Thursday, May 27, 2010

Characteristics of Inflammation

Characteristics of inflammation

We all have inflammation in our body at one point or the other caused during activities, physical stress, accidents, animal or insect bites, pathogenic organisms etc. Inflammation can occur on the skin and subcutaneous tissue, respiratory tract, urinary tract, gastrointestinal tract etc. Usually we find swelling, pain, redness, or infection in that area. What is inflammation and what all happens when our body has an inflammation and what are the clinical features of inflammation?


When an area of the body is injured or altered from its normal structure, it is invaded by bacteria, virus, or parasite etc. and the body produces a defense mechanism by which the harmful antigens are destroyed or removed. A series of actions occur which protects our body from the harmful agent and all these constitute an inflammation or inflammatory reaction. These are detected by its clinical features, which are the 5 signs of inflammation.

Cardinal signs of inflammation:

1. Rubor (redness)
2. Calor (heat)
3. Dolor (pain)
4. Tumor (swelling)
5. functio laesa (loss of function).

The area becomes hot, red, and painful. There will be swelling all over the area and subsequently loss of function of the body part. The redness and heat are due to the increased blood flow to the inflamed site, swelling is caused due to accumulation of fluid and pain is due to the release of chemicals that stimulate the nerve endings.


Process of inflammation: The inflammatory process is initiated by cells present in the tissues such as resident macrophages, dentritic cells, histiocytes, Kuppfer cells and mastocytes. When a burn, injury, or infection occurs these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation mentioned above. Inflammation is characterized by marked vasodilation, increased permeability, and slowing of blood flow. Vasodilation or the dilation of the blood vessels in the affected area produce a net increase in the blood flow to that area causing redness (rubor) and heat (calor). The increased permeability of the blood vessels results in exudation or leakage of the of plasma proteins and fluid into the tissue which manifests as the swelling (tumor). The mediators that are released such as histamine and bradykinin increases the sensitivity to pain and cause pain(dolor). Increased permeability of the blood vessel results in movement of plasma proteins and fluid into the tissues with resultant stasis of blood due to increased concentration of cells in the blood, a condition characterized by engorged blood vessels filled with blood cells. Stasis or slowing of the blood occurs and results in migration of the white blood cells or leukocytes which is mainly neutrophils that move towards the walls of the blood vessel into the tissues called margination. The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury. The loss of function (functio laesa) is the result of a neurological reflex in response to pain.

Neutrophil margination during inflammation


Cellular changes: The main cellular component that takes part in inflammation are the leukocytes or the white blood cells. These cells move from the blood into the inflamed tissue by extravasation to assist inflammatory process. Some act as phagocytes ingesting bacteria, virus, and cellular debris etc. Others release enzymatic granules which damage the pathogenic invaders and releases substances which mediate and develop the inflammatory response. When the bacteria have invaded the inflamed area, the emigrated leukocytes are attracted to the bacteria in the infected tissues by a process called chemotaxis.The leukocytes which include neutrophils, eosinophils, and monocytes, phagocytose (swallow) the bacteria and digest them. So bacteria and other foreign bodies are digested and destroyed from the site of inflammation. Some leucocytes die along with other degenerated tissue and dead bacteria is turned into a white liquified form called the pus.


Mediators of inflammation: There are a number of cellular and plasma based mediators which helps in modifying the inflammatory process

1) The cell based (RBC, WBC, platelets) mediators are lysosome granules, histamine, IFN-y, IL-8, leucotriene B4, nitrous oxide, prostaglandins, TNF-alfa, and IL-1.
Lysosome granules are present in granulocytes. These cells contain a large number of enzymes which perform certain functions to facilitate inflammation.
Histamines are vasoactive amines present in mast cells, basophils, and platelets. Histamine causes areteriolar dilation and increased venous permeability.
Interferons are found in T-cells and NK cells. They have antiviral, immunoregulatory, and anti-tumour properties.
Interleukins are found primarily in macrophages. It helps in activation and chemoattraction of neutrophils, monocytes, and eosinophils.
Leukotrienes are found in leukocytes. It is ble to mediate leukocyte adhesion and activation, allowing them to bind to the endothelium and migrate across it.
Nitric oxide is found in macrophages and endothelial cells. It is a potent vasodilator. It relaxes smooth muscle, reduces platelet aggregation, aids in leukocyte recruitment, and antimicrobial activity in high concentrations.
Prostaglandins are found in mast cells. These are a group of lipids which can cause vasodilation, fever, and pain.

 
2) The plasma based (fluid in the blood)  mediators include bradykinin, plasmin, thrombin, C3, C5a, Factor XII etc.
Bradykinin is produced by the kinin sytem. It is a vasoactive protein which is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain.
C3 is produced by the complement system. It cleaves to produce C3a and C3b. C3a stimulates histamine release by mast cells and thereby producing vasodilation. C3b  binds to bacterial cell wall and act as an opsonin, which marks the invader as a target for phagocytosis.
C3a is produced by the complement system. It stimulates histamine release by mast cells, thus producing vasodilation. It also act as a chemoattractant to direct cells by chemotaxis to the site of inflammation.
Factor XII is produced in the liver. It is a protein which circulates inactively in the blood plasma, until activated by collagen, platelets, or exposed basement membranes. When activated, it is able to activate three plasma systems involved in inflammation: the kinin system, fibrinolysis system, and coagulation system.
Plasmin is produced by the fibrinolysis system. It is able to break down fibrin clots, cleave complement protein C3, and activate Factor XII.
Thrombin is produced by the coagulation system. It cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a blood clot.

An acute inflammation usually resolve with resolution of symptoms and relief of associated infection if proper measures are undertaken. It can also go into a severe or more chronic phase when those underlying causes are not controlled or eliminated.


These are some of the processes that happen when an acute inflammation occurs in the part of our body. Hope you get an idea about what actually inflammation is, what the signs of inflammations are, what processes that happen in an acute inflammation at the cellular level and about the mediators of inflammation.






 

Monday, May 17, 2010

Compatibility In Human Blood Groups

We come across circumstances where there is a need to transfuse blood in conditions of medical emergency or undergoing surgeries when patient will require blood transfusion. Good precautions are taken in testing the blood between the donor and the recipient. When blood from one person is transfused to another person, it must be ensured that donor's blood perfectly matches with the blood of the recipient, otherwise mismatch between these blood groups occur. If a unit of incompatible blood is transfused between the a donor and a recipient it results in serious reaction, like an acute hemolytic reaction which occurs with hemolysis of RBC, renal failure, and shock leading the death of the individual. Whereas Rh incompatibility in pregnancy is a hazard while delivering a child.

The blood group or blood type is a classification of the blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glucolipids depending on the blood group system.


The RBC cell membrane contains 2 main classes of antigens, namely 1) ABO and 2) Rh system.
1) The ABO system is the most important blood group system. The cell membrane of RBC contains antigen called agglutinogens. There are 2 such agglutinogens, A and B and so blood in human beings can be classified into 4 groups based on this.

i. Persons whose RBC membrane contains A agglutinogen in their blood can be categorized as group A.
ii. Similarly persons whose RBC membrane contains B agglutinogen in their blood can be called group B.
iii. Some persons have both A and B agglutinogens in their blood and therefore called AB group.
iv. Some persons have no agglutinogen in their RBC membrane and so is named as O blood group.

The plasma (fluid) in the blood also contains agglutinins which are antibodies present in the blood. There are 2 main classes of antibodies in the blood called 1) anti A antibody or alpha antibody, and 2) anti B antibody or beta antibody. Based on the agglutinins present in the human plasma the blood can be classified into 4 groups.

i. Persons whose blood plasma contains anti A antibody or alpha antibody.
i. Persons whose blood plasma contains anti B antibody or beta antibody.
iii. Persons whose blood plasma contains both anti A antibody and anti B antibody.
iv. Persons whose blood plasma contains no antibodies.

Blood Groups:



When group A blood is admised with the serum or plasma containing A agglutinin and the RBC containing A agglutinogen, the anti A agglutinin attacks the A agglutinogen and the blood gets agglutinated or the RBCs are clumped together. The clumped RBCs can cause 1) blocking the circulation in a small blood vessel or arteriole producing disaster and 2) undergo hemolysis and produce hazards including free Hb blocking renal tubules causing jaundice.

A person whose blood group is A, cannot have anti A agglutinin in his or her blood. Also in a person with B group, there can be no anti B agglutinin in his or her blood. Likewise in a person whose blood group is AB group there cannot be any agglutinin either A or B present in his or her plasma, and in a person whose blood group is O group there will be both A and B agglutinin present in his or her plasma.

For example, group A blood is transfused in a person belonging to group B,

Donor's blood contains A agglutinogen in the RBC and beta agglutinin in the plasma, while the recipeint's blood contains B agglutinogen in the RBC and alpha agglutinin in the plasma. The donor's RBC will be clumped and lysed by the recipient's alpha agglutinin. However the beta agglutinin of the donor will be so much diluted in the recipients blood that it will cause no harm of the recipient's RBCs.

So in a mismatched blood transfusion, donor's RBCs are lysed but the recipients RBCs remain unharmed.
O group of blood can be transfused (donated) to all groups of the ABO system, so it is called as the universal donor. AB  group of blood is called the universal recipient because any of the blood groups can be safely transfused (received) in the AB group person All these groupings are safe provided there is no Rh incompatibility.

a) Individuals with type A blood can receive blood from donors of type A and type O blood.
b) Individuals with type B blood can receive blood from donors of type B and type O blood.
c) Individuals with type AB blood can receive blood from donors of type A, type B, type AB, or type O blood. Type AB blood is called the universal recipient.
d) Individuals with type O blood can receive blood from donors of only type O.
e) Individuals of type A, B, AB and O blood can receive blood from donors of type O blood. Type O blood is called the universal donor.


RBC Compatibility Diagram




Plasma Compatibility Diagram

2) Rh System:

Rh owes the name to the rhesus monkey in whom this group was first discovered. There are several Rh groups but only factor D is clinically important. When Rh D is present in the RBC, the person is said to be
Rh +ve and when Rh is absent in the RBC, the person is Rh -ve. About 90% of the population is Rh +ve and about 10% is Rh -ve. Rh -ve persons provided they have not received an Rh +ve blood group have no Rh antibodies.

In ABO system agglutinins or antibodies occur naturally, that is without being exposed to the corresponding antigen. In Rh system, Rh antibodies are not naturally occurring and it appears only when Rh +ve RBC's enter in a Rh -ve person's blood. The exposure clinically occurs under 2 instances, i) when a Rh -ve person recieves Rh +ve blood through transfusion and ii) when Rh -ve mother conceives a Rh +ve fetus.
An Rh D-negative patient who does not have any anti-D antibodies (never being previously sensitized to D-positive RBCs) can receive a transfusion of D-positive blood once, but this would cause sensitization to the D antigen, and a female patient would become at risk for hemolytic disease of the newborn. If a D-negative patient has developed anti-D antibodies, a subsequent exposure to D-positive blood would lead to a potentially dangerous transfusion reaction. Rh D-positive blood should never be given to D-negative women of child bearing age or to patients with D antibodies.

There are the main blood groupings which we have to consider when doing a blood transfusion. Hope you will keep these in mind when you come across blood any transfusion procedure in the future.