Chapter 22: Alterations of Hematologic Function

Blood Composition

Plasma & Formed Elements (RBCs, WBCs, Platelets)

Plasma (55%)

Comprised of water, proteins, electrolytes, nutrients & hormones

Formed Elements (45%)

• RBCs transporting oxygen

• WBCs immune defense 

• Platelets for clotting 

Plasma

Transport nutrients, hormones & waste products. Maintain BP & volume and regulate body temperature 

Plasma Proteins

Albumins, Globulins, Fibrinogen

Albumins

Maintains osmotic pressure & transports substances. Most abundant.

Low Albumin

Will cause edema due to fluid shifting (Ex; Liver Disease)

Globulins

Antibodies (immunobodies) that fight infections by binding to specific antigens like bacteria & viruses 

Fibrinogen

Blood clotting factor precursor

Hematopoiesis 

Formation of ALL blood cells in the bone marrow 

Stem Cells (Hematopoiesis)

Able to differentiate into RBCs, WBCs & Platelets

Erythropoiesis

Production of Red Blood Cells in the bone marrow

Erythropoietin

Hormone that is produced primarily by kidneys in response to low oxygen levels that are stimulated by hypoxia 

Erythropoietin role in Erythropoiesis

They stimulate the bone marrow in order to increase the production of Red Blood Cells

Low erythropoietin

Chronic Kidney Disease (Normocytic Anemia) from low RBCs

Destruction of Senescent Erythrocytes

Occurs in the spleen & liver when macrophages break down old red blood cells into hemoglobin & other components 

Hemoglobin Breakdown

Heme to biliverdin (green pigment) to bilirubin (yellow pigment)

Hemoglobin

Carries oxygen from the lungs to tissues & carbon dioxide back to the lungs 

Hemoglobin Structure

4 polypeptide chains + 4 heme groups, each with 1 iron

Oxygen Binding (Hemoglobin)

Cooperative binding that allows hemoglobin to carry 4 oxygen molecules because of its spherical shape 

Hemolysis

Breakdown of Red Blood Cells (Erythrocytes)

Excessive Hemolysis

Can lead to jaundice (yellow of skin/eyes)

Bilirubin

Enters the bloodstream bounded to albumin & is transported to liver. Processed by the liver & excreted as bile.

Metabolism of Bilirubin

In the liver, it is conjugated with glucuronic acid to form water-soluble bilirubin 

Unconjugated Bilirubin

Bilirubin when bounded to albumin, converted to this in the small intestine. Excreted as stool or urine.

Iron & Hemoglobin

Iron is essential for Heme Synthesis because it is stored in Ferritin & Hemosiderin in the liver/spleen. Able to be absorbed in duodenum, enhancing Vitamin C 

Platelets role in Hemostasis

To form a temporary platelet plug after vessel injury, process of stopping bleeding. 

Platelet Dysfunction Disorders

Thrombocytopenia, von Willebrand Disease

Blood Clotting Mechanism Steps

• Release of clotting factors from injured tissue cells & sticky platelets (temporary platelet plug)

• Chemical Reactions leads to the formation of thrombin, which converts fibrinogen to fibrin

• Fibrin traps blood cells & platelets, forming a clot 

Process of Hemostasis

1. Vascular Spasm

2. Platelet Plug Formation

3. Platelet Activation

4. Coagulation Cascade

5. Fibrin Clot

6. Fibrinolysis

Vascular Spasm (Hemostasis)

Blood vessels constricting at the site of injury, reducing blood flow

Platelet Plug Formation (Hemostasis)

Platelets adhere to damaged blood vessels & release substances that activate & aggregate other platelets = temporary plug 

Temporary Platelet Plug

Helps prevents further blood loss

Platelet Activation

Platelets undergo conformational change in GPIIb/Illa receptors, resulting in their ability to bind adhesive proteins, including fibrinogen & von Willebrand factor 

Coagulation Cascade/Aggregation

Series of events that convert fibrinogen into fibrin. Activation of coagulation factors, thrombin & fibrin

Clot Retraction/Dissolution

Clot contracts, squeezing out excess fluid making it more compact. Regulated by thrombin & plasminogen activators 

Fibrinolysis

Once healed, clot is gradually broken down by enzyme & is back to normal

Coagulation Factors

Factors 1 - 13, excluding Factor 6 play vital roles in the Coagulation Cascade

Clinical Relevance (Coagulation Cascade)

Anticoagulants like Heparin & Warfarin target specific stages of the Coagulation Cascade

Intrinsic Pathway

Triggered by damage inside the blood vessel that is done in slowly & in multiple steps. Involves Factors XII, XI, IX & VIII (12, 11, 9, 8). aPTT

Extrinsic Pathway

Triggered by external trauma/tissue factor that is done fast. Involves Tissue Factor & Factor VII (7). PT/INR

Common Pathway

Both pathways converging at Factor X (10) Activation

Fibrin Formation

Thrombin converts to fibrinogen to fibrin which forms a clot

Purpose of Fibrinolytic System

Take care & bust clots

Fibrinolysis Initiation

Plasminogen (plasma protein) binds to fibrin to begin fibrinolysis

Tissue Plasminogen Activator t-PA

Initiates intravascular fibrinolysis by activating plasminogen bound to fibrin 

Urokinase Plasminogen Activator u-PA

Major activator of fibrinolysis in tissues (extravascular)

Plasmin

Digests fibrin into smaller soluble pieces known as fibrin degradation products 

Urokinase-like Plasminogen Activator Receptor u-PAR

Receptor that facilitates Urokinase Plasminogen Activator u-PA, binding to activate plasminogen at injury site

Transferrin

What iron is transported with & is stored as Ferrition

Clot Breakdown

Done by Fibrinolysis, it is gradually broken down by enzyme & is back to normal