Pathoma Neo Blood RBC WBC Flashcards
What problem are you likely to get from a rattlesnake bit? Scorpion sting?
Rattlesnake = DIC; Scorpion = acute pancreatitis
Person had a laparoscopic surgery and now has multifocal ischemic necrosis of bone?
Caisson Disease; a chronic form of gas embolism, from the gas in the pneumoperitoneum
What is the general purpose of primary and secondary hemostasis?
Primary = platelet plug; Secondary = stabilize the platelet plug, i.e. fibrin
Why does Hairy Cell Leukemia present with splenomegaly?
Hairy cells get trapped in the red pulp
Which cancer involves mature CD4 positive cells in the skin?
Mycosis fungoides
What kind of molecule is c-KIT? What cancer is it implicated in?
Growth factor receptor; Gastrointestinal Stromal Tumor (interstitial cells of Cajal)
Which forms of autoimmune hemolytic anemia cause intra and extravascular hemolysis?
IgG (warm) causes extravascular; IgM (cold) causes intravascular
What is the genetic makeup of HBV and HCV?
HBV = DNA, HCV = RNA
What would kill a person deficient in Cystathione Beta Synthase?
Thrombosis
What anatomic locations require prophylaxis with B-ALL?
Testes and CSF
What are crystal aggregates of myeloperoxidase referred to as?
Auer rods
What is producing the antiboides in ITP?
Splenic plasma cells (make IgG against GPIIb/IIIa); The splenic MO then eat the platelets = thrombocytopenia
Why to OCP’s increase risk of thrombosis?
Estrogen increases production of coagulation factors
What is the most common cause of thrombotic thrombocytopenic purpura?
autoantibody to ADAMTS13
Where in the kidney are RBC’s most likely to sickle?
Renal medulla because it is hypoxic and hypertonic
What does chromogranin stain for?
Neuroendocrine cells
What is the most common cause of thrombocytopenia in both children and adults?
ITP
How can you differentiate DIC from a disorder of fibrinolysis?
DIC will have decreased platelet count and D-dimer? Fibrinolysis does not have fibrin split products and there is no consumptive platelet issue
Regarding infection with EBV (heterophile Ab positive IM), generalized LAD is from hyperplasia of what?
paracortex of LNs
Which cancers are N-MYC and L-MYC implicated in?
N-myc = neuroblastoma (adrenal medulla, kid, no HTN); L-MYC = lung carcinoma
Who is G6PD the most severe in, Africans or Mediterraneans?
Mediterranian variant is the worst
First line Tx of CML
imatinib
What is a major way that tumor cells can evade “immune surveillance”?
downregulating MHC I
What is the main role of FGF in the body?
angiogenesis (although it seems like it should be collagen synthesis)
Which vitamin functions as a cofactor in protoporphyrin synthesis?
B6 (water soluble)
Why do splenic macrophages eat spherocytes in hereditary spherocytosis?
Because they don?t navigate the sinusoids as well due to their large bulky shape (Tx: splenectomy)
Why do you have to correct the reticulocyte count in cases of anemia?
Because there is a decrease in total RBC so the retic count is falsely elevated
A patient with follicular lymphoma whose lymph node is now enlarging may have__________
transformed to diffuse large B-cell lymphoma
What lab test is elevated in Hemophilia A and B?
PTT as factors VIII and IX are both part of the intrinsic pathway
What is the function of haptoglobin? When is its value decreased?
To bind to hemoglobin in the blood, decreased in cases of intravascular hemolysis because it is binding up all of the hemoglobin
What is the most common cause of death in children with Sickle Cell?
HiB because of autosplenectomy
Splenomegaly in mono is due to hyperplasia of Downey lymphocytes where?
in PALS (within the adventitia of splenic arteries)
How can you use the presence of tingible body macrophages to differentiate between follicular hyperplasia and follicular lymphoma?
there are no tingible body macrophages in follicular lymphoma
What receptor is acted on by malignant plasma cells in multiple myeloma that leads to hypercalcemia?
RANK receptor on osteoclasts
Describe the basic biochemistry of a mutated Ras protein
Ras is a G protein that should cleave GTP to GDP to make it inactive. Mutated Ras basically has no “off switch” so GTP stays on.
What is eosinophilic granuloma?
Benign proliferation of langerhans cells in bone that presents as a pathologic fracture
What is a metabisulfite screen?
Causes cells with any amount of HbS to sickle, useful in sickle cell anemia
Why do obstetric complications cause DIC?
Tissue thromboplastin in the amniotic fluid causes DIC
Regarding platelet disorders, what is the most common type of mucosal bleed?
Epistaxis (also keep Osler-Weber Rendu in mind if there are bleeds elsewhere)
What are two ways in which hepcidin (anemia of chronic disease) sequesters Fe?
limits iron transfer from macrophages to erythroid precursors; decreases EPO production
What is the characteristic finding of HbC disease on blood smear?
HbC crystal
Explain why issues with protoporphyrin synthesis lead to ringed sideroblasts
The ferrochetalase reaction occurs in the mitochondria? Here, protoporphyrin is added to Fe to form Heme. When protoporphyrin is defective iron accumulates in the mitochondria forming ringed sideroblasts
Reed-Sternberg cells are classically positive for what CD markers?
CD15 and CD30
What is the most common leukemia overall?
Chronic lymphocytic leukemia
What is the glutamic acid to lysine mutation on B globin?
HbC disease (typified by HbC crystal on blood smear)
Discuss the regulation of the Retinoblastoma tumor suppressor gene
Rb holds the E2F transcription factor. When the cyclinD/CDK4 complex phosphorylates Rb it releases E2F allowing for progression of G1 to S
What is the best test for immune hemolytic anemias?
Direct Coombs
Hemoglobin is made of heme and globin. The heme is made of Fe and Protoporphyrin IX. What is called if there isnt enough Fe? Enough Protoporphyrin?
Fe = Iron Deficiency Anemia (or in some cases, anemia of chronic disease); Protoporphyrin = Sideroblastic anemia
What does the term diffuse mean in diffuse large B cell lymphoma?
You cannot identifiy a mantle, follicle , marginal zone, etc.
What is the main cause of death in paroxysmal nocturnal hemoglobinuria? Why?
Thromboses i.e. Budd Chiari and cerebral vein thrombosis? Because damage to platelets releases enzymes that activate more platelets and cause thrombosis
What kind of molecule is TdT? (Used to identify acute lymphoblastic leukemia)
DNA polymerase
What is the earliest sign of whole body radiation?
lymphopenia
What cluster of differentiation marker identifies a hematopoietic stem cell
CD34
What will you see on spiral CT of a person with pulmonary embolus?
vascular filling defect
What is the screening test for paroxysmal nocturnal hemoglobinuria and the confirmatory test?
Sucrose test; acidified serum test
Which aspects of platelet plug formation are impaired in uremia?
impaired platelet adhesion and aggregation
Explain how gastrectomy predisposes to both Fe def and B12 anemia
Acid helps maintain Fe2 which is desirable over Fe3? Loss of stomach means loss of parietal cells, no IF = no B12
Describe a Sezary cell
Ceribriform nuclei
What region is characteristically involved in acute monocytic leukemia?
infiltration of the gums
In which cancer is basophilia classically seen?
Chronic myelogenous leukemia
What does vimentin stain for?
Mesenchymal tissue (mesoderm, bone etc.)
Which kidney cells produce EPO?
peritubular interstitial cells
What feature do many leukemic blast cells have in their nucleoli?
The nucleoli are often punched out
Differentiate among DMT-1, Ferroportin, and transferrin.
DMT-1 takes heme from the intestine and into the enterocyte (DMT-1); Ferroportin takes heme from the enterocyte to the blood (basolateral); Transferrin takes iron through the blood to liver and bone marrow for storage in MO as ferritin
What does desmin stain for?
Muscle
What is Hand-Schuler-Christian disease?
Malignant proliferation of Langerhans cells characterized by scalp rash, lytic skull defects, diabetes insipidus, and exophthalmos in a kid
Explain the relationship between p53 and BAX
p53 upregulaes BAX which disrupts bcl-2? Thus, if DNA damage is beyond repair, p53 is expressed, upregulates BAX, BAX disrupts the anti-apoptotic bcl-2 which leads to apoptosis by allowing cytochrome c to leak out
Why is there an increased risk of gout in polycythemia vera but not in essential thrombocythemia?
Because in PV you are making too many RBC’s in the process, the nucleus must be extruded = purines = gout. In ET, it is just too many platelets, they have no nuclei.
Name 4 small B cell lymphomas; 1 intermediate; 1 large
Small B: follicular lymphoma, Small lymphocytic lymphoma, mantle cell lymphoma, marginal zone lymphoma? Intermediate = Burkitt’s; Large = diffuse large B
How can you use the reticulocyte count to differentiate the two broad causes of normocytic anemia?
Low retics = underproduction anemia; High retic = destructive anemia
When B12 donates the methyl group given to it by folate, it donates it to homocysteine to form _______
methionine
PNH predisposes to what cancer?
AML since the mutation in the GPI anchor is ultimately a myeloid line mutation.
Where doe the term mononucleosis come from?
Atypical (Downey) lymphocytes (CD8 positive) look like monocytes
Which disease would lead to heparin being useless?
ATIII deficiency (as in nephrotic syndromes) ;you would have to give coumadin to these pts to stop them from being in a hypercoagulated state
Which growth factor induces cellular growth in some astrocytomas?
PDGFB
Why would Whipple’s Disease lead to easy bruising?
Malabsorption syndrome would decrease absorption of ADEK and K is responsible for gamma carboxylation of II, VII, IX, X, and C/S
Discuss the treatment of Hairy cell leukemia
Tx = Cladribine which is an adenosine deaminase inhibitor; basically induces ADA deficiency
Extravascular hemolysis may lead to gallstones of what color?
Black bilirubin gallstones
When will you see follicular hyperplasia?
HIV and Rheumatoid arthritis
Why does sepsis cause DIC?
LPS causes IL-1 and IL-6 production which causes endothelial cells to make tissue factor
Why does PNH attack at night?
The shallow breathing of sleep yields a respiratory acidosis that activates complement. The mutated GPI anchor means that DAF (decay accelerating factor) cannot shut off and they get lysis of RBCs and hemoglobin in urine and hemosiderin in tubular cells
What makes up the bulk of the mass of Hodgkin lymphoma?
Reactive cells against Reed-Sternberg cells
In Hodgkin lymphoma, what is a lacunar cell?
A reed sternberg cell, they are often present in lake like spaces
Explain why thalassemia is a microcytic anemia but sickle cell anemia is a hemolytic anemia
Both have mutations in globin chains. Thalassemia leads to underproduction of globin which leads to low Hb = anemia; SS anemia results in abnormal globin that cause the cells to sickle and hemolyze = hemolytic anemia
What are 3 ways to differentiate CML from a leukemoid reaction?
1 )Negative Leukocyte Alkaline Phosphatase; BASOPHILIA; t(9;22)
What are 4 general causes of microcytic anemias?
Iron deficiency anemia, Anemia of chronic disease, Sideroblastic anemia, Thalassemia
What can be given to treat leukopenia?
GM-CSF or G-CSF
What is a normal bleeding time?
2-7 minutes
Where can you find ADP in a platelet?
Dense granules? Released upon binding to vWF on endothelium and leads to upregulation of GpIIb/IIIa receptor for secondary hemostasis
How do you differentiate an acquired Factor VIII inhibitor (antibody) from a true hemophilia A patient?
mixing study? In hemophilia A, PTT would correct; in coagulation factor inhibitor PTT would not correct
Germline mutations in the Retinoblastoma gene predispose to what 2 cancers?
Retinoblastoma and Osteosarcoma
A person has been chronically on antibiotics and now finds that they bruise easily? Dafuq?
Chronic antibiotics can kill of gut flora leading to vitamin K deficiency = no gamma carboxylation of II, VII, IX, and X and C/S
Why would a high cortisol state (initially) cause leukocytosis?
Causes WBCs to separate from the pulmonary vasculature
What is a heterophile antibody?
IgM antibody that reacts with horse or sheep RBC
What drug may cause a sideroblastic anemia?
Isoniazid since it depletes B6. B6 is used in the first reaction by ALAS
What is the significance of CD16?
It may be seen in the blood when an immature cell (leukocyte) is released prematurely into the blood as in a leukocytosis (i.e. an infection)? IT INDICATES A DECREASED NUMBER OF Fc RECEPTORS
What are 4 myeloproliferative disorders?
These are MATURE myeloid cancers: Chronic myelogenous leukemia, Polycythemia vera, Essential thrombocythemia, and Myelofibrosis
What genotype is associated with ALL?
Trisomy 21
Which Langerhans cell Histiocytosis can present with diabetes insipidus and exophtalmos?
Hand-Schuler-Christian disease
If petechiae are from a hemostatic disorder what is probably the issue?
platelets (thrombocytopenia); not typically seen in coagulation cascade issues
What is prothrombin 20210A?
point mutation that leads to increased expression of prothrombin = hypercoagulable state
What is the TIBC actually measuring?
The amount of transferrin (i.e. if this is high then ferritin will be low)
Differentiate a sezary cell from a HTLV-1 affected cell
Ceribriform nuclei; cloverleaf nuclei
Which translocations in B-ALL are associated with good and bad prognoses?
GOOD: t(12;21)? BAD t(9;22) i.e. the Philadelphia chromosome in a kid IS BAD NEWS!!!
Discuss the ristocetin assay. What does an abnormal test indicate?
Ristocetin causes platelet GpIb to bind to vWF leading to agglutination. Lack of vWF as in von Willebrand Disease = abnormal ristocetin assay
Name the 4 hematogenous spreading carcinomas
Renal Cell Carcinoma (renal vein); Hepatocellular carcinoma (hepatic vein; budd chiari, no JVD), Follicular carcinoma of the thyroid, and Choriocarcinoma
Which chemotherapeutic agent may lead to megaloblastic anemia?
5-FU, methotrexate etc.
Where does ferrochetalase attache iron to protoporphyrin to from heme?
mitochondria
Mutations for alpha thalassemia occur on which chromosome?
16
Using tDt and myeloperoxidase (MPO) would distinguish what?
tDt = lymphoblasts, it is not present in mature lymphocytes; MPO = myeloblasts
What is the deal with Heparin Induced Thrombocytopenia? What is the deal with warfarin skin necrosis?
HIT = antibodies to heparin/platelet factor 4 complex? The rupturing of platelets leads to activation of other platelets and thrombosis; Warfarin skin necrosis occurs in protein C deficient pts who enter a transient hypercoagulable state
A B cell may express its light chains using which 2 proteins?
Kappa or Lambda, more commonly kappa
What lab values are elevated in von Willebrand’s disease?
both bleeding time and PTT (mildly) because vWF protects factor VIII
Definitive test for EBV
Serological test for EBV capsid antigen
What kind of lymphoma is a gastric MALToma? It may regress with Tx of what?
Marginal zone lymphoma; H. pylori
What 2 bugs can cause Fe deficiency anemia? What causes B12 def anemia?
Ancylostoma duodenale, Necator americanus; Diphyllobothrium latum
The transformation of chronic lymphocytic leukemia to a diffuse large B cell lymphoma is called _________
Richter transformation
A cell with a decreased number of Fc receptors is identified with ______
CD16
vWF is from the Weibel-Palade bodies of the endothelium (along with P-selectin) and also from the _______ granules of the platelet
alpha granules of platelet contain von Willebrand factor
What does thrombomodulin do?
Redirects thrombin to activate protein C
What is Letterer Siwe Disease
Langerhans histiocytosis that presents with rash and cystic skeletal defects
Which factors get activated by 1) Tissue thromboplastin 2) Subendothelial collagen
1) Factor VII (extrinsic) 2) Factor XII (intrinsic)
What does naphthylamine cuase? Where can you find it?
urothelial carcinoma of the bladder (in cigarrettes)
What disease is diagnosed with an osmotic fragility test?
Hereditary spherocytosis
What symptoms are different in HUS and TTP?
HUS more commonly has kidney involvement and TTP more commonly has CNS involvement
What is the general cause of a microcytic anemia?
Decreased production of hemoglobin with excess divisions leading to microcytosis. That is the bone marrow is attempting to correct the problem by making more RBCs but they are smaller
Which cancer may be associated with eosinophilia?
Hodgkin lymphoma
What is a macroovalocyte?
A large RBC seen in megaloblastic anemia
What is the leading cause of death in children?
accidents
What does it mean if there is a high Free Erythrocyte Protoporphyrin?
That there is a lot of protoporphyrin that is not bound to Iron, in other words there is Iron deficiency anemia
Disease with decreased ADAMTS13
Thrombotic Thrombocytopenic purpura (schistocytes = helmet cells)
What does a D-Dimer tell you about fibrinogen?
NOTHING it only tells you that there are FIBRIN split products
What is the most common cause of death in multiple myeloma and why?
infection since the IgG or IgA being produced is crappy and lacks antigen specificity
Why is CLL more likely to involve lymph nodes than ALL?
CLL involves more mature lymphocytes, since they are more like what they are actually supposed to be they go to LN, where they truly belong
