Hematology (I and II) Flashcards
What is the basic physiology of blood?
- Transport dissolved gases, nutrients, hormones and wastes.
- Regulate pH and ionic composition.
- Restrict fluid loss at injury sites.
- Defend against pathogens and toxins.
- Stabilize body temperature.
What is the role of hemoglobin and the influence of erythropoietin (EPO)?
Hemoglobin is responsible for the body’s ability to transport oxygen and carbon dioxide.
Erythropoietin is the hormone that stimulates erythropoiesis;
Released:
1) during anemia
2) when blood flow to kidneys decreases
3) when oxygen content of air in lung decreases
4) when respiratory surfaces of lungs are damaged
What is the average lifespan of RBCs?
What is the normal percentage of reticulocytes?
Typical lifespan of RBCs is 120 days.
Normal percentage of reticulocytes is 0.8%.
What is polycythemia?
An increased in RBC per unit volume of peripheral blood.
- Absolute: increase in total red cell mass
- Relative: results from dehydration.
(1 of 3)
Define the following terms:
1) reticulocytes
2) hematocrit
3) macrocytosis
4) microcytosis
Reticulocytes:
- immature RBC’s that had just shed its nucleus.
Hematocrit (HCT):
- percentage of formed elements (RBC, WBC, PLT) in sample of blood
Macrocytosis:
Enlargement of RBC defined by MCV > 101 μm3/cell.
Microcytosis:
Small RBC as measured by MCV. < 82 μm3/cell.
(2 of 3)
Define the following:
5) MCV
6) MCH
7) RDW
8) MCHC
MCV - mean corpuscular volume
= average volume per RBC
MCH - mean cell hemoglobin
= average mass of hemoglobin per RBC
RDW - red cell distribution width
= coefficient of variation RBC volume
MCHC - mean cell hemoglobin concentration
= average concentration of hemoglobin in a given volume of packed RBCs
(3 of 3)
Define the following:
9) Hypochromic
10) Megaloblastic
11) Haptoglobin
12) Hemoglobinopathy
Hypochromic
- pale RBC due to average weight of hemoglobin in one RBC is < 27 ug/RBC (poorly hemoglobinized)
Megaloblastic
- condition that causes larger than normal erythroid progenitors with delicate, finely reticulated nuclear chromatin (nuclear immaturity)
Haptoglobin
- protein in serum that binds to and removes free hemoglobin from blood stream
Hemoglobinopathy
- hereditary condition involving abnormality in the structure of hemoglobin
What is anemia and the mechanism in which it may occur?
Condition as a result from low hematocrit or reduced hemoglobin.
Mechanism:
Blood loss
— acute (trauma)
— chronic (GI tract lesions, gyn disturbances)
Intrinsic factors
— hereditary (membrane abnormalities, enzyme deficiencies)
— acquired (paroxysmal nocturnal hemglobinuria)
Extrinsic factors
— Ab-mediated (transfusion rxn, lupus)
— mechanical (injury)
— infection (malaria)
Impaired RBC production
— disturbed stem cell, erythrocyte production, marrow replacement/inflitration
Describe the patterns of anemia seen in both acute and chronic blood loss.
Acute:
- decreased intravascular volume leading to cardiovascular collapse, shock and death.
- diluted hematocrit, kidneys release EPO
Chronic:
- rate of blood loss exceeds regenerative capacity of marrow
- depletion of iron reserves (Fe deficiency)
What is the difference between extravascular and intravascular causes of hemolytic anemia and their characteristic physiologic responses.
Extravascular
- caused by defects that increase destruction of RBC by phagocytes, particularly in spleen
- hyperbilirubinemia, jaundice, splenomegaly, gallstones and cholelithiasis
Intravascular
- caused by mechanical injuries, complement fixation or intracellular parasites resulting in RBC rupture
- anemia, hemoglobinemia,
hemoglobinuria, hemosiderinuria, jaundice
Describe the following for hereditary spherocytosis:
1) underlying defect
2) life expectancy of RBCs
3) common clinical features
4) treatment of anemia
5) complications
1) Underlying defect
- – intrinsic defect in RBC membrane skeleton
- – RBC is spheroid, less deformable, vulnerable to splenic sequestration and destruction
2) Life expectancy
- – 10-20 days
3) Common clinical features
- – anemia
- – splenomegaly
- – jaundice
4) Treatment of anemia
- – increased EPO
- – transfusion v. splenectomy
5) Complications
- – aplastic crises, parvovirus infection w/o new RBC
Describe the following for G6PD deficiency:
1) underlying genetics
2) typical patient
3) common triggers
4) two highly characteristic findings
1) Underlying genetics
- – Recessive, X-linked
- – G6PD A-
2) Typical patients
- – males
- – Middle East > African Americans
3) Common triggers
- – oxidant stress (infection, drugs, foods)
4) Two highly characteristic findings:
- – Heinz bodies (oxidized Hgb denatures and precipitates)
- – Bite cells (plucked out Heinz bodies by spleen)
Describe the following for sickle cell anemia:
1) underlying pathogenesis
2) mendelian heritage
3) organs affected by vaso-occlusive crises.
1) Underlying pathogenesis
- – caused by single amino acid substitution in beta-globin resulting in deoxygenated Hgb to self-associate into long polymers that deform into “sickle” shape.
2) Mendelian heritage
- – autosomal recessive
3) Organs affected
- – brain, retina, lungs, kidneys, liver, bones, skin
What is the underlying cause of ALPHA-thalassemia as compared to BETA-thalassemia?
ALPHA:
- deletions of one or more alpha-globulin genes.
BETA:
- no beta-globulin chains are produced
- reduced beta-globulin synthesis
Describe the anemia caused by ALPHA-thalassemia and BETA-thalassemia.
- Inadequate HbA formation resulting in small, poorly hemoglobinized cell
(microcytic, hypochromic) - Accumulation of unpaired alpha-globin chains which form toxic precipitates that damages RBC membranes.
What factor is required for Vitamin B12 absorption? Where is this factor secreted from?
Intrinsic factor - secreted from parietal cells of the fundic mucosa
What is the typical patient with pernicious anemia
Older adults (~60 y/o)
Caucasians and Scandinavians
Genetic predisposition suspected
Most have chronic gastritis.
What is the neurologic effects of severe, persistent Vitamin B12 deficiency?
Spastic pareparesis
Sensory ataxia
Severe paresthesia in lower limbs
Changes in ganglia of posterior roots and peripheral nerves
What are the three mechanisms a person may become folate deficient?
1) Decreased intake/diet (alcoholics, elderly, malabsorption, etc)
2) Increased requirement/demand (pregnancy, cancer, hemolytic anemia)
3) Folate antagonists (methotrexate)
Are there any neurologic findings in folate deficiency? If so, what are they?
There are NO neurologic findings in folate deficiency. Folate does not prevent neurologic findings seen in Vitamin B12.
What are the four (4) mechanisms a person may become iron deficient? Which of the four is most common in the US?
- Chronic blood loss (most common in US) - GI bleed, cancer
- Low intake, poor bioavailability - vegetarian diets
- Increased demands during pregnancy and infancy
- Malabsorption with celiac disease or after gastrectomy.
Describe the resulting anemia of iron deficiency.
Microcytic anemia.
Due to iron store depletion.
What is pica?
Neurobehavorial compunction to consume non-foodstuffs such as dirt and clay. Affected individuals periodically move their limbs during sleep.
What is aplastic anemia and pancytopenia?
Aplastic anemia:
- disorder which multipotent myeloid stem cells are suppressed leading to bone marrow failure and pancytopenia
Pancytopenia:
- deficiency of all three components of blood (RBC, WBC, PLT)
What is common clinical features of aplastic anemia and pancytopenia?
Weakness, pallor and dyspnea.
Thrombocytopenia causes petechiae and ecchymoses.
AA does not cause splenomegaly.
What is the diagnostic gold-standard of aplastic anemia and pancytopenia?
Bone marrow biopsy and CBC.
What is polycythemia? Distinguish between relative and absolute.
Polycythemia:
- abnormally high RBC with increased Hgb
Relative:
- decrease in plasma volume from dehydration, vomiting, diarrhea, diuretics
Absolute
- increase in total RBC mass
What is the etiologies of primary v. secondary polycythemia?
1° - intrinsic abnormality of hematopoietic precursors (low EPO) Polycythemia vera Inherited EPO receptor mutations (rare) 2° - red cell progenitor responding to increased erythropoietin (high EPO) Compensatory Lung disease High-altitude living Cyanotic heart disease Paraneoplastic
Define thrombocytopenia. List the 4 common etiologic categories of thrombocytopenia.
Decrease in number of platelets (<150K/microL).
- Decreased PLT production.
- Decreased PLT survival
- Sequestration
- Dilution
Describe the causes and clinical features of the following causes of thrombocytopenia:
1) immune thrombocytopenic purpura
Cause:
- Ab directed at PLT membrane glycoproteins, clear in spleen
- Increased megakaryoctyes
Clinical features:
Petechiae, easy bruising, epistaxis, gum bleeding, hemorrhages post-minor injury
Describe the causes and clinical features of the following causes of thrombocytopenia:
2) heparin-induced thrombocytopenia
Causes:
- medication induced (heparin)
- IgG Ab at binds to PLT membranes
Clinical features:
- PLT activation (aggregation/thrombosis)
- arterial and venous thrombosis ( can cause limb loss and death)
Describe the causes and clinical features of the following causes of thrombocytopenia:
3) thrombotic thrombocytopenia purpura
Causes:
- PLT-rich thrombi in circulation
- acquired or inherited deficiencies of metalloprotease –> PLT activation
Clinical features:
- fever, thrombocytopenia, hemolytic anemia, neurologic deficits, renal failure
Describe the causes and clinical features of the following causes of thrombocytopenia:
4) hemolytic uremic syndrome
Causes:
- deficiency of complement regulatory proteins or agents that damage endothelial cells (Shiga-like toxins)
Clinical features
- hemolytic anemia, renal failure, in children, lack of neurologic symptoms
What are the causes and clinical features of von Willebrand disease?
Cause:
- Defects/decrease in Factor VIII-vWF complex
- autosomal dominant
Clinical features:
- Defects in platelet function and coagulation
- spontaneous bleeding from mucous membranes, excessive bleeding from wounds and menorrhagia
What are the causes and clinical features of hemophilia A (Factor VIII deficiency)?
Causes:
- defects/decrease in Factor VIII-vWF complex
- X-linked recessive
Clinical features:
- mild/severe hemophilia
- easy bruising, hemorrhage
- prolonged PTT
What is DIC and the two major mechanisms that trigger it?
DIC
- disseminated intravascular coagulation
- disorder which proteins that control blood clotting is abnormally active causing blood clots in microcirculation (prevent blood flow to vital organs)
Mechanism
1) release of tissue factor or thromboplastic substances
2) widespread endothelial damage
What is the common conditions associated with DIC?
Sepsis (infection)
Obstetric complications
Malignancy (neoplasm)
Major trauma (tissue injury)
What are the two outcomes of DIC?
1) Tissue hypoxia and microinfarcts d/t myriad microthrombi
2) bleeding disorder related to pathologic activation of fibrinolysis and depletion of hemostasis elements
Both may occur
Describe the most common transfusion reaction.
Febrile nonhemolytic reaction:
Fever
Chills
Dyspnea
Occurs 6 hours post-transfusion of RBCs or PLTs. Likely due to inflammatory mediators.
Patients respond to anti-pyretics.
Define:
- Leukopenia
- Neutropenia
- Agranulocytosis
Leukopenia
- decrease in granulocytes (WBCs)
Neutropenia
- decreased number of circulating neutrophils
Agranulocytosis
- severe and dangerous leukopenia
What are the two mechanisms in which leukopenia, neutropenia and agranulocytosis occur?
- Decreased granulocyte production
(bone marrow failure/hypoplasia, chemotherapy, aplastic anemia, leukemia) - Increased granulocyte destruction
(immune-mediated, infection, splenomegaly)
What are the common clinical features in which leukopenia, neutropenia and agranulocytosis occur?
Infections risk increases and becomes major problem (ulceration, necrotizing lesions of gingiva)
Malaise, chills, fever
What are the distinctions in clinical presentations between leukemias, lymphomas and plasma cell tumors?
Leukemia: Anemia, thrombocytopenia, neutropenia Fatigue Pallor Bleeding Infection
Lymphomas:
- lymphadenopathy
Plasma cell tumors:
- Bone disease +/- hypercalcemia
- Recurrent infections
- Anemia and fatigue
- Renal failure due to multiple causes
- Neuropathy
- Asymptomatic in a minority of the patients
What type of cells do lymphoid neoplasms arise from?
Transformed B cells and T cells.
Derived from a single transformed cell and are therefore clonal.
They disrupt normal immune function.
What are the clinical features of acute leukemias?
Depression of marrow function
- fatigue d/t anemia
- fever d/t infections
- bleeding d/t thrombocytopenia
Mass effects d/t neoplastic infiltration
- bone pain
- lymphadenopathy, splenomegaly, hepatomegaly
- compression of large vessels and airways in mediastinum
CNS manifestation
- headache, nausea vomiting, nerve palsies
What are the laboratory findings of acute leukemias?
- WBC count
- Aleukemic (no circulating blasts)
- Anemia
- PLT below 100 K/microL.
- Neutropenia
What is the clinical features or clinical course of ACUTE LYMPHOBLASTIC LEUKEMIA?
Most common cancer of children.
Neoplasms of immature B or T cells (lymphoblasts)
Signs/Sx of bone marrow failure
What is the clinical features or clinical course of CHRONIC LYMPHOCYTIC LEUKEMIA?
Asymptomatic.
Easily fatigability, weight loss, anorexia.
Generalized lymphadenopathy, hepatosplenomegaly.
Hypogammaglobulineremia.
Leukocyte count increased slightly.
What is the clinical features or clinical course of MULTIPLE MYELOMA?
One of the most common lymphoid malignancies.
Median age 70
African-origin males
Bone marrow
Lytic lesions throughout skeletal system.
Excessive immunoglobulins, suppression of humoral immunity
Pathologic fractures due to bone resoprtion
What is the clinical features or clinical course of HODGKIN LYMPHOMA?
Presence of tumor giant cell, Reed-Sternberg (RS) cell.
Single lymph node (LN) or chain of LN.
Spread in stepwise fashion.
Arises from germinal center B cells.
What is the clinical features or clinical course of ACUTE MYELOID LEUKEMIA?
Neoplastic cell blocked at early stage of myeloid cell development.
Immature myeloid cells accumulate in marrow.
Old adults (~50 y/o)
Fatigue, pallor, abnormal bleeding, infections.
What is the clinical features or clinical course of CHRONIC MYELOGENOUS LEUKEMIA?
25-60 y/o Presence of chimeric BCR-ABL gene. Insidious onset. Easy fatigability, weakness, weight loss. Splenomegaly.
Elevated leukocytes.
Circulating neutrophils, metamyelocytes and myelocytes.
What are Reed-Sternberg (RS) cells and what disease is it associated with?
Reed-Sternberg cells
- “owl-eye” cells in enlarged lymph nodes; enormous multilobate nucleus, prominent nucleoli, abundant cytoplasm, slightly eosinophilic
Hodgkin’s disease
What is the general principles of the Ann Arbor classification system for staging lymphomas?
The more the lymph node (LN) region involved, the higher the stage.
Stage 1: single LN region
Stage 2: 2+ LN region, same side of diaphragm
Stage 3: LN regions on both sides of diaphragm
Stage 4: Multiple/disseminated foci involvement of 1+ extralymphatic organs/tissues
What is the difference between Hodgkin (HL) and non-Hogkin (NHL) Lymphoma?
Location:
HL - localized to single axial group of nodes
NHL - multiple peripheral nodes
Spread:
HL - orderly
NHL - non-contiguous
Mesenteric nodes/Waldeyer Ring:
HL - rare
NHL - common
Extranodal involvement:
HL - uncommon
NHL - always
