Haematopoiesis

Question 1

___________ is the development of all blood cells.

Answer 1

Haematopoiesis

Question 2

Mature blood cells have a limited lifespan, and only ____________ are capable of renewing themselves.

Answer 2

Lymphocytes

Question 3

Replacement of peripheral haematopoietic cells is a function of the ___________ __________ cells (HSCs) found in the bone marrow.

Answer 3

Haematopoietic stem

Question 4

Haematopoietic stem cells are capable of _____-__________, and differentiation into all blood cell lines.

Answer 4

Self-renewal

Question 5

Committed _________ stem cells are destined to develop into distinct cell lines.

Answer 5

Progenitor

Question 6

Committed lymphoid stem cells will be involved in _________, producing lymphocytes.

Answer 6

Lymphopoiesis

Question 7

Differentiation is determined by various growth factors, or ___________, such as erythropoietin’s ability to stimulate the production of red blood cells.

Answer 7

Cytokines

Question 8

True or false: differentiation and maturation of the stem cells into the functional cellular elements is the initial step of blood cell formation.

Answer 8

True

Question 9

Proliferation, differentiation, and maturation of haematopoietic cells occurs in the ________ __________ and the widespread lymphatic system.

Answer 9

Bone marrow

Question 10

Only erythrocytes are made in the ____ ____ of the embryo.

Answer 10

Yolk sac

Question 11

Aorta-gonads-mesonephros (AGM) is located along the developing _________.

Answer 11

Aorta

Question 12

When the bone marrow becomes the chief site of haematopoiesis, leucocyte and _____________ production become more prevalent.

Answer 12

Thrombocyte

Question 13

Haematopoiesis in the bone marrow is called ___________ haematopoiesis.

Answer 13

Medullary

Question 14

Haematopoiesis in areas other then the _______ __________is called extramedullary haematopoiesis.

Answer 14

Bone marrow

Question 15

______________ __________ can lead to hepatomegaly and/or splenomegaly (increase in size of the liver or spleen).

Answer 15

Extramedullary haematopoiesis

Question 16

Haematopoietically active tissue is found in the _______ marrow.

Answer 16

Red

Question 17

Inactive, fatty marrow is the ______ marrow.

Answer 17

Yellow

Question 18

In certain pathologic states, the bone marrow can increase its activity to 5-___ times its normal rate.

Answer 18

10

Question 19

When activity is increased, bone marrow is said to be hyperplastic/__________, because it replaces the yellow marrow with red marrow.

Answer 19

Hypercellular

Question 20

List two pathological states with which increase bone marrow activity is associated.

Answer 20

Excess bleeding, and malignant disease

Question 21

Haematopoietic tissue may also become inactive or _________ (hypocellular), due to chemicals, genetics, etc..

Answer 21

Hypoplastic

Question 22

Myeloproliferative disease (MPD), that replaces haematopoietic tissue with __________ tissue.

Answer 22

Fibrous

Question 23

List three functions of the spleen.

Answer 23

Extramedullary haematopoiesis, pitting of RBC, and immune response

Question 24

The ___________ ___________ ________ (also called the reticular endothelial system or RES) is involved in cellular destruction.

Answer 24

Mononuclear phagocytic system

Question 25

______________ is the development of WBC, or leucocytes.

Answer 25

Leucopoiesis

Question 26

List the stages of granulocytopoiesis.

Answer 26

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)

Question 27

List the stages of thrombopoiesis.

Answer 27

HSC Progenitor cells Megakaryocyte Platelets are released by fragmentation of the cytoplasm Thrombopoietin (TPO) stimulates the production of platelets

Question 28

Megakaryocytes have a highly _________ DNA content.

Answer 28

Polyploid

Question 29

The reference range for ____________ for a male is 4.5-5.9x1012/L, and for a female is 3.8-5.2x1012/L.

Answer 29

Erythrocytes

Question 30

What are the two components of an erythrocyte?

Answer 30

Cytoplasm and plasma membrane

Question 31

______________ are dedicated to respiratory gas transport.

Answer 31

Erythrocytes

Question 32

Erythroblastic islands, and central macrophages, surrounded by developing erythroblasts, are found scattered throughout the bone marrow, close to marrow ________.

Answer 32

Sinuses

Question 33

Outline the steps of erythropoiesis.

Answer 33

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

Question 34

What are the three phases of the erythrocyte development pathway?

Answer 34

Ribosome synthesis in early erythroblasts [Hb] accumulation in late erythroblasts Ejection of the nucleus from erythroblasts and formation of reticulocytes

Question 35

True or false: reticulocytes have a nucleus.

Answer 35

False

Question 36

Polychromatic erythrocytes may also be called ____________.

Answer 36

Reticulocytes

Question 37

Too few RBC leads to tissue ________.

Answer 37

Hypoxia

Question 38

Too many RBC causes undesirable blood ___________.

Answer 38

Viscosity

Question 39

Erythropoiesis is hormonally controlled, and depends on adequate supplies of _______, amino acids, and B vitamins.

Answer 39

Iron

Question 40

Erythropoietin (EPO) secretion by the _________ is triggered by hypoxia due to decreased RBC or haemoglobin content.

Answer 40

Kidneys

Question 41

Intracellular iron is stored in protein-iron complexes such as ferritin and ______________.

Answer 41

Haemosiderin

Question 42

Circulating iron is loosely bound to the transport protein ___________.

Answer 42

Transferrin

Question 43

Vitamin B12 or __________ deficiency will cause problems with nuclear maturation.

Answer 43

Folate

Question 44

No mitochondria means no citric acid cycle can be undertaken, and there is only __________ ATP production in erythrocytes.

Answer 44

Anaerobic

Question 45

The life span of an erythrocyte is ______ - ______ days.

Answer 45

100-120

Question 46

Dying RBC are engulfed by macrophages of the mononuclear phagocytic system in ___________ haemolysis.

Answer 46

Extravascular

Question 47

Haem and globin are separated and the ______ is salvaged for reuse in intravascular haemolysis.

Answer 47

Iron

Question 48

_______________ consists of four haem groups, and four polypeptide chains (globins; two alpha, two beta).

Answer 48

Haemoglobin

Question 49

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.

Answer 49

Protoporphyrin

Question 50

Globins are two pairs of polypeptide chains, typically consisting of 141-____ amino acids each.

Answer 50

146

Question 51

List the globin chain types.

Answer 51

α, β, y, and Δ chains, as well as paediatric Ɛ (epsilon) and ζ (zeta).

Question 52

How many oxygen molecules can a haemaglobin molecule carry?

Answer 52

Four

Question 53

Outline the synthesis of haemoglobin.

Answer 53

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

Question 54

In adults, an alpha and a non-alpha chain of haemoglobin combine to form a ____________.

Answer 54

Heterodimer

Question 55

Two heterodimers spontaneously combine to form ____________.

Answer 55

Tetramers

Question 56

For females, reference range for haemoglobin is 120-___g/L.

Answer 56

160

Question 57

For males, the haemoglobin reference range is ____-174g/L.

Answer 57

140

Question 58

98.5% of oxygen is _________ (oxyhaemoglobin), and 1.5% is in plasma.

Answer 58

HgbO2

Question 59

What is the primary function of haemoglobin?

Answer 59

Carriage of oxygen from the lungs to the tissues

Question 60

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.

Answer 60

Hb

Question 61

Reaction of [Hb] and oxygen is ________________.

Answer 61

Oxygenation

Question 62

When oxygenated, 2,3-BPG (bisphosphoglycerate) (also known as 2,3-DPG (diphosphoglycerate)) is __________.

Answer 62

Expelled

Question 63

________ chains are pulled apart when oxygen is unloaded, permitting entry of 2,3-BPG, resulting in lower affinity of O2.

Answer 63

Beta

Question 64

___________ is [Hb] bound to oxygen.

Answer 64

Oxyhaemoglobin

Question 65

____________ is [Hb], after oxygen diffuses into tissues (reduced [Hb]).

Answer 65

Deoxyhaemoglobin

Question 66

Carbaminohaemoglobin occurs when [Hb] is bound to carbon dioxide; it binds to globin’s ___________ _______.

Answer 66

Amino acids

Question 67

Carbon dioxide loading takes place in the ___________.

Answer 67

Tissues

Question 68

What is haemoglobin's P50?

Answer 68

26.6 mmHg

Question 69

Left shifts indicate ___________ oxygen affinity.

Answer 69

Increased

Question 70

________ shifts show decreased oxygen affinity.

Answer 70

Right

Question 71

List the factors that affect the normal shape of the curve.

Answer 71

Concentration of 2,3-DPG (2,3-BPG) H+ ion concentration (pH) CO2 in red blood cells Structure of [Hb]

Question 72

What is required for a right shift of the curve?

Answer 72

High 2,3-DPG High H+ High CO2 [Hb]S

Question 73

Low 2,3-DPG and [Hb]F are associated with ________ shifts.

Answer 73

Left

Question 74

True or false: haemoglobin can be altered by drugs and chemicals.

Answer 74

True

Question 75

______________ is iron in the ferric (Fe+++) state (incapable of binding with oxygen) .

Answer 75

Methaemoglobin

Question 76

Sulfhaemoglobin arises from irreversible oxidation of haemoglobin, and when a __________ atom combines with haem group.

Answer 76

Sulfur

Question 77

________________ cannot transport O2, as the haemoglobin has greater affinity for carbon dioxide.

Answer 77

Carboxyhaemoglobin

Question 78

List two fates of haemoglobin.

Answer 78

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

Question 79

Porphyrin is degraded to a green pigment, ___________.

Answer 79

Biliverdin

Question 80

Biliverdin is converted to a ___________ pigment called bilirubin.

Answer 80

Yellow

Question 81

The _____________ metabolise bilirubin into urobilinogen and stercobilinogen.

Answer 81

Intestines

Question 82

____________ are metabolised into amino acids, and released into the circulation.

Answer 82

Globins

Question 83

Outline the process of intravascular haemolysis.

Answer 83

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