MHC & HLA

In humans, the Major HistoCompatibility (MHC) molecule is called the Human Leukocyte Antigen (HLA) system.

The MHC genes are codominantly expressed, which means that each individual expresses these genes from both the alleles on the cell surface. Furthermore, they are inherited as haplotypes, or one from each parent. This makes a person half identical to each of his or her parents with respect to the MHC complex. This also leads to a 25% chance that an individual might have a sibling who is HLA identical.

Human HLA genes code for 3 major class I alleles (HLA-A, -B, -C), and 3 major class II alleles (HLA-DR, -DQ, -DP). Polymorphisms in HLA, especially HLA-A, -B, and -DR loci, are important biological barriers to a successful transplantation, and may be part of many autoimmune diseases.

The MHC molecules are divided into 2 classes. The class I molecules are normally expressed on all nucleated cells, whereas the class II molecules are expressed only on the professional antigen-presenting cells (APCs), such as dendritic cells, activated macrophages, and B cells. The physiologic function of the MHC molecules is to present antigenic peptides to T cells. The class I molecules present antigenic peptides from within the cell (eg, self-antigens, intracellular viruses, tumor antigens) to CD8 T cells. The class II molecules present extracellular antigens such as extracellular bacteria to CD4 T cells.

Diabetes mellitus (DM) comes from the Greek roots 'diabetes' which means (pass through; a lot of urine) and the Latin word 'mellitus' meaning (honey-like, sweet), while the word insipidus in diabetes insipidus (DI) comes from Latin which basically means (tasteless).

This is because in times gone, when a patient urinated a lot, he was said to have diabetes. But to distinguish whether it was DM or DI, physicians had to taste the urine of the patient; if it was sweet, that is, mellitus, then it's DM. If it was tasteless, or insipidus, then it's DI.

It is possible for patients to be misdiagnosed with PCOS when in fact they have Cushing's syndrome, some form of congenital adrenal hyperplasia, or an androgen-secreting tumor as they all have a highly similar phenotype.

This is why the Rotterdam criteria explicity states that you can only make the diagnosis of PCOS after the exclusion of other etiologies.

Acute tubular necrosis (ATN)

• Damage to epithelial cells in kidney tubules.
• Leads to oliguria that is unresponsive to fluids, which becomes polyuria in the recovery phase.
• Muddy-brown casts on urinalysis.
• Causes:-
- Severe kidney ischemia
- Contrast agent
- Medications (aminoglycosides, amphotericin)
- Hemo-/myoglobinuria
- Uric acid

Acute interstitial nephritis (AIN)

• Type IV hypersensitivity reaction against the tubules & interstitium of the kidney.
• Polyuria.
• Sterile pyuria, WBC cast ± hematuria.
• possibly fever, rash, & eosinophiluria (rare, but eosinophilia is more common).

• Causes:
   - PPIs
- Antibiotics
- NSAIDs
- Loop diuretics
- Anticonvulsants

Papillary necrosis

• Renal papillary ischemia & necrosis.
• Sloughing of necrotic material may lead to ureteral obstruction
• Flank pain
• Hematuria, proteinuria, sterile pyuria
• Usually due to:-
   - DM
   - NSAIDs
   - Sicke cell anemia
   - Pyelonephritis
   - TB

.

.

أحسنت

نتعلم منك استاذي🍻

Calcium, PTH, vitamin D, and calcitonin

While some studies report a high correlation between loss of cremasteric reflex and testicular torsion, there are a surprising number of studies reporting the persistence of the reflex during verified cases of torsion. Additionally, other studies confirm that it is also absent from significant numbers of males and more so at younger ages. The frequency of the intact reflex has been reported in 61.7% to 100% of boys between 24 months and 12 years of age.

You can think of the midbrain like a set of highways with factories and a lot of service areas in the vicinity.

The highways are multiple descending and ascending pathways that connect the brain with the body and brain parts to one another. Some of the descending tracts include the crus cerebri, which are part of the corticospinal tract. There is the rubrospinal tract, the tectospinal tract, and the medial longitudinal fasciculus. Ascending fibers include the medial lemniscus, the trigeminal lemniscus, spinal lemniscus, and the lateral lemniscus.

While the factories are dopamine-, GABA-, serotonin-, and norepinephrine-producing areas like the pars compacta, pars reticularis, dorsal raphe nuclei, and the locus ceruleus, respectively. These are very important for myriad of brain functions and they project (i.e. send their products) to extensive places throughout the CNS.

The service areas, those restaurants and gas stations you find along the road include the colliculi, motor & parasympathetic nuclei for 3rd cranial nerve, nucleus for 4th cranial nerve, and some of 5th cranial nerves, in addition to the red nucleus, periaqueductal gray matter, and pretectal nuclei (which are involved in orchestrating bilateral pupil constriction).

It's a busy area where a lot of connections and axons pass through it and either descend or ascend to multiple areas, and a lot of essential nuclei reside in it. In this regard, it's more like a city downtown than a highway.

I wasn't much interested in the midbrain because it was a relatively small area and I thought, erroneously, that it wasn't as clinically relevant as other areas of the brain, like the cortices or the hypothalamus, but from a neuroanatomical point of view, this comparatively small area is very essential for the normal function of the brain to occur. You can see just how essential it is when you consider syndromes like Benedikt or Weber, which cause widespread dysfunction and clinical signs that are seemingly haphazarad... that is, until you learn about the midbrain anatomy.

Clinical features:
• Gross hematuria.
• Blood at urethral meatus.
• Reduced urine output.

Diagnosis: retrograde cystography is the gold standard (CT with contrast is insufficient).

Treatment:
• Suprapubic or transurethral (foley) catheterization, or even percutaneous nephrostomy if needed.
• Intraperitoneal rupture is always treated surgically.
• Extraperitoneal rupture can be managed conservatively unless it's a complicated injury.

• A bladder rupture is complicated if it affects the bladder neck, or is associated with pelvic ring fracture, or rectal/vaginal injury.

Clinical features:
• Blood at the urethral meatus.
• Gross hematuria.
• Urgent need to urinate (suprapubic pain) yet inability to do so.
• Anterior urethral injury may lead to blood accumulating under the scrotum.
• Posterior injury may lead to blood accumulating under the perineum.

Diagnosis: retrograde urethrography.

Treatment:
• Suprapubic catheterization
• Transurethral catheterization (foley's catheter) is a relative contraindication and may sometimes be tried once by an experienced practitioner to allow the urethral epithelium to heal around it.
• The definitive treatment is surgical repair, delayed (if blunt trauma) or immediate (if penetrating).