Blood 2 A&P II Lecture

Ititiated by either the intrinsic or extrinsic pathway (usually both)

• -triggered by tissue-damaging events
• -involves a series of pro-coagulents
• -each pathways cascades towards factor X

Factor X complexes with Ca²⁺, PF₃, and factor V to form prothrombin activator

*phase 1 is the slowest part. once prothrombin actovator is formed, clot is created in 10-15 seconds*

• Intrinsic Pathway:
• -is triggered by nefatively charged surfaces (Activated platelets, collagen, glass)
• -Uses factors present within the blood (intrinsic)

• Extrinsic Pathway:
• -Is triggered by exposure to tissue factor (TF) or factor III (an extrinsic factor)
• -by passes several steps of the intrinsic pathway, so it is faster
• 

• Prothrombin activator catalyzes the transformation of prothrombin to the active enzyme thrombin
• 

Thrombin converts the soluable fribrinogen into fibrin

fibrin strands form the structural basis of a clot

Fibrin causes plasma to become a gel-like trap for formed elements

• Thrombin (with Ca²⁺) activates factor VIII which:
• -cross links fibrin
• -strengthens and stabilizes the clot until it can become permanently repairs

• Clot retraction:
• -Actin and Myosin in platelets contract within 30-60 minutes
• -Platelets pull on fibrin strands, squeezing out serum from the clot 

• Clot repair:
• -platelet derived growth factor (PDGF) stimulates division of smooth muscle cells and fibroblasts to rebuild blood vessel wall
• -Vascular endothelial growth factor (VEGF) stimulates endothelial cells toe multiply and restore the endothelial lining

Keeps clots from growing and getting out of control

Plasminogen in clot is converted into plasmin by tissue plasminogen actovator (tPA), factor XII, and thrombin

Plasmin is a fibrin-digesting enzyme

1. Swift removal and dillution of clotting factors

2. Inhibition of activated clotting factors

Most thrombin is bound to fibrin threads, preventing it from acting elsewhere

Antithrombin III, protein C, and heparin inactivate thrombin and other procoagulents

Hepain, another anticoagulent, also inhibits thrombin activity

• Platelet adhesion is prevented by
• -smooth endothelial lining of blood vessels
• -antithrombic substances, NO, annd prostacylin secreted by endothelial cells
• -Vitamin E quinine (VitE plus O²) acts as potent anticoagulent

Thromboembolytic disorders: undesireable clot formation

Bleeding Disorders: abnormalities that prevent clot formation

• Thrombus: clot that develops and persists in an unbroken blood vessel
• -may block circulation, leading to tissue deat (like a heart attack)

• Embolus: a thrombus freely floating in the blood stream
• -pulmonary emboli impair the ability of the body to obtain O²
• -cerebral emboli can cause strokes

• Prevented by:
• -Asprin: antiprostaglandin that inhibits thromboxane A2
• -Hepatin: anticoagulent used clinically for pre and post operatice cardiac care
• -Warfarin (Coumadin)-used for those prone to A-fib

Disseminated Intravascular Coagulation (DIC)

Widepread clotting blocks intact blood vessels

Severe bleeding occurs because residual blood unable to clot

Most common in pregnancy, septicemia, or incompatible blood transfusions

Bleeding Disorder where there is a deficient number of circulating platelets

Petechiae (small purplish spots) appear due to spontaneous, widespread hemorrhage

Due to suppression or destruction of bone marrow (such as cancer, radiation)

Diagnosed by a platelet count less than 50,000/mm³

Treatment: transfusion of concentrated platelets

Abnormal and sever bleeding occurs

Inability to sythesize procoagulants

causes include Vitamin K deficiency, Hepatitis, and Cirrhosis

Liver disease can also prevent the liver from producing bile, impairing fat, and Vit K absorption (vit K is fat soluable)

Hemophilia: several hereditary bleeding disorders

• Hemophilia A: most common (77%); due to a deficiency factor in factor VIII
• Hemophilia B: deficiency of factor IX
• Hemophilia C: mild tyoe, deficiency of factor IX

Symptoms: prolonged bleeding, especially into joint cavities

Treatment: plasma transfusions and injection of missing factors

• RBC membranes bear 30 types of glycoprotein antigens that are:
• -perceived as foreign if transfused blood is mismatched
• -unique to each individual
• -promotors of agglutination and are called agglutinogens (antigens)

Presence or absence of each antigen is used to classify blood cells into different groups

Antigens of the ABO and Rh blood groups case major transfusion reactions

Other blood groups (MNS, Duffy, Kell, and Lewis) are usually weak agglutinogens

A, B, AB, and O

based on the presence of A and/or B agglutinogens on the surface of RBCs

blood may contain anti-A or anti-B antibodies (agglutinins) that act against transfused RBcs with ABO antigens not normally present (react)

Anti-A or Anti-B form in the blood at about 2 months of age

• O- is the universal Donor because it has no antigens
• AB+ is the universal receiver because it has no anti-bodies

• O+ is the most common ABO in US
• AB- is the lease common ABO in US

There are 45 different Rh agglutinogens (Rh factors)

C,D,E the most common

Rh+ indicates the presence of D (85% of USA is Rh+)

Anti-Rh antibodies are not spontaneously formed in Rh_ individuals

Anti-Rh antibodies form in an Rh- indicidual receives a Rh+ blood and a second exposure will result in a transfusion reaction

Rh- mother becomes sensitized when exposure to Rh+ blood causes her both to synthesize anti-Rh antibodies


Anti-Rh antibodies can cross the placenta and destroy the RBCS of an Rh+ baby

Baby can be treated with prebirth transfusion and exchange transfusions after birth

RhoGAM serum containing anti-Rh can prevent the Rh_ mother from becoming senstized

Occurs if mismatched blood is transfused

• Donor cells...
• -are attacked by the recipients plasma agglutinins
• -agglutinate and clog small vessels
• -rupture and release free hemoglobin into the blood stream

• Results in...
• -diminished oxygen carrying capacity
• -Hb in kidney tubules will cause lethal renal failure

death from shock may result from low blood volume

• Volume must be replaced immeadiately with:
• -Normal saline or multiple-electrolyte solution that mimics the plasma electrolyte composition
• -Plasma expanders that mimic osmotic properties of albumin
• (but these may be more $$$ and cause significant complications)

• Hematocrit
• Blood glucose tests
• Microscopic examination reveals changes in RBCs
• Differential WBC count
• Prothrombin time and platelet count assess hemostasis
• SMAC- a blood chemistry profile
• Complete blood count (CBC)

-Fetal blood cells form in the fetal yolk sac, liver, and spleen

Red bone marrow is the promary hematopoietic area by the 7th month

blood cells develop from the mesenchymal cells called blood islands

The fetus forms HbFm which has a higher affinity for O2 than Hb A formed after birth

• Blood diseases of the aging:
• Chronic Leukemias, anemias, clotting disorders-usually precipitated by disorders of the heart, blood vessels, and the immmune system