بسم الله الرحمن الرحيم
DIAGNOSIS
🔴proxysmal nocturnal haemoglobinuria
⭕a rare acquired life-threatening disease of the blood characterized by destruction of red blood cells by the complement system..
🔴pathophysiology ??
All cells have proteins attached to their membranes often serving as a mode of communication❗ or signaling between the cell and the surrounding environment
➡ These signaling proteins are physically attached to the cell membrane in various ways
➡ commonly anchored by glycolipids such‼ asglycosyl phosphatidylinositols (GPI)‼‼
The most common defect in PNH is phosphatidylinositol glycan A(PIGA)
➡ needed to make GPI‼‼mutation in the PIGA gene can lead to the absence of❗ GPI anchorssed on the cell membrane several of theproteins that anchor to GPI on the cell membrane
➡ are used to protect the cell from destruction by the complement system and❗without these anchors the cells are more easily targeted by the complement proteins
➡The main proteins that protect blood cells from destruction are‼‼decay accelerating factor (DAF/CD55) which disrupts formation of C3-convertase ❗ and protectin (CD59/MIRL) which ❗binds the membrane attack complex and prevents ‼C9 from binding to the cell👍soo the abcense of GPI.anchored ❗prevent the protein from binding to red membrane ‼this protein are DAF ❓and MIRL ❓
➡those two protein if absence directly the red cell become ❗sensitive to complement
➡that lead to intravascular haemolysis by ❗alternative pathway of complement ....
⭕بمعني انو لو حصل خلل او طفره في جين يسمي PIGA الموجود في haemopotic cell مباشره حايتاثر GpI anchor ❗باعتبار GpI بروتين يحتاج للارتباط بالخليه الي وجود PIGA 👍طيب حصل خلل في GPI معناها يكون في خلل في المستقبلات تبعه
⬅فبالتالي حايمنع ارتباط بعض البروتينات علي سطح الخليه الحمراء مثل ❗ DAF .و MIRL ❗وظيفتهم شنو للخليه الحمراء ؟؟
⭕DAF
يمنع تكون C3 لجهاز المتممه
⭕MIRL
بيرتبط مع MAC ويمنع ارتباطه بسطح الخليه الحمراء
هكذا البروتنين ☝☝ بيحافظوا علي الخليه الحمراء من انها يحصل ليها تك