RBC AND DISORDERS 1 Flashcards
Factors for normal erythrocyte survival and function
- RBC membrane
- Hemoglobin Structure
- Metabolic pathways
Red Cell Membrane Structure
Membrane : Trilaminar structure (dark-light-dark band arrangement of layers)
- Outer hydrophilic portion
- glycolipid, glycoprotein & protein - Central hydrophobic portion
- protein, cholesterol and phospholipid - Inner hydrophilic portion
- protein
Principal structural element of RBC membrane; plays a major role in the RBC
cytoskeletal membrane organization (membrane integrity)
Spectrin
Primary determinant of primary mechanical coupling of the lipid bilayer to the membrane skeleton (membrane integrity)
Ankyrin
Promotes the association of spectrin with F-actin in a manner similar to band 4.1
Adducin
Dual function:
1. Promotes high affinity association between spectrin and F actin
2. Link the skeleton to the membrane by virtue of its associations with glycophorin
and band 3
Band 4.1
Catalyzes chloride-bicarbinate exchange; contains binding sites for ankyrin, band 4.1,
band 4.2 and several glycolytic enzymes; play a role in recognition and removal of
normal senescent RBCs
Band 3
Unknown function; deficiency is associated with several hemolytic anemias
Band 4.2
Transport negatively charged sialic acid
Glycoporins
Enzyme that converts protophorphyrin IX and Iron in ferrous form to Heme
Ferrochelatase
• Occurs in the cytoplasm of the normoblast and reticulocyte
- Polypeptide chains are manufactured in the ribosomes
- Made through transcription of the genetic code to messenger RNA and
translation of mRNA to the globin polypeptide chain
Globin Synthesis
Six structural genes control the synthesis of globin chains:
- Chromosome 16 : α, ζ
- Chromosome 11 : γ, β, δ, ε
Synthesis is stimulated by tissue hypoxia (decreased Oxygen)
Hemoglobin
Hemoglobin Reference
- Men
- Women
- Newborn
Men: 14-18 g/dL
Women: 12-15g/dL
Newborn: 16.5 - 21.5 g/dL
– glycoprotein that stimulates proliferation and differentiation of erythrocytes
– produced primarily in the kidney; also liver
– responds to hypoxia
Erythropoietin (EPO)
Rate Key rate limiting enzyme of Heme
α-Aminolevulinate synthase (ALAS)
+ Production is regulated by the rate at which DNA is transcribed tomRNA
+ Amount of the specific globin synthesized = to the content of their individual globin mRNAS
- α-Chain contains 141 amino acids
- β-Chain contains 146 amino acids
globin
Functions:
1. Binds oxygen readily in the lung and transport it to the peripheral tissues.
– 1 Hemoglobin molecule carry up to 4 Oxygen molecule
– 1.34 ml O2 is bound to each gram of Hemoglobin
– Red cell mass of adult contain approximately 600 grams of hemoglobin, capable of carrying 800 ml of O2
2. Transport of carbon dioxide from the peripheral tissues to the lung for excretion.
Hb
Embden-Meyerhof Pathway
Anaerobic Glycolysis
- Hexose monophosphate shunt
- Methemoglobin Reductase Pathway
- Rapaport-Leubering Pathway
Glycolysis Diversion Pathways (Shunts)
- Reduction of oxidized form of glutathione and detoxifies accumulated peroxide
- Methemoglobin reducing capacity within the red cell
- Generates 2,3 Biphophoglycerate/ 2,3 diphosphoglycerate which regulates oxygen
release
- Hexose Monophosphate shunt/Pentose Phospate Pathway
- Methemoglobin Reductase pathway
- Rapoport Leubering Pathway
QUALITATIVE ERYTHROCYTES DISORDERS Parameters:
- Degree of Hemoglobinization – Hypochromia
- Anisocytosis
- Polychromasia
- Poikilocytosis
- Red Blood Cell Inclusions
- Red Blood Cell Indices
- “low color”. When an RBC contains a control area which is greater than 1/3 (>3 um) the diameter of the cell.
- decreased surface-to-volume ratio; decreased or absent central pallor
- Hypochromia
- Hyperchromia
- Measures red cell immaturity
- Correlates with reticulocyte count (%)
Polychromasia
Normal red cell immaturity: RBC/10hpf and %Retic Normal: Slight: Moderate: Marked:
RBC/10hpf Normal: 0-1 Slight: 1-3 Moderate: 4-6 Marked: >6
%Retic Normal: 1-2% Slight: 2-4% Moderate: 4-6 % Marked: >6%
Type fo Poikilocyte:
- 3-12 pointed projections ofvarious lengthand irregular spacing
- intensely stained
- Spur cells, thorn cells
Acanthocyte
Type fo Poikilocyte:
- Contains one or more vacuoles that resembles a blister on the skin
- Seen in Microangiopathic Hemolytic Anemias
Blister Cell
Type of Piokilocytes:
- 10-30 pointed RBC projections evenly distributedaround the cell
- Burr Crenated cells
- Seen in Uremias, Enzyme deficiencies, Post -splenectomy patients
Echinocytes
Type of Poikilocytes
- Narrow & elongated, resembling rod or cigar. Pencil cell. seen in Hereditery Elliptocytosis
- Oval or egg - like in appearance
- Elliptocyte
- Ovalocytes
Type of Poikilocytes
- Fragment in which the volume is close to normal
- Helmet cell, horned cell
- Seen in G6PD deficiency and Pulmonary emboli
Keratocyte
Type of Poikilocytes
- Narrow band of cell hemoglobin acrossthe center of the cell
- pinch bottle cell
Knizocyte
Type of Poikilocytes
- Fragment in which the volume is reduced
- Schizocyte
- Seen in Microangiopathic Hemolytic Anemias(DIC, TTP, HUS) Severe Burns, Prosthetic Valves and Clostridial Infection
Schistocyte
Type of Poikilocytes
- Crescent-shaped with at least one end that is pointed
- Drepanocyte
- Seen in Sickle Cell Anemia and Hemoglobin C
Sickle cell
Type of Poikilocytes
- Any cell with projections
- Seen in post-Splenectomy patients, Uremias and Myelofibrosis
Spiculated RBC
Type of Poikilocytes
- Compact and round; has lost its area of central pallor; stains intensely
- Seen in Hereditary Spherocytosis , Hemolytic Anemias and post-transfusion
Spherocyte
Type of Poikilocytes
- central slit-like opening resembling na mouth
Stomatocyte
Type of Poikilocytes
- Contains a central bull’s eye surrounded by a clean ring and then outer red ring
- Codocyte
- Seen in Thalassemia, Liver Disease, Hb SC Disease, Hemoglobin C and Lecithin cholesterol acyltransferase (LCAT) deficiency, Iron Deficiency Anemia and Post-splenectomy patients
Target cell
Type of Poikilocytes
- Resembles a tear has one elongated end
- Dacrocyte
- Seen in Myelofibrosis
Teardrop cell
Type of Erythrocyte Inclusion
- single, occasionally, double, rarely multiple red purple coccoid bodies
- DNA, nuclear or chromosomal remnant composition
- Seen in Megaloblastic Anemia and Hyposplenism
Howell-Jolly
Type of Erythrocyte Inclusion
- Non - heme Iron
- Clusters of small blue coccoid bodiesl ocated at the periphery of the cell
- Seen in Sideroblastic Anemia and Hemolytic Anemias
Pappenheimer
Type of Erythrocyte Inclusion
- multiple, uniform dark, dots distributed evenly throughout the cell
- Altered RNA
- Seen in Lead and Heavy Metal Poisoning, After treatment for Iron deficiency and
Megaloblastic Anemias
Basophilic Stippling
Type of Erythrocyte Inclusion
- Mitotic spindle remnant
- Red-purple ring at the periphery periphery of the cell; may be in the term of a figure 8
- Seen in Hyposplenism and Anemias
Cabot ring
Type of Erythrocyte Inclusion
- Invisible Denatured/ Body
- Green when stained with brilliant green
- Denatured/Precipitated hemoglobin
- Seen In G6PD Deficiency and other Hemolytic Anemias
Heinz-Erlich Body
Formula for Mean corpuscular volume (MCV) f1
Hematocrit x 10
_______________
RBC
Formula for Mean cell Hemoglobin (MCH) pg
Hemoglobin x 10
_________________
RBC
Formula for Mean Corpuscular Hemoglobin Concentration (MCHC) mg/dl
Hb x 100
________
Hct
– Measures the degree of anisocytosis
– Coefficient of variation of red blood cell volume
– obtained from histogram
– normally: 11.5-14.5
Red cell distribution Width (RWD)
- Pseudoagglutination doe to the tendency of RBCs to lie with an overlapping edges “Pile of coins”
- Seen in patients with hyperproteinemias – Multiple Myeloma, Waldenstrom Macroglobulinemias
Rouleaux Formation
Irregular red cell aggregates
Hemagglutination
