Heamatology Flashcards
What does the blood consist of ?/
Blood composition:
~ 55% Plasma
~45% Red blood cells (RBCs)
< 1% Buffy coat ( platelets and white blood cells)
THE FUCTION OF RED BLOOD OF CELLS?
RBC’s major function is to transport Haemoglobin.
Haemoglobin carries O2 from the lungs to the tissues.
Other functions of RBCs.
Where in the body are RBCs produced?
Erythrocytes are made in the bone marrow.
After age 20-years bone marrow of the long bones (humeri and tibiae) becomes fatty and RBCs production stop.
Name the bones in which RBCs production still continues after the age of the 20 years.
RBCs production continue mainly from bones -vertebrae, sternum, ribs, and ilia in individuals > 20-years
Explain the formation of RBCs.
The formation of RBCs - Erythropoiesis
Multipotent haematopoietic stem cells in the bone marrow give rise to erythroblasts.
The growth and production of RBCs is modulated by growth inducer e.g. erythropoietin.
Erythrocyte are derived from committed stem cell called a —————————————————
Colony forming unit-erythrocyte (CFU-E)
explain the formation of RBCs. 5 marks
The proerythroblast is the 1st RBC formed from CFU-E stem cells during Erythropoiesis.
Basophil erythroblast 1st generation.
Polychromatophil erythroblasts – Haemoglobin appearance
Orthochromatic - the nucleus condenses, and haemoglobin occupy the large intracellular space.
Reticulocytes – enter circulation through capillaries by diapedesis and mature to erythrocyte (RBCs) within 1 – 2 days.
The life span of RBC’s
RBCs have a life span of ~120 days before being are destroyed.
RBCs membrane become fragile over time.
Narrow capillaries and spleen rapture RBC membrane.
Raptured RBCs are ingested by monocyte-macrophage cells and haemoglobin released.
The Metabolic product of RBC
Raptured RBCs are ingested by monocyte-macrophage cells and haemoglobin released.
Macrophages metabolize haemoglobin to form the bile pigment - bilirubin.
Iron release by macrophage is stored mainly in the ferritin pool to be used when need for the formation of new Haemoglobin.
The nutrients required to form mature RBCs.
Maturation of RBCs require Vitamin B12 and Folic Acid.
Vitamin B12 and Folic Acid are essential for DNA synthesis – contribute to the formation of DNA building block thymidine triphosphate.
Defiance of Vitamin B12 and Folic Acid cause abnormal DNA formation - RBC maturation failure.
Erythoblastic cells fail to proliferate – enlarge RBCs called megaloblasts = Megaloblastic Anaemia.
Macrocytes can transport O2 but have fragile cell membrane that rupture easily = short life span.
Poor GIT absorption of vitamin B-12 is called?
Anamia
Poor GIT absorption of Vitamin B12- Anaemia
Vitamin B12 absorbed in the GIT is stored mainly in the liver and release when need by bone marrow for RBC production.
Pernicious anaemia - Poor absorb vitamin B12 from the gastrointestinal tract – RBC maturation failure Pernicious anaemia can be caused by atrophic gastric mucosa that fail to produce normal gastric secretion (intrinsic factor).
Intrinsic factor binds Vitamin B12 and protect it from digestion.
Lack of intrinsic factor decreases availability of vitamin B12 because of faulty GIT absorption.
Pernicious Anaemia
Pernicious anaemia is an autoimmune disease - plasma cells in the gastric mucosa secrete antibody against intrinsic factor.
Poor GIT absorption of folic Acid
Folic acid is source mainly from green vegetables, some fruits and meats (liver)
Folic acid can be easily destroyed during cooking.
Gastrointestinal absorption abnormalities, such as sprue (diarrhea) impair absorbing of both folic acid and vitamin B12.
The formation of haemoglobin
Four clinically important types of globin - α, β, γ, and δ.
All types of haemoglobin contain 4 globins per molecule of haemoglobin.
Common haemoglobins - Haemoglobin A (composition: α2β2) and haemoglobin F (composition: α2γ2).
Haemoglobin synthesis begins in polychromatophil erythroblasts and continues into the reticulocyte stage of the RBCs production.
Abnormality of the globin polypeptide can change physical characteristics of the hemoglobin. molecule which may result in ———————-
An amino acid substitution occurs on the 2β chains - valine is substituted for glutamic acid at one point in each of the 2 β chains.
This abnormal hemoglobin forms elongated crystals when exposed to low O2.
These crystals rupture the cell membranes and lead to sickle cell anaemia.
The role of iron metabolism in haemoglobin
Iron is essential in the formation of Haemoglobin.
Iron is absorbed from the small intestine.
In the blood plasma irons binds with a beta globulin protein called apotransferrin to form transferrin.
Transferrin is circulating in the plasma.
Shortage of transferrin in the blood can cause hypochromic anaemia – due to insufficient iron transported to the erythroblasts.
How is iron binding to transferrin?
The iron is loosely bound in the transferrin and can be released to any tissue cell.
Extra iron in the blood that is not bound to apotransferrin is stored in liver cells - hepatocytes.
(some iron is up taken by the reticuloendothelial cells of the bone marrow).
Intracellular (cytoplasm) - iron binds to apoferritin and form ferritin.
Iron stored as ferritin is called storage iron.
Storage iron can form insoluble compounds called hemosiderin
Name a hormone secreted by the liver responsible for transporting iron
Hepcidin is a hormone secreted by the liver to
Hepcidin , macrophages in the spleen, Kupffer cells in the liver, and macrophages in the bone marrow.
Inflammation and high iron stores in the liver stimulate hepcidin secretion and thus reduce the concentration of iron in the blood.
Patients with chronic inflammation likely to become anaemic due to insufficient release of iron from stores.
In contrast, ineffective erythropoiesis, anaemia, and hypoxia reduce hepcidin secretion.
The role of tissue Oxygenation in RBC production
A high altitudes:
=O2 n the air decreases.
=Insufficient O2 is transported to the tissues.
=RBC production increases.
Congestive heart failure and lung diseases cause tissue hypoxia result in increases RBC production.
Renal disease – anaemic
What Erythropoietin: secretion
EPO- secretion is stimulated by hypoxia, which is detected by an oxygen sensor located in the kidney.
Cells found in the cortex and outer medulla of the kidneys synthesize erythropoietin and release it into the bloodstream.
Approx. 90% of erythropoietin in synthesized by the kidneys
The liver synthesizes ~ 10% of erythropoietin.
The hormonal control of RBC production.
Low tissue O2 stage stimulate the mainly kidneys to secrete a hormone called erythropoietin.
Erythropoietin stimulate RBC production.
The mechanism:The hormonal control of RBC production
Mechanism:
Low renal tissue O2 (hypoxia) increase tissue levels of hypoxia-inducible factor-1 (HIF-1).
(HIF-1) is a transcription factor for many hypoxia-inducible genes, including the erythropoietin gene.
HIF-1 binds to a hypoxia response element in the erythropoietin gene, inducing transcription of messenger RNA.
Increased erythropoietin synthesis.
the Recombinant Erythropoietin
In kidney disease, kidneys no longer secrete enough erythropoietin cause deficient in RBCs.
The liver does not synthesize sufficient erythropoietin.
Recombinant erythropoietin is injected to stimulated RBC production in patients with severe kidney malfunction.
