Rapid Review Pathophysiology Of Diseases Flashcards
Lesch-Nyhan syndrome
Absent HGPRT -> high de novo purine synthesis -> high uric acid production
Osteogenesis imperfecta
Type 1 collagen defect due to inability to form triple helices
Menkes disease
Defective ATP7A protein -> impaired copper absorption and transport -> low lysyl oxidase activity -> low collagen cross-linking
Marfan syndrome
FBN1 mutation on chromosome 15 -> defective fibrillin (normally forms sheath around elastin)
Prader-Willi syndrome
Uniparental disomy or imprinting leading to silencing of maternal gene. Disease expressed when paternal allele deleted or mutated
Angelman syndrome
Silenced gene leading to mutation, lack of expression, or deletion of UBE3A on maternal chromosome 15
Cystic fibrosis
Autosomal recessive ΔF508 deletion in CFTR gene on chromosome 7 -> impaired ATP-gated Cl − channel (secretes Cl − in lungs and GI tract and reabsorbs Cl − in sweat glands)
Duchenne muscular dystrophy
Dystrophin gene frameshift mutations -> loss of anchoring protein to ECM -> (dystrophin) -> myonecrosis
Fragile X syndrome
Trinucleotide repeat in FMR1 gene -> hypermethylation -> expression
Kwashiorkor
Protein malnutrition -> oncotic pressure ( -> edema), low apolipoprotein synthesis ( -> liver fatty change)
Lactic acidosis, fasting hypoglycemia, hepatic steatosis in alcoholism
High NADH/NAD + ratio due to ethanol metabolism
Hereditary fructose intolerance
Aldolase B deficiency -> Fructose-1-phosphate accumulates -> low available phosphate -> inhibition of glycogenolysis and gluconeogenesis
Classic galactosemia
Galactose-1-phosphate uridyltransferase deficiency -> accumulation of toxic substances (eg, galactitol in eyes)
Cataracts, retinopathy, peripheral neuropathy in DM
Lens, retina, Schwann cells lack sorbitol dehydrogenase -> intracellular sorbitol accumulation -> osmotic damage
Type I hypersensitivity
Immediate (minutes): antigen cross links IgE on mast cells -> degranulation -> release of histamine and tryptase
Late (hours): mast cells secrete chemokines (attract eosinophils) and leukotrienes -> inflammation, tissue damage
Type II hypersensitivity
Antibodies bind to cell-surface antigens -> cellular destruction, inflammation, cellular dysfunction
Type III hypersensitivity
Antigen-antibody complexes -> activate complement -> attracts neutrophils
Type IV hypersensitivity
T cell-mediated (no antibodies involved). CD8 + directly kills target cells, CD4 + releases cytokines
DiGeorge syndrome
22q11 microdeletion -> failure to develop 3rd and 4th branchial (pharyngeal) pouches
Tetanus
Tetanospasmin prevents release of inhibitory neurotransmitters (GABA and glycine) from Renshaw cells
Botulism
Toxin (protease) cleaves SNARE -> low neurotransmitter (ACh) release at NMJ
Gas gangrene
Alpha toxin (phospholipase/lecithinase) degrades phospholipids -> myonecrosis
Toxic shock syndrome, scarlet fever
TSST-1 and erythrogenic exotoxin A (scarlet) cross-link β region of TCR to MHC class II on APCs outside of antigen binding site -> IL-1, IL-2, IFN-γ, TNF-α
Shock and DIC by gram ⊝ bacteria
Lipid A of LPS -> macrophage activation (TLR4/CD14), complement activation, tissue factor activation
Diphtheria
Exotoxin inhibits protein synthesis via ADP-ribosylation of EF-2
Virulence of M tuberculosis
Cord factor activates macrophages (promoting granuloma formation), induces release of TNF-α; sulfatides (surface glycolipids) inhibit phagolysosomal fusion
Tuberculoid leprosy
Th1 immune response -> mild
Influenza pandemics
RNA segment reassortment -> antigenic shift
Influenza epidemics
Mutations in hemagglutinin, neuraminidase -> antigenic drift
CNS invasion by rabies
Binds to ACh receptors -> retrograde transport (dynein)
HIV infection
Virus binds CD4 along with CCR5 on macrophages (early), or CXCR4 on T cells (late)
Granuloma
Macrophages present antigens to CD4 + and secrete IL-12 -> CD4+ differentiation into Th1 which secrete IFN-γ -> macrophage activation
Tissue invasion by cancer
Low E-cadherin function -> low intercellular junctions -> basement membrane and ECM degradation by metalloproteinases -> cell attachment to ECM proteins (laminin, fibronectin) locomotion -> vascular dissemination
Persistent truncus arteriosus
Failure of aorticopulmonary septum formation
D-transposition of great arteries
Failure of the aorticopulmonary septum to spiral
Atherosclerosis
Endothelial cell dysfunction -> macrophage and LDL accumulation -> foam cell formation -> fatty streaks -> smooth muscle cell migration, extracellular matrix deposition fibrous plaque -> complex atheromas
Thoracic aortic aneurysm
Cystic medial degeneration
Myocardial infarction
Rupture of coronary artery atherosclerotic plaque -> acute thrombosis
Non–ST-segment elevation MI
Subendocardial infarcts (subendocardium vulnerable to ischemia)
ST-segment elevation MI
Transmural infarcts
Death within 0-24 hours post MI
Ventricular arrhythmia
Death or shock within 3-14 days post MI
Macrophage-mediated ruptures: papillary muscle (2-7 days), interventricular septum (3-5 days), free wall (5-14 days)
Wolff-Parkinson-White
Abnormal accessory pathway from atria to ventricle bypasses the AV node -> ventricles begin to partially depolarize earlier -> delta wave. Reentrant circuit -> supraventricular tachycardia.
Hypertrophic obstructive cardiomyopathy
Sarcomeric proteins gene mutations (myosin binding protein C and β-myosin heavy chain) -> concentric hypertrophy (sarcomeres added in parallel). Death due to arrhythmia
Hypovolemic shock
Low preload -> low CO
Cardiogenic shock
Low CO due to left heart dysfunction
Distributive shock
Low SVR (afterload)
Rheumatic fever
Antibodies against M protein cross react with self antigens; type II HSR
Most common form of congenital adrenal hyperplasia
21-hydroxylase deficiency -> low mineralocorticoids, low cortisol, high sex hormones, high 17-hydroxyprogesterone
Heat intolerance, weight loss in hyperthyroidism
High Na+-K +ATPase -> high basal metabolic rate -> high calorigenesis
Myxedema in hypothyroidism
High CAGs in interstitial space
Graves ophthalmopathy
Lymphocytic infiltration, fibroblast secretion of GAGs -> high osmotic muscle swelling, inflammation
1° hyperparathyroidism
Parathyroid adenoma or hyperplasia -> high PTH
2° hyperparathyroidism
High Ca 2+ and/or PO4 3– -> parathyroid hyperplasia -> high PTH, high ALP
Euvolemic hyponatremia in SIADH
High ADH -> water retention -> low aldosterone, high ANB, high BNP -> high urinary Na+ secretion
Small/large vessel disease in DM
Nonenzymatic glycation of proteins
Diabetic ketoacidosis
Low Insulin or high insulin requirement -> high fat breakdown -> high free fatty acids -> high ketogenesis
Hyperosmolar hyperglycemic state
Hyperglycemia -> high serum osmolality, excessive osmotic diuresis
Zollinger-Ellison syndrome
Gastrin-secreting tumor (gastrinoma) of pancreas or duodenum -> recurrent ulcers in duodenum/jejunum and malabsorption
Duodenal atresia
Failure to recanalize
Jejunal/ileal atresia
Disruption of SMA -> ischemic necrosis of fetal intestine
