Heme Unit 2 Flashcards
What is Colony Stimulating Factors?
Cytokines that are produced by the stromal cells to stimulate the development of blood cells.
What is cell commitment?
Hematopoietic precursor cell genetically commits to differentiate into a certain cell type.
What is maturation?
The actual stages of development. **Expression of commitment and differentiation.
Types of hematopoietic stem cells
Pluripotent
Multipotent
What is differentiation?
The process of generating several different cell lines.
**Allow expression of certain genes while restricting others.
Where does hematopoiesis occur in the bone marrow?
Medulla
Functions of the spleen include:
*Culling
*Pitting
*Reservoir for platelets and RBCs
(2nd lymphoid organ)
Where does antigen dependent lymphopoiesis occur?
*Spleen
*Lymph nodes
(actually perform their roles)
Where does antigen independent lymphopoiesis occur?
*Bone marrow
*Thymus
(learn to function)
Bones that remain hematopoietically active?
End of long bones
Pelvis, iliac crest
Skull
Sternum
Scapula
Vertebrae
Clavicles
What is the role of fibroblasts in hematopoietic microenvirnment?
They produce a support network of collagen for developing cells.
(extracellular matrix)
What is the role of adipocytes in hematopoietic microenvironment?
They produce fatty yellow bone marrow.
What is the role of macrophaphes in hematopoietic microenvironment?
They produce cytokines to stimulate cell development
What are the 3 main stromal cells?
- Macrophage
- Adipocytes
- Fibroblasts
What are the secondary lymphoid tissues?
Spleen
Lymph nodes
What are the primary lymphoid tissues?
Bone Marrow
Thymus
In utero, when does hematopoiesis shift to the bone marrow?
6 month gestation
When does the liver become the chief hematopoietic ogran for the embryo?
3 month gestation
How many days gestation does hematopoiesis begin?
18 days
How many RBCs do we produce each day?
2 x 10^11
What is tissue homeostasis?
The balance maintained between cellular proliferation, differentiation, and apoptosis.
Multipotent Hematopoietic Stem cells can go which 2 paths?
Differentiate into myeloid or lymphoid stem cells OR
Self-renew
What cells are highly mitotic cells?
Progenitor cells
Progenitor cells are also called?
CFU: colony forming units
BFU: burst forming units
Progenitor cells lose what capibility?
Self renewal
What do progenitor cells become with each division?
progressively committed
What do Precursor cells lose the capability to do?
Divide
**except lymphocytes
What are Erythroblasts also known as?
Nucleated RBCs
Normoblasts
Reticulocytes are also known as?
Polychromatophilic RBCs
What is the sequence of the RBC maturation?
- Rubriblast
- Prorubricyte
- Rubricyte
- Metarubricyte
- Reticulocytes
- Erythrocyte
How long do Normoblasts (nucleated RBCs) take to mature in the bone marrow?
5-7 days
How long do Reticulocytes mature in the bone marrow?
2-3 days
Hypoxia stimulates the production of what by specialized kidney cells?
Erythropoietin (EPO)
Difference between EPO and CSF?
CSF are produced by stromal cells and are responsible for the proliferation of precursor cells.
EPO only stimulates development of RBC precursors
Hormones other than EPO that can have an effect on hematopoiesis
Adrenal cortical hormones: Androgens, Aldosterone, and Cortisol
Thyroid hormone
Growth hormone
What is the earliest recognizable RBC precursor?
Rubriblast
What is Rubriblast also known as?
Pronormoblast
What is Prorubricyte also known as?
Basophilic Normoblast
What is the cracked appearance of the nucleus in Prorubricyte and Rubricyte called?
Parachromatin clearing
What is the last stage capable of undergoing mitosis in RBC maturation?
Rubricyte
What is Metarubricyte also known as?
Orthochromic Normoblast
What is the last stage of RBC maturation with a nucleus?
Metarubricyte
The last 20% of Hgb is made in what stage of RBC maturation?
Reticulocyte
Normal % of reticulocytes in peripheral blood?
0.5-2.5% of all circulating RBCs
What stain is needed to ID Reticulocytes?
Supravital Stain
If using Wright Stain what are reticulocytes called?
Polychromatophilic erythrocytes
What is the purpose of Supravital stain?
Makes the residual RNA visible
(New Methylene Blue used)
What are the functions of the Erythrocyte membrane?
Oxygen transport
Durability/strength
Balance ion and water concentration
Flexibility to fit through small vessels
What is responsible for the Zeta Potential of RBCs
Integral Proteins in the erythrocyte membrane
What do the peripheral proteins in RBCs do?
Form the cytoskeleton
Provide flexible, fluid structure
How do RBCs produce ATP?
Anaerobic glycolysis
What is the purpose of Pyruvate Kinase in RBC ATP production?
Turns sugar into ATP
A deficiency in Pyruvate Kinase can cause?
hypoglycemic erythrocytes
What is the purpose of glutathione in RBC metabolism?
Becomes oxidized instead of Hgb
What does the Hexose Monophosphate Shunt do?
Protects hgb from being chemically oxidized
Rubriblast
Prorubricyte
Rubricyte
Metarubricyte
Reticulocyte
If using a wright stain, what is a reticulocyte called?
Polychromatophilic erythrocyte
Glutathione is oxidized instead of Hgb in what pathway?
Hexose Monophosphate Shunt
Important enzyme in HMP
G6PD
Glucose-6-phosphate dehydrogenase
What pathway returns methemoglobin to a reduced state?
Methemoglobin reductase pathway
What does the methemoglobin reductase pathway ensure?
That Hgb can bind and transport oxygen
What does a methemoglobin reductase deficiency cause?
Decreased oxygen carrying
hypoxia results in cyanosis
What forms 2,3 BPG
Rapoport-Leubering Shunt
What does the Rapoport-Leubering Shunt regulate?
Oxygen affinity by releasing the oxygen off heme
An important enzyme in Rapoport-Leubering Shunt
BPG-Synthetase
What is the porphyrin ring in heme called?
protporphyrin IX
What is deoxygemoglobin
Iron ions in the ferrous state
What is oxyhemoglobin
Iron ions in the ferric state
The predominant form of Hgb in adults
Hemoglobin A
2 alpha
2 beta
Predominent form of Hbg in the fetus and newborns
Hemoglobin f
2 alpha
2 gamma
How is Hgb F different from Hgb A?
the gamma chain is a beta chain with a SERINE in place of Histidine at the 143rd position
What does the serine interference in the gamma chain do?
Interferes with 2,3 BPG allowing Hgb F to have a higher affinity for Oxygen
Normal adult Hbg composition
> 95% Hbg A
1-4% Hbg A2
<2% Hgb F
What Hgb is associated with Sickle Cell Anemia
Hgb S
What Hgb state can’t bind to oxygen?
Methemoglobin
Fe in ferric state
What is carboxyhemoglobin
Hbg has a higher affinity for CO than oxygen
What are culled RBC degraded by?
macrophages
After iron is extracted from heme, what does it further break down to?
unconjugated bilirubin
What binds to Hgb to render it non toxic?
Haptoglobin
What is the definition of anemia?
A decrease in oxygen carrying capacity of blood
What is elevated in Anemia that increases oxygen utilization?
2,3 BPG
MCV at birth
108fL
macrocytic
MCV 6 months-2 years
77fL
microcytic
MCV 18+ years
90fL
normocytic
What is indicated by an elevated RDW?
Anisocytosis
Anisocytosis
-variation in RBC size
Polychromatic RBC
What are acanthocytes also known as?
Spur or thorn cells
Clinical Conditions of acanthocytes
Liver disease
Lipid metabolism disorders
fat malabsorption
increased membrane cholesterol
acanthocytes
What are schistocytes also known as?
Fragmented RBCs
“crap cells”
Clinical conditions of Schistocytes
Microangiopathic hemolytic anemia (MAHA)
Uremia
HDN
DIC
What is a subcategory of Schistocytes?
Keratocytes
aka Helmet cells
What are drepanocytes also known as?
Sickle Cells
Clinical conditions of Drepanocytes
Sickle cell anemia
Hgb SC disease
Drepanocyte
Clinical conditions of Spherocytes
Hereditary spherocytosis
PK deficiency
Severe burns
Immune mediated hemolysis
Spherocyte
What are dacrocytes also known as?
Teardrop cells
Clinical conditions of dacrocytes
Sign of extramedullary hematopoesis
Myelophthisic anemia
Dacrocyte
What are Echinocytes also known as?
Burr cells
Crenated cells
Clinical conditions for echinocytes
Uremia
liver disease
stomach cancer
Echinocyte
What are ovalocytes also know as?
elliptocytes
Clinical conditions of ovalocytes
Hereditary ovalocytosis
Misc anemia
-Thalassemia
-iron deficiency
-sickle cell anemia
Ovalocyte
What are stomatocyte also known as?
Mouth cells
Clinical conditions of stomatocytes
Abnormal membrane ion exchange
Hereditary stomatocytosis
Liver disease
Lead poisoning
Stomatocyte
What are codocytes also known as?
Target cells
Clinical conditions for codocytes
Thalassemia
Liver disease
Misc anemias
codocyte
Clinical conditions that cause Basophilic Stippling
Lead poisoning
Thalassemia
Sideroblastic anemia
Misc anemias
Basophilic Stippling
What is Basophilic Stippling composed of?
Aggregated rRNA
Clinical conditions that cause Howell-Jolly Bodies
Post-splenectomy
Hemolytic anemia
Megaloblastic anemia
What are Howell-Jolly Bodies composed of?
Residual nuclear DNA
Howell-Jolly Bodies
Clinical conditions that cause Pappenheimer Bodies
Post-splenectomy
Sideroblastic anemia
Megaloblastic anemia
Hemoglobinopathies
Pappenheimer bodies are composed of?
Aggregated Fe
Pappenheimer Bodies
Clinical conditions that cause Heinz Bodies
G6PD deficiency
Hemoglobinopathies
Heinze Bodies are composed of?
Precipitated Hgb
Heinz bodies
What are the 4 types of Microcytic Anemia?
- Sideroblastic
- Iron deficiency
- Anemia of Chronic Disease
- Thalassemia
Microcytic anemias that have abnormal iron metabolism?
Sideroblastic
Iron deficiency
Anemia of Chronic disease
Microcytic anemia that has abnormal globin production?
Thalassemia
Lab results for Iron Deficiency Anemia
Decreased Ferritin
Increased Transferrin
Increased TIBC
Decreased serum iron
Elevated RDW
What is Pica
Craving Non food
Causes of Sideroblastic Anemia
Hereditary: enzyme deficiency
Toxins
Myelodysplastic syndrome
What anemia has partial/abnormal heme synthesis?
Sideroblastic
Sideroblastic Anemia
What can help us differentiate between Iron deficiency anemia and Thalassemia?
RDW
RDW is elevated in Iron Deficiency
RDW is normal in Thalassemia
What anemia is from ineffective erythropoiesis due to poor globin synthesis?
Thalassemia
What anemia causes BM hyperplasia?
Thalassemia
What does BM hyperplasia cause?
Bone deformitites
What happens bc of Thalassemia’s abnormal RBCs?
Excessive extravascular hemolysis
-Jaundice
Leads to gallstones
Spleen Overload
What happens from transfusion dependency?
Development of hemochromatosis
What is hemochromatosis?
Iron overload which leads to iron toxicity
Inclusions that are seen in Thalassemia?
Howell Jolly Bodies
Basophilic stippling
Alpha Thalassemia affects?
The quantity of production of alpha globin chains
What Thalassemia is asymptomatic?
(-a/aa)
Single deletion
What Thalassemia causes mild anemia?
(–/aa)
Double deletion
What Thalassemia causes Hgb H disease?
(–/-a)
Triple deletion
What Thalassemia causes development of hydrops fetalis?
(–/–)
Quadruple deletion
What Thalassemia is from a genetic mutation?
Beta Thalassemia
What is Beta + Thalassemia
A partial block in Beta chain synthesis
What is Beta 0 Thalassemia
A complete absence of Beta Chain synthesis
What does the reduction of Beta chain synthesis affect?
Production of Hgb A
What are the 3 stages of Iron Deficiency Anemia development?
- Iron depletion
- Iron deficient erythropoiesis
- Iron deficiency anemia
The 3 types of Megaloblastic anemia?
- B12 deficiency
- Folate deficiency
- Hematologic neoplasms
Non-megaloblastic anemia is from?
Chronic liver disease
What is a megaloblast?
A large, abnormal nRBC
Inclusions seen in Megaloblastic anemia
Pappenheimer bodies
Howell Jolly Bodies
What is seen in only megaloblastic anemia patients?
Hypersegmented neutrophils
Folate deficiency can cause?
Decreased hematopoiesis
Increased apoptosis
Megaloblastic maturation
Birth defects
Neurological problems from B12 deficiency
Psychotic symptoms
Motor and sensory abnormalities
Defective Fatty Acid degradation (affects myelin sheath)
What is Intrinsic factor deficiency known as
Pernicious anemia
What produces intrinsic factor
Gastric parietal cells
what is intrinsic factor necessary for?
Absorption of B12
Types of Normocytic Anemia
Hypoproliferative anemia
Hemolytic anemia
What can cause Hypoproliferative anemia
Bone marrow disorders
Chronic renal disease
What are the types of Hypoproliferative anemias
Aplastic
Myelophthisic
Aplastic anemia is caused by?
bone marrow failure
What lab finding is seen in aplastic anemia
Pancytopenia
Myelophthisis is caused by
Bone marrow being infiltrated by malignant cells
What are the membrane abnormalities seen in hemolytic anemia?
- Hereditary spherocytosis
- Hereditary acanthocystosis
- Hereditary stomatocytosis
- Hereditary ovalocytosis
- Hereditary pyropoikilocytosis
- Paroxysmal nocturnal hemoglobinuria (PNH)
How does hereditary spherocytosis cause anemia?
From excessive extravascular hemolysis
What hemolytic anemia is caused by liver disease and the lipid problems from that?
Hereditary acanthocytosis
Hereditary stomatocytosis is from what abnormality?
Membrane ion exchange
Abnormal structural proteins causes what hemolytic anemia?
Hereditary ovalocytosis
What hemolytic anemia is sensitive to heat
Hereditary pyropoikilocytosis
Complications of PNH
Development of Fe or folate deficiency anemia
Thrombosis
Renal disease
What membrane abnormality is aqcuired
PNH
What hemolytic anemia occurs mostly at night?
PNH
What two enzyme deficiencies result in hemolysis
G6PD
Pyruvate kinase
What happens in G6PD deficiency
Oxidized heme accumulates
Poor Oxygen carrying capability
Heinz bodies cause membrane damage
What is kernicterus
Brain damage from extreme buildup of bilirubin in the brain
What enzyme deficiency can cause kernicterus
G6PD
What enzyme deficiency causes decreased haptoglobin
G6PD
Pyruvate deficiency causes what
Ion pumps being impaired
Cellular dehydration
Increased 2,3 BPG production
An increased 2,3 BPG does what to Oxygen
increases the dissociation from Hgb
Qualitative hemoglobinopathy causes?
Sickle cell anemia
What is substituted on the Beta chain in Sickle Cell Anemia
Valine instead of glutamic acid at the 6th position
Sickle cell occurs because?
Deoxygenated hgb S allows polymerization of surrounding hgb S molecules
What anemia can cause bone pain (cortical thinning)?
Sickle cell
What is vaso-occlusive crisis
Sickle cells block blood flow and the tissues lack oxygen
What is substituted in Hgb C Disease?
Lysine for glutamic acid in the 6th position
Hgb C crystal
Types of Extrinsic Hemolytic Anemia
Antibody Mediated
Malaria
Chemical/Physical
Mechanical
Malaria is caused by?
Plasmodium falciparum
Malaria in the ring form
What is MAHA
Microangiopathic hemolytic anemia
Caused by destruction of RBC in small blood vessels when forced through fibrin strands
What is HUS
Hemolytic uremic syndrome
-bacterial toxins injure glomerular endothelial cells
What are the mechanical anemias
Maha
Hus
DIC
What is DIC
simultaneously clotting and hemorrhaging