introduction to blood L2 Flashcards
what percentage of body weight is made up of blood
8%
what is the volume distribution of blood
0.6L- lungs
2L- systemic venous circulation
1.4 L- the heart, systemic arteries, arterioles and capillaries
describe 3 functions of blood
- gas transport and exchange
- distributing solutes
- plasma transports: ions (thus helps regulate ion concentrations in tissues) nutrients , hormones, metabolic waste - immune functions: leukocytes (WBC) and immune system proteins are transported in blood
describe 4 more functions of blood
- maintains body temp
- blood carries away heat - a byproduct of many chemical reactions in body - regulates blood clotting
- platelets and certain proteins form blood clot; seals damaged blood vessels to prevent blood loss - Preserving acid-base homeostasis
- pH of blood wants to be in range of 7.35-7.45
- blood contains several buffer systems to maintain pH - stabilising blood pressure
- blood volume is a major factor in determining blood pressure
what are the 4 main components of blood
- plasma (complex liquid in which cells are suspended)
- Erythrocytes- Red Blood Cells
- Leukocytes- White Blood Cells
- Thrombocytes- Platelets
- fewer white blood cells than red
how do Blood Constituents settle in tube
bottom (most heavy): red blood cells
middle: buffy coat layer- white blood cells and platelets
top: plasma
what is the percentage of RBC layer
44%
what is the percentage of buffy coat
1%
what is the percentage of plasma
55%
- composed of mainly water and soluble factors
what is serum
plasma without clotting factors
define Haematocrit and give its normal percentage for men and women
the ratio of the volume of red blood cells to the total volume of blood.
M: 45%
W: 42%
what is blood made up of
plasma
cellular elements
- RBC, WBC, platelets
what is plasma made up of
water, ions, organic molecules, trace elements and vitamins, gases
what organic molecules make up plasma
amino acids, proteins, glucose, lipids, waste
what important proteins make up plasma
albumins, globulins, fibrinogens (important clotting factor)
what are the two main functions of plasma
- thermoregulation
- transport
what are the three main components of plasma
- water >90%
- plasma proteins 8%
- dissolved small molecules 1-2%
describe role of water in plasma
High capacity to hold heat; blood temperature only undergoes small changes.
- Heat not needed is lost to the environment.
Percentage of water determines blood viscosity:
- less water -> thicker blood -> sluggish flow
describe role of the 3 main plasma proteins in plasma
Serum albumin (~55%):
- maintains osmotic pressure of plasma
- assists in transport of lipids and steroid hormones
- large protein, synthesised in the liver
Globulins (~38%):
- bind to and transport ions, hormones and lipids otherwise incompatible with water-based plasma
- immune proteins: Antibodies or gammaglobulins, made by leukocytes
Clotting proteins (fibrinogen) (~7%):
- essential for blood clotting
- synthesised in liver
Remainder (~1%):
- Regulatory proteins such as enzymes, proenzymes, and hormones.
how can plasma proteins be identified
electrophoresis
- used in diagnostics of myeloma
- those with myeloma have band indicating monoclonal component (uncontrolled growth) which is not on normal band patterning
describe role of dissolved small molecules in plasma
Nutrients: Glucose, amino acids, lipids, vitamins
Waste Products : Creatinine, bilirubin, urea
Dissolved gases: Oxygen, Carbon Dioxide
Hormones, vitamins and minerals
- Transported in solution and Readily exchanged between blood and interstitial fluid
what is the structure and function of erythrocytes
bioconcaved disk that contains haemoglobin and functional enzymes
transports oxygen to respiring cells and removes carbon dioxide
what is the volume of erythrocytes
80-96 femtolitres (10 to the power of -15)
what is MCV
Mean Cell Volume
- measures the average size of your red blood cells
what does it mean if your RBC are microcytic or macrocytic
MICRO: they are small caused by iron deficiency and will often be seen as pale
- anaemia
MACRO: RBC are large
- folate (vitamin B9) deficiency anaemia
describe synthesis of RBC
- starts in bone marrow
- multipotent hematopoietic stem cell (hemocytoblast) may become any type of formed element - hemocytoblast goes down myeloid pathway to go on to form erythrocyte
- hemocytoblast becomes erythrocyte-CFU and cell is committed to becoming erythrocyte
- forms proerythroblast (requires erythropoietin to happen)
- early erythroblast made which starts to synthesise haemoglobin
- late erythroblast ejects organelles
- reticulocyte formed and enters blood
continues maturing in vessel forming erythrocyte
synthesis of RBC is a feedback loop, describe it
low RBC cause hypoxia
reduce O2 causes kidney to release erythropoietin which stimulates red bone marrow to start synthesising RBC
leads to increase O2 levels so synthesis slows down
describe what happens to damaged RBC
RBC become damaged from squeezing through capillaries
in the liver or spleen, haemoglobin in ruptured RBC is decomposed to haem and globin
haem is recycled to form bile or iron ions
globin, membrane and other proteins are broken down into amino acids and used to make new RBC
what is the function of haemoglobin
transport O2 as it is poorly soluble in water
- 98% of O2 bound to haemoglobin
describe the structure of haemoglobin
The globin part –made up of four protein chains
Four iron containing haem groups – each iron atom can reversibly bind one molecule of oxygen
describe the structure of the haem group
Haem is an iron containing pigment
Consists of a porphyrin ring containing one atom of iron
Due to its iron content it appears reddish when combined with oxygen and bluish when deoxygenated
Iron: Fe2+ (ferrous) in absence of O2, Fe3+ (ferric) when O2 bound
describe structure of globins
there are 4 kinds- alpha, beta, gamma, delta
97% of adults have 2 beta and 2 alpha (HbA)
2.5% of adults have two alphas and two deltas (HbA2)
foetal haemoglobin is two alphas and two gammas (HbF)
alpha coded for by 2 genes on chromosome 16
beta coded for by 1 gene on chromosome 11
what is oxygen binding to haemoglobin determined by
partial pressure of oxygen (pO2).
number of free oxygen binding sites available in the molecule
O2 binding is cooperative – binding of one oxygen molecule encourages O2 binding by the other three haem molecules
what are the two forms of haemoglobin
taut (t) and relaxed (r)
- r form: high O2 affinity, exists at high pO2 – firmly binds oxygen (e.g. in the lungs)
- t form: low O2 affinity, exists at low pO2 - releases oxygen (in peripheral tissues)
other than oxygen, what else can haemoglobin bind to
- carbon dioxide
- The acidic hydrogen ion portion (H+) of carbonic acid –generated in tissues from carbon dioxide, Hb buffers the acid
- Carbon monoxide (CO) –not normally in blood but if inhaled preferentially binds to Hb (carboxyhaemoglobin) causing carbon monoxide poisoning.
- Nitric oxide – an important regulatory molecule
what are two types of HB production abnormalities
Haemoglobinopathies:
- Abnormal globin chains are made: - sickle cell anaemia
The Thalassaemias:
- Normal globin chains are made but in decreased amounts OR are absent because of defects at the level of gene expression.
describe sickle cell anaemia
Genetic disease: Mutation in the -globin gene -> a glutamic acid residue is replaced by valine in the protein (βS). Creates ‘sticky patches’ on the molecule.
Resultant haemoglobin (HbS) polymerises at low pO2 forming long crystals of HbS. RBCs deform and become sickle-shaped.
what can sickle cell anaemia result in
Sickled RBCs become trapped within and block small blood vessels depriving downstream tissues of oxygen and causing ischemia and infarction
Damaged cells go to spleen and can block it so normal removal systems do not work
Can get trapped in lungs or joints- inflammation
describe Thalassemias
Diseases where synthesis of one or both of the alpha or beta globins is reduced
Disease severity varies from minor, intermediate to major
RBC prone to damage and short lived -> anaemia
Recessive genetic disease, either:
Gross deletion of one or more globin genes
Gene mutation
what are the two classes of Thalassemias
α and β
α – production of α globin is deficient
found predominantly in India and surrounding regions
β – production of β globin is defective
predominantly in Mediterranean region
Haemoglobin fails to form correctly -> RBC attempt to make Hb with the globin chains that are available
describe α Thalassaemia
Production of α globins is reduced
Leads to excess β chains; unstable tetramers of four β chains (called Haemoglobin H (HbH)) form.
Leads to abnormal oxygen dissociation curves (high O2 affinity, reduced oxygen carrying capacity) and RBC damage.
Short lived RBC -> anaemia
describe β Thalassaemia
Relative excess of α chains
do not form tetramers
bind to and damage RBC membranes
at high concentrations form toxic aggregates.
RBC are fragile and short lived-> anaemia
which form of Thalassaemia is clinically most important
β Thalassaemia
Results in iron overload –> organ damage (heart, liver, endocrine system).
Treatment: iron chelation therapy otherwise patients accumulate potentially fatal iron levels.
how can Thalassaemia be diagnosed
electrophoresis
α Thalassaemia: Reduced HbA, presence of HbH
β Thalassaemia: Production of β globins is reduced or absent; decreased HbA on electrophoresis
types of haemoglobin
Remember:
HbA = two alpha and two beta globins.
HbA2 = two alpha and two delta globins
HbF = two alpha and two gamma globins
HbH = four beta chains.
HbS = sickle cell
