Review Pathophysiology - I

[Intro: 85 BPM. A lone, twangy acoustic guitar plucks a dark minor chord and a rattling trap cymbal builds tension before the massive 808 drop.] [Block 1: Massive 808 sub-bass and a stomping kick drum hit. Rapid-fire Southern MC precision starts here.] Lesch-Nyhan, (Deep Voice) MECHANISM Defective HGPRT so increase de novo purine synthesis (snare) NEXT Beta-thalassemia, Mutation at splice site or promoter sequences on chromosome 11 (snare) NEXT Osteogenesis imperfecta MECHANISM Mutation in COL1A1 and A2 so Type 1 collagen cannot form triple helices (snare) NEXT Ehlers-Danlos (Deep Voice) MECHANISM Faulty collagen synthesis so hyperextensible skin, hypermobile joints, easy bruising NEXT Menkes disease MECHANISM ATP7A so impaired copper absorption and transport so decrease lysyl oxidase so decrease collagen cross-linking (snare) NEXT Marfan syndrome MECHANISM FBN1 mutation on chromosome 15 so defective fibrillin-1, which forms sheath around elastin (snare) NEXT [Block 2: Bassline pitches down, getting dirtier. A picking banjo joins in. The MC's flow accelerates into tight rhythmic pockets.] Prader-Willi MECHANISM Imprinting or maternal uniparental disomy so deletion of paternal allele on chromosome 15 NEXT Angelman syndrome MECHANISM Imprinting or paternal uniparental disomy so deletion or mutated expression of UBE3A on maternal chromosome 15 (snare) NEXT Cystic fibrosis MECHANISM CFTR gene on chromosome 7 so impaired secretion of Cl⁻ in lungs/GI tract and reabsorption of Cl⁻ in sweat glands (snare) NEXT Duchenne (Deep Voice) MECHANISM Dystrophin frameshift or nonsense mutations so myonecrosis NEXT Becker Non-frameshift deletion Myotonic dystrophy CTG trinucleotide repeat in DMPK (snare) NEXT Fragile X CGG trinucleotide repeat in FMR1 (snare) NEXT [Block 3: Drums strip back to a filtered acoustic stomp-and-clap loop. Rising, vocal intensity.] Bitot spots in vitamin A deficiency due to decrease differentiation of epithelial cells into specialized tissue so conjunctival squamous metaplasia so keratin buildup (snare) NEXT Pellagra in malignant carcinoid syndrome MECHANISM Tryptophan is diverted towards serotonin by tumor so niacin deficient (snare) NEXT Kwashiorkor, decrease in plasma oncotic pressure so edema, decrease apolipoprotein synthesis so fatty changes in the liver NEXT Lactic acidosis, fasting hypoglycemia, hepatic steatosis in patient with alcohol use disorder MECHANISM increase NADH NAD⁺ ratio due to ethanol metabolism NEXT Aspirin-induced hyperthermia due to uncoupling in mitochondria NEXT [Block 4: Heavy 808 trap drums slam back in. Squealing slide guitars ] Hereditary fructose intolerance MECHANISM Aldolase B deficiency so Fructose-1-phosphate accumulate so inhibition of glycogenolysis and gluconeogenesis (snare) NEXT Essential fructosuria (Deep Voice) MECHANISM Fructokinase deficient so increase fructose; hexokinase pathway converts fructose to fructose-6-phosphate (snare) NEXT Classic galactosemia (Deep Voice) MECHANISM Galactose-1-phosphate uridyltransferase deficiency so accumulation of toxic substances like galactitol in lens so cataracts NEXT Galactokinase deficiency (Deep Voice) MECHANISM increase galactose; aldose reductase converts galactose to galactitol (snare) NEXT In diabetes, Lens, retina, kidney, and Schwann cells lack sorbitol dehydrogenase so sorbitol accumulates so osmotic damage so Cataracts, retinopathy, nephropathy, neuropathy (snare) NEXT [Block 5: Southern Trap chaos. Distorted 808 bass, rapid-fire hi-hats, and screaming vocals .] Hereditary angioedema (Deep Voice) MECHANISM C1 inhibitor deficiency so kallikrein activation so bradykinin (snare) NEXT Paroxysmal nocturnal hemoglobinuria (Deep Voice) MECHANISM PIGA gene mutation so decrease in GPI anchors for complement inhibitors (DAF/CD55, MIRL/CD59) so complement-mediated intravascular hemolysis so decrease haptoglobin (snare) NEXT Type I hypersensitivity Immediate (minutes): IgE on mast cells so release of histamine, tryptase, leukotrienes. Late (hours): mast cells secrete chemokines (snare) NEXT X-linked (Bruton) agammaglobulinemia MECHANISM Defect in BTK gene so no B-cell maturation so absent B cells in peripheral blood, decrease Ig of all classes (snare) NEXT DiGeorge syndrome failure to develop 3rd and 4th branchial pouches so absent thymus and parathyroid (snare) NEXT Hyper-IgM syndrome (Deep Voice) MECHANISM Defective CD40L on Th so class switching defect (snare) NEXT Leukocyte adhesion deficiency (type 1) (Deep Voice) MECHANISM LFA-1 integrin (CD18) defect so impaired phagocyte migration and chemotaxis NEXT Chédiak-Higashi (Deep Voice) MECHANISM LYST mutation so microtubule dysfunction so phagosome-lysosome fusion defect (snare) [Outro: Beat stops. A heavy 808 sub-bass drop.] Chronic granulomatous disease MECHANISM NADPH oxidase defect so decrease respiratory burst in neutrophils so increase susceptibility to catalase + like Staph aureus, Serratia, B cepacian [END]