Transfusion Related Acute Lung Injury : Introduction & Mechanism

 Transfusion Related Acute Lung Injury :

The cause of TRALI is currently not fully understood. 80–85% of cases are thought to be immune mediated.

 Antibodies directed toward human leukocyte antigens (HLA) or human neutrophil antigens (HNA) have been implicated, with transfused antibodies shown to bind antigens expressed on pulmonary endothelial cells to initiate acute inflammation in the lungs.

 Women who are multiparous (have carried more than one pregnancy to viable gestational age) develop these antibodies through exposure to fetal blood; transfusion of blood components obtained from these donors is thought to carry a higher risk of inducing immune-mediated TRALI.

Previous transfusion or transplantation can also lead to donor sensitization. 

To be at risk of TRALI via this mechanism, the blood recipient must express the specific HLA or neutrophil receptors to which the implicated donor has formed antibodies. 

A two-hit hypothesis has been suggested wherein pre-existing pulmonary pathology (i.e., the first-hit) leads to localization of neutrophils to the pulmonary microvasculature. 

The second hit occurs when the aforementioned antibodies are transfused and attach to and activate neutrophils, leading to release of cytokines and vasoactive substances that induce non-cardiac pulmonary edema.

A proposed mechanism for non-antibody-mediated TRALI involves the accumulation of bioactive lipids in stored blood components (red cells, platelets, or plasma) that are capable of priming neutrophils.

TRALI is typically associated with plasma products such as fresh frozen plasma. 

TRALI can also occur in recipients of packed red blood cells, whether adult or pediatric patients.

Due to the higher risk of TRALI resulting from donations by females, the AABB (formerly the American Association of Blood Banks) has recommended that those blood components with a high volume of plasma not be used for transfusion, but for further processing into other therapeutic products.

 To mitigate the risk of TRALI, female donors are excluded from fresh frozen plasma donation in Germany as of 2009 if they have a history of pregnancy and there are no HLA/HNA screening results available, which has resulted in a significant reduction of TRALI reports.

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Sarcomere : Structure and Function

A sarcomere is the fundamental unit of striated muscles, such as skeletal and cardiac muscles, that is responsible for muscle contraction and performance. Sarcomeres are made up of many parallel thin actin filaments and thick myosin filaments, and are arranged in a stacked pattern throughout muscle tissue. 

Here are some key facts about sarcomeres:

Structure

Sarcomeres are arranged between two Z-lines, and contain an M-band and an elastic filament system made of titin. 

Function

Sarcomeres generate force and bear loads. The interaction between actin and myosin proteins is the basis of how sarcomeres shorten, which causes muscles to change length. 

Size

In vertebrate skeletal muscle, a sarcomere's resting length is about 2.5 millimeters. 

Number

A single muscle cell can contain thousands of sarcomeres. 

Disease

Understanding the molecular structure of sarcomeres can help us understand their role in health and disease. For example, the M-band is a shock absorber in contracting muscles, and its dysfunction can contribute to muscle disease.

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Severe Combined Immune Deficiency Syndrome:

 Severe Combined Immune Deficiency Syndrome:

SCID is a rare, inherited disorder that affects the development and function of white blood cells. 

It's characterized by a deficiency of T and B cell development and function, which makes people with SCID highly susceptible to infections. 

SCID is also known as the “bubble boy disease” or “boy in the bubble” syndrome. 

This is due to the publicity surrounding David Vetter, a boy with X-linked SCID who lived in a germ-free plastic bubble for 12 years.

Management:

Gene therapy can be used to treat severe combined immunodeficiency (SCID) by correcting the root cause of the disease.

 Gene therapy involves: 

Inserting healthy human genes into a patient's stem cells.

Washing the virus from the cells.

Transplanting the corrected cells back into the body.

The corrected cells divide and proliferate, passing on the normal gene copies to all the blood cells. 

Gene therapy has been successful in treating children with XSCID and ADA deficiency SCID. 

However, some treatments and trials have been halted due to concerns over the safety of viral vectors. 

Other treatments for SCID include: 

Bone marrow transplantation, 

Enzyme therapy, 

Avoiding live vaccines, 

Antimicrobial prophylaxis, and 

Isolation to prevent catching an infection.

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Porphyria Cutanea Tarda

 Porphyria cutanea tarda :

It results from underactivity of the enzyme uroporphyrinogen decarboxylase, which leads to accumulation of porphyrins in the liver. 

Liver disease is common. 

About 35% of people develop cirrhosis and 7 to 24% develop liver cancer.

Symptoms of Porphyria:

The acute (hepatic) porphyrias are characterized by episodes of abdominal pain (the most common symptom), constipation and other gastrointestinal symptoms.

Photosensitivity leading to pain immediately upon exposure to sunlight (e.g. EPP) or blistering and fragility of the skin in areas exposed to sunlight is seen in Porphyria cutanea tarda. 

How is PCT diagnosed?

 Diagnosisof (PCT) relies on the identification of characteristic symptoms, a comprehensive patient history, and a thorough clinical evaluation involving specialized tests.

Diagnosis is established by finding substantial increases in porphyrins in urine or plasma and excluding other blistering cutaneous porphyrias.

What is the drug of choice for porphyria cutanea tarda? :

Porphyria cutanea tarda may be treated by simply avoiding the precipitating factors.

 However, phlebotomy and hydroxychloroquine are both effective in achieving biochemical and clinical remission.

Primary Vs Secondary Data

 Primary Data Vs Secondary Data :

The main difference between primary and secondary data is that primary data is original information collected by a researcher for a specific purpose, while secondary data is information that has already been collected by someone else.

Primary data:

Original information gathered by the researcher for a specific purpose. 

Primary data is unique, first-hand, and from an original data source. 

Examples of primary data include interviews, original artwork, and personal narratives. 

Secondary data :

Information that has already been collected by someone else. 

Secondary data is usually gathered from published sources, such as statistical synopses, census records, and government reports. 

Researchers use secondary data to gain a broad overview of a topic, understand how other researchers have approached it, and support or contrast their arguments with other researchers' ideas. 

However, there are some limitations to using secondary data, including:

The quality of the secondary sources can affect the validity of the data.

The information may not fit the same boundaries as the primary data.

The data may address some issues but not others.