WEEK 4- Lect 8: Haematology I

• lecture ILO's:

  
• what is blood (general), how much blood in the average adult, and how much is as a percentage of body weight?

  •Component of cardiovascular system– heart and blood vessels

  •A fluid connective tissue

  •Average adult has blood volume of 5L

  •Accounts for approx. 7% of your weight
• what does blood consist of? (3 main sections)

  plasma = approx 55% •[normal range 46 - 63%]

  WBC's and platelets = <1%

  RBC's = 45%

  
• what does plasma consist of? what's its function?


  •Components:

  Water (92%),

  Plasma proteins (7%)  -> Albumin, Globulin, Fibrinogen, regulatory proteins

  Other solutes (1%) –Electrolytes, organic nutrients and waste

  •Function: transport – inorganic and organic molecules, formed elements and heat
• what does blood do? (hint: transport(4) and defence (2) )

  Transport

  •Gases (O2 and CO2)

  •Nutrients

  •Excretory products (waste)

  •Temperature

  Defense

  •Antibodies, white blood cells

  •clotting factors
• What is haematopoiesis?


  Haematopoiesis is blood cell production. Your body continually makes new blood cells to replace old ones

  Word origin: Ancient greek haima ('blood') + poiesis ('to make')
• (p) diff between haemopoiesis and erythropoiesis


  • 'Hematopoiesis refers to the formation of all mature blood cells, including red blood cells (erythrocytes), white blood cells (leukocytes), and platelets.
  • Erythropoiesis specifically focuses on the production of mature red blood cells (erythrocytes).'
• name the cells stages in erythropoieses


  hemocytoblast (stem cell)

  -> proerythroblast (commited cell)

  -> early erythroblast (phase 1: ribosome synthesis?)

  -> late erythroblast (phase 2: haemoglobin accumulation)

  ->normoblast (nucleus eventually removed)

  -> reticulocyte

  -> erythrocyte

  
  

  notes: -blast = precursor, -cyte = cell

  
• what are 5 requirements for erythropoiesis?


  Requirements

  -Erythropoietin (EPO)

  -Iron

  -Vitamins B12 & folic acid (B9)

  -Intrinsic factor

  -Amino acids

  (p) note: EPO is s growth factor in RBC's and is 'used in sports'
• Where does erythropoiesis occur? (foetus, infant and adult), whats the rate per second of RBC's produced?


  •Foetus: early in yolk sac, then liver & spleen later in bone marrow

  •Infant: all bone marrow

  •Adult: only red bone marrow (ribs, vertebrae, skull, upper ends of long bones)

  Rate: 2 -3 million red blood cells per second!

  
• describe the structure and function of red blood cells


  •Highly flexible and deform readily,

  Red blood cell contents:

  • no organelles

  •Haemoglobin

  Main function:

  •Carriage of gases->Oxygen, Carbon dioxide, Carbon monoxide, H+

  •Lifespan

  ('about 120 days')

  shape: concave, roughly 8um long (look at diagram for height its like 1um smallest and 2um at tallest)

  
• (idk if you need to learn this) describe the life cycle of red blood cells

  macrophage breaks down aged and damaged RBC's, the Hb turns into heme (and then bilirubin and iron) and globin (turns into amino acids)

  the iron then gets reused in erythropoiesis, added to transferrin to be stored in the spleen or into ferritin which is reused in erythropoiesis

  bilirubin is then added to to serum albumin and from the livers gets secreted into the bile (found in gallbladder)

  
• list some causes of hypoxia (4)


  Causes of hypoxia:

  -Increase in exercise

  -High altitude

  -Smoking

  -Bleeding
• Describe erythrocyte homeostasis (low O2)


  1. stimulus = low O2 blood level ->
  2. kidneys increase production of erythropoietin) ->
  3. Stem cells increase red blood cell production ->
  4. O2 blood level returns to normal (stimulus resolved)

  
• how much Hb molecules per red blood cell? when does Hb synthesis begin?


  •Approx. 280 million haemoglobin molecules per red cell

  •Synthesis begins in proerythroblast

  •65% at erythroblast stage

  •35% at reticulocyte stage

  (Before the red blood cell is fully mature!)

  
• what gasses does Hb transport to tissues and lungs? how many g/dl of blood is Hb? 


  •Transports O2 from lungs to tissues

  •Transport CO2 from tissues to lungs

  •Approx. 15g/dl of blood  – Females 12 - 16g/dL  and  Males 13.5 - 17.5g/dL
• describe the structure of Haemoglobin (adult) HbA


  -4 subunits: 2 alpha (α) and 2 beta (β) subunits

  -Each subunits consists of :    (i) “haem” bound to (ii) long polypeptide chain  “globin”

  -In centre of Haem group is a ferrous iron atom (Fe2+)

  -Fe2+ can reversibly bind with one molecule of oxygen (O2)

  
• what is anaemia? name 3 types


  •Definition : Haemoglobin concentration in whole blood below the accepted normal range(World Health Organisation)

  • Iron deficiency anaemia
  • Megaloblastic anaemia
  • Sickle cell anaemia
• What's considered low Hb levels in blood in adult men and women? how muchof the population does anaemia affect?


  Low level of haemoglobin in blood:

  •Less than13.5g/dL for men

  •Less than 12.0g/dL for women

  •Common problem worldwide affecting 1/3 world population!
• what causes Anaemia? (3)


  Causes:

  •Decreased RBC production

  •Increased RBC destruction

  •Blood loss
• how common is iron deficiency anaemia as an anaemia? what are the causes?is a diagnosis of it sufficient?

  •Most common anaemia worldwide

  •Causes – pregnancy, bleeding from GI tract (ulcer, malignancy), malabsorption, menorrhagia, malnutrition (dietary)

  
  

  •Diagnosis of iron deficiency in itself is not adequate – always seek the cause
• three features of iron deficient anaemia RBC's



  •Hypochromic

  •Microcytic red blood cells

  •decreased mean cell volume (MCV)

  
• hypochromia reference

  
• (p)def Microcytosis



  Microcytosis refers to red blood cells that are smaller than normal

  (image from google)

  
• (p) further context: what is megaloblastic anameia?

  (p) 'Megaloblastic anaemia is a type of anaemia characterised by the production of abnormally large red blood cells called megaloblasts.

  These cells are larger than normal and often have a deformed nucleus. This condition occurs when there is a deficiency of either vitamin B12 or folate (vitamin B9).'
• whats megaloblastic anameia caused by?

  Vitamin B12 deficiency or Folate deficiency
• name 4 traits in RBC's with megaloblastic anaemia


  •Abnormal RBC

  •Reduced haemoglobin concentration

  •Macrocytic

  •Increased mean cell volume (MCV)
• what's a feature you can see with neutrophils under a microscope from a smear of RBC's with megaloblastic anaemia?


  Hypersegmented neutrophil (centre of picture)

  
  

  (p)'The presence of hypersegmented neutrophils is an important diagnostic feature ofmegaloblastic anaemias.'- wiki

  
• is there a difference between Vitamin B12 and folate? (/gen idfk)


  Theyre similar but different? im unsure but im more certain theyre different and maybe absorbed from different dietary things
• Megaloblastic anaemia: Folate deficiency, a general description (3)


  Folic acid / Folate deficiency-

  •Characteristics similar to Vitamin B12

  •Macrocytic anaemia

  •Causes: Pregnancy, elderly, dietary deficiency

  
• Megaloblastic anaemia: vitamin B 12 deficiency -> what does B12 need and what's it secreted by?


  Need intrinsic factor (IF) – secreted by stomach for vitamin B12 absorption;
• Megaloblastic anaemia: vitamin B 12 deficiency-> what are the causes and treatment


  Causes:

  •Lack of IF – PERNICIOUS ANAEMIA

  •Crohn’s, coeliac disease (absorption)

  Treatment:

  •Vitamin B12 intramuscular injections

  
• why is B12 deficiency treated with intramuscular injections?

  tablets would lead back to the same issue; absorption issues of vitamin B12 so has to be directly injected (though note and ignore: tablet treatments are still an option but the slides says intramuscular injections)
•  Sickle cell anaemia - hereditary origin, structure and cure?


  • hereditary; African, West Indian
  • Abnormal haemoglobin structure: sickle shape cells, RBCs get stuck in blood vessels
  • no cure…..

  
• Thalassaemias: hereditary origins and cause

  hereditary; Mediterranean, Middle/Far Eastern

  Abnormal haemoglobin production - a and b thalassaemias

  • (p)'Pathophysiology: mutations in globin genes lead to reduced globin chain production, causing accumulation of unpaired chains, unstable red blood cell precursors, and increased red cell destruction. Severe forms result in insufficient oxygen delivery to tissues.' (a and b thalassemia in ref to a or b chains respectively)
• check list: