Physiology: Blood cells and Hemostasis (Blood Clotting) Chapter 23

Blood Functions:

Transports O2, nutrients, hormones, and other substances to the tissue

• Transports waste products and Co2 away from the tissue 

• Maintains homeostasis (fluid balance, thermoregulation, buffering activity, and hemostasis)

• Contributes to immunity; protection against pathogens

Composition of Blood:

 Blood is a suspension of cells in a liquid medium

what does Plasma: Liquid Medium contain?

• Water, Ions, nutrients, waste products, gases, hormones

What are the proteins that plasma makes up?

• : albumin, globulins, clotting factors

What percent of water does plasma make up?

90%

Blood Cells- Erythrocytes:

• Red blood cells- gas transport 

Blood Cells- Leukocytes

•  White blood cells- immunity

Blood Cells- Thrombocytes (platelets):

•  Hemostasis- not quite cells- cell fragments

Plasma Proteins: Albumin

Maintains colloid osmotic pressure (25mmHg) in vessels; acts as a transport protein

Plasma Proteins: Globulins

 Maintain colloid osmotic pressure; acts as transport/carrier proteins; inhibits proteases; y globulins are immunoglobulins (antibodies) produced by plasma cells (humoral immunity)

Plasma Proteins: Fibrinogen and Clotting Factors:

• Important in coagulation 

Electrolytes

(Na+, K+, Ca2+, Cl-, Mg2+) regulation of fluid balance, pH, and muscle function

What is the Osmolality in plasma proteins?

• 275-295 mOsm/L

What is Plasma

•  Blood mixed with anticoagulant (EDTA, heparin, sodium citrate) before cen trifugation; thus clotting factors are present in plasma

What is serum?

• NO anticoagulant used; blood is allowed to clot before centrifugation; Serum is devoid of most clotting factors, most notably fibrinogen

What is Hematocrit (HCT)=

Percent (%) of whole blood volume that is comprised of RBCs

• Blood is centrifuged- blood cells collect at bottom of tube, plasma at top

What is hematocrit influenced by?

• Number and size of RBCs

• Amount (volume) of plasma

What is the formula for calculating hematocrit?

RBC volume/ total blood volume

Regulation of Erythropoiesis

Key Player:

The hormone erythropoietin (EPO) produced by the KIDNEY 

• Stimulus for increased EPO production by kidney is decreased oxygen delivery to kidneys 

• EPO will then be released into blood stream and reach the red bone marrow to stimulate increased RBC production

• RBC output increases oxygen carrying ability of blood 

What is the primary function of Red Blood Cells (RBCs)= Erythrocytes

• Transports O2 from lungs to tissues (hemoglobin), and CO2 from tissues to lungs (* carbonic anhydrase)

• CO2+H2O <–> H2CO3- ←-> HCO3- + H+

• No nucleus, no mitochondria (glycolytic metabolism), no organelles …“Bags of hemoglobin”

What is the lifespan for red blood cells?

~120 days: Senescent RBCs removed from circulation by macrophages- spleen, liver, and bone marrow

What is Hemoglobin:

Iron(Fe2+): Containing oxygen transport protein of RBCs

• Composed of 4 globin chains, each with a heme group- binding site for O2

• Each heme molecule contains one Fe2+atom

• Buffers H+ ions, allowing CO2 transport

What is Hemolysis:

Breakdown of “used up” RBCs

What is Phagocytosis by macrophages in spleen and liver:

RBCs broken down into heme and globin chains

What is Heme Pigment

Metabolized to bilirubin and iron

• Bilirubin secreted into bile and eliminated in feces

• Iron “Recycled” back to bone marrow to be reutilized to make new RBCs

• Globin broken down into what that may be refused to make protein?

• amino acids

What is jaundice

Excess amounts of bilirubin in the bloodstream

What is NORMAL hemostasis

• Normal: Blood usually fluid; Seals broken blood vessels

What is ABNORMAL hemostasis

 Inappropriate clotting or Insufficient clotting

What is the Goal for Hemostasis/Thrombosis(Prothrombiotic):

Repairing Micro and micro vascular injury, and limiting blood loss

What is the Goal for Endogenous Fibrinolysis:

Preventing vessel occlusion and inadequate perfusion of vital organs

What are the Steps in Hemostasis?

A. Primary Hemostasis: Platelet plug and vasoconstriction

1. Injury to blood vessel

2. Smooth muscle contraction

3. Platelet plug formation

      B.   Secondary Hemostasis: Coagulation cascade that results in thrombus (fibrin-containing blood clot) (4-5)

4. Activation of coagulation cascade

5. Thrombus Generation

     C.    Fibrinolysis: degradation of blood clot (6-7)

6. Activation of anticlotting systems

7. Fibrinolysis

What is Platelet Plus Formation

1. Adhesion: Platelet deposition and adhesion

2. Activation: Platelet secretion 

3. Aggression: Platelet aggregation 

Megakaryocytes are found in?

bone marrow and LUNG 

Platelet Plug Formation

Adhere to exposed collagen, fibronectin, laminin

• Adherence To activates platelets 

• TXA2- vasoconstriction and adhesion/aggregation

• ADP- aggregation

• Von Willebrand factor- further platelet activation and adhesion to collagen

• Fibrinogen- fibrin (in blood) binds to activated platelet receptor, promoting platelet aggregation

Clotting Factors:

Except for Ca++, all are plasma proteins

• Synthesized mainly be liver as inactive precursors (proenzymes or zymogens- activated by proteolytic cleavage)

• Four clotting factors require Vitamin K for synthesis (II, VII, IX, and X)

What are the Coagulation Cascades: Thrombin formation- 2 pathways?

Intrinsic (Vessel damage) and Extrinsic (Tissue trauma)

Extrinsic (Tissue trauma)

Intrinsic and extrinsic pathways- generation of Factor Xa (1st molecule in the common pathway- prothrombin to thrombin)

Intrinsic Pathway:

Activated when blood comes in contact with subendothelial matrix

• Involves factors intrinsic to blood

• Quantitatively the most important of the 2 pathways, but slower

Extrinsic Pathway:

Activated by tissue factor: released by damaged- vascular, non-formed elements’, cell membranes

• Rapid response (initiates coagulation)

• Augments intrinsic pathway

Anticoagulants: Agents that depress the action of procoagulants or inhibit anit-clotting factors:

• Heparin, Anti-Thrombin (dabigatran), Anti-thromboplastin, Anti-X factor 

Anticoagulants: Agents that remove calcium from the blood (in vitro):

• EDTA, Citrate, Oxalate (calcium chelators)

Anticoagulants: Agents that inhibit the synthesis of clotting factors by blocking Vitamin K activity:

• Warfarin (Coumadin), Dicoumarol

Anticoagulants: Agents that interfere with platelet plug process:

• Aspirin, COX inhibitors, many others

True or false: Anticoagulants and antiplatelet agents cannot dissolve a clot once formed; these are “preventative” treatments

True

“Fibrinolysis” is what?

the process of breaking down fibrin in the clot 

Thrombolysis is?

 More general multifactorial process of dissolving a clot

• Plasminogen= zymogen

• Activated by tissue plasminogen activator (t-PA) and urokinase (u-PA) to form plasmin

• T-PA & u-PA= “thrombolytics”

• T-PA & u-PA used in acute medical crises (MI, stroke, PE) tha require rapid clot dissolution

What do Anti-Thrombotic Blood-Endothelial Cell Interface do?

• Secrete t-PA

• Synthesize prostacyclin (PGI2): Inhibits platelet activation and degranulation, and promotes vasodilation

• Secrete nitric oxide (NO), inhibiting platelet adherence

• Bind thrombin- clotting factor breakdown (negative feedback)

• Display heparin-like molecules- bind anti-thrombin (activates)- inactivating thrombin and other clotting factors