Hemodynamic disorders (1 of 3)

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

By secreting tissue factor

Like TNF and IL-1

Hemostasis, cont’d

= factor III = thromboplastin

also activates platelets

Degraded by adenosine diphosphatase produced by endothelial cells

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

•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

protein Cto cleaving and activating

•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

Coagulation cascade

We need phospholipid surface (by endothelium and platelets, and calcium ions

The ability of coagulation factors II, VII, IX, and X to bind to calcium requires vit. K

Lab tests

• Prothrombin time (PT)…for activity

of proteins of extrinsic pathway

• Partial thromboplastin time (PTT)

…for activity of intrinsic pathway

proteins

-II -V -VII -X -Fibrinogen

-II -V -VIII -IX -X -XI -XII -fibrinogen

Can be used for monitoring heparin activity

The fibrinolytic system