Haematology I Flashcards
What system is blood a component of?
Cardiovascular system
What is the blood volume of an average adult?
5L
How much of your weight does blood account for?
about 7%
What sort of tissue is blood and what does this mean
- it is a fluid connective tissue
- It circulates in a fluid liquid matrix
What is the cell: plasma ratio in blood?
45% cells: 55% plasma
What is blood made up of?
- red blood cells
- platelets (cell fragments)
- white blood cells (WBCs)
- plasma (water and other things)
What does blood transport?
- Gases (O2 and CO2)
- nutrients
- excretory products
How is blood involved in defence?
- has antibodies and white blood cells
- clotting factors
How does blood regulate temperature?
Absorb and distribute heat throughout the body
What are the roles of blood in the body?
- transportation
- regulation of temperature
- defence
Why do we need a massive supply of red blood cells?
So oxygen is readily available to out cells
What is hemopoiesis?
the formation of blood cells
How does hemopoiesis work?
- stars with pluripotent hematopoietic stem cells which divide to form either a myeloid progenitor or common lymphoid progenitor. These are committed cells (it is determined what they will go on to be)
- These cells differentiate to form the precursor cells which give rise to our final blood cells
how are more stem cells made?
hematopoietic stem cells can give rise to more stem cells
What do lymphoid progenitors become?
lymphocytes
What does the myeloid progenitor become?
megakaryocyte, erythrocyte, mast cell, myeloblast as well as many other cells of the immune system
What is an erythrocyte?
a red blood cell
What is erythropoiesis?
the formation of a red blood cell
What are the stages in erythropoiesis?
- Hemocytoblast (becomes committed)
- Proerythroblast
- Early erythroblast (ribosome synthesis takes place)
- Late erythroblast (haemoglobin acculmulation)
- Normoblast (haemoglobin accumulation continues and the nucleus and most other organelles are ejected)
- Reticulocyte (nucleus is ejected.) Has a scant network of clumped ribosomes which stain blue
- Erythrocyte (stain pinkish because of haemoglobin)
How long does erythropoiesis take?
15 days at most but the reticulocyte may still be maturing when it is released into circulation and will take 1-2 days to fully mature
What are the requirements of erythropoiesis?
- Erythropoietin (EPO) which stimulates the production of the red blood cells. Small amounts circulate at all times. Kidneys play a major role in their production
- iron
- vitamins B12 and folic acid (B9)
- intrinsic factor (needed for absorption of vitamin B12)
- amino acids
Where does erythropoiesis happen in a foetus, an infant and an adult?
- Foetus: first in the yolk sac, then liver, then spleen and later in the bone marrow
- Infant: in all bone marrow including yellow bone marrow
- Adult : only in the red bone marrow (ribs, vertebrae, skull, upper ends of long bones)
How many red blood cells do we need per second?
2-3 million
What is the shape and size of red blood cells?
- biconcave disc shape
- 7.5-8 um in diameter
What makes red blood cells able to move through blood vessels 3x smaller than them?
They are highly flexible and deform readily
What are the contents of red blood cells?
- no organelles
- haemoglobin makes up the majority of the cell
What is the main function of red blood cells and how does this occur?
- to carry O2 around the body
- this happens because haemoglobin binds reversibly to O2
How long do red blood cells live for and why is it such a short amount of time?
- about 120 days
- short amount of time because RBC has no nucleus so they can’t repair themselves
Where are red blood cells broken down and by what?
- broken down in mainly the spleen and occasionally the kidney
- macrophages break them down
What are red blood cells broken down into?
Heme and Globin
What happens to heme?
- some of it turns into bilirubin which is secreted into the bile from the liver and will end up being secreted into the faeces giving it it’s colour
- the rest of the iron containing heme is combined with the transport protein transferrin and it is either carried to the spleen for storage or stored as ferritin in the liver. The iron here is recycled
What happens to globin?
Changes into amino acids which are absorbed into the blood and then used for general protein production
What happens in the process of erythrocyte homeostasis?
- Low O2 blood level detected by cells in the kidneys (hypoxia) (stimulus)
- Kidneys increase production of erythropoietin
- Stem cells increase red blood cell production
- O2 blood level returns to normal
- Normal O2 blood level (stimulus of hypoxia is resolved)
What are the causes of hypoxia?
- Increase in exercise
- High altitude
- Smoking
- Bleeding
How many molecules of oxygen does one RBC carry?
About a trillion
How many haemoglobin molecules per red blood cell?
about 280 million
Where does haemoglobin synthesis start and what percent takes place at each stage?
- synthesis begins in proerythroblast
- 65% at erythroblast stage
- 35% at reticulocyte stage
- all the haemoglobin is synthesised before the red blood cell is fully mature
Where does a red blood cell transport oxygen and carbon dioxide?
- transports O2 from lungs to tissues
- transports CO” from tissues to lungs
What is the average blood volume for males and females
- 12-16g/dl blood for women
- 12.5-17g/dl blood for men
15g/dl as an average
What is the structure of haemoglobin?
- 4 subunits: 2 alpha and 2 beta subunits
- each subunit consists of
(i) ‘haem’ bound to
(ii) long polypeptide chain ‘globin’ - in the centre of the haem group is a ferrous iron atom (Fe2+)
What can the Fe2+ group in each haem in haemoglobin do?
Can bind reversibly with a molecule of oxygen. Therefore one molecule of haemoglobin can carry 4 molecules of oxygen as there are 4 haem groups.
What gases does haemoglobin carry?
- Oxygen
- Carbon dioxide
- Carbon monoxide
- H+
How long do RBCs take to circulate the body once?
20 seconds
What is anaemia?
When the haemoglobin concentration in whole blood (cells and plasma) is below the accepted normal range
What is defined as a low level of haemoglobin in the blood?
- less than 13.5g/dL for men
- less than 12.9g/dL for women
What can be the causes of anaemia?
- Decreased RBC production
- Increased RBC destruction (prematurely destroyed)
- Blood loss (could be chronic – over a period of time or acute due to some traumatic event)
How much of the world’s population does anaemia affect?
about 1/3 of the worlds population
Give features of iron deficiency anaemia
- most common
- lots of research on it
- easy to diagnose
what happens in iron deficiency anaemia?
- RBCs become hypochromic (lose their red colour and become pale) because of the reduction of haemoglobin
- Reduced cell count
- You can identify it on a blood film
- Produce microcytic red blood cells (has a smaller mean cell volume)
What are the causes of iron deficiency anaemia?
- Pregnancy (increased demand of iron for foetal growth)
- Bleeding from GI tract (ulcer, malignancy)
- malabsorption (affects the intestinal tract where we absorb iron)
- menorrhagia (excessive bleeding during the menstrual cycle)
- malnutrition (dietary)
What is megaloblastic anaemia due to?
vitamin B12 or folate (B9) deficiency
What are the symptoms of megaloblastic anaemia?
- abnormal red blood cells
- reduced haemoglobin
- macrocytic (increased mean cell volume) because of the effect the vitamin B and folate deficiency has on the cell
- Hyper segmented neutrophil (many more segments on the neutrophil nucleus than we would usually see) due to the effect the deficiency has on chromatin
What are the causes of megaloblastic anaemia?
pregnancy, elderly, dietary deficiency
What is Pernicious anaemia?
- often autoimmune condition attacks parietal cells in stomach which means they can’t produce intrinsic factor (IF)
- IF is needed for Vitamin B12 absorption
- often patients with Crohn’s and coeliac disease have this (as absorption of B12 is affected)
- type of megaloblastic anaemia
What is the treatment for Pernicious anaemia?
Vitamin B12 intramuscular injections. Allows us to bypass stomach and goes directly into circulation
Talk about sickle cell anaemia
- Hereditary: African, west-Indian
- abnormal haemoglobin structure
- sickle shaped red blood cells get stuck in blood vessels
- Causes pain and has an affect of oxygenation on tissues
What is Thalassaemia’s?
- Hereditary; Mediterranean, middle/far eastern
- Abnormal haemoglobin production - alpha and beta thalassaemia’s
What is the haematocrit?
The percentage of formed elements (cells) in the blood
What is the haematocrit in men and women and why is it higher in men?
- 46 in men
- 42 in women
- the male hormone adrogens stimulates RBC production whereas Oestrogen doesn’t
How is the haematocrit determined?
By spinning a blood sample in a centrifuge so that all the formed elements come out of suspension. Whole blood contains about 1000 red blood cells for each white blood cell. After centrifugation the white blood cells, and platelets form a very thin buffy coat above a thick layer of RBCs
Why does the haematocrit alone not provide specific diagnostic information?
Because many factor scan affect the haematocrit such as dehydration and blood loss
What is whole blood?
The combination of plasma and the formed elements
What do transport globins do?
bind small ions, hormones and other compounds. They are a plasma protein
What is the cytoplasmic surface of a RBC plasma membrane?
a meshwork of flexible proteins
What are the important effects of biconcave shape and plasma membrane of a red blood cell?
- Give RBC a large surface area to volume ratio which speeds up exchange
- Enables RBCs to forms stacks that smooth blood flow through narrow blood vessels
- Enables RBCs to bend and flex when entering small capillaries
What does it mean that red blood cells are anucleate?
without nuclei
What does the lack of mitochondria in red blood cells ensure?
that absorbed oxygen will be carried to peripheral tissues, not ‘stolen’ by mitochondria in the RBC
What structure do haemoglobin molecules have?
a quaternary structure
What colour is a haemoglobin molecule bound to oxygen and what is this called?
- called an oxyhaemoglobin (HbO2).
- This makes the blood bright red
What colour is a haemoglobin molecule that is not bound to oxygen and what is this called?
- It is called a deoxyhaemoglobin
- it is dark red
Why does foetal haemoglobin bind more strongly to oxygen than adult haemoglobin?
so it can ‘steal’ oxygen from the maternal blood stream at the placenta.
Why is the binding of oxygen with haemoglobin reversible?
The iron-oxygen interaction in haemoglobin is very weak
When does haemoglobin release oxygen?
- when plasma oxygen is low
- This is typical in the peripheral capillaries: the O2 level is low and the CO2 level is high in the plasma
What happens after the haemoglobin molecule releases the O2 molecule at the peripheral capillaries?
- the alpha and beta chains then bind to CO2 forming carbaminohaemoglobin
- the reverse happens in the lungs
What are some symptoms of anaemia?
makes people weak and lethargic
When may areas of yellow marrow convert to red marrow in adults?
- Under extreme simulation such as severe and sustained blood loss
- it will do this to increase RBC formation
What hormones is Erythropoiesis stimulated by?
Erythropoiesis is stimulated directly by the hormone EPO and indirectly by several hormones including thyroxine, androgens and growth hormone
What type of protein is Erythropoietin?
- glycoprotein
- formed by the kidneys and liver
what are the two main effects of EPO?
- Stimulates cell division rates in erythroblasts and in the stem cells that produce erythroblasts
- Speeds up maturation of RBCs by accelerating Hb synthesis
What is blood doping?
when athletes activate their haematocrits by administering EPO to themselves to increase red blood cell production. Very dangerous
What happens to haemoglobin’s alpha and beta chains after it is broken down?
filtered by the kidneys and eliminated in urin
What happens to the iron of each haeme unit once haemoglobin is broken down?
It’s recycled
When does haematuria occur?
occurs after kidney damage or damage to vessels along the urinary tract and is when intact RBCs are in your urine
When does Jaundice occur?
when bilirubin diffuses into peripheral tissues giving them a yellow colour that is most apparent in the skin
What type of protein is transferrin?
a plasma protein
