors, regulate blodo pressure, salt excretion, sympathetic activation
  • Embryogenesis: promote surfactant production
88
Q

List the complications of long-term steroid use

A
  • Immunodeficiency: decreased function and # of neutrophils, lymphocytes, macrophages predisposing to infectin
  • Adrenal insufficiency if steroids withdrawn
  • Cushing syndrome: bilateral adrenal cortical atrophy, decreased ACTH
  • hyperglycemia: DM, insulin resistance
  • Osteoporosis, cataracts, HTN, hypothyroidism, growth failure, glaucoma, slow wound healing
89
Q

List 4 occupations at increased risk of lead poisonning

A
  • Lead miners, plumbers, welders, battery recylers
90
Q

List organ systems affected by lead and their clinical presentation

A

CNS: decreased IQ, peripheral neuropathy, behavioural changes, coma

Bone: lead lines in epiphysis

Hematopoetic: microcytic anemia, basophilic stippling, ringed siderblasts

Kidney: proximal tubular damage

GI: diffuse abdominal pain, gingiva lead line

91
Q

Name 3 methods to measure cell proliferation, give advantages and disadvantages

A

Ki67/mib1:

  • easy in FFPE, established marker, captures all proliferating cells regardless of stage in cell cycle
  • only in formalin-fixed, not a true measure of mitoses

Mitotic count:

  • specific for mitotic cells, can identify aberrant mitoses, recognized in H&E sections
  • tumor heterogenetity, can’t identify those outside of mitotic phase (can confuse apoptosis)

Flow cytometry/FACS:

  • can count cells in each phase, can determine ploidy, used as ancillary technique in cytology
  • fresh tissue only, technical expertise, 2-3d turn-around-time
92
Q

Describe principles of PCR

A
  • technique used to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating thousands–>millions of copies of DNA sequence
  • Amplification of a target sequence of DNA using 3’ and 5’ primers, each cycle has 3 steps:
    1. heat denaturation (dsDNA to ssDNA)
    2. primer addition + cooling to anneal
    3. DNA synthesis by DNA polymerase
  • after 25 cycles, 10^7 copies are made
93
Q

List 3 applications of PCR as diagnostic tool

A
  • Direct sequencing: cancer gene translocations, forensics for identity
  • clonality assays: T-cell receptor genes in lymphomas
  • DNA mismatch repair: MSI
  • infectious agent identification: TB, HPV, HepC
94
Q

Describe Southern Blot and Northern Blot assays

A

Southern: detection of specific DNA sequence, combines DNA fragments separated by electrophoresis on a filter membranes with probes. Do it by electrophoresing DNA fragments (after restriction enzyme digest), transfer to filter membrane, hybridize complementary dsDNA probes to filter to detect specific gene of interest. Useful for DNA fingerprinting, syndrome detection eg. trinucleotide repeats

Northern: detects specific RNA sequences. Same protocol as Southern (place RNA on nitrocellulose filter after running through gel electrophoresis), add radiolabelled DNA/RNA probes to asses mRNA levels/expression. Used for comparison of gene expression in tumors, detection of mRNA, prognostic information.

95
Q

Describe the principles of FISH and gives some clinical applications.

A

FISH: targetted probes bind specific DNA seqences on intact chromosomes prepared from interphase nuclei

Fusion probes; translocations. 2 colours come together to give 1 signal. Breakapart: give 3rd colour when separate

Applications: trisomies 13,18, 21; aneuploidy in cancers, amplifications in cancers, cancer specific translocations, HER2, 1p/19q deletion

96
Q

Describe the principles of array CGH

A
  • CGH-microarrays compare DNA content from 2 differentially labelled genomes
  • 2 genomes (typically test/reference) are labelled w/different dyes, the co-hybridized onto solid support (such as glass slide) on chich synthesized DNA fragments have been immobilized
  • Arrays may have oligonucleotides, cDNA, etc.
  • Over or underexpression is expressed by the dye colours
97
Q

Describe the main steps in CGH microarrays

A
  • Label genomic DNA from test tissue/control tissue with different dyes
  • Affix microarray DNA gene probes to glass slide to form microarray
  • Hybrizide genomic DNA on slide
  • Compare levels of fluorescence between test/control for each gene
98
Q

Give some clinical examples of CGH-based microarrays

A
  • tumor molecular classification: eg. breast, lymphoma
  • metastatic tumor of unknown primary
  • prediction of response to therapy
  • prognostication
  • study of pathogenesis
99
Q

Electron microscopy: Describe the technical process

A
  • Fixation and processing: fix in glutaraldehyde, apply osmium tetroxide, dehydrate in graded series of ethanols, impregrnate with epoxy resin
  • Embed tissue in mold
  • Section: heat resin-infiltrated tissue and harden into blocks, cut sections 60-90um thick, collect onto grids
  • Microscopy: image under electron microscope and capture image
100
Q

List examples of clinical applications of EM

A
  • Pediatric pathology: storage diseae, ciliary diskinesia, small blue cell tumors, etc.
  • Renal: basement membrane change, depositis
  • Adult tumors: poorly differentiated, adenocarcinoma vs mesothelioma
  • Infections: bacteria (whipple disease), viral particles
  • Neuropathology: CADASIL, mitochondrial disease, metabolic storage disease
101
Q

Describe the principles of flow cytometry

A
  • Label cells with specific dyes
  • Either to cell lineage markers or to cell components
  • Measure fluorescence of dyes after exposure to argon laser (liquid medium containing cells flows past laser)
102
Q

Describe the applications of flow cytometry

A
  • Cell marker/cell type analysis (CD markers) for lymphoma
  • DNA ploidy
  • cell size analysis (again for lymphomas)
  • cell cycle analysis (G2, S, G2, M phases)
103
Q

Describe principles of DNA hybridization and list 3 applications

A
  • DNA strand complementary to that of intersest is labeled with fluorescent/radio-labelling to create probe
  • specimen DNA is denatured & transferred to a solid media
  • Spcimen DNA is incubated with labelled probe at a specific temp.
  • Excess probe washed off and image produced using appropriate detection method.

Applications : This is basis of linear array for HPV, southern blots for mutations, comparative CGH, even FISH

104
Q

If you were to make a tissue microarray, how would you do it?

A
  • take specimen from donor block, and remove tissue with punch
  • transfer core to blacnk wax block
  • now IHC can be used on the tissue array
  • Can be used to compare protein expression across multiple tissues/tumor types
105
Q

CISH vs FISH: Benefits?

A

CISH: no loss of signal over time, no need for fluorescent microscope

106
Q

List one CISH test currently used, and the component tested

A

EBER: Epstein-Barr virus. CISH for EBER-1/2 EBV encoded snRNA

107
Q

List 5 basic stains needed for any IHC lab

A

pan cytokeratin, CD45, S100, neuroendocrine marker, PLAP

108
Q

List the principles of ulabeled antibody peroxidase/anti-peroxidase method of IHC testing

A
  • Primary antibody recognizes epitope of interest (rabbit IgG)
  • Linking antibody recognizes primary Ab (anti-rabbit IgG)
  • ANtiperoxidase antibody from same species as primary (rabbit antiperoxidase) is complexed with peroxidase, and incubated
  • Peroxidase polymerizes when it binds into a pigment that stains tissue
109
Q

Histochemical stain for acid mucopolysaccharides. Describe how it stains.

A
  • Alcian blue: it’s a copper-based dye that binds electrostatically to negatively charged acidic mucins giving a blue colour
110
Q

How do silver stains work? What are their applications in histology?

A
  • Silver stains tissues at sites of reduction of silver ions
  • Argyrophilic: reducing agent is light/external substance eg. grimelius for neuroendocrine
  • Argentaffin: reducing substance is in tissue stained. eg. Masson-fontana for melanin
111
Q

What’s the biochemistry behind PAS staining and its applications in histology

A

PAS: periodic acid schiff reagent interacts with diols on carbohydrates (glycogen, glycoproteins, proteoglycans) resulting in red colour

applications: identify glycogen producing tumors, staining basement membranes, mucin, fungal walls

112
Q

Give 5 IHC stains and their utility

A

CD45: hematopoetic lineage marker

S100: neurological/neural crest marker

Synaptophysin: neuroendocrine marker

Desmin: muscle marker

Inhibin: germ cell line marker

113
Q

List 5 histochemical stains and their utility

A

gram: Gram positive bacteria are purple/blue, gram negative are pink
grocott: silver stain to detect fungi

Ziehl-Neelsen: identify mycobacteria

PAS/Alcian blue: neutral/acidic mucin

congo red: amyloid

114
Q

S100 and HMB45: what are they and their use in IHC?

A

S100: calcium binding protein, found in neural-crest derived cells

HMB45: human melanoma black protein, melanoma and others with melanocytic differentiation

115
Q

What causes hereditary angioedema?

A
  • Deficiency of C1 protease inhibitor of the complement cascade
  • Causes accumulation of Factor XII and bradykinins
  • leads to episodes of edema of skin, larynx, GI tract
116
Q

What genetic syndrome causes dgenerative arthropathy and black urine?

A
  • Alkaptonuria (ochronosis): AR deficiency in homogenistic oxidasae
  • Arthropathy: deposits of homogenistic acid into cartilage/connective tissue, with bluish-black pigment in joits
  • looks like solar elastosis
  • Hardened connective tissue can have FB giant cell rxn
  • Can cause pigment excretion into ducts (breast, prostate, sweat)
117
Q

Von- Hippel Lindau: Describe the features of the disease

A
  • AD condition, mutation of VHL tumor suppressor gene on chromosome 3
  • Associated with: renal cysts (75%), clear cell RCC, angiomyolipoma, hemangioblastomas in cerebellum, spinal cord and retinal hemangiomas, pheochromocytomas, pancreatic cysts
118
Q

A person with renal cysts and berry aneurysms has what syndrome?

A
  • Autosomal dominal polycystic kidney disease (ADPKD), mutations on PKD1 (16) and PKD2 (4)
  • Large multicystic kidneys, liver cysts, berry aneurysms
  • Presents in adulthood with hematuria, flank pain, UTI, stones, HT, CRF at 40-60yrs
  • Autosomal recessive (ARPKD), mutations in PKHD1 (6)
  • cystic kidneys at birth + hepatic fibrosis
  • death in infancy/childhood
119
Q

Define Gaucher disease

A
  • Rare hereditary AR disorder causes glucocerebroside to accumulate in spleen/liver/lungs/bones/brain with organ dysfunction
120
Q

What are the types of Gaucher disease?

A

Type 1: most common, hepatosplenomegally, bone pain, bone fractures, no brain involvement. Presents at any age

Type 2: Severe brain damage, appears in infants, early death

Type 3: intermediate, hepatospenomegally, gradual brain involvement.

All glucocerebrosidase deficient

121
Q

What are the morphologic characteristics of Gaucher’s disease?

A
  • Gaucher cells are found in liver, spleen, bone marrow, lymphoid tissue with abundant tissue paper cytoplasm
  • Positive with PAS, also perl’s prussian blue
  • EM: numerous elongated single-membrane bound lysosomes in cytoplasm
122
Q

Define Niemann pick and describe the clinical variants

A

Niemann pick: hereditary AR biochemical disorder, caused by intracellular accumulation of sphingomyelin, resulting in hepatosplenomegally, lymphadenopathy, anemia, mental/physical deterioration

Variants: classical infantile (A), visceral (B), Subacute (C), Nova Scotia variant (D), Adult (E)

123
Q

List 3 disorders caused by sex chromosome imbalance

A

XO: Turner’s

XXY: Klinefelters

XYY: ?

124
Q

List 3 trisomies

A

13: Patau
18: Edwards
21: Down syndrome

125
Q

List 4 specific HLA subtypes and associated diseases

A

HLA-DR3: DM type 1, SLE, Sjogren

HLA-B27: ankylosing spondylitis

HLA-DQ2/8: celiac

HLA-DR15: MS

126
Q

What’s phenyl ketonuria

A
  • AR inheritable mutation in phenylalanine hydroxylase
  • pts cannot metabolize phenylalanine, leading to toxic accumulation and neurologic deficits
  • restrict phenylalanine in diet
127
Q

What is Down Syndrome

A
  • most common chromosomal disorder in live infants, due to extra chromosome 21
  • Causes: mental retardation, characteristic facies with flat face, low nasal bridge, epicanthal fold, narrowing of palate, congenital heart defects (endocardial cushion defects), duodenal atresia, risk of leukemia
128
Q

VHL: genetic abnormality and associated malignancies

A

mutation in VHL protein, resulting in constitutive hypoxia signalling

RCC, pheochromocytoma, pancreatic cysts, retinal/cerebellar hemangiomas and hemangioblastomas

129
Q

What’s the genetic abnormality in neurofibromatosis type 1

A

NF1: mutation in NF1 gene encoding neurofibromin

associated with neurofibromas (plexiform), cafe-au-lait, lish nodules in iris, malignant peripheral nerve sheath tumor, scoliosis, optic gliomas

130
Q

Name some malignancies associated with EBV

A
  • Burkitt lymphoma
  • B-cell lymphoma
  • Nasopahryngeal carcinoma
  • Post-transplatn lymphoproliferative
  • Lymphomatoid granulomatosis
  • Plasmablastic lymmphoma
  • peripheral T-cell lymphoma
  • Classic hodgkins

NK-Tcell

131
Q

List 4 methods for identifying EBV in neoplasms

A
  • PCR
  • EBER (small nuclear RNAs)
  • IHC (EBV latent membrane protein)
  • other tests such as peripheral smears/monospot test for EBV infection
132
Q

Describe the role of EBV in associated neoplasms

A
  • Infection with EBV leads to expression of EBNA1, EBNA2 and LMP-1 oncogene
  • EBNA2 increases transcription of cell cycle proteins like cyclin D1
  • LMP1 activates NFB and JAK/STAT pathways
  • NKB enters nucleus leading to transcription of cell cycle proteins
  • LMP prevents apoptosis by increasing expression of BCL2
  • Translocation (8;14) leads to c-MYC translocation (Burkitt lymphoma)
133
Q

List non-neoplastic disorders associated with EBV

A
  • Mononucleosis (pharyngitis, fever, lymphadenitis, splenomegally)
  • fever of unknown origin
  • generalized rash
  • splenomegally
  • EBV hepatitis
  • Meningitis
  • Pneumonia
  • Encephalitis
134
Q

Define oncogene and what is its normal counterpart

A
  • Oncogene: a gene found in cancer cells which, when expressed, directly or indirectly contributes to tumor cell growth, immortalization, dedifferentiation and metastatic potential.
  • Normal counterpart is a proto-oncogene; responds to appropriate signals for growth etc.
  • When mutated or abnormally expressed, contributes to cancer growth
135
Q

What are some of the roles of oncogenes in carcinogenesis

A
  • Anti-apoptosis
  • Defective DNA repair proteins that cause accumulation of mutated/damaged DNA
  • Can result in increased cell motilty and metastasis
  • Can cause growth factor receptors to become constitutively activated without need for growth factors
  • Can cause continuous cell cycling or prevent cell cycle arrest
  • Can cause de-differentiation
  • Can cause abnormal mitoses, resulting in aneuploidy
  • Can induce telomerase expression and overcome cellular senescence
136
Q

What methods are used to identify oncogenes?

A
  • Microarrays- compare expression of DNA/RNA/Proteins in cancer vs control
  • Clonality assays (PCR)
  • RNA interference (gene knock-out) to study gene function in mice
  • Transfection assays (introduction of genes + promoter sequences into cells)
  • Laser microdissection-cutting out area of interst on slide, using in microarray
  • Cytogenetics (chromosomal translocations)
  • Mutational analylsis (introduction of mutagen into cell culture)
  • cell motility assays
  • Epigenetics (study of DNA or histone modifications such as methylation/acetylation in differential gene expression(
  • Cell cycle analysis- study role of oncogene in cell cycle distrubition-uses FACS
  • TUNEL assays (detect apoptotic cells by detecting caspase induced DNA cleavage products)
137
Q

List 5 common oncogenic viruses

A
  • EBV (Burkitt, Hodgkin, Nasopharyngeal carcinoma)
  • HHV8-Kaposi Sarcoma
  • HPV 16,18-SCC/adenoCA of cervix
  • HTLV (human T-cell leukemia virus)
  • HCV-hepatocellular carcinoma
138
Q

List 5 neoplasms encountered in a patient with AIDS

A
  • Kaposi Sarcoma
  • CNS lymphoma (HIV associated, EBV driven)
  • systemic lymphomas (DLBCL, Burkitt)
  • Plasmablastic lymphoma
  • Primary effusion lymphoma
  • SCC of anus
  • SCC cervix
  • HCC (in those who are HCV/HBV postiive)
139
Q

Describe the relationship between malignancy and thrombosis

A
  • Malignancies cause hypercoagulable state; CD142 (factor III, tissue factor) expressed on tumor induces thrombin formation
  • Pancreatic/bronchogenic carcinoma can cause Trusseau phenomenon; secretion of mediators promoting thrombosis (migratory thrombophlebitis)
140
Q

What are 3 possile chromosomal changes in cancer?

A
  • Translocation (eg. BCR-ABL in CML)
  • Deletion (eg. 3p in lung ca)
  • Amplification (eg. HER2 in breast CA)
  • ring chromosomes (12 in liposarc)
141
Q

What are oncofetal antigens and what is their cliical significance?

A
  • Oncofetal antigens are those expressed during embryonic development but lost during normal adulthood
  • Commonly re-expressed in malignancies–eg. AFG in HCC, CEA in colon CA
142
Q

For each sarcoma listed name the genetic abnormality:

Alveolar soft part sarcoma

Synovial sarcoma

Myxoid liposarcoma

A

ALVEOLAR SOFT PART: T (X;17) TFE3

SYNOVIAL SARCOMA: T (X; 18) SYT-SSX

MYXOID LIPOSARCOMA: T (12;16) EWSR1-DDIT3

143
Q

List 4 familiar cancer syndromes and one tumor associated with each

A
  • Peutz-Jeghers syndrome: STK11/LKB1. Adenocarcinoma colon
  • MEN1: Menin. Gastrointestinal carcinoid
  • Familial atypical melanoma mole syndrome. P16/INK4a. Melanoma
  • Fanconi anemia. FANCA gene group mutations DNA repair. Acute myeloid leukemia
144
Q

For thoe following cancers, list the mutated gene.

Mantle cell lymphoma

Follicular lymphoma

Chronic myeloid leukemia

GIST

A
  • Mantle: t 11;14 cyclin D1-IGH
  • Follicular lymphoma t 14, 18 IGH- BCL2
  • Chronic myeloid leukemia: t 9;22 BCR-ABL
  • GIST: Ckit gene mutations chromosome 4
145
Q

List 3 syndromes related to abnormal DNA repair and give an example of the associated neoplasm

A
  • Fanconi anemia: colon CA
  • Ataxia-telangiectasia: lymphomas/leukemia
  • Xeroderma pigmentosum: melanoma, SCC
146
Q

List 3 tumors that can be treated with tyrosine kinase receptor inhibitors

A
  • GIST- treated with imatinib mesylate
  • Chronic myeloid leukemia-treated with imatinib
  • EGFR positive non-small cell lung carcinoma-treated with gefitinib and erlotinib
147
Q

List 2 genetic mutations that predict poor response to EGFR inhibitor therapy

A
  • KRAS, BRAF mutations
148
Q

For acute lymphoblastic leukemia/lymphoma (B-cell), list good and bad genetic alterations

A

Good: t (12;21), hyperdiploidy

Bad: t (9;22) philadelphia chromosome, translocations involving MLL gene 11q23

149
Q

What is the genetic alteration seen in ALCL

A

t (2;5) ALK-NMP

150
Q

List 3 common mutations in Burkitts

A
  • t 8;14 Cmyc-IGH
  • t 2;8 Cmyc-kappa
  • t 8,22 c-myc lambda
151
Q

AML: list 2 good, 2 intermediate, 1 poor translocations with prognostic significance

A
  • Good : t 8;21, inv 16
  • intermediate: t (15;17), 17-RAR- alpha
  • Bad t 11; 23
152
Q

Give the CML translocation

A
  • t (9;22) BCR-ABL fusion protein with tyrosine kinase activity
153
Q

DLBCL

A

t 14;18 BCL2 in 20%

BCL6 translocations in 30%

154
Q

follicular lymphoma translocation

A

14;18 BCL2-IGH

155
Q

Mantle cell lymphoma translocation

A

11;14 cyclin D1 IGH

156
Q

marginal zone lymphoma

157
Q

Angelman/prader Willi-genetic cause

A
  • ANgelman: 15q deletion on maternally derived chromosome
  • Prader-Willi: 15q deletion on paternally derived chromosome
158
Q

ADPKD

A

polycystin 1 & 2, 16p, 4q

159
Q

Cystic fibrosis: gene and deletion

A
  • CFTR (cystic fibrosis transmembrane conductance receptor) 7q
  • chloride channel
  • delta F508 most common mutation
160
Q

For the following conditions, list the enzyme deficiency:

Gauchers

Mucopolysaccharidoses

Niemann Pick

Tay Sachs

A

Gauchers: glucocerebrosidase deficiency

Mucopolysaccharidoses (hunters, hurlers): enzymes degrades mucopolysaccharides

Niemann pick: sphingomyelinase

Tay sachs: alpha subunit of hexosaminidase, leading to GM2-ganglioside accumuation

161
Q

X-linked agammaglobulinemia, Hyper IGM. What’s the problem?

A

X-linked agammaglobunemia: BTK (B-cell tyrosine kinase) mutation

Hyper IgM: CD40L (on T cells, X-q26) or CD40 (on B cells) mutation, can’t class switch from IgM

162
Q

List 2 conditions caused by trinucleotide repeats

A
  • Huntington-4p16, CAG repeats
  • Fragile X-Xq27 (FMR-1) CGG repeats
163
Q

Hemochromatosis: Gene and mutation

A

HFE on chromosome 6, C282Y mutation

164
Q

Ehlers-Danlos and Marfan, what are the underlying problems?

A

Ehlers-Danlos: defects in collagen synthesis.

  • Fibrous proteins: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB
  • Enzymes: ADAMTS2, PLOD1, B4GALT7

Marfan syndrome: defect in Fibrillin-1, glycoprotein scaffolding for elastin deposition 15q21 (is a dominant negative mutation)

165
Q

Give translocations: Alveolar soft part sarcoma, clear cell sarcoma of soft parts, congenital fibrosarcoma, desmoplastic small round cell tumor, DFSP

A

Alveolar soft part: t (X;17) TFE3-ASPL

cell cell sarcoma: t (22;22) EWS-ATF1

Congenital fibrosarcoma: t (12;15) ETV6-NTRK3

DSRCT: 11;22 (EWS-WT1)

DFSP (t 17;22) COLA1-PDGFB

166
Q

For each of breast, colon and endometrial carcinomas, give some common mutations/risk groups

A
  • Breast: low-grade 16q deletions. Also BRCA1 17q and BRCA2 13q. p53 mutations in hg
  • colon: APC, B-catenin, MSH, p53, KRAS
  • endometrial: type 1: MSI, PTEN, KRAS, Bcatenin. Type 2: p53
167
Q

What are 2 biochemical pathways involved in hypertrophy

A
  • PI3K/AKT
  • Gprotein-receptor pathways
168
Q

Name 5 cellular responses to injury

A

Hyperplasia, hypertrophy (increaed demand, increased growth stimulation)

Atrophy: decreased nutrients, decreased stimulation

Metaplasia: chronic irritation

Cellular swelling/fatty change-acute/transient injury (reversible)

necrosis/apoptosis: progressive/severe injury, irreversible cell death

169
Q

Give 3 physiologic examples of hypertrophy

A

Skeletal muscle-weightlifting

Myocardium-increased demand

Smooth muscle-uterus, gravid

170
Q

Name 3 transcription factors

A

Myc, FOS, Jun

171
Q

What is the mechanism of hyperplasia

A
  • It’s the result of growth factor driven proliferation of mature cells and in some cases increased output of new cells from tissue stem cells
172
Q

Give some common causes of atrophy

A
  • decreased workload
  • loss of innervation
  • diminished blood supply
  • inadequate nutrition
  • loss of endocrine stimulation
  • pressure
173
Q

List reversible and irreversible cell damage

A

Reversible: generalized cell swelling/organelle swelling, blebbing of plasma membrane, detachment of ribosomes from ER, clumping of nuclear chromatin

Irreversible: severe mitochondrial damage with depletion of ATP, rupture of lysosomes, rupture of plasma membranes

174
Q

Compare the features of necrosis and apoptosis

A

Necrosis: enlarged, swollen cell. Nucleus is pyknotic–>karryorrhetic. Plasma membrane disrupted. Enzymatic digestion of cell contents. Frequent associated inflammation. Invariably pathologic.

Apoptosis: reduced cell size. fragmentation of nucleus. Intact plasma membrane. Intact cellular contents, may be released in apoptotic bodies. No adjacent inflammation. May be physiologic or pathoogic.

175
Q

Name 3 inheritant free-radical scavenging systems

A
  • Catalase (in peroxisomes)
  • Superoxide dismutase
  • Glutathione peroxidase
176
Q

What are the pathways and functions of the complement system?

A
  • 3 pathways: classical, alternative, lectin

Classical: fixation of C1 to IgG/IgM that has met its antigen

Alternative: fixation of C1 to LPs, polysaccharides etc. in absence of antibody

Lectin: lectin binds to microbes and activates C1

  • 3 functions: increased vascular permeability, chemotaxis and opsonization
177
Q

Describe the complement pathways leading to the 3 effector functions of membrane attack complex, phagocytosis and inflammation

A
  • Activation of C1 by either classical, alternative or lectin pathway
  • C3 convertase splits C3–>C3a and C3b
  • C3b binds to surface of cell, C3a is released
  • C5 convertase splits C5–C5a and C5b
  • C5b binds to surface of cell, C5a is released
  • C5b on cell binds late components C6-C9, forming membrane attack complex (multiple C9s)
  • Receptors also recognize bound C3b–>phagocytosis
  • What about C3a, C5a? Recruitment and activation of leukocytes, leading to destruction of microbes by leukocytes
178
Q

List some inflammatory mediators involved in the following functions: vasodilation, increased vascular permeabiity, chemotaxis/leukocyte recruitment, fever, pain, tissue damange

A

Vasodilation: prostaglandins, NO, histamine

Permeability: histamine, bradykinin, leukotrienes, platelet activating factor

chemotaxis: TNF, IL1, chemokines, C3a/C5a
fever: TNF, IL1, prostaglandins

Pain: prostaglandins, bradykinin

tissue damage: lysosomal enzymes, reactive oxygen species

179
Q

VEGF: list the proteins, production sites, inducing agents, receptors and functions

A

proteins: VEG (A, B, C, D). Dimeric proteins with multiple isoforms.

Production: low levels in adult tissue, more in glomerulus/myocardium. Higher expression in pathologic states.

induced by: hypoxia, TGF-B, TGF-a, PDGF

receptors; VEGFR-1, 2, 3

functions: promotes angiogenesis, increases vascular permeabiity, simulates endothelial cell migration, stimulations endothelial cell proliferation, can induce hyperplasia of lymphatic vasculature

180
Q

What are 7 changes in cell physiology that determine the malignant phenotype?

A
  • Self-sufficiency in growth signals
  • Insensitivity to growth-inhibitory signals
  • Evasion of apoptosis
  • Limitless replicative potential
  • sustained angiogenesis
  • ability to invade/metastasize
  • defects in DNA repair
  • escape from immune attack
181
Q

Give a simple rundown of the molecular basis of cancer

A

Normal cell: acquires DNA damage (viral, radiation, chemical etc.)

Failure of DNA repair–>mutations in genome of somatic cells (+/- inherited mutations)

Activation of growth-promoting oncogenes, inactivation of tumor suppressing genes, alterations in genes that control apoptosis

Unregulated cell proliferation + decreased apoptosis=clonal expansion

Add angiogenesis, escape from immunity + additiona mutations=tumor progression

etc. etc. invasion and metastasis

182
Q

What are some features of digeorge syndrome?

A
  • 22q11.2 deletion syndrome
  • encompasses digeorge syndrome and velocardiofacial syndrome
  • congenital heart defects, developmental delay, t-cell immunodeficiency, hypocalemia, facial dysmorphism, cleft palate
  • thymic hypoplasia & parathyroid hypoplasia are characteristic
  • high risk of schizophrenia, bipolar, ADHD

General Pathology Theory (6 decks)

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