Syndromes and Diseases - ASCPBOC

chediak-higashi syndrome

protein trafficking defect (autosomal recessive) characterized by impaired phagolysosome formation
clinical features: increased risk of pyogenic infections, neutropenia, giant granules in leukocytes, defective primary hemostasis, albinism, peripheral neuropathy

tay-sachs disease

autosomal recessive lysosomal storage disease which is the most common of the all gangliosidoses and caused by the loss of function mutations in the enzyme hexosaminidase; characterized by a cherry red spot on the retina due to swollen ganglion cells; most common among Ashkenazi Jews

niemann pick disease (A and B)

autosomal recessive lysosomal storage disease characterized by accumulation of sphingomyelin; most common in Ashkenazi Jews

type C

what subtype of niemann pick disease is associated with accumulation of cholesterol?

gaucher disease

autosomal recessive lysosomal storage disease resulting from a mutation in the gene that encodes glucocerebrosidase and leads to an accumulation of glucocerebroside; most common lysosomal storage disorder

systemic lupus erythematous

type III hypersensitivity reaction characterized by Malar and discord rashes and anti-ANA (not specific), anti-dsDNA (specific), and anti-sM (specific)

rheumatoid arthritis

autoimmune disorder with mutation of HLA-DR4; usually characterized by synovitis of the PIP joints leading to pannus formation (DIP usually spared); leads to destruction of cartilage and ankylosis (fusion and immobility)

RA affects PIP joint and usually spares DIP, unlike osteoarthritis

how to distinguish rheumatoid arthritis and osteoarthritis?

sjogren syndrome

autoimmune destruction of salivary and lacrimal glands; lymphocytic sialadenitis on lip bx is diagnostic; increased risk of mantle cell lymphoma

CREST (calcinosis, raynauds, esophageal dysmotility, sclerodactyly, telangiectasia of skin)

what are the systemic symptoms of limited systemic sclerosis?

diffuse

type of systemic sclerosis that involves the entire skin and includes early visceral involvement especially vessels, GI, lungs, an kidneys; anti-DNA topoisomerase

systemic sclerosis

autoimmune disorder involving abnormal deposition of collagen leading to hardening of the skin and some visceral organs

marfan syndrome

autosomal dominant connective tissue disorder caused by mutation in the FBN1 gene which encodes the structural protein, fibrillin; clinical features include tall stature, long fingers, bilateral subluxation of lens, mitral valve prolapse, aortic aneurysm, and aortic dissection

ehlers-danlos syndrome

group of diseases characterized by defects in collagen synthesis or structure leading to fragile, hyperextensible skin, vulnerability to trauma, hypermobile joints, poor wound healing, and ruptures involved the colon, cornea, or large arteries

phenylketonuria

results from mutations that cause a severe lack of the enzyme phenylalanine hydroxylase; leads to severe mental retardation, seizures, and decreased pigmentation of skin; avoided with restriction of phenylalanine intake in the diet

trisomy 21 (down)

epicanthal folds, flat facial profile, simian crease, oblique palpebral fissures, congenital heart defects

trisomy 18 (edwards)

prominent occiput, micrognathia, low set ears, congenital heart defects, overlapping fingers, short neck, renal malformation

trisomy 13 (patau)

polydactyly, cleft palate, rocker bottom feet, umbilical hernia, microcephaly

klinefelter syndrome

male hypogonadism; usually 47, XXY; testicular atrophy, sterility, reduced body hair, gynecomastia, eunuchoid body habitus

turner syndrome

female hypogonadism; usually 45 X; short stature, webbing of the neck, cubitus valgus, CV malformations, coarctation of the aorta, amenorrhea, lack of secondary sex characteristics, fibrotic ovaries, cavernous lymphangiomas/cystic hygromas

potter sequence

cascade of anomalies that stem from the primary issue of renal agenesis which leads to oligohydramnios (can’t produce urine) that causes downstream features including pulmonary hypoplasia (most clinically significant), limb deformities (due to compression), and flat face

neonatal respiratory distress syndrome

disorder of prematurity characterized by inadequate surfactant leading to collapse of air sacs and formation of hyaline membranes

immune hydrops

accumulation of edema fluid in the fetus during intrauterine growth resulting from an antibody-induced hemolytic disease in the newborn that is caused by blood group incompatibility between mother and fetus (Rh or ABO); severe anemia → heart failure → widespread fetal edema

cystic fibrosis

autosomal recessive disorder caused by mutations in the CFTR gene causing defected chloride ion transport; high salt concentrations in sweat and in viscous luminal secretions in the respiratory and GI tracts; can lead to cardiopulmonary, pancreatic and hepatic complications; most common lethal genetic disease affecting caucasians

retinoblastoma

most common intraocular malignancy in children

beckwith-wiedemann syndrome

congenital overgrowth disorder characterized by macroglossia, omphaloceles, macrosomia, Wilms tumor, neonatal hypoglycemia

syphilis

chronic venereal infection caused by the spirochete Treponema pallidum

trichomonas vaginalis

STD caused by a protozoan that causes nongonococcal urethritis and cervicitis

osteomalacia

vitamin D deficiency in adults leading to an excess of unmineralized bone matrix; leads to weak bones and an increased risk for fractures

rickets

vitamin D deficiency in children leading to excess of unmineralized bone matrix; frontal bossing, pigeon-breast deformity, lumbar lordosis, and bowing of legs

monckeberg medial calcific sclerosis

non-obstructive calcification of the media of muscular arteries usually occurring in patients > 50 years; incidental findings on x-ray or mammogram and usually clinically insignificant

true aneurysm

dilation of blood vessel wall involving all three layers (intima, media, and adventitia)

false aneurysm

blood vessel wall rupture leads to formation of extravascular hematoma that communicates with the intravascular space (pulsating hematoma) by extravascular connective tissues

aortic dissection

intimal tear in the wall of the aorta leads to blood entering the wall of the vessel within the layers of the media; most common in the proximal 10 cm of the aorta and most commonly caused by hypertension

giant cell (temporal) arteritis

granulomatous vasculitis classically involving branches of the carotid artery and leads to headaches, visual disturbances, and jaw claudication; most common in females over 50

takayasu artertitis

granulomatous vasculitis involving the aortic arch and branches; presents in young asian females; “pulseless disease” due to weak or absent pulse in the upper extremities

polyarteritis nodosa

necrotizing vasculitis involving multiple organs but sparing the lungs; associated with skin lesions and fibrinoid necrosis; serum HBsAg; type III HSR

kawasaki disease

vasculitis involving the coronary arteries and affecting asian kids under 4 years; nonspecific symptoms such as conjunctivitis, erythematous rash of palms and soles, enlarged cervical lymph nodes

thromboangiitis obliterans (buerger disease)

necrotizing vasculitis involving digits and presenting with ulceration, gangrene, and autoamputation; highly associated with smoking

granulomatosis with polyangiitis (wegener)

necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys; 90% p-ANCA

churg-strauss syndrome (allergic granulomatosis/eosinophilic granulomatosis with polyangiitis)

necrotizing granulomatous inflammation with eosinophils involving multiple organs, especially lungs and heart; asthma and peripheral eosinophilia; p-ANCA elevated

pyogenic granuloma

capillary hemangiomas that present as rapidly growing red, pedunculated lesions on the skin, gingiva, or oral mucosa; easily bleed and often ulcerate; commonly develop after trauma or in pregnant women

aschoff bodies

collections of lymphocytes (T cells), scattered plasma cells, anitschkow cells (plump activated macrophages) and zones of fibrinoid necrosis; pathognomonic of rheumatic heart disease and acute rheumatic fever

libman-sacks endocarditis

sterile vegetations on either side of the valve leaflets in patients with SLE

myocarditis

inflammation of the myocardium, most commonly caused by viral infections

myxoma

most common cardiac tumor in adults; pedunculated mass most commonly in the left atrium

rhabdomyoma

most common cardiac tumors in kids; “spider cells” in ventricles

sickle cell anemia

autosomal recessive mutation of B-chain hemoglobin; glutamine replaced with valine; “crew-cut” x-ray, splenomegaly in children, autosplenectomy in adults

pernicious anemia

autoimmune disorder affecting the gastric mucosa when it cannot produce enough intrinsic factor; leads to vitamin B12 deficiency and demyelination of the dorsal and lateral tracts of the spinal cord; type II HSR

aplastic anemia

bone marrow disorder in which intrinsic stem cells are damaged leading to a deficiency in all blood cell types

polycythemia

abnormal increase in RBC number per unit of blood volume leading to thickened blood and poor circulation

polycythemia vera (primary)

overproduction of RBCS by the bone marrow, usually due to a JAK2 mutation; leads to thickened blood and poor circulation that increases the risk of clots, stroke, and heart attack

small lymphocytic lymphoma (chronic lymphocytic leukemia)

indolent, slow growing tumor of CD5+ B cells where the increased survival of the tumor cells is more significant than the increased proliferation

burkitt lymphoma

highly aggressive germinal center B cell lymphoma often associated with t(8;14) c-myc gene and EBV; common in African children affecting the jaw; “starry sky” microscopy

multiple myeloma

malignant proliferation of plasma cells in the bone marrow leading to lytic lesions of the skeletal system, especially the vertebral column and skull; hallmark tumor marker are bence jones proteins produced by abnormal plasma cells which can lead to renal dysfunction

hodgkin lymphoma

reed-sternberg cells are characteristic; spreads in stepwise, chronological pattern in lymph nodes; nodular sclerosis is the most common type (lacunar RS cells)

acute myelogenous leukemia (AML)

most common adult leukemia; aggressive cancer of the blood and bone marrow characterized by rapid accumulation of immature myeloid cells (myeloblasts); MPO +

chronic myelogenous leukemia (CML)

slow-growing cancer of the blood and bone marrow characterized by the philadelphia chromosome mutation BCR-ABL; associated with t(9;22)

disseminated intravascular coagulation (DIC)

widespread activation of the coagulation cascade leading to ischemia and infarction; this consumes platelets and factors leading to severe bleeding, especially on mucosal surfaces and IV sites

immune thrombocytopenic purpura (ITP)

blood disorder involving autoimmune production of IgG antibodies against platelets antigens (GPIIb/IIIa) in the spleen; splenic macrophages consume antibody-bound platelets

thalassemia

autosomal dominant anemia caused by mutations in globin genes that decrease the synthesis of alpha- or beta- globin chains

thrombotic thrombocytopenic purpura (TTP)

blood disorder involving widespread formation of platelet-rich thrombi in microcirculation leads to platelet consumption leading to thrombocytopenia; platelet-rich thrombi narrow blood vessels leading to microangiopathic hemolytic anemia; associated with fever, neural deficits, and renal failure; *ADAMTS13 mutation

hemophilia A (factor VIII deficiency)

x-linked disorder involving mutation in factor VIII; primarily affects males leading to severe bleeding into joints and soft tissues

hemophilia A (factor VIII deficiency)

most common hereditary cause of serious bleeding

atelectasis

aka lung collapse; loss of lung volume caused by inadequate expansion of air spaces; results in shunting of adequately oxygenated blood from pulmonary arteries into vein resulting in ventilation perfusion imbalance and hypoxia

acute respiratory distress syndrome (ARDS)

progressive respiratory insufficiency caused by diffuse alveolar damage in the setting of sepsis, severe trauma, or diffuse pulmonary infection; characteristics include alveolar edema, epithelial necrosis, neutrophils, and hyaline membranes

emphysema

permanent enlargement of the air spaces distal to the terminal bronchioles (acini), accompanied by wall destruction without significant fibrosis; high correlation with smoking and characteristically “pink puffers”

centrilobular

most common type of emphysema

panacinar

what type of emphysema is associated with alpha-1 antitrypsin deficiency

asthma

reversible obstructive pulmonary disease associated with eosinophils and charcot-leyden crystals; can be IgE mediated type I hypersensitivity reaction; spiral shaped mucus plugs = curschmann spirals

bronchiectasis

obstructive pulmonary disease with permanent dilation of bronchi and bronchioles caused by destruction of smooth muscle and supporting elastic tissue; typically associated with chronic necrotizing infections

idiopathic pulmonary fibrosis

restrictive pulmonary disease with patchy, progressive bilateral interstitial fibrosis and cystic spaces (honey comb lung)

pneumoconiosis

collection of chronic fibrosing diseases of the lung resulting from occupational exposure to organic and inorganic particles (e.g. coal dust, silica, asbestos); pulmonary alveolar macrophages contribute by promoting inflammation and producing ROS and fibrogenic cytokines

sarcoidosis

disease of exclusion characterized by the presence of noncaseating granulomas in various tissues with lung involvement in 90% of cases; classic presentation is african american female under 40 years

goodpasture syndrome

type II HSR; autoimmune disorder with antibodies against type IV collagen which affects the basement membrane of the lungs and kidneys

Potts disease

tuberculosis involving the lumbar vertebral column

acute nephritic syndrome

inflammation of the glomeruli characterized by hematuria with RBC casts, mild proteinuria (<3.5 g/day), azotemia (increase BUN), and hypertension

nephrotic syndrome

derangement in the capillary walls of the glomeruli that results in increased permeability of plasma proteins; characterized by mass proteinuria (>3.5 g/day), generalized edema, hypoalbuminemia, and hyperlipidemia

focal segmental glomerulosclerosis

hardening of some (but not all) glomeruli that involves only a part of each affected glomerulus; one of the most common causes of nephrotic syndrome in adults; effacement of foot processes on electron microscopy and negative for immunofluorescence; associated with HIV and heroin

IgA nephropathy (berger disease)

one of the most common causes of recurrent microscopic or gross hematuria and the most common glomerular disease revealed by renal biopsy worldwide; usually affects children and young adults, characteristically hematuria or proteinuria and dense deposition of IgA in the mesangium

acute pyelonephritis

suppurative inflammation of the kidney and renal pelvis caused by bacterial infection, most commonly E. coli (klebsiella, enterobacter); characterized by liquefactive necrosis and abscess formation with the kidney

acute tubular necrosis

most common cause of acute kidney injury resulting from ischemic or nephrotoxic injury to renal tubules and associated with intrarenal vasoconstriction resulting in reduced GFR and diminished delivery of oxygen and nutrients to tubular epithelial cells; clinically electrolyte abnormalities, acidosis, uremia, and signs of fluid overload with oliguria

benign nephrosclerosis

sclerosis of small renal arteries and arterioles that is strongly associated with hypertension leading to bilateral cortical atrophy and hyaline arteriolosclerosis

peutz-jeghers syndrome

autosomal dominant disorder defined by the presence of multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation with increased risk of malignancies (colon, pancreas, breast, lung, ovaries, uterus, testes); LKB1/STK11 loss of function mutations

achalasia

triad of incomplete relaxation of the lower esophageal sphincter, increased LES tone, and esophageal aperistalsis (absence of coordinated muscle contractions)

mallory-weiss tears

esophageal lacerations from severe retching or vomiting that usually cross the GEJ

stress ulcers

gastric ulcers in critically ill patients with shock, sepsis, or severe trauma

curling ulcers

ulcers most common in the proximal duodenum associated with severe burns or trauma

cushing ulcers

ulcers arising in the stomach, duodenum or esophagus of persons with intracranial disease; high incidence of perforation

krukenberg tumor

metastatic, bilateral mucinous ovarian tumors usually from the stomach or GI tract

mallory-denk bodies

abnormal eosinophilic inclusions found in the cytoplasm of hepatocytes which are linked to chronic liver injury such as steatohepatitis

hemochromatosis

excessive absorption of iron due to decreased hepcidin that controls iron absorption in the gut; iron deposition in the liver, pancreas, heart, pituitary gland, joints

wilson disease

autosomal recessive disorder with toxic accumulation of copper in the liver, brain, and eyes; Kayser-fleischer rings in the eyes are characteristic

linitus plastica

diffuse gastric adenocarcinoma with rugal flattening, rigid and thickened wall, and signet ring cells

primary sclerosing cholangitis

inflammation and obliterative fibrosis of intra and extrahepatic bile ducts that can be diagnosed on x-ray; common in younger males and strong association with UC

primary biliary cirrhosis

autoimmune nonsuppurative destruction of intrahepatic bile ducts; affects females and anti-mitochondrial antibodies are present

budd-chiari syndrome

thrombosis of two or more major hepatic veins causing obstruction of blood outflow and leading to liver enlargement, ascites, pain and severe congestion

lichen sclerosis

smooth white plaques on the vulvar mucosa with atrophic epithelium, subepithelial dermal fibrosis, bandlike chronic inflammation; small percentage develop SCC

lichen simple chronicas

mucosal lesion appearing as an area of leukoplakia; thickened epithelium (stratum granulosum) and hyperkeratosis

1. hypertension

2. proteinuria

3. edema

three characteristics of preeclampsia