Hemodynamic disorders (1 of 3) Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

What will we discuss today? Hyperemia & congestion Edema Hemorrhage Hemostasis

Hyperemia & congestion Both = increase in blood volume within a tissue Hyperemia Congestion active passive red blue-red arterial venous

Morphology Acute VS chronic pulmonary congestion Acute VS chronic hepatic congestion

Edema, an introduction

Edema

Edema, clinical manifestations According to the tissue involved Can be life-threatening Examples………?

Hemorrhage = extravasation of blood from vessels Chronically congested tissues…capillary hemorrhages Hemorrhagic diathesis…susceptibility to bleed even with minor trauma Trauma, atherosclerosis, inflammation, or neoplasms can lead to hemorrhage

Hemorrhage, cont’d External or internal From trivial (bruises) to fatal (large vessels such as aortic dissection) Large bleeds in body cavities…give some names..

Hemorrhage, different sizes Petechiae…1-2mm …skin, mucous membranes and serosal surfaces …problems in platelets or vessel wall (e.g., vit. C deficiency) Purpura…3-5mm …same causes of petechiae …vasculitis is an important cause Echymoses…1-2cm …subcutaneous …= bruises …hemoglobin bilirubin hemosiderin

Hemorrhage consequences Hypovolemic shock Death Iron deficiency anemia No consequences

Hemostasis A series of regulated processes that maintain blood in a fluid, clot-free state in normal vessels while rapidly forming a localized hemostatic plug at the site of vascular injury The pathologic counterpart of hemostasis is thrombosis 3 main players: -vascular wall -platelets -coagulation cascade The endothelium can have anticoagulant functions, and can be induced to activate coagulation due to triggers such as microbes, hemodynamic forces, and inflammatory mediators Like TNF and IL-1 By secreting tissue factor

Hemostasis, cont’d also activates platelets = factor III = thromboplastin Degraded by adenosine diphosphatase produced by endothelial cells

The primary hemostatic plug is now formed Hemostasis, cont’d Platelets bind via glycoprotein 1b (GpIb) receptors to von Willebrand factor (vWF) on exposed extracellular matrix (ECM) …then they are activated shape change granule release …Released adenosine diphosphate (ADP) and thromboxane A2 (TxA2) additional platelet aggregation through binding of platelet GpIIb-IIIa receptors to fibrinogen The primary hemostatic plug is now formed

Hemostasis, cont’d The secondary hemostatic plug is now formed Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) fibrin polymerization The secondary hemostatic plug is now formed larger and more stable than the primary plug and contains entrapped red cells and leukocytes

Homeostasis, cont’d t-PA (tissue plasminogen activator, a fibrinolytic product) & thrombomodulin (interfering with the coagulation cascade) are of the counter-regulatory mechanisms that limit the process to the site of injury

Some inhibitors of coagulation Heparin-like molecules…on endothelial surface …they are cofactors for the plasma protein anti-thrombin III Thrombomodulin…change thrombin activity from cleaving fibrinogen to cleaving and activating protein C Tissue factor pathway inhibitor…inhibits tissue factor–factor VIIa complex and factor Xa Inhibits factor Va and factor VIIIa protein S is a cofactor for it

Abnormalities

We need phospholipid surface (by endothelium and platelets, and calcium ions Coagulation cascade The ability of coagulation factors II, VII, IX, and X to bind to calcium requires vit. K

Lab tests Prothrombin time (PT)…for activity -II -V -VII -X -Fibrinogen Prothrombin time (PT)…for activity of proteins of extrinsic pathway Partial thromboplastin time (PTT) …for activity of intrinsic pathway proteins -II -V -VIII -IX -X -XI -XII -fibrinogen Can be used for monitoring heparin activity

The fibrinolytic system

Thank You