Week 2 Flashcards
Global cerebral ischemia caused by
Low perfusion (atherosclerosis of large vessel) Acute decrease in blood flow (shock) Chronic hypoxia (anemia) Repeated hypoglycemia (insulinoma)
Ischemic stroke occurs in
focal regions of the brain causing specific deficits
Ischemic strokes are caused by either
thrombosis or emboli
Lacunar strokes are most often associated with
diabetes and HTN in small blood vessels (from MCA)
Intracerebral hemorrhage is
bleeding into the brain parenchyma
Intracerebral hemorrhage is most often due to
rupture of Charcot-Bouchard microaneurysms (result of HTN often in lenticulostriate vessels)
Most often in basal ganglia
Subarachnoid hemorrhage associated with
Marfan and ADPKD
ITP - immune thrombocytopenia
IgG against platelet antigens (GPIIb/IIIa)
Antibodies produced in the spleen and macrophages consume platelets in the spleen
TTP - Thrombotic thrombocytopenic purpura
Microangiopathic hemolytic anemia
ADAMS TS13 deficiency
Prevents degradation of vWF, increasing platelet adhesion and creating microthrombi
Microthrombi lead to helmet cells/schistocytes
Bernard Soulier Syndrome
Genetic GPIb deficiency
Impairs platelet adhesion to vWF
Enlarged platelets
No agglutination on ristocetin cofactor assay
Glanzmann Thrombasthenia
Genetic GPIIb/IIIa deficiency
Impairs platelet aggregation and adhesion to each other
Platelets dont clump on blood smear, but will agglutinate with ristocetin cofactor assay
Primary hemostasis bleeding
occurs at mucosal surfaces - skin, gums
Secondary hemostasis bleeding
occurs in deep tissues - muscles, joints
Usually after surgical procedurs
PT measures
extrinsic and common pathway
PTT measures
intrinsic and common pathways
Hemophilia A
Genetic factor VIII deficiency
X-linked recessive
Deep tissue bleeding
Increased PTT
Hemophilia B
Genetic Factor IX deficiency
X-linked recessive
Deep tissue bleeding
Increased PTT
Hemophilia C
Genetic factor XI deficiency
Autosomal recessive
Von Willebrand Disease
Genetic vWF deficiency (AD)
increased BT and PTT (carries factor VIII)
Decreased agglutination of ristocetin
Microangiopathic hemolytic anemia with schistocytes
TTP, HUS, DIC
Most common inherited coagulation disorder
Von Willebrand Disease (AD)
Treat Von Willebrand disease with
Desmopressin - increases vWF release from Weibel Palade bodies
Vit K deficiency occurs most often in
Newborns, those on long term antibiotics, malabsorption, and with chronic liver disease
DIC
Pathologic activation of the entire coag cascade
DIC results in
consumption of platelets and factors
Results in bleeding, especially from IV sites and mucosa
Decreased platelets and clotting factors, and fibrinogens
Increased BT, PT, PTT, and D DIMER
Schistocytes on smear due to microthrombi (like TTP and HUS)
DIC is caused by/secondary to
Sepsis, Trauma, Obstetric complications, acute Pancreatitis, Malignancy (leukemia, adenocarcinoma), Nephrotic syndrome, Transfusion
STOP Making New Thrombi
And also rattlesnake bites
tPA converts
Converts plasminogen into plasmin to break down fibrinogen and fibrin clots
Thrombomodulin
allows thrombin to selectively activate Protein C and S to work as anticoagulants
Protein C/S Deficiency
Unable to inactivate Factor V and VIII, causing hypercoagulability
Can cause warfarin skin necrosis without a heparin bridge
Factor V Leiden
Mutated factor V that can’t be cleaved by protein C or S
Excessive activation of coagulation cascade
Most common inherited cause of hypercoagulability in whites
Factor V Leiden
Prothrombin Gene mutation
increases production of prothrombin resulting in hypercoagulation
Mutation in 3’ untranslated region
Antithrombin III deficiency
Decreases inhibition of Factors II and X
Antithrombin III deficiency has what effect on PT and PTT?
Little to no direct effect but diminishes the effect of Heparin
(Heparin won’t increase PTT as much as you would expect it to)
Heme is composed of
Iron and protoporphyrin
Microcytic anemias
Iron deficiency anemia (late), anemia of chronic disease (late), Sideroblastic anemia, thalassemia (alpha and beta)
Macrocytic anemias
Megaloblastic anemia (from B12 and B9 deficiency), anemia due to alcoholism, pancreatitis. alcoholism, liver disease
Normocytic Extravascular Hemolytic anemias
Hereditary spherocytosis, Sickle cell anemia, Hemoglobin C anemia, and autoimmune anemia (IgG)
Normocytic Intravascular Hemolytic anemias
Paroxysmal Nocturnal Hemoglobinuria, G6PD deficiency, Autoimmune anemia (IgM), Microangiopathic hemolytic anemia
Normocytic Nonhemolytic anemia
Aplastic anemia and myelophthisic processes
Iron absorption is regulated by
enterocytes in the duodenum
Microcytic, hypochromic anemia with increased RDW
Iron deficiency anemia
Iron deficiency anemia lab iron values
Decreased ferritin, increased TIBC, decreased serum iron, decreased % saturation Increased FEP (free protoporphyrin)
Anemia of chronic disease differs from iron deficiency anemia in that
Ferritin is increased and TIBC is decreased (more stored iron that you can’t get to)
Ringed sideroblasts on blood smear
Sideroblastic anemia (microcytic)
Protoporphyrin synthesis requires
ALAS (rate limiting), ALAD, and Vit. B6
Final step in heme synthesis
Ferrochelatase binds protoporphyrin to iron in the mitochondria to make heme
Target cells are seen in
Hemoglobin C disease, asplenia, liver disease, and Thalassemia
Beta Thalassemia Major on xray
Crew cut appearance and thickened facial bones
Binds intrinsic factor and carries it to the ileum to be absorbed
B12
B12 deficiency presents as
Macrocytic anemia w/ hypersegmented neutrophils, glossitis, and subacute combined degeneration of the spinal cord (methylmalonic acid cant be converted and builds up in the cord)
Increased homocysteine, normal methylmalonic acid
Folate deficiency (B12 will have increased methylmalonic acid as well)
Crew Cut Xray caused by
Sickle cell and B thalassemia major
Signs of Sickle cell vaso-occlusion
Dactylitis, autosplenectomy with Howell Jolly Bodies, Acute chest syndrome, renal papillary necrosis
Sickle cell caused by
AR mutation in B chain where glutamic acid is replaced by valine
Hemoglobin C caused by
AR mutation in B chain where glutamic acid is replaced by lysine
Paroxysmal Nocturnal Hemoglobinuria is caused by
Acquired defect in myeloid stem cell - impaired synthesis of GPI anchor
Increased incidence of AML
GPI anchor holds what to the membrane of RBC’s
Decay accelerating factor (DAF) and MIRL to prevent complement destruction
PNH confirmatory test
Flow cytometry to detect lack of CD55 (DAF)
Anemia with intravascular hemolysis shows
decreased haptoglobin, hemoglobinemia, hemoglobinuria, and eventually hemosiderinuria
Anemia with extravascular hemolysis will show
Splenomegaly, jaundice, and increased risk for bilirubin gallstones
XR disorder that decreases available glutathione
G6PD Deficiency
Prevents oxidative stress and damage to RBC’s
Glutathione
G6PD biproduct
NADPH which regenerates glutathione. So without G6PD we dont get NADPH or glutathione
G6PD on blood smear
Heinz bodies and bite cells (degmacytes)
Causes of oxidative stress
infection, sulfa drugs, fava beans
Diagnose autoimmune hemolytic anemia
Coombs test
Aplastic anemia caused by
damage to hematopoietic stem cell => pancytopenia
