Overview of Hemolysis

This article is part of a series under the module GEK1524. Click here for a link to other articles under this module series

Introduction

The Red Blood Cell and Hemolysis

Erythrocytes, also called red blood cells play an important role in our body. Red blood cells are responsible for the transport of oxygen from the lungs to the rest of our body, such as the muscles, where it releases oxygen for use. The metalloprotein called hemoglobin is the main component in red blood cells which aids in the oxygen transport by binding to the oxygen molecule.

Red blood cells are produced by the liver in the early stages of the foetal development, and then later taken over by the bone marrow.  The typical lifespan of a red blood cell is about 120 days. Aging red blood cells are destroyed by phagocytes by the process of phagocytosis in the spleen, liver and bone marrow. Premature or abnormal breakdown of red blood cells is called hemolysis. Hemolysis can usually be identified from the colour of plasma. Blood plasma containing red blood cells with hemolysis would appear red as free hemoglobin is leaked out from the cells.

 
The picture shows (left) a sample of a suspension of red blood cells in saline solution, (middle) a similar suspension that has been settled, and (right) a sample of red blood cells that underwent hemolysis.

Hemolysis has numerous causes and in substantial cases may lead to hemolytic anemia.  Hemolysis can be classified in various ways:
 

Intravascular Hemolysis: The breakdown of red blood cells directly in the blood vessels. Free hemoglobin released from the fragmented red blood cells may saturate the plasma in blood, causing conditions that may lead to renal failure.
 

Extravascular Hemolysis: The breakdown of red blood cells through the reticuloendothelial system (RES), which is part of the immune system.  Excessive removal of red blood cells may lead to anemia.
 

In-vivo Hemolysis: The breakdown of red blood cells inside the body. The breakdown of red blood cells might be due to various causes such as damaged blood vessels and prostethic blood vessels.
 

In-vitro Hemolysis: The breakdown of red blood cells outside the body, usually caused by mechanical trauma during specimen collection of blood. Examples of causes will be using the wrong needle size or insecure line connections.

Hemolytic anemia, a condition caused by the excessive breakdown of red blood cells, can be classified as hereditary hemolytic anemia and acquired hemolytic anemia.
 

Hereditary Hemolytic Anemia: Hemolytic anemia caused by abnormal red blood cells resulting from mutated genes that may be passed down from generation to generation.

Acquired Hemolytic Anemia: Hemolytic anemia that is acquired from a disease or other factors. Hemolysis may be caused by the immune system producing antibodies that destroy the red blood cells, or mechanical means, where breakage is caused by physical trauma.
 
Mechanical hemolysis is usually caused by physical damage due to turbulence in blood. In the process of hemolysis, the cell membrane of the red blood cell is ruptured due to high sheer stress.  Turbulence in blood can be formed in various ways, such as in stenoic blood vessels or blood vessels with damaged valves. In most cases, the laminar flow of blood is disrupted due to the narrowing of the blood vessel's lumen. Taking this into consideration, prosthetic devices used to aid the circulatory system have to be designed to maintain the laminar flow of blood and avoid causing turbulence.

Medical Consequences of Hemolysis

Main Article: Medical Consequences of Hemolysis

Hemolysis may cause various medical conditions. They include Hemolytic Anemia, Hemoglobinemia and Hemoglobinuria. These conditions could pose serious health risk if left unattended. Hemolytic Anemia is an abnormal rate of red blood cells destruction, Hemoglobinemia is the build up of Hemoglobin in the blood plasma and Hemoglobinuria is the presence of Hemoglobin in the urine.

In this section, we will provide more details on the different medical consequences caused by the breakage of the Red Blood Cells, as well as the warning signs of these conditions.

Feeling of weakness, fatigue, especially during physical exertion is one of the syndrome of Hemolytic Anemia.

Turbulence

Main Article : Turbulence

Turbulence is the condition where the streamlines of a column of fluid becomes chaotic with the formation of eddies. It is a common phenomenon that can occur in fluids, commonly observed in fast flowing bodies of water such as waterfalls. Blood is also a fluid made of plasma and red blood cells; hence it is useful to understand the effects of turbulence on blood which ultimately influences the human body.

Blood is a viscous fluid. This means that its movement in the blood vessel exerts shear stress on the vessel wall and resists deformation. In this case, shear stress is a force exerted by the flow of the blood on the endothelial surface. In laminar flows, fluids generally have a parabolic velocity profile as seen in figure 1. When blood is forced through a narrow opening, the normal laminar flow pattern may break down into a turbulent flow pattern.

Generally, blood flow in the body is laminar; that is, the streamlines are continuous, ordered and do not cross. There are natural occurrences in the body when the flow becomes turbulent. Turbulence may be typical in vessels where the blood pressure is normally high, such as in the aorta. It may also occur where blood flow is impaired by a smaller orifice, such as flow through diseased heart valves and vessels.

Turbulence in post-stenoic regions of blood vessels

Main Article : Turbulence in post-stenoic regions of blood vessels

The build-up of plague is common in the regions of disturbed flow within our vascular systems. As the plague develop, stenosis, the narrowing of the lumens of the affected blood vessels, will occur. In this section, we will look into how a stenosed region can cause turbulent flow within the vascular system, which may in turn, cause hemolysis to occur.

Behavior of Red Blood Cells

Main Article: Behavior of Red Blood Cells

Red blood cells (RBCs) is 45% by volume of the human body. They are biconcave disc shaped objects with a 10nm thick viscoelastic membrane. RBSc are suspended in a Newtonian fluid called cytoplasm with a viscosity of 6.5mPas. The diagrams below show how RBCs look like:

Blood is a non-Newtonian fluid. Its biconcave disc shape gives it large surface area for deformation and diffusion. It has 6% (max.) stretching limit before rupture. Hemolysis is the untimely damage of red blood cells. At rest, blood would aggregate into coin-stack-shaped structures. As the shear stress increases, red blood cells would disperse individually, tank-treading starts at >1 Pa. Extensive Hemolysis occurs at >150 Pa. The measure of Hemolysis in a blood sample is a reliable indicator of the overall blood damage. Hemolysis is measured as the concentration of the free hemoglobin in blood stream. The Membrane Model using Finite Element method, The Immersed Boundary method and the Blood Damage model are used in describing Hemolysis Correleation.

Mechanical Valves

Main Article : Mechanical Valves

Valves are found in the heart as well as the veins. Our heart consists of four main chambers: the right atrium, the right ventricle, the left atrium, and the left ventricle. For both the Heart valves and the Venous valves, their purpose is to prevent the backflow of blood, and ensure the proper direction of blood flow through the circulatory system. However, in some cases, external valves are implanted into our body.

In this section, we will cover the linkage between such valves and haemolysis due to turbulence.

Blood Pumps & Hemolysis

Main Article : Blood Pumps & Hemolysis

Heart disease, in particular heart failure remains on of the leading causes of death in most countries. The most common method to deal with this disease is heart transplantation but is negated due to limited heart donors. In light of this, alternatives to the heart transplant are developed. This comes in the form of implantable ventricular assist devices like (1) continuous flow axial and centrifugal pumps. For example, BioPump is a centrifugal pump seen in the picture below and MicroVad is an axial one (2) Pulsed flow devices. These autonomous devices are intended as a medium-term bridge to transplant, and hopefully as a permanent clinical solution in light of progress/research being done at the Baylor College of Medicine.

Reference

1. Dhruv Arora, Computational Hemodynamics: Hemolysis and Viscoelasticity http://www.cats.rwth-aachen.de:8080/publications/Arora2005.pdf retrieved 21st January 2009
2. NK Shinton. CRC Desk Reference for Hematology. CRC Press LLC, 1998.
3. David E Mohrman, Lois Jane Heller. Cardiovascular Physiology. McGraw-Hill Book Co, 1997.
4. A V Hoffbrand, J E Pettit, P A H Moss. Essential Haematology. Blackwell Science, 2001.

Further Reading

Bruce R. Munson, Donald F. Young, Theodore H. Okiishi, (2002) Fundamentals of Fluid Mechanics ISBN-10: 0471675822

See Also

Other articles under module series GEK1524

1. Hypertension

2. Atherosclerosis

3. Coronary by-pass surgery

4. Thrombosis

5. Hemolysis

6. Endothelial Damage

7. High Blood Viscosity

8. Lecturer's Introduction

External Links

http://www.calgarylabservices.com/HealthcareProfessionals/SpecimenCollection/HemolysisEffects.htm