Blood Disorders Flashcards
Erythropoiesis:
synthesis of RBC
What are the organs that contribute to erythropoiesis?
Second trimester:
- liver
- spleen
- lymph nodes
Late third trimester & after birth:
- exclusively in bone marrow
What are the stages of differentiation of RBC?
- Proerythroblast
- Basophil erythroblast
- Polychromatophil
- Orthochromatic erythroblast
- Reticulocyte
Proerythroblast:
- the first cell in RBC series
Basophil erythroblast:
- stain with basic dyes
- low level of hemoglobin
Polychromatophil erythroblast:
- increase in hemoglobin
- condensation of nucleus
Orthochromatic erythroblast:
- increase in hemoglobin
- condensation of nucleus
Reticulocyte:
- small amount of cytoplasmic organelle
- nucleus absorbed or extruded
- maturation to erythrocyte: 1-2 days
Which of the stages of differentiation of RBCs are in the BONE MARROW?
Proerythroblast
Basophil erythroblast
Polychromatophil erythroblast
Orthochromatic erythroblast
Reticulocyte
Which of the stages of differentiation of RBC’s are in the BLOOD (<1%)?
Reticulocyte
Erythrocytes
(shouldn’t be in bloodstream esp. immature ones for the most part, but if they are then there is an issue)
What are the major functions of RBC?
- Transport hemoglobin (and O2)
- Contain carbonic anhydrase (CO2 transport)
CO2 + H2O CA H2CO3 - Hemoglobin is an acid-base buffer
What is the regulation of RBC production?
- Tissue oxygenation
- high altitude (less O2 at high altitudes)
- cardiac failure (when HF happens, not enough BF therefore O2)
- lung diseases (b/c of low tissue levels of O2)
- Erythropoietin
Normal life span of RBC is about _____
120 days (~4 months)
RBCs are destroyed in the ____
spleen
Hemoglobin is released and phagocytized by the ______ (liver, spleen, bone marrow)
macrophages
Hemoglobin is converted to _____ and conjugated in the _____
bilirubin
liver (& excreted through body in feces & urine)
Iron is released and bound to ______ in blood or stored in form of _____ in liver
transferrin
ferritin
(free iron is toxic in body)
What are the different types of hemoglobin?
- HbA
- HbA2
- HbF
HbA:
- major form of ADULT Hb
- 2 alpha and 2 BETA chains
HbA2:
- 2 alpha and 2 DELTA chains
HbF:
- major type of FETAL Hb
- 2 alpha and 2 GAMMA chains
What do all the 3 types of Hb have in common?
have alpha-chains, therefore if problem with it, it can cause big issues
Describe the lab assessment for a complete blood cell count (CBC)
includes the following measurements:
* Hb: expressed as grams of Hb per 100 ml blood * Hct: percentage of RBC to total blood volume
males > females
* MCV: mean cell volume
* MCH: mean cell hemoglobin
* MCHC: average concentration of hemoglobin in a given volume of packed RBC
* WBC, RBC, platelet count
What is Anemia?
Anemia is defined as reduced number of RBC (↓Hb, ↓Hct)
What is the classification of anemia based on RBC morphology?
SIZE:
- normocytic
- microcytic
- macrocytic
Hb level:
- normochromic
- hypochromic
What are the clinical symptoms of anemia?
- weakness
- paleness (if # of RBCs decrease, it leads to paleness)
- malaise
- fatigue
- dyspnea (↓ O2 content)
- spoon shape nail
- myocardial hypoxia
- CNS symptoms (may cause faint) - b/c not enough O2 to brain
- kidney hypoxia
What is the classification of anemia based on underlying mechanism?
1) Blood loss:
- acute (trauma)
- chronic (GI tract lesions, gynecologic disturbances)
2) Increased rate of destruction (hemolytic anemia) A) Hereditary
- membrane disorders
- enzyme deficiencies
- deficient globin synthesis (thalassemia)
- structurally abnormal globin (sickle cell anemia))
B) Acquired (means there’s a factor in the body)
- antibody mediated (blood transfusions)
- autoantibodies (Systemic Lupus Erythematosus) - infections (Malaria - parasite that lives in RBC & can cause anemia over time)
3) Impaired RBC production
A) ↓ Proliferation / differentiation of stem cells
- aplastic anemia
- renal failure (b/c no prod. of erythropoietin in kidney)
- endocrine disorders
B) ↓ Maturation of erythroblasts
● defective DNA synthesis
- Vitamin B12 deficiency
- Folic acid deficiency
● ↓ Hb synthesis:
- ↓ heme synthesis (iron deficiency)
- ↓ globin synthesis (thalassemia)
Describe Anemia of acute blood loss
- normocytic normochromic anemia
- caused by external or internal bleeding
- loss of intravascular volume
- may lead to cardiovascular collapse, shock, and death
- blood volume is rapidly restored by shift from interstitial fluid
- renal hypoxia causes ↑erythropoietin
- increase in reticulocytes after a few days
- leukocytosis (mobilization of granulocytes)
Describe Hemolytic anemia
share the following features:
- shortened RBC life span
- increase in erythropoietin
- increase in erythropoiesis in bone marrow
- accumulation of products of Hb catabolism
(rate of destruction is increased, therefore lifespan of RBC are shorter)
What is Sickle cell anemia?
- Is caused by production of a defective Hb (HbS)
- A point mutation in beta globin chain
- Higher incidence in black Americans
- Protects against malaria
What does Sickle cell anemia look like?
- When deoxygenated, HbS molecules aggregate and forms polymers
- Defective RBCs: phagocytosis in spleen
- ↑ Bilirubin
- Enlarged spleen (tries to make more RBC to compensate)
- Bone marrow hypreplasia
- Chronic hypoxia may cause organ damage (spleen, heart, kidney, lung)
- Autosplenectomy (infarction, fibrosis) (spleen is enlarged & then becomes smaller & smaller)
What is Thalassemia?
- ↓ Synthesis of alpha or beta globin chains * Microcytic hypochromic anemia
- ↑ RBC destruction
- ↑ Erythropoietin (due to anemia)
- Erythroid hyperplasia in bone marrow
- Extramedullary hematopoiesis (liver, spleen)
- ↑ Iron absorption (tries to make more RBCs - precipitates in diff tissues & damages)
- ↑ HbF and HbA2 in thalassemia major
What are the types of Thalassemia?
β-thalassemia
α-thalassemia
β-thalassemia:
classified into 2 categories:
β0: total absence of β chain β+: ↓β chain synthesis
Surgically removed spleen of a thalassemic child (15 times larger than normal)
α-thalassemia:
- Reduced or absent synthesis of α-globin chains
- α-thalassemia major is lethal (all Hbs contain α-chain)
Describe Impaired RBC production
A) Megaloblastic anemia
* Vitamin B12 deficiency (pernicious anemia)
* Folic acid deficiency
What is Megaloblastic anemia characterized by?
- impaired DNA synthesis
- normochromic macrocytic anemia
- decrease in RBC, WBC, platelets
- large hypersegmented neutrophils
- bone marrow is hypercellular (b/c trying to make more RBCs)
- ineffective hematopoiesis and ↑RBC destruction
What are the causes of Vitamin B12 deficiency?
- Decreased intake
- inadequate diet
- vitamin B12 cannot be produced by human body, must
be obtained from diet - impaired absorption
- Intrinsic factor deficiency
- intrinsic factor is produced by
parietal cells of gastric mucosa - pernicious anemia (antibodies
to parietal cells & intrinsic factor - gastrectomy
food
–> ____
Vit B12 - protein –>
released by proteases in small intestine –>
Vit B12 - intrinsic factor –> absorbed in ileum
What is a Folic acid deficiency?
- Humans are dependent on diet folic acid.
- Causes of folic acid deficiency:
- Decreased intake
- inadequate diet
- impaired absorption
- Increased loss or need
- hemodialysis (kidney disease) - increased need (pregnancy)
What is Iron deficiency anemia?
- Most common nutritional disorder (children, infants, females)
- Microcytic hypochromic anemia
- ↓Erythroid progenitors
- Iron is absorbed in duodenum
- Free iron is highly toxic
- Iron is bound to ferritin or transferrin
- Mimics the symptoms of anemia in
chronic disease (e.g. infections, cancer)
Koilonychia (spoon- shaped nails)
What is Aplastic anemia?
- Bone marrow failure associated with ↓WBC, ↓RBC, and ↓platelet
- Suppression of multi-potent myeloid stem cells
- Caused by exposure to infections, chemicals,
radiation or drugs - Could be reversible or irreversible
- Hypocellular bone marrow
What is Polycythemia?
- Abnormally increased number of RBC, WBC, platelets
- ↑ Hb and/or ↑ HCT level
- Hypercellular bone marrow
- Relative polycythemia:
- results from any cause of dehydration
What is Absolute polycythemia?
- primary polycythemia:
caused by intrinsic abnormality of myeloid stem cells - secondary polycythemia: caused by ↑erythropoietin
What is leukemia?
Leukemia is cancer of blood-forming tissues, including bone marrow and lymphatic system.
* It usually involves WBCs
What are factors that ↑ risk of leukemia?
- chemotherapy/radiation therapy for other cancers
- exposure to chemicals (e.g. benzene)
- smoking cigarettes
- genetic disorders (e.g. Down syndrome)
- family history of leukemia
Classification of leukemia based on PROGRESSION:
- Acute leukemia
- immature blood cells (blasts) replicate rapidly
- disease worsens quickly
- cells cannot carry out normal function
- requires timely treatment
- Chronic leukemia
- involves more mature blood cells
- replicate more slowly
- typically can function normally
Classification of leukemia based on type of affected WBC:
- Lymphocytic leukemia
- affects lymphoid cells (lymphocytes)
- lymphocytes are part of immune system
- Myelogenous leukemia
- affects the myeloid cells
- myeloid cells give rise to RBCs, WBCs, platelets
The major types of leukemia are:
- Acute lymphocytic leukemia (ALL):
- most common type of leukemia in young children
- Acute myelogenous leukemia (AML)
- occurs in children and adults
- most common type of acute leukemia in adults
- Chronic lymphocytic leukemia (CLL)
- most common chronic adult leukemia
- patient may feel well for years without treatment
- Chronic myelogenous leukemia (CML)
- mainly affects adults
- patient may have no symptoms for years
What are the signs & symptoms of leukemia?
- Symptoms depends on the type of leukemia
- Common signs and symptoms include:
- fever or chills, ↑sweating especially at night
- persistent fatigue, weakness
- losing weight without trying
- swollen lymph nodes, enlarged liver or spleen
- frequent or severe infections
- easy bleeding or bruising
- recurrent nosebleeds
- petechiae (red spots in skin) * bone pain or tenderness
What is Thrombocytopenia?
Low blood platelet count (<150,000 per microliter blood)
What are the major causes of thrombocytopenia?
A) Trappingofplateletsinspleen:
- Enlarged spleen harbor platelets → ↓blood platelets
B) Decreased platelet production
- leukemia, other cancers
- some types of anemia (e.g. folic acid deficiency)
- viral infections (e.g. hepatitis C, HIV)
- chemotherapy, radiation therapy
- heavy alcohol consumption
C) Increased destruction of platelets
* pregnancy: usually mild and improves after childbirth
* immune related: autoimmune disease (e.g. lupus,
rheumatoid arthritis)
* bacteremia (bacteria in blood)
* thrombotic thrombocytopenic purpura (small blood clots form throughout body so platelets are used)
* hemolytic uremic syndrome (↓platelets, ↓RBC, impaired kidney function)
* medications (e.g. heparin)
