PATHOPHYSIOLOGY OF IMPORTANT DISEASES Flashcards by tarfuah taylor

(38,425) Mutation at splice site or promoter sequences retained intron in mRNA

β-thalassemia

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(35) Absent HGPRT leading to increase de novo purine synthesis leading to increase uric acid production

Lesch-Nyhan syndrome

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(37,395)Failure of mismatch repair during the S phase microsatellite instability

Lynch syndrome

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(45) N-acetylglucosaminyl-1-phosphotransferase defect leading to Golgi mediated
mannose residues phosphorylation failure (leading to decrease mannose-6-phosphate)
leading to increase cellular debris in lysosomes

I-cell disease

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(49) Type 1 collagen defect due to inability to form triple helices

Osteogenesis imperfecta

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(49) Defective ATP7A protein leading to impaired copper absorption and transport
leading to decrease lysyl oxidase activity leading to derease collagen cross-linking

Menkes disease

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(50) FBN1 mutation on chromosome 15 leading to defective fibrillin (normally forms
sheath around elastin)

Marfan syndrome

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

Prader-Willi syndrome

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

Angelman syndrome

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(58) Autosomal recessive
ΔF508 deletion in CFTR gene on chromosome 7
leading to impaired ATP-gated Cl− channel (secretes Cl− in lungs and GI tract,
then reabsorbs Cl− in sweat glands)

Cystic fibrosis

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(59) Dystrophin gene frameshift mutations leading to loss of anchoring protein to ECM
(dystrophin) leading to myonecrosis

Duchenne muscular dystrophy

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(59) CTG trinucleotide repeat expansion in DMPK gene leading to abnormal expression
of myotonin protein kinase leading to myotonia

Myotonic dystrophy

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(60) Trinucleotide repeat in FMR1 gene leading to hypermethylation leading to decrease expression

Fragile X syndrome

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(64) decrease differentiation of epithelial cells into specialized tissue leading to squamous
metaplasia

Bitot spots in vitamin A deficiency

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(64) Thiamine deficiency leading to impaired glucose breakdown leading to ATP depletion
worsened by glucose infusion

Wernicke encephalopathy in alcoholic
patient given glucose

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(65) Tryptophan is diverted towards serotonin synthesis leading to B3
deficiency (B3
is
derived from tryptophan)

Pellagra in malignant carcinoid
syndrome

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(69) Protein malnutrition leading to decrease oncotic pressure (leading to edema), decrease apolipoprotein
synthesis (leading to liver fatty change)

Kwashiorkor

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(70) increase NADH/NAD+ ratio due to ethanol metabolism

Lactic acidosis, fasting hypoglycemia,
hepatic steatosis in alcoholism

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(76) permeability of mitochondrial membrane leading to decrease proton [H+] gradient and
increase O2
consumption leading to uncoupling

Aspirin-induced hyperthermia

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(78) Aldolase B deficiency leading to Fructose-1-phosphate accumulates leading to decrease available
phosphate leading to inhibition of glycogenolysis and gluconeogenesis

Hereditary fructose intolerance

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

Classic galactosemia

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(79) Lens, retina, Schwann cells lack sorbitol dehydrogenase leading to intracellular
sorbitol accumulation leading to osmotic damage

Cataracts, retinopathy, peripheral
neuropathy in DM

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(10 Terminal complement deficiencies (C5–C9) failure of MAC formation5)

Recurrent Neisseria bacteremia

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(105) C1 esterase inhibitor deficiency leading to unregulated activation of kallikrein
leading to decrease bradykinin

Hereditary angioedema

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(105) PIGA gene mutation leading to decrease GPI anchors for complement inhibitors (DAF/ CD55, MIRL/CD59) leading to complement-mediated intravascular hemolysis

Paroxysmal nocturnal hemoglobinuria

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

Type I hypersensitivity

(110) Antibodies bind to cell-surface antigens leading to cellular destruction, inflammation, cellular dysfunction

Type II hypersensitivity

(111) Antigen-antibody complexes leading to activate complement leading to attracts neutrophils

Type III hypersensitivity

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

Type IV hypersensitivity

(112) Type II hypersensitivity reaction against donor RBCs (usually ABO antigens)

Acute hemolytic transfusion reaction

(114) Defect in BTK gene (tyrosine kinase) leading to no B-cell maturation leading to absent B cells in peripheral blood, decrease Ig of all classes

X-linked (Bruton) agammaglobulinemia

(114) 22q11 microdeletion leading to failure to develop 3rd and 4th branchial (pharyngeal) pouches

DiGeorge syndrome

(115) Defective CD40L on Th cells leading to class switching defect

Hyper-IgM syndrome

(115) LFA-1 integrin (CD18) defect leading impaired phagocyte migration and chemotaxis

Leukocyte adhesion deficiency (type 1)

(115) LYST mutation leading to microtubule dysfunction leading to phagosome-lysosome fusion defect

Chédiak-Higashi syndrome

(115) NADPH oxidase defect leading to decrease ROS, decrease respiratory burst in neutrophils

Chronic granulomatous disease

(116) decrease granulocytes (systemic), decrease T cells (local)

Candida infection in immunodeficiency

(117) Type IV HSR; HLA mismatch leading to donor T cells attack host cells

Graft-versus-host disease

(126) Catalase ⊕ organisms degrade H2 O2 before it can be converted to microbicidal products by the myeloperoxidase system

Recurrent S aureus, Serratia, B cepacia infections in CGD

(130) Shiga/Shiga-like toxins inactivate 60S ribosome leading to increase cytokine release

Hemolytic uremic syndrome

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

Tetanus

(130)Toxin (protease) cleaves SNARE leading to decreasie neurotransmitter (ACh) release at NMJ

Botulism

(131) Alpha toxin (phospholipase/lecithinase) degrades phospholipids leading to myonecrosis

Gas gangrene

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

Toxic shock syndrome, scarlet fever

(131) Lipid A of LPS leading to macrophage activation (TLR4/CD14), complement activation, tissue factor activation

Shock and DIC by gram ⊝ bacteria

(126,133) Biofilm production

Prosthetic device infection by S epidermidis

(126,134) Dextrans (biofilm) production that bind to fibrin-platelet aggregates on damaged heart valves

Endocarditis 2° to S sanguinis

(136) Toxins A and B damage enterocytes leading to watery diarrhea

Pseudomembranous colitis 2° to C difficile

(137) Exotoxin inhibits protein synthesis via ADP-ribosylation of EF-2

Diphtheria

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

Virulence of M tuberculosis

(139) Th1 immune response leading to mild

Tuberculoid leprosy

(140) Antigenic variation of pilus proteins

No effective vaccine for N gonorrhoeae

(143) Fimbriae (P pili)

Cystitis and pyelonephritis by E coli

(143) K capsule

Pneumonia, neonatal meningitis by E coli

(146) Lack of classic peptidoglycan (reduced muramic acid)

Chlamydiae resistance to β-lactam antibiotics

(166) RNA segment reassortment leading to antigenic shift

Influenza pandemics

(166) Mutations in hemagglutinin, neuraminidase antigenic drift

Influenza epidemics

(169) Binds to ACh receptors leading to retrograde transport (dynein)

CNS invasion by rabies

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

HIV infection

(213) Macrophages present antigens to CD4+ and secrete IL-12 CD4+ differentiation into Th1 which secrete IFN-γ leading to macrophage activation

Granuloma

(217) Reactivation of telomerase leading to maintains and lengthens telomeres leading to prevention of chromosome shortening and aging

Limitless replicative potential of cancer cells

(217) Decrease E-cadherin function leading to decrease intercellular junctions leading to basement membrane and ECM degradation by metalloproteinases leading to cell attachment to ECM proteins (laminin, fibronectin) leading to locomotion leading to vascular dissemination

Tissue invasion by cancer

(302) Failure of aorticopulmonary septum formation

Persistent truncus arteriosus

(302) Failure of the aorticopulmonary septum to spiral

D-transposition of great arteries

(302) Crying, fever, exercise leading to increase RV outflow obstruction leading to increase right-to-left flow across VSD; Squatting leading to increase SVR leading to decrease right-to-left shunt cyanosis

Tet spells in tetralogy of Fallot

(303) Uncorrected left-to-right shunt leading to increase pulmonary blood flow leading to remodeling of vasculature leading to pulmonary hypertension leading to RVH leading to right to left shunting

Eisenmenger syndrome

(305) Endothelial cell dysfunction leading to macrophage and LDL accumulation leading to foam cell formation leading to fatty streaks leading to smooth muscle cell migration, extracellular matrix deposition leading to fibrous plaque leading to complex atheromas

Atherosclerosis

(306) Cystic medial degeneration

Thoracic aortic aneurysm

(308) Rupture of coronary artery atherosclerotic plaque leading to acute thrombosis

Myocardial infarction

(308) Subendocardial infarcts (subendocardium vulnerable to ischemia)

Non–ST-segment elevation MI

(308) Transmural infarcts

ST-segment elevation MI

(309,314) Ventricular arrhythmia

Death within 0-24 hours post MI

(309,314) Macrophage-mediated ruptures: papillary muscle (2-7 days), interventricular septum (3-5 days), free wall (5-14 days)

Death or shock within 3-14 days post MI

(311) Abnormal accessory pathway from atria to ventricle bypasses the AV node leading to ventricles begin to partially depolarize earlier leading to delta wave. Reentrant circuit leading to supraventricular tachycardia.

Wolff-Parkinson-White

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

Hypertrophic obstructive cardiomyopathy

(315) Asymmetric septal hypertrophy, systolic anterior motion of mitral valve outflow obstruction

Syncope, dyspnea in HOCM

(317) decrease preload leading to decrease CO

Hypovolemic shock

(317) Decrease CO due to left heart dysfunction

Cardiogenic shock

(317) Decrease SVR (afterload)

Distributive shock

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

Rheumatic fever

(339) 21-hydroxylase deficiency leading to decrease mineralocorticoids, decrease cortisol, increase sex hormones, increase 17-hydroxyprogesterone

Most common form of congenital adrenal hyperplasia

(344) Increase Na+-K+ ATPase leading to increase basal metabolic rate leading to increase calorigenesis

Heat intolerance, weight loss in hyperthyroidism

(344) Increase CAGs in interstitial space

Myxedema in hypothyroidism

(346) Lymphocytic infiltration, fibroblast secretion of GAGs leading to increase osmotic muscle swelling, inflammation

Graves ophthalmopathy

(349) Parathyroid adenoma or hyperplasia leading to increase PTH

1° hyperparathyroidism

(349) Decrease Ca2+ and/or increase PO4 3– leading to parathyroid hyperplasia leading to increase PTH, increase ALP

2° hyperparathyroidism

(342) Increase ADH leading to water retention leading to decrease aldosterone, increase ANB, increase BNP leading to increase urinary Na+ secretion

Euvolemic hyponatremia in SIADH

(350) Nonenzymatic glycation of proteins

Small/large vessel disease in DM

(351) decrease Insulin or increase insulin requirement leading to increase fat breakdown leading to increase free fatty acids leading to increase ketogenesis

Diabetic ketoacidosis

(351) Hyperglycemia leading to increase serum osmolality, excessive osmotic diuresis

Hyperosmolar hyperglycemic state

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

Zollinger-Ellison syndrome

(366) Failure to recanalize

Duodenal atresia

(366) Disruption of SMA leading to ischemic necrosis of fetal intestine

Jejunal/ileal atresia

(370) Compression of transverse (third) portion of duodenum by SMA and aorta

Superior mesenteric artery syndrome

(383) Loss of postganglionic inhibitory neurons (contain NO and VIP) in myenteric plexus leading to failure of LES relaxation

Achalasia

(385) Replacement (metaplasia) of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells)

Barrett esophagus

(386) Decrease PGE2 leading to decrease gastric protection

Acute gastritis 2° to NSAIDs

(388) Autoimmune-mediated intolerance of gliadin (found in wheat) malabsorption (distal duodenum, proximal jejunum), steatorrhea

Celiac disease

(389) Transmural inflammation

Fistula formation in Crohn

(391) Persistence of the vitelline (omphalomesenteric) duct

Meckel diverticulum

(391) Loss of function mutation in RET leading to failure of neural crest migration leading to lack of ganglion cells/enteric nervous plexuses in distal colon

Hirschsprung disease

(395) Loss of APC (decrease intercellular adhesion, increase proliferation) leading to KRAS mutation (unregulated intracellular signaling) leading to loss of tumor suppressor genes (TP53, DCC)

Adenoma-carcinoma sequence in colorectal cancer

(396) Stellate cells

Fibrosis in cirrhosis

(397)

Reye syndrome

(398) Cirrhosis leading to portosystemic shunts leading to decrease NH3 metabolism

Hepatic encephalopathy

(400) Misfolded proteins aggregate in hepatocellular ER leading to cirrhosis. In lungs, decrease α1 -antitrypsin leading to uninhibited elastase in alveoli leading to panacinar emphysema

α1 -antitrypsin deficiency

(402) Mutated hepatocyte copper-transporting ATPase (ATP7B on chromosome 13) leading to decrease copper incorporation into apoceruloplasmin, excretion into bile leading to decrease serum ceruloplasmin, increase copper in tissues and urine

Wilson disease

(402) HFE mutation on chromosome 6 decrease hepcidin production, increase intestinal absorption leading to iron overload (increase ferritin,increase iron, decrease TIBC leading to increase transferrin saturation)

Hemochromatosis

(403) Fistula between gallbladder and GI tract leading to stone enters GI lumen leading to obstructing ileocecal valve (narrowest point)

Gallstone ileus

(403) Biliary tree obstruction leading to stasis/bacterial overgrowth

Acute cholangitis

(404) Autodigestion of pancreas by pancreatic enzymes

Acute pancreatitis

(411) Rh ⊝ mother form antibodies (maternal anti-D IgG) against RBCs of Rh ⊕ fetus

Rh hemolytic disease of the newborn

(425) Lead inhibits ferrochelatase and ALA dehydratase leading to decrease heme synthesis, increase RBC protoporphyrin.

Anemia in lead poisoning

(427) Inflammation leading to increase hepcidin leading to decrease release of iron from macrophages, decrease iron absorption from gut

Anemia of chronic disease

(428) Defect in G6PD leading to decrease NADPH leading to decrease reduced glutathione leading to increase RBC susceptibility to oxidant stress

G6PD deficiency

(428) Point mutation leading to substitution of glutamic acid with valine in β chain leading to low O2 , high altitude, acidosis precipitates sickling (deoxygenated HbS polymerizes) leading to anemia, vaso-occlusive disease

Sickle cell anemia

(432) Decrease GpIb leading to decrease platelet-to-vWF adhesion

Bernard-Soulier syndrome

(432) Decrease GpIIb/IIIa leading to decrease platelet-to-platelet aggregation, defective platelet plug formation

Glanzmann thrombasthenia

( 432) Decrease ADAMTS13 (a vWF metalloprotease) leading to decrease degradation of vWF multimers leading to increase platelet adhesion and aggregation (microthrombi formation)

Thrombotic thrombocytopenic purpura

(433) Decrease vWF leading to decrease platelet-to-vWF adhesion, possibly possibly PTT (vWF protects factor VIII)

von Willebrand disease

(433) Mutant factor V (Arg506Gln) that is resistant to degradation by protein C

Factor V Leiden

(450) Fractured surgical neck or anterior dislocation of humerus leading to flattened deltoid

Axillary nerve injury

(450) Compression of axilla (use of crutches), midshaft humerus fracture, repetitive pronation/supination of forearm leading to wrist/finger drop, decreased grip strength

Radial nerve injury (“Saturday night palsy”)

(450) Proximal lesion: supracondylar fracture leading to loss of sensation over thenar eminence, dorsal and palmar aspect of lateral 3½ fingers Distal lesion: carpal tunnel syndrome

Median nerve injury (Ape’s hand/ Pope’s blessing)

(450) Proximal lesion: fractured medial epicondyle leading to radial deviation of wrist on flexion Distal lesion: fractured hook of hamate leading to ulnar claw on digital extension

Ulnar nerve injury

(452) Traction/tear of C5-C6 roots during delivery on the neck of the infant, and due to trauma in adults

Erb palsy (waiter’s tip)

(452) Traction/tear of C8-T1 roots during delivery on the arm of the infant, and on trying to grab a branch in adults

Klumpke palsy

(452) Injury to long thoracic nerve (C5-C7), like on axillary node dissection during mastectomy

Winged scapula

(457) Trauma on lateral aspect of leg or fracture of fibular neck leading to foot drop with steppage gait

Common peroneal nerve injury

(457)Iatrogenic injury during IM injection at gluteal region leading to Trendelenburg sign: lesion contralateral to side of hip that drops due to adductor weakness

Superior gluteal nerve injury

(457) Injury during horseback riding or prolonged cycling; can be blocked during delivery at the ischial spine

Pudendal nerve injury

(466) Nursemaid’s elbow; due to sudden pull on arm (in children)

Radial head subluxation

(466) Obese young adolescent with hip/knee pain. Increased axial force on femoral head leading to epiphysis displaces relative to femoral neck like a scoop of ice cream slips off a cone

Slipped capital femoral epiphysis

(467) Constitutive activation of FGFR3 leading to decrease chondrocyte proliferation leading to failure of endochondral ossification leading to short limbs67)

Achondroplasia

(467) Increase osteoclast activity leading to increase bone resorption secondary to decrease estrogen levels and old age.

Osteoporosis

(468) Carbonic anhydrase II mutations leading to decrease ability of osteoclasts to generate acidic environment leading to decrease bone resorption leading to dense bones prone to fracture, pancytopenia (decrease marrow space)

Osteopetrosis

(468) Increase osteoclast activity followed by increase osteoblast activity leading to poor quality bone formed that is prone to fractures.

Osteitis deformans

(472) Mechanical degeneration of articular cartilage causing inflammation with inadequate repair and osteophyte formation.

Osteoarthritis

(472) Autoimmune inflammation due to HLA-DR4 causing pannus formation. Type III Hypersensitivity reaction.

Rheumatoid arthritis

(474) Autoimmune Type IV hypersensitivity reaction leading to lymphocyte mediated damage of exocrine glands

Sjogren syndrome

(476) Predominantly a Type III hypersensitivity reaction with decrease clearance of immune complexes. Hematologic manifestations are a type II hypersensitivity reaction.

Systemic lupus erythematosus

(472) Mechanical degeneration of articular cartilage causing inflammation with inadequate repair and osteophyte formation.

Osteoarthritis

(472) Autoimmune inflammation due to HLA-DR4 causing pannus formation. Type III Hypersensitivity reaction

Rheumatoid arthritis

(474) Autoimmune Type IV hypersensitivity reaction leading to lymphocyte mediated damage of exocrine glands.

Sjogren syndrome

(476) Predominantly a Type III hypersensitivity reaction with decreased clearance of immune complexes. Hematologic manifestations are a type II hypersensitivity reaction.

Systemic lupus erythematosus

(478) Ophthalmic artery occlusion

Blindness in giant cell (temporal) arteritis

(480) Autoantibodies to postsynaptic nicotinic (ACh) receptors

Myasthenia gravis

(480) Autoantibodies to presynaptic calcium channels leading to decrease ACh release

Lambert-Eaton myasthenic syndrome

(484) Normal melanocyte number, decrease melanin production

Albinism

(484) Autoimmune destruction of melanocytes

Vitiligo

(485) Epidermal barrier dysfunction, genetic factors (ie, loss-of-function mutations in the filaggrin [FLG] gene), immune dysregulation, altered skin microbiome, environmental triggers of inflammation

Atopic dermatitis

(485) Type IV HSR. During the sensitization phase, Allergen activates Th1 cells leading to memory CD4+ cells and CD8+ form. Upon reexposure leading to CD4+ cells release cytokines and Cd8+ cells kill targeted cells

Allergic contact dermatitis

(485) Disrupted skin barrier leading to activation of dendritic cells via inflammatory cytokines (IL-1B, IL-6, TNF) leading to activated dendritic cells release IL-23 leading to Naive T cells form Th1 (IL-12) and Th17 (IL-23) cells that secrete IFN-y and IL-17A/IL-22 respectively leading to Acanthosis, parakeratosis, hypogranulosis

Psoriasis

(489) Type II HSR. IgG autoantibodies form against desmoglein 1 and 3 in desmosomes leading to separation of keratinocytes in stratum spinosum from stratum basale

Pemphigus vulgaris

(489) Type II HSR. IgG autoantibodies against hemidesmosomes leading to separation of epidermis from dermis

Bullous pemphigoid

(501)Failure of caudal neuropore to fuse by 4th week of development

Spina bifida occulta, meningocele, myelomeningocele, myeloschisis

(501) Failure of rostral neuropore to close leading to no forebrain, open calvarium

Anencephaly

(501) Failure of the forebrain (prosencephalon) to divide into 2 cerebral hemispheres; developmental field defect typically occurring at weeks 3-4 of development; associated with SHH mutations

Holoprosencephaly

(501) Failure of neuronal migration leading to smooth brain surface lacking sulci and gyri

Lissencephaly

(502) Downward displacement of cerebellar tonsils inferior to foramen magnum

Chiari I malformation

(502) Herniation of cerebellum (vermis and tonsils) and medulla through foramen magnum leading to noncommunicating hydrocephalus

Chiari II malformation

(502) Agenesis of cerebellar vermis leading to cystic enlargement of 4th ventricle that fills the enlarged posterior fossa; associated with noncommunicating hydrocephalus

Dandy-Walker malformation

(502) Fluid-filled, gliosis-lined cavity within spinal cord, associated with Chiari I malformation (low-lying cerebellar tonsils), less commonly with infections, tumors, trauma

Syringomyelia

(526) Lesion in the dominant parietal cortex leading to agraphia, acalculia, finger agnosia, left-right disorientation

Gerstmann syndrome

(526) Lesion in the nondominant parietal cortex

Hemispatial neglect syndrome

(526) Bilateral lesions in the amygdala; seen in HSV-1 encephalitis leading to disinhibition, including hyperphagia, hypersexuality, hyperorality

Klüver-Bucy syndrome

(526) Lesion in the dorsal midbrain; often due to pineal gland tumors

Parinaud syndrome (inability to move eyes up and down)

(527) Fluid accumulation in the brain parenchyma leading to increase ICP; may be cytotoxic (intracellular fluid accumulation due to osmotic shift; associated with early ischemia, hyperammonemia, SIADH) or vasogenic (extracellular fluid accumulation due to increased permeability of BBB; associated with late ischemia, trauma, hemorrhage, inflammation, tumors)

Cerebral edema

(528) Stroke in dominant (usually left) hemisphere, in either the superior temporal gyrus of temporal lobe (Wernicke; receptive aphasia) or inferior frontal gyrus of frontal lobe (Broca; expressive aphasia)

Aphasia

(528) Stroke of the basilar artery

Locked-in syndrome (loss of horizontal, but not vertical, eye movements)

(528) Stroke of the anterior inferior cerebellar artery

Lateral pontine syndrome

(529) Stroke of the posterior inferior cerebellar artery

Lateral medullary (Wallenberg) syndrome

(529) Stroke of the anterior spinal artery

Medial medullary syndrome

(529) Reduced glial fiber support and impaired autoregulation of BP in premature infants leading to bleeding into the ventricles, originating in the germinal matrix (a highly vascularized layer within the subventricular zone)

Neonatal intraventricular hemorrhage

(530) Rupture of middle meningeal artery, often secondary to skull fracture involving the pterion

Epidural hematoma

(530) Rupture of bridging veins; acute (traumatic, high-energy impact, sudden deceleration injury) or chronic (mild trauma, cerebral atrophy, increase age, chronic alcohol overuse, shaken baby syndrome)

Subdural hematoma

(530) Trauma, rupture of aneurysm (such as a saccular aneurysm), or arteriovenous malformation leading to bleeding

Subarachnoid hemorrhage

(530) Systemic hypertension (most often occur in the putamen of basal ganglia, thalamus, pons, and cerebellum), amyloid angiopathy, arteriovenous malformation, vasculitis, neoplasm, or secondary to reperfusion injury in ischemic stroke leading to bleeding

Intraparenchymal hemorrhage

(531) Most commonly following amputation leading to reorganization of primary somatosensory cortex leading to sensation of pain in a limb that is no longer prese

Phantom limb pain

(531) Traumatic shearing of white matter tracts during rapid acceleration and/or deceleration of the brain (eg, motor vehicle accident) leading to multiple punctate hemorrhages involving white matter tracts leading to neurologic injury, often causing coma or persistent vegetative state

Diffuse axonal injury

(531) Damage to the arcuate fasciculus

Conduction aphasia

(531) Damage to both Broca (inferior frontal gyrus of frontal lobe) and Wernicke (superior temporal gyrus of temporal lobe) areas

Global aphasia

(532) Inability of body to dissipate heat (eg, exertion) leading to CNS dysfunction (eg, confusion), rhabdomyolysis, acute kidney injury, ARDS, DIC

Heat stroke

(534) Irritation of CN V, meninges, or blood vessels (release of vasoactive neuropeptides [eg, substance P, calcitonin gene-related peptide])

Migraine

(536) Loss of dopaminergic neurons of substantia nigra pars compacta

Parkinson disease

(536) Trinucleotide (CAG) repeat expansion in huntingtin (HTT) gene on chromosome 4 leading to toxic gain of function leading to atrophy of caudate and putamen with ex vacuo ventriculomegaly leading to increase dopamine, decrease GABA, decrease ACh in brain leading to neuronal death via glutamate excitotoxicity

Huntington disease

(536) Widespread cortical atrophy, narrowing of gyri and widening of sulci; senile plaques in gray matter composed of beta-amyloid core (formed by cleavage of amyloid precursor protein); neurofibrillary tangles composed of intracellular, hyperphosphorylated tau protein; Hirano bodies (intracellular eosinophilic proteinaceous rods in hippocampus)

Alzheimer disease

(536) Frontotemporal lobe degeneration leading to decrease executive function and behavioral inhibition

Frontotemporal dementia

(537) Multiple arterial infarcts and/or chronic ischemia

Vascular dementia

(537) Secondary to diffuse gray matter and subcortical atrophy

HIV-associated dementia

(538) Increased ICP, associated with dural venous sinus stenosis; impaired optic nerve axoplasmic flow leading to papilledema

Idiopathic intracranial hypertension

(538)Reduced CSF absorption by arachnoid granulations (eg, arachnoid scarring post-meningitis leading to increase ICP, papilledema, herniation

Communicating hydrocephalus

(538) Idiopathic, CSF pressure elevated only episodically, no increase subarachnoid space volume; expansion of ventricles distorts the fibers of the corona radiata

Normal pressure hydrocephalus

(538) Structural blockage of CSF circulation within ventricular system (eg, stenosis of aqueduct of Sylvius, colloid cyst blocking foramen of Monro, tumor)

Noncommunicating hydrocephalus

(539) Autoimmune inflammation and demyelination of CNS (brain and spinal cord) leading to axonal damage

Multiple sclerosis

(540) Rapid osmotic changes, most commonly iatrogenic correction of hyponatremia but also rapid shifts of other osmolytes (eg, glucose) leading to massive axonal demyelination in pontine white matter

Osmotic demyelination syndrome

(540) Autoimmune destruction of Schwann cells via inflammation and demyelination of motor and sensory fibers and peripheral nerves; likely facilitated by molecular mimicry and triggered by inoculations or stress

Acute inflammatory demyelinating polyneuropathy (subtype of GuillainBarré syndrome)

(540) Defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath

Charcot-Marie-Tooth disease

(540) Destruction of oligodendrocytes secondary to reactivation of latent JC virus infection leading to demyelination of CNS

Progressive multifocal leukoencephalopathy

(541) Somatic mosaicism of an activating mutation in one copy of the GNAQ gene leading to congenital anomaly of neural crest derivatives leading to capillary vascular malformation, ipsilateral leptomeningeal angioma with calcifications, episcleral hemangioma

Sturge-Weber syndrome

(542) Hyperplasia of only one type of endocrine cells found in pituitary (most commonly from lactotrophs, producing prolactin)

Pituitary adenoma

(546) Congenital degeneration of anterior horns

Spinal muscular atrophy

(546) Can be caused by defect in superoxide dismutase 1

Amyotrophic lateral sclerosis

(546) Degeneration/demyelination of dorsal columns and roots leading to progressive sensory ataxia (impaired proprioception leading to poor coordination)

Tabes dorsalis

(546) Poliovirus infection spreads from lymphoid tissue of oropharynx to small intestine and then to CNS via bloodstream leading to destruction of cells in anterior horn of spinal cord (LMN death)

Poliomyelitis

(547) Trinucleotide repeat disorder (GAA) on chromosome 9 in gene that encodes frataxin (iron-binding protein) leading to impairment in mitochondrial functioning leading to degeneration of lateral corticospinal tract, spinocerebellar tract, dorsal columns, and dorsal root ganglia

Friedreich ataxia

(550) Damage to stereociliated cells in organ of Corti leading to loss of high-frequency hearing first; sudden extremely loud noises can lead to tympanic membrane rupture leading to hearing loss

Noise-induced hearing loss

(550)Destruction of hair cells at the cochlear base (preserved low-frequency hearing at apex) leading to aging-related progressive bilateral/symmetric sensorineural hearing loss (often of higher frequencies)

Presbycusis

(550) Abnormal growth of keratinized squamous epithelium in middle ear

Cholesteatoma

(550) Increased endolymph in inner ear leading to vertigo, hearing loss, tinnitus and ear fullness

Ménière disease

(551) Eye too short for refractive power of cornea and lens leading to light focused behind retina

Hyperopia

(551) Eye too long for refractive power of cornea and lens leading to light focused in front of retina

Myopia

(551) Abnormal curvature of cornea leading to different refractive power at different axes

Astigmatism

(552) Aging-related impaired accommodation, primarily due to decrease lens elasticity

Presbyopia

(553) Optic neuropathy causing progressive vision loss (peripheral leading to central), usually accompanied by increased intraocular pressure

Glaucoma

(533) Associated with increased resistance to aqueous humor drainage through trabecular meshwork

Open-angle glaucoma

(533Anterior chamber angle is narrowed or closed; associated with anatomic abnormalities (eg, anteriorly displaced lens resting against central iris) leading to decrease aqueous flow through pupil leading to increase pressure in posterior chamber leading to peripheral iris pushed against cornea obstruction of drainage pathways by the iris)

Angle-closure glaucoma

(554) Chronic hyperglycemia leading to increase permeability and occlusion of retinal vessels leading to microaneurysms, hemorrhages (nonproliferative); retinal neovascularization due to chronic hypoxia (proliferative)

Diabetic retinopathy

(554) Chronic hypertension leading to spasm, sclerosis, and fibrinoid necrosis of retinal vessels

Hypertensive retinopathy

(554) Blockage of central or branch retinal artery usually due to embolism (carotid artery atherosclerosis > cardiogenic); less commonly due to giant cell arteritis

Retinal artery occlusion

(554) Primary thrombosis leading to central retinal vein occlusion; secondary thrombosis at arteriovenous crossings (sclerotic arteriole compresses adjacent venule causing turbulent blood flow) leading to branch retinal vein occlusion

Retinal vein occlusion

(554) Separation of neurosensory retina from underlying retinal pigment epithelium leading to loss of choroidal blood supply leading to hypoxia and degeneration of photoreceptors; due to retinal tears (rhegmatogenous) or tractional or exudative (fluid accumulation) (nonrhegmatogenous)

Retinal detachment

(554) Progressive degeneration of photoreceptors and retinal pigment epithelium

Retinitis pigmentosa

(554) Increase ICP (eg, secondary to mass effect) leading to impaired axoplasmic flow in optic nerve leading to optic disc swelling (usually bilateral)

Papilledema

(556) Unilateral or asymmetric lesions of afferent limb of pupillary reflex (eg, retina, optic nerve)

Relative afferent pupillary defect

(557) Lesions along the sympathetic chain: 1st neuron (pontine hemorrhage, lateral medullary syndrome, spinal cord lesion above T1 like BrownSequard syndrome or late-stage syringomyelia); 2nd neuron (stellate ganglion compression by Pancoast tumor); 3rd neuron (carotid dissection)

Horner syndrome

(559) Secondary to pituitary tumor mass effect, carotid-cavernous fistula, or cavernous sinus thrombosis related to infection (spreads due to lack of valves in dural venous sinuses)

Cavernous sinus syndrome

(577) Usually secondary to illnesses (eg, CNS disease, infection, trauma, substance use), or medications (eg, anticholinergics)

Delirium

(579) Altered dopaminergic activity, increase serotonergic activity, decrease dendritic activity

Schizophrenia

(613) Inability of α-intercalated cells to secrete H+ leading to no new HCO3– generated leading to metabolic acidosis

Distal RTA (type 1)

(613) Defective PCT HCO3– reabsorption leading to increase excretion of HCO3– in urine leading to metabolic acidosis

Proximal RTA (type 2)

(613) Hypoaldosteronism/aldosterone resistance leading to increase K+ leading to NH3 synthesis in PCT leading to decrease NH 4 + excretion

Hyperkalemic tubular acidosis (type 4)

(615) Glomerular inflammation leading to GBM damage leading to loss of RBCs in urine leading to dysmorphic RBCs, hematuria

Nephritic syndrome

(615) Podocyte damage leading to impaired charge barrier leading to proteinuria

Nephrotic syndrome

(615) Severe GBM damage leading to loss of RBCs in urine + impaired charge barrier leading to hematuria + proteinuria

Nephritic-nephrotic syndrome

(616) Type III HSR with consumptive hypocomplementemia

Infection-associated glomerulonephritis

(617)Type IV collagen mutation (X-linked dominant) leading to irregular thinning and thickening and splitting of GBM leading to nephritic syndrome

Alport syndrome

(620) Outlet incompetence (urethral hypermobility/intrinsic sphincter deficiency) leading to leak on increase intraabdominal pressure

Stress incontinence

(620) Detrusor overactivity leading to leak with urge to void

Urge incontinence

(620) Incomplete emptying (detrusor underactivity or outlet obstruction) leading to leak with overfilling

Overflow incontinence

(622) Decrease RBF leading to decrease GFR leading to increase reabsorption of Na+/H2O and urea

Prerenal azotemia

(622) Patchy necrosis leading to debris obstructing tubules and fluid backflow leading to decrease GFR

Intrinsic renal failure

(622) Outflow obstruction (bilateral)

Postrenal azotemia

(645) Twisting of ovary/fallopian tube around infundibulopelvic ligament and ovarian ligament leading to venous/lymphatic blockage leading to arterial inflow continued leading to edema leading to blockade of arterial inflow leading to necrosis

Adnexal torsion

(662) Abnormal placental spiral arteries leading to endothelial dysfunction, vasoconstriction, ischemia leading to new-onset HTN with proteinuria

Preeclampsia

(663) Supine position leading to compressed abdominal aorta and IVC by gravid uterus leading to decrease placental perfusion and decrease venous return

Supine hypotensive syndrome

(665) Severe caloric restriction, increase energy expenditure, and/or stress leading to altered pulsatile GnRH secretion leading to decrease LH, FSH, estrogen

Functional hypothalamic amenorrhea

(665) Hyperinsulinemia and/or insulin resistance leading to altered hypothalamic feedback response leading to increase LH:FSH, increase androgens, decrease rate of follicular maturation leading to unruptured follicles (cysts) + anovulation

Polycystic ovarian syndrome

(671) Dilated veins in pampiniform plexus due to increase venous pressure leading to enlarged scrotum

Varicocele

(690) Oxidized Hb secondary to dapsone, local anesthetics, nitrites leading to Hb oxidization (Fe2+) leading to decrease O2 binding but leading to cyanide affinity leading to tissue hypoxia

Deep venous thrombosis

(697) Noncaseating granulomas leading to increase macrophage activity leading to increase 1α-hydroxylase activity in macrophage leading to vitamin D activation leading to increase Ca2+

Sarcoidosis associated hypercalcemia

(699) Alveolar injury leading to inflammation leading to capillary endothelial damage and increase vessel permeability leading to leakage of protein-rich fluid into alveoli leading to intra-alveolar hyaline membranes and noncardiogenic pulmonary edema leading to decrease compliance and V/Q mismatch leading to hypoxic vasoconstriction leading to increase pulmonary vascular resistance

Acute respiratory distress syndrome

(699) Respiratory effort against airway obstruction (obstructive); impaired respiratory effort due to CNS injury/toxicity, CHF, opioids (central); obesity leading to hypoventilation leading to increase PaCO2 during waking hours

Sleep apnea

(35) Gout, intellectual disability, self-mutilating behavior in a boy

Lesch-Nyhan syndrome (HGPRT deficiency, X-linked recessive)

(47) Situs inversus, chronic ear infections, sinusitis, bronchiectasis, infertility

Primary ciliary dyskinesia (Kartagener syndrome)

(49) Blue sclera, multiple fractures, dental problems, conductive hearing loss

Osteogenesis imperfecta (type I collagen defect)

(49) Elastic skin, hypermobility of joints, bleeding tendency

Ehlers-Danlos syndrome (type V collagen defect, type III collagen defect seen in vascular subtype of ED)

(50) Arachnodactyly, lens dislocation (upward and temporal), aortic dissection, hyperflexible joints

Marfan syndrome (fibrillin defect)

(50) Arachnodactyly, pectus deformity, lens dislocation (downward)

Homocystinuria (autosomal recessive)

(55) Café-au-lait spots (unilateral), polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities

McCune-Albright syndrome (Gs-protein activating mutation)

(58) Meconium ileus in neonate, recurrent pulmonary infections, nasal polyps, pancreatic insufficiency, infertility/subfertility

Cystic fibrosis (CFTR gene defect, chromosome 7, ∆F508)

(59) Calf pseudohypertrophy

Muscular dystrophy (most commonly Duchenne, due to X-linked recessive frameshift mutation of dystrophin gene)

(59) Child uses arms to stand up from squat

Duchenne muscular dystrophy (Gowers sign)

(59) Slow, progressive muscle weakness in boys

Becker muscular dystrophy (X-linked non-frameshift deletions in dystrophin; less severe than Duchenne

(61) Infant with cleft lip/palate, microcephaly or holoprosencephaly, polydactyly, cutis aplasia

Patau syndrome (trisomy 13)

(61) Infant with microcephaly, rocker-bottom feet, clenched hands, and structural heart defect

Edwards syndrome (trisomy 18)

(61) Single palmar crease, intellectual disability

Down syndrome

(62) Microcephaly, high-pitched cry, intellectual disability

Cri-du-chat (cry of the cat) syndrome

(64) Confusion, ophthalmoplegia/nystagmus, ataxia

Wernicke encephalopathy (add confabulation/memory loss for Korsakoff syndrome)

(64) Dilated cardiomyopathy/high-output heart failure, edema, alcoholism or malnutrition

Wet beriberi (thiamine [vitamin B1] deficiency)

(65) Burning feet syndrome

Vitamin B5 deficiency

(65) Dermatitis, dementia, diarrhea

Pellagra (niacin [vitamin B3] deficiency)

(67) Swollen gums, mucosal bleeding, poor wound healing, petechiae, corkscrew hairs, perifollicular hemorrhages

Scurvy (vitamin C deficiency: can’t hydroxylate proline/ lysine for collagen synthesis); tea and toast diet

(68) Bowlegs (children), bone pain, and muscle weakness

Rickets (children), osteomalacia (adults); vitamin D deficiency

(69) Hemorrhagic disease of newborn with increase PT, increase aPTT

Vitamin K deficiency

(82) Intellectual disability, musty body odor, hypopigmented skin, eczema

Phenylketonuria

(82) Bluish-black connective tissue, ear cartilage, sclerae; urine turns black on prolonged exposure to air

Alkaptonuria (homogentisate oxidase deficiency; ochronosis)

(85) Infant with hypoglycemia, hepatomegaly, cardiomyopathy

Cori disease (debranching enzyme deficiency) or von Gierke disease (glucose-6-phosphatase deficiency, more severe)

(85) Chronic exercise intolerance with myalgia, fatigue, painful cramps, myoglobinuria

McArdle disease (skeletal muscle glycogen phosphorylase deficiency)

(86) Cherry-red spots” on macula

Tay-Sachs (ganglioside accumulation; no hepatosplenomegaly); Niemann-Pick disease (sphingomyelin accumulation; hepatosplenomegaly); central retinal artery occlusion

(86) Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of femoral head, bone crises

Gaucher disease (glucocerebrosidase [β-glucosidase] deficiency)

(92) Achilles tendon xanthoma

Familial hypercholesterolemia (decrease LDL receptor signaling)

(114) Male child, recurrent infections, no mature B cells

Bruton disease (X-linked agammaglobulinemia)

(114) Anaphylaxis following blood transfusion

IgA deficiency

(114) Recurrent cold (noninflamed) abscesses, eczema, high serum IgE, increase eosinophils

Hyper-IgE syndrome (Job syndrome: neutrophil chemotaxis abnormality)

(115) Late separation (>30 days) of umbilical cord, no pus, recurrent skin and mucosal bacterial infections

Leukocyte adhesion deficiency (type 1; defective LFA-1 integrin)

(115) Recurrent infections and granulomas with catalase ⊕ organisms

Chronic granulomatous disease (defect of NADPH oxidase)

(133) Fever, vomiting, diarrhea, desquamating rash following use of nasal pack or tampon

Staphylococcal toxic shock syndrome

(134) “Strawberry tongue

Scarlet fever (sandpaper rash); Kawasaki disease (lymphadenopathy, high fever for 5 days

(135) Colon cancer associated with infective endocarditis

Streptococcus bovis

(136) Flaccid paralysis in newborn after ingestion of honey

Clostridium botulinum infection (floppy baby syndrome)

(136) Abdominal pain, diarrhea, leukocytosis, recent antibiotic use

Clostridioides difficile infection

(137) Tonsillar pseudomembrane with “bull’s neck” appearance

Corynebacterium diphtheria infection

(138) Back pain, fever, night sweats

Pott disease (vertebral TB)

(140) Adrenal insufficiency, fever, bilateral adrenal hemorrhage

Waterhouse-Friderichsen syndrome (meningococcemia)

(143) Red “currant jelly” sputum in patients with alcohol overuse or diabetes

Klebsiella pneumoniae pneumonia

(144) Fever, chills, headache, myalgia following antibiotic treatment for syphilis

Jarisch-Herxheimer reaction (due to host response to sudden release of bacterial antigens

(144) Large rash with bull’s-eye appearance

Erythema migrans from Ixodes tick bite (Lyme disease: Borrelia)

(145) Ulcerated genital lesion

Nonpainful, indurated: chancre (1° syphilis, Treponema pallidum) Painful, with exudate: chancroid (Haemophilus ducreyi)

(145) Smooth, moist, painless, wartlike white lesions on genitals

Condylomata lata (2° syphilis)

(145) Pupil accommodates but doesn’t react to light

Neurosyphilis (Argyll Robertson pupil)

(147) Dog or cat bite resulting in infection (cellulitis, osteomyelitis)

Pasteurella multocida (cellulitis at inoculation site)

(148) Atypical "walking pneumonia" with x-ray looking worse than the patient

Mycoplasma pneumoniae infection

(148) Rash on palms and soles

Coxsackie A, 2° syphilis, Rocky Mountain spotted fever

(150) Black eschar on face of patient with diabetic ketoacidosis and/or neutropenia

Mucor or Rhizopus fungal infection

(153) Chorioretinitis, hydrocephalus, intracranial calcifications

Congenital toxoplasmosis

(161)Child with fever later develops red rash on face that spreads to body

Erythema infectiosum/fifth disease (“slapped cheeks” appearance, caused by parvovirus B19

(156) Pruritus, serpiginous rash after walking barefoot

Hookworm (Ancylostoma spp, Necator americanus)

(167)Fever, cough, conjunctivitis, coryza, diffuse rash

Measles

(167) Small, irregular red spots on buccal/lingual mucosa with blue-white centers

Koplik spots (measles [rubeola] virus)

(296) Bounding pulses, wide pulse pressure, diastolic heart murmur, head bobbing

Aortic regurgitation

(296) Systolic ejection murmur (crescendo-decrescendo), narrow pulse pressure, pulsus parvus et tardus

Aortic stenosis

(296) Continuous “machinelike” heart murmur

PDA (close with indomethacin; keep open with PGE analogs)

(308 )Chest pain on exertion

Angina (stable: with moderate exertion; unstable: with minimal exertion or at rest)

(308) Chest pain with ST depressions on ECG

Angina (⊝ troponins) or NSTEMI (⊕ troponins)

(314) Chest pain, pericardial effusion/friction rub, persistent fever following MI

Postcardiac injury syndrome (autoimmune-mediated post-MI fibrinous pericarditis, 2 weeks to several months after acute episode)

(317) Distant heart sounds, distended neck veins, hypotension

Beck triad of cardiac tamponade

(318) Painful, raised red lesions on pads of fingers/toes

Osler nodes (infective endocarditis, immune complex deposition)

(318) Painless erythematous lesions on palms and soles

Janeway lesions (infective endocarditis, septic emboli/ microabscesses)

(318) Splinter hemorrhages in fingernails

Infective endocarditis

(318) Retinal hemorrhages with pale centers

Roth spots (infective endocarditis)

(320) Telangiectasias, recurrent epistaxis, skin discoloration, arteriovenous malformations, GI bleeding, hematuria

Hereditary hemorrhagic telangiectasia (Osler-WeberRendu syndrome

(342) Polyuria, polydipsia

Primary polydipsia, diabetes insipidus (central, nephrogenic)

(343) No lactation postpartum, absent menstruation, cold intolerance

Sheehan syndrome (severe postpartum hemorrhage leading to pituitary infarction)

(343) Heat intolerance, weight loss, palpitations

Hyperthyroidism

(343) Cold intolerance, weight gain, brittle hair

Hypothyroidism

(343) Cutaneous/dermal edema due to deposition of mucopolysaccharides in connective tissue

Myxedema (caused by hypothyroidism or hyperthyroidism [Graves disease])

(348) Facial muscle spasm upon tapping

Chvostek sign (hypocalcemia)

(348) Carpal spasm upon inflation of BP cuff

Trousseau sign (hypocalcemia)

(351) Rapid, deep, labored breathing/hyperventilation

Diabetic ketoacidosis (Kussmaul respirations)

(353) Skin hyperpigmentation, orthostatic hypotension, fatigue, weakness, muscle aches, weight loss, GI disturbances

Chronic 1° adrenal insufficiency (Addison disease) leading to increase ACTH, increase MSH

(353) Shock, altered mental status, vomiting, abdominal pain, weakness, fatigue in patient under glucocorticoid therapy

Acute adrenal insufficiency (adrenal crisis)

(356) Pancreatic, pituitary, parathyroid tumors

MEN1 (autosomal dominant MEN1 mutation)

(356) Medullary thyroid carcinoma, parathyroid hyperplasia, pheochromocytoma

MEN2A (autosomal dominant RET mutation)

(356) Medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, marfanoid habitus

MEN2B (autosomal dominant RET mutation)

(357) Cutaneous flushing, diarrhea, bronchospasm, heart murmur

Carcinoid syndrome (increase urinary 5-HIAA); indicates systemic dissemination (eg, post liver metastases)

(357) Jaundice, palpable distended non-tender gallbladder

Courvoisier sign (distal malignant obstruction of biliary tree)

(384) Vomiting blood following gastroesophageal lacerations

Mallory-Weiss syndrome (alcohol use disorder, bulimia nervosa)

(384) Dysphagia (esophageal webs), glossitis, iron deficiency anemia

Plummer-Vinson syndrome (may progress to esophageal squamous cell carcinoma

(386) Enlarged, hard left supraclavicular node

Virchow node (metastasis from abdominal malignancy)

(387) Hematemesis, melena

Upper GI bleeding (eg, peptic ulcer disease)

(387) Hematochezia

Lower GI bleeding (eg, colonic diverticulosis

(388) Arthralgias, cardiac and neurological symptoms, diarrhea

Whipple disease (Tropheryma whipplei)

(390) Severe RLQ pain with palpation of LLQ

Rovsing sign (acute appendicitis)

(390) Severe RLQ pain with deep tenderness

McBurney sign (acute appendicitis)

(394) Hamartomatous GI polyps, hyperpigmented macules on mouth, feet, hands, genitalia

Peutz-Jeghers syndrome (inherited, benign polyposis can cause bowel obstruction; increase breast/GI cancer risk)

(394) Multiple colon polyps, osteomas/soft tissue tumors, impacted/supernumerary teeth

Gardner syndrome (subtype of FAP)

(401) Severe jaundice in neonate

Crigler-Najjar syndrome (congenital unconjugated hyperbilirubinemia)

(402) Golden brown rings around peripheral cornea

Wilson disease (Kayser-Fleischer rings due to copper accumulation)

(403) Female, fat (obese), fertile (multiparity), forty, fair

Cholelithiasis (gallstones)

(405) Painless jaundice with enlarged gallbladder

Cancer of pancreatic head obstructing the bile duct

(425) Bluish line on gingiva

Burton line (lead poisoning)

(427) Short stature, café-au-lait spots, thumb/radial defects, increase incidence of tumors/leukemia, aplastic anemia

Fanconi anemia (genetic loss of DNA crosslink repair; often progresses to AML)

(428) Red/pink urine, fragile RBCs

Paroxysmal nocturnal hemoglobinuria

(429) Painful blue fingers/toes, hemolytic anemia

Cold agglutinin disease (autoimmune hemolytic anemia caused by Mycoplasma pneumoniae, infectious mononucleosis, CLL

(432) Petechiae, mucosal bleeding, prolonged bleeding time

Platelet disorders (eg, Glanzmann thrombasthenia, Bernard Soulier, HUS, TTP, ITP, uremic platelet dysfunction)

(434) Fever, night sweats, weight loss

B symptoms of malignancy

(435) Skin patches/plaques, Pautrier microabscesses, atypical T cell

Mycosis fungoides (cutaneous T-cell lymphoma) or Sézary syndrome (mycosis fungoides + malignant T cells in blood)

(352) Neonate with arm paralysis following difficult birth, arm in “waiter’s tip” position

Erb-Duchenne palsy (superior trunk [C5–C6] brachial plexus injury)

(455) Anterior drawer sign ⊕

Anterior cruciate ligament injury

(468) Bone pain, bone enlargement, long bone chalk-stick fractures

Osteitis deformans (Paget disease of bone, increase osteoblastic and osteoclastic activity)

(472) Swollen, hard, painful finger joints in an elderly individual, pain worse with activity

Osteoarthritis (osteophytes on PIP [Bouchard nodes], DIP [Heberden nodes])

(473) Sudden swollen/painful big toe joint, tophi

Gout/podagra (hyperuricemia)

(474) Dry eyes, dry mouth, arthritis

Sjögren syndrome (autoimmune destruction of exocrine glands)

(475) Urethritis, conjunctivitis, arthritis in a male

Reactive arthritis associated with HLA-B27

(476) “Butterfly” facial rash, arthritis, cytopenia, and fever in a young female

Systemic lupus erythematosus

(478) Cervical lymphadenopathy, desquamating rash, coronary aneurysms, red conjunctivae and tongue, hand-foot changes

Kawasaki disease (mucocutaneous lymph node syndrome, treat with IVIG and aspirin)

(479) Palpable purpura on buttocks/legs, joint pain, abdominal pain (child), hematuria

Immunoglobulin A vasculitis (Henoch-Schönlein purpura, affects skin and kidneys)

(480) Painful fingers/toes changing color from white to blue to red with cold or stress

Raynaud phenomenon (vasospasm in extremities)

(486) Dark purple skin/mouth nodules in a patient with AIDS

Kaposi sarcoma, associated with HHV-8

(491) Pruritic, purple, polygonal planar papules and plaques (6 P’s)

Lichen planus

(525) Dorsiflexion of large toe with fanning of other toes upon plantar scrape

Babinski sign (UMN lesion)

(526) Truncal ataxia, nystagmus, head tilting, fall towards injured side

Cerebellar lesion (lateral affects voluntary movement of extremities; medial affects axial and proximal movement

(526) Hyperphagia, hypersexuality, hyperorality

Klüver-Bucy syndrome (bilateral amygdala lesion)

(526) Resting tremor, athetosis, chorea

Basal ganglia lesion

(529) Dysphagia, hoarseness, decrease gag reflex, nystagmus, ipsilateral Horner syndrom

Lateral medullary (Wallenberg) syndrome (posterior inferior cerebellar artery lesion)

(530) Lucid interval after traumatic brain injury

Epidural hematoma (middle meningeal artery rupture; branch of maxillary artery

(530) “Worst headache of my life”

Subarachnoid hemorrhage

(536) Resting tremor, rigidity, akinesia, postural instability, shuffling gait, micrographia

Parkinson disease (loss of dopaminergic neurons in substantia nigra pars compacta)

(536) Chorea, dementia, caudate degeneration

Huntington disease (autosomal dominant CAG repeat expansion)

(538) Urinary incontinence, gait apraxia, cognitive dysfunction

Normal pressure hydrocephalus

(539) Relapsing and remitting nystagmus, intention tremor, scanning speech, bilateral internuclear ophthalmoplegia

Multiple sclerosis

(540) Rapidly progressive limb weakness that ascends following GI/upper respiratory infection

Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy)

(541) Café-au-lait spots, Lisch nodules (iris hamartoma), cutaneous neurofibromas, pheochromocytomas, optic gliomas

Neurofibromatosis type I

(541) Vascular birthmark (port-wine stain) of the face

Nevus flammeus (benign, but associated with SturgeWeber syndrome)

(541) Renal cell carcinoma (bilateral), hemangioblastomas, angiomatosis, pheochromocytoma

von Hippel-Lindau disease (deletion of VHL on chromosome 3p)

(541) Bilateral vestibular schwannomas

Neurofibromatosis type II

(545) Hyperreflexia, hypertonia, Babinski sign present

UMN damage

(545) Hyporeflexia, hypotonia, atrophy, fasciculations

LMN damage

(547) Staggering gait, frequent falls, nystagmus, hammer toes, diabetes mellitus, hypertrophic cardiomyopathy

Friedreich ataxia

(548) Unilateral facial drooping involving forehead

LMN facial nerve (CN VII) palsy; UMN lesions spare the forehead

(550) Episodic vertigo, tinnitus, sensorineural hearing loss

Ménière disease

(557) Ptosis, miosis, anhidrosis

Horner syndrome (sympathetic chain lesion)

(560) Conjugate horizontal gaze palsy, horizontal diplopia

Internuclear ophthalmoplegia (damage to MLF; may be unilateral or bilateral)

(577) “Waxing and waning” level of consciousness (acute onset), decrease attention span, decrease level of arousal

Delirium (usually 2° to other cause)

(606) Polyuria, renal tubular acidosis type II, growth retardation, electrolyte imbalances, hypophosphatemic rickets

Fanconi syndrome (multiple combined dysfunction of the proximal convoluted tubule)

(615) Periorbital and/or peripheral edema, proteinuria (> 3.5 g/ day), hypoalbuminemia, hypercholesterolemia

Nephrotic syndrome

(617) Hereditary nephritis, sensorineural hearing loss, retinopathy, anterior lenticonus

Alport syndrome (mutation in type IV collagen)

(626) Wilms tumor, macroglossia, organomegaly, hemihyperplasia, omphalocele

Beckwith-Wiedemann syndrome (WT2 mutation)

(657) Streak ovaries, congenital heart disease, horseshoe kidney, cystic hygroma, short stature, webbed neck, lymphedema

Turner syndrome (45,XO)

(667) Ovarian fibroma, ascites, pleural effusion

Meigs syndrome

(670) Red, itchy, swollen rash of nipple/areola

Paget disease of the breast (sign of underlying neoplasm)

(671) Fibrous plaques in tunica albuginea of penis with abnormal curvature

Peyronie disease (connective tissue disorder)

(694) Pink complexion, dyspnea, hyperventilation

Emphysema (“pink puffer,” centriacinar [tobacco smoking] or panacinar [α1-antitrypsin deficiency])

(695) Hypoxemia, polycythemia, hypercapnia

Chronic bronchitis (hypertrophy and hyperplasia of mucus-secreting glands, “blue bloater”

(697) Bilateral hilar adenopathy, uveitis

Sarcoidosis (noncaseating granulomas)

(58) Colonies of Pseudomonas in lungs

Cystic fibrosis (autosomal recessive mutation in CFTR gene leading to fat-soluble vitamin deficiency and mucous plugs)

(61) Decrease AFP on second trimester screening

Down syndrome, Edwards syndrome

(61) Decrease β-hCG, decrease PAPP-A on first trimester screening

Down syndrome

(67) Increase serum homocysteine, increase methylmalonic acid, decrease folate

Vitamin B12 deficiency

(113) Anti-histone antibodies

Drug-induced lupus

(114) Decrease T cells, decrease PTH, decrease Ca2+, absent thyme shadow on CXR

Thymic aplasia (DiGeorge syndrome, velocardiofacial syndrome)

(115) Recurrent infections, eczema, thrombocytopenia

Wiskott-Aldrich syndrome

(115) Large granules in phagocytes, immunodeficiency

Chédiak-Higashi disease (congenital failure of phagolysosome formation)

(132) Optochin sensitivity

Sensitive: S pneumoniae; resistant: viridans streptococci (S mutans, S sanguis)

(132) Novobiocin response

Sensitive: S epidermidis; resistant: S saprophyticus

(132) Bacitracin response

Sensitive: S pyogenes (group A); resistant: S agalactiae (group B)

(137) Branching gram ⊕ rods with sulfur granules

Actinomyces israelii

(138) Hilar lymphadenopathy, peripheral granulomatous lesion in middle or lower lung lobes (can calcify)

Ghon complex (1° TB: Mycobacterium bacilli

(140) “Thumb sign” on lateral neck x-ray

Epiglottitis (Haemophilus influenzae)

(147) Bacteria-covered vaginal epithelial cells, ⊕ whiff test

Clue cells” (Gardnerella vaginalis)

(153) Ring-enhancing brain lesion on CT/MRI in AIDS

Toxoplasma gondii (multiple), CNS lymphoma (may be solitary

(155) Dilated cardiomyopathy with apical atrophy, megacolon, megaesophagus

Chagas disease (Trypanosoma cruzi)

(162) Atypical lymphocytes, heterophile antibodies

Infectious mononucleosis (EBV infection)

(167) Narrowing of upper trachea and subglottis (Steeple sign) on x-ray

Croup (parainfluenza virus)

(169) Eosinophilic inclusion bodies in cytoplasm of hippocampal and cerebellar neurons

Negri bodies of rabies

(207) Psammoma bodies

Meningiomas, papillary thyroid carcinoma, mesothelioma, papillary serous carcinoma of the endometrium and ovary

(302) “Boot-shaped” heart on x-ray

Tetralogy of Fallot (due to RVH)

(304) Rib notching (inferior surface, on x-ray)

Coarctation of the aorta

(311) “Delta wave” on ECG, short PR interval, supraventricular tachycardia

Wolff-Parkinson-White syndrome (bundle of Kent bypasses AV node)

(317) Electrical alternans (alternating amplitude on ECG)

Cardiac tamponade

(319) Granuloma with giant cells after pharyngeal infection

Aschoff bodies (rheumatic fever)

(347) Empty-appearing nuclei with central clearing of thyroid cells

“Orphan Annie” eyes nuclei (papillary carcinoma of the thyroid)

(349) “Brown” tumor of bone

Hyperparathyroidism or osteitis fibrosa cystica (deposited hemosiderin from hemorrhage gives brown color)

(354) Hypertension , hypokalemia, metabolic alkalosis

1° hyperaldosteronism (eg, Conn syndrome)

(386) Mucin-filled cell with peripheral nucleus

“Signet ring” cells (diffuse gastric carcinoma)

(388) Anti-transglutaminase/anti-gliadin/anti-endomysial antibodies

Celiac disease (diarrhea, weight loss)

(389) Narrowing of bowel lumen on barium x-ray

String sign” (Crohn disease)

(389) Lead pipe” appearance of colon on abdominal imaging

Ulcerative colitis (loss of haustra)

(394) Thousands of polyps on colonoscopy

Familial adenomatous polyposis (autosomal dominant, mutation of APC gene)

(395) Apple core” lesion on barium enema x-ray

Colorectal cancer (usually left-sided)

(398) Eosinophilic cytoplasmic inclusion in liver cell

Mallory body (alcoholic liver disease)

(398) Triglyceride accumulation in liver cell vacuoles

Fatty liver disease (alcoholic or metabolic syndrome)

(398) Anti-smooth muscle antibodies (ASMAs), anti-liver/ kidney microsomal-1 (anti-LKM1) antibodies

Autoimmune hepatitis

(399) “Nutmeg” appearance of liver

Chronic passive congestion of liver due to right heart failure or Budd-Chiari syndrome

(402) Antimitochondrial antibodies (AMAs)

1° biliary cholangitis (female, cholestasis, portal hypertension)

(402) Low serum ceruloplasmin

Wilson disease (hepatolenticular degeneration; KayserFleischer rings due to copper accumulation)

(405) Migratory thrombophlebitis (leading to migrating DVTs and vasculitis)

Trousseau syndrome (adenocarcinoma of pancreas)

(421) Hypersegmented neutrophils

Megaloblastic anemia (vitamin B12 deficiency: neurologic symptoms; folate deficiency: no neurologic symptoms)

(422) Basophilic nuclear remnants in RBCs

Howell-Jolly bodies (due to splenectomy or nonfunctional spleen)

(422) Basophilic stippling of RBCs

Sideroblastic anemias, thalassemias

(424) Hypochromic, microcytic anemia

Iron deficiency anemia, lead poisoning, thalassemia (fetal hemoglobin sometimes presen

(425) Hair on end” (“crew cut”) appearance on x-ray

β-thalassemia, sickle cell anemia (marrow expansion)

(432) Anti-GpIIb/IIIa antibodies

Immune thrombocytopenia

(433) High level of d-dimers

High level of d-dimers

(434) Giant B cells with bilobed nucleus with prominent inclusions (“owl’s eye”)

Reed-Sternberg cells (Hodgkin lymphoma)

(435) Sheets of medium-sized lymphoid cells with scattered pale, tingible body–laden macrophages (“starry sky” histology)

Burkitt lymphoma (t[8:14] c-myc activation, associated with EBV; “starry sky” made up of malignant cells

(436) Lytic (“punched-out”) bone lesions on x-ray

Multiple myeloma

(436) Monoclonal spike on serum protein electrophoresis

Multiple myeloma (usually IgG or IgA) Waldenström macroglobulinemia (IgM) Monoclonal gammopathy of undetermined significance

(436) Stacks of RBCs

Rouleaux formation (high ESR, multiple myeloma)

(437) Myeloperoxidase ⊕ cytoplasmic inclusions in myeloblasts, with increase circulating myeloblasts

Auer rods (APL)

(437) WBCs that look “smudged”

CLL

(439) “Tennis racket”-shaped cytoplasmic organelles (EM) in Langerhans cells

Birbeck granules (Langerhans cell histiocytosis)

(470) “Soap bubble” in femur or tibia on x-ray

Giant cell tumor of bone (generally benign)

(471) Raised periosteum (creating a “Codman triangle”)

Aggressive bone lesion (eg, osteosarcoma, Ewing sarcoma

(471) Onion skin” periosteal reaction

Ewing sarcoma (malignant small blue cell tumor)

(472) IgM antibody that targets IgG Fc region

Rheumatoid arthritis (systemic inflammation, joint pannus, boutonniere and swan neck deformities)

(473) Rhomboid crystals, ⊕ birefringent

Pseudogout (calcium pyrophosphate dihydrate crystals)

(473) Needle-shaped, ⊝ birefringent crystals

Gout (monosodium urate crystals

(473) Increase uric acid levels

Gout, Lesch-Nyhan syndrome, tumor lysis syndrome, loop and thiazide diuretics

(475) “Bamboo spine” on x-ray

Ankylosing spondylitis (chronic inflammatory arthritis: HLA-B27)

(476) Antinuclear antibodies (ANAs: anti-Smith and antidsDNA)

LE (type III hypersensitivity)

(479) Antineutrophil cytoplasmic antibodies (ANCAs)

Microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and primary sclerosing cholangitis (MPO-ANCA/p-ANCA); granulomatosis with polyangiitis (PR3-ANCA/c-ANCA)

(481) Anticentromere antibodies

Limited scleroderma (CREST syndrome)

(481) Anti-Scl-70 (anti-DNA topoisomerase-I) and anti-RNA polymerase III antibodie

Diffuse scleroderma

(489) Anti-desmoglein (anti-desmosome) antibodies

Pemphigus vulgaris

(489) Antihemidesmosome antibodies

Bullous pemphigoid

(493) Keratin pearls on a skin biopsy

Squamous cell carcinoma

(501) increase AFP in amniotic fluid/maternal serum

Dating error, anencephaly, spina bifida (open neural tube defects)

(530) Bloody or yellow tap on lumbar puncture

Xanthochromia (due to subarachnoid hemorrhage)

(536) Eosinophilic cytoplasmic inclusion in neuron

Lewy body (Parkinson disease and Lewy body dementia)

(536) Extracellular amyloid deposition in gray matter of brain

Senile plaques (Alzheimer disease)

(536)Depigmentation of neurons in substantia nigra

Parkinson disease (basal ganglia disorder: rigidity, resting tremor, bradykinesia)

(536) Protein aggregates in neurons from hyperphosphorylation of tau protein

Neurofibrillary tangles (Alzheimer disease) and Pick bodies (Pick disease)

(536) Silver-staining spherical aggregation of tau proteins in neurons

Pick bodies (frontotemporal dementia: progressive dementia, changes in personality)

(542) Pseudopalisading pleomorphic tumor cells on brain biopsy

Glioblastoma

(544) Small blue cells surrounding central area of neuropil

Homer-Wright rosettes (neuroblastoma, medulloblastoma)

(614) “Waxy” casts with very low urine flow

Chronic end-stage renal disease

(614) WBC casts in urine

Acute pyelonephritis, transplant rejection, tubulointerstitial inflammation

(614) RBC casts in urine

Glomerulonephritis

(616) Anti–glomerular basement membrane antibodies

Goodpasture syndrome (glomerulonephritis and hemoptysis)

(616) Cellular crescents in Bowman capsule

Rapidly progressive (crescentic) glomerulonephritis

(617) “Wire loop” glomerular capillary appearance on light microscopy

Diffuse proliferative glomerulonephritis (usually seen with lupus)

(616) Linear appearance of IgG deposition on glomerular and alveolar basement membranes

Goodpasture syndrome

(616) “Lumpy bumpy” appearance of glomeruli on immunofluorescence

Infection-related glomerulonephritis (due to deposition of IgG, IgM, and C3)

(616) Necrotizing vasculitis (lungs) and necrotizing glomerulonephritis

Granulomatosis with polyangiitis (PR3-ANCA/c-ANCA) and Goodpasture syndrome (anti–basement membrane antibodies)

(617) “Tram-track” appearance of capillary loops of glomerular basement membranes on light microscopy

Membranoproliferative glomerulonephritis

(618) Nodular hyaline deposits in glomeruli

Kimmelstiel-Wilson nodules (diabetic glomerulonephropathy)

(618) Nodular hyaline deposits in glomeruli

Kimmelstiel-Wilson nodules (diabetic glomerulonephropathy

(618) Podocyte fusion or “effacement” on electron microscopy

Minimal change disease (child with nephrotic syndrome)

(618)“Spikes” on basement membrane, “domelike” subepithelial deposits

Membranous nephropathy (nephrotic syndrome)

(621) Thyroidlike appearance of kidney

Chronic pyelonephritis (usually due to recurrent infections)

(623) Granular casts in urine

Acute tubular necrosis (eg, ischemia or toxic injury)

(654) hCG elevated

Multifetal gestation, hydatidiform moles, choriocarcinomas, Down syndrome

(664) Dysplastic squamous cervical cells with “raisinoid” nuclei and hyperchromasia

Koilocytes (HPV: predisposes to cervical cancer)

(667) Sheets of uniform “fried egg” cells, increase hCG, increase LDH

Dysgerminoma

(667) Glomeruluslike structure surrounding vessel in germ cells

Schiller-Duval bodies (yolk sac tumor)

(667) Disarrayed granulosa cells arranged around collections of eosinophilic fluid

Call-Exner bodies (granulosa cell tumor of the ovary)

(668) “Chocolate cyst” of ovary

Endometriosis (frequently involves both ovaries)

(669) Mammary gland (“blue domed”) cyst

Fibrocystic change of the breast

(673) Rectangular, crystal-like, cytoplasmic inclusions in Leydig cells

Reinke crystals (Leydig cell tumor)

(693) Thrombi made of white/red layers

Lines of Zahn (arterial thrombus, layers of platelets/ RBCs)

(695) Hexagonal, double-pointed, needlelike crystals in bronchial secretions

Bronchial asthma (Charcot-Leyden crystals: eosinophilic granules)

(695) Desquamated epithelium casts in sputum

Curschmann spirals (bronchial asthma; can result in whorled mucous plugs

(696) “Honeycomb lung” on x-ray or CT

Idiopathic pulmonary fibrosis

(698) Iron-containing nodules in alveolar septum

Ferruginous bodies (asbestosis: increase chance of lung cancer)

(706) Bronchogenic apical lung tumor on imaging

Pancoast tumor (can compress cervical sympathetic chain and cause Horner syndrome)

(55) 57 Mitochondrial inheritance

Disease occurs in all offspring of affected females (maternal inheritance pattern), heteroplasmy

(60) 61 Intellectual disability

Down syndrome, fragile X syndrome

(66) Vitamin deficiency (USA)

Folate (pregnant women are at high risk; body stores only 3- to 4-month supply)

(98) HLA-DR3

DM type 1, SLE, Graves disease, Hashimoto thyroiditis, Addison disease

(86) Lysosomal storage disease

Gaucher disease

(98) HLA-DR4

Rheumatoid arthritis, type 1 DM, Addison disease

(144) H pylori

Bacteria associated with gastritis, peptic ulcer disease, and gastric malignancies (eg, adenocarcinoma, MALToma)

(151) Opportunistic respiratory infection in AIDS

Pneumocystis jirovecii

(162) HSV-1

Viral encephalitis affecting temporal lobe

(171) Hepatitis C

Viral infection 2° to blood transfusion

(175) S aureus, B cereus

Food poisoning (exotoxin mediated)

(176) S aureus, Pseudomonas, other gram ⊝ rods

Healthcare-associated pneumonia

(177) S pneumoniae

Bacterial meningitis (> 6 months old

(177) Group B streptococcus/E coli/Listeria (newborns) Group B streptococcus/E coli/Listeria (newborns)

Bacterial meningitis (newborns 0–6 months old)

(177) Salmonella and S aureus

Osteomyelitis in sickle cell disease

(177) S aureus (most common overall)

Osteomyelitis

(177) S aureus, Pseudomonas, Candida

Osteomyelitis with injection drug use

(179) E coli, Staphylococcus saprophyticus

UTI

(180) C trachomatis

Bacterial STI

(182) C trachomatis (subacute), N gonorrhoeae (acute

Pelvic inflammatory disease

(219) Prostate, breast >> lung > kidney, colon

Metastases to bone

(219) Lung > breast >> melanoma > colon, prostate

Metastases to brain

(219) Lung > breast >> melanoma > colon, prostate

Metastases to brain

(219) Colon > breast >> pancreas, lung, prostate

Metastases to liver

(292) Increase ventricular filling pressure (eg, MR, AR, HF, thyrotoxicosis), common in dilated ventricles

S3 heart sound

(292) Stiff/hypertrophic ventricle (aortic stenosis, restrictive cardiomyopathy)

S4 heart sound

(296) VSD, tricuspid regurgitation, mitral regurgitation

Holosystolic murmur

(296) Aortic stenosis

Ejection click

(296) Rheumatic heart disease (late and highly specific sequelae of rheumatic fever)

Mitral stenosis

(296) Mitral stenosis

Opening snap

(296) Mitral valve prolapse

Heart murmur, congenital

(302) Tetralogy of Fallot (most common), D-transposition of great arteries, persistent truncus arteriosus, total anomalous pulmonary venous return, tricuspid atresia

Cyanotic heart disease (early)

(303) Eisenmenger syndrome (caused by VSD, ASD, PDA)

Late cyanotic shunt (uncorrected left to right becomes right to left)

(303) VSD > ASD > PDA

Congenital heart disease (left-to-right shunts)

(304) Renal/renovascular diseases (eg, fibromuscular dysplasia), atherosclerotic renal artery stenosis, 1° hyperaldosteronism, or obstructive sleep apnea

Hypertension, 2°

(306) Marfan syndrome (cystic medial degeneration), 3° syphilis (obliterative endarteritis of vasa vasorum)

Aortic aneurysm, thoracic

(306) Atherosclerosis, tobacco use

Aortic aneurysm, abdominal

(305) Abdominal aorta > coronary artery > popliteal artery > carotid artery

Sites of atherosclerosis

(307) Hypertension (most important risk factor)

Aortic dissection

(311)Atrial fibrillation (associated with high risk of emboli)

Irregularly irregular rhythm on ECG with no discrete P waves

(316) Cor pulmonale

Right heart failure due to a pulmonary cause

(318) Mitral > aortic, tricuspid (injection drug use)

Heart valve in infective endocarditis

(318) S aureus (acute, injection drug use, tricuspid valve), viridans streptococci (subacute, dental procedure), S gallolyticus (colon cancer), gram ⊝ (HACEK), culture ⊝ (Coxiella, Bartonella)

Infective endocarditis presentation associated with bacterium

(320) Metastasis, myxoma (90% in left atrium; “ball valve”)

Cardiac tumor (adults)

(343) Pituitary adenoma (usually benign tumor)

Hypopituitarism

(320) Rhabdomyoma (associated with tuberous sclerosis)

Cardiac 1° tumor (kids)

(339) 21-hydroxylase deficiency

Congenital adrenal hyperplasia, hypotension

(354) Thyroid dysgenesis/dyshormonogenesis, iodine deficiency

Congenital hypothyroidism (cretinism)

(347) Papillary carcinoma (RET/PTC rearrangements, BRAF mutations)

Thyroid cancer

(348) Accidental excision during thyroidectomy

Hypoparathyroidism

(349) Adenomas, hyperplasia, carcinoma

1° hyperparathyroidism

(349) Hypocalcemia of chronic kidney disease

2° hyperparathyroidism

(352)* Exogenous glucocorticoids * Adrenocortical adenoma (secretes excess cortisol) * ACTH-secreting pituitary adenoma (Cushing disease) * Paraneoplastic (due to ACTH secretion by tumors)

Cushing syndrome

(354) Bilateral adrenal hyperplasia or adenoma (Conn syndrome)

1° hyperaldosteronism

(354) Neuroblastoma (malignant)

Tumor of the adrenal medulla (kids)

(355) Pheochromocytoma (usually benign)

Tumor of the adrenal medulla (adults)

(357) Zollinger-Ellison syndrome (gastrinoma of duodenum or pancreas), associated with MEN1

Refractory peptic ulcers and high gastrin levels

(385) Squamous cell carcinoma (worldwide); adenocarcinoma (US)

Esophageal cancer

(386) Cushing ulcer (increase vagal stimulation leading to increase ACh leading to increase H+ production)

Acute gastric ulcer associated with CNS injury

(386) Curling ulcer (hypovolemia leading to mucosal ischemia)

Acute gastric ulcer associated with severe burns

(386) Krukenberg tumor (mucin-secreting signet ring cells)

Bilateral ovarian metastases from gastric carcinoma

(386) Predisposition to gastric carcinoma (can also cause pernicious anemia)

Chronic atrophic gastritis (autoimmune)

(389) Skip lesions (Crohn disease)

Alternating areas of transmural inflammation and normal colon

(390) Sigmoid colon

Site of diverticulosis

(391) Zenker diverticulum

Diverticulum in pharynx

(399) HBV (+/– cirrhosis) or other causes of cirrhosis (eg, alcoholic liver disease, hemochromatosis), aflatoxins

Hepatocellular carcinoma

(401) Dubin-Johnson syndrome (inability of hepatocytes to secrete conjugated bilirubin into bile)

Congenital conjugated hyperbilirubinemia (black liver)

(401) Gilbert syndrome (benign congenital unconjugated hyperbilirubinemia)

Hereditary harmless jaundice

(402) Hereditary ATP7B mutation (copper buildup in liver, brain, cornea [Kayser-Fleischer rings], kidneys)

Wilson disease

(402) Multiple blood transfusions or hereditary HFE mutation (can result in heart failure, “bronze diabetes,” and increase risk of hepatocellular carcinoma)

Hemochromatosis

(404) Gallstones, alcohol

Pancreatitis (acute)

(404) Alcohol (adults), cystic fibrosis (children)

Pancreatitis (chronic)

(424) Iron deficiency, thalassemias, lead poisoning, sideroblastic anemia

Microcytic anemia

(428) Sickle cell anemia (hemoglobin S)

Autosplenectomy (fibrosis and shrinkage), Howell-Jolly bodies

(432) Bernard-Soulier syndrome (defect in platelet adhesion to von Willebrand factor)

Platelet disorder with GpIb deficiency

(432) Glanzmann thrombasthenia (defect in platelet-to-platelet aggregation and platelet plug formation)

Platelet disorder with GpIIb/IIIa deficiency

(433) von Willebrand disease

Inherited bleeding disorder

(433) Leiden (also associated with recurrent pregnancy loss)

Hereditary thrombophilia

(433) Stroke, snake bite, sepsis, trauma, obstetric complications, acute pancreatitis, malignancy, nephrotic syndrome, transfusion

DIC

(434) Hodgkin lymphoma

Malignancy associated with noninfectious fever

(434) Nodular sclerosis

Type of Hodgkin lymphoma (most common)

(435) Follicular lymphoma (BCL-2 activation, anti-apoptotic oncogene)

t(14;18)

(435) Burkitt lymphoma (c-myc fusion, transcription factor oncogene)

t(8;14)

(435) Diffuse large B-cell lymphoma

Type of non-Hodgkin lymphoma (most common in adults)

(436) Multiple myeloma

1° bone tumor (older adults)

(437) ALL: child, CLL: adult > 60, AML: adult ∼ 65, CML: adult 45–85

Age ranges for patient with ALL/CLL/AML/CML

(437) Leukemia, brain tumors

Malignancy (kids)

(437) Philadelphia chromosome, CML (BCR-ABL oncogene, tyrosine kinase activation), more rarely associated with ALL

t(9;22)

(467) Osteoporosis

Vertebral compression fracture

(475) Psoriatic arthritis, ankylosing spondylitis, IBD-associated arthritis, reactive arthritis

HLA-B27

(476) Renal disease (most common), infections, cardiovascular disease (accelerated CAD)

Death in SLE

(478) Risk of ipsilateral blindness due to occlusion of ophthalmic artery; polymyalgia rheumatica

Giant cell arteritis

(478) Buerger disease (strongly associated with tobacco smoking, Raynaud phenomenon)

Recurrent inflammation/thrombosis of medium-vessels in extremities

(486) Strawberry hemangioma (grows rapidly and regresses spontaneously by 5–8 years of age)

Benign vascular tumor of infancy

(491) Pityriasis rosea

Herald patch (Christmas tree distribution)

(493) Precursor to squamous cell carcinoma

Actinic keratosis

(502) Chiari I malformation (associated with spinal cord cavitations [eg, syringomyelia]

Cerebellar tonsillar herniation

(526) Wernicke-Korsakoff syndrome (with bilateral lesions)

Bilateral mamillary body lesions with thiamine deficiency

(530) Rupture of middle meningeal artery (trauma; lentiform shaped)

Epidural hematoma

(530) Rupture of middle meningeal artery (trauma; lentiform shaped)

Epidural hematoma

(530) Rupture of bridging veins (crescent shaped)

Subdural hematoma

(536) Alzheimer disease, vascular dementia (multiple infarcts)

Dementia

(539) Multiple sclerosis

Demyelinating disease in young women

(542) Metastasis, glioblastoma (malignant), meningioma, hemangioblastoma

Brain tumor (adults)

(542) Prolactinoma

Galactorrhea, amenorrhea

(544) Infratentorial: medulloblastoma (cerebellum) or supratentorial: craniopharyngioma

Brain tumor (children)

(546) Amyotrophic lateral sclerosis

Combined (UMN and LMN) motor neuron degeneration

(546) Tabes dorsalis (3° syphilis), subacute combined degeneration (dorsal columns, lateral corticospinal, spinocerebellar tracts affected)

Degeneration of dorsal column fibers

(618) Minimal change disease

Nephrotic syndrome (children)

(619) Uric acid

Kidney stones (radiolucent)

(619) Calcium (most common), struvite (ammonium), cystine (faintly radiopaque)

Kidney stones (radiopaque)

(625) Renal cell carcinoma: associated with tobacco smoking and VHL (clear cell subtype); paraneoplastic syndromes (EPO, renin, PTHrP, ACTH)

Renal malignancy (in males)

(567) Turner syndrome (45,XO or 45,XO/46,XX mosaic)

1° amenorrhea

(658) Kallmann syndrome (neuron migration failure)

Hypogonadotropic hypogonadism with anosmia

(664) DES exposure in utero

Clear cell adenocarcinoma of the vagina

(666) Serous cystadenoma

Ovarian tumor (benign, bilateral)

(66) Serous carcinoma

Ovarian tumor (malignant)

(668) Leiomyoma (estrogen dependent, not precancerous)

Benign tumor of myometrium

(663-668) Endometrial carcinoma (most common in resource-rich countries); cervical cancer (most common worldwide)

Gynecologic malignancy (most common)

(669) Fibrocystic change (in premenopausal females); carcinoma (in postmenopausal females)

Breast mass

(669) Fibroadenoma

Breast tumor (benign, young woman)

(670) Invasive ductal carcinoma

Breast cancer

(672) Seminoma (malignant, radiosensitive), increase PLAP

Testicular tumor

(674) BPH

Bladder outlet obstruction in men

(692) Virchow triad (increase risk of thrombosis)

Hypercoagulability, endothelial damage, blood stasis

(700) Idiopathic, left heart disease, lung diseases/hypoxia, chronic thromboembolism, multifactorial

Pulmonary hypertension

(705) Small cell carcinoma of the lung

SIADH

(229) Volume of distribution

Vd= amount of drug in the body/plasma drug concentration

(229) Half-life

t = 0.7 x Vd/CL ½

(229) Loading dose

LD= Cp x Vd / F

(229) Drug clearance

CL= rate of elimination of drug/plasma drug concentration=Vd x Ke (elimination)

(233) Therapeutic index

TI = median toxic dose/median effective dose = TD50/ED50

(229) Maintenance dose

Maintenance dose = Cp x CL x τ/F

(258) Odds ratio (for case-control studies)

OR=_a/c =_ad b/d bc

(258) Relative risk

RR= __a/(a + b) c/(c + d)

(258) Attributable risk

AR = __a - __c a +b c+ d

(258) Relative risk reduction

RRR = (ARC – ART)/ARC

(258) Absolute risk reduction

ARR = __a - __c a +b c+ d

(258) Number needed to treat

NNT = 1/ARR

(258) Number needed to harm

NNH = 1/AR

(259) Likelihood ratio +

LR+ = sensitivity/(1 – specificity) = TP rate/FP rate

(259) Likelihood ratio –

LR– = (1 – sensitivity)/specificity = FN rate/TN rate

(260) Sensitivity

Sensitivity = TP / (TP + FN)

(260) Specificity

Specificity = TN / (TN + FP)

(260) Positive predictive value

PPV = TP / (TP + FP)

(260) Negative predictive value

NPV = TN / (TN + FN)

(290) Cardiac output

*CO= rate of O2 consumption/(arterial O2 content − venous O2 content) *CO = stroke volume × heart rate

(290) Mean arterial pressure

MAP = CO × total peripheral resistance (TPR) MAP (at resting HR) = 2⁄3 DBP + 1⁄3 SBP = DBP + 1⁄3 PP

(290) Stroke volume

SV = EDV – ESV

(290) Ejection fraction

EF= __SV = __EDV - ESV EDV EDV

(291) Resistance

Resistance = driving pressure (ΔP)/ flow (Q) = 8η (viscosity) × length/ πr4

(301) Capillary fluid exchange

Jv = net fluid flow = Kf[(Pc − Pi) − σ(πc − πi)]

(423) Reticulocyte production index

RPI = % reticulocytes × (actual Hct/normal Hct) / maturation time

(602) Renal clearance

Cx= (UxV)/Px

(602) Glomerular filtration rate

Cinulin = GFR = Uinulin × V/Pinulin = Kf [(PGC – PBS) – (πGC – πBS)

(602) Effective renal plasma flow

eRPF = (U)PAH × V/(P)PAH = (C)PAH

(603) Filtration fraction

FF = GFR/RPF

(604) Fractional excretion of sodium

FeNa+ = V × UNa / GFR × PNa = PCr × UNa / UCr × PNa

(612) Henderson-Hasselbalch equation (for extracellular pH)

pH = 6.1 + log[HCO3−]/0.03 Pco 2

(612) Winters formula

Pco2 = 1.5 [HCO3–] + 8 ± 2

(612) Anion gap

Na+ − (Cl– + HCO3–)

(684) Physiologic dead space

VD = VT × PaCO2 − PECO2/PaCO2

(686) Pulmonary vascular resistance

PVR = (P)pulm artery – (P)L atrium/ Cardiac output

(687) Alveolar gas equation

Pao2 = Pio2 – Paco2/RQ = 150 mm Hga – Paco2 / 0.8

K+-sparing diuretic

Amiloride

K+ channel blocker (class III antiarrhythmic)

Amiodarone

Dihydropyridine Ca2+ channel blocker

Amlodipine

Parkinson disease (cholinergic antagonist)

Benztropine

Parkinson disease (dopamine agonist; rarely used)

Bromocriptine

Generalized anxiety disorder (partial 5-HT1A-receptor agonist)

Buspirone

Depression, smoking cessation (NE-DA reuptake inhibitor)

Bupropion

Gastritis, peptic ulcer (H2-receptor antagonist)

Cimetidine

Gastritis, peptic ulcer (H2-receptor antagonist)

Cimetidine

Allergy (2nd-generation antihistamine)

Cetirizine

Antibiotic (blocks 50S subunit)

Chloramphenicol

Long-acting benzodiazepine

Chlordiazepoxide

Typical antipsychotic

Chlorpromazine

1st-generation sulfonylurea

Chlorpropamide

1st-generation antihistamine

Chlorpheniramine

Thiazide diuretic

Chlorthalidone

Atypical antipsychotic

Clozapine

Tricyclic antidepressant

Clomipramine

Infertility due to anovulation (selective estrogen receptor modulator in hypothalamus)

Clomiphene

Hypertensive urgency, ADHD (α2-agonist)

Clonidine

Tricyclic antidepressant

Doxepin

BPH, HTN (α1-antagonist)

Doxazosin

K+-sparing diuretic

Eplerenone

Depression (selective serotonin reuptake inhibitor)

Fluoxetine

Na+ channel blocker (class Ic antiarrhythmic)

Propafenone

Typical antipsychotic

Fluphenazine

Pregnancy termination (progesterone receptor antagonist)

Mifepristone

Used with mifepristone for pregnancy termination (PGE1-synthetic analog)

Misoprostol

Opioid receptor antagonist (treats toxicity)

Naloxone

Opioid receptor antagonist (prevents relapse)

Naltrexone

Hypertensive emergency (increase cGMP/NO)

Nitroprusside

Antianginal (increase cGMP/NO)

Nitroglycerin

Proton pump inhibitor (inhibits H+/K+-ATPase in parietal cells)

Omeprazole

Antifungal (inhibits fungal sterol synthesis)

Ketoconazole

Atypical antipsychotic (D2 partial agonist)

Aripiprazole

ER ⊕ breast cancer in postmenopausal women (aromatase inhibitor)

Anastrozole

Hepatic encephalopathy (decrease ammoniagenic bacteria)

Rifaximin

Antituberculous drug/antimicrobial (inhibits DNA-dependent RNA polymerase)

Rifampin

Depression, PTSD (selective serotonin reuptake inhibitor)

Sertraline

Parkinson disease (MAO-B inhibitor)

Selegiline

Insomnia (blocks 5-HT2, α1-adrenergic, and H1 receptors); also weakly inhibits 5-HT reuptake

Trazodone

Chronic pain (weak opioid agonist)

Tramadol

Smoking cessation (nicotinic ACh receptor partial agonist)

Varenicline

Serotonin-norepinephrine reuptake inhibitor

Venlafaxine

PATHOPHYSIOLOGY OF IMPORTANT DISEASES Flashcards

(730 cards)