Reason for increase in B2-microglobulin levels in HIV infection
Beta-2 microglobulin (B2M) is a component of the MHC class I molecules, which are present on all nucleated cells.
In HIV infection, there is a high rate of cellular turnover and immune activation, leading to increased shedding of B2M into the bloodstream.
Therefore, serum B2M levels are elevated and correlate with disease progression.
The following immunological changes are seen in progressive HIV:
Reduction in CD4 count
Increase B2-Microglobulin (IBM)
Decrease IL-2 production (DIL=DELL) } IBM & DELL
Polyclonal B-cell activation
NK cell function
delayed hypersensitivity responses
Which cytokine is responsible for the chemotaxis of neutrophils?
IL-8
It is secreted from macrophages and some epithelial tissues.
What is the most common cardiac defect seen in patients with Down’s syndrome?
Endocardial cushion defect, also known as atrioventricular septal defect (AVSD) or atrioventricular canal defect.
Seen in 40-50%
The defect results from incomplete fusion of the endocardial cushions during cardiac development, leading to abnormalities of the atrioventricular septum and valves. This creates both atrial and ventricular communication and often involves abnormalities of the mitral and tricuspid valves.
Other common defects: ventricular septal defect (c. 30%)
secundum atrial septal defect (c. 10%)
tetralogy of Fallot (c. 5%)
isolated patent ductus arteriosus (c. 5%)
Congenital infection associated with chorioretinitis
Toxoplasma gondii
All the C’s - Cats 🐈 cause congenital toxoplasmosis, causing chorioretinitis 👀 and cerebral calcification 🧠
The classic triad of congenital toxoplasmosis includes chorioretinitis, intracranial calcifications, and hydrocephalus. The chorioretinitis typically presents as a necrotising retinitis that can lead to scarring, and whilst it may be present at birth, it can also develop later in life. The retinal lesions are often bilateral and can affect the macula, potentially causing significant visual impairment.
Rapid onset vision loss
FHx of visual loss
Fundoscopy: peripapillary telangiectasia
Leber’s Hereditary Optic Neuropathy: mitochondrial inheritance pattern
It affects males more than females for unknown reasons and it demonstrates a mitochondrial pattern of inheritance. In mitochondrial diseases, since the sperm contributes negligible amounts of mitochondrial DNA to the zygote, a mother passes the disease to all of her children. Both sexes may therefore be affected.
HLA-DR2
Dr - has 2 good features - He is Nice and Good :)
DR2 - Narcolepsy and Goodpasture
CD59 deficiency
Involved in the pathogenesis of paroxysmal nocturnal haemoglobinuria.
Intracellular proteins tagged with mannose-6-phosphate
Golgi adds mannose-6-phosphate to proteins for trafficking to lysosomes
Mannose-6-phosphate (M6P) is a specific molecular marker that targets proteins to lysosomes. This targeting system involves the addition of M6P residues to proteins in the Golgi apparatus, which are then recognised by mannose-6-phosphate receptors (M6PRs). These receptors facilitate the transport of the tagged proteins from the trans-Golgi network to lysosomes. This system is crucial for the proper functioning of lysosomes, as it ensures that hydrolytic enzymes and other essential lysosomal proteins reach their intended destination.
Ubiquitin tagged –> proteosome
Mannose tagged –> lysosome
Pathophysiology of adrenoleukodystrophy (ALD)
X-linked peroxisomal disorder characterized by the accumulation of very long chain fatty acids (VLCFAs) due to impaired peroxisomal beta-oxidation
Peroxisomes are specifically responsible for the initial oxidation of VLCFAs before they can be further metabolized by mitochondria. In ALD, mutations in the ABCD1 gene result in defective transport of VLCFAs into peroxisomes, leading to their accumulation in plasma and tissues. The clinical features described - progressive spastic paraparesis, visual disturbances, hearing loss, and characteristic parieto-occipital demyelination on MRI - are classic for the adult cerebral form of ALD. The elevated VLCFAs in blood tests provide the key diagnostic clue, directly pointing to peroxisomal dysfunction.
Proteins tagged with ubiquitin
Proteasome - Along with the lysosome pathway involved in degradation of protein molecules that have been tagged with ubiquitin
Presentation of adrenoleukodystrophy (ALD)
Progressive weakness in lower limbs
Visual disturbances
Hearing loss
Spastic paraparesis
Reduced visual acuity
Elevated very long chain fatty acids
MRI brain shows demyelination in the parieto-occipital regions.
Goodpasture’s syndrome - Autoantibodies against what?
Collagen type IV
The diagnosis here is Goodpasture’s syndrome, given the constellation of presenting symptoms - cough, haemoptysis, crackles on auscultation, oedema and impaired renal function. The antibodies typically found in this condition are anti-glomerular basement membrane antibodies (anti-GBM), which target collagen type IV.
Radiological changes in rheumatoid - early, intermediate and late
Early changes:
* may be no identifiable changes in early disease * soft-tissue swelling
* juxta-articular osteoporosis
* osteopenia
Intermediate changes:
* joint space narrowing due to loss of cartilage.
Late changes:
* bone and joint destruction
* subluxation.
