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Eclampsia/Preeclampsia

August 10th, 2010

Pathophysiology

1) symptoms complex occurring in second or third trimester of pregnancy, with hypertension, proteinemia, edema, and convulsions 2) exact pathogenesis remains elusive

Signs and Symptoms

1) hypertension (diastolic > 85 mmHg and systolic > 140 mmHg in third trimester 2) hyperreflexia (preeclampsia) 3) convulsions (eclampsia) 4) edema secondary to sodium retention 5) positive “rollover” test (diastolic pressure increases at least 20 mmHg when changing from lateral recumbent to supine position) 6) oliguria

Characteristic Test Findings

Laboratory1) proteinuria 2) coagulopathy

Histology/Gross Pathology

1) fibrin thrombi in liver, glomeruli, and brain 2) placental infarcts 3) atherosis of placental vessels

Biochemistry

1) dysregulation of vascular cell adhesion molecule 1 (VCAM-1) 2) increased sensitivity to angiotensin 2

Treatment

1) bedrest 2) removal of undue stress and stimulation 3) magnesium sulfate to control neurologic manifestations 4) hydralazine and methyldopa for blood pressure control 5) “best treatment is delivery of fetus

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Hashimoto’s Disease

July 12th, 2010

Pathophysiology

1) autoimmune thyroiditis marked by progressive destruction of thyroid follicular cells, decreased production of thyroid hormone, and hypothyroidism 2) described as both an end-stage process of another disease and an idiopathic condition

Alagille’s Syndrome (Arteriohepatic Disease)

July 7th, 2010

Pathophysiology

infantile intrahepatic cholestasis owing to an interstitial gene deletion on chromosome 20

Signs and Symptoms

1) broad forehead 2) deep-set eyes 3) bulbous nose 4) butterfly vertebrae 5) pulmonic stenosis

Histology/Gross Pathology

paucity of intrahepatic bile ducts

Inheritance/Epidemiology

1) both autosomal dominant and sporadic cases are reported 2) occurs in 1/70,000 3) deletion is on chromosome 20 (p11.23)

Treatment

Liver transplantation

Tips for USMLE

If question mentions infant with increased bilirubin, must consider Alagille’s, Gilbert’s, Crigler-Najjar, and Dubin’s syndromes

Berry Aneurysm

July 2nd, 2010


Pathophysiology

1) usually congenital saccular dilation of artery in brain 2) most commonly located at bifurcations of cerebral arteries (especially bifurcation of the anterior communicating artery with anterior cerebral artery; the internal carotid artery and posterior communicating arery; or the trifurcation of the middle cerebral artery


Wegener’s Granulomatosis

July 1st, 2010

Pathophysiology

1) necrotizing granulomatous disease of the upper and lower respiratory tract in setting of glomerulonephropathy 2) most cases have other systemic manifestations 3) strongly associated with production of cytoplasmic antineutrophilic antibodies (c-ANCA)

Signs and Symptoms

1) purulent or bloody nasal discharge 2) sinus pain 3) destruction of nasal septum with saddle-nose deformity 4) serous otitis media 5) cough 6) dyspnea 7) chest pain 8) hemoptysis 9) airway obstruction from subglottic stenosis 10) fever

Characteristic Test Findings

Radiology-1) multinodular, bilateral cavitary infiltrates grouped around vascular structures on chest radiograph 2) bronchial obstruction with atelectasis on chest radiograph Laboratory-3) positive c-ANCA 4) increased sed rate 5) increased C-reactive protein 6) leukocytosis 7) thrombocytosis 8) anemia 9) positive rheumatoid factor 10) hematuria and red cell masts

Histology/Gross Pathology

1) necrotizing granulomatous vasculitis of small arteries and veins 2) granuloma formation 3) glomerulonephritis with crescents 4) rare granulomas in kidney

Associated Conditions

1) eye-50% of cases; episcleritis, retro-orbital mass 2) skin-45% of cases; papules, purpura, ulcers, subcutaneous nodules 3) neurologic-25%of cases; cranial neuritis, mononeuritis multiplex 4) cardiac-10% of cases; pericarditis, coronary vasculitis

Biochemistry

c-ANCA antibodies are directed against proteinase-3

Inheritance/Epidemiology

1) slight male predominance 2) rare in blacks 3) mean age of onset is 55 years 4) incidence peaks in winter months with some patients reporting a viral-like prodrome

Treatment

1) long-term cyclophosphamide plus glucocorticoids early in the course 2) alternate regimens-methotrexate or azathioprine plus glucocorticoids 3) some benefit is gained by adding trimethoprim-sulfamethoxazole (may cut relapse rate by eradicating nasal Staphylococcus aureus)

Tips for USMLE

1) Wegener’s involves the nasal passagways 95% of the time; so if it does not mention nasal pathology, it is not Wegener’s 2) classic triad-upper respiratory tract disease, lower respiratory tract disease, and kidney disease

Amyloidosis

June 30th, 2010

Pathophysiology

1) deposition of fibrous, insoluble amyloid protein in extracellular matrices of body 2) clinically ranges from benign to severe sequelae 3) classification is based on fibril-forming protein 4) most common systemic types – primary (idiopathic), secondary, and familial amyloid polyneuropathy (FAP)

Signs and Symptoms

Primary type – 1) nephrotic syndrome 2) hepatomegaly 3) carpal tunnel 4) GI disturbance 5) cardiomyopathy with heart block 6) peripheral neuropathy 7) waxy plaques in skin Secondary type – 8) hepatomegaly 9) GI disturbances 10) proteinuria FAP-11) neuropathy 12) vitreous opacities 13) “scalloped pupils 14) GI disturbances 15) cardiomyopathy with heart block

Histology/Gross Pathology

1) abnormal B-pleated sheet conformation 2) presence of the nonfibrillar component SAP (serum amyloid P; pentraxin) 3) presence of glycosaminoglycans in deposits

Associated Conditions

1) multiple myeloma 2) osteomyelitis 3) leprosy 4) TB 5) rheumatoid arthritis 6) familial Mediterranean fever

Biochemistry

Primary-1) fibrils are M-antibody light chains Secondary – 2) in inflammation – Il-1/IL-6 stimulate excess production of serum amyloid A (component of HDL) that then deposits in tissues FAP – 3) fibrils are transthyretin (most common), apolipoprotein A-I, gelsolin, and cystatin C

Raynaud’s Phenomenon

June 14th, 2010

Pathophysiology

1) intermittent ischemia of fingers and toes 2) if occurs as an isolated event, then it is called Raynaud’s disease or primary Raynaud’s phenomenon 3) proposed theories – it is an exaggerated sympathetic reflex vasoconstriction or an exaggerated response to cold stimuli 4) if ischemia occurs in association with other conditions it is called Raynaud’s phenomenon or secondary Raynaud’s phenomenon

Reiter’s Syndrome

June 12th, 2010

Pathophysiology

1) a type of spondyloarthropathy 2) marked by arthritis nongonococcal urethritis or cervicitis, and conjunctivitis

Signs and Symptoms

1) arthritis resembles rheumatoid arthritis 2) dysuria, urinary frequency, urethral discharge 3) keratoderma blennorrhagicaum (type of pustular psoriasis) over soles, palms, and torso (50%) 4) usually remits over 12 months 5) low back pain (20%) 6) joints most affected are knees, ankles, and feet (usually asymmetrically) 7) if toes or fingers are affected, tendon synovitis resembles “sausage digits” 8) pain over nonarticular bony areas 9) painless mouth ulcers 10) heel pain 11) fevers

Characteristic Test Findings

Laboratory – 1) increased sed rate 2) increased C-reactive protein 3) negative for rheumatoid factor Joint aspiration – 4) accumulating evidence that bacteria persist at sites of primary infection (previously thought to be negative) Radiology – 5) periosteal reactions, especially at the calcaneus with formation of heel spurs 6) bony fusion across joints

Associated Conditions

1) HLA-B27 is present in 90% of cases 2) strong association with HLA-B51 3) progressive arthritis, including ankylosing spondylitis (20%) 4) AIDS 5) increased incidence of cerebral vasculitis 6) strong association with previous gastrointestinal and genitourinary infections, especially Yersinia, Cyclospora, Salmonella, Shigella, Campylobacter, Helicobater, and Chlamydia trachomatis 8) dilation of ascending aorta

Crohn’s Disease

June 6th, 2010

Pathophysiology

1) transmural inflammatory disease of the GI tract (may involve other organs) GI involvement – 2) anorectum (15%) 3) colon only (20% and typically in older age presentation) 4) small intestine only (15%) 5) mainly ileum and cecum (50% and especially in young presentation 6) can occasionally involve stomach, esophagus, and mouth   Extraintestinal involvement – 7) arthritis (20%) 8) erythema nodosum 9) uveitis 10) ankylosing spondylitis (10%)

Signs and Symptoms

1) abdominal pain (relieved by defecation) 2) diarrhea 3) fever 4) weight loss 5) growth retardation 6) intestinal obstruction 7) bowel perforation 8) palpable right lower quadrant mass 9) fecaluria and pneumonuria (feces and air from urethra, aka “bubbles in urine”)

Characteristic Test Findings

Barium enema – 1) string sign, owing to strictures 2) “cobblestoning” 3) skip areas (disease is discontinuous) 4) thickened and edematous bowel walls 5) aphthous (superficial) ulcers in mucosa 6) deep ulcers and fissures in mucosa Laboratory – 7) leukocytosis 8) hypocalcemia 9) hypoalbuminemia 10) pellagra (niacin deficiency) 11) megaloblastic anemia (vitamin B12 deficiency) 12) antibodies against Saccharomyces cerevisiae (ASCA) in 70% of patients

Histology/Gross Pathology

1) transmural inflammation 2) transmural nodular lymphoid aggregates and fibrosis 3) mesenteric fat wraps 4) noncaseating granulomas 5) pneumatosis cystoides intestinalis (air in bowel wall)

Associated Conditions

1) adenocarcinoma of small bowel (100 times increased risk) 2) sclerosing cholangitis 3) cholelithiasis 4) amyloidosis 5) oxalate kidney stones 6) culture of Pseudomonas and atypical mycobacteria (role is unknown) from small bowel lesions 7) most patients have smoking history (role is unknown)

Gaucher’s Disease

June 5th, 2010

Pathophysiology

1) metabolic disease due to defect in beta-glucocerebrosidase (beta-glucosidase) Type 12) adult onset, chronic, highly variable course 3) no defects in eye movement 4) lacks neurological deficits Type 25) infantile onset, acute course 6) defects in eye movement 7) neurological defects are present Type 38) childhood to adult onset, highly variable course 9) defects in eye movement 10) late neurological defects

Signs and Symptoms

1) massive hepatomegaly (especially in type 3) 2) splenomegaly 3) bone destruction with aseptic necrosis of femoral head and femoral neck fractures 4) skin pigment changes 5) episodic “bone crisis” with fever, erythema over affected bones, and leukocytosis 6) severe neurologic involvement (types II and III) with seizures and dementia 7) infiltrative lung disease with dyspnea

Characteristic Test Findings

Laboratory1) thrombocytopenia 2) anemia 3) increased serum ferritin 4) increased serum ACE levels 5) increased plasma chitotriosidase 6) leuckocytosis Radiology7) ground-glass appearance to lung fields 8) bone infarctions seen on nuclear medicine scans 9) flaring of diaphysis and metaphysis

Histology/Gross Pathology

1) presence of Gaucher’s cells (macrophages with abnormal buildup of glucocerebroside) in liver, spleen, and lung 2) increased osteoclasts in bone 3) decreased mineral density of bone

Biochemistry

1) Beta-glucosidase catalyzes cleavage of glucocerbroside to glucoceramide 2) if this enzyme is missing, glucocerebroside (glucosylceramide) accumulates in macrophages 3) types I and III have some residual enzyme activity

Inheritance/Epidemiology

1) most common lysosomal storage disease 2) occurs in 1/60,000 births overall; in 1/900 births in Ashkenazi Jews (type 1) 3) gene defect is at 1q21 4) type III is most common in people of Swedish descent 5) autosomal recessive

Treatment

1) enzyme replacement therapy with beta-glucosidase (this reduces hepatosplenomegaly over 1 year and reduces bone lesions over 3-4 years; the neurologic deficits do not reverse) 2) some patients benefit from splenectomy 3) gene therapy trials are underway 4) joint replacement as needed

Tips for USMLE

1) if Gaucher’s cells are mentioned, obviously it is Gaucher’s disease 2) if macrophages filled with glucocerebroside are mentioned, think Gaucher’s 3) if bone crisis is mentioned, think Gauchers.

Sickle Cell Disease

May 31st, 2010

Pathophysiology

1) family of hemoglobinopathies with deformation of deoxygenated erythrocytes into a sickle shape 2) homozygous individuals are severely affected, with sickled hemoglobin (HbS) making up 80-95% of hemoglobin 3) sickled cells obstruct the small blood vessels, creating the many sequelae of the disease 4) heterozygous state has a protective effect against malaria, especially in children

Signs and Symptoms

1) presents 8-10 weeks after birth (patient is protected by residual fetal hemoglobin) 2) typical disease course is marked by episodic “sickle crisis” with greatly increased severity of symptoms 3) severe pain in abdomen, chest (acute chest syndrome), and bones 4) swollen hands and feet (hand-foot syndrome) 5) skin ulceration (especially on ankles) 6) cardiomegaly 7) cholecystitis (due to pigment stones) 8) osteomyelitis (especially Salmonella typhimurium) 9) blindness 10) stroke 11) priapism

Characteristic Test Findings

Laboratory – 1) chronic hemolytic anemia Radiology – 2) bilateral lung infiltrates

Histology/Gross Pathology

1) RBCs with classic sickle morphology 2) erythrocyte ghosts (complete lack of hemoglobin) with sickle shape 3) splenic infarcts with fibrosis and atrophy 4) Howell-Jolly bodies 5) infarcts in femoral head 6) renal infarcts

Associated Conditions

increased incidence of 1) aplastic crisis with severe anemia secondary to infection (especially parvovirus B19) 2) sequestration crisis with anemia (especially in infants and young children) 3) life-threatening infections with encapsulated bacteria (especially Streptococcus pneumoniae) 4) Mycoplasma pneumoniae infections

Biochemistry

1) caused by point mutation (glutamic acid replaced by valine in the beta-globin chain) 2) causes HbS to aggregate at a low oxygen tension with contraction of RBC around it 3) overall effect is to make cells less deformable and more likely to act as obstruction point 4) increased adhesion to endothelium

Inheritance/Epidemiology

1) autosomal recessive 2) defect is on chromosome 11p) 3) sickle cell disease is homozygous for HbS gene 4) sickle cell trait is heterozygous for HbS gene (10% of American blacks; does not affect life span and no treatment is needed) 5) sickle cell disease affects 50,000 people in the USA (almost entirely in black population) 6) also affects populations in India, Middle East, and Mediterranean

Treatment

1) hydroxyurea (increases amount of protective fetal hemoglobin) 2) clotrimazole (blocks RBC adhesion) 3) vigorous hydration 4) narcotics 5) vaccination against pneumococci and Haemophilus 6) antibiotic prophylaxis for invasive procedures 7) bone marrow transplantation (best in children)

Tips for USMLE

if acute chest syndrome or hand-foot syndrome is mentioned, think sickle cell disease

Mononucleosis

May 31st, 2010

Pathophysiology

infection with Epstein-Barr virus (or sometimes CMV with slightly different clinical presentation) in adolescence or early adulthood

Signs and Symptoms

1) prodrome of fatigue, malaise, and myalgias 2) tender but mobile lymphadenopathy (especially in posterior cervical chain) 3) fever 4) exudate pharyngitis 5) splenomegaly 6) splenic rupture (0.5%) 7) mouth petechiae 8) gingivitis 9) abdominal pain 10) rash (10%) 11) symptoms usually resolve in 3-4 weeks

Characteristic Test Findings

Laboratory1) leukocytosis with at least 10% lymphocytes 2) presence of Paul-Bunnell heterophile antibody (this is the basis of the diagnostic monospot test) 3) presence of transient cold agglutinins 4) increased AST, ALT, alkaline phosphatase

Histology/Gross Pathology

1) atypical lymphcytes (mostly CD8+ T-cells) with clumped chromatin and irregular nuclei surrounded by RBCs (ballerina-skirt) 2) atypical lymphocytes resemble Reed-Sternberg cells, causing diagnostic confusion 3) infiltration of splenic red pulp (and lymph node sinuses) with atypical lymphocytes 4) EBV is a linear, double-stranded DNA virus 5) CMV intranuclear with “halos”

Associated Conditions

1) splenic rupture (0.5%) 2) bacterial superinfection (10%) 3) autoimmune hemolytic anemia (2%) 4) rash if ampicillin is given (90% of cases not considered a true allergic reaction) 5) fulminant liver failure 6) CNS involvement (ataxia, hemiplegia, psychosis) 7) Guillain-Barre syndrome 8) pneumonia 9) arthritis

Biochemistry

1) virus binds to nasopharyngeal cells and B-lymphocytes, which carry it systemically 2) activated T-lymphocytes kill Ebstein-Barr infected B-lymphocytes

Inheritance/Epidemiology

1) prodrome lasts 4-6 weeks 2) asymptomatic carriers intermittently shed virus 3) person-to-person contact is via infected oral secretions

Treatment

supportive in immunocompetent individuals

Tips for USMLE

1) CMV mononucleosis differs from EBV mononucleosis – CMV etiology usually does not cause pharyngitis or posterior neck lymphadenopathy and does not have Paul-Bunnell heterophile antibodies 2) a heterophile antibody is a human antibody that reacts with the blood cells of another species, such as a sheep or guinea pig 3) if question mentions an 18 year old college freshman who develops a “dragged-out feeling” in the middle of the semester and then develops a headache, sore throat, and enlarged posterior neck lymph nodes during finals, think mononucleosis from EBV.

Homocystinuria

May 30th, 2010

Pathophysiology

1) group of seven different disorders 2) most common variant is caused by deficiency in cystathionine-beta-synthase 3) thought to involve abnormal cross-linking of collagen, fibrillin, and macromolecules

Signs and Symptoms

1) mental retardation/psychiatric problems 2) tall stature 3) skeletal defects (osteoporosis) 4) retinal detachment 5) increased thromboses 6) lens dislocation (downward and medially) 7) severe atherosclerosis

Characteristic Test Findings

Laboratory1) increased serum homocystine 2) increased urine homocytine 3) increased serum methionine in some variants 4) positive cyanide-nitroprusside test

Associated Conditions

1) myocardial infarction 2) pulmonary embolus 3) cerebral vascular accidents 4) deep venous thrombosis 5) peripheral artery disease 6) vision loss and glaucoma

Biochemistry

second most common variant has defect in methionine synthase

Treatment

1) early pyridoxine (induces cystathionine beta synthase activity) to blunt development of sequelae 2) low protein diet to methionine intake 3) maintenance of physiologic levels of cofactors folate, vitamin B6, and vitamin B12

Tips for USMLE

1) clinical features can be confused with Marfan’s disease 2) best way to differentiate is the mental retardation that occurs in homocystinuria but not Marfan’s 3) the lens subluxation in Marfan’s is upward and outward; in homocystinuria, it is downward and inward

Q Fever

May 24th, 2010

Pathophysiology

1) Rickettsial infection caused by Coxiella burnetii 2) acute and chronic forms exist

Signs and Symptoms

1) Severe headache 2) fever/chills/sweats 3) myalgias 4) extreme fatigue 5) dry cough 6) hepatosplenomegaly 7) nausea/vomiting 8) in immunocompetent hosts usually self-limited over 10-14 days 9) chronic form almost always involves endocarditis with a wide variety of other syndromes (see below)

Characteristic Test Findings

Radiology1) chest radiograph shows focal bronchopneumonia 2) CT scan shows “doughnut ring” pattern in liver parenchyma Laboratory3) positive rheumatoid factor 4) increased erythrocyte sed rate 5) increased C-reactive protein 6) increased gamma-globulin 7) thrombocytopenia initially followed by reactive thrombocytosis 8) diagnosis is by positive serology via indirect immunofluorescence

Histology/Gross Pathology

1) organism is small, pleomorphic, gram-negative coccobacillus 2) liver granulomata

Associated Conditions

chronic form has increased incidence of – 1) endocarditis 2) pericarditis 3) myocarditis 4) hepatitis 5) pancreatitis 6) deep vein thrombophlebitis 7) optic neuritis 8) Guillain-Barre syndrome 9) SIADH 10) orchitis 11) lymphadenopathy 12) erythema nodosum

Biochemistry

organism enters cells after being phagocytocized by macrophages

Inheritance/Epidemiology

1) infection is via inhalation, drinking infected milk, or contact with infected products of gestation (placenta) 2) vectors are goats, sheep, and cattle 3) most commonly found in butchers, veterinarians, and dairy workers 4) person-to-person contact is possible 5) initial presentation varies by geographical region – pneumonia in Canada and hepatitis in France

Treatment

1) acute disease – doxycycline for 2-3 weeks 2) chronic form – doxycycline and rifampin for 18-36 months

Tips for USMLE

1) unlike most rickettsial infections, there is usually no skin rash 2) WBC are usually normal 3) if sheep herder in France develops severe headache, fever, chills with enlarged tender liver, inflamed blood clots in his left calf, and a platelet count of 800,000/dL, think Q fever

Fabry’s Disease

May 23rd, 2010

Pathophysiology

1) type of lysosomal storage disease 2) cause is defect (multiple types possible) in alpha-galactosidase with altered metabolism of glycosphingolipid 3) onset is in childhood

Signs and Symptoms

1) angiokeratomas (telangiectasias of skin) that are blue-black to red and do not blanch – they increase in size and number as patient ages and are most dense on upper legs 2) acroparesthesias 3) small vessel disease of the brain, heart, and kidneys 4) hypohidrosis 5) abdominal pain that is worse with stress or fatigue 6) early coronary artery disease 7) lens and corneal opacities 8) leg lymphedema 9) episodic diarrhea 10) arthropathy of finger joints

Characteristic Test Findings

Laboratory – 1) hematuria 2) proteinuria

Histology/Gross Pathology

1) cellular accumulation of trihexosylceramide (THC), especially in endothelium 2) characteristic myeloid bodies seen on kidney biopsy

Associated Conditions

1) renal failure 2) leg lymphedena 3) hypertension 4) left ventricular hypertrophy 5) angina 6) congestive heart failure 7) stroke 8) focal segmental glomerulosclerosis 9) restrictive cardiomyopathy

Biochemistry

alpha-galactosidase A enzyme cleaves the terminal end of THC, which is a step in the metabolism of glycosphingolipid

Inheritance/Epidemiology

1) X-linked disorder (GLA gene on Xq22) 2) occurs in 1/40,000 3) most severe in men – heterozygous females have some symptoms but lack the severe organ involvement

Treatment

1) phenytoin and carbamazepine decrease the acroparesthesias 2) hemodialysis and kidney transplantation for renal failure 3) enzyme therapy

Tips for USMLE

angiokeratomas tend to be most numerous on thighs