The principal chemical mediator of the immediate phase of acute inflammation is Histamine. Here's a detailed explanation of the options given:

1. Serotonin: While serotonin is a vasoactive substance that can cause blood vessels to constrict or dilate, it is not the primary mediator of the immediate phase of acute inflammation. It is mainly associated with the regulation of mood, appetite, and sleep. In the context of inflammation, it plays a minor role compared to histamine.

2. Histamine: Histamine is indeed the correct answer. It is a potent chemical mediator released from mast cells and basophils in response to injury or antigenic stimulation. Upon release, histamine acts on blood vessels to cause vasodilation, increased permeability, and increased blood flow to the injured area, which are hallmark features of the immediate phase of acute inflammation. This results in the cardinal signs of inflammation: redness (rubor), heat (calor), swelling (tumor), and pain (dolor).

3. Kinin-Kallikrein system: The kinin-kallikrein system is another important mediator of inflammation, but it is more involved in the later phases. When activated, it results in the formation of kinins, such as bradykinin, which contribute to increased vascular permeability and pain. However, it is not the first line mediator in the immediate phase.

4. Complement system: The complement system is a group of proteins in the blood that work with antibodies to destroy pathogens and trigger inflammation. It is a key component of the innate immune response, but its activation and role are more pronounced in the later stages of inflammation rather than the immediate phase. The complement system is involved in the opsonization of pathogens, recruitment of phagocytes, and the formation of the membrane attack complex, which can lyse certain bacteria and cells.

The immediate phase of acute inflammation is characterized by the rapid response to tissue injury, which includes vasoactive changes and increased vascular permeability to allow fluid, cells, and proteins to move into the interstitial space. Histamine is quickly released from mast cells and basophils and acts on H1 receptors of blood vessels to induce vasodilation and increased permeability. This leads to the early symptoms of inflammation, such as swelling, redness, heat, and pain, and is crucial for the initiation of the inflammatory response to protect the body from harm.

Indirect chemical carcinogens differ from direct acting agents in that they require metabolic activation to exert their carcinogenic effects. This means that indirect carcinogens must undergo a chemical transformation within the body before they can damage DNA and induce cancer. Direct acting carcinogens, on the other hand, can interact directly with DNA without the need for metabolic conversion. Therefore, the correct answer is:

2. Induce carcinogenicity after chemical transformation


1. Induce carcinogenicity without chemical transformation: This statement is incorrect for indirect chemical carcinogens. Indirect carcinogens are typically non-reactive or less reactive in their original form and must undergo metabolic activation to become DNA-reactive. This metabolic conversion is crucial for their carcinogenic potential.

2. Induce carcinogenicity after chemical transformation: This is the correct explanation. Indirect carcinogens require metabolic activation by the body's enzyme systems, particularly phase I enzymes such as cytochrome P450, to convert them into electrophilic or reactive intermediates that can interact with DNA. This activation process can occur in various tissues, often the liver, where these enzymes are present. The reactive metabolites then form DNA adducts, which can lead to mutations and ultimately cancer if not repaired properly by the cell's DNA repair mechanisms.

3. Don’t require metabolic conversion: This statement is incorrect. Indirect carcinogens do require metabolic conversion to become active carcinogens. It is the direct acting carcinogens that can interact with DNA without the need for such activation because they are already electrophilic or reactive in their original form.

Gas Gangrene, also known as clostridial myonecrosis or anaerobic cellulitis, is a severe and rapidly progressing form of necrotizing soft tissue infection caused by the bacterial genus Clostridium. The condition is characterized by the production of gas within the tissues due to the fermentation of carbohydrates by the bacteria. The most common species implicated in gas gangrene is Clostridium perfringens.

1. Clostridium tetani: This bacterium is the causative agent of tetanus, which is a neurotoxic disease that leads to muscle spasms and rigidity. It is not directly associated with gas gangrene, although both are anaerobic infections that can occur in deep puncture wounds and both produce exotoxins. However, the primary symptom of tetanus is muscular rigidity and spasms due to the production of tetanospasmin, not the tissue destruction and gas production seen in gas gangrene.

2. Clostridium perfringens: This is the most common cause of gas gangrene. C. perfringens produces alpha toxin, which is a powerful enzyme that can break down tissue and release gas as a byproduct. The infection typically occurs in the deep layers of the skin and muscles following a severe trauma, surgery, or burns, where there is a lack of oxygen, allowing the anaerobic bacteria to thrive. The rapid spread of infection is due to the bacteria's ability to produce multiple exotoxins that cause tissue necrosis and vasoconstriction, leading to ischemia and further tissue damage.

3. Clostridium difficile: Although a member of the Clostridium genus, C. difficile is mainly associated with antibiotic-associated diarrhea and pseudomembranous colitis. It is a hospital-acquired infection that affects the intestinal tract and is not typically involved in causing gas gangrene. While it is an anaerobic bacterium, its pathogenicity is primarily due to the production of toxins that damage the colon's mucosal lining rather than invading tissues outside the gut.

4. Peptostreptococci: These are anaerobic bacteria that can be part of the normal skin and mucosal flora. They are involved in various infections, particularly in immunocompromised individuals or those with underlying medical conditions. Peptostreptococci are more commonly associated with mixed anaerobic infections such as abscesses, osteomyelitis, and other soft tissue infections, but they are not typically the sole cause of gas gangrene.

Sickle cell disease results from mutation, or change, of certain types of hemoglobin chains in red blood cells (the beta hemoglobin chains).

When the oxygen concentration in the blood is reduced, the red blood cell assumes the characteristic sickle shape. This causes the red blood cell to be stiff and rigid, and stops the smooth passage of the red blood cells through the narrow blood vessels.

The newly formed collagen in the scar tissue is arranged differently compared to the organized collagen fibers in the unwounded skin, leading to a weaker structure. The 70-80% tensile strength is typically what is seen in well-healed sutured wounds. This remaining deficit is because scar tissue is less elastic and more prone to dehiscence (reopening) under tension compared to normal skin.