PATH 201 - LECTURE 4

What is the process of blood cell production called

haemotopoeisis

what is a hematopoietic cell

immature stem cell that produces all the different types of blood cells

how many cells can arise from a haematopoietic cell

millions

what are teh two main lineages of blood cells

• myeloid

• lymphoid

which lineage are blood cells/erythrocytes a part of

myeloid

what blood cells are part of the myeloid lineage

• erythrocytes

• platelets

• basophil

• eosinophil

• monocyte

• neutrophil

what blood cells are part of the lymphoid lineage

• B cells

• T cells

• NK cells

what is the site of haematopoiesis in 0-2 month fetus

yolk sac

what is the site of haematopoiesis in 2-7 month fetus

liver

spleen

what is the site of haematopoiesis in 3-9 month fetus

bone marrow

thymus

what is the site of haematopoiesis in infants

• bone marrow of all bones

what is the site of haematopoiesis in adults

• bone marrow of central skeleton. proximal humerus and femur

is all of our bone marrow active

• no part of it is active (red) and part of it is inactive (yellow)

what is yellow bone marrow mostly made up of

adipocytes

compare active bone marrow in infants and adults

• infants have mostly all red bone marrow

• as we age it regresses into the central part of the skeleton

• adults have 50/50

what are the two types of lymphoid tissue

primary lymphoid and secondary lymphoid tissue

where is primary lymphoid tissue

• bone marrow

• thymus

where are B and T cells produced

• primary lymphoid tissue

• (bone marrow and thymus)

where is secondary lymphoid tissue

• spleen

• lymph nodes

• tonsils and adenoids

• gut associated lymphoid tissue

what is the function of secondary lymphoid tissues

• lymphocyte activation

• immune cells are set up in follicles in sites where we have interactions with pathogens

• these follicles allow antigen presentation and the development of immune responses in local sites

what is the function of the spleen

• filters circulating blood

• removes old/damaged cells

• stores platelets

• checks for pathogens that have capsules around them

what are people without a spleen more prone to

• pathogenic organisms that have polysaccharide capsules around them that hide them from the immune ssytem

what is the kidneys role in red blood cell production

• 20% of our blood passes through kidneys

• it detects oxygenation of the blood

• if it detects low oxygenation it releases erythropoietin which is growth factor for RBCs

what is the liver's role in haematopoeisis

• site for fetal haematopoiesis

• makes proteins for when we have infections

• breaks down Hb

• provides growth factors for platelets

• produces coagulation factors

what are the two main ways that blood can be examined

• qualitative

• quantitative

describe the quantitative method of blood examination

• blood that is drawn is run through a haemotology analyser

• it uses laser light to determine cell size and granularity

• electrical impedance measures cell number and volume

• light absorbance measures haemoglobin

what is done if quantitative exam is not conclusive

• qualitative exam

describe qualitative exam

• blood smear

• view under microscope

• allows us to see morphology

if qualitative and quantitive were not conclusive, what is done

• bone marrow examination

what are the two forms of bone marrow exam

• aspirate and biopsy

describe bone marrow aspirate

• just taking the fluid portion

describe bone marrow biopsy

• chunk of bone is also taken

what conditions may a bone marrow exam be used for

• unexplained anaemia

• blood conditions with too many or too few of types of blood cells

• cancers that have spread into marrow

• hemochromatosis (excess iron absorption)

• fevers of unknown origin

what form of an exam is being displayed

• left is bone marrow biopsy

• right is bone marrow aspirate

decribe what each of the coloured dots is referring to

• blue: fat cells get washed out so we are left with these large spaces

• green: millions of haematopoeitic stem cells and all of the cells that have divided from them

• black: bone walls that are full of osteoblasts

• red: bone tissue, if we look super closesly, can see blue dots which is osteocytes sitting within lacunae

describe the shape of platelets

• round/oval

describe the size of platelets

2-4 micrometres diameter

describe the nucleus of a platelet

anucleate

what are platelets derived from and where

fragmentation of megakaryocytes in the bone marrow

describe the granularity of platelets

• slightly granular

describe the shape of erythrocytes

flexible biconcave disk

describe the size of RBCs

6-8 micrometers

what is the central pallor

• the centre of an RBC is thinner than the rest and so under a light microscope it shows up as a lighter circle

what does it mean if the central pallor doesnt exist in RBC

• it means the cell is shaped differently and something might be going on

• like a disease

what proportion of the RBC is central pallor

1/3

what does the cytoplasm of RBC contain

haemoglobin

enzymes

why is it important for haemoglobin to be within RBCs

• it would thicken the blood too much if it was free floating

how does an RBC carry out energy production

glycolysis

what is the function of haemoglobin

• delivers oxygen to tissues and returns carbon dioxide to the lungs

describe the structure of Hb

• tetramer with 2 globin chains

describe the lifecycle of an RBC

• erythropoetin released by kidney

• RBC produced in bone marrow

• circulate in blood for 120 days

• old cells are killled and phagocytosed

what determines when RBCs are too old and need to be killed

• as theyre circulating, they undergo changes to the surface proteins as a sign of aging

• macrophages in the spleen recognise these proteins and phagocytose the RBC

• another way is cells must squeeze through sinusoids of MPS, if their ability to squeeze and rebound to original shape is diminished, then thats another sign of their age, and macrophages in the MPS will phagocytose them

what happens to RBCs that have been phagocytosed

• the haem gets split into iron and bilirubin

• iron goes back into the blood

• bilirubin goes into the liver into biles (give it the yellow colour)

what are immature erythrocytes

reticulocytes/polychromatic cells

when are reticulocytes released from the bone marrow

2 dyas

what does reticulocytes contain

• residual RNA and organelles

how long does it take for a reticulocyte to mature

1-2 days in the blood

what happens to a reticulocyte as it matures

• looses its RNA and organelles

what is the difference between polychromatic cells and reticulocytes

• essentially the same thing

• reticulocytes arent visible with normal stains - need special staining

• polychromatic cells show up as purple on giema stained blood film (basically routine staining)

what type of cell is this

• reticulocyte

what type of cell is this

• polychromatic cell

describe the membrane of RBC

• super strong and super elastic

describe the components of the membrane of RBC

• phosphlipid bilayer with cholestrol

• glycophorin proteins

• spectrin and ankyrin

what do glycophorin proteins do in the RBC membrane

• protect against injury and damage

what do spectrin and ankyrin do in the RBC membrane

• part of cytoskeleton

• anchor everything in place

what allows blood cells to be able to deform

biconcave shape

whats this image showing

• an RBC squeezing through a sinusoid in the MPS

what is anaemia

• low haemoglobin

what does low hameoglobin mean

• less oxygen carrying capacity

• less ability for cells to make ATP

what are some symptoms of anaemia

• weakness

• fatigue

• angina

• shortness of breath (trying to take more o2 in)

what are some signs of anaemia

• pallor

• tachycardia

• jaundiced eyes

what causes jaundiced eyes due to anaemia

• too much RBC breakdown>too much billirubin>yellow

what causes tachycardia due to anaemia

ischaemic pain due to build up of lactic acid

how are anaemic classified based on cell size (MCV)

• small cell is microcytic

• big cell is macrocytic

• normal cell is normacytic

how are anaemia classified based on cell colour (MCH)

• hypochromic: pale

• normochromic: normal

• relates to Hb btw

what causes macrocytic cells

• problem with maturation

• missing things like b12 and folate that are essential to cell division and so cells arent dividing at the same rate and we end up with bigger cells

what is normochromic anaemia

• mean cell haemoglobin is within the normal range

• MCH

what is aetiology

referring to the cause of the disease

what are the 3 classes of anaemia based on aetiology

• reduced RBC or Hb production

• haemolysis

• blood loss

describe causes for anaemia due to reduced RBC or Hb production

• nutritional deficiencies

• globin gene defects

• kidney disease (low erythropoetin)

• bone marrow disease

what nutritional deficiencies can lead to anaemia

• iron

• b12

• folate

what disease is an example of a globin gene defect

thalassaemia

what disease is an example of bone marrow disease

leukemia

what is haemolysis

increased destruction of RBC

how does someone get haemolytic anamia

can be inherited or accquired

how can haemolytic anaemia be inherited

• sickle cell disease

• heriditary spherocytosis

• G6PD

how can haemolytic anaemia be acquired

malaria

autoimmune disease>antibodies attack RBCs

describe blood loss anaemia

• pretty self explanatory

• u loose blood from acute trauma, surgery, menorrhagia

describe what happens to a cell during sickle cell disease

• when the cell is deoxygenated, an area that is phobic to the blood is exposed, it tries to avoid it and the cell collapses (sickles)

why is sickle cell shape a problem

• gets stuck in the vessels and occludes them

• they also have decreased oxygen carrying capacity

describe the genetic mutation that causes sickle cell

• chromosome 11 point mutation resulting in altered B-blobin

• glutamine to valine

why is sickle cell disease selected for in some places

• selected for in areas where malaria is endemic

• malaria cannot infect sickle cells

what is hereditary spherocytosis

• it is a defect in the membrane proteins of RBCs that causes them to become spherical

• affects proteins such as ankyrin

• makes RBCs less deformable, so they get trapped in the sinusoids and get destroyed by macrophages

describe the structure of the membrane proteins in an RBC

2 spectrin polypeptide chains a and b form a chain like heterodimer

• spectrin then vinds to actin and ankyrin

what does hereditary spherocytosis look like on a blood film

• missing central pallor

• polychromasia (presence of immature Reticulocytes)

describe the consequences of hereditary spherocytosis

anaemia

jaundice, gallstones (bilirubin)

what is happening here

• the cells are becoming more spherical due to hereditary spherocytosis

what is G6PD

• glucose 6 phosphate dehydrogenase

• enzyme that produces glutathione and NADH

• oxidised glutathione converted into GSH which protects against oxidant radicals

what is G6PD deficiency

• lack of protective HSG

• damage from oxidant radicals

• RBC membrane damage

• creates heinz bodies: unfolded, corss linked Hb that looks like a perm