Rapid Review Pathophysiology Of Diseases

Question 1

Lesch-Nyhan syndrome

Answer 1

Absent HGPRT Ž-> high de novo purine synthesis Ž-> high uric acid production

Question 2

Osteogenesis imperfecta

Answer 2

Type 1 collagen defect due to inability to form triple helices

Question 3

Menkes disease

Answer 3

Defective ATP7A protein Ž-> impaired copper absorption and transport Ž-> low lysyl oxidase activity Ž-> low collagen cross-linking

Question 4

Marfan syndrome

Answer 4

FBN1 mutation on chromosome 15 -> defective fibrillin (normally forms sheath around elastin)

Question 5

Prader-Willi syndrome

Answer 5

Uniparental disomy or imprinting leading to silencing of maternal gene. Disease expressed when paternal allele deleted or mutated

Question 6

Angelman syndrome

Answer 6

Silenced gene leading to mutation, lack of expression, or deletion of UBE3A on maternal chromosome 15

Question 7

Cystic fibrosis

Answer 7

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)

Question 8

Duchenne muscular dystrophy

Answer 8

Dystrophin gene frameshift mutations -> loss of anchoring protein to ECM -> (dystrophin) Ž-> myonecrosis

Ž

Question 9

Fragile X syndrome

Answer 9

Trinucleotide repeat in FMR1 gene -> hypermethylation -> expression

Question 10

Kwashiorkor

Answer 10

Protein malnutrition -> oncotic pressure (Ž -> edema), low apolipoprotein synthesis (Ž -> liver fatty change)

Question 11

Lactic acidosis, fasting hypoglycemia, hepatic steatosis in alcoholism

Answer 11

High NADH/NAD + ratio due to ethanol metabolism

Question 12

Hereditary fructose intolerance

Answer 12

Aldolase B deficiency Ž-> Fructose-1-phosphate accumulates Ž-> low available phosphate Ž-> inhibition of glycogenolysis and gluconeogenesis

Question 13

Classic galactosemia

Answer 13

Galactose-1-phosphate uridyltransferase deficiency -> accumulation of toxic substances (eg, galactitol in eyes)

Question 14

Cataracts, retinopathy, peripheral neuropathy in DM

Answer 14

Lens, retina, Schwann cells lack sorbitol dehydrogenase -> intracellular sorbitol accumulation -> osmotic damage

Question 15

Type I hypersensitivity

Answer 15

Immediate (minutes): antigen cross links IgE on mast cells Ž-> degranulation Ž-> release of histamine and tryptase
Late (hours): mast cells secrete chemokines (attract eosinophils) and leukotrienes Ž-> inflammation, tissue damage

Question 16

Type II hypersensitivity

Answer 16

Antibodies bind to cell-surface antigens -> cellular destruction, inflammation, cellular dysfunction

Question 17

Type III hypersensitivity

Answer 17

Antigen-antibody complexes Ž-> activate complement Ž-> attracts neutrophils

Question 18

Type IV hypersensitivity

Answer 18

T cell-mediated (no antibodies involved). CD8 + directly kills target cells, CD4 + releases cytokines

Question 19

DiGeorge syndrome

Answer 19

22q11 microdeletion Ž-> failure to develop 3rd and 4th branchial (pharyngeal) pouches

Question 20

Tetanus

Answer 20

Tetanospasmin prevents release of inhibitory neurotransmitters (GABA and glycine) from Renshaw cells

Question 21

Botulism

Answer 21

Toxin (protease) cleaves SNARE -> low neurotransmitter (ACh) release at NMJ

Question 22

Gas gangrene

Answer 22

Alpha toxin (phospholipase/lecithinase) degrades phospholipids -> myonecrosis

Question 23

Toxic shock syndrome, scarlet fever

Answer 23

TSST-1 and erythrogenic exotoxin A (scarlet) cross-link β region of TCR to MHC class II on APCs outside of antigen binding site Ž-> IL-1, IL-2, IFN-γ, TNF-α

Question 24

Shock and DIC by gram ⊝ bacteria

Answer 24

Lipid A of LPS Ž-> macrophage activation (TLR4/CD14), complement activation, tissue factor activation

Question 25

Diphtheria

Answer 25

Exotoxin inhibits protein synthesis via ADP-ribosylation of EF-2

Question 26

Virulence of M tuberculosis

Answer 26

Cord factor activates macrophages (promoting granuloma formation), induces release of TNF-α; sulfatides (surface glycolipids) inhibit phagolysosomal fusion

Question 27

Tuberculoid leprosy

Answer 27

Th1 immune response Ž-> mild

Question 28

Influenza pandemics

Answer 28

RNA segment reassortment Ž-> antigenic shift

Question 29

Influenza epidemics

Answer 29

Mutations in hemagglutinin, neuraminidase -> antigenic drift

Question 30

CNS invasion by rabies

Answer 30

Binds to ACh receptors Ž-> retrograde transport (dynein)

Question 31

HIV infection

Answer 31

Virus binds CD4 along with CCR5 on macrophages (early), or CXCR4 on T cells (late)

Question 32

Granuloma

Answer 32

Macrophages present antigens to CD4 + and secrete IL-12 Ž-> CD4+ differentiation into Th1 which secrete IFN-㠎-> macrophage activation

Question 33

Tissue invasion by cancer

Answer 33

Low E-cadherin function Ž -> low intercellular junctions Ž-> basement membrane and ECM degradation by metalloproteinases Ž-> cell attachment to ECM proteins (laminin, fibronectin) Ž locomotion Ž-> vascular dissemination

Question 34

Persistent truncus arteriosus

Answer 34

Failure of aorticopulmonary septum formation

Question 35

D-transposition of great arteries

Answer 35

Failure of the aorticopulmonary septum to spiral

Question 36

Atherosclerosis

Answer 36

Endothelial cell dysfunction -> macrophage and LDL accumulation -> foam cell formation Ž-> fatty streaks -> smooth muscle cell migration, extracellular matrix deposition Ž fibrous plaque Ž-> complex atheromas

Question 37

Thoracic aortic aneurysm

Answer 37

Cystic medial degeneration

Question 38

Myocardial infarction

Answer 38

Rupture of coronary artery atherosclerotic plaque -> acute thrombosis

Question 39

Non–ST-segment elevation MI

Answer 39

Subendocardial infarcts (subendocardium vulnerable to ischemia)

Question 40

ST-segment elevation MI

Answer 40

Transmural infarcts

Question 41

Death within 0-24 hours post MI

Answer 41

Ventricular arrhythmia

Question 42

Death or shock within 3-14 days post MI

Answer 42

Macrophage-mediated ruptures: papillary muscle (2-7 days), interventricular septum (3-5 days), free wall (5-14 days)

Question 43

Wolff-Parkinson-White

Answer 43

Abnormal accessory pathway from atria to ventricle bypasses the AV node Ž-> ventricles begin to partially depolarize earlier Ž-> delta wave. Reentrant circuit Ž-> supraventricular tachycardia.

Question 44

Hypertrophic obstructive cardiomyopathy

Answer 44

Sarcomeric proteins gene mutations (myosin binding protein C and β-myosin heavy chain) Ž-> concentric hypertrophy (sarcomeres added in parallel). Death due to arrhythmia

Question 45

Hypovolemic shock

Answer 45

Low preload -> low CO

Question 46

Cardiogenic shock

Answer 46

Low CO due to left heart dysfunction

Question 47

Distributive shock

Answer 47

Low SVR (afterload)

Question 48

Rheumatic fever

Answer 48

Antibodies against M protein cross react with self antigens; type II HSR

Question 49

Most common form of congenital adrenal hyperplasia

Answer 49

21-hydroxylase deficiencyŽ -> low mineralocorticoids, low cortisol, high sex hormones, high 17-hydroxyprogesterone

Question 50

Heat intolerance, weight loss in hyperthyroidism

Answer 50

High Na+-K +ATPase -> high basal metabolic rate -> high calorigenesis

Question 51

Myxedema in hypothyroidism

Answer 51

High CAGs in interstitial space

Question 52

Graves ophthalmopathy

Answer 52

Lymphocytic infiltration, fibroblast secretion of GAGs -> high osmotic muscle swelling, inflammation

Question 53

1° hyperparathyroidism

Answer 53

Parathyroid adenoma or hyperplasia -> high PTH

Question 54

2° hyperparathyroidism

Answer 54

High Ca 2+ and/or PO4 3– -> parathyroid hyperplasia -> high PTH, high ALP

Question 55

Euvolemic hyponatremia in SIADH

Answer 55

High ADH Ž-> water retention -> low aldosterone,  high ANB, high BNP Ž -> high urinary Na+ secretion

Question 56

Small/large vessel disease in DM

Answer 56

Nonenzymatic glycation of proteins

Question 57

Diabetic ketoacidosis

Answer 57

Low Insulin or high insulin requirement -> high fat breakdown -> high free fatty acids -> high ketogenesis

Question 58

Hyperosmolar hyperglycemic state

Answer 58

Hyperglycemia -> high serum osmolality, excessive osmotic diuresis

Question 59

Zollinger-Ellison syndrome

Answer 59

Gastrin-secreting tumor (gastrinoma) of pancreas or duodenum Ž-> recurrent ulcers in duodenum/jejunum and malabsorption

Question 60

Duodenal atresia

Answer 60

Failure to recanalize

Question 61

Jejunal/ileal atresia

Answer 61

Disruption of SMA Ž-> ischemic necrosis of fetal intestine