-
Inherited defect in RBC membrane with a deficiency of spectrin
Hereditary spherocytosis
-
Blood smear shows Reticulocytosis in peripheral blood
Hereditary spherocytosis
-
Splenomegaly, cholelithiasis, anemia
hereditary spherocytosis
-
Hereditary spherocytosis tx
Splenectomy to correct anemia, but red cell defect persists
-
Mutation in the gene coding for a b –globin chain
SCA
-
What is the difference between a homozygote and heterozygote in SCA?
- Homo: all Hb Is replaced by Hbs
- Hetero: One half is replaced by hemoglobin S
-
Most common form of familial hemolytic anemia worldwide
SCA
-
What determines severity of SCA?
Amount of HbS
-
Microvascular obstructions put people with SCA at risk for what?
MI
-
Substitution of valine for glutaminic acid on b chain
SCA
-
What are signs and symptoms of SCA?
- Fatty changes in the heart, liver, and renal tubules
- Erythropoesis with new bone formation due to hemolytic anemia
- Initial splenomegaly followed by autosplenectomy
- Vascular congestion, thrombosis, infarction
-
Describe vasoocclusive crisis in sickle cell
Something will trigger the dehydration and sickle crisis --> pain in abdomen, joints, chest which is precipitated by dehydration, infection or acidosis
-
cessation of erythropoiesis
anaplastic crisis (associated with SCA)
-
Lack of or decreased synthesis of globin chains
Thalassemia
-
Genetic cause of beta thalassemia
Single base changes as opposed to gene deletions
-
Why are beta thalassemia cells hypochromic?
reduced synthesis of beta-globin causes inadequate HbA formation
-
What causes hemolysis in beta thalassemia?
Excess of alpha globin chains precipitating and causing phagocytosis
-
Why does iron absorption increase in beta thalassemia?
body things there is an IDA
-
Due to deletions of alpha globin gene loci
Alpha thalassemia
-
Difference in hemolysis between beta and alpha thalassemia
Alpha hemolysis is less severe
-
Microcytic hypochromic red cells
Thalassemia
-
Poikilocytosis, anisocytosis, reticulocytosis
Thalassemia
-
hair on end appearance
thalassemia
-
Secondary hemochromotosis
thalassemia
-
What is the prognosis of thalassemia major?
need blood transfusions, develop secondary hemochromatosis, average age of death is 17
-
What is the prognosis of thalassemia minor?
mild microcytic hypochromic anemia with a nl life expectancy
-
-
What causes G6PD deficiency?
Lack of GSH leading to oxidation injury
-
Chronic intravascular hemolysis
Paroxysmal Nocturnal Hemoglobinuria
-
Membrane defect from mutation affecting myeloid stem cells
Paroxysmal Nocturnal Hemoglobinuria
-
Paroxysmal Nocturnal Hemoglobinuria has a risk of what?
progression to leukemia
-
Yields RBCs, granulocytes, and platelets that are very sensitive to lytic activity of complement
Paroxysmal Nocturnal Hemoglobinuria
-
pts RBCs coated with human antibodies that react with anti human globulin serum
Direct Coombs test associated with immunohemolytic anemia
-
Used to detect antibodies in pts serum, incubate normal RBCS with pts serum followed by a direct Coombs test on the incubated RBC
Indirect COombs test associated with immunohemolytic anemia
-
Opsonization of rbc by IgG and phagocytosis by splenic macrophages
- Warm antibody immunohemolytic anemia
- Activated at 37C
- Primary 60%, secondary to lymphoma, SLE, drugs
- Splenomegaly
-
Cold antibody immunohemolytic anemias
- igM bindes to RBC at temp below 37C
- Cooler parts of the body (fingers, toes)
- RBC sequestered in the liver
- Hemolysis is extravascular, usually in spleen
-
What are causes of mechanical hemolysis?
Prosthetic cardiac valves, atherosclerosis, DIC [RBCs hit thrombi and becomes sheared]
-
Hemolytic anemia associated with high fever, HA, sweating, delerium
malaria
-
M/C nutritional deficiency
IDA
-
low hb ,low hematocrit, low mcv,low transferin saturation, increased total iron binding capacity
IDA
-
Plummer-Vinson syndrome
IDA
-
IDA is what kind of anemia?
microcytic hypochromic
-
Decline in serum ferritin and stainable iron in bone marrow
IDA
-
What conditions can cause anemia of chronic disease?
Osteomyelitis, endocaritis, RA, HL, lung and breast Ca
-
What is the biggest difference between IDA and anemia of chronic dz?
Anemia of chronic dz has a reduced total iron-binding capacity, while it is increased in IDA
-
Abundant stored iron in mononuclear phagocytic cells as well as high serum ferritin
Anemia of chronic dz
-
What are the two types of megaloblastic anemias?
Folate deficiency and pernicious anemia
-
enlarged erythroid precursors accumulate in bm yielding too few erythrocytes
Megaloblastic anemia
-
What do you see in the peripheral blood of someone with megaloblastic anemia?
Large oval erythrocytes, hypersegmented granulocytes, and large mishapen platelets
-
Fatigue , Weakness, Cheilosis, Sore tongue, Neurologic abnormalities absent
Folate deficiency anemia
-
Cause of pernicious anemia
Usually from inadequate production of or function of intrinsic factor, appears to be an autoimmune dz
-
Describe the autoimmune nature of pernicious anemia
- Autoantibodies block binding of if to b12
- Autoantibody binds to if and ifb12 complex
- Autoantibody binds to parietal cell border
-
What procedures can cause pernicious anemia?
- Gastrectomy,
- resection of ileum
- tropical sprue
- Whipple's disease
-
Demyelination of posterior and lateral columns of spinal cord
Pernicious anemia
-
Numbness ,tingling, unsteadiness of gait
Fatigue ,pallor
Pernicious anemia
-
Pts with pernicious anemia are at an increased risk for what?
gastric cancer
-
What test helps you differentiate between pernicious anemia and folate defeciency?
Schilling test: inability to absorb oral dose of cobalamin
-
shutting down production of RBCs, neutrophils and platelets
Aplastic anemia
-
Normochromic normocytic anemia, Neutropenia,
thrombocytopenia
aplastic anemia
-
What are causes of aplastic anemia?
- Metastatic Ca
- Liver dz, chronic renal dz
- Whole body irradiation or chemo
-
Absolute increase in red cell mass and low erythropoetin level
P vera
-
Hypercellular bone marrow with proliferation of granulocytic and megakaryocytic and megakaryocytic elements
P vera
-
Long term survivors may undergo transition to myeloid metaplasia with myelofibrosis
P vera
-
What are the two causes of neutropenia agranulocytosis?
- Inadequate granulopoiesis (drugs)
- Accelerated destruction of neutrophils (drugs, idiopathic)
-
When do you see PMNs?
Bacteria, tissue necrosis (infarctions)
-
When do you see eosinophils?
Parasites, allergies, drug rxs
-
When do you see monocytess?
Chronic infections, collage vascular dz
-
When do you see lymphocytes?
viral infections
-
Bartonella henselae
Cat scratch dz
-
Granulomas with central necrosis
cat scratch dz
-
How does cat scratch dz present?
Lymphadenopathy of the head and neck 2 weeks after the scratch; regresses within 2-4 mo
-
Where can leukemic cells infiltrate?
Blood, liver, spleen, and LN
-
Anemia,fever,bleeding, easy bruising, fatigue, Bone pain and tenderness
Acute leukemia
-
Cns: ha,nerve palsies, vomiting
Acute leukemia
-
What is the age difference between the acute leukemias?
- Acute lymphoblastic: <15, peak 4 yo
- Acute myeloblastic: mostly adults, med age 50 years
-
red rod shaped lysosomes
Auer rods, seen in myelblastic leukemias
-
What is the age difference between the chronic leukemias?
- Chronic myeloid: 25-60
- Chronic lymphoid over age 50
-
White counts usually > 100k; massive splenomegaly
chronic myeloid leukemia
-
Circulating cells mostly neutrophils and myelocytes
chronic myeloid leukemia
-
Leukemic cells have decreased alkaline phosphatase activity
CML
-
2-3 year course without tx; Tx induces 2-5 year remission followed by blast crises and death
CML
-
What is the only cure for CML?
BM transplant
-
Nonfunctioning B cells produce a hypogammaglobulinemia – no production of plasma cells
CLL
-
May have an autoimmune hemolytic anemia
CLL
-
Median survival is 4-6 years; Pts may live over 10 years
CLL
-
Leukemic cells have fine hair-like cytoplasmic projections
Hairy cell leukemia
-
Tartrate resistant acid phosphatase in neoplastic B cells
Hairy cell leukemia
-
Leukemia affecting Older males, insidious onset characterized by splenomegaly and pancytopenia
Hairy cell leukemia
-
Cells have Birbeck granules in the cytoplasm
Langerhan's cell histiocytosis
-
What are the three components of Langerhan's cell histiocytosis?
- Letter-Siwe dz
- Unifocal Langerhan's cell histiocytosis
- Multifocal Langerhan's cell histiocytosis
-
What age group does Letter-Siwe affect?
Before two years old
-
What are characteristics of Letter-Siwe?
Skin lesions, H-S megaly, lympadenopathy, pulmonary lesions, bone lesions, anemia and infections
-
Rapidly fatal without chemotherapy
Letter-Siwe
-
Expansive erosive lesions in bones with siilar lesions found in skin, lungs, or stomach
Unifocal Langerhan's cell histiocytosis
-
What is the Hand-Schuller-Christian triad?
Calavarial bone defects, diabetes insipidus, and exophthalmos (associated with multifocal Langerhan's cell)
-
OM, mastoiditis, URI infections with lesions on the scalp and ear canal
Multifocal Langerhan's cell
-
tests for extrinsic and common coagulation pathways
PT
-
evaluates the common and intrinsic clotting pathways
PTT
-
What can cause a prolonged PT time?
deficiency of factors V,VII, or X, prothrombin or fibrinogen
-
What can cause an increased PTT time?
deficiency of factors V,VIII,IX,X,XII, prothrombin or fibrinogen
-
What is DIC secondary to?
Sepsis, prolonged deliveries, fat or amniotic fluid emboli
-
Activation of coagulation sequence: Excessive clotting at first and using up platelets and coagulation fa
DIC
-
What are pathological steps of DIC?
- Consumption of plts and coag factors
- Activation of fibrinolysis
- Tissue infarcts and hypoxia
- Bleeding DO
-
What is the difference between acute and chronic DIC?
- acute: bleeding DO
- chronic: thrombotic complications
-
Spontaneous bleeding, Prolonged bleeding time, with nl PT/PTT
thrombocytopenia
-
What causes thrombocytopenia?
- Decreased production of plts: BM disease
- Decreased plt survival: immunologic and nonimmunologic destruction
-
Bleeding disorder that is one of the most common manifestations of AIDs
Thrombocytopenia
-
Idiopathic thrombocytopenic purpura tends to affect who?
Adults and females
-
Production of antibodies against plts in the spleen
Idiopathic thrombocytopenia purpura
-
Hemorrhages in skin, epicardium, GIT,UT
Idiopathic thrombocytopenia purpura
-
How do you tx idiopathic thrombocytopenic purpura?
splenectomy
-
What population does thrombotic thrombocytopenic pupura tend to affect?
Adult females
-
Bleeding DO with transient neurological deficits: Can mimic stroke, MS, bells palsy
Thrombotic thrombocytopenic purpura
-
What is the biggest complication people with thrombotic thrombocytopenia face?
Renal failure
-
Thrombocytopenia with microangiopathic
hemolytic anemia but no neurologic symptoms
Hemolytic uremic syndrome
-
Hemolytic uremic syndrome usually follow what?
E coli gastereneritis
-
When is Hemolytic uremic syndrome's onset?
childhood
-
Spontaneous bleeding from mucous membranes-usually not a lot of bleeding
Von Willebrand Disease
-
Menorrhagia, prolonged bleeding time, nl plt count
Von Willebrand Disease
-
What causes Von Willebrand Disease?
compound defect of plt function and coag pathway
-
Most common hereditary disease associated with serious bleeding
Hemophilia A
-
Reduced amount or reduced activity of factor VII
Hemphilia A
-
X linked, usually in males
Hemophilia A
-
What are lab levels in Hemophilia A?
Nl PT, PTT, platelet counts
-
How do you treat Hemophilia A?
Infusion of factor VIII
-
Factor IX deficieny
Hemphillia B
-
Which Hemophilia is more common?
A
-
What are the two major differences between Hemophilia A and B?
- A is Factor 8 deficiency, B is factor 9
- B has prolonged PTT while A is nl
-
Appearance of lymphoid follicles in the medulla and seen in MG, SLE, RA
Thymic hyperplasia
-
Tumors with a neoplastic epithelial component
Thymoma
-
What are the three kinds of thymomas?
- Benign thymoma: cytologically and biologically benign
- Malignant thymoma I :cytologically benign but biologically malignant
- Malignant thymoma II: cytologically and behaviorly malignant
|
|
