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Step 1 11.27.12

Hematology VII

What is a menomic for the WBC differential from highest to lowest? Neutrophils Like Making Everything Better: Neutrophils (57-67%)Lymphocytes, Monocytes, eosinophils, basophils
What is the major energy source for RBCs and how does it use it? glucose. 90% anaerobically degraded to lactate, 10% by HMP shunt
What is the use of RBC chloride-bicarbonate antiport? alloes to accomplished chloride shift allowing RBC to transport CO2 from periphery to lungs
What is the survival time of RBCs? 120 days
What is polycythemia? too many RBCs = erythrocytosis
What is anisocytosis? varying sizes of RBCs
What is Poikilocytosis? varying shapes of RBCs
What is a reticulocyte? immature RBC
What is a thrombocyte and in what process is it primarily invovled? small cytoplasmic remanant of megakaryocyte. involved in primary homeostasis
What happens when a thrombocyte is activated by endothelial injury? aggregates with other platelets and interacts with fibrinogen to form hemostatic plug
What are in the alpha and dense granules of thrombocytes? dense: ADP ,calcium. alpha: vWF, fibrinogen
Where are platelets stored and what is their lifespan? 1/3 of pool stored in spleen. life span= 8-10 d
What is the Pe sign of thrombocytopenia or platelet dysfunction? petichiae
What is the receptor for vWF? GpIIb
What is the receptor for fibrinogen? GpIIb/IIIa
What types of cells are included in leukocytes? granulocytes ( basophils, eosinophils, neutrophils), mononuclear cells ( monocytes, lymphocytes)
What is the major process that leukocytes are invovled in and what is their normal level? response to infection. normally 4000-10000 per microliter
What is the morphology and process that neutrophils are primarily invovled in? acute inflmmatory response cell. phagocytic and multilobed
What is carried in a neutrophils granules? azurophiulic granulues which contain hydrolytic enzymes, lysozymes, myeloperoxidase, lactoferrin
What is the role of lactoferrin? binds iron and inhibits growth of phagocytosed bacteria and some fungi
In what condition might you see hypersegmented polys (neutrophils)? B12/folate deficiency
What is the morphology and fate of momocytes? large, kidney shaped nucleus. extensive frosted glass cytoplasm. differentiates into macrophages in tissues
Where do macrophages come from and what are their major roles? come from circulating monocytes with long life in tissues. phagocytoses bacteria, cell debris, and senescent red cells and scavenges damaged tissues
What activates macrophages? gamma interferon
Via what molecule can macrophages be APCs and what is a cell surface marker for them? APCs via MHCII, CD14 is the cell surface marker for macrophages
What is the morphology and major function of eosinophils? bilobate nucleus paked with large eosinophilic granules. defends against helminths (major basic protein) and phagocytoses Ag-Ab complexes
What are 2 major enzymes made by eosinophils and what is their role? histaminase, arylsulfatase, help limit reaction following mast cell degranulation
What is mnemonic for the causes of eosinophilia? NAACP: neoplasm, astma, allergies, collagen vascular disease, parasites
What is the morphology and major role of basophils? mediates allergic reaction. bilobate nucleus with densely basophilic granules
What is contained in basophil granules? heparin (anticoagulant), histamine (vasodilator) and other vasoactive amines like LTD4 (leukotirnes)
What reaction are mast cell primarily involved in? allergic reaction. mediates type I hypersensitivity
What is released when a mast cell degranulates? histamine, heparin, eosinophil chemotactic factors
what is the morphology of mast cells and what can they bind? resemble basophils, but not the same cell
What can be given to prevent mast cell degranulation and what would be the appropriate setting? cromylyn sulfate used for astma prophylaxis
What is the role of dendritic cells and what types of surface proteins do they express? professional APCs, express MHC II and Fc receptor on surface. main inducers of the primary immune response
What are denritic cells on the skin called? Langerhans cells
What is the morphology of lymphocytes? round, densely staining nucleurs, small amount of pale cytoplasm
What immune response do B cells participate in and where do they mature? Where do they go initially? part of humoral ummune response. arises from stem cells in bone marrow where they mature. then migrates to peripheral lymphoid tissue (follicles of LN, white pulp of spleen, lymphoid tissue)
What happens when a B cell encounters its Ag and how can it act as an APC? when it encounters its Ag, it becomes a plasma cell. has memory and can be APC via MHCII
What is the morphology of a Plasma cell? off center nucleus, clock face chromatin distrobution, abundanat RER and well developed Golgi apparatus
What type of neoplasm is multiple myeloma? plasma cell neoplasm
What are the cell surface markers for a B lymphocyte? CD19, CD20
What are the cell surface markers of a T lymphocyte? Th and Tc? Th:CD4 CD3 Tc: CD3, CD8
What is the role of T cells, where do they originate and where do they mature? mediates cellular immune response. originates from stem cells in bone marrow but matures in thymus
What are the 3 mature fates of T lymphocytes? Tc: MHCI,CD8. Th(MHCII, CD4), or T surpressors
What is the costimulatory signal for T cell sctivation? CD28
What type are the majority of circulating lymphocytes? T cells
What ag and Ab are seen in Blood group A? A ag on RBC, B Ab in plasma
What ag and Ab are seen in Blood group B? B ag on RBC, A ab in plasma
What ag and Ab are seen in Blood group AB? A and B Ag on RBC. no Ab in plasma making this the universal recipient
What ag and Ab are seen in Blood group O? no A or B Ag. A and B Ab in plasma. Universal donor
What is eryhtroblastosis fetalis? Rh - monthers exposed to fetal Rh+ blood may make antiRh IgG that can cross placenta in subsequent pregnancies in next fetus which is Rh+
What is the Tx for prevention of erythroblastosis fetalis? Rho(D) Ig for mother at first delivery to prevent future problems
What happens when a person is given an incompatible blood transfusion? immunologicx repsonse, hemolysis, renal failure, shock, death
Which types of blood type Ab cross the placenta? WHY? anti-ABO are IgM so don't cross. anti-Rh are IgG so they can cross
What is the coagulation deficiency of hemophilia A? deficiency of factor VIII
What is the coagulation deficiency seen in hemophilia B? deficiency of factor IX
What is the coagulation deficiency seen in vitamin K deficiency? decr synth of factors: II, VII,IX, X, protein C, protein S
What is the coagulation deficiency seen in antithrombin? how is it activated? inhibits thrombin and factors VIIa, IXa,Xa, XIa, XIIa, activated by heparin
What 2 processes activate XII--->XIIa? What is this called? HMWK, collagen or basement membrane or activated platelets. this is the intrinsic coagulation pathway
What are the 2 actions of XIIa? converts XI-->Xia, also converts prokalikrein to kallikrein
What is the role of XIa? IX---IXa
What is the role of IIa? converts VIII--->VIIIa, also V-->Va
What is the extrinsic coagulation pathway? VII--->VIIa via thromboplastin (TF)
What are the 2 ways X can be activated to Xa? either by IXa and VIIIa or by VIIa
What is the role of Xa? with Va converts II (prothrombin) to IIa (thrombin)
What are the 2 actions of kallikrein? converts HMWK to bradykinin and plasminogen to plasmin
What are the actions of bradykinin? incr vasodilation, incr permeability, incr pain
What are the 2 roles iof plasmin? C3-->C3a to start complement cascade and starts to degrade clot
What activates bradykinin? ACE
What converts vitamin K to its activated state? epoxide reductase
What is the action of warfarin? inhibits epoxide reductase locking vit K in an inactivated state
Why do neonates have a Vit K deficiency? lack enteric bacteria which are responsible for Vit K production
What does vWF carry/protect? VIII
Which factors does antithrombin inactivate? II,VII,IX,X,XI,XII
What activates protein C? thrombomodulin from endothelial cells
What allows activated protein C to cleave and inactivate Va and VIIIa? protein S
What is the derangement in factor V leiden? mutation produces a factor V resistant to APCs inhibitis
What is the clinical use of tPA? thrombolytic
What is the action of tPA? converts plasminogent to plasmin which cleaves the fib rin mesh
What happens in the injury phase of platelet plug formation? vWF binds to exposed collagen upon endothelial damage
What happens during the adhesion phase of platelet plug formation? platelets bind vWF via GpIb receptor on site of injury only. platelets then release Ca++ which is needed for the coagulation cascade
What is the role of ADP in the platelet plug formation? helps platelets adhere to the epithelium
What happens during the activation phase of the platelet plug formation? ADP binding to receptor induces GpIIb/IIIa expression at platelet surfaces
What happens during the aggregation phase of the platelet plug formation? fibrinogen binds GpIIb/IIIa receptors and links platelets
What is TXA2? What releases it and what does it do? proaggregation factor released by platelets decr blood flow and incr platelet aggregation
What is PGI2 and NO? What releases them? What do they do? anti-aggregation factors. released by endothelial cells, incr blood flow and decr platelet aggregation
How does aspirin inhibit thrombogenesis? inhibits cyclooxygenase and prevents TXA2 synthesis
How doe ticlopidine and clopidogrel inhibit thrombogenesis? inhibit ADP induced expression of GpIIb/IIIa
How does abciximab inhibit thrombogenesis? inhibits GpIIb/IIIa directly
What is the deficiency in Bernard-Soulier disease? GpIb
What is the principle behind erythrocyte sedimentation rate? acute phase reactants in the plasma like fibrinogen cause RBCs to aggregate and therefore incr the ESR
In what settings is ESR elevated? infections, inflammation (temporal arterits, polymyalgia rheumatica), malignant neoplasms, GI disease (ulcerative colitis), pregnancy
In what settings is ESR decreased? polycythemia, SCA, CHF, microcytosis, hypofibrinogenimia
What is the associated pathology of an acanthocyte (spur cell)? liver disease, abetalipoportienemia
What is the associated pathology of basophilic stippling? thalasesemias, anemia of chronic disease, iron deficiency, lead poisoning: Baste the ox TAIL
What is the associated pathology of a bite cell? G6PD deficiency
What is the associated pathology of an eliptocyte? hereditary elliptocytosis
What is the associated pathology of micr-ovalocyte? megaloblastic anemia (also hypersegmented PMNs), marrow failure
What is the associated pathology of ringed sideroblasts? sideroblastic anemia
What is the associated pathology of schistocytes/helmet cells? DIC, TTP/HUS, traumatic hemolysis
What is the associated pathology of a sickle cell? SCA
What is the associated pathology of spherocyte? hereditary spherocytosis, autoimmune hemolysis
What is the associated pathology of tear drop cells? bone marrow infiltration (myelofibrosis)
What is the associated pathology of a target cell? HbC disease, Asplenia, Liver disease, Thalassemia (HALT)
What is the process behind and Heinz body? oxidation of iron from ferrous to ferric leads to denature Hb ppt and damage to RBC membrane. these lead to bite cells
What is the associated pathology of Heinz bodies? seen in alpha thalassemia, G6PD deficiency
What is the underlying process of Howell-Jolly bodies? basophilic nuclear remnants found in RBCs
What is the associated pathology of Howell-Jolly bodies? senn in patients with functional hyposplenia or asplenia
What is the DDx if MCV <80 (microcytic) anemia? iron deficency, ACD(can be normocytic first), thalssemias, lead poisoning, sideroblastic anemia
What is the DDx if MCV 80-100 (normocytic) and it is non hemolytic? ACD (can progress to moncytic), aplastic anemia, kidney disease
What is the DDx if MCV 80-100 (normocytic) and there is intrinsic hemolysis? RBC membrane defect ( hereditary spherocytosis), enzyme deficincy such as G6PD or PK, HbC, SCA, paroxysmal nocturnal hemoglobinuria
What is the DDx if MCV 80-100 (normocytic) and there is an extrinsic hemolysis? autoimmune, MIHA, MAHA, infections
What is the DDx if MCV >100 (macrocytic) and is megaloblastic? folate deficiency, B12 deficiency
What is the DDx if MCV >100 (macrocytic) and is non megaloblastic? liver disease, alcoholism, reticulocytosis, metabolic disorders, drugs
What are some causes of iron deficiency anemia? decr iron due to chronic bleeding (GI, menses), malnutrition or absorbtion disorders or incr demand (preganacy) leading to decr heme synthesis
What are the key findings in iron deficiency anemia? microcytosis and hypochromia may manifest as Plummer-Vinson syndrome
What is Plummer-Vinson syndrome? triad of iron defieicny anemia, esophageal web, and atrophic glossitis
What is the defect and epidemiology of alpha thalassemia? alpha globin gene mutation = decr alpha globin synthesis. seen in asians and AA
What is the varying severities of differing levels of alpha thalassemia? 4 genes: Hb Barts= hydrops fetalis (gamma 4) 3 genes: HbH disese (beta 4) 1-2 genes: no significant anemia
What is the defect and epidemiology of beta thalassemia? point mutations in splice sites and promoter regions = decr beta globin synth. prevelent in Mediterranean populations
what are the clinical signs of Beta- thalassemia minor? heterozygote. 1. beta chain is underproduced 2. usually asx 3. dx confirmed via incr HbA2 (>3,5%) on electrophoresis
What are the clinical signs of beta-thalassemia major? homozygote. 1. beta chain is absent= severe anemia requiring blood transfusion 2. marrow expansion (crew cut on skull CXR)--> skeletal deformaties and chipmunk facies
What is a common hemoglobin finding in beta thallassemia both major and minor? incr HbF (alpha 2 gamma 2)
What is seen in an HbS/Beta thalasemmia heterozygote? mild to moderate sickle cell disease depending on level of beta globin production
What is the mech of lead poisoning and where is it common? lead inhibits ferrochealatase and ALA dehydratase= decr heme synth. also inhibits rRNA degeneration. high risk in houses with chipped pain
What are the key findings in lead poisoning? LEAD: Lead lines on gingivae (Burtons) and on epiphyses on long bones, Encephalopathy and eryhtrocyte basophilic stipling, abdominal colic and sideroblastic anemia, drops: wrist and foot
What is the fisrt line or tx for lead poisoning, what should be given to kids? dimercaprol and EDTA, succimer for kids
What is the defect in hereditary sideroblastic anemia and what are 2 reversible types of sideroblastic anemia? defect in heme synth. X linked defect in delta aminolevulinic acid synthase gene, reversible: alcohol, lead
Created by: tjs2123



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