Physiology Flashcards
What is blood?
Specialised fluid composed of cells suspended in a liquid called plasma
What is the average adult blood volume in litres?
4.5-6 litres
What are the 3 types of blood cell?
Red blood cell
White blood cell
Platelets
What are the main components of plasma?
Water (90%)
Proteins (mostly albumin, Ig, clotting factors)
Nutrients
Salts
What are the 2 types of white cells?
Granulocytes
Agranulocytes
List the main granulocytes
Neutrophils
Eosinophils
Basophils
List the main agranulocytes
Lymphocytes
Monocytes
What do red blood cells do?
Carry oxygen
Buffer CO2
What do platelets do?
Stop bleeding
What do white blood cells do?
Fight infection and pathology
What is the process by which blood cells are produced?
Haemopoiesis from pleuripotent stem cells
Where are the sites of haematopoiesis in the embryo?
Yolk sac
Liver
Spleen
Where are the sites of haematopoiesis from birth to maturity?
Bone marrow
Liver
Spleen
Where are the sites of haematopoiesis in the adult?
Bone marrow of skull, ribs, sternum, pelvis and proximal femur
What processes have to occur to a stem cell in order to make blood?
Proliferation
Differentiation
Self-renewal
Quiescence
Outline the cell stages of erythropoiesis
Pronormoblast - early normoblast - intermediate normoblast - late normoblast - reticulocyte - erythrocyte
Describe the structure of a neutrophil
Segmented nucleus (polymorph) Neutral-staining
What are the functions of a neutrophil?
Phagocytose invaders
Attract other immune cells
Describe the structure of a eosinophil
Bi-lobed
Bright orange-red granules
What are the functions of an eosinophil?
Fight parasitic infections
Involved in hypersensitivity
Describe the structure of a basophil
Infrequent in circulation
Large deep purple granules with obscured nucleus
What are the functions of a basophil?
Circulating version of a mast cell
Mediates hypersensitivity
Describe the structure of a monocyte
Large single nucleus
Faintly staining granules, often vacuolated
What are the functions of a monocyte?
Enter tissues and become macrophages
Phagocytose invaders
Attract other immune cells
Live longer than neutrophils
Describe the structure of a lymphocyte
Mature: small with condensed nucleus and cytoplasm
Activated: blue cytoplasm extending neighbouring red cells with more open nucleus
What are the functions of a lymphocyte?
Numerous subtypes and functions
Cognate response
What methods can be used to identify primitive precursors?
Immunophenotype (antigen on cell surface)
Bio-assay (culture in vitro)
What is a common site for bone marrow biopsy?
Posterior iliac crest
Do red blood cells have a nucleus and/or mitochondria?
No nucleus or mitochondria, thus no DNA either
What is the average life-span of a red blood cell?
120 days
Red blood cells are produced from pleuripotent stem cells. True/False?
True
What happens to old red blood cells?
Phagocytic cells of the liver and spleen engulf old red blood cells
What happens to the haem group of broken down red blood cells?
Converted into bilirubin that is conjugated by the liver
Which hormone regulates erythrocyte production?
Erythropoietin
What stimulates erythropoietin release by the kidney?
Reduced oxygen carrying capacity of erythrocytes
At which stage of erythropoiesis does no further cell division take place? (i.e. not pleuripotent cells)
When polychromatic erythroblast forms (Hb in cytoplasm)
How do red blood cells synthesise ATP/energy? N.B. remember no mitochondria
Anaerobic glycolysis
Which compound is produced when there is reduced phosphate in the blood? What effect does this compound exert?
2,3-BPG
This releases O2 from Hb
Glutathione is a tripeptide consisting of which amino acids?
Glutamate
Cysteine
Glycine
What does glutathione protect against?
Toxic effects of oxygen free radicals
In what 3 forms is CO2 transferred to the lungs?
Physically dissolved (10%) Bound to Hb (30%) As bicarbonate (60%)
Which enzyme is vital for CO2 transport?
Carbonic anhydrase
How does the composition of adult and foetal Hb differ?
Foetal: alpha2-gamma2
Adult: alpha2-beta2
Foetal Hb has a higher affinity for O2 than adult Hb. True/False?
True
Foetal Hb has a higher affinity for 2,3-BPG than adult Hb. True/False?
False
Foetal Hb has less affinity for 2,3-BPG than adult Hb, favouring O2 transfer from mother to foetus during pregnancy
What is haemopoiesis?
Formation of blood cells
What are mature red blood cells called?
Erythrocytes
List the main groups of mature white blood cells
Granulocytes (neutrophils, basophils, eosinophils)
Monocytes (macrophages)
Lymphocytes (B cells, T cells, NK cells)
State the lifespan for a red blood cell, neutrophil and platelet
Red cell: 120 days
Neutrophil: 7-8 hours
Platelet: 7-10 days
Why is a reticulocyte blue on blood film?
Doesn’t have the full amount of Hb yet
Outline the progression from precursor to mature neutrophil
Myeloblast - promyelocyte - myelocyte - metamyelocyte - neutrophil
Where do precursor cells of blood cells come from? (what is the precursor of the precursors?!)
Haemopoietic progenitor cell, derived from stem cells
Self-renewal is a property of all haemopoietic cells. True/False?
False
Only occurs in stem cells; lost in descendants
Which germ cell layer are haemopoietic stem cells derived from?
Mesoderm
Circulating haemopoietic progenitors are detectable as early as week _ of life
Circulating haemopoietic progenitors are detectable as early as week 5 of life
What is the first site of erythroid activity? When does this activity stop?
Yolk sac
Stops by week 10
When does the liver begin erythroid activity?
Week 6
When does the spleen begin erythroid activity?
Week 12
When does the bone marrow begin erythroid activity?
Week 16
List the main bony sites of haemopoiesis post-natally
Tibia and femur
Vertebra
Sternum
Ribs
Osteoblasts form/resorb bone and osteoclasts form/resorb bone
Osteoblasts form bone and osteoclasts resorb bone
What part of long bones - epiphysis, metaphysis or diaphysis - involves the most haemopoiesis?
Metaphysis
What is “red” and “yellow” marrow?
Red marrow: haemopoietically active
Yellow marrow: fatty and inactive
With age, yellow marrow replaces red marrow
What regulates neutrophil maturation?
Granulocyte-colony stimulating factor (G-CSF)
How is haemopoiesis assessed?
Blood count
Cell indices
Morphology (blood film)
Bone marrow examination
What specialist tests can be done to analyse haemopoietic precursor cells?
Immunophenotyping
Cytochemistry
Clonogenic assay
Animal modelling
Where are haemopoietic stem cells of lymphoid cells located?
Liver in foetus
Bone marrow post-natally
Where are precursor lymphoid cells located?
Bone marrow (B-cells) Thymus (T-cells)
List the main peripheral (secondary) lymphoid tissues
Spleen
Lymph nodes
Tonsils
What are the functions of the lymphatic system?
Return lymph (tissue fluid) to circulation in homeostasis
Prevent accumulation of fluid in tissues (oedema)
Filter lymph of toxins
What is haemostasis?
Cessation of bleeding whilst maintaining vascular patency
List the main components/processes of normal haemostasis
Formation of platelet plug (primary haemostasis)
Formation of fibrin clot (secondary haemostasis)
Fibrinolysis
Anticoagulation
What is the lifespan of a platelet?
7-10 days
Following endothelial vessel wall damage, collagen is exposed and releases which factor to attract platelets to adhere?
Von Willebrand Factor
Why is platelet plug formation impaired in older people, causing easy bruising?
Lose collagen from vessel wall with age - less Von Willebrand Factor and thus less platelet adherance and aggregation
List some consequences of failure of platelet plug formation
Spontaneous bleeding
Purpura
Mucosal bleed (epistaxis, GI, conjunctival)
Haemorrhage
What is the main screening test/investigation for primary haemostasis?
Platelet count
Which factor is released from damaged vascular endothelium during fibrin clot formation? Which factor does it activate?
Tissue factor
activates factor VIIa
Which factors are activated by factor VIIa, VIII and IXa in fibrin clot formation?
V
Xa
What is the effect of factors V and Xa in the propagation step of fibrin clot formation?
Encourage formation of thrombin from prothrombin
What is the effect of thrombin in fibrin clot formation?
Encourages formation of fibrin from fibrinogen
Single clotting factor deficiency is usually hereditary - give an example of a condition
Hereditary haemophilia
Multiple clotting factor deficiency is usually acquired - give an example of a condition
Disseminated intravascular coagulation
Describe the fibrinolytic pathway (breakdown of a clot)
Tissue plasminogen factor causes plasmin formation from plasminogen
Plasmin causes breakdown of fibrin to fibrin degradation products (D-dimers)
What are the main screening tests/investigations for secondary haemostasis?
Prothrombin time (PT time) Activated partial thromboplastin time (APTT)
If the PT time is prolonged and the APT time is normal, which factors are causing the problem?
Tissue factor
VIIa
If the PT time is normal and the APT time is prolonged, which factors are causing the problem?
VIII
IXa
Warfarin affects the PT time and heparin affects the APT time. True/False?
True