Supposedly CV physiology… but not Hauxwell’s lectures!!

Where does haematopoiesis occur? [3] Yolk sac (trimester one) Liver and spleen (trimester two) Red marrow (trimester three onwards)

What controls haematopoiesis? [2] Local cell-to-cell contacts Growth factors Paracrine (G-CSF) or endocrine (EPO) Control proliferation, differentiation, maturation

EPO speeds erythropoiesis by what two mechanisms? Increases rate of mitoses Decreases maturation time What four things are required? [4] EPO, iron, folic acid, vitB12

Steps of erythropoiesis?

Haematopoeisis Site: Bone marrow (but also liver and spleen) Stimulant: Mainly EPO (but also G- CSF) Requirements: Iron – stored as Ferritin. Levels controlled by the amount absorbed Folic Acid - absorbed in small intestine B12 – absorbed in terminal ileum. Requires intrinsic factor EPO Committed Stem Cell Proerythroblast Early Erythroblast (Basophilic) Intermediate Erythroblast (polychromatic) Late erythroblast (Orthochromatic) Reticulocyt e Erythrocyte

RBCs What does RBC maturation involve? [3] Decrease in cell size Haemoglobin production Loss of organelles Acquisition of eosinophilic cytoplasm Extrusion of nucleus Acquisition of biconcave disc shape Why are we aiming for that shape? [4] Increased surface area Increased flexibility Resists turgor Minimise Distance

Blood Vessel Histology Layers 1.Intima a)Endothelium – simple squamous Allows thing to pass through b)Basement Membrane c)Connective Tissue d)Internal Elastic Lamina 2.Media Circumferentially arranged smooth muscle 3.Adventitia Connective tissue containing vascular and neural supply Different vessel types contain differing amounts of these layers if present at all

3 key components of haemostasis 1.Endothelial Wall 2.Platelets 3.Coagulation cascade

Role of Endothelium In what ways is the endothelium normally anti-thrombotic? [3] Antiplatelet Protects blood from vWF Anticoagulant Secretes Heparin like molecules Fibrinolysis Can secrete t-PA Drugs: statins protect the endothelium

2 main roles of platelets 1.Form haemostatic plug 2.Provide a surface for recruitment and concentration of coagulation factors Antiplatelet drugs? Aspirin Clopidogrel

Role of the coagulation cascade Just remember…. THROMBIN Links inflammation, coagulation and repair pathways. Remind yourself of the anticoagulation drugs: In particular warfarin and heparin Do you know any new ones? Dabigatran - direct thrombin inhibitor Rivaroxaban/apixaban - direct factor Xa inhibitor

Vascular response to inflammation Remember your 4 cardinal signs? Cardinal signs (MACROSCOPIC) 1.Rubor 2.Tumor 3.Calor 4.Dolor 5.Functio Laesa

What vascular changes occur to bring about redness and heat in acute inflammation? [2] There is an increase in calibre and flow in the vessels Increased calibre due to vasodilation as a result of inflammatory mediators Opening up of new capillary beds increases flow.

Explain why the fluid produced in acute inflammation swelling is protein rich [2] There is an increase in vascular permeability Proteins and fluid leak out by diffusion down a concentration gradient

Cellular changes Recruitment and migration of neutrophils occurs in 4 steps 1.Margination 2.Adhesion 3.Emigration 4.Chemotaxis What is the name for the movement of cells across the endothelial wall? Diapedesis