RBC membrane has what transporter?
Membrane contains chloride- HCO3- antiporter, which allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for elimination.
Anisocytosis:
varying sizes of RBCs
Poikilocytosis:
varying shapes
platelet
- dense granules:
- alpha granules:
- dense granules = ADP, calcium
- a granules = vWF, fibrinogen
WBC differential from highest to lowest
-mnemonic:
Neutrophils Like Making Everything Better. Neutrophils (54–62%) Lymphocytes (25–33%) Monocytes (3–7%) Eosinophils (1–3%) Basophils (0–0.75%)
Neutrophils
-granules contain what?
- ALP, collagenase, lysozyme, and lactoferrin.
- azurophilic granules (lysosomes) contain proteinases, acid phosphatase, myeloperoxidase, and β-glucuronidase.
Band cells
-what are they?
immature neutros
Cell surface marker for macrophage?
CD14
Eosinophil
- phagocytic?
- role in type 1 HSR?
- Highly phagocytic for antigen-antibody complexes.
- Produces histaminase and arylsulfatase (helps limit reaction following mast cell degranulation).
Causes of eosinophilia =
-mnemonic?
NAACP: Neoplasia Asthma Allergic processes Connective tissue diseases Parasites (invasive)
Isolated basophilia found in:
CML.
Mast cell degranulation releases:
Histamine, heparin, and eosinophil chemotactic factors.
Universal donor of plasma?
-which blood type
AB
Universal recipient of plasma?
-which blood type?
O
- anti-A and anti-B antibodies =
- anti-Rh=
-what type of Ab and does it cross the placenta?
- IgM (do not cross placenta)
- IgG (cross placenta)
Erythryoblastosis fetalis
-Tx:
Treatment: Rho(D) IgG for mother during every pregnancy to prevent initial sensitization of Rh- mother to Rh antigen.
In basic terms, what is coagulation?
Coagulation = soluble fibrinogen converting to insoluble fibrin.
-property of plasma. dont need anything else.
Heparin sulfate
-what hooks onto it?
-antithrombin 3
Antithrombin inhibits activated forms of factors:
II, VII, IX, X, XI, XII.
-1972 + 11 & 12
thrombomodulin
-binds what? which activates what?
- thrombin
- thrombin activates protein C which inhibits factors 5 & 8.
Effects of thrombin on factor 5 & 8?
-coag. starts slow, but once thrombin made, thrombin goes back and activates factors 8 and 5 which accelerate the pathway. This speeds up coag.
-Protein C and S inactivate factor 8a and 5a. They’re the
“brakes” to coag pathway.
Endothelial cell: Weiber-palody body contains:
-vWF in the endothelial cell. These contain vWF & ps-electin.
Ticlopidine and clopidogrel:
- inhibit ADP-induced expression of GpIIb/IIIa.
- irreversibly bind ADP receptor.
Ristocetin:
- Activates vWF to bind to GpIb.
- Useful for diagnosis: normal platelet aggregation response is not seen in von Willebrand disease.
Acanthocyte (spur cell)
-associated w/
-Liver disease, abetalipoproteinemia (states of cholesterol dysregulation).
Basophilic stippling
-mnemonic
BASically, ACiD alcohol is LeThal.
- Anemia of Chronic Disease
- alcohol abuse
- Lead poisoning
- Thalassemias.
Bite cell
-which disease?
G6PD deficiency.
Elliptocyte
-which disease?
Hereditary elliptocytosis.
Macro-ovalocyte
-which disease?
- Megaloblastic anemia (also hypersegmented PMNs)
- marrow failure.
Mechanical trauma (ie. prosthetic valve) vs. trauma from microthrombi:
Look at the platelet count! if its normal, then its a prosthetic, if platelet count is down then its a microthrmbi.
Spherocyte
-which disease?
-Hereditary spherocytosis, autoimmune hemolysis.
Target cell
- which disease?
- mnemonic?
“HALT,” said the hunter to his target.
-HbC disease, Asplenia, Liver disease, Thalassemia.
Heinz bodies
- Oxidation of hemoglobin sulfhydryl groups.
- Turn into bite cells
- G6PD def.
Corrected reticulocyte count
(hct/45)*(retic count).
- if there are polychromatic cells, then divide by 2
- 3%+ = good marrow response, 2% and lower = bad marrow response.
TIBC inversely related to what?
Serum ferritin
Law of RBC size
RBC always wants to maintain normal concentration of Hb. So if you have low Hb, RBC will be made smaller so that conc. will still be the same!
Microcytic anemias
-mnemonic?
TAILS
- Thalassemias
- ACD
- Iron def. anemia
- Lead poisoning
- Sideroblastic anemia
Megaloblastic anemias
-mnemonic?
FOBs have nutrition deficiencies.
- Folate def
- Orotic aciduria
- B12 def.
Copper deficiency can what type of anemia?
microcytic sideroblastic anemia.
- koilonychia & pica
- which disease?
- iron def. anemia
- koilonychia = spoon shaped nails
- pica = eating random things
How to measure transferrin?
TIBC
RDW & FEP in iron def anemia
-inc or dec?
- RDW inc. (RBC distribution width)
- FEP inc. (Free erythrocyte protoporphyrin)
alpha-thal
- gene mutations/deletions?
- cis = asian or african?
- trans = asian or african?
- gene deletions.
- cis deletion prevalent in Asian populations.
- trans deletion prevalent in African populations.
Hb Barts
- what is it?
- what fetal problem does it cause?
- all 4 alpha-globin genes deleted
- excess gamma globin forms gamma(4) = Hb Barts
- causes hydrops fetalis
*incompatible w/life
HbH disease
- 3 alpha-globin allele deletion
- Excess β-globin forms β4 (HbH).
- very severe anemia.
hydrops fetalis:
-Extensive compensatory erythropoiesis in the liver disrupts portal blood flow, contributing to dec. albumin synthesis, hypoalbuminemia, and generalized edema (anasarca).
How do thalassemias lead to abdominal pain?
1) splenic infarction
2) inc hemolysis -> bilirubin gallstones -> RUQ pain.
beta-globin genes
-on which chrom?
11
beta-thal major
-why is there marrow expansion?
- severe anemia due to lack of HbA.
- tons of EPO released by kidney.
- marrow hyperplasia and expansion.
beta-thal
-mutations or deletions?
-point mutations
Beta-thal minor
-How do you diagnose?
-Dx confirmed by inc. HbA2 (> 3.5%) on electrophoresis.
Beta-thal major
- what causes RBC damage?
- how can it lead to secondary hemochromatosis?
- no beta chains, so you get alpha tetramers = damages RBC. Spleen will destroy these RBCs w/alpha tetramers.
- lots of blood transfusions can overload you w/iron.
How long after birth does beta-thal major Sxs show up?
- after 5 months
- HbF is protective
How does lead poisoning lead to basophilic stippling?
Inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA (basophilic stippling).
Zn-protoporphyrin
- seen in what disease?
- why/how?
Lead poisoning
-ferrochelatase knocked off, cant add iron to protoporphyrin, so Zn inserts itself instead, you get Zn-protoporphyrin.
Lead poisoning
- Sxs:
- mnemonic?
LEAD:
-Lead Lines on gingivae (Burton lines) and on metaphyses of long bones D on x-ray.
-Encephalopathy and Erythrocyte basophilic
stippling.
-Abdominal colic and sideroblastic Anemia.
-Drops—wrist and foot drop
Lead poisoning
-Tx:
- Dimercaprol and EDTA are 1st line of treatment.
- Succimer for kids.
Sideroblastic anemia
- inheritance?
- whats the problem?
- X-linked defect in δ-ALA synthase gene.
- also non-inherited causes as well.
Cofactor for δ-ALA synthase?
B6
Sideroblastic anemia
-non-genetic causes:
-acquired: myelodysplastic syndromes
-reversible: alcohol is most common, lead, vitamin B6
deficiency, copper deficiency, and isoniazid.
Isoniazid can cause which type of anemia?
-sideroblastic anemia due to B6 deficiency
Sideroblastic anemia
- serum iron?
- serum ferritin?
- TIBC?
- inc iron
- inc ferritin
- normal/dec TIBC
Sideroblastic anemia
-Tx:
pyridoxine (B6)
Ferrochelatase
-where is this reaction going down?
- mitochondria.
- must be, or else why would the iron be accumulating in the mitochondria when this enzyme doesn’t work in lead poisoning or sideroblastic anemia?
Ringed sideroblasts seen in which diseases?
- Lead poisoning
- Sideroblastic anemia
- iron getting trapped in mitochondria.
If a diabetic is under great glycemic control but the HbA1c still really high, what one possible explanation?
-Could just mean less HbA1 like w/beta-thalassemia.
which anemia can alcohol cause? and how?
alcohol can cause macrocytic anemia via toxicity to bone marrow.
Folate deficiency
- homocysteine: inc or dec?
- methylmalonic acid: inc or dec?
-inc. homocysteine: less folate = less B12 taking
methyl group = less passing methyl to homocysteine
= less conversion to methionine = pile up of homocyst.
-methylmalonic acid -> succinyl coa: B12 needed, &
B12 normal here, so methylmalonic acid is normal. This
is good to cancel out B12 def.
How does phenytoin lead to megaloblastic anemia?
-Folate absorbed in jejunum. Intestinal conjugase (inhib. by phenytoin) req for absorption.
How can Crohns disease lead to megaloblastic anemia?
- B12 resorbed in terminal ileum.
- terminal ileum often involved in Crohns disease.
PPIs
-what kind of anemia can these lead to?
B12 deficiency megaloblastic anemia.
-
Most common cause of B12 deficiency?
-Whats test called to Dx this cause?
- pernicious anemia
- Schilling test
Pancreatic insufficiency
-can lead to what anemia?
- B12 deficiency megaloblastic anemia
- need pancreatic proteases to cleave R-binder from B12.
Orotic aciduria
- can lead to what anemia?
- what enzyme is defective?
-megaloblastic anemia
-UMP synthase (pyrimidine synth).
-
Nonmegaloblastic macrocytic anemias
-causes?
- liver disease; alcoholism; reticulocytosis => inc. MCV
- drugs (5-FU, zidovudine, hydroxyurea).
Normocytic, normochromic anemia
-what are the 2 classes?
hemolytic & non-hemolytic
Intravascular hemolysis
-haptoglobin, inc or dec?
-dec
Extravascular hemolysis
- where is hemolysis taking place?
- what type of cells will you see in smear?
- Spleen via splenic macrophages
- spherocytes
Extravascular hemolysis
-which bilirubin will be inc?
-unconjugated bilirubin inc = can cause jaundice.
Which 2 vitamins does breast milk not have adequate amounts of?
- vitamin K and D.
- must give vitamin K when baby is born or could get hemorrhagic disease of newborn.
henoch schonlein purpura
-Sxs:
IgA vasculitis
- palpable purpura
- arthralgias
- GI probs: melena, colicky pain
- IgA nephropathy
Warfarin or heparin
- which can be used in pregnancy?
- mnemonic?
- heparin can be used in pregnancy, does NOT cross placenta.
- Do not wage WAR on baby. Keep is HEPpy w/heparin.
Tenderness of calf to dorsiflexion = sign of what?
- DVT
- Homan’s sign.
LMWH vs unfractinoated heparin
-difference?
LMWH has more activity against factor Xa.
Sickling test for sickle cell anemia
-sodium metabisulfite added should make the cells sickle if you have sickle cell.
Sickle cell trait
-whats the only Sx they usually get?
hematuria
Bleeding from venous puncture sites is highly suggestive of what?
DIC
spur cells (acanthocytes) -usually seen in which disease?
abetalipoproteinemia
Fatigue & heart palpitations (& inc. CO)
-characteristic of which anemias?
common to all anemias.
Pancytopenia w/o spenomegaly
-DDx:
- severe B12/folate def.
- aleukemic leukemia
- myelodysplastic syndrome
aplastic anemia
-whats the bone marrow look like?
hypocellular filled w/fat cells and fibrotic stroma
Warfarin
-prolongs PT or PTT more?
-PT
Heparin
-prolongs PT or PTT more?
-PTT
Which pro-coag protein is not made in the liver?
vWF
-made in endothelial cells.
hypercoag, hemolytic anemia, & pancytopenia
-this triad points toward what disease?
paroxysmal nocturnal hematuria
DIC
- fibrinogen levels?
- PT?
- factor 5?
- factor 8?
- fibrinogen = dec.
- PT = increased
- 5 & 8 = decreased
Whats monitored in a pt to Dx DIC?
serum fibrinogen
What does a reticulocyte look like?
Slightly larger and more blue than mature RBC.
-retains some rRNA which appears blue.
Diphyllobothrium latum
-can cause what anemia?
B12 def. megaloblastic anemia.
ACD
- serum iron?
- ferritin
- TIBC
- iron = low (has to be)
- ferritin = high
- TIBC = dec
What does hepcidin bind?
ferroportin on enterocytes & macrophages
What does hepcidin bind?
ferroportin on enterocytes & macrophages
-dec. release of iron from macrophages.
Aplastic anemia
-which chemicals/drugs can cause it?
-benzene, chloramphenicol, alkylating agents, antimetabolites.
Aplastic anemia
-which viruses can cause it?
-parvovirus B19, EBV, HIV, HCV.
Fanconi anemia
- what is it?
- which anemia can it cause?
DNA repair defect
-aplastic anemia
Aplastic anemia
-Tx:
-RBC and platelet transfusion, G-CSF, or GM-CSF.
aplastic anemia
-is splenomegaly present?
NO
If you have normal bilirubin levels, what can you rule out?
hemolysis
Pts w/hemolytic anemia are predisposed what deficiency?
Pts w/hemolytic anemia are predisposed to folate deficiency b/c of inc. RBC turnover.
-Iron is effectively recycled & we have a lot of B12 stores.
Which proteins can be defective in hereditary spherocytosis?
ankyrin, band 3, protein 4.2, spectrin
hereditary spherocytosis
- MCHC: inc or dec?
- RDW: inc or dec?
- splenomegaly?
- inc. MCHC,
- inc. red cell distribution width
- yes, splenomegaly.
- osmotic fragility test (+) .
- Eosin-5-maleimide binding test useful for screening.
hereditary spherocytosis
hereditary spherocytosis
-Tx:
splenectomy
Most common enzymatic disorder of RBCs?
G6PD deficiency
G6PD deficiency
- presentation?
- possible triggers?
- Back pain, hemoglobinuria a few days after oxidant stress.
- sulfa drugs, antimalarials, infections, fava beans, TMP-SMX (link btwn UTI & G6PD def.)
*Hb = nephrotoxic & gives you back (kidney) pain.
Heinz body
-what is it?
- oxidized Hb
- G6PD deficiency
N-MYC
-associated w/which cancers?
- neuroblastoma
- small cell carcinoma of lung
Where in the LN do B-cells proliferate & isotype switch?
Cortex
-thats where germinal centers are.
argatroban, bivalirudin
- directly inhibit thrombin.
- derivative of hirudin (used by leeches).
- used instead of herparin in pts w/HIT (heparin induced thrombocytopenia).
Whats the most common cause of thrombocytopenia in hospitalized pts?
Heparin (esp. unfractionated heparin).
-HIT => paradoxical thrombosis rather than bleeding.
cilostazol, dipyridamole
PDE 3 inhibitor
- inc. cAMP in platelets, thus inhibiting platelet aggregation.
- also vasodilates.
Which leukemia has similar presentation to leukamoid reaction?
CML
-except in CML the L-ALP (leukocyte alkaline phosphatase) will be low.
G6PD def.
-inheritance?
X-linked recessive
-Most structural abnormalities = what inheritance?
- auto dom
- ie. hereditary spherocytosis
-Most enzymes deficiencies = what inheritance?
-auto recessive
Name an X-linked dominant disease
vitamin D resistant rickets
what drives extramedullary hematopoiesis?
Lots of EPO!
-most often caused by severe chronic hemolytic anemias (ie. beta-thal).
“crew cut” skull & chipmunk facies
- due to what?
- see in what?
marrow expansion/extra medullary hematopoiesis.
-diseases w/chronic anemia like beta-thal.
Bleeding after tooth extraction
-sign of what?
Hemophilia
-this is NOT a platelet problem, its a coagulation problem.
B12 and folate deficiency
-how can these lead to inc risk of thrombosis?
-both inc. homocysteine levels.
