Proteopathies
أمراض تنتج من مشاكل ببُنية البروتين

البُنية الأولية:
فقر الدم المنجلي ينتج من مشكلة بالبُنية الأولية للهيموغلوبين. بهذا المرض، الحمض الأميني رقم 6 اللي هو glutamate، رح يتبدل بـ valine بسبب طفرة جينية، وهالشي ينطينا هيموغلوبين بيه هواي مشاكل، إسمه Hemoglobin S (HbS).
مرض ثاني هو الـ cystic fibrosis عادةً ينتج بسبب حذف حمض أميني من فد بروتين (CFTR) وبالنتيجة يعطّله.

البُنية الثانوية:
الـ amyloidosis هو إسم لعدّة أمراض تصير لما فد بروتين معيّن، لأسباب مختلفة، يتحول من شكله الحلزوني المُعتاد للشكل المسطّح (الورقي)، هالشي رح يخليه يفقد وظيفته ويتكتّل بالأنسجة مثل الدماغ والقلب واللسان والمفاصل ويتسبب بفشل الأعضاء. الزهايمر مثلًا، ينتج بسبب تجمّع نوع من البروتينات بالدماغ بشكل تدريجي وبالنتيجة يتآكل الدماغ وتموت الخلايا العصبية.
مرض ثاني هو الـ prion disease ينتج لما بروتين بالدماغ يصيرله misfolding يعني يتصفط بطريقة غلط، وهمين يتحول من شكله الحلزوني للشكل الورقي المسطّح ويتجمع بالدماغ لحدما يموت المريض تدريجيًا.

البُنية الثلاثية:
تتذكر الـ Hbs مال فقر الدم المنجلي؟ هذا مشكلته أنه بمجرد ما يقل الأوكسجين بالدم، رح تتغير بُنيته الثلاثية ويصير يشبه الكريستال وبالنتيجة يؤدي لموت كرية الدم الحمراء.
عندك همين الـ CFTR لما ينحذف منه حمض أميني، رح تتغير تركيبته الثلاثية ويتحلل بداخل الخلية وما يؤدي وظيفته وبالنتيجة يتسبب بالـ cystic fibrosis.

البُنية الرباعية:
أعتقد الثلاسيميا تنحسب ضمن هالنوع؛ اللي يصير مثلًا بالثلاسيميا بيتا هو أنّ الجين المسؤول عن تصنيع الـ β-globin رح يتعطل، وبالنتيجة الجسم ما يكدر يصنع هالبروتين، وهالشي يؤدي لتخريب البُنية الرباعية مال الهيموغلوبين.

A weird case:
It started years earlier, the older woman told her. Almost every night, she would get these crazy fevers. First came bone-rattling, shaking chills; she couldn’t get warm even under a pile of quilts. Then suddenly she would be roasting hot, with sweat pouring off her. Her temperature would spike to 38.5 or 39. And her whole body would hurt, right down to her bones. She popped Tylenol constantly for the fever and the pain. Then an hour after her temperature spiked, she would start to feel sick and throw up until she had nothing left in her. This happened almost every night.

During the day, she felt weak and tired, and her bones hurt. It made any movement painful. She also had a rash. Hives, the doctors told her. It didn’t itch, and no one could figure out why she had it. And, her daughters added, she had no appetite. The very thought of food made her want to vomit. She’d lost over eighty pounds this past year.

Reviewing her tests, the doctor saw that the patient had a persistently elevated white-blood-cell count. Normal is under ten; the patient’s was at nearly twenty—and had been for a couple of years. CT scans showed enlarged lymph nodes throughout her body. These findings could be from a chronic infection. Or from a cancer. But her hometown doctors found neither.

According to current thinking, in Schnitzler syndrome the most primitive part of the immune system—a type of white blood cell known as the macrophage—goes wild and instructs the body to act as if it is infected by releasing interleukin-1 (IL-1). The body responds with fever and chills, a loss of appetite, flu-like body aches, hives, and high levels of one specific type of antibody: IgM. Exactly why and how this occurs is still unclear.
The disorder was first described in 1972 by the French dermatologist Liliane Schnitzler, who had identified five patients with hives, episodes of prolonged fever, bone pain, and enlarged lymph nodes. These symptoms, plus an elevated level of IgM, Schnitzler proposed, defined a new disease.

It's a rare disease, and only some 300 cases have been reported so far

Incidentaloma
(incidental imaging finding)

These are lesion found incidentally and of dubious clinical significance. When you find them, it's hard to tell if they are related to the patient's current condition or not. That's what makes them really annoying. Incidentalomas usually take the form of adenomas found in the adrenal glands, but they can be found elsewhere, such as liver hemangiomas.

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Acute rheumatic fever, pathophysiology

The heart actually starts as 2 endocardial tubes that fuse together to form the primitive heart tube. The latter then grows and rotates on itself so that the inferior portion (which forms the atria) becomes superior, and the superior (which forms the ventricles) becomes inferior.

Development of great vessels

Aorticopulmonary septum

The rubella congenital malformations are widespread and involve primarily the heart (e.g., patent ductus arteriosus), the eyes (e.g., cataracts), and the brain (e.g., deafness and mental retardation).

Here's a mnemonic:
من تتغزل بيها شتكول الها؟ انتي گلبي وعيوني وماخذة عقلي

Streptococcus pyogenes also causes toxic shock syndrome (TSS), which has clinical findings similar to those of staphylococcal TSS. However, streptococcal TSS typically has a recognizable site of pyogenic inflammation and blood cultures are often positive, whereas staphylococcal TSS typically has neither a site of pyogenic inflammation nor positive blood cultures.

Patients suspected to have acute rheumatic fever (ARF) or post-strep glomerulonephritis (PSGN) must first be confirmed to have had a previous strep infection. This is done by measuring ASO & anti-DNAase B titers. The latter is better since it remains high for months after the infection, while ASO titers decline after a few weeks.

Also, ASO is usually high in strep throat cases, while anti-DNAase B is higher in strep skin infections.