Anaemia and Bone Marrow Overview - Week 8

Anaemia

Condition characterized by insufficient red blood cells.

Erythropoietin (EPO)

Hormone controlling red blood cell production. Produced primarily in kidney by Type-1 fibroblastoid cells and partially in liver. Stimulates Erythropoiesis and reduces apoptosis.

Primary site for RBC production

Bone Marrow

Vitamin B12

Essential for red blood cell formation and DNA synthesis

Folate

Vitamin crucial for DNA synthesis in cells.

Haematocrit

Percentage of blood volume occupied by red cells.

Spherocytes

Abnormal red blood cells lacking a pale center.

Schistocytes

Fragmented red blood cells indicating damage.

Granulocytes

Type of white blood cells with granules.

Lymphocytes

White blood cells crucial for immune response.

Thrombocytes

Another term for platelets, involved in clotting.

Chronic Anaemia

Long-term condition with compensatory erythropoietin production.

MCV

Mean corpuscular volume, measures red cell size.

Microcytic: <80 fL, Normocytic: 80-100 fL, Macrocytic: >100 fL.

MCHC

Mean corpuscular hemoglobin concentration, measures hemoglobin per cell.

RDW

Red cell distribution width, indicates size variation.

Sickle Cells

Abnormal red blood cells in sickle cell anemia.

Target Cells

Red blood cells with a bull's-eye appearance.

Howell-Jolly Bodies

Nuclear remnants in red blood cells.

Bite Cells

Red blood cells with membrane loss.

Agranulocytes

Leukocytes without granules in cytoplasm.

B-cells

Lymphocytes that produce antibodies.

T-Cells

Lymphocytes that regulate immune responses.

Natural Killer Cells

Lymphocytes that attack infected or cancerous cells.

Haematopoietic Stem Cells

Stem cells that differentiate into blood cell types.

Common Myeloid Progenitor

Gives rise to various blood cell lineages.

Common Lymphoid Progenitor

Gives rise to lymphocytes and NK cells.

Erythrocytes

Red blood cells, derived from myeloid progenitors.

Megakaryocytes

Precursor cells that produce platelets.

Extramedullary Haematopoiesis

Blood cell production outside bone marrow.

Bone Marrow Stroma

Supportive tissue for blood cell development.

Erythropoiesis

Process of red blood cell development.

Duration of Haematopoiesis

Takes approximately 7 days for blood cell formation.

Increased Hb

More eosinophilic hemoglobin in erythrocytes.

Nuclear extrusion

Nucleus is expelled during erythroblast stage.

Organelle loss

Mitochondria are lost in erythrocyte maturation.

RBC cell size over time

Erythrocytes decrease in size during maturation.

Myeloid stem cell

Precursor cell for erythrocyte lineage.

Megakaryocyte-erythroid precursor

Common precursor for platelets and erythrocytes.

BFU-E

Burst-forming unit; develops EPO receptors.

CFU-E

Colony-forming unit; dependent on EPO.

Pro-erythroblast

Initial stage before erythroblast formation.

Erythroblast

Normoblast; stops dividing, nucleus extruded.

Erythrocyte destruction

Occurs mainly in the spleen.

RBC lifespan

Approximately 120 days before destruction.

Phagocytosis of RBC

Macrophages engulf old RBCs for breakdown.

Bilirubin

Product of heme breakdown, excreted.

Colony Stimulating Factors

Cytokines promoting blood cell production.

Iron requirements

Men need 8 mg, women 18 mg.

Iron Absorption Process

Involves heme dissociation and transporter HCP1.

Heme Iron

Iron from hemoglobin, absorbed in the duodenum.

Inorganic Iron Forms

Includes ferrous (Fe2+) and ferric (Fe3+) iron.

Ferrireductase Enzyme

Converts ferric iron to ferrous form in duodenum.

DMT1 Transporter

Transports ferrous iron into enterocytes.

Ferroportin

Transporter that releases iron from enterocytes.

Hepcidin Function

Regulates iron levels by degrading ferroportin.

Transferrin

Protein that transports ferric iron in plasma.

Iron Storage Forms

Stored as ferritin (soluble) or haemosiderin (insoluble).

Vitamin B12 Sources

Found in meat, liver, fish, and dairy.

Vitamin B12 Requirement

Minimum adult requirement is 2ug/day.

Intrinsic Factor

Protein necessary for B12 absorption in ileum.

Methionine Synthase

Enzyme requiring B12 for DNA synthesis pathway.

Methylmalonyl CoA Conversion

B12 converts it to succinyl CoA, a TCA intermediate.

Vitamin B12 Deficiency Causes

Includes vegan diet and malabsorptive conditions.

Folate Sources

Found in greens, liver, and yeast.

Folate Absorption

Occurs in duodenum and jejunum as 5-methyl THF.

Folate Function

Essential for purine DNA precursor synthesis.

Folate Deficiency Causes

Includes nutritional reasons and malabsorptive conditions.

B12 Deficiency

Causes neurological symptoms via methylmalonyl-CoA buildup.

Ineffective Erythropoiesis

Qualitative defect in red blood cell production.

Megaloblastic Anaemia

Caused by low B12 or folate levels.

Thalassaemia

Genetic disorder affecting hemoglobin production.

Sideroblastic Anaemia

Ineffective erythropoiesis due to iron metabolism issues.

Myelodysplastic Syndrome

Disorder caused by poorly formed or dysfunctional blood cells.

Insufficient Erythropoiesis

Quantitative lack of erythrocyte precursors.

Renal Failure

Leads to decreased erythropoietin production.

Iron Deficiency

Common cause of insufficient red blood cell production.

Anaemia of Chronic Disease

Associated with chronic inflammatory conditions.

Aplastic Anaemia

Failure of blood cell production in bone marrow.

Bone Marrow Replacement

Displacement of normal marrow by abnormal cells.

Haemorrhage

Loss of blood leading to decreased RBCs.

Haemolysis

Destruction of red blood cells.

Intravascular Haemolysis

Destruction of RBCs within blood vessels.

Extravascular Haemolysis

Destruction of RBCs in the spleen.

Koilonychia

Thin, spoon-shaped nails associated with anaemia.

Angular Stomatitis

Ulcers at the edges of the lips.

Atrophic Glossitis

Smooth, inflamed tongue due to anaemia.

Compensatory Mechanisms

Body's response to maintain oxygen delivery during anaemia.

Chronic Anaemia Symptoms

Includes pallor, fatigue, dyspnoea, and tachycardia.

2,3-Diphosphoglycerate (2,3 DPG)

Regulatory molecule enhancing oxygen release from hemoglobin.

O2 extraction

Increased oxygen uptake by tissues from hemoglobin.

HbO2 curve shift

Rightward shift indicates decreased hemoglobin affinity for O2.

Cardiac Output (CO)

Volume of blood pumped by heart per minute.

Afterload

Resistance the heart must overcome to eject blood.

Vasodilatation

Widening of blood vessels, reducing vascular resistance.

HIF-1

Oxygen sensor regulating EPO production in kidneys.

Hydroxylation

Chemical modification affecting HIF-1 stability.

Ubiquitination

Process marking proteins for degradation.

Bone marrow suppression

Reduced production of blood cells in the marrow.

O2 dissociation from Hb

Release of oxygen from hemoglobin to tissues.

Hb

Measure of haemoglobin concentration in blood.