What are the 4 stages of wound healing?
Haemostasis
Inflammation
Proliferation
Remodelling
Describe the haemostasis stage of wound healing
- Platelet adhesion, activation and aggregation
- Activation of coagulation cascade
- Waterproof layer of fibrin and fibronectin forms
Describe the inflammation stage of wound healing
- Infiltration by neutrophils
- Infiltration by macrophages on day 3
- Basal epithelial cells respond to epithelial growth factor to proliferation and migrate under the clot
- Platelets secrete platelet derived growth factor to stimulate fibroblasts
Describe the proliferation stage of wound healing
- VEGF stimulates new blood vessels to form
- Fibroblasts (on day 3-5) secrete type 3 collagen and fibronectin to plug the gap
- Myofibroblasts contract reducing the size of the wound
Describe the remodelling stage of wound healing
- Type 3 collagen is replaced by type 1 collagen (scar tissue) on day 5
- Blood vessels regress
Describe wound healing by secondary intention
- The defect fills with granulation tissue
- Epithelial regeneration occurs to cover the surface
- Myofibroblasts within granulation tissue contracts leading to scar formation
Describe the activation of a B-cell
- Matures in the bone marrow
- Circulates in the peripheral blood until they recognise an antigen (free or on antigen-presenting-cell)
- Ingests the antigen and displays fragments to attract a T-helper Cell
- Cytokines released by the T-cell helps the B-cell mature into plasma cells or memory cells
What are the 2 types of mature B-cell and describe them:
Plasma Cell
- found in the bone marrow and spleen
- live 1-2 weeks
- secrete large quantities of immunoglobulins
Memory Cell:
- needed in the secondary response of the adaptive immune system
Where does the maturation of T-cells happen?
In the thymus as they travel from the cortex to the medulla
What are the 2 types of mature T-cells?
CD4+ (helper)
CD8+ (cytotoxic)
How are CD4+ T cells activated and what is their response?
Recognise antigen in association with HLA II molecules found on antigen-presenting cells
Secrete cytokines to recruit and activate macrophages, cytotoxic T-cells, NK cells as well as activate B-cells to produce immunoglobulin
How are CD8+ T cells activated and what is their response?
Recognise antigen only on association with HLA I molecules found on endogenous antigens (found on cells infected by virus and bacteria)
Their response is the cytotoxic killing of target cells by inducing apoptosis
What are natural killer cells?
Cytotoxic CD8 cells that lack a T-cell receptor
What is the relation of HLA I molecules and the ability of a NK-cell to kill its target?
HLA I displayed on a target cell has an inhibitory effect on the NK-cell. Therefore when HLA molecules are absent (viral infections and malignancy) the NK-cell can kill its target
Name the causes of lymphocytosis
(Common in children vs neutrophil reaction in adults)
- Viral and bacterial infections
- CLL and ALL
- Non-Hodgkin lymphoma
- Thyrotoxicosis
What investigation results would you expect to see in Hodgkin Lymphoma?
Reed-Sternburg cells!
- Normocytic, normochromic anaemia
- Neutrophilia
- Lymphopenia
- Raised platelets (Early disease)
- Low platelets (Late disease)
- Raised ESR and CRP
- Raised LDH
Describe the regenerative properties of labile cells and give examples
Constantly dividing and regenerating
- Surface skin epithelium
- GI tract
- Blood cells
Describe the regenerative properties of stable cells and give examples
Generally dormant or very slowly replicating however can rapidly regenerate if stimulated to do so
- Liver
- Renal tubular epithelium
- Endocrine glands
Describe the regenerative properties of permanent cells and give examples
Cells have left the cell cycle so are incapable of division
- Skeletal muscle
- Brain
- Myocardium
Describe the epidemiology of CML vs CLL
CML: 40-60 but can be any age
CLL: 60-80, males
What investigation results would you expect to see in CML?
- Leucocytosis (predominantly neutrophils, and myelocytes)
- Raised basophils
- Normochromic, normocytic anaemia
Philadelphia chromosome in 98% of cases
What is the treatment of CML?
Tyrosine kinase inhibitors
How does the presentation of CML vs CLL differ?
Both are normally picked up on routine bloods
CML: massive splenomegaly
CLL: enlarged lymph nodes
What investigation results would you expect to see in CLL?
- Lymphocytosis
- Normochromic, normocytic anaemia
- Thrombocytopenia
