Episode 8 Overview of Hematological Pathology Flashcards
What is anemia?
A reduction one or more of the major RBC measurements - Hg concentration, hematocrit, and/or RBC count
What is the most common cause of anemia worldwide?
Iron deficiency
What is the result of defective Hb synthesis on RBC formation?
Microcytic (MCV is low) and Hypochromic (low MCH and MCHC)
Why do pencil cells appear in a blood smear?
Unbalanced surface membrane to cytoplasmic volume due to reduced Hb
What does a reduced rate of Hb synthesis result in?
More cell division and smaller cells
How do lower levels of Hb affect the appearance of RBCs?
They look pale
What are the major causes of iron deficiency?
Blood loss, decreased iron absorption (GI tract problem or drug induced), Dietary, Increased iron requirements (pregnancy and growth spurts)
What is the effect of vitamin B12 deficiency on RBCs?
RBCs become macrocytic (MCV is elevated)
What are enlarged RBCs sometimes referred to as?
Megaloblasts - “megalobalstic anemia”
Which is affected by vitamin B12 - RNA or DNA?
DNA, RNA is unaffected and protein synthesis continues and accumulates making the RBC larger
What are the main causes of Vitamin B12 deficient anemia?
Lack of intrinsic factor (IF), dietary, and gastrectomy or other stomach procedures
What does the lack of IF lead to?
Decreased absorption of vitamin B12
What is pernicious anemia?
Vitamin B12 deficiency specifically due to decreased IF
What are the causes in a lack of IF?
Lack of gene, autoimmune attack on IF or on the Parietal cells in the stomach
What does an attack on parietal cells produce, besides lack of IF?
Chronic atrophic gastritis
T/F Vitamin B12 deficiency and folate deficiency both produce very similar RBCs under the microscope
True, both produce increased MCV
Does folate absorption require IF?
No, only Vit. B12 does
What are the potential causes of folate deficiency?
Poor nutrition, increased requirements (pregnancy), malabsorption (inflammatory diseases of the intestines), Drugs interfering with absorption
What are the general features of anemia due to acute blood loss?
Increased HR and Low BP
Why would Hb concentration and a full blood count taken immediately after acute blood loss be normal?
B/c RBCs and plasma are lost together
When MCV remains normal during this is called what?
Normocytic
Where must the movement of fluid go to develop anemia after acute blood loss?
From the extravascular space to the intravascular
What is anemia due to chronic blood loss most often associated with in the developed world?
Iron deficient anemia
What are examples of anemia due to chronic blood loss?
Unrecognized loss from a bleed gastric ulcer or heavy menstrual flow
What is typical of anemia of chronic disease?
It is typically normocytic
Why would chronic renal failure cause anemia?
Kidney’s produce erythropoeitin, w/o which RBCs production cannot respond to falling oxygen levels in tissues
What is a hemolytic anemia?
Disorder in which the RBCs are destroyed faster than normal - bone marrow cannot keep pace with the rate of destruction
How few days may RBCs live when someone has hemolytic anemia?
As few as 20 days
What is the autoimmune response directed against in Acquired Autoimmune Hemolytic Anemia?
RBCs own antigens
Virtually all hereditary anemias are what?
Hemolytic
Inherited anemias may be classified into what three major groups of disorders?
Those affecting:
1) RBC membrane - spherocytosis, elliptocytosis
2) RBC enzymes - G6PD deficiency
3) Hb molecules - sickle cell, thalassemia
What defects cause hereditary spherocytosis?
Molecular defects in genes that code for Ankryn, Protein 4.2, Spectrin, Band 3 protein
What is the most helpful RBC index in hereditary spherocytosis?
Mean Cell Hemoglobin Concentration (MCHC), which is routinely elevated
What does an elevated MCHC indicate?
membrane loss and RBC dehydration
What does an elevated RDW favor the diagnosis of?
hereditary spherocytosis
What is the difference between Hereditary Elliptocytosis (HE) and pencil cells in iron deficient anemia?
Pencil cells in iron deficient anemia appear occasionally by with HE the vast majority of cells look elliptical
When would an Osmotic Fragility Test (OFT) be performed?
When one is suspected of having spherocytosis or elliptocytosis
What is the OFT?
Measure of RBC lysis in an NaCl concentration at which 50% lysis occurs - spherocytes and elliptocytes lyse more readily than normal RBCs
G6PD is the only source of what in RBCs?
NADPH, which maintains glutathione in its reduced form
The RBCs of G6PD often show what characteristics?
Heinz Bodies (a cluster of denatured Hb) and Bite cells (removal of HBs afterr processing thru the spleen)
Where are HBs usually located on an RBC?
Periphery - look like olives with pits
What is the sickle cell anemia a result of?
Point mutation in the Beta globin gene - resulting in the change of amino acid number 6 - Glutamate to Valine
What is Thalassemia?
Unbalanced globin chain production
Where is thalassemia prevalent?
Some of the same areas as sickle cell anemia - Africa, Mediterranean, Middle East, India, and Asia
How is thalassemia classified?
Classified after the gene affected - alpha-thalassemia if the alpha-globin gene is altered, or beta-thalassemia etc
What is the consequence of thalassemia?
RBCs that are microcytic and hypochromic
What cells get cancer in Leukemia?
WBC precursors
What are the two classic leukemia forms?
Acute and chronic
What happens in leukemia?
progressive accumulation of abnormal WBCs in the bone marrow and other organs, which spill out into the peripheral blood; progressive bone marrow failure with a reduction in other normal cell types. Tend to have reduced number of RBCs and Megakaryocytes
What is Acute Myeloid Leukemia (AML)?
Cancer of myeloid line of stem cells. Rapid growth of abnormal WBCs that accumulate in bone marrow an interfere with production of normal blood cells
What is the most common acute leukemia?
AML
What are the symptoms of AML?
Tiredness, infections, bruising, bone pain, respiratory and neurological symptoms
What are the symptoms of AML caused by?
drop in RBCs, platelets, and normal WBCs
What is acute lymphoblastic leukemia (ALL)?
cancer of lymphoid line of stem cells
At what age is ALL most common? AML?
ALL is most common in ages 2-5. AML is most common in adults and increases with age
What is the difference b/w acute (AML) and chronic (CML) myeloid leukemia?
CML has the presence of the Philadelphia chromosome
What is the Philadelphia chromosome?
Translocation in which two parts of two chromosomes 9 and 22 are swapped
What does the Philadelphia chromosome mutation lead to?
Transcription of proteins with high tyrosine kinase activity
What does the drug Gleevec treat?
CML
What are three phases of CML?
Chronic phase, Accelerated phase, and Blast Crisis
Where is the Chronic Lymphoblastic Leukemia most common?
Western societies w/ a peak incidence in pts b/w 60-80 and a male:female ratio of 2:1
CLL is a slow-growing disorder characterized by progressive accumulation of cancerous cells where?
Bone marrow, spleen, liver, and lymph nodes
What is the difference between leukemia and lymphoma?
Leukemia is a cancer of WBC precursors that occurs in the bone marrow. Lymphoma is a solid mass tumor that can originate w/in many different lymphoid tissues - lymph nodes (most common), spleen, liver, GI tract, thymus or bone marrow
What are the symptoms of Hodgkin’s lymphoma?
Itchy skin, night sweats, unexplained weight loss, enlarged lymph nodes, splenomegaly, hepatomegaly
What type of cells are characteristically seen in biopsies of Hodgkin’s lymphoma?
Reed-Sternberg cells - AKA “popcorn cells”
What are Reed-Sternberg cells - AKA “popcorn cells”?
B lymphocytes that have lost the ability to produce antibodies
What is the prognosis for Hodgkin’s Lymphoma?
Good prognosis (unlike Non-Hodgkin’s Lymphoma)
What is Non-Hodgkin’s Lymphoma (NHL)?
A group of lymphoma’s that includes everything Hodgkin’s Lymphoma. No good prognosis for treatment or cure
