Physiology Flashcards
How long do red cells live?
120 days
How long do platelets live?
7 days
How long do granulocytes live?
7 hours
Where and when does haemopoeisis begin?
Yolk sac
3 weeks gestation
What are the two main properties of stem cells?
Self-renewal
Proliferation
What do stem cells divide into?
Progenitor cells
What regulates red cell growth?
Glycoproteins
Give examples of red cell growth factors
IL-3, 6, 7, 11, 12
EPO
Flt3
Which growth factors control platelet growth?
TPO
IL6, 11
What is primary haemostasis?
Formation of the platelet plug
What is secondary haemostasis?
Formation of the fibrin clot
Which factors prevent platelet adhesion to endothelium under normal circumstances?
Heparan sulphate
Thrombomodulin
PGI2 and NO
Plasminogen activator
What is exposed when the vessel wall is damaged?
vWF, collagen and proteins
Which glycoprotein complex creates a binding site for vWF?
IIa-IIIb
What do platelets release on adhesion that allows glycoprotein IIa-IIIb complex to bind to fibrinogen?
ADP and TXA2
What is the role of fibrinogen in primary haemostasis?
Binds platelets together to form activated aggregates
What is the first thing which starts the coagulation cascade?
Damage causes exposure of tissue factor
What does TF bind to?
Factor VII
What does the TF-VII complex activate?
V and X
Some IX
What happens when factor X is activated?
Tissue factor pathway inhibitor is released
What is the role of tissue factor pathway inhibitor?
Prevent more X and IX becoming active
What activates thrombin?
Xa and Va
What does thrombin activate?
Fibrinogen to fibrin
VIII
IX
Which factors are involved in the intrinsic pathway?
XII, X, XI, VIII
Which factors are involved in the extrinsic pathway?
TF, VII, V
What is the role of calcium in the formation of the fibrin clot?
Sticks to negatively charged phospholipids to allow more platelet adhesion
What is the role of factor XIII?
Stabilise the fibrin clot by forming cross links
What is anti-thrombin III?
Serine protease inhibitor
What is the role of protein C?
Inactivates factors V and VIII
Protein C is vitamin K dependent
true/false
True
Protein S is vitamin K dependent
true/false
False
What is the role of protein S?
Enhances binding of protein C to phospholipid
What do endothelial cells release in order to activate plasminogen to plasmin?
tPA
tissue plasminogen activator
What is the role of tPA?
Convert plasminogen to plasmin
What is the role of plasmin?
Breaks down fibrinogen and fibrin
What occurs as a result of fibrin breakdown?
Fibrin degradation products
What is d-Dimer a breakdown product of?
Fibrin cross-links
Haemophilia A is a deficiency of which factor?
VIII
Haemophilia B is a deficiency of which factor?
IX
Give examples of causes of multi-factor deficiency
DIC
Liver disease
Increased fibrinolysis
Which pathway does PT test?
Extrinsic and final common
Describe PT measurement
TF and Ca2+ added to plasma and time taken to clot measured
Give example of what may cause an increased PT?
Liver disease
Warfarin therapy
Vit K deficiency
Factors II, VII, IX, X deficiency
What pathways does APTT test?
Intrinsic
Describe APTT test
Ca2+, phospholipid and an activator added to plasma and time taking to clot measured
Give examples of what would prolong APTT?
Haemophilia A or B
Heparin
Factor deficiency
Some small effect with Warfarin
What does thrombin time measure?
Time taken for convert fibrinogen to fibrin
What would prolong thrombin time?
Heparin
Dysfibrinogenaemia
What shape is a red cell?
Biconcave disc
What is the red cells only source of energy?
Glycolysis
What keeps the membrane in place?
Protein spars
Ankyrin
Describe the structure of Hb
Tetrameric
2 alpha 2 beta
What forms the porphyrin ring of Hb?
Haem and fe2+
Where are red cells mostly destroyed?
Spleen
What do reticulocytes contain that erythrocytes don’t?
Ribsomal RNA
Where is the gene for EPO?
Chromosome 7
Where is EPO produced?
Peritubular cells of kidneys
Some in liver
When is EPO produced?
In response to hypoxia
What is the role of EPO?
Stimulate growth of erytrhoblasts
Which molecule reduces Fe3+ to Fe2+?
GSH
Glutathione
When GSH reduces Fe3+, GSH becomes…
GSSG
What converts GSSG back to GSH?
NADPH
Which molecule replenishes GSSG stores?
G6PD
glucose-6-phosphate dehydrogenase
Where is most of the CO2 in the body carried?
Bound to bicarbonate
Where is 30% of the CO2 in the body carried?
Hb and carbamino-Hb
What is CO2 converted into in the red cell?
Carbonic acid
What converts CO2 to carbonic acid?
Carbonic anhydrase
What is carbonic acid in the red cell converted to?
H+ and bicarb
Describe the O2 binding curve
Sigmoidal
Increase in 2,3-DPG shifts the oxygen-binding curve to the….
Right
Increase in temperature shifts the oxygen binding curve to the….
Right
Increase in pH shifts the oxygen binding curve to the….
Left
How much oxygen does a fully saturated Hb molecule carry?
1.34ml
What do neutrophils develop from?
Myeloblasts
What do myeloblasts develop into?
Promyelocytes
What do promyelocytes develop into?
Myelocytes
What do myelocytes develop into?
Neutrophils
Describe neutrophils
Multi-lobed nucleus with granules
What is found in the granules of a neutrophil?
Lysozyme, lactoferrin and collagenase
What is the main function of a neutrophil?
Kill bacteria, fungi and damaged cells
Chemotaxis
In which scenarios would neutrophils be increased?
Infection, trauma, infarction
Describe an eosinophil
Granulocyte with a bi-lobed nucleus
What colour do eosinophils’ granules stain?
Bright red/orange
What is the function on an eosinophil?
Allergic reaction
Defence against parasites
In which scenarios would eosinophils be increased?
Asthma, atopic rhinitis, and other allergic conditions
Some malignancies
Describe a basophil
Large, deep-purple stained granules which obscure the nucleus
What do basophil granules contain?
Heparin, histamine and some enzymes
What causes release of histamine from basophils?
IgE binding to surface Fc receptors
In which scenarios would basophils be increased?
Myeloproliferative disorders
Describe a monocyte
Large, single nucleus
What is a monocyte a precursor of?
Macrophages and dendritic cells
What is the function of a monocyte?
Phagocytose invaders
Attract other cells
Why would monocytes be increased?
Chronic bacterial infection
Myelodysplasia
Describe a lymphocyte
Central, dark nucleus with a thin rim of cytoplasm
Describe an activated nucleus
Large, blue-staining cytoplasm
What is the function of a lymphocyte?
Respond to infection
When would lymphocytes be increased?
Viral infection
What is the main role of a basophil?
Modulate hypersensitivity reactions
What is the role of B cells?
Make antibodies
Involved in humoral immunity
What is the precursor to red cells?
Erythroblasts
What is the pre-cursor to white cells?
Myeloblasts
When does the liver start haemopoeisis?
week 6 gestation
When does the spleen get involved in haemopoeisis?
week 16 gestation
Where is the most common site for bone marrow aspiration?
PSIS
What is the normal range for the myeloid : erythroid ratio?
1.5:1 - 3.3:1
What are proplatelets?
Branching processes of megakaryocytes which reach out into sinusoidal blood vessels
What regulates neutrophil precursor maturation?
G-CSF
What is plasma?
The liquid component of blood which contains fibrinogen
What is the main role of the erythrocyte?
Transport O2 from lungs to tissues
When does haemopoeisis begin to occur in the liver?
Week 6
When does haemopoeisis being to occur in the spleen?
Week 12
What changes occur during growth than limits adult haemopoeisis sites?
Active red marrow in kids is gradually replaced by fat (yellow marrow)
Where does haemopoeisis occur in adult long bones?
Trabecular area
Where is TOP produced?
Liver
Outline the developmental stages of neutrophil growth
Promyelocyte > myelocyte > metamyelocyte > neutrophil
Give the stages of cell growth and development of monocytes
Monoblast > promonocytes > marrow monocytes > blood monocytes (then tissue macrophages
What does an elevated RDW indicate?
Variation in cell size
What is the normal level of reticulocyte?
<2%
What does ESR measure?
Acute phase response to pathological processes by red cells (rate of red cell decline)
Where is CRP made?
Liver
How long do reticulocytes last in the circulation before maturing to erythrocytes?
1-2 days
Where does Hb synthesis occur?
Mitochondria
What is the major rate limiting step of Hb synthesis?
Conversion of glycine and succinic acid to delta-aminolaevulinic acid by ALA synthase
Which vitamin is cofactor for the conversion of glycine and succinic acid to delta-ALA?
B6
What are the two confirmations of Hb?
T (taut) and R (relaxed)
What is the T conformation of Hb?
No O2 boudn
Globin chains held together by electrostatic bonds
What is the R conformation of Hb?
O2 bound
Remaining O2-binding sites more exposed to give a higher affinity for oxygen
How does 2,3-BPG affect Hb O2 binding?
Reduces it