Haematopoiesis Flashcards
___________ is the development of all blood cells.
Haematopoiesis
Mature blood cells have a limited lifespan, and only ____________ are capable of renewing themselves.
Lymphocytes
Replacement of peripheral haematopoietic cells is a function of the ___________ __________ cells (HSCs) found in the bone marrow.
Haematopoietic stem
Haematopoietic stem cells are capable of _____-__________, and differentiation into all blood cell lines.
Self-renewal
Committed _________ stem cells are destined to develop into distinct cell lines.
Progenitor
Committed lymphoid stem cells will be involved in _________, producing lymphocytes.
Lymphopoiesis
Differentiation is determined by various growth factors, or ___________, such as erythropoietin’s ability to stimulate the production of red blood cells.
Cytokines
True or false: differentiation and maturation of the stem cells into the functional cellular elements is the initial step of blood cell formation.
True
Proliferation, differentiation, and maturation of haematopoietic cells occurs in the ________ __________ and the widespread lymphatic system.
Bone marrow
Only erythrocytes are made in the ____ ____ of the embryo.
Yolk sac
Aorta-gonads-mesonephros (AGM) is located along the developing _________.
Aorta
When the bone marrow becomes the chief site of haematopoiesis, leucocyte and _____________ production become more prevalent.
Thrombocyte
Haematopoiesis in the bone marrow is called ___________ haematopoiesis.
Medullary
Haematopoiesis in areas other then the _______ __________is called extramedullary haematopoiesis.
Bone marrow
______________ __________ can lead to hepatomegaly and/or splenomegaly (increase in size of the liver or spleen).
Extramedullary haematopoiesis
Haematopoietically active tissue is found in the _______ marrow.
Red
Inactive, fatty marrow is the ______ marrow.
Yellow
In certain pathologic states, the bone marrow can increase its activity to 5-___ times its normal rate.
10
When activity is increased, bone marrow is said to be hyperplastic/__________, because it replaces the yellow marrow with red marrow.
Hypercellular
List two pathological states with which increase bone marrow activity is associated.
Excess bleeding, and malignant disease
Haematopoietic tissue may also become inactive or _________ (hypocellular), due to chemicals, genetics, etc..
Hypoplastic
Myeloproliferative disease (MPD), that replaces haematopoietic tissue with __________ tissue.
Fibrous
List three functions of the spleen.
Extramedullary haematopoiesis, pitting of RBC, and immune response
The ___________ ___________ ________ (also called the reticular endothelial system or RES) is involved in cellular destruction.
Mononuclear phagocytic system
______________ is the development of WBC, or leucocytes.
Leucopoiesis
List the stages of granulocytopoiesis.
HSC
Progenitor cell
Myeloblast (18-20µm)
Promyelocyte (22-25µm)
Myelocyte (18-20µm)
Metamyelocyte (14-20µm)
Band neutrophil
Neutrophil (segmented neutrophil; polymorphonuclear (PMN) cell) (12-15µm)
List the stages of thrombopoiesis.
HSC
Progenitor cells
Megakaryocyte
Platelets are released by fragmentation of the cytoplasm Thrombopoietin (TPO) stimulates the production of platelets
Megakaryocytes have a highly _________ DNA content.
Polyploid
The reference range for ____________ for a male is 4.5-5.9x1012/L, and for a female is 3.8-5.2x1012/L.
Erythrocytes
What are the two components of an erythrocyte?
Cytoplasm and plasma membrane
______________ are dedicated to respiratory gas transport.
Erythrocytes
Erythroblastic islands, and central macrophages, surrounded by developing erythroblasts, are found scattered throughout the bone marrow, close to marrow ________.
Sinuses
Outline the steps of erythropoiesis.
Haematopoietic stem cells (HSC)
Committed erythroid progenitor cell (CMP)
Differentiates to burst-forming unit-erythroid (BFU-E)
Differentiates to colony-forming unit-erythroid (CFU-E)
Proerythroblast (EPO stimulation transforms CFU-E to proerythroblast)
Basophilic erythroblast
Polychromatic erythroblast
Orthochromatic erythroblast
Erythroblasts mature to reticulocyte stage in marrow (5-7 days)
Reticulocytes are released into peripheral blood where they circulate for one to two days before becoming mature red blood cells
What are the three phases of the erythrocyte development pathway?
Ribosome synthesis in early erythroblasts
[Hb] accumulation in late erythroblasts
Ejection of the nucleus from erythroblasts and formation of reticulocytes
True or false: reticulocytes have a nucleus.
False
Polychromatic erythrocytes may also be called ____________.
Reticulocytes
Too few RBC leads to tissue ________.
Hypoxia
Too many RBC causes undesirable blood ___________.
Viscosity
Erythropoiesis is hormonally controlled, and depends on adequate supplies of _______, amino acids, and B vitamins.
Iron
Erythropoietin (EPO) secretion by the _________ is triggered by hypoxia due to decreased RBC or haemoglobin content.
Kidneys
Intracellular iron is stored in protein-iron complexes such as ferritin and ______________.
Haemosiderin
Circulating iron is loosely bound to the transport protein ___________.
Transferrin
Vitamin B12 or __________ deficiency will cause problems with nuclear maturation.
Folate
No mitochondria means no citric acid cycle can be undertaken, and there is only __________ ATP production in erythrocytes.
Anaerobic
The life span of an erythrocyte is ______ - ______ days.
100-120
Dying RBC are engulfed by macrophages of the mononuclear phagocytic system in ___________ haemolysis.
Extravascular
Haem and globin are separated and the ______ is salvaged for reuse in intravascular haemolysis.
Iron
_______________ consists of four haem groups, and four polypeptide chains (globins; two alpha, two beta).
Haemoglobin
Haem is a ring of carbon, hydrogen, and nitrogen atoms (______________ ring), with an attached iron atom, positioned in a poly peptide chain, close to the surface of the [Hb] molecule. Each haem combines reversibly with oxygen molecules.
Protoporphyrin
Globins are two pairs of polypeptide chains, typically consisting of 141-____ amino acids each.
146
List the globin chain types.
α, β, y, and Δ chains, as well as paediatric Ɛ (epsilon) and ζ (zeta).
How many oxygen molecules can a haemaglobin molecule carry?
Four
Outline the synthesis of haemoglobin.
Synthesis begins in the proerythroblast. 65% is produced during erythroblast stage; 35% is at reticulocyte stage. Haem is produced in the mitochondria. Porphyrins are tetrapyrroles (four pyrrole rings). The main site contains ALAS. Globin is produced in polyribosomes. In the nucleus, transcription of DNA to mRNA occurs. tRNA is translated to globin polypeptide chains on the ribosomes, then proceeds to be released from the ribosomes to the cytoplasm of the cell. The genes encoding globin chains are α, ζ, y, β, and Ɛ. There is one copy of each globin gene per chromatid, meaning that per person, two of each globin gene are found (excepting a and gamma). Eight functional globin chains exist, arranged in two clusters. b-cluster (β, Δ, e, and y genes) on the short arm of Chromosome 11. a-cluster, located on the short arm of chromosome 16, contains α and ζ genes). Globin synthesis starts at the third week of gestation. Embryonic [Hb] includes Gower I and II, and Portland. Foetal [Hb]F outstrips [Hb]A. Haemoglobin F, made of α2y2, is found in the foetus.
In adults, [Hb]A, [Hb]A2, and [Hb]F are present; [Hb]A makes up the moiety
In adults, an alpha and a non-alpha chain of haemoglobin combine to form a ____________.
Heterodimer
Two heterodimers spontaneously combine to form ____________.
Tetramers
For females, reference range for haemoglobin is 120-___g/L.
160
For males, the haemoglobin reference range is ____-174g/L.
140
98.5% of oxygen is _________ (oxyhaemoglobin), and 1.5% is in plasma.
HgbO2
What is the primary function of haemoglobin?
Carriage of oxygen from the lungs to the tissues
Less importantly, the carriage of CO2 from the tissues to the lungs is another role of [___], but only 13% of CO2 is bound to it.
Hb
Reaction of [Hb] and oxygen is ________________.
Oxygenation
When oxygenated, 2,3-BPG (bisphosphoglycerate) (also known as 2,3-DPG (diphosphoglycerate)) is __________.
Expelled
________ chains are pulled apart when oxygen is unloaded, permitting entry of 2,3-BPG, resulting in lower affinity of O2.
Beta
___________ is [Hb] bound to oxygen.
Oxyhaemoglobin
____________ is [Hb], after oxygen diffuses into tissues (reduced [Hb]).
Deoxyhaemoglobin
Carbaminohaemoglobin occurs when [Hb] is bound to carbon dioxide; it binds to globin’s ___________ _______.
Amino acids
Carbon dioxide loading takes place in the ___________.
Tissues
What is haemoglobin’s P50?
26.6 mmHg
Left shifts indicate ___________ oxygen affinity.
Increased
________ shifts show decreased oxygen affinity.
Right
List the factors that affect the normal shape of the curve.
Concentration of 2,3-DPG (2,3-BPG)
H+ ion concentration (pH)
CO2 in red blood cells
Structure of [Hb]
What is required for a right shift of the curve?
High 2,3-DPG
High H+
High CO2
[Hb]S
Low 2,3-DPG and [Hb]F are associated with ________ shifts.
Left
True or false: haemoglobin can be altered by drugs and chemicals.
True
______________ is iron in the ferric (Fe+++) state (incapable of binding with oxygen) .
Methaemoglobin
Sulfhaemoglobin arises from irreversible oxidation of haemoglobin, and when a __________ atom combines with haem group.
Sulfur
________________ cannot transport O2, as the haemoglobin has greater affinity for carbon dioxide.
Carboxyhaemoglobin
List two fates of haemoglobin.
Extravascular haemolysis, involving macrophages in the spleen (or the liver and bone marrow, to a lesser extent), and intravascular haemolysis, which involves the disassociation of haemoglobin into αβ dimers
Porphyrin is degraded to a green pigment, ___________.
Biliverdin
Biliverdin is converted to a ___________ pigment called bilirubin.
Yellow
The _____________ metabolise bilirubin into urobilinogen and stercobilinogen.
Intestines
____________ are metabolised into amino acids, and released into the circulation.
Globins
Outline the process of intravascular haemolysis.
Dimers are bound to haptoglobin, then carried to liver (too large to be excreted by kidneys, and processed. Haptoglobin levels may decrease in acute haemolytic states. When haptoglobin is depleted, free αβ dimers may be filtered by kidneys. Dimers that are reabsorbed are catabolised to bilirubin and iron enter plasma pool. Some iron remains in tubular cells, and it complexes with ferritin and haemosiderin. Tubular cells loaded with iron are sloughed off and excreted in urine, and may be detected as haemosiderinuria
