Episode 8- Overview of Hematological Pathology Flashcards
A reduction in one or more of the major RBC measurements: hemoglobin concentration, hematocrit or RBC count is classified as ________
Anemia
Typical signs and symptoms of anemia include:
- Tiredness/fatigue/exercise intolerance
- Fainting
- Shortness of breath
- Pallor
- Tachycardia/ palpitations
- Worsening of angina
Acquired anemias are caused by:
- Specific deficiencies (iron, vit B12, folate)
- Blood loss (acute or chronic)
- Chronic disease (chronic infections or inflammatory diseaes)
- Hemolysis (AIHA)
What is the most common cause of anemia worldwide?
Iron deficient anemia
What are the characteristics of iron deficient anemia?
- Defective hemoglobin synthesis leads to microcytic (decreased MCV) and hypochromic (decreased MCH & MCHC). 2. ‘Pencil cells’ are seen in blood smear due to unbalanced surface membrane 3. Low rate of hemoglobin results in MORE cell division and smaller ‘pale’ cells with lower levels of hemoglobin.
What is characteristic of this blood smear?
Pencil cells, characteristic in iron deficient anemia
What are the 4 common causes of iron deficiency?
- Overt or occult blood loss (Major cause in affluent countries)
- Dietary (vegans and old timers)
- Dcreased Fe absorption (GI tract problems or drugs impairing absorption)
- Increased Fe requirements (pregnancy & growth spurts)
What are the characteristics of Vitamin B12 deficient anemia?
RBCs are macrocytic (elevated MCV). Macrocytic RBCs often called Megaloblasts –> Megaloblastic anemia.
Why is the physiology behind Vitamin B12 deficient anemia?
DNA synthesis cannot occur without B12 or Folate (therefore cannot divide), but RNA synthesis & protein synthesis continue to occur. Accumulation of protein causes fatty RBCs.
Using your well trained eyes, what is characteristic of this blood smear?
Megaloblasts (Macrocytic RBCs)
What are the main causes of Vitamin B12 deficiency?
- Lack of Intrinsic Factor (IF). Due to autoimmune attack of IF itself or against Parietal cells of stomach (site of IF synthesis). This leads to decreased B12 absorption and is called Pernicious Anemia
*If autoimmune attack is against parietal cells also causes chronic atrophic gastritis*
- Dietary: strict vegans are most susceptible
- Total/Partial Gastrectomy & other stomach procedures: on the rise with more peeps getting these surgeries.
What are the characteristics of folate deficient anemia?
The other key player in DNA synthesis is folate. Does not require intrinsic factor to be absorbed. Produces the same clincial signs of a blood smear as B12 (increased MCV)
What are the 4 main causes of folate deficient anemia?
- Poor nutrition: poverty, elderly, alcoholics
- Increased requirements: pregnancy
- Malabsorption: inflamatory diseases of intestines
- Drugs: inhibiting absorption (anti-epileptics & oral contraceptives)
What are the two general features of large blood volume loss?
Increased HR and low BP
What are the characteristics of Anemia due to ACUTE blood loss?
Initial hemoglobin levels are normal for several hours because RBCs and plasma is lost evenly.
Anemia develops once blood volume is restored (extravascular moves intravascular)
MCV is normal and anemia is called Normocytic.
Anemia due to CHRONIC blood loss is often associated with what other anemia?
Iron deficient anemia (especially in developed countries)
Examples: bleeding gastric ulcer or heavy menstrual flow
What are the characteristics of Anemia of Chronic Disease (ACD)?
Anemia is normocytic. Chronic diseases (like renal failure) produce anemia but mechanisms are poorly understood.
Are Hemolytic anemias acquired or inherited?
Can be either acquired or inherited
What are causes of hemolytic anemias?
Destruction of RBCs at a faster than normal rate leading to a reduced lifespan. RBCs can live as little as 20 days.
Increased RBC breakdown leads to increased RBC synthesis. If bone marrow is working well it may offset the hemolysis anemia
What is the cause of Acquired autoimmune hemolytic anemia (AIHA)?
Autoimmune response directed against the RBCs own antigens.
What nature are virtually all hereditary anemias?
Hemolytic
What are the 3 major groups of hereditary anemias?
- Red cell membrane (hereditary spherocytosis & hereditary elliptocytosis)
- Red cell enzymes (G6PD deficiency)
- Hemoglobin molecules (sickle cell disease & thalassemias)
What is the cause of hereditary spherocytosis?
Molecular defects in genes that code for the peripheral proteins:
Spectrin (alpha/beta)
Ankyrin
Protein 4.2
Band 3
Other erythrocyte membrane proteins
What are the diagnostic tests for hereditary spherocytosis?
- Elevated MCHC (reflecting membrane loss & RBC dehydration)
- Elevated RDW
Using your eagle eyes (except for Jordan who needs to see a optomatrist) what does this blood smear show?
Hereditary spherocytosis
What is the cause of hereditary elliptocytosis?
Molecular defects in the same genes that affect/cause hereditary spherocytosis.
Defects destabilize the cytoskeletal scaffolding of cells
What do you see in this blood smear?
Hereditary elliptocytosis
What is the Osmotic Fragility Test? What is the solution added? What is the mean corpuscular fragility?
- This test is used to detect spherocytosis & elliptocytosis. The test measures the lysis of RBCs in NaCl solutions.
- Curves are generated for normal and test samples. The MCF is the concentration at which 50% lysis occurs.
- Normal RBCs remain intact until the NaCl concentration reaches 50%. Then cells begin to lyse as solution becomes more hypotonic.
- Spherocytes and elliptocytes lyse more readily due to lower surface area to volume ratio
What is the most common enzymatic disorder of RBCs in humans, affecting 400 million worldwide?
Glucose 6-phosphate dehydrogenase (G6PD) deficiency
What is the role of G6PD in the RBC?
The only source of NADPH in RBCs. Necessary to maintain glutathione in a reduced form.
In addition to hemolytic anemia, what are 2 other characteristics of G6PD deficiency?
- Heinz bodies: clusters of denatured hemoglobin. (seen with particular stains where hemoglobin has been rendered unstable due to oxidant damage)
- Bite cells: though to result from the processing of cells through the spleen and removal of Heinz bodies.
What is shown in this here smear of blood?
Heinz bodies
And what do you see in this blood smear?
Bite cells
What is the cause of sickle cell anemia?
A point mutation in the Beta globin gene causing a Glutamate to Valine amino acid mutation in protein 6.
The resulting hemoglobing produces is called hemoglobin S (HbS).
How are sickle cell RBCs different than normal RBCs?
Sickle cell hemoglobin elongate under conditions of reduced oxygenation & form sickle shaped cells.
Sickle cell RBCs are more adherent than normal RBCs to vascular endothelium, leading to sickle cell crises.
Sickle cells have reduced lifespans & result in chronic hemolysis.
See this here blood smear. What see you?
Sickle cells
Where is sickle cell gene most widespread?
Africa, the Middle East and parts of India
What is the cause of Thalassemias?
Arises as a result of diminished or absent production of one or more of the globin chains. This leads to unbalanced globin chain production.
Globin chains in excess precipitate with the red cells leading to chronic hemolysis.
Thalassemia is classified after the gene affected (ex: alpha thalassemia is where the alpha globin gene is affected.
What are the 2 main characteristics of Thalassemia RBCs?
The consequence of impaired production of globin chains leads to RBCs being MICROCYTIC and HYPOCHROMIC
Leukemia attacks what cells?
White blood cell precursors (colony forming units of WBCs)
What are the characteristics of acute leukemia?
Tends to present more dramatically. Must be treated early or death will occur within a short period of time
What are the characteristics of chronic leukemia?
More idolent (slow growing) & in some cases will not require therapy for years. Chronic leukemias are discovered by chance.
What are common characteristics between acute and chronic leukemias?
- Progressive accumulation of abnormal WBCs in bone marrow & other organs that eventually spill out into the peripheral blood.
- Progressive bone marrow failure with a reduction of other normal cell types (patients tend to also have a reduced number of RBCs and megakaryocytes)
What is Acute Myeloid Leukemia (AML)/ Acute Myelogenous Leukemia?
Cancer of the myeloid line stem cells. Characterized by rapid growth of abnormal WBCs that accumulate in bone marrow & interfere with production of normal blood cells.
What is the most common acute leukemia affecting adults with an increased incidence with age?
Acute myeloid leukemia
What are the symptoms of AML?
- Reduced RBCs (tiredness, shortness of breath, anemia)
- Reduced WBCs (increased susceptibility to infections)
- Reduced platelets (bruising, bleeding)
- Bone pain (accumulation of leukemic cells in long bones
- Respiratory & neurological symptoms (large numbers of WBCs in blood causing hyperviscosity & “sludging” og blood.
What is Acute Lymphoblastic Leukemia (ALL)/ acute lymphocytic Leukemia?
Cancer of the lymphoid line stem cells. Characterized by rapid growth of abnormal WBCs that accumulate in bone marrow and interfere with production of normal blood cells.
What is the most common childhood leukemia with a peak incidence at 2-5 years of age?
ALL
What are the symptoms of ALL?
Similar to AML…
What is Chronic Myeloid Leukemia (CML)? What is the most common age of presentation? What is the defective chromosome and downstream effect?
- Cancer of the myeloid line of stem cells.
- Presents between 40-60 years of age
- Prescenc of the philidelphia chromomosome (a translocation where chromosomes 9 & 22 swap places)
- Mutation leads to transcriptions of proteins with high tyrosine kinase activity
What are the 3 main phases of CML?
- Chronic Phase: Asymptomatic or mild symptoms (fatigue, left side pain, joint/hip pain & abdominal fullness) Duration is ~5 years. ~85 patients are in chronic phase at time of diagnosis. Treatments are most effective in this stage
- Accelerated Phase: Severity of symptoms increas. Labs reflect greater shifts in numbers. Therapies used are less effective.
- Blast Crisis: Resembles an acute leukemia, with rapid progression and short survival
What is Chronic Lymphoblastic Leukemia (CLL)? What are the characteristics?
Cancer of the lymphoid line of stem cells. Slow-growing disorder characterized by progressive accumulation of cancerous cells in bone marrow, spleen, liver and lymph nodes.
What is the most common adult leukemia in Western societies? What is the peak incidence and the male to female ratio?
- CLL
- Peak age: 60-80
- 2:1 male to female ratio
What is the difference between leukemia and lymphomas?
Leukemia is a cancer that occurs in WBC precursors and hence bone marrow.
Lymphomas are solid tumor masses & can originate in many different lymphoid tissues (LN, spleen, liver, GI tract, thymus or bone marrow)
What is the most common location for a lymphoma?
Lymph nodes
Who was the first person to describe a lymphoma?
Thomas Hodgkin (Hodgkin’s lymphoma)
What is the cause of Hodgkin’s lymphoma? What is the incidence? What are the characteristics?
- Unknown cause
- 2-3/100k
- Itchy skin, night sweats, unexplained weight loss, enlarged lymph nodes, splenomegaly, hepatomegaly & Reed-Sternberg cells
What are Reed-Sternberg cells (popcorn cells)?
B lymphocytes that have lost their ability to produce antibodies (commonly seen in biopsied lymph nodes of patients with Hodgkin’s lymphoma)
What doth thou see in yonder smear of blood?
Thou shouldst have seen the Reed-Steinberg “popcorn” cell
What is a non-hodgkin’s lymphoma? What is the cause? How many new cases each year? What are the symptoms?
- NHL’s are any lymphoma that is not a Hodgkin’s.
- Cause unknown
- 66k new cases/year
- Similiar symptoms to Hodgkin’s lymphoma
