Shit - Heme Flashcards
Platalets:
- lifespan
- dense granules
- alpha granules
- lifespan 8-10d
- dense = APD and Ca
- alpha = vWF and fibrinogen
Neutrophils:
- specific granules:
- azuriphilic granules:
specific = ALP, collagenase, lactoferrin, lysozyme* (cell wall breaking)
Azurophilic = proteinase, acid phosphatase, MPO (makes green pus), b-glucuronidase
Macrophages and shock
Macro CD14 —-Lipid A of LPS
causes of eosinophilia
Il-5, asthma, allergy, neoplasia, parasites, chronic adrenal insufficiency
Content of eosinophils vs basophils vs mast cells
eos = MBP and histaminase
baso = histamine, heparin, late LTs
mast = histamine, heparin, tryptase, eosinophil chemotactic factor
Prevention of mast cell degranulation
Cromolyn sodium
NK markers
CD16 and CD56
Kleihauer-Betke test
%HbF in maternal blood, determines rhogam dosing
Extrinsic coagulaton pathway: players and test
VII to VIIa by III
III = thromboplastin = tissue factor; activated by endothelial injury
PT
plasminogen to plasmin
tPA (endogenous)
Alteplase, reteplase, streptokinase, tenecteplase
Stops plasmin formation:
a2-anti-plasmin (endogenous)
Aminocaproic acid
Factors activated by vit K
II, VII, IX, X, C, S
Protein C role
Inactivate Va and VIIIa
Factor V liden mutation
Factor V that can’t be inactivated by protein C –> clotting disease
Antithrombin inactivates:
enhanced by:
II, VII, IX, X, XI, XII
*most important = II and Xa
enhanced by heparin
Platelet activation:
- activated by:
- release:
Activated by platelet GpIb ——- vWF—endotheium
Release ADP, CA and TXA2
ADP ——ADP-R of other platelets –> GPIIb/IIIa espression, which binds fibrinogen causing platelet aggregatoin
Where does vWF come from?
Weibel-palade bodies of endothelium
Alpha-granules of platelets
ADP-R inhibitors
Clopidogrel, prasugrel, triclopidine
Direct GPIIb/IIIa inhibitors
Abciximab, eptifibatide, tirofiban
Ristocetin
promotes vWF — GpIb
decreased agglutinatoin in test indicated von Willibran disease or bernard soulier (GpIb deficiency)
Direct thrombin inhibitors:
agatroban, dabigatran, bivalirudin
Direct Xa inhibitors
Apixaban, rivaroxaban
*fondaparineux
Spur cells (acanthocytes)
vs echinocyte (burr cell)
spur = liver disease, abetalipoproteinemia, vit E deficiency
burr = EDTA artifact, uremia, PK deficiency, hypo-Mg, hypo-P, hemolytic anemia, mechanical damage
Basophilic stippling vs ringed sideroblasts
basophilic stippling = lead poisoning
ringed sideroblasts = sideroblastic anemia, IRON in the mitochondria becasue d-ala-synthase deficiency MA (also can be from lead poisoning)
bite cells other name:
degmacyte
target cells:
HbC, Asplenia, Liver disease, Thalassemias
Plumer-Vinson
IDA, esophageal webs, atrophic glossitis
alpha-thal
- chrom/problem
- Types
Cr16; deletions
cis = asian = same strand (worse, creates HbBarts)
trans = african = different
HbBarts = hydrops = 0/4
HbH = 1/4
Beta-thal
- chrom/problem
- types
Cr 11, point mutations in spice sites/promoters
Medeterranian
Major = high HbF
Minor = high HbA2
Lead roles:
Blocks ALA-dehydratase (2) and ferrocheletase (7, last)
Inhibits rRNA degradatoin (basophilic stippling)
Causes sideroblastic anemia
S/S foot/wrist drop, encephalopathy, GI
Lead poisoning Rx
Dimercaprol
EDTA
Succimer (kids)
Penicillamine
Causes of sideroblastic anemia
Hereditary: ALA synthase (1, RLS); XR
Acquired: MDS
Reversible: alcohol, lead poisoning, B6 defic., Cu defic., INH
Drug causes of folate deficiency
TMP, MTX, phenytoin
Orotic aciduria:
cause
labs
UMP synthase deficiency (AR); builup of orotic acid, no pyrimidine de novo
Megaloblastic anemia refractory to B9 and B12, orotic acid in urine, NO hyperammonemia
Non-megaloblastic macrocytic anemia causes
alcoholism
liver disease
hypothyroidism
reticulocytosis
5-FU
hepcidin
- MOA
- disease and causes
- Rx
ARP form liver, increase by inflammation (or high Fe)
blocks ferroportin, preventing intestal cells from BL transport to transferrin, and macrophage release
ACD: SLE, RA, neoplasm, CKD
Rx = EPO
Aplastic anemia
- causes
- S/s
Causes:
- radiation.drugs (benzene, alkyl, chloramphenicol)
- B19, HIV, HCV, EBV
- Fanconi anemia
S/s: fatigue, infections, bleeding (petechiae, purpura)
Hemolytic anemia in a newborn
Pyruvate kinase deficiency
PNH: triad and long-term sequale
Triad = Coombs negative HA, pancytopenia (acquired SC defect), venous thrombosis (RBCs relelase pro-coagulant stuff)
Increased incidence of ALL
HbS vs HbC mutations
Test for both
both Cr.11 pos 6
HbS = valine (/) for glutamate (-); H-phobic, sickles
HbC = lysine (+) for glutamate (-)
*think about electrophoresis bands*
Test = sodium metabisulphite screen (both will sickle)
AHA warm vs cold: coombs, causes, and Abs
Coombs +
Warm = IgG = SLE and CLL
Cold = IgM = mycoplasma, mono, malignancy, CLL
Pregnancy/OCP effect on iron handling
increases TIBC(transferrin); so decreases %transferin saturation
Corticosteroids on blood cell profile
Neutrophilia (prevents extravasation)
Eosinopenia (sequesters them in LNs)
Lymphopenia (apoptosis)
Lead poisoning steps affected + location + buildup
2 = ADA dehydratase = cytoplasm = d-ALA
7 = ferrocheletase = mitochondria = iron and protoporphyrin
Acute Intermittent Porphyria step blocked and buidup
Exacerbated by:
Rx:
3 = porphobilinogen deaminase = PBG buildup
Exacerbated: 450 inducers, alcohol, starvation
Rx = glucose
Porphyria cutanea tarda enzyme and buildup:
Uroporphyrinogen decarboxylase; uroporphyrinogen III buids up
Iron poisoning microscopy and major s/s
Membrane lipid peroxidation
GI bleed
Desmopresin Rx for:
Hemophilia A (VIII) and vWF deficiency
(endothelial release)
Cagualtion factor inhibitor disease
Abs to CFs
MC = VIII; looks like hemophilia A, but when you mix it with test blood PTT doesnt normalize becasue the ABs just attack the fresh cells
Bernard soulier defect
GpIb of platelets (doesnt bind vWF on endothelium)
no agglutination with ristocetin
Glanzmann’s Thromblasthenia
GpIIb/IIIa deficiency
no platelet crosslingking because cant bind fibrinogen
ITP
Rx
Anti-GpIIb/IIIa
Rx = steroids (decrease Ab production via lymphocyte apoptosis), IVIG (gives Abs something else to bind)
Killer T-cell MOA killing
Perforin and granzyme –> activate CASPASES
Features of anaplastic cells
loss of polarity, nuclear polymorphism, irregular mitoses, high N:C, giant multinucleated tumour cells
etoposide/teniposide inhibit:
topotecan/irinotecan inhibit:
topo II reannealling their dsDNA breaks
topo I
*1 can has 2 sides*
Rb-P means:
inactivated
cell can progress thru cell cycle (G1 to S)
Role of protecin C (and S)
deactivate factors V and VIII by proteolysis
AT-III deficiency labs, cause
NORMAL PT, PTT, TT
Heparin deos NOT increase PTT
AD or acquired (proteinuria)
Propthombin 20210A mutation
Point mutation in 3’UTR, which increases protheombin production
Fibrinolysis disorders
radical prostatectomy (urokinase release)
liver cirrhosis –> low a2-anti-plasmin
s/s = DIC but NORMAL platelet count; increased fibrinogen split products (not fibrin)
Rx = aminocaproic acid (inhibits plasminogen)
Cryoprecipitate: contents and when its used
Fibrinogen, vWF, VIII, XIII, fibroniectin
Fibrinogen or VIII deficiencies
CD 15 and CD30+
Reid Sternberg Hodgkins B-cell lymphoma
Types of Hodgkins lymphoma + histology
Reid-sternberg owl-eyes
Nodular sclerosing: M=F, 70%, cervical or mediatinal, lacunae
Lymphocyte risk: good Px
Mixed or Lymphocyte depleted: bad Px
Types of burkitts + location
Endemia = africa = jaw
Sporatic = pelvis or abdomen
Immunodeficient
painless waxing and waning LAD: Dx
Follicular lymphoma (bcl-2; 14;18)
mantle cell TL and CD
11;14, CD5
ATCL s/s
lytic bone lesions, hypercalcemia, generalized LAd with HSM
mycoses fungioides vs. sezary syndrome
Histo
MF = cutaneous, lymphoma
SS = cutaneous and systemic, leukemia
Criberiform nuclei
lytic bone lesions in MM: pathophysiology
Neoplastic B-cells secrete Il-1 and IL-6
IL-1 activates osteoclasts
MM vs MGUS vs WM
MM = IgG (MC) or IgA M-spike with CRAB s/s
MGUS = IgG or IgA spike with NO s/s (can become MM)
WM = IgM M-spike, hyperviscocity syndromes (blurred vision, raynauds)
Myelodysplastic syndrome: disease, causes, sequale
de novo mutation or enviro (benzene, radiation, chemo)
>20% blasts = AML
Pseudo-Pelger-Huet anomaly
bilobed PMNs, seen after chemo
Sickle cell and MCHC
high via RBC dehydration
