Hematology Flashcards
(53 cards)
1
Q
Fever of unknown origin
A
- body temp >38.3 on >1 occasion
- duration >3wk
- no dx after 3d inpatient eval or 3 outpt apt
2
Q
Hyperpyrexia
A
excessive fever >41.5 caused by increase in body’s thermal set point
3
Q
Hyperthermia
A
increase in body temperature beyond the body’s thermal set point
4
Q
Exogenous pyrogens
A
- substances (microbial cell wall components, Lipopolysaccharides on bacteria) that induce formation of endogenous pyrogens from host cells (macrophages)
5
Q
Pyrogenic cytokines
A
cytokines (IL-6) that act on hypothalamus to increase body temperature by releasing PGE2
6
Q
Antipyretics mechanism of action
A
Inhibit synthesis of PGE2
7
Q
Corticosteroids mechanism of action
A
Inhibit phospholipase A2
8
Q
ASA and NSAID mechanism of action
A
Inhibit cyclooxyrgenase
9
Q
Cell-mediated immunity
A
- composed of T lymphocytes, macrophages, and NK cells
- major defence against intracellular pathogens
- cytotoxic T cells directly attack and lyse host cells expressing foreign antigens
- helper T cells stimulate B cell proliferation and production of immunoglobulin (Ab)
- reticuloendothelial system = monocyte-derived phagocytes in liver, spleen, LN, lung that clear circulating microorganisms
defects predispose to intracellular pathogen infection - bacteria, fungi, parasitic, viral (various species)
vs. hypogammaglobulinemia and asplenia predispose to infection with encapsulated bacteria (S. pneumonia, H. influenza, N. meningitidis)
10
Q
Humoral immune system
A
- Ab, complement system, phagocytes
- defends against extracellular pathogens (encapsulated bacteria)
- Ab produced by mature B cells that recognize and bind foreign antigens
- proteins of complement system can act as opsonins, ‘tagging’ pathogens for destruction by phagocytes - terminal complement proteins can directly kill some pathogens via membranes attack complex
11
Q
Neutrophils re: immunity
A
- engulf and destroy pathogenic microbes
- circulating neutrophils localize sites of infection via adhesion molecules expressed by endothelial cells
- diapedesis into extravascular space and further localize via chemokine and chemoattractants
12
Q
Vaccinations in asplenic patients
A
S. pneumo
HiB
N. meningitides
Influenza
13
Q
T cells
A
- primary mediators of CMI
- Ab production requires intact T-cell number and function (stimulation of B cell proliferation by IL2)
14
Q
Leukocytosis
A
high WBC count
15
Q
Leukopenia
A
low WBC count
16
Q
Neutrophils and what are derived from the same common progenitor?
A
erythrocytes, megakaryocytic, monocytes
proliferation from common progenitor via IL-3 and GM-CSF
later differentiation via granulocyte colony-stimulating factor
17
Q
Migration of neutrophils
A
To sites of infection or inflammation via paracellular and transcellular routes through endothelial cell layers
18
Q
Are polymorphonuclear leukocytes (PML) granules toxic?
A
Yes
19
Q
Neutropenia
A
- ANC <1.5 x1^9/L
- decreased production (primary marrow disorder, B12/folate deficiency, infection/sepsis, drugs)
- increased destruction (autoimmune disease, drugs)
- sequestration (splenomegaly)
- constitutional/normal variant (African descent)
20
Q
Neutrophilia
A
- ANC >7.5 x10^9/L
- increased production (reactive, myeloproliferative disease)
- decreased destruction (hyposlenism, asplenism)
- decreased margination (drugs, vigorous physical exertion, stress)
21
Q
Lymphocytosis
A
> 4 x10^9/L
- infection (often viral, pertussis, toxoplasmosis)
- hypersensitivity (drug induced, serum sickness)
- neoplastic (ALL, CLL, lymphoma)
- stress (cardiac, trauma, status epileptics, post-splenectomy)
- autoimmune (RA, malignant thymoma)
22
Q
Leukemoid reaction
A
- persistent neutrophilic with ABC 30,000-50,000/ microL; circulating neutrophils tend to be mature, not globally derived (vs. leukaemia)
- often with septicaemia and severe bacterial infections (shigellosis, salmonellosis, meningococcemia)
- if 12% all cells immature then LEFT SHIFT (rapid release of cells from bone marrow)
- may see increased band forms
- higher degree of left shift = more immature neutrophil precursors = serious bacterial infection, trauma, burns, surgery, acute hemolysis, hemorrhage
23
Q
BCR-ABL
A
aka Philadelphia chromosome
CML
24
Q
Primary hemostasis
A
- platelets and vWF
- endpoint = platelet plug formation
bleeding - mucocutaneous (epistaxis, gingival, menorrhagia, petechia/ecchymoses) - immediate onset of bleeding after injury
25
Secondary hemostasis
- coagulation cascade
- result in fibrin cross linking = reinforcement and stabilization of platelet plug
bleeding - deep tissue (hemarthrosis, intramuscular hematoma)
- delayed onset of bleeding after injury
26
Intrinsic coagulation pathway
```
collagen (injured vessel) = XII -> XIIa
XIIa = XI -> XIa
XIa = IX -> IXa
platelet phospholipids, calcium, VIIIa
to common pathway
```
27
Extrinsic coagulation pathway
Tissue factor = VII -> VIIa
platelet phospholipids, calcium
to common pathway
28
Common coagulation pathway
```
IXa + VIIa = X -> Xa
platelet phospholipids, calcium, Va
= II -> IIa (thrombin) -> XIII
IIa = fibrinogen -> fibrin
XIIIa = fibrin -> cross linked fibrin
```
29
Tests for hemostasis
primary
- platelet count, platelet function test
secondary
- PTT: intrinsic pathway factors (VII, IX, XI, XII), monitors heparin tx
- PT/INR: extrinsic pathway factor (VII), monitors warfarin tx
- TT (thrombin time): measures fibrinogen deficiency or reduced prothrombin activation
30
PTT 1:1 dilution
- if PTT corrects with 1:1 dilution = absolute deficiency in factor level
- if PTT remains high = factor inhibitor present
31
Ddx hypercoagulable state
inherited - thrombopilia
- antithrombin deficiency
- protein c & s deficiency
- factor V Leiden
- prothrombin 20210 mutation
acquired
- cellular elements (hypercoagulability) - malignancy, pregnancy, OCP, HRT, HIT, DIC, TTP, other
- vascular endothelium - surgery, trauma
- circulatory - pregnancy, immobilization, a. fib
32
HIT with subsequent thrombosis
- patient has Ab to PF4-heparin complex
- reduction in platelet count and 30-fold increase risk of thrombosis
- d/c heparin and cannot replace with LMWH (cross reactivity) or warfarin (skin necrosis)
- switch to direct thrombin inhibitor or heparinoid anticoagulation
33
Diagnostic testing re: VTE/ hypercoagulable
- compression U/S gold standard veins above calf
- V/Q scan if PE (not if parenchymal lung disease present)
- spiral CT if PE (not if reduced renal function or pregnancy)
- pulmonary angiography is fold standard for PE (rarely used - CI if compromised renal function)
34
Ddx splenomegaly
Increased splenic function demand
- clearance of abnormal RBC (thalassemia major, abnormal RBC shape)
- infection (bacterial, viral, fungal, parasitic)
- autoimmune (RA - Felty syndrome, SLE, collagen vascular disease, drug rxn)
Altered splenic circulation
- cirrhosis, portal HTN, protein vein obstruction, hepatic vein obstruction, splenic vein obstruction, CHF
Splenic infiltration
- Myeloproliferative disorders, malignancy, amyloidosis, sarcoidosis, storage disease
35
Major causes splenomegaly acronym
ICE MASS
- infectious
- congestive splenomegaly
- chronic liver disease
- extra medullary hematopoesis
- malignancy
- amlyoidosis
- sarcoidosis, storage disease
36
Castell sign
- percussion in 8-9 intercostal space in left anterior axillary line of supine patient elicits resonant note throughout respiratory cycle if spleen normal
- > castell sign = percussion on full inspiration produces dull note (splenic enlargement)
37
Anemia
- decrease in number of circulating RBC
- result from reduced production, increased destruction, or blood loss
* MCV must be taken into account
38
B12 (cobalamin) absorption
- cobalamin-protein complex from diet enters stomach -> stomach acid release cobalamin from protein
- cobalamin + R proteins (parietal cells)
- pancreatic enzymes in stomach release cobalamin from R-protein
- cobalamin binds intrinsic factor -> to terminal ileum
- cobalamin-IF complex binds cubuilin (R on mucosal cells in ileum) = endocytosis
- cobalamin binds transport proteins -> TCII-cobalamin complex endocytose; cobalamin released and converted to coenzymes
39
B12 deficiency causes
Decreased intake - vegans
Altered metabolism
- pernicious anemia (antibodies to parietal cells or IF)
- achlorhydria (acid needed to release cobalamin from protein)
- H2 blockers (decrease IF secretion)
- postgastrectomy
- pancreatic insufficiency (can't digest R-binders off)
Decreased absorption
- ileal disease
- celiac disease
- pancreatic insufficiency
40
Neuro sx B12 deficiency
```
dementia
peripheral neuropathy (esp. lower limbs)
subacute combined degeneration - cortocospinal tract (spasticity, hyperreflexia) and dorsal column (decreased proprioception and vibration sense)
```
41
Fe-deficiency labs
- ferritin = ++ decreased
- serum iron = decreased/normal
- TIBC = increased/high normal
- % saturation = ++decreased
42
Ddx microcytic anemia
MCV <80fL
- iron deficiency
- thalassemia
- anemia of chronic disease
- lead poisoning
- siberoblastic anemia
43
Ddx normocytic anemia
```
MCV 80-100fL
Low/normal reticulocytes
- anemia of chronic disease
- renal failure
- combined iron and B12/folate deficiency
- marrow infiltration
- aplastic anemia
```
High reticulocytes
- acute blood loss
- hemolysis
- splenic sequestration
44
Ddx microcytic anemia
MCV >100fL
- megaloblastic (B12/folate deficiency, drugs)
- liver disease
- EtOH
- MDS
- hypothyroidism
- reticulocytosis (response to hemorrhage or hemolysis)
45
Polycythemia
Increase in hemoglobin (increase RBC mass or decrease plasma volume)
- primary = polycythemia vera
- secondary = increased EPO
46
Ratio of RBC mass to plasma volume
Hemoglobin and hematocrit
| - sensitive to changes in either RBC mass or plasma volume
47
Polycythemia vera characteristics
- absolute increase of RBC mass and decreased EPO
- median age dx 60
- venous and arterial thrombosis in unusual sites
- headache
- blurry vision
- erythromelagia
- gouty arthritis
- pruritus
- splenomegaly
- easy bleeding (GI bleed, epistaxis)
48
Polycythemia vera dx
Dx requires both major criteria and one minor criterion OR first major criterion and two minor criteria:
Major criteria
- elevated hemoglobin (>185 males, >165 females)
- JAK2 mutation
Minor criteria
- hyper cellular bone marrow with trilineage myeloproliferation (panmyelosis)
- decreased serum EPO
- endogenous erythroid colony growth in vitro
49
EPO stimulation, production, action
Stimulation - reduced oxygenation of blood
Production - peritubular kidney cells
Action - bone marrow, increase RBC production
50
Lymphadenopathy and ddx
LN >1cm = abnormal
- LN have cortex and medulla (germinal enters in cortex)
DDx
- infectious - viral, bacterial, fungal, parasitic
- malignancy - lymphoma, leukaemia, metastatic CA
- immunologic/ inflammatory - serum sickness, collagen vascular disease, drug hypersensitivity
- other - sarcoidosis, amyloidosis, endocrine (hyperthyroidism), storage disease
51
Lymphatic system constituents
LN and vessels
Thymus
Spleen
Peyer patches in gut
52
Activation of adaptive immunity
Recognition stage
- antigens recognized by lymphocytes and macrophages
Proliferation stage
- dominant lymphocytes proliferate and differentiate into cytotoxic (killer) T cells or B cells
Response stage
- cytotoxic T and B cells perform cellular and hum oral functions
Effector stage
- antigens destroyed or neutralized through action of antibodies, complement, macrophages, and cytotoxic T cells
53
LN characteristics (normal, inflammation, lymphoma, metastatic)
normal - soft, discrete, mobile
inflammation - tender, mobile
lymphoma - large, rubbery, non-tender, mobile
metastatic cancer - hard,non-tender, matted, non-mobile
