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

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49 Terms

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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

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Composition of Blood:

 Blood is a suspension of cells in a liquid medium

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what does Plasma: Liquid Medium contain?

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

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What are the proteins that plasma makes up?

  • : albumin, globulins, clotting factors

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What percent of water does plasma make up?

90%

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Blood Cells- Erythrocytes:

  • Red blood cells- gas transport 

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Blood Cells- Leukocytes

  •  White blood cells- immunity

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Blood Cells- Thrombocytes (platelets):

  •  Hemostasis- not quite cells- cell fragments

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Plasma Proteins: Albumin

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

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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)

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Plasma Proteins: Fibrinogen and Clotting Factors:

  • Important in coagulation 

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Electrolytes

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

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What is the Osmolality in plasma proteins?

  • 275-295 mOsm/L

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What is Plasma

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

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What is serum?

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

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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

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What is hematocrit influenced by?

  • Number and size of RBCs

  • Amount (volume) of plasma

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What is the formula for calculating hematocrit?

RBC volume/ total blood volume

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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 

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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”

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What is the lifespan for red blood cells?

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

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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

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What is Hemolysis:

Breakdown of “used up” RBCs

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What is Phagocytosis by macrophages in spleen and liver:

RBCs broken down into heme and globin chains

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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

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

  • amino acids

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What is jaundice

Excess amounts of bilirubin in the bloodstream

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What is NORMAL hemostasis

  • Normal: Blood usually fluid; Seals broken blood vessels

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What is ABNORMAL hemostasis

 Inappropriate clotting or Insufficient clotting

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

Repairing Micro and micro vascular injury, and limiting blood loss

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What is the Goal for Endogenous Fibrinolysis:

Preventing vessel occlusion and inadequate perfusion of vital organs

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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)

  1. Activation of coagulation cascade

  2. Thrombus Generation

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

  1. Activation of anticlotting systems

  2. Fibrinolysis

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What is Platelet Plus Formation

  1. Adhesion: Platelet deposition and adhesion

  2. Activation: Platelet secretion 

  3. Aggression: Platelet aggregation 

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Megakaryocytes are found in?

bone marrow and LUNG 

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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

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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)

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

Intrinsic (Vessel damage) and Extrinsic (Tissue trauma)

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Extrinsic (Tissue trauma)

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

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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

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Extrinsic Pathway:

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

  • Rapid response (initiates coagulation)

  • Augments intrinsic pathway

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

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

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

  • EDTA, Citrate, Oxalate (calcium chelators)

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

  • Warfarin (Coumadin), Dicoumarol

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Anticoagulants: Agents that interfere with platelet plug process:

  • Aspirin, COX inhibitors, many others

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

True

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“Fibrinolysis” is what?

the process of breaking down fibrin in the clot 

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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

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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