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Semester 3 Medical School > Mini 3 - Heme/Lymph/Musk 2 > Flashcards

Mini 3 - Heme/Lymph/Musk 2 Flashcards

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USMLE® Step 1 flashcards
1
Q

What is the structure of heme?

A

One Fe2+ in the center, protoporphyrin IX (tetrapyrrole ring).

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2
Q

Where is heme synthesized? Is it mostly excreted or recycled?

A

Mostly in BM, some in liver (for cyt P450), other minor locations.

Mostly excreted.

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3
Q

What is the rate limiting step of heme synthesis?

A

Porphyrin synthesis - delta-aminolevulinate synthetase (ALAS1 (liver)/ALAS2 (BM)) combine glycine and succinyl CoA to make ALA.

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4
Q

What controls ALAS1 and ALAS2 expression?

A

Hemin and low iron decrease ALAS1 and ALAS2 expression respectively.

ALAS2 also regulated by EPO.

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5
Q

What is X-linked sideroblastic anemia?

A

ALAS2 deficiency. Ringed sideroblasts, nucleated erythroblasts with mitochondrial iron granules.

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6
Q

Describe heme synthesis after ALAS.

A

In the cytosol, 2 ALAs are condensed to porphobilogen with ALA dehydrogenase.

Then condensation to hydroxymethilbilane by hydroxymethylbilane synthase.

Then macrocycle closure by uroporphyrinogen III synthase.

Then decarboxylation by uroporphyrinogel decarboxylase to make methy groups, and hen oxidation to make vinyl groups - end product coproporphyrinogen III.

Then linkers oxidized from methyl to methine groups to make protoporphyrin IX (intermediate is protoporphyrinogen IX).

Then mitochondrial ferrochelatase adds Fe2+.

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7
Q

What parts of heme synthesis can be inhibited by lead?

A

Ferrochelatase (can result in creation of ZnPP instead).

ALA dehydrogenase can also be inhibited by lead.

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8
Q

When is a porphyria photosensitive?

A

If there is a closed ring structure.

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9
Q

What are the erythropoietic porphyrias?

A

Congenital (Uroporphyrinogen III synthase deficiency - Hydroxymethylbilane (and uroporphyrinogen I and coproporphyrinogen I accumulate))

Protoporphyria (ferrochelatase defect - protoporphyrin IX accumulates)

Skin rashes, blisters in early childhood. Eventually complicated by cirrhosis/liver failure. Photosensitive.

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10
Q

Describe ALA dehydratase deficiency porphyria.

A

Acute hepatic. ALA accumulates.

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11
Q

Describe acute intermittent porphyria.

A

Acute hepatic. Deficiency in hydroxymethylbilane synthase - porphobilinogen and deltaaminolevulinic acid (ALA) accumulate. Urine darkens on exposure to air and light. Not photosensitive.

Acute attacks of GI, neuro, and motor symptoms.

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12
Q

Describe Variegate porphyria.

A

Acute hepatic. Deficiency in protoporphyrinogen oxidase - protoporphyrinogen IX accumulates. Photosensitive.

Acute attacks of GI, neuro, and motor symptoms.

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13
Q

Decribe Hereditary coproporphyria.

A

Acute hepatic. Deficiency in coproporphyrinogen oxidase - coproporphyrinogen III accumulates. Photosensitive.

Acute attacks of GI, neuro, and motor symptoms.

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14
Q

Describe Congenital Erythropoetic Porphyria.

A

Erythropoietic. Defieicnty in uroporphyrinogen III synthase - Hydroxymethylbilane (and uroporphyrinogen I and coproporphyrinogen I) accumulate. Photosensitive.

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15
Q

Describe Porphyria cutanea tarda.

A

Hepatic chronic - the most common porphyria. Onset in 4-5th decade of life, clinical expression influenced by iron load, alcohol use, sunlight exposure, Hep B/C, HIV, estrogen therapy.

Skin eruptions, discoloured urine.

Deficiency in uroporphyrinogen decarboxylase - accumulation of uroporphyrinogen III.

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16
Q

Describe heme degradation.

A

Inside macrophages Heme oxygenase (uses NADPH) releases the iron and breaks protoprphyrin IX into biliverdin (and CO2). Biliverdin reductase (uses NADPH) reduces the bonds and produces bilirubin.

Then it travels on albumin to the liver, where propionic acids react with UDP-glucuronide and its conjugated to bilirubin diglucuronide. It’s deconjugated in the intestine and converted to urobilinogen. Bacteria mostly converted it to brown sternocobilin (excreted), but some is reabsorbed, oxidized in the kidney, and excreted as yellow urobilin.

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17
Q

What is neonatal jaundice and how do you treat it?

A

Incomplete expression of bilirubin glucuronyl transferase. Treat with UV light to make soluble bilirubin isomers.

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18
Q

What is Gilbert Disease?

A

An unconjugated hyperbilirubinemia. Familial, can occur with neonatal jaundice, yellow tinge, slight increase of unconjugated bilirubin.

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19
Q

What is Crigler-Najjar Disease? Describe Type I vs Type II.

A

An unconjugated hyperbilirubinemia. Little or no UDP glucuronyl transgerase in liver, requires lifelong phototherapy.

Type I is AR, no enzyme

Type II is AD, decreased levels, can treat with phenobarbitone

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20
Q

What is Kernicterus?

A

Bilirubin-induced brain dysfunction, can occur in newborns.

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21
Q

What is Dubin-Johnson Syndrome?

A

A conjugated hyperbilirubinemia. Defective bilirubin secretion from hepatocytes into bile (dark brown liver)/

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22
Q

What is Rotor Syndrome?

A

A conjugated hyperbilirubinemia. Transporter defect in hepatocytes, mild elevation of conjugated bilirubin.

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23
Q

Describe how IMP (purine precursor) is synthesized? How are the relevant enzymes regulated?

A

Glucose to R5P via PPP to PRPP by PRPP synthetase (activated by Pi, inhibited by IMP/AMP/GMP).

PRPP to IMP by phosphoribosylphosphate amidotransferase (activated by PRPP, inhibited by IMP/AMP/GMP)

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24
Q

What do sulfonamides do?

A

Inhibit bacterial folate synthesis.

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25
Q

How does IMP turn into AMP?

A

Adenylosuccinate synthase (uses Asp, GTP) to make adenylosuccinate, and then adenylosuccinase to remove a Fumarate and make AMP.

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26
Q

How does IMP turn into GMP?

A

IMP dehydrogenase (makes an NADH, neg feedbacked by GMP) to make Xanthosine MP. Then GMP synthase to turn Gln into Glu.

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27
Q

What does mycophenolic acid do?

A

Block IMP dehydrogenase - is an immunosuppressant.

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28
Q

How are purines converted to uric acid?

A

Ps removed, riboses removed. Hypoxanthine and guanine further converted to xanthine which is converted to uric acid (both done by xanthine oxidase).

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29
Q

What enzyme turns adenosine to inosine and AMP to IMP? What’s special about it?

A

Adenosine deaminase.

Lack of it causes SCID.

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30
Q

How is adenine recycled back into AMP?

A

Via APRT (adenosine phosphoribosyl transferase) at the cost of a PPRP.

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31
Q

How is guanine recycled back int GMP?

A

Via HGPRT (hypoxanthine guanine phosphoribosyl transferase) at the cost of a PPRP.

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32
Q

What is Lesch-Nyhan syndrome?

A

X-linked HGPRT loss. Increased PPRP levels and stimulation of de novo purine synthesis - gout and mental aberrations.

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33
Q

What are the dietary risk factors for gout?

A

Meat, seafood, ethanol.

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34
Q

How is gout treated?

A

Antiinflammatory agents (colchicine, prednisone, indomethacin).

Allopurinol to lower synthesis (competitive inhibitor of xanthine oxidase, metabolized to oxipurinol which is also an inhibitor).

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35
Q

What is 6-mercaptopurine?

A

An antimetabolite - a xanthine analog, competes with HGPRT and is used with methotrexate.

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36
Q

What is azaserine?

A

An antimetabolite - a glutamine analog, blocks glutamine PRPP amidotransferase.

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37
Q

What are methotrexate and aminopterin?

A

Folic acid analogs - antimetabolites.

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38
Q

Describe de novo pyrimidine synthesis.

A

Gln and CO2 and 2ATP made into carbamoyl phosphate by CPSII (downregulated by UTP, upregulated by PPRP).

Carbamoyl phosphate made into carbamoyl Asp by Asp transcarbamoylase. Carbamoyl Asp made to dihydroorotate by dihydroorotase.

Dihydroorotate made into Orotate by dihydroorotate dehydrogenase.

Orotate made into OMP (orotidine 5’MP) by orotate phosphoribosyl transferase.

OMP made into UMP by OMP decarboxylase.

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39
Q

What are the symptoms of orotate aciduria?

A

Orotate in urine, megaloblastic aemia, poor growth.

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40
Q

How is UTP made into CTP?

A

CTP synthetase (converts Gln into Glu).

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41
Q

How is dUMP made into dTMP?

A

Via thymidylate synthase (needs THF for process).

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42
Q

How does 5-fluorouracil affect nucleotide synthesis?

A

Is a thymidylase synthase suicide inhibitor - makes 5F-dUMP.

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43
Q

How are deoxyriboses made from riboses?

A

Via ribonucleotide reductase.

Uses reduced thioredoxin, which is regenerated by thioredoxin reductase at the cost of an NADPH.

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44
Q

Generally describe Type I hypersensitivities.

A

Sensitization (IgEs produced and bind to mast cells)

Challenge (Ags bind to IgEs, IgEs cross link and bind to FCepsilonRI receptor on mast cell/eosinophil/basophil, triggers degranulation)

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45
Q

What is atopy?

A

A genetic predisposition to Th2 response and IgE production.

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46
Q

What types of antigens make allergens?

A

Proteins or chemicals that modify human proteins.

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47
Q

How do basophils drive Th2 response?

A

By IL-4 and IL-13 production.

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48
Q

What do you look for in the blood to determine a type I hyperimmune reaction?

A

Tryptase. Has a long t 1/2.

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49
Q

Describe phase 1 of IgE-caused mast cell enzyme release.

A

Histamine, heparin (toxic to parasites, increases vascular permeability, SM contraction).

Also tryptase, chymase, cathepsin G, carboxypeptidase (remodels CT matrix).

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50
Q

Describe phase 2 of IgE-caused mast cell enzyme release.

A

TNFalpha is released (some was preformed in granules). It causes inflammation, cytokine production, activates endothelium.

Also IL-4, IL-13,
IL-3, IL-5, and GM-CSF (eosinophil production and activation), CCL3, LTC4, D4, E (SM contraction, vasc. permeability, mucus secretion), and PAF.

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51
Q

What is RAST allergy test?

A

Radioallergosorbent test. In vitro.

Insoluble antigen incubated first in test serum and then in radiolabeled anti-human IgE. Then enzyme fluorescence is quantified.

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52
Q

What are the effects of type I hypersensitivity?

A

Increased GI peristalsis and fluid secretions, decreased airway diameter, increased mucus, increased blood vessel permeability.

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53
Q

What is an anaphylactoid reaction?

A

Mast cell degranulation that is IgE independent.

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54
Q

How do you treat type I hypersensitivity and anaphylaxis?

A

Antihistamines, anti-LTs, corticosteroids, cromolyn sodium, Epinephrine (IM E is treatment for anaphylaxis).

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55
Q

Describe type II hypersensitivity.

A

IgG binds Ag that is on cell, complement/MAC causes cell death.

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56
Q

What kind of hypersensitivitiy reaction can penicillin trigger?

A

Type I (other haptens ca do this too) and II (can modify cells to display foreign Ag).

Binding of Abs to penicillin-modified RBCs makes them susceptible to complement-mediated lysis or phagocytosis via Fc and complement receptors.

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57
Q

Describe a type III hypersensitivity.

A

Immune complex mediated. Soluble Ag bound, complex deposited, then there is chemokine-neutrophil activation.

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58
Q

How are immune complexes normally cleared?

A

RBCs bind via CR1 and take them up.

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59
Q

What is serum sickness?

A

Systemic inflammation reaction due to immune complexes in many parts of the body. Has limited duration, used to be caused by horse serum IgGs.

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60
Q

What is arthus reaction?

A

(Type III). Soluble antigen subcutaneously injected into a sensitized person (already had preexisting Abs).

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61
Q

What is SLE?

A

Abs to nuclear antigens.

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62
Q

What is poststreptococcal glomerulonephritis?

A

Immune reaction to strep cell wall antigens after an infection - causes kidney disease.

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63
Q

What is polyarteritis nodosa?

A

Systemic vasculitis caused by immune reaction to Hep B antigens.

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64
Q

What is reactive arthritis?

A

Immune reaction to bacterial antigens.

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65
Q

Describe type IV hypersensitivity.

A

Delayed. T cell associated. Th1 for soluble Ags, CD8 for cell-associated ones. Effector cells largely macrophages.

Th1 releases chemokines (recruits macrophages), IFNgamma (activates macrophages and increases release of inflammatory mediators), TNFalpha and LT (adhesion molecules on local BVs), IL-3 and GM-CSF (monocyte production in BM).

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66
Q

Describe poison ivy/oak reaction.

A

Type IV hypersensitivity to pentadecacathenol. Crosses PM and modifies IC proteins.

1st exposure minor and undetectable, 2nd onward has memory Th1 and CD8 cells. Lesions due to heavy leukocyte infiltration.

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67
Q

Describe the tuberculin skin test.

A

A type IV hypersensitivity. TB Ags put in intradermally, reaction 24-72 (mean 48) hours later.

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68
Q

What are the requirements for pathologic autoimmunity?

A

Immune reaction to self Ag/tissue, evidence that the reaction is not secondary to tissue damage, absence of another cause of disease.

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69
Q

Are men or women more prone to autoimmune illness?

A

Women.

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70
Q

Describe the antibodies in rheumatoid arthritis.

A

Anti-CCP Abs. Affiliated with DRB1 alleles (HLA). 4 and 12 OR respectively depending on 1 or 2 alleles.

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71
Q

Describe the genetics that predispose someone to ankylosing spondylitis.

A

B2075 and B2072 B*27 alleles (HLA). 100-200 OR.

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72
Q

What ANAs are in SLE?

A

Native DNA (40-60% cases), Anti-Sm (30-40%), U1RNP (30-40%)

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73
Q

What ANAs are in drug-induced LE?

A

Histones (>95% cases).

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74
Q

What ANAs are in Systemic Sclerosis?

A

Sci-70 Ab (Topoisomerase I) (28-70% cases).

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75
Q

What ANAs are in Limited Scleroderma/CREST?

A

Anticentromere (90% cases).

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76
Q

What ANAs are in Sjogren syndrome?

A

SS-A (Ro) (70-95% cases) and SS-B (La) (60-90% cases).

RNPs.

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77
Q

What does a homogenous indirect immunofluorescence ANA pattern mean?

A

Abs to chromatin and histones.

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78
Q

What does a rim indirect immunofluorescence ANA pattern mean?

A

Abs to dsDNA.

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79
Q

What does a centromeric indirect immunofluorescence ANA pattern mean?

A

Abs to centromere.

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80
Q

What does a speckled indirect immunofluorescence ANA pattern mean?

A

Abs to non-nuclear components like Sm, SS-A, SS-B.

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81
Q

What does a nucleolar indirect immunofluorescence ANA pattern mean?

A

Abs to RNA.

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82
Q

How can you tell apart chronic discoid lupus (DLE)?

A

Normal skin shows no Abs, skin manifestations without systemic manifestations.

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83
Q

Describe subacute cutaneous Lupus and Drug induced LE.

A

Widespread superficial skin rash, mild systemic symptoms consistent with drug induced LE.

Drug induced has anti histone ABs, rash, serositis, arthralgias, fever, is associated with HLA DR4. Drugs that can cause it are hydralazine, procainamide, isoniazid, alphapenicillamine.

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84
Q

Describe Sjogren syndrome.

A

AKA Mikulicz syndrome. Mostly in women 50-60. Dry eyes (keraconjunctivitis sicca), dry mouth (xerostomia), generally another autoimmune disease. Primary form is sicca syndrome. Lymphocytic infiltration and fibrosis of lacrimal and secondary glands. Confirmed with biopsy of lip (look at minor salivary glands).

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85
Q

What is CREST?

A

Part of systemic sclerosis/scleroderma. Calcinosis (calcium in skin), Raynaud’s phenomenon (red/white/blue hands in response to cold/stress), Esophageal dysfunction, Sclerodactyly, Telangiectasis (dilation of capillaries causing red marks on skin surface).

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86
Q

Describe diffuse vs limited scleroderma.

A

Limited is that skin involvement is confined to fingers, forearms, face. Difuse is widespread skin involvement at onset and rapid progression and early visceral involvement.

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87
Q

What is the most common mutation causing scleroderma?

A

Fibrillin 1.

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88
Q

What is orthotopic vs heteroropic transplantation?

A

Put into the same location vs put into a different location.

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89
Q

What’s the difference between hyperacute and acute rejection?

A

Hyperacute is minutes to hours and is mainly a type III sensitivity. Recipient must have been previously sensitized.

Acute is days-months and mainly a type IV hypersensitivity. Interstitial mononuclear infiltrate usually appears a month after transplant. APCs present Ag to T cell.

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90
Q

What’s direct vs indirect allorecognition?

A

Direct is donor graft DC presents the donor peptide, indirect is the recipient DC.

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91
Q

How is the survival of grafts that lack lymphatic drainage?

A

Better.

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92
Q

What are the transplant requirements?

A

HLA matching, ABO matching, cross matching (add donor cells to recipient plasma).

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93
Q

Describe HLA matching.

A

D must match, +2 must match (B>A/C). Look for least mismatch.

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94
Q

What is an antiinflammatory agent given for transplant?

A

Prednisolone

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95
Q

What are cytotoxic agents given for transplant?

A

Azathioprine, mycophenilate mofetil, cyclophosphamide, methotrexate

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96
Q

What are T cell activation inhibitor agents given for transplant?

A

Cyclosporin A, tacrolimes(?), rapamycin, anti-TCR, anti-CD3

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97
Q

What kind of transplants can cause chimerism?

A

Hematopoietic stem cell.

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98
Q

What are the screening tests for B cell defects?

A

B cell count, quantitative Igs, isohemagglutinins (anti-A/Bs).

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99
Q

What are the screening tests for T cell defects?

A

Total lymphocyte count, lateral chest xray (for infants), delayed hypersensitivity skin test (for >2 y/o).

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100
Q

What are the screening tests for neutrophil defects?

A

WBC and differential CBC, nitroblue tetrazolium dye test, chemotaxis, chemoluminescence/flow cytometry.

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101
Q

What are the screening tests for complement defects?

A

Total hemolytic complement test - CH50, C1 INH, C3, C4, C8.

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102
Q

Describe transient hypogammaglobulinemia of infancy.

A

3-9months is a physiological phase of hypoIgs - maternal IgGs mostly have been catabolized by 6 months.

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103
Q

Describe X-linked/Brutons hypogammaglobulinemia.

A

Mutation in Bruton TK (long arm of X-chrom), problem is signalling through preB cell receptor (cannot mature).

No/few mature B cells, no IgGs, small LNs, no tonsils. ~20% go onto develop autoimmune diseases, extreme susceptibility to pyogenic bacterial infections at 4-8months.

Treat with IVIgs.

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104
Q

Describe hyperIgM syndrome.

A

X-linked, CD40/CD40L/AID issue, macrophage function also impaired.

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105
Q

Describe selective IgA Deficiency.

A

Most common immunodeficiency (~20% also deficient in IgG2 and IgG4).

Recurrent infections, allergy, autoimmune disease.
Don’t give IgAs!!! Can cause serum sickness!

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106
Q

What other cell type is affected in a T cell deficiency?

A

NK cells.

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107
Q

Describe DiGeorge Syndrome. How do you treat it?

A

22q11.2 deletion - defect on 3rd and 4th pharyngeal pouch development - no thymus or parathyroid glands.

Few/no T cells - B cells present but of variable function. Postnatal hypocalcemic tetany/seizures, CHF (outflow tract defects), developmental delay, hyperactivity, craniofacial deformities (low ears, wide and slanting down eyes, cleft palate, short philtrum, bifid uvula, fish mouth).

Give Calcium, VitD, PTH.

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108
Q

Describe Wiscott-Aldrich Syndrome. How do you treat it?

A

X-linked (WASp gene on short arm of X). Sialophorin/CD43/WASp affected (cytoskeleton of lymphoid cells). Affects B cells, T cells, platelets.

Thrombocytopenia, defective T cells, often IgM deficiency (normal IgGs, increased IgA/E). Severe eczema (atopic dermatitis).

Give PLT transfusions, do splenectomy (bleeding), antibiotics, IVIg, avoid frequent baths, use bath oils and moisturizing creams, avoid offending foods. BM transplant is curative.

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109
Q

How do people die from Wiscott-Aldrich Syndrome?

A

Bleeding (very young), infection (children), lymphoid malignancies (adolescent/adult).

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110
Q

What are the inheritances of SCIDs?

A

75% X-linked, 25% AR.

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111
Q

How do you treat SCIDs?

A

Antibiotics, IVIg, prophylaxis for pneumocystis jirovecis (trimethoprim-sulfamethoxazole).

BM transplant curative.

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112
Q

Describe X-linked SCI.

A

T cells lack gamma chain of IL-2 receptor.

T and NK -
B +

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113
Q

Describe Adenosine Deaminase deficiency. How do you treat it?

A

Most common AR SCID. Defective enzyme in purine salvage pathway - accumulation of dATP/dAdenosine. T,B,NK -. Abnormal bone development.

Give polyethylene glycol-modified bovine ADA. BM tranplant curative.

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114
Q

What does a defect in C3 cause?

A

Decreases opsonization. Increased susceptibility to encapsulated bacterial infection.

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115
Q

What does a defect in C5-9 (MAC) cause?

A

Increased susceptibility to disseminated Neisseria infections.

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116
Q

What does a defect in CD18 cause?

A

Decreased margination, diapedesis, increased leukocytosis (but no leuks at the infection site/inflammatory response at site).

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117
Q

What is chronic granulomatosis disease?

A

X-linked NADPH oxidase deficiency.

Persistent lymphadenopathy, recurrent abscesses, frequent pneumonia, low NBT, normal chemotaxis.

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118
Q

What is Chediak-Higashi disease?

A

Defect in neutrophil - poor organelle trafficking/vesicle fusion. No enzyme release.

Recurrent infections, albinism, ataxia, persistent lymphadenopathy, low NBT, low chemotaxis.

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119
Q

What is the host of plasmodium berghei?

A

Rats.

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120
Q

What is the host of plasmodium yoelii?

A

Mice.

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121
Q

What is the host of plasmodium knowlesi?

A

Monkeys.

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122
Q

What are the hosts of Plasmodium malariae?

A

Sporogony cycle is female anopheles mosquito. Schizogony cycle is vertebrates.

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123
Q

Describe the life cycle of Plasmodium malariae.

A

Sporozote enters human and replicates in liver parenchymal cells. Schizont forms and ruptures, releasing merozoites.

Merozoites enter RBCs, schizont forms, cycle repeats, Eventually gametocyte forms and a mosquito ingests that to complete sporogenic cycle.

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124
Q

What are the symptoms of malaria?

A

Fever, nausea, vomiting, headache, body aches, malaise/weakness.

Malaria is considered uncomplicated if there is no organ involvement.

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125
Q

What are the fever spike paterns of Plasmodium malariae, vivax, and falciparum.

A

Malariae - quartan

Vivax - tertian

Falciparum - malignant

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126
Q

How can you diagnose malaria?

A

Blood smear (parasite in RBCs), HRP2 detection, parasite LDH.

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127
Q

What are some protective factors against malaria?

A

Absence of receptor, G6PD deficiency, Sickle cell trait, Thalassemia.

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128
Q

What is the Plasmodium vivax receptor?

A

Duffy Ag

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129
Q

What are hypozoites?

A

Get latent in the liver - P. vivax, P. ovale.

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130
Q

What is recrudescence vs relapse?

A

Recrudescence is recurrence of symptoms after temporary abatement (days, weeks).

Relapse is return of disease after resolution of primary infection.

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131
Q

What is the vector is babesiosis?

A

Ixodes ticks.

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132
Q

What are the babesiosis species that we care about?

A

Babesia microti, Babesia divergens.

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133
Q

What are the symptoms of babesiosis?

A

Usually none unless hte person is immunocompromised or splenectomised.

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134
Q

How do you diagnose babesiosis?

A

Blood smear (tetrads/maltese cross).

Clindamycin+quinine, entovaquone+azithromycin.

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135
Q

What are the genomes of viral hemorrhagic fevers?

A

enveloped, (-)ssRNA

Except Flaviviridae - (+)ssRNA

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136
Q

How do you treat viral hemorrhagic fevers?

A

Antipyretics, Analgesics (not salycilates), fluid management

Ribavirin and passive immunity (Arenaviridae).

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137
Q

Describe Flaviviridae - vector, illnesses.

A

Vector Aedes spp. Reservoir is primates (humans are accidental host).

Yellow Fever (biphasic symptoms - 24-48hr pause).
Dengue (normal or severe phase)
Zika (Aedes aegypti - in fetuses can cause microcephaly/Guillain-Barre, in adults microcephaly/rash).

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138
Q

Describe Filoviridae - vector, illnesses.

A

Reservoir is bats, can also get from direct contact with fluids of infected hosts.

Species Marbury and Ebola (subspecies Zaire, Sudan, Cote d’Ivoire, Reston(not pathogenic in humans))

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139
Q

Describe Bunyaviridae - vector, illnesses.

A

Insect vectors, direct contact with body fluids. Reservoir is rodents, sheep, cattle.

Hanta Pulmonary Syndrome (late symptoms - coughing, SOB, edema) CFR 38%

Hanta Fever w/ Renal Syndrome (early symptoms - petechial rash, bilateral conjunctivitis, flushing, blurred vision, others; late symptoms - low BP, vasc leakage, kidney failure, shock)

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140
Q

Describe Arenaviridae - vector, illnesses.

A

Transmission by aerosols/droplets, dust. Reservoir is rodents.

Neurologic (LCMV) - aseptic meningitis, encephalitis, meningoencephalitis (CFR <1%)

HF: fever, headache, dizziness, asthenia, pharyngitis, cough, vomiting, retrosternal andp haryngeal pain, confusion, convulsion/coma, ARDS. CFR 5-30%

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141
Q

What are amastigotes and trypomastigotes?

A

Parasite forms found in tissues/within cells and free in blood respectively.

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142
Q

Describe African Tryponosomiasis.

A

Sleeping sickness - Trypanosoma gambiense and Trypanosoma rhodiense. Vector is tsetse fly.

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143
Q

Describe American Tryponosomiasis.

A

Chagas’ Disease - Tryponosoma cruzi. Reduviid bug via animal.

ENlarged heart and intestine, facial edema (Romana sign).

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144
Q

Where are amastigotes found in Leishmania sp.s?

A

Macrophages.

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145
Q

What is the vector for Leishmania sp.s?

A

Phlebotomus sandfly.

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146
Q

What kind of Leishmaniasis is gotten from L. tropica?

A

Dermal cutaneous or diffuse cutaneous form.

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147
Q

What kind of Leishmaniasis is gotten from L. brasiliensis?

A

Musculocutaneous form.

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148
Q

What kind of Leishmaniasis is gotten from L. donovanii?

A

Most severe visceral form.

Irregular fever, weight loss, anemia, hepatosplenomegaly. Pancytopenia (high putput HF) - myocarditis, pericarditis. Fever, cachexia, hypergammaglobulinemia, hypoalbuminemia.

Amastigotes in deep tissue - liver, spleen, BM.

Treat with pentosan, glucantine, allopurinol, miltefosin.

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149
Q

Describe Entamoeba histolytica.

A

Fecal-oral transmission cycle parasite. AIDS patients susceptible. Chlorine resistant.

Intestinal dissease, extraintestinal spread, liver abscesses, rupture, then pericardial disease.

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150
Q

Describe Toxoplasma gondii.

A

Cat is definitive host, many vertebrates are intermediate.

Fecal-oral transmission (of oocyte), ingestion of undercooked meat, transfusion, transplant, transplacental transmission.

Infection usually subclinical (flu-like symptoms), can be latent and reactivate - encephalitis, chorioretinitis, myocarditis, pericarditis, CHF.

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151
Q

What parasites cause heart issues?

A

Trichinella spiralis, Echinococcus granulosus (hydatid cysts), Taenia salium (cystercosis).

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152
Q

What parasites cause cardiac pathology via severe anemia?

A

Necator americanus, Acylostoma duodenale, Diphyllobothrium latum.

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153
Q

What parasites cause lymphatic filariasis/elefantiasis?

A

Wucheria bancrofti, Brugia malayi, Brugia timori.

Wolbrachia bacteria play a role in the hypereosinophilia (they’re gram(-))

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154
Q

How do you diagnose and treat elefantiasis?

A

Adult worms found in lymphatics.

Diagnose: chyluria, hypereosinophilia, ingreased IgEs, increased IgG4, increased antifilarial Abs, ELISA, card test, microfilariae blood smear.

Treat with Antihelminths (DEC, Albendazole+DEC, Albendazole+ivermectin), Antibacterials (Tetracycline, Rifampin, Doxycycline).

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155
Q

What does Onchocerca volvulvus cause? What’s the vector, how is it diagnosed and treated?

A

River blindness. Vector is simulium sandfly (mature larvae are injected subq, microfilariae released and go to skin and eye - onchodermatitis and keratitis).

Diagnose with microfilariae in skin nip, slit lamp microscopy.

Treat with DEC, Ivermectin, Suramin/Antrypol.

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156
Q

What’s the structure of retroviridae?

A

Diploid (+)ssRNA, enveloped icosahedral capsid.

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157
Q

Are retroviridae lytic?

A

No.

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158
Q

What is HIV p24?

A

Capsid protein.

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159
Q

What is HIV gp41?

A

HIV TM protein - does fusion.

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160
Q

What is HIV gp120?

A

HIV surface protein.

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161
Q

What are the genes in all retroviridae?

A

Gag, Pol (has IN and RT), Env.

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162
Q

What are the two forms of HIV?

A

M-tropic/CCR5 (mostly responsible for transmission, goes into macrophages)

T-tropic/CXCR4 (mostly responsible for progression to AIDS).

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163
Q

How does HIV get to T cells?

A

DCs internalize it (DC-SIGN protein has affinity for gp120) then it meets CD4 T cells in LNs.

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164
Q

What is an ‘inverted ratio’ as it pertains to HIV?

A

CD8:CD4 2:1.

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165
Q

How do you diagnose HIV?

A

Screening ELISA (p24), confirm with western blot (must have 2 or more of p24, gp41, gp120, gp160).

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166
Q

What are the phases of untreated HIV infection?

A

Acute: CD8 high, CD4 drop, lots of RNA copies, HIV-Abs start building.

Asymptomatic: HIV-Abs stay constant, RNA drops low then stays constant, CD8 stays constant, CD4 drops.

AIDS: CD4<400, RNA increases.

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167
Q

Which lines of HTLV are cell transforming?

A

HTLV1 and HLTV2.

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168
Q

How is HTLV1 transmitted and what disease does it cause?

A

Transmitted by breastfeeding, blood transfusion/needle sharing, sex.

HTLV1-associated myopathy/topical spastic paraparesis. Associated with alveolitis, polymyositis, dermamyositis, arthritis, ovestra, dermatitis.

Has been linked to Adult T-cell Lymphoma (ATL).

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169
Q

How is HTLV diagnosed? How is it treated?

A

Diagnosed with ELISA screening for HTLV1-Abs (particle agglutination also used), and WB or RTPCR to confirm.

ATL found to have ‘flower cells’.

Treat with combination chemo, ART/IGNalpha/chemo, hematopoietic cell transplant.

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170
Q

What is the difference between hyperemia and congestion?

A

Hyperemia is an increase of blood in arteries, congestion is increase of blood in veins.

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171
Q

What’s the cutoff for exudate vs transudate?

A

Exudate >3g/dL of protein.

172
Q

What is anasarca?

A

Generalized and severe edema.

173
Q

What does SIADH result in?

A

Hyponatremia, cerebral (but not peripheral) edema.

174
Q

How does edema from renal dysfunction typically manifest?

A

Initially in tissues with LCT (e.g. periorbital), then anasarca.

Rapid and significant weight gain, hyperlipidemia, hyperlipiduria, proteinuria (>3g/dL per day)

175
Q

What is dependent edema?

A

Influenced by gravity - legs when standing, sacrum when recumbent.

176
Q

What are some consequences of edema?

A

Subq: impaired wound/infection healing, potential sign of underlying cardiac/renal disease

Pulm: LVHF, renal failure, acute RDS, pneumonia, abnormal ABGs, favourable environment for infections.

Cerebral: Life threatening, tonsillar herniation (through foramen magnum).

177
Q

What are the symptoms of defects of primary hemostasis (PLTs, vW disease)?

A

Petechiae and purpura, epistaxis, GI bleeding, menorrhagia, severe may result in fatal intracranial hemorrhage.

178
Q

What are the symptoms of defects of secondary hemostasis (coagulation factor defects)?

A

Bleeding into soft tissue like muscle (hematomas), bleeding into joints (hemarthrosis) after minor trauma.

179
Q

Name some vessel wall abnormalities with normal PLT, BT, PT, PTT.

A

Infections, drug rxns, scurvy, Ehlers-Danlos, Henoch-Schonlein purpura (immune complex deposition), hereditary hemorrhagic telangiectasis (immune complex deposition), perivascular amyloidosis.

180
Q

What determines if cells are normocytic?

A

MCV - PCV/RBC#

181
Q

What determines if cells are normochromic?

A

MCHC (Hb/PCV)

182
Q

What do PT and PTT measure and what are normals?

A

PT - Extrinsic and common pathway (12-16s)

PTT - Intrinsic and common pathway (25-35s)

183
Q

What is the cutoff for thrombocytopenia? What level results in spontaneous bleeding?

A

<100KPLT/uL.

<20KPLT/uL results in spontaneous bleeding.

BT prolonged but PT and PTT normal.

184
Q

What % of platelets does thee spleen sequester?

A

30-35%

185
Q

Describe Chronic and Acute Immune Thrombocytopenia (ITP). How do you treat it?

A

Can be primary or secondary - autoAbs to PLT antigens. Common in women under 40.

Increased megakaryocytes, large immature PLTs in PBS. Treat with glucocorticoids, IVIg, splenectomy, anti-CD20 Abs.

Acute ITP affects kids about two weeks after viral infections (self-limited and resolves in 6 months).

186
Q

Describe Drug-induced thrombocytopenias. Type I vs Type II.

A

Type I is heparin induced and clinically insignificant.

Type II occurs 5-14 days after heparin treatment (generally high molecular weight) but can also be caused by quinine, quinidine, vancomycin.

Caused by Abs against PLT factor 4 - results in activation of PLTs and thrombosis.

187
Q

Descroibe HIV-associated thrombocytopenia.

A

HIV infection results in B cell hyperplasia and dysregulation - autoAbs produced against PLTs.

188
Q

What is Bernard-Soulier Syndrome?

A

Defect of PLT adhesion - GPIb/IX.

189
Q

What is Glanzmann Thrombasthenia?

A

Defect of PLT aggregation (GPIIb-IIIa).

190
Q

What is Thrombotic Thrombocytopenia Purpura (TTP)?

A

Caused by ADAMTS13 deficiency (a vWF metalloprotein).

Excessive PLT activation. Fever, thrombocytopenia, intravascular PLT hyaline thrombi, microangiopathic hemolytic anemia, renal failure, transient neurologic defects.

Increased BT, normal PT and PTT.

191
Q

What is Hemolytic Uremic Syndrome?

A

Associated with infectious gastroenteritis secondary to E.coli.

Similar symptoms to TTP (Excessive PLT activation. Fever, thrombocytopenia, intravascular PLT hyaline thrombi, microangiopathic hemolytic anemia, renal failure) BUT without neurologic defects.

192
Q

What is Hemophilia A?

A

Factor VIII deficiency.

193
Q

What is Hemophilia B?

A

AKA Christmas disease. Factor IX deficiency.

194
Q

What are ecchymoses?

A

Large (>1-2cm) bruises.

195
Q

What do the diff bruise colours mean?

A

Red-blue (hemoglobin), Blue-green (bilirubin), Brown (hemosiderin).

196
Q

What are the most common causes of blood loss in men under and over 50, and pre and post menopausal women?

A

Men under 50 - PUD
Men over 50 and postmenopausal women - GI cancer
Premenopausal women - fibroids

197
Q

What are the stages of shock?

A

I/Nonprogressive, II/Progressive (tachycardia and tachypnea), III/Irreversible (low temperature, bradycardia, bradypnea, hypotension).

198
Q

What is Virchow’s Triad of thrombosis?

A

Endothelial injury, abnormal blood flow, hypercoagulability.

199
Q

What are the most common causes of inherited hypercoagulability?

A

Factor V (Leiden) mutation, Prothrombin (Factor II) mutation.

200
Q

Does elevated homocysteine contribute to arterial or venous thrombosis?

A

Both!

201
Q

What are some causes of acquired hypercoagulability?

A

HF, trauma, stasis, vascular injury

202
Q

What is APAS (Antiphospholipid A Syndrome)?

A

Hypercoagulant syndrome. Increased PTT in vitro only.

False positive screening for syphilis.

Primary, or secondary associated with well-defined autoimmune disease.

Catastrophic!

203
Q

What are Lines of Zahn?

A

Laminations in arterial thrombi - means it was formed in flowing blood, alternating dark RBC and pale PLT layers and fibrin deposits.

204
Q

What are the most common sites of arterial thrombi?

A

Coronary, cerebral, femoral arteries.

205
Q

What’s a mural thrombus?

A

A thrombus in the heart chambers or aortic lumen.

206
Q

How do you tell between antemortem and postmorten clots?

A

Antemortem ones are firm and focally attached, adherent to wall, have lines of Zahn.

Postmortem ones are gelatinous, moist, glistening dark red, not attached to vessel wall, yellow ‘chicken fat’ upprt portion.

207
Q

What are some causes of aseptic cardiac valve vegetations?

A

Hypercoagulable states (nonbacterial thrombotic endocarditis), verrucous endocarditis in SLE “Libman-sacks”.

208
Q

What’s a mycotic aneurysm?

A

An aneurysm from infected thrombi e.g. subclavian a. (associated with congenital cervical rib).

209
Q

Where is a DVT common?

A

Popliteral, femoral, iliac veins.

210
Q

What’s an amniotic fluid embolism?

A

Defect in placenta - clot goes to uterine veins then to vena cava.

Common complication of birth.

211
Q

What’s a paradoxical embolism?

A

When a DVT embolizes to systemic circulation through interatrial or interventricular defect.

212
Q

How much air needs to be in an air embolus to have clinical effects?

A

100CCs.

213
Q

What is the difference between the bends and the chokes?

A

Bends:gas in skeletal muscle and surrounding tissues in and around joints.

Chokes: Respiratory distress secondary to gas bubbles in lung vasculature.

214
Q

What is anemia?

A

Decreased RBC#, Hct, Hb

215
Q

What should the Hb:Hct ratio be?

A

1:3

216
Q

Where is EPO made?

A

In the kidney.

217
Q

What are some physical and serum characteristics of hemolytic anemia?

A

Pallor, jaundice, RUQ tenderness (bilirubin gallstones/hyperbilirubinemia), increased serum indirect (unconjugated) bilirubin, increased urine urobilinogen and fecal stercobilinogen.

Increased serum LDH, increased corrected reticulocyte count, decreased serum free haptoblogin (all bound).

218
Q

What are some differences in intravascular and extravascular hemolytic anemia?

A

Extravascular has splenomegaly.

Intravascular has much lower hemoglobin and hemopexin than extravascular.

Extravascular has no hemoglobinuria and hemosiderinuria.

219
Q

What do Howell-Jolly bodies signify?

A

Decreased splenic function.

220
Q

What are spherocytes?

A

No central pallor RBCs.

221
Q

Describe Hereditary Spherocytosis and how it’s treated.

A

AD most common, AR more severe. Most commonly a mutation of Ankyrin (sometimes spectrin) - ends up as mutation of spectrin assembly.

Spherocytes, normochromic, normocytic anemia. Hemolysis in spleen.

Splenomegaly, increased indirect bilirubin, increased reticulocytes, erythroid BM hyperplasia, increased osmotic fragility.

Treat with splenectomy.

222
Q

Describe Sickle Cell Anemia.

A

Glu replaced by Val - point mutation. Sickle cell phenotype, microvascular occlusions.

Sickling can be initial (give O2), recurrent (irreversible due to membrane damage), irreversible (increased adhesion to endothelium/expression of adhesion molecules).

Fatigue, pallor, jaundice, fever, delayed growth/puberty, greater infection rate, chronic leg ulcers.

HbA 60%, HbS 40%, normal HbA2 and HbF

223
Q

Describe the complications of Sickle Cell Anemia.

A

Acute: pancytopenia (aplastic crisis (B19 can cause), sequestration (hypovolemia), vasoocclusive crises).

Longterm: Gallstones, splenomegaly (autosplenectomy in adults), susceptibility to infections (S. pneuomiae, H. influenzae, meningitis, osteomyelitis).

224
Q

How do you induce in vitro sickling?

A

Sodium meta bisulfite (reducing agent).

225
Q

Describe beta thalassemia major.

A

AKA Cooley’s/severe/transfusion-dependent anemia.

Onset 6-9months, hemolysis in spleen. Microcytic hypochromic anemia.

Ineffective erythropoiesis, erythroid hyperplasia (bony deformities), progressive splenomegaly, excess Fe absorption.

HbF increased, HbA2 normal/increased.

226
Q

Describe alpha thalassemia.

A

Microcytic anemia.

2 alpha alleles is alpha thalassemia trait, one is HbH Disease/Barts, zero is hydrops fetalis.

227
Q

Describe paroxysmal nocturnal hemoglobinuria. How is it tested for?

A

PIGA and other GPI (lipid membrane linked proteins) mutated. RBCs more prone to destruction by complement.

Normocytic/microcytic anemia, pancytopenia, hemosiderinuria (Fe deficiency), thrombosis.

Decreased haptoglobin, increased LDH, increased unconjugated bilirubin, BM hyperplasia.

Screen with sucrose hemolysis test (10% sucrose), acidified serum/Ham test, flow, PIGA gene mutation analysis, deficiency of CD55/CD59/

228
Q

Describe G6PD deficiency.

A

X-linked recessive - Mediteranean variant severe, Black american variant episodic.

Primarily intravascular hemolysis - peroxide oxidizes Hb, which precipitates as Heinz bodies (removed by Bite Cells).

Can be triggered by fava beans, antimalarials (Primaquine, nitrofurantoin, chloroquin), sulfonamides, phenacetin, aspirin, dapsone, infections - back pain and hemoglobinuria 2-3 days after oxidative stress.

229
Q

Describe Autoimmune Hemolytic Anemia.

A

Normocytic, spherocytsis, +ve direct and indirect Combs.

70% warm type (IgGs at 37C, idiopathic or secondary, moderate splenomegaly), 30% cold type (0-4C, cold leads to red cell agglutination, can also be caused by mono, mycoplasma).

230
Q

What is hemolytic anemia due to mechanical trauma?

A

Direct trauma (valve prosthesis/obstruction) or Turbulent flow in BVs (platelet thrombi, fibrin thrombi, long distance running/march hemoglobinuria).

231
Q

Describe the lab results of acute blood loss.

A

Low Hb, Low PCV (make take 24048 hrs), Increased TLC (earliest change), polychromasia in more than 5-7 days, increased platelets, increased reticulocytes (5-7 days).

232
Q

What fraction of the time is aplastic anemia idiopathic?

A

2/3

233
Q

What is Fanconi anemia?

A

Hereditary aplastic anemia.

234
Q

What is myelophthisic anemia?

A

BM infiltration by metastatic cancer, granulomas, myelofibrosis.

Teardrop cells, leuko-erythroblastic reaction.

235
Q

What is sideroblastic anemia?

A

Microcytic hypochromic anemia - mitochondrial defect prevents Fe incorporation into Hb.

Ringed sideroblasts in BM.

Can be caused by alcoholism, lead poisoning, B6 deficiency.

236
Q

Describe the effects of lead poisoning.

A

Abdominal colic, diarrhea, cerebral edema, lead deposits in epiphysis, foot drop (peroneal nerve palsy), proximal tubules damaged.

Microcytic hypochromic anemia with basophilic stippling.

Increased urine delta-ALA, increased RBC protoporphyrin. Increased iron.

Decreased TIBC/transferrin.

237
Q

Describe megaloblastic anemia.

A

Hypersegmented neutrophil with 6 lobed nucleus. Vitamin B9/B12 deficiency.

238
Q

What is the most common anemia of hospitalized patients?

A

Anemia of chronic disease.

239
Q

Describe anemia of chronic disease.

A

Microcytic hypochromic or normocytic normochromic.

Decreased RBC proliferation and impaired Fe utilization. Chronic immune disorders/infections.

Decreased EPO, abnormality in Fe transfer (IL-1, TNF, IFNgamma inhibits Fe release from iron storage pool)

240
Q

How much does one unit of packed RBCs raise Hct and Hb?

A

Hct 3% and Hb 1g/dL

241
Q

For what conditions do you give RBCs?

A

Low Hb, signs of hypoxia, significant/ongoing blood loss.

242
Q

For what conditions do you give fresh-frozen plasma?

A

Life threatening bleed, DIC, warfarin effect, liver disease when bleeding present with abnormal coagulation, following a massive transfusion/cardiac bypass.

243
Q

For what conditions do you give cryoprecipitate?

A

Fibrinogen deficiency when clinical bleeding present, trauma, DIC, before invasive procedure.

244
Q

Describe febrile non-hemolytic reaction.

A

Fever, chills, mild dyspnea within 6 hours of packed RBCs and PLT transfusion.

Caused by inflammatory mediators.

245
Q

Describe acute hemolytic reaction.

A

Fever, chills, flank pain, hemoglobinuria, shock, DIC, renal failure, death.

Caused by IgMs.

246
Q

Describe delayed hemolytic reaction.

A

Positive Coombs, decreased haptoglobin, decreased LDH.

Caused by previous sensitization to Abs.

247
Q

Describe transfusion-related lung injury.

A

Neutrophils in lung - sudden respiratory failure, diffuse pulmonary infiltrates, fever, lowered BP.

248
Q

What kind of cancer can HTLV1 lead to?

A

Adult T cell leukemia/lymphoma.

249
Q

What kind of cancer can KSHV/HHV8 lead to?

A

B cell primary effusion lymphoma.

250
Q

What kind of cancer can HIV lead to?

A

B cell lymphoma

251
Q

What kind of cancer can H. pylori lead to?

A

Gastric B cell lymphoma.

252
Q

What’s the difference between acute and chronic leukemia?

A

The blast count in the BM - for acute the count is over 20%, for chronic its under.

253
Q

What are the typical age brackets for ALL, AML, CML, and CLL?

A

ALL 0-14, AML 15-39, AML/CML 30-60, CLL >60

254
Q

What are myeloblast specific stains?

A

MPO, Sudan black B

255
Q

What is a lymphoblast specific stain?

A

PAS (Periodic acid Schiff)

256
Q

What does non specific esterase stain for?

A

Monoblasts

257
Q

What is a Hairy Cell Leukemia specific stain?

A

TRAP

258
Q

What is a TdT stain specific for?

A

Immature T and B cells (lymphoblasts)

259
Q

What are some flow cytometry B cell markers?

A

CD10 (marrow preB cells and germinal center B cells), CD19/CD20 (marrow preB cells and mature B cells), Cd21/CD23 (mature B cells).

260
Q

What are some flow cytometry T cell markers?

A

CD1 (thymocyte), CD3 (thymocyte, peripheral T cells), CD4, CD8, CD5 (also some B cells have)

261
Q

What is CD34 a marker for?

A

Stem cells.

262
Q

What are some NK markers for flow cytometry?

A

CD16, CD56.

263
Q

What us CD35 a marker for?

A

Common Leukocyte Antigen (LCA).

264
Q

What are some monocyte/myelocyte markers?

A

CD13, CD14, CD15, CD33.

265
Q

What are some Reed-Sternberg cell markers?

A

CD15, CD30

266
Q

What are the AML subtypes?

A

M3 (Promyelocytic), M5 (Monocytic), M6 (Erythroblastic), M7 (Megakaryocytic).

267
Q

What are Auer Rods?

A

Found in myeloblastic leukemic cells - clumps of azurophilic material that come from abnormal fused lysosomes.

268
Q

Describe M3 AML. How is it treated?

A

Promyelocytic. Myltiple auer rods, high incidence of DIC.

t15;17 RAR alpha fused with PML.

Treat with ATRA (all trans retinoic acid).

269
Q

What is characteristic of M5 AML (Monocytic)?

A

Gum infiltration.

270
Q

What population is AML most common in?

A

Black women age 15-39.

271
Q

What’s true about AML t8;21?

A

Has a better prognosis.

272
Q

What has a better prognosis in ALL, B or T cells?

A

B!

273
Q

What kind of anemia is in leukemia?

A

Normochromic normocytic.

274
Q

What are some poor prognostic factors in ALL?

A

age <2 or >12, t9;22, CD10-ve.

275
Q

What are the symptoms of small and chronic lymphocytic leukemias?

Who is it more common in?

A

Fatigue, anorexia, weight loss, generalized lymphadenopathy.

More common in men, >50y/os.

276
Q

What do you see in CLL PBS?

A

Lymphocytes small with scant cytoplasm, spherocytes, smudge cells (fragile lymphocytes disrupted when preparing smear).

277
Q

Describe SLL LN biopsy results.

A

Effacement of architecture by small lymphocytes, proliferation centers (aggregates of larger prolymphocytes).

278
Q

Describe the progression of SLL/

A

Progresses slow (survives 4-6, up to 10 years)/ Aggressive transformation (prolymphocytic leukemia 15-30%, diffuse large B cell lymphoma / Richter’s syndrome ~10%)

279
Q

Who does HCL affect?

A

Men 4x as much as women.

280
Q

Describe HCL.

A

Massive splenomegaly, pancytopenia, dry tap on BM, PBS Hairy cells (cytoplasmic projections).

TRAP, CD11c, CD103 positie.

281
Q

What is common in myeloproliferative disorders?

A

Splenomegaly, BM fibrosis.

282
Q

What is LAP (leukocyte alkaline phosphatase) a marker for?

A

Mature neutrophila.

283
Q

Describe CML.

A

Low LAP score, philadelphia chromosome t9;22.

Has chronic stable phase (40% asymptomatic, increased TLC, basophilia, thrombocytosis) and accelerated/blast phase - rapid progression to death.

284
Q

What is polycythemia and what is the difference between primary and secondary?

A

Low plasma volume/hemoconcentration. Pancytosis. Increased Hct, blood viscosity. Hepatosplenomegaly.

Primary (cancerous) is polycythemia vera, a rare EPO receptor mutation (low EPO).

Secondary is high EPO (lung disease, cyanotic heart disease, high altitude, EPO-decreting tumours).

285
Q

How do you treat polycythemia vera?

A

Phlebotomy, BMT, myelosuppressive drugs (alkylating agents or P32 modulators).

286
Q

What is essential thrombocythenia?

A

> 600,000PLTs/uL, mild increase in WBCs, increased megakaryocytes.

287
Q

What cells are characteristic in primary myelofibrosis? What are the types of primary myelofibrosis?

A

Tear drop cells.

Chronic idiopathic or agnogenic myeloid metaplasia.

288
Q

What are the symptoms of primary myelofibrosis?

A

Abnormal stem cells, damaged hemotopoietic cells (esp. megakaryocytes), massive splenomegaly, reactive myelofibrosis (EMH).

289
Q

What are myelodysplastic syndromes and what are the causes?

A

Ineffective hemotopoiesis, morphologic dysplasia. Erythroid series, myeloid series, megakaryocytic series.

Causes are idiopathic or iatrogenic (2-8yrs post genotoxic drug/radiation therapy)/

290
Q

What are the CODs of myelodysplastic syndromes?

A

Bleeding, infections. Avg 9-29 month survival.

Progresses to AML 10-40% cases.

291
Q

What are Reed-Sternberg cells?

A

Characteristic cells in Hogkin Lymphoma. Large, binucleate, eye-shaped prominent eosinophilic nuclei.

Secrete IL-5 and chemokines.

292
Q

Describe the differences between HL and NHL?

A

HL mostly B cells, young and old people, localized LN spread, rarely extranodal involvement, 50% association with EBV.

NHL 90%B, 10%Tcells, 20-40 year olds, commonly has extranodal involvement, chance association with EBV, association with HIV.

293
Q

Who is HL common in?

A

Young adult makes (young females in nodular sclerosis type).

294
Q

How do you differentiate between classical and non-classical HL?

A

Classical are CD15 and CD30 +ve.

Nonclassical are CD15 and CD30 -ve but CD20 and BCL6 +ve.

295
Q

What is nodular sclerosis type HL?

A

60% cases, usually EBV-ve, usually found stage I-II.

Frequent mediastinal involvement, fibrous bands developing cellular areas into nodules, background infiltrate of T-lymphs, eosinophils, macrophages, plasma cells.

296
Q

What is mixed cellularity type HL?

A

30% cases. 70% are EBV+ve, usually found stage III-IV.

Frequent mononuclear and diagnostic RS cells, background lymphocytes, eosinophils, histiocytes, plasma cells.

297
Q

Describe lymphocyte-predominant HL esp in terms of markers.

A

No EBV, CD15 and CD30 -ve, CD20 +ve.

298
Q

Describe lymphocyte-rich HL esp in terms of markers.

A

EBV in 40% cases. CD15 and CD30 +ve.

299
Q

Describe lymphocyte-depleted HL esp in terms of markers.

A

Extensive necrosis and fibrosis. CD15 and CD30 +ve.

300
Q

What are the characteristic clinical features of HL?

A

Painless LN enlargement, weight loss (>10%), night sweats, Pel-Ebstein fever (comes and goes).

301
Q

What’s more important for HL prognosis, stage or histological type?

A

Stage.

302
Q

Describe HL staging.

A

I (1 LN region or extralymphatic organ/site)

II (2 or more LN regions on same side of diaphragm or 1 with localzed contiguous involvement of extranodal organ/site)

III (LN regions on both sides of diaphragm w/ or w/o involvement of spleen or extranodal organ/site)

IV (multiple/disseminated involvement of more than 1 extralymphatic organs/tissues w/ or w/o LN involvement.)

303
Q

Describe Follicular Lymphoma.

A

NHL most common indolent type in US. CD10, CD19, S. Ig +ve
BCL2 +ve in 90% cases, t14;18 in >90% cases.

85% cases have BM involvement, 10% cases peripheral blood involvement.

LN biopsy shows centrocytes, centroblasts, mature B cells.

Can progress to diffuse large B cell lymphoma (30-50%) or Burkitts.

304
Q

Describe Burkitt Lymphoma.

A

NHL. African/endemic type (EBV 100%), American/sporadic type (EBV 10-25%, abdo. involvement), HIV-associated involvement (EBV 25%).

Related to t8;14 (C-MYC overexpression).

“Starry sky” LN biopsy - macrophages ingested debris.

305
Q

Describe Diffuse Large B Cell Lymphoma.

A

NHL. Can present at extranodal sites, diffuse pattern. CD10, CD19, CD20, BCL-6 +ve.

306
Q

Describe Mantle Cell Lymphoma.

A

NHL. Origin at pregerminal center.

Associated with t11;14. Cyclin D1 positive.

Mucosal involvement of small bowel/colon produces polyps in terminal ileum.

307
Q

Describe Marginal zone Lymphoma.

A

NHL. Tumour cells resemble normal marginal zone B-cells. Associated with chronic inflammatory disorders.

308
Q

What is multiple myeloma? Describe its symptoms.

A

A plasma cell dyscrasia (expansion of single clone of Ig secreting cells).

Terminally differentiated B-lineage cells. Make IL-6, RANKL.

CRAB (Calcium rise, Renal insufficiency, Anemia, Bone pain/path. fractures).

309
Q

Describe multiple myeloma lab results, xray analysis, BM aspirate.

Prognosis / COD.

A

Monoclonal Ig peaks - 55% IgG, 25% IgA, sometimes M/E/D/ monomers. In urine miht have Bence-Jones proteins (free light chains).

On xray, punched out lytic lesions/defects (1-4cm).

BM aspirate shows hypercellular, Russell Bodies, plasma cells >30%.

Poor prognosis - multiple bone lesions means survival <6mo. COD is infections, renal insufficiency, amyloidosis.

310
Q

Describe solitary plasmacytoma.

A

Proliferation of plasma cells. Osseus form usually in vertebral column (MM 10-20 yrs later often). Extraosseus/soft tissue form in upper resp. tract, fix by local resection, rarely progresses to MM.

M spike may be present.

311
Q

What is Waldenstrom’s Macroglobulinemia?

A

AKA Lympho-plasmacytic lymphoma.

No free light chains. Increased viscosity of blood due to increased IgMs (causes Raynaud’s, neuro symptoms, visual impairment, bleeding, cryoglobulinemias).

Can cause CLL, SLL, rare IgM-producing myeloma.

312
Q

What is Mycois Fungoides / Sezary Syndrome?

A

Tumour of CD4+ cells. Has marked skin predilection/erythrodema.

Epidermotropism (atypical PAS+ lymphocytes in epidermis) - when they aggregate, it’s Poutrier’s microabscesses, nuclei with cerebriform apperance (infolding of nuclear membrane),

Premycotic phase (scaly red-brown patches), Plaque phase, Tumor phase.

Sezary syndrome is in the peripheral blood.

313
Q

What’s Anaplastic Large Cell Lymphoma?

A

Extranodal, gene rearrangement on Chr. 2 p23 (ALK) with TK activity.

Large anaplastic ‘hallmark’ cells with horseshoe shaped nucleus. Resemble metastatic carcinoma, closter around valves, infiltrate lymphoid sinuses.

314
Q

Describe Adult T cell Leukemia/Lymphoma.

A

Neoplasm of CD4+ cells. Happens in adults infected with HTLV1.

Distinctive clover-shaped nuclei.

Skin lesions, increased calcium, generalized lymphadenopathy, hepatosplenomegaly.

315
Q

Describe Large Granular Lymphocytic Leukemia.

A

T cell variant in indolent course (CD3+), NK cell variant in aggressive course (CD3-, CD56+).

Anemia, neutropenia, increased incidence of ehrumatologic disease.

316
Q

Describe extranodal NK/T cell lymphoma.

A

Associated with EBV infection.

Highly aggressive, respond well to radiation, resistant to chemo, nasopharynx is more common site (destructive midline masses).

317
Q

How are histiocyte disorders diagnosed?

A

Langerhans cells (CD1a+), grooved coffee-bean nucleus on H&E, Birbeck granules on EM.

318
Q

What are the 3 histiocyte disorders?

A

Eosinophilic granuloma - benign variant (unifocal lytic lesions). Older kids/young adults, pain, pathologic fractures.

Hand-Schuller-Christian disease - disabling variant (multifocal defects in skull). Kids 2-6, common presentation otitis media. Exophthalmos, diabetes insipidus.

Letterer-Sime Disease - most aggressive (kids <3, diffuse eczematous rash, organ infolvement, multifocal defects in skull, pelvis, long bones).

319
Q

Describe a thymoma.

A

Tumour of epithelial tissue of thymus. Benign (70%) is circumscribed mass, malignant (30%) resembles squamous cell carcinoma.

Symptoms of myasthenia gravis often. Associated with hypogammaglobulinemia, pure RBC aplasia, increased autoimmune disorders.

320
Q

What are the types of fractures?

A

Simple (skin intact), Compound (bone communicates with skin surface - highest risk of embolus), Comminuted (bone fragmented), Displaced (bone ends not aligned), Stress, Pathologic, Greenstick (extends only partway through bone).

321
Q

What’s a pseudoarthrosis?

A

A fake joint in fracture healing - non-union/ malformed callus.

322
Q

What are the symptoms of subchondral infarcts?

A

Initially pain upon activity, then constant pain.

323
Q

Describe the symptoms of bone medullary infarcts?

A

Usually clinically silent except in Bends/Dysbarism, Gaucher, Sickle Cell Anemia.

324
Q

What is a hip fracture in boys 4-10 indicative of?

A

Legg-Calve-Perthes Diseas.

325
Q

What bacterium causes 80-90% of osteomyelitis where it’s identified?

A

S. aureus.

326
Q

Describe osteomyelitis in kids vs adults.

A

In kids is usually hematogenous spread (metaphysis and/or epiphysis of long bones affected).

In adults its a complication of fractures, surgery, diabetic infections of feet (epiphyses and subchondral regions).

327
Q

Describe the phases of osteomyelitis.

A

Subacute phase (no symptoms, Brodie’s abscesses)

Acute phase (necrosis of bone cells and marrow - may travel through Haversian system to reach periosteum)

Chronic phase (rare)

328
Q

What is involucrum?

A

New bone that forms shell of living tissue around devitalized infected bone.

329
Q

What is sequestrum?

A

Dead/necrotic bone.

330
Q

What is sclerosing osteomyelitis of Garre?

A

New bone formation in jaw.

331
Q

What kind of osteomyelitis infections are common to who?

A

E. coli, Pseudomonas, Klebsiella most frequently in patients with GU infections, IV drug users

Mixed bacterial infections seen in direct spread / inoculation of organisms in surgery,

H. influenzae and GBS common in neonates

Salmonella in sickle-cell people

332
Q

What aer some complications of chronic osteomyelitis?

A

Acute flareups, pathological fractures, secondary amyloidosis, endocarditis, sepsis, sarcoma, development of squamous cell carcinoma in draining sinus tracts.

333
Q

What’s more destructive, pyogenic or TB-caused osteomyelitis?

A

TB

334
Q

What is Pott Disease?

A

AKA TB Spondylitis. Spine is involved in 40% of mycobacterial osteomyelitis. Infection breaks through intervertebral discs to affect multiple vertebrae - can cause scoliosis/kyphosis. Can cause sinus tract or psoas abscesses.

335
Q

Describe congenital skeletal syphilis.

A

Bone lesions appear in 5th month of gestation. Spirochetes localize to areas of active endochondral ossification or periosteum. “Saber shin” deformity common.

336
Q

Describe acquired skeletal syphilis.

A

Bone disease in tertiary stage, usually 2-5 years after initial infection.

Most frequently affects bones of the nose, palate, skull, extremities.

337
Q

Describe Osgoid-Schlatter Disease.

A

Painful inflammatory swelling/lump below the patella - occurs in children and adolescents experiencing growth spurts in puberty.

338
Q

What’s the difference between skeletal dystosis and dysplasia?

A

Dystosis is localized problems in migration/condensation of mesenchyme, dysplasia is globalized disorganization of bone and/or cartilage.

339
Q

What gene is affiliated with brachydactyly types D&E?

A

HOXD13.

340
Q

Describe Osteogenesis Imperfects types I-IV.

A

I (AD - mutation not in Gly, decreased synthesis of proalpha1(1) or proalpha2(1) chains) - normal stature

II (AR mostly - mutation in Gly, abnormally short proalpha1(1), abnormal/insufficient proalpha2(1)) - perinatal lethal

III (AD 75%, AR 25%, altered proalpha2(1), blue sclera at BIRTH but become white) - progressive, deforming

IV (AD, short proalpha2(1), Normal sclera, moderate fragility of bones, sometimes short stature).

341
Q

What is achondrogenesis type 2?

A

Type II collagen mutation - short trunk.

342
Q

What is metaphyseal dysplasia (Schmid type)?

A

Type X collagen mutation - mildly short stature.

343
Q

What types of collagen are important in hyaline cartilage?

A

II, IX, X, XI.

344
Q

Describe osteopetrosis late onset type 2.

A

Chloride channel problem, increased bone density and fragility.

AD.

345
Q

Describe osteopetrosis with renal tubular acidosis (type 1).

A

CA problem, increased bone density and fragility, renal tubular acidosis. AR. Has impaired osteoclast functiona and interferes with dissolution of hydroxyapatite in the matrix.

EMH (need BMT) - results in hepatosplenomegaly.

Fracture, anemia, hydrocephaly perinatally, CNS defects, leukopenia/infections.

346
Q

How can mucopolyssacharides affect bone?

A

Accumulation can lead to chondrocyte apoptosis.

347
Q

What’s the cutoff for osteopenia?

A

Osteopenia is a T score under -1.0.

348
Q

What are the types of osteoporosis?

A

Idiopathic, Postmenopausal (high turnover variant, due to estrogen loss), Senile (low turnover variant, due to decreased proliferative capacity of osteoblasts because of decreased response to growth factors.

349
Q

What is Paget’s Disease?

A

AKA Osteoitis deformens. Get newly formed lamellar bone (eventually). Mosaic pattern of lamellar bone, unually large osteoclasts.

Has initial osteolytic phase, mixed osteoclas/blast phase, and quiescent osteosclerotic phase.

Characteristic wedge-shaped lytic leading edge, increased ALP. Normal calcium/phosphate.

350
Q

What is von Recklinghausen’s disease?

A

Severe hyperparathyroidism - large hollowed out area in T-shaped bone spicule, appeares as radiolucent cysts.

351
Q

What is high calcium of malignancy?

A

High calcium but low PTH.

352
Q

What are the genetics of achondroplasia?

A

FGFR3 mutation - AD. 80% new mutations.

FGFR3 inhivits bone growth so this is a GoF mutation.

Thanatopic dysplasia is a more severe variant, hypochondroplasia is a less severe variant.

353
Q

Describe the structure of collagen.

A

1/3AAs are Gly, 2 A1 strands and 1 A2 strand. Processing includes winding from C-term to N-term as well as hydroxylation involving vit C.

354
Q

Are collagen mutations closer to the C-term or N-term worse?

A

C-term.

355
Q

Describe Marfan Syndrome.

A

AD Fibrillin (FBN1) mutation. Triad is ectopia lentis, aortic aneurysm, arachnodactyly.

Tall, long, mild pectus excavatum, myopia, often mitral valve prolapse.

356
Q

What is the Ehlers-Danlos triad?

A

Skin hyperextensibility, joint hypermobility, CT fragility.

357
Q

Describe classical and vascular type Ehlers-Danlos.

A

Classical (I&II): type V or rarely type I collagen mutation. AR.

Vascular type (IV): AD. Mutation in type III collagen. Major components are arterial rupture, colon rupture, rupture of gravid uterus.

Minimal hyperfleibility in skin, no hypermobility in large joints.

358
Q

Describe type VI and VII Ehlers-Danlos.

A

VI: AR. Lysyl hydroxylase mutation. Can also include scoliosis, ocular fragility, marfanism.

VII: Severe hypermobility! Type I collagen exon 6 deletion (cleavage site) (AD). Or mutation in procollagen N protease (AR).

359
Q

What are the processes involved in pain?

A

Transduction, Transmission, Modulation, Perception.

360
Q

What are the psychological factors involved in pain perception?

A

Attention, Cognitive appraisal, Emotional rxns, Behavioural rxns.

361
Q

What is fibromyalgia and what does it respond to?

A

Mostly adult women, generalized widespread pain >3mo unknown etiology.

Most respond to selected antidepressants/anticonvulsants, exercise program/

362
Q

What is an osteoma and osteoblastoma? How are they treated.

A

Benign bone tumours. Round radiolucency with central mineralizations.

Osteoma <2cm, any bone, pain relieved by NSAIDs, treated by radiofrequency ablation.

Osteoblastoma >2cm, more frequent posterior spine, not relieved by NSAIDs, treat by curettage/excise en bloc.

363
Q

What is an osteosarcoma?

What are some genetic abnormalities associated with it?

A

Cancerous bone tumour. 50% about the knee, in metaphysis. See triangular shell of reactiv ebone known as Codman triangle.

Spreads hematogenously to lungs, brain, other bones.

RN, TP53, INK4a (encodes tumor suppressors p14 and p16), MDM2 and CDK4.

364
Q

What’s an osteochondroma? What genes are associated with it?

A

Hyaline cartilage forming benign tumour in metaphysis of long bones. Can be solitary or multiple, hereditary (AD_ or sporadic.

50% of hereditary multiple may progress to osteosarcoma.

EXT1/2 ggenes associated with it (reduced expression) - multiple chondromas.

365
Q

What genes are associated with an endochondroma?

A

Heterozygous mutations in IDH1/2 - cause isocitrate dehydrogenase to acquire new enzymatic activity that leads to 2-hydroxyglutarate (antimetabolite).

366
Q

What is Ollier Disease?

A

Nonhereditary mltiple endochondromas.

367
Q

What is Maffucci syndrome?

A

Nonhereditary multiple endochondromas and spindle cell hemangiomas, also has risk of ovarian carcinomas and brain gliomas.

368
Q

What is a chondrosarcoma?

A

Malignant cartilage forming tumour (conventional = hyaline). Commonly in axial skeleton.

Low grade causes reactive thickening of cortex, high grade destroys cortex and forms a soft tissue mass.

Can arise from osteochondromas or endochondromas.

369
Q

How are chondrosarcomas treated?

A

Surgery - mesenchymal and dedifferentiated tumours also are given chemo.

370
Q

What is a Ewing sarcoma?

A

Tumour of unknown origin found in the diaphysis of long bones.

Sheets of primitive small, round cells. Age 10-20, amputate.

371
Q

What is a Giant Cell Tumour / Osteoclastoma?

A

Primitive osteoblast precursor tumour - express high levels of RANKL - most of tumour comprises osteoclasts.

Arise in epiphysis but may extend to metaphysis - near the joints may cause arthritis-like symptoms.

372
Q

Describe Aneurysmal Bone Cysts. What are the genetics and features?

A

Unknown origin. Multi-loculated blood-filled cystic spaces (treat surgically).

Pathologic fractures rare. Have to do with 17p13 resulting in USP6 overexpression and increased NFkB activity (bone reabsorption).

Eccentric expansile lesion with well-defined margins, thin shell of reactive bone at periphery - MRI shows internal septa and fluid-fluid levels.

About 1/3 cases have densely calcified matrix called ‘blue bone’.

373
Q

What makes storiform/pinwheel patterns?

A

Benign spindle cells with scattered osteoclasts.

Caused by fibrous cortical defects and nonossifying fibromas (up to 5-6cm).

Vast majority arise eccentrically in metaphysis of distal femur/proximal tibia. Generally asymptomatic.

374
Q

What is Fibrous dysplasia?

A

Benign tumour that has been likened to a localized developmental defect. Normal components present but do not differentiate into mature structures. Can be monostotic or polystotic.

Lesions are well-circumscribed, intramedullary. “Chinese characters” appearance.

375
Q

What does a GoF in GNAS1 cause?

A

If in embryogenesis, then McCune-Albright (polyostotic, cafe au lait spots, precocious puberty).

If after birth, then monostotic fibrous dysplasia.

376
Q

What is Mazabraud syndrome?

A

Fibrous dysplasia (usually polyostotic) and soft tissue myxomas.

377
Q

What’s the difference between monostotic and polyostotic fibrous dysplasia? How are they treated?

A

Monostotic manifests in teens, stops enlarging at the time of growth plate closure, may cause pain, fracture, deformity - ground-glass appearance, well-defined margins on x-ray. Treat with curettage.

Polyostotic manifests earlier, may cause problems into adulthood, often have craniofacial involvement. May need corrective orthopedic surgery.

378
Q

Where do 75% of metastatic bone tumours originate from?

A

Prostate, breasts, kidneys, lungs.

379
Q

Describe metastatic bone tumours.

A

Axial skeleton involved because of red active BM. Can be lytic, blastic (prostatic adenocarcinoma), or mixed (kidney, lung, GI carcinoma, malignant melanoma).

Sclerotic metastases caused by tumour cells secreting WNT to stimulate bone formation.

380
Q

What are soft tissue tumours?

A

Not epithelial, CNS, skeleton, joints, hamatopoietic/lymphoid tissue.

381
Q

Give two examples of simple karyotype soft tissue tumours.

A

Ewing and synovial sarcoma.

382
Q

Give two examples of complex karyotype soft tissue tumours.

A

Leiomyosarcoma and undifferentiated sarcoma.

383
Q

What is liposarcoma?

A

Malignant tumour of fat cells. Amplification of 12q13-q15 is characteristic of well-differentiated sarcoma. t12;16 is characteristic of myxoid lymhoma.

384
Q

What is the painful type of lipoma?

A

Angiolipoma.

385
Q

Describe nodular fasciitis.

A

Fibrous tumour - t17;22 produces MYH9-USP6 fusion gene. Generally self-limited, grey zone between reactive and neoplastic proliferations. Abundant mitotic figures. Arises in deep dermis, subcutis, or muscle.

386
Q

Describe fibromatoses.

A

Grey-white, firm, poorly-demarcated masses (histo resembles scar). Marked infiltration of surrounding tissue.

Superficial is local but innocuous, occasionally painful (palmar = Dupuytren’s, penile = Peyronie)

Deep/Desmoid are large/infiltrative masses. Arise in musculo-aponeurotic structures (anterior abdominal wall, limb girdles, mesentery). APC or beta-catenin mutations increase Wnt signalling.

387
Q

Describe the types of Rhabdomyosarcoma (skeletal muscle tumours).

A

Alveolar (<20yrs, t2;13 (FOXO1+PAX3 or t1;13 (FOXO1+PAX7)).

Embryonal (<20yrs, visible cross-striations).

Pleimorphic (>20yrs, myogenin found in immunohistochemistry).

388
Q

What is sarcoma botyroides?

A

Variant rhabdomyosarcoma - cambium layer (submucosal zone of hypercellularity), occurs in walls of hollow, mucosal lined structures.

389
Q

How is rhabdomyosarcoma treated? Which types respond worst/best?

A

Chemo, surgery, maybe also radiation.

Botyroides responds best, pleimorphic subtype responds best.

390
Q

What’s leiomyoma?

A

Most common neoplasm in women. Smooth muscle tumor.

Can also be in erector pili muscles.

Benign, minimal atypia, few mitotic figures.

391
Q

What is HLRCC?

A

Hereditary leiomyoma and renal cell carcinoma. AD Fumarate dehydratase LoF.

392
Q

What is a leiomyosarcoma?

A

Painless, firm masses retroperitoneally - malignant smooth muscle cells.

Stain with Abs to actin and desmin.

393
Q

What is a sinovial sarcoma?

How is it treated?

A

Soft tissue tumour of uncertain origin. Most show t(x;18)(p11;q11) making SS18-SSX1, -SSX2, -SSX4 fusion genes.

Monophasic: uniform spindle cells with scant cytoplasm and dense chromatin, growing in tightly packed fascicles. Tumour may calcify.

Biphasic: spindle cell, gland-like structures made of cuboidal/columnar epithelial cells (immunohistochemistry positive for keratins).

Treated with limb-sparing surgery and frequently chemotherapy.

394
Q

Describe UPS (Undifferentiated Pleimorphic Sarcoma).

A

AKA Malignant Fibrous Histiocytoma.

Malignant mesenchymal tumours with high grade pleiomorphic cells. Largest category of adult sarcomas - mostly in soft tissues of extremity.

Most tumours aneuploid, large, grey-white fleshy masses (can grow large, hemorrhage and necrosis common), mitotic figures abundant, sheets of large, anaplastic spindles to polygonal cells, irregular, hyperchromatic nuclei.

395
Q

What’s the current recommended ART for treatment-naive HIV patients?

A

2 NRTIs + one inhibitor, NNRTI, or PI.

396
Q

What’s induction therapy at the time of organ transplant?

A

ATG and ALG.

397
Q

What is the most common organ transplant maintenance therapy?

A

Prednisone + calcineurin inhibitor + antimetabolite (can replace one of calcineurin inhibitor or antimetabolite with mTOR inhibitor).

398
Q

What is the established rejection therapy?

A

Some kind of agent against T cells.

399
Q

What is usually given to treat Graft vs Host Disease?

A

Usually high dose glucocorticoid + Calcineurin inhibitor, cntimetabolite, or mTOR inhibitor.

400
Q

What is given for malaria prophylaxis?

A

Chloroquine, Mefloquine for C-resistant, Doxycycline for multidrug resistant, then Primaquine.

401
Q

What is the drug therapy for Chloriquine-sensitive P. falciparum and P. malariae?

A

Chloroquine.

402
Q

What is the drug therapy for Chloroquine-sensitive P. vivax and P. ovale?

A

Chloroquine then Primaquine.

403
Q

What is the drug therapy for uncomplicated infections with Chloroquine-resistant P. falciparum?

A

ACT of Mefloquine.

404
Q

What is the drug therapy for uncomplicated infections with Chloroquine-resistant P. vivax or P. ovale?

A

ACT and then Primaquine.

405
Q

What is the drug therapy for severe/complicated infections of P. falciparum?

A

IV artesunate then doxycycline or IV quinine/quinidine.

406
Q

How do you treat an asymptomatic intestinal amoebiasis infection?

A

Paromomycin.

407
Q

How do you treat a symptomatic intestinal amoebiasis infection?

A

Metronidazole followed by Paromomycin.

408
Q

How do you treat ameboma and other extraintestinal issues as a result of amoebiasis?

A

Metronidazole followed by Paromomycin.

409
Q

How do you treat amebiasis that has progressed to hepatic abscesses?

A

Metronidazole + Chloroquinone.

410
Q

What drugs are given to reverse nondepolarizing blocker skeletal muscle relaxants?

A

Neostigmine and sugammodex for aminosteroids (Vecuronium, Rocuronium, Pancuronium).

411
Q

What drugs increase bone loss?

A

Glucocorticoids, antiepileptics, loop diuretics, PPIs, anticoagulants.

412
Q

What is the standard theumatoid arthritis therapy?

A

Methotrexate + Leflunamide, a biologic, or sulfalazine+hydroxychloroquinone.

413
Q

What do you see in Rheumatoid arthritis that you don’t see in SLE?

A

Periarticular erosions, subchondral cysts.

414
Q

What are the three phases of osteoaerthritis?

A

Chondrocyte injury, Early OA (chondrocytes proliferate and secrete inflammatory mediators / matrix remodeled), Late OA (chondrocyte drop out).

415
Q

Does rheumatoid arthritis cause ankylosis?

A

Yes.

416
Q

What genes/alleles are linked to rheumatoid arthritis?

A

HLA-DRB1 alleles, PTPN22 gene (tyr phosphatase).

417
Q

What’s a pannus?

A

A mass of edematous synovium and inflammatory cells. It grows over articular cartilage and causes its erosion, and bridges over bones to form fibrous ankyloses.

418
Q

What is a baker cyst?

A

A rheumatic cyst at the back of the knee.

419
Q

What are the criteria for it to be juvenile idiopathic arthritis?

A

<16 years old for over 6 weeks.

420
Q

Describe psoriatic arthritis.

A

Typically affects the peripheral and axial joints and entheses. DIPs affected first and asymmetrically (pencil-in-cup deformity).

421
Q

What kind of joints are usually affected in mycobacterial arthritis?

A

Weight-bearing joints.

422
Q

What is the plasma urate level that qualifies it as gout?

A

> 6.8mg/dL

423
Q

What is a ganglion cyst?

A

A small tumour almost always near joint capsules/tendon sheathes (usually around wrists), results from cystic or myxoid degeneration of CT. Have no communication with the joint space.

424
Q

What is a synovial cyst?

A

A herniation of synovium through a joint capsule or a massive enlargement of a bursa.

425
Q

What is a tenosynovial giant cell tumour?

Describe diffuse vs localized type.

A

Benign neoplasm in synovial lining, tendon sheaths, bursae.

Diffuse type tends to involve large joints - pain, locking, recurrent swelling.

Localized type is paiinless.

Semester 3 Medical School (5 decks)

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