Hematopoietic and Lymphoid 1 Flashcards
What are the three “formed blood elements?”
- RBCs
- WBCs
- Platelets
What is the general definition of anemia?
Decreased oxygen transporting ability of the blood.
What are the clinical manifestations of anemia (5)?
- Pallor of the skin and mucous membranes
- Shortness of breath, fatigue
- Heart palpitations
- Short systolic murmurs
- Lethargy
Can you be anemic as a result of blood loss?
Yeah
Compare intrinsic (intracorpuscular) vs. extrinsic (extracorpuscular) hemolytic anemia.
Intrinsic (intracorpuscular) anemia is caused by factors inside the RBC (enzyme problems, Hb disorders) or defects in the RBC membrane.
Extrinsic (extracorpuscular) anemias are mainly acquired and caused by factors outside the red blood cell, e.g. hypersplenism, anti-RBC antibodies, drugs, infections, toxins and mechanical RBC destruction due to trauma.
How are anemias classified?
Based on underlying mechanism or RBC morphology
What are the three histologic classifications of anemia?
- Normocytic-normochromic
- Microcytic-hypochromic
- Macrocytic-hyperchromic
What type of anemia does iron deficiency cause?
microcytic-hypochromic
What type of anemia do the thalassemias cause?
microcytic-hypochromic
What type of anemia does chronic disease cause?
Most often normocytic-normochromic but sometimes microcytic-hypochromic (20-30%)
What type of anemia does blood loss cause?
normocytic-normochromic
What type of anemia does hemolytic anemia cause?
normocytic-normochromic
What type of anemia does B12 or folate deficiency cause?
Macrocytic-hyperchromic
What type of anemia does alcoholism cause?
Macrocytic-hyperchromic
What type of anemia causes hyperbilirubinemia, jaundice, and pigment gallstones?
hemolytic anemia
Ineffective hematopoiesis can cause iron overload, leading to ________ and _______ failure.
heart and endocrine failure
Severe forms of anemia can cause three things. Name them.
Growth retardation, skeletal abnormalities, cachexia
What are the two compensatory mechanisms seen in anemia?
Hyperplasia of erythroid precursors in bone marrow; extramedullary hematopoiesis in secondary hematopoietic organs (liver, spleen, lymph nodes).
What is the normal life span of a RBC?
120 days
What is hemolytic anemia?
Accelerated destruction of RBCs
What is reticulocytosis? What disease is it seen in?
It is increased circulating immature RBCs. Seen in hemolytic anemia.
What is hereditary spherocytosis?
A type of intracorpuscular hemolytic anemia
By what mechanism is hereditary spherocytosis inherited?
Autosomal dominant most of time, 25% are autosomal recessive
What molecular defects are involved in hereditary spherocytosis?
Mutations in structural RBC proteins (spectrin, ankyrin, band 3 protein) –> spherical RBCs - limited deformability, killed off in the spleen
How is hereditary spherocytosis treated surgically? What is the biggest risk associated with this?
Splenectomy. Risk for infections increases.
What are Howell-Jolly bodies and in what disease are they seen?
They are small dark nuclear remnants seen in spherical RBCs (spherocytes) in the case of hereditary spherocytosis. (Santa is JOLLY and SPHERICAL)
Describe the clinical course of hereditary spherocytosis.
RBC life span is 10-20 days. Anemia is moderate, splenomegaly, jaundice, pigment stones, systemic hemosiderosis (systemic hemosiderin accumulation from RBC breakdown)
What percentage of African-Americans are heterozygous for sickle cell anemia? What proportion have the disease?
8% are heterozygous, 1 in 600 have it
What mutation is involved in sickle cell anemia?
Single AA substitution in the B-globin chain (valine for glutamic acid)
What percentage of hemoglobin is of the HbS type in peeps who are heterozygous for sickle cell anemia?
40%
Describe the progression of membrane damage in the case of sickle cell anemia.
Deoxy HbS –> polymerization. After repeated oxygenation and deoxygenation the cells undergo irreversible damage and accumulate calcium, become permanently sickled and are rapidly hemolyzed.
What is anisocytosis? What is poikilocytosis? What disease are these characteristic of?
Anisocytosis — considerable variation in the size of cells that are normally uniform.
Poikilocytosis — RBC of irregular shape.
Characteristic of sickle cell anemia
What are the two major clinical consequences of sickle cell anemia?
- Hemolytic anemia (HCT is 18-30% when normal is 35-45%)
2. Microvascular obstruction
Why does homozygous sickle cell anemia not show up until 6 months of life?
That is when HbF is replaced by HbS
Name eight other clinical manifestations of sickle cell anemia.
- RBC life span is only 20 days
- Reticulocytosis
- Hyperbilirubinemia
- Avascular necrosis in bones, bone marrow
- Infarction of organs
- Hemosiderosis
- Gallstones
- Splenomegaly (childhood) –> autosplenectomy (damage results in a shrunken and nonfunctional spleen) in adults
What are the two leading causes of ischemia related death from sickle cell anemia?
- Acute chest syndrome with pulmonary dysfunction, systemic hypoxemia, vaso-occlusion
- CNS stroke
How is sickle cell anemia treated? How does it work?
Hydroxyurea reduces pain crises, increases HbF levels, has anti-inflammatory effects, increases mean cell volume, and produces NO –> vasodilation and inhibits platelet aggregation
What is an aplastic crisis?
A temporary cessation of erythropoiesis
G-6-P dehydrogenase deficiency is a _______ ________ disorder characterized by RBC sensitivity to ________ stress that manifests as _______ _______.
x-linked recessive disorder that causes RBCs to be sensitive to oxidative stress –> hemolytic anemia.
Is G-6-P dehydrogenase deficiency most prevalent in areas where malaria is historically endemic (African and parts of the Mediterranean) and does it appear to provide some protection against malaria?
Yeah
What variant of G-6-P dehydrogenase deficiency is associated with reduced enzyme activity (10% of normal) due to decreased enzyme half life? What population is it seen in predominantly?
A- variant. Seen in 10-15% of African-Americans
What is the normal function of G-6-P dehydrogenase?
Regeneration of reduced glutathione, which helps deal with oxidative stress
What types of things are bad for people with G-6-P dehydrogenase deficiency (4)?
- Drugs including antimalarials, some antibiotics, analgesics, vitamin K derivatives.
- Fava beans
- Napthalene (moth balls)
- Infections (phagocytosis leads to free radical production)
Oxidation of Hb causes its precipitation in the cytoplasm as ______ bodies, increased cell ridigity –> hemolysis or BITE CELLS (cells with some of their membrane removed). This is commonly seen in what disease?
Heinz bodies.
Seen in G-6-P dehydrogenase deficiency
In someone with G-6-P dehydrogenase deficiency, how long does it take for acute hemolysis to show up?
2 or 3 days
What is a treatment for someone with G-6-P dehydrogenase deficiency that is in the acute phase of hemolysis?
blood transfusion
People with G-6-P dehydrogenase deficiency may take a ______ ______ supplement.
folic acid
Bite cells
G-6-P dehydrogenase deficiency
Name the disease associated with this: decreased rate of synthesis of either alpha or beta globin chains.
Thalassemia
In which populations are the thalassemia diseases most common?
Mediterranean, African, Asian
Thalassemias are characterized by reduced concentration of _____ and abnormal ______ of alpha to beta chains, resulting in _______ deposits and target cells which are prone to _______.
reduced concentration of HbA, abnormal alpha-beta chain ratio, resulting in intracellular deposits and target cells prone to hemolysis
What type of thalassemia is most common? How are cells damaged?
beta-thalassemia is most common. Unpaired alpha globin chains form aggregates that damage red cell precursors and impair erythropoiesis
Describe the clinical differences between homo and heterozygotes of beta-thalassemia.
Thalassemia major (Cooley anemia): homozygotes develop hemolysis, splenomegaly, bone marrow hyperplasia, and bone deformities. Shows up early as HbF decreases. Growth retardation.
Thalassemia minor: mild anemia in heterozygotes. Mild microcytic hypochromic anemia. Normal life expectancy
alpha-thalassemia is caused by deletion of one or more alpha globin genes and severity depends on…..
the number of genes deleted
Describe the clinical manifestations of thalassemia (5)
- Hyperplasia of erythroid progenitors
- Cachexia
- Skeletal deformities due to marrow expansion
- Splenomegaly
- Iron overload –> hemosiderosis
True or false: patients with beta-thalassemia major need repeated blood transfusions, have systemic iron overload, and fail to thrive.
true
Name the disease: x-ray showing new bone formation on the outer table, producing perpendicular radiations resembling a crewcut
thalassemia
What is the most common form of nutritional deficiency?
Iron deficiency
What is the most common form of anemia?
Iron deficiency anemia
What most often causes iron deficiency in the Western world vs. in developing countries?
Western: blood loss
Developing: inadequate iron
By what mechanisms can iron deficiency anemia be caused by inadequate iron absorption?
Celiac, achlorhydria (poor gastric acid secretion –> poor iron absorption. Remember, drink orange juice to absorb iron!)
By what mechanisms can iron deficiency anemia be caused by excessive iron loss?
Menstruation, GI bleeding
By what mechanisms can iron deficiency anemia be caused by increased iron demand?
Pregnancy, lactation, infancy
Describe some lab tests that are characteristic of iron deficiency anemia (4)
- Low serum iron
- Low serum ferritin
- Low transferrin saturation
- High total iron binding capacity (TIBC)
How can B12 and/or folate deficiency cause anemia?
DNA synthesis is inhibited –> bone marrow can’t make blood cells.
What is pernicious anemia?
Autoimmune attack on gastric mucosa that makes intrinsic factor –> no B12 absorption
What are some other diseases, other than pernicious anemia, that result in bad B12 absorption?
gastritis, Crohns, Celiac, GI parasitic infection
Methotrexate is an antagonist that interferes with the absorption of _____.
folate
Hypersegmented neutrophils is characteristic of what type of anemia?
B12/Folate deficiency anemia
Bone marrow with numerous megaloblasts (megalocytic anemia) and atrophy of gastric fundic glands are characteristics of what type of anemia?
B12/Folate deficiency anemia
Name the disease: Central nervous system lesions with demyelination of dorsal and lateral tracts of the spinal cord (PA), may not resolve even with proper supplementation.
B12 deficiency only
What is aplastic anemia?
A disease in which the bone marrow, and the multipotent myeloid stem cells that reside there, are damaged, causing a deficiency of all three blood cell types (pancytopenia)
What are the causes of aplastic anemia?
Most are idiopathic, others can be to drugs, toxins, radiation, viral infection.
Does the immune system play a role in aplastic anemia?
Yeah because immunosuppressive therapy is helpful. Auto-reactive T cells play role
What happens to cells in the bone marrow in the case of aplastic anemia?
They are replaced by FAT
Do people with aplastic anemia experience hemorrhages, infections, and repeated transfusions that lead to hemosiderosis?
Yeah
How do you best differentiate B12 and folate deficiencies?
Neurologic abnormalities do NOT occur in folate deficiency.
