Red Blood Cell Survival Flashcards
How are RBCs produced?
RBC production= Erythropoiesis
It starts in bone marrow with stem cells (hemocytoblasts) and goes through many stages under cytokine influence
Describe the process of erythropoiesis
Proerythroblast is the 1st recognizable cell. It’s a large cell w loose, lacy chromatin and clearly visible nucleoli. Its cytoplasm is basophilic due to polyribosomes.
The next stage is the basophilic erythroblast, w a strongly basophilic cytoplasm, a condensed nucleus but no nucleolus. The basophilia is caused by the large number of polyribosomes involved in Hb synthesis.
Describe regulation of RBC production
The number of RBCs is inversely related to ambient 02 pressure. Epo is a glycosylated polypeptide hormone, produced by the kidneys. It stimulates marrow rbc production:
What is HIF?
(hypoxia inducible transcription factor). HIF determines Epo gene expression in kidneys.
During hypoxia, it enhances expression of iron-absorbing genes like ferroportin (FPN), and of EPO. FPN helps the iron be transported from the cell into the blood.
Why is Iron an important substrate? Describe sources of it
Iron is a major component of Hb. Its regulated by hepcidin (made in liver), which binds to FPN
Sources = meat, eggs, vegetables, dairy foods
Western diet provides 15mg/day –10% absorbed in duodenum and jejunum. HCl and ascorbic acid help absorption.
DMT-1 at brush border brings iron into cells
Ferroportin at basal membrane brings iron from enterocyte into circulation. Given therapeutically as ferrous sulphate
Give causes of Fe deficiency
What is the difference between normal and Iron deficiency anaemia in a blood labs?
Low Hb level.
Microcytic (smaller sized cells)
hypochromic (paler cells) anaemia
MCV < 80fl(m)
Normal Mean Cell Vol: male 80-95; female 78-95
What is the importance of B12 and folic acid?
Both needed for formation of thymidine triphosphate and RBC maturation.
B12 is coenzyme for methionine synthase in methylation of homocysteine to methionine, essential for DNA synthesis.
Deficiency leads to failure of nuclear maturation of RBC.
Folic acid deficiency leads to megaloblastic anaemia
Give causes of B12 deficiency
Pernicious anaemia= commonest B12 def cause. Parietal cells produce IF which absorbs B12. Autoimmune gastric atrophy results in loss of intrinsic factor production required for absorption of B12.
Incidence increases >40 years and often associated w other autoimmune problems, e.g. hypothyroidism.
What does this show?
Labs: MCV > 95fl. oval macrocytes (bigger cells)
Megaloblastic anaemia, with macroovalocytes (loss of biconcave shape) and hypersegmented neutrophil (nucelus of neutrophils are too segmented).
Shows B12 and folate deficiency
Treatments: B12 - Hydroxycobalamin: 1mg im. Folate: -Folic acid: 5mg/day oral
Describe classification of haemolytic anaemia
Differentiate between acquired and hereditary blood disorders
What is the difference between auto and allo immune?
Autoimmune is caused by antibodies against red cell membranes
It is divided into warm and cold antibody types (literally antibodies that work better in warm/cold temps), and each may be idiopathic or secondary to other diseases.
Alloimmune is caused by antibody produced by one individual reacting against red cell of another- eg Rhesus disease or blood transfusion
Describe RBC Metabolism & Survival
Red cells have no mitochondria so can’t metabolize glucose aerobically and produce the ATP that way.
The metabolism of RBCs= the Glycolytic pathway and the Hexose Monophosphate shunt.
What is the role of G6PD in RBC survival?
G6PD generates reduced NADP, which protects RBC from oxidative stress.
In G6PD deficiency, NADPH and GSH generation impaired, ROS accumulates. Oxidative stress causes haemolysis.
Drugs, fava beans or infections can cause oxidative stress and Hb precipitation (Heinz bodies). Patients must avoid particular oxidative drugs, e.g. quinone anti-malarial drugs
Blood sample creates basket cells (below)
What is the role of PK in RBC survival?
Pyruvate kinase forms pyruvate and generates energy in ATP. This maintains red cell shape and deformability.
It also regulates intracellular cation conc via cation pumps (Na/K pump).
PK deficiency is an autosomal recessive disorder. ATP is depleted- cells lose mucho potassium & water, becoming dehydrated & rigid. Causes chronic non-spherocytic haemolytic anaemia
Describe sickle cell disease
Point mutation in the β globin gene: eg T is replaced by A, resulting in the non polar aa valine instead of polar glutamic acid (HbSS most clinically significant)
Hb is less soluble. In low 02 levels, molecules form long fibres that stick juntos in the RBCs, distorting its shape. Sickle shaped cells carry less 02 and block blood vessels.
Other sickling syndromes have slightly diff mutations- see below
