Physiology Flashcards
What is blood?
Cells suspended in plasma
What is the purpose of blood?
Fight infection
Transport Oxygen
Prevent bleeding
Define haematopoiesis
Production of blood from pluripotent stem cells in bone marrow
In an embryo where does haematopoiesis occur?
Yolk sac
Liver
Marrow
In a baby/young child where does haematopoiesis occur?
Bone marrow
Spleen and liver
As we mature what happens to the bone marrow?
The sites remain in the axial skeleton as the bones grow it decreases in size
Describe the first three steps of the haematopoeisis tree
- LT HSC
- ST HSC
- Multilineage progenitor
What two precursors can the multilineage progenitor become?
Myeloid
Lymphoid
Describe the fate of the myeloid precursor
Megakaryocyte erythrocyte precursor
- erythrocyte or platelet
Granulocyte monocyte precursor
- granulocyte or macrophage
What is the fate of the lymphoid precursor?
B cell
T cell
NK cells
What is the key difference between the precursors and mature cells?
Precursors - morphologically unremarkable and infrequent
Mature - specific characteristics and frequent
What happens to the cell morphology as the cell divides?
It gets smaller, the nucleus condenses and eventually is removed
Describe the characteristics of platelets
Lots of nuclei in one big cell, bud off to form platelets
Name the three types of granulocyte
Eosinophil
Basophil
Neutrophil
Describe neutrophils
Segmented nucleus with neutral staining granules
Phagocytose invaders and kill with granule contents
Attract other cells - complement and chemokine causing body stress
What situations cause an increase in neutrophils?
Infection
Infarction
Trauma
Describe eosinophils
Bi lobed with red staining granules
Fight parasitic infections and involved in hypersensitivity
What type of patients often have high eosinophils?
Patients with allergies
Describe basophils
Infrequent, purple granules with obscuring nucleus
IgE receptors and histamine - involved in hypersensitivity
What are monocytes?
Single nucleated cells often with vacuoles
Circulate for a week and then enter tissues to become macrophages which phagocytose and attract other cells
What type of immune molecule are macrophage?
MHC class II
Name two methods of assessing blood constituents
Immunophenotyping
Bio-assays
Examination
What is immunophenotyping?
Surface proteins, monoclonal antibodies with tags
What is bio-assay?
Culture in vitro and show lineage of progeny in different growth conditions
What can be examined to determine blood constituents?
Blood
Bone marrow
Special tests of bone marrow
Spleen, liver, lymph nodes
Name two methods to obtain bone marrow sample
Posterior iliac crest aspiration
Core biopsy
What is the difference between the two bone marrow sampling techniques?
Aspiration - see individual cells
Biopsy - can see cells in context and structure of marrow
Describe the structure and function of RBC
Biconcave, full of Hb
No nucleus or mitochondria with a high SA to volume ratio
Flexible
What does the high SA to volume ratio allow?
Gas exchange
What aspects of the RBC membrane help with its function?
Lipid bilayer
Protein spars
Protein anchor
Sodium potassium pump
Describe the structure of haemoglobin
Tetrameric globular protein with 2 alpha and 2 beta
Heme Fe2+ in a flat porphyrin ring - one heme per subgroup binds to one oxygen
What is the function of haemoglobin?
Delivers oxygen
Buffers hydrogen ions
Carbon dioxide transport
What is the name for the cellular mechanisms that generate RBC?
Erythron
What are the raw materials of RBC?
Iron B12 folate
What is the immediate cell before a RBC?
Reticulocyte
What is the key difference between a RBC and reticulocyte?
There is some RNA in reticulocyte and so it acts as a marker of bone marrow function
Name the hormone that senses hypoxia in the kidneys
Erythropoietin
What is the effect of erythropoietin on bone marrow function?
Stimulates the erythron to increase red cell production
State the average life span of an RBC
120 days
How are red cells removed from the body?
Taken up by macrophage in the spleen and broken down into heme and globin
What happens to the heme?
Iron can be stored as ferritin or related to transferrin for future use
What happens to the globin?
recirculated
What happens to the porphyrin ring?
Unconjugated bilirubin taken up in the liver and excreted in bile
How do RBC produce energy?
Glycolysis
What are the problems with glycolysis?
Low energy yield
Lots of free radicals produced
State the net generation from glycolysis
ATP - energy
NADH - electron donor to stop oxidation
What are reactive oxygen species?
Hydrogen peroxide/superoxide have unpaired free electrons that interact with DNA and proteins
How are reactive oxygen species dealt with?
Glutathione reacts with hydrogen peroxide to form water and an oxidised glutathione
How is oxidised glutathione converted back to glutathione?
NADPH
What enzyme is needed to produce NADPH?
Glucose 6 phosphate dehydrogenase
Name the shunt where NADPH is produced?
Hexose Monophosphate
Name three ways carbon dioxide can be removed from the body
Dissolves
Binds to haemoglobin
Bicarbonate
What ion is exchanged for bicarbonate in the red blood cell?
Chloride
How is fetal haemoglobin different to adult?
Higher affinity - saturates more at the same oxygen concentration
What shape is the oxygen/saturation curve?
Sigmoidal
Describe the allosteric effect
As one oxygen binds to haem the Hb changes shape - this interacts with the adjacent globin and changes its shape and thus affinity
Other than oxygen what else can alter the shape/position of haemoglobin?
Small molecules e.g 2,3 BPG
Describe 2,3, BPG
Produced in glycolysis it interacts with Hb and shifts the curve to the right to allow higher release of oxygen into tissues
What shifts the curve to the right?
Decreased pH, increased temp, increased CO2 (Bohr)
What shifts the curve to the left?
Increased pH, reduced temp, increased oxygen (haldane)
What would cause a reduced cell count?
Increased distribution e.g haemorrhage
Reduced production e.g iron deficiency
Redistribution e.g liver disease
What would cause an increased cell count?
Stimulus e.g altitudes, hypoxia, allergy
Malignancy
Redistribution e.g splenic, trauma, steroids
How do steroids cause an increased cell count?
Demargination - they move neutrophils away from the vessel wall
