Pathophysiology
1) caused by infection with the yeast-like fungus Cryptococcus neoformans 2) two distinct subtypes
Cryptococcosis
March 11th, 2010Polyarteritis Nododa (PAN)
March 6th, 2010Pathophysiology
1) systemic necrotizing vasculitis of small- and medium-sized arteries 2) mostly affects renal, hepatic, and visceral arteries 3) variants – classic polyarteritis nodosa, microscopic angiitis, and Churg-Strauss variant; much overlap among variants 4) classic finding – development of multiple aneurysms along the involved arteries
Signs and Symptoms
1) hypertension 2) renal failure 3) myalgia 4) arthralgia 5) peripheral neuropathy (polyneuropathy multiplex) 6) abdominal pain 7) nausea and vomiting 8) infarction of viscera 9) subcutaneous (skin) red nodules 10) purpura and rash 11) cutaneous infarcts 12) congestive heart failure 13) myocardial infarction 14) fever 15) weight loss 16) headache 17) painful testes
Characteristic Test Findings
Laboratory – 1) increased leukocyte count 2) anemia 3) increased sed rate 4) positive p-ANCA (but much more common in microscopic angiitis variant) Radiology – 5) multiple aneurysms along affected arteries
Histology/Gross Pathology
1) segmental fibrinoid necrotizing inflammation and occlusion of small- and medium-size arteries, especially at branch points 2) microscopic angiitis – also associated with venitis and pulmonary and bronchial artery involvement (not seen in classic variant)
Associated Conditions
1) variants overlap and there is inexactness as to defining parameters of each disease 2) hepatitis B antigen occurs in 30% of cases of classic variant and hepatitis C antigen occurs in 5% 3) increased incidence in hairy cell leukemia
Biochemistry
likely immunologic component as circulating hepatitis B antigen/IgM complexes found in walls of affected blood vessels
Treatment
1) prednisone 2) cyclophosphamide 3) (vidarabine) antihepatitis B treatment 4) plasmapheresis 5) alpha-IFN
Tips for USMLE
1) if question mentions granulomas, it is not PAN 2) if eosinophils are mentioned, it is not PAN 3) if question mentions multiple aneurysms in hepatic, renal, or mesenteric arteries, think PAN (although this is not strictly pathognomonic)
Schizophrenia
March 6th, 2010Pathophysiology
1) group of disorders marked by disturbances in thought patterns, speech, behavior, and perception 2) subtypes – paranoid, disorganized, catatonic, and residual 3) cause is unknown, but major risk factors are genetic susceptibility, early developmental insults, in utero viral influenza exposure, and winter birth (possibly related to influenza exposure)
Signs and Symptoms
Positive symptoms – 1) disorganized thought 2) delusions 3) hallucinations Negative symptoms – 4) social withdrawal 5) loss of functioning 6) flat affect 7) anhedonia
Histology/Gross Pathology
1) enlarged third and lateral ventricles 2) cortical atrophy 3) decreased size of hippocampus, amygdala, right prefrontal cortex
Associated Conditions
1) birth complications 2) Rh factor incompatibility 3) prenatal nutritional deficiency
Biochemistry
1) neuroleptics work on basis of diminishing dopaminergic activity 2) these drugs induce expression of c-fos gene in nucleus accumbens (dopaminergic connection between prefrontal and limbic cortices)
Inheritance/Epidemiology
1) onset classically in late adolescence or early adulthood 2) negative symptoms have a worse prognosis than positive symptoms 3) 300,000 new cases in USA each year 4) 50% concordance rate for monozygotic twins
Treatment
1) drugs – clozapine (blocks 5HT2 receptors), risperidone, haloperidol, chlorpromazine 2) behavioral and family education
Tips for USMLE
if 18 year-old college freshman has a history of appearing disheveled and having angry outbursts in class over a 3-month period and when summoned to the dean’s office about his behavior appears with a dead cat draped over his neck and shoulders, think schizophrenia
Henoch-Schonlein Purpura (Anaphylactoid Purpura)
March 6th, 2010Pathophysiology
1) type of small vessel vasculitis thought to be secondary to immune complex deposition 2) most commonly occurs in children, but can occur in adults 3) typically self-limited
Signs and Symptoms
1) palpable purpura – most common over legs and buttocks 2) polyarthralgias – typically knees and ankles 3) GI complaints – colicky abdominal pain, nausea, vomiting, bloody diarrhea, and constipation 4) blood and mucus per rectum 5) glomerulonephritis – usually resolves spontaneously 6) myocardial dysfunction – adults only
Characteristic Test Findings
Laboratory – 1) proteinuria 2) microscopic hematuria 3) RBC casts in urine 4) increased serum IgA 5) eosinophilia 6) mild leukocytosis 7) all coagulation tests are normal
Histology/Gross Pathology
1) IgA deposits in walls of dermal blood vessels 2) increased vascular permeability 3) glomerular lesions identical to IgA nephropathy (Berger’s disease)
Associated Conditions
increased incidence with – 1) upper respiratory tract infection 2) immunizations 3) insect bites 4) streptococcus pharyngitis
Biochemistry
IgA is predominant antibody class in deposited immune complexes
Inheritance/Epidemiology
1) peak incidence in spring 2) slightly more common in males
Treatment
1) glucocorticoids (prednisone) decrease GI complaints and joint pain but do not alter overall course 2) if renal failure is rapidly progressive (which is uncommon), plasmapheresis and immunosuppressive drugs are used
Tips for USMLE
if questions mentions a 6 year-old boy with a bad cold who 2 weeks later develops red, raised lesions on his buttocks and the back of his thighs, sore ankles, and abdominal pain, think Henoch-Schonlein purpura
Chagas Disease
March 3rd, 2010Pathophysiology
1) systemic infection caused by protozoan Trypanosoma cruzi 2) occurs in an acute and chronic form (which is usually asymptomatic but can affect heart and cause megacolon and megaesophagus) 3) transmitted via bite of triatomine or reduviid bug, which defecates onto skin after taking a blood meal
Signs and Symptoms
Acute phase – 1) fever 2) malaise 3) anorexia 4) indurated lesion at site of parasite entry (chagoma) 5) hyperplasia of regional lymph nodes 6) positive Romana’s sign – unilateral painless swelling of periocular tissue 7) morbilliform rash 8) facial swelling 9) lower extremity edema 10) hepatosplenomegaly 11) in virtually patients, the acute illness resolves Chronic phase – 12) can appear years to decades later 13) chronic constipation 14) abdominal pain 15) volvulus 16) chest pain 17) dysphagia 18) odynophagia 19) regurgitation 20) aspiration pneumonitis due to achalasia 21) sudden cardiac arrest (especially in young people)22) sudden cardiac rupture
Characteristic Test Findings
EKG - 1) right bundle branch block 2) complete AV block 3) bradyarrhythmias and tachyarrhythmias Laboratory – 4) diagnosis in acute phase is by direct visualization of organism; in chronic phase, by antibody titers
Histology/Gross Pathology
1) apical aneurysms in heart 2) mural thrombi 3) thinned ventricular walls 4) biventricular enlargement 5) lymphocytic infiltrate and interstitial fibrosis in myocardium 6) myocardial cell atrophy 7) pseudocysts in affected tissue 8) decreased number of neurons in myenteric plexus 9) C-shaped organism
Associated Conditions
1) increased mortality in HIV/AIDS 2) increased mortality in transplant patients
Inheritance/Epidemiology
1) most common in extreme southern USA and throughout Central and South America in poor rural areas 2) occurs in USA in immigrant population from these areas – likely 100,000 people at least living in USA are infected 3) not screened for in many blood and organ donors in USA and many cases of transfusion-related infection have occurred
Treatment
1) nifurtimox for 90-120 days with variable results (only drug available in the USA) 2) benznidazole (available in South America)
Tips for USMLE
1) Romana sign is the classic finding in acute Chagas disease and is painless unilateral swelling of periocular tissues when portal is the eye/conjunctiva 2) the two main areas of involvement are the heart and the GI tract 3) most deaths in Chagas disease are the result of cardiac involvement
Systemic Lupus Erythematous (SLE)
February 24th, 2010Pathophysiology
1) systemic disorder with tissue damage secondary to autoantibodies and immune complex deposition 2) cause is unknown but likely requires an environmental stimulus (example is ultraviolet light) in presence of many susceptibility genes
Signs and Symptoms
1) butterfly rash on face 2) short hairs in frontal scalp (”lupus hairs”) 3) “carpet tack” skin lesions 4) pericarditis 5) pericardial effusions 6) pleurisy 7) pleural effusions 8) focal or diffuse proliferative nephritis 9) abdominal pain 10) blindness 11) fatigue (often debilitating) 12) cognitive dysfunction (”lupus cerebritis”) 13) subcutaneous nodules 14) puffiness of hands and feet 15) swan-neck deformities of fingers
Characteristic Test Findings
Laboratory – 1) anti-ANA antibody (98%) 2) anti-DNA antibody (70%) 3) antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody) 4) anti-Smith (Sm) antibody (30%) 5) increased sed rate 6) low complement (especially CH50) 7) pancytopenia 8) warm antibody hemolytic anemia
Histology/Gross Pathology
1) Libman-Sacks lesions (wart-like endocardial lesions) 2) marrow hypoplasia 3) thrombotic microangiography in kidney 4) deposition in glomerulus and mesangium of immune complexes (”wire-loop” deposition) 5) proliferative nephritis
Associated Conditions
1) HLA-DR2 or DR3 2) defective c4AQO class III allele 3) drugs – procainamide, quinidine, sulfonamides, barbiturates, cephalosporins 4) Raynaud’s phenomenon 5) increased rate of abortion and stillbirth (especially if lupus anticoagulant and anticardiolipin antibodies are present)
Inheritance/Epidemiology
1) 90% are women (especially premenopausal women) 2) occurs most commonly in blacks 3) clear genetic predisposition exists
Treatment
1) photoprotection for skin lesions 2) NSAIDS (especially Cox-2 inhibitors) and salicylates 3) antimalarials (hydroxychloroquine) or aminoquinoline in skin lesions 4) dehydroepiandrosterone (best in mild cases) 5) glucocorticoids 6) cytotoxic drugs – azathioprine, cyclophosphamide (especially in kidney disease), methotrexate, mycophenolate mofetil 7) anticoagulation if thrombosis is present 8) plasmapheresis with cytotoxic drugs 9) intravenous immunoglobulin
Tips for USMLE
1) repeat negative tests for anti-ANA antibody makes lupus very unlikely (but anti-ANA is positive in many diseases other than lupus 2) anti-SM antibody is highly specific for lupus 3) anti-double-stranded DNA antibody is relatively specific 4) most patients with systemic disease have discoid lupus (chronic cutaneous lupus), but only 10% with discoid lupus progress to systemic disease 5) skin lesions predominate in sun-exposed areas 6) if Libman-Sacks endocarditis is mentioned, think lupus 7) if low complement is mentioned (especially CH50), think SLE 8) some clinicians feel that Lyme disease may sometimes be misdiagnosed as lupus
Scleroderma
February 20th, 2010Pathophysiology
1) progressive systemic sclerosis owing to deposition in tissues of circulating immune complexes that cause systemic manifestations 2) initiating event is unknown 3) mild form occurs in CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal dysfuction, sclerodactyly, telangiectasias
Signs and Symptoms
1) often presents with Raynaud’s phenomenon 2) edema of fingers and hands followed by tightening and thickening of skin 3) ulcerations of fingertips 4) polyarthralgias 5) stone facies/restricted eye and mouth movements 6) dysphagia (esophageal hypomotility) 7) decreased intestinal motiliy with bacterial overgrowth/malabsorption 8) dyspnea on exertion 9) the “sclerodermal renal crisis” of progressive renal failure, microangiopathic hemolytic anemia, and acute onset of uncontrollable hypertension
Characteristic Test Findings
Laboratory – 1) anticentromere antibodies 2) antinuclear antibodies 3) antibodies to SCL-70 (topoisomerase I) 4) presence of male fetal cells 5) decreased CD8 T suppressor cells 6) antibodies against thyroid, salivary glands, and smooth muscle and type I and type IV collagen 7) positive rheumatoid factor
Huntington’s Chorea
February 19th, 2010Pathophysiology
1) progressive neurodegenerative disease with selective neuronal loss – caused by an excessive repeat of the CAG nucleic acid sequence in the gene on chromosome 4 that codes for the Huntington protein 2) unclear how altered Huntington protein contributes to the specific symptoms 3) the protein HAP-1, which binds to the Huntingtin protein, possibly contributes to the pathogenesis 4) usual duration from onset of symptoms to death is about 15 years 5) marked by involuntary movements, progressive dementia, striking emotional changes
Signs and Symptoms
1) the greater the expansion, the earlier the onset of disease 2) onset is earlier by 3-4 years if condition is inherited from father 3) usual presenting signs – emotional and cognitive deficits (often by years) 4) most striking sign – choreoathetoid movements
Characteristic Test Findings
Brain biopsy – marked decrease in brain levels of GABA, glutamic acid decarboxylase, and acetylcholine
Histology/Gross Pathology
1) atrophic frontal cortex 2) striking atrophy of caudate nucleus and to lesser degree the putamen 3) lateral ventricles appear enlarged owing to caudate nucleus atrophy 4) protein aggregrations and intranuclear inclusions
Associated Conditions
some pateints also develop a parkinsonism with rigidity in late disease
Biochemistry
1) the normal number of repeats of CAG, which codes for glutamine is 10-35; Huntington’s disease has 40-100 repeats 2) effect is probably an altered protein-protein interaction secondary to the polyglutamate area at the N-terminal of the protein
Inheritance/Epidemiology
1) affected chromosome region is 4p16.3 2) autosomal dominant 3) occurs in 1/15,000 births in affected populations, mostly in western European and Scandinavian descent 4) some spontaneous mutations are known to exist 5) heterozygotes have same severity of disease as homozygotes 6) age of onset is typically 30-50 years
Tips for USMLE
1) other diseases caused by a CAG trinucleotide repeat expansion – Machado-Joseph disease, spinal-bulbar musculat atrophy, olivopontocerebellar disease, dentatorubro-pallidoluysian atrophy (DRPLA) 2) if a brain biopsy shows loss of striatal neurons, think Huntington’s
Esophageal Cancer
February 18th, 2010
Pathophysiology
most common types by far are adenocarcinoma and squamous cell carcinoma
Signs and Symptoms
1) difficulty swallowing (dysphagia) – most common presenting symptom 2) pain on swallowing (odynophagia) 3) anorexia 4) cachexia 5) hoarseness (owing to compression of recurrent laryngeal nerve) 6) chronic cough (owing to tracheoesophageal fistula) 7) aspiration pneumonia 8) chest pain
Characteristic Test Findings
Laboratory – 1) hypercalcemia (even in absence of bone metastates) Endoscopy – 2) test of choice for obtaining tissue biopsy
Histology/Gross Pathology
1) occurs in polypoid, ulcerating, and infiltrative forms 2) spread is to regional lymph node basin, draining affected part of esophagus – cervical lymph nodes from upper third, mediastinal lymph nodes from middle third, and celiac and gastric lymph nodes from lower third 3) adenocarcinoma almost always arises from Barrett’s metaplasia 4) adenocarcinoma is located in lower third of esophagus 5) squamous cell carcinoma is more common in upper two thirds of esophagus
Associated Conditions
increased incidence with – 1) Plummer-Vinson syndrome 2) Barrett’s esophagus 3) heavy smoking and alcohol use (squamous carcinoma) 4) achalasia 5) chemical injury with stricture 6) presence of webs, rings, or diverticula 7) large amount of ingested nitrates 8) smoked opiates 9) deficiencies in dietary zinc, molybdenum, and vitamin A
Inheritance/Epidemiology
1) worldwide, squamous cell more common; in USA adenocarcinoma predominates 2) increased incidence in lower socioeconomic classes 3) esophageal cancer belt stretches across central Asia with incidence 300 times greater than areas of low incidence
Treatment
1) chemoradiation and surgery (if resectable) 2) anti-angiotenic drugs (endostatin, alpha-IFN) are being tried to stabilize disease 3) prognosis for adenocarcinoma is better than squamous, but overall 5 year survival is 5%
Tips for USMLE
1) if patient is a 56 year-old man with heavy alcohol and smoking history who develops weight loss and difficulty swallowing solids over a 3 month period, think esophageal cancer 2) if patient is a 67 year old man with a 25 year history of poorly controlled severe heartburn who has “pain in this throat” when he swallows, think esophageal cancer
Hand-Schuller-Christian Disease
February 18th, 2010
Pathophysiology
1) characterized by proliferation of histiocytes (Langerhans’ cells) 2) considered a variant of Langerhans’ cell histiocytosis (along with eosinophilic granuloma disease and Letterer-Siwe disease 3) mostly affects children 4) usually fairly indolent in nature with an intermediate prognosis between eosinophilic granuloma (best) and Letterer-Siwe (worst)
Signs and Symptoms
1) classic triad (occurs in one third of cases) – exophthalmos, diabetes insipidus, and multiple cystic effects of skull 2) lymphadenopathy 920%) 3) red crusty sores on trunk, hairline, and dorsum of hands and feet 4) bony lesions are typically the most impressive findings
Characteristic Test Findings
Radiology – 1) lytic bone lesions most commonly in the skull and in scapulae, ribs, pelvis, and jaw (causing “floating teeth”) 2) infiltrates in lung fields (20%)
Histology/Gross Pathology
1) Langerhans cells – proliferation and contain racket-shaped Birbeck’s granules 2) nucleus on H and E stain has a “kidney bean” appearance
Associated Conditions
1) hypopituitarism 2) deafness
Inheritance/Epidemiology
1) most commonly affects children age 2-5 years 2) occurs equally in boys and girls 3) makes up 20% of all cases of Langerhans’ cell histiocytosis
Treatment
1) radiation to destroy masses of histiocytes, especially if they are in the retro-orbital area 2) corticosteroids 3) cyclophosphamide 4) diabetes insipidus does not always reverse with treatment
Tips for USMLE
1) if question mentions cells that contain granules shaped like tennis rackets or nuclei that look like kidney beans, think Hand Schuller Christian disease 2) if the question mentions a 5 year-old girl with lytic bone lesions in her skull and exophthalmos, think Hand-Schuller-Christian disease 3) Langerhans cells – another term for histiocyte