Diseases

Front 1

Familial Mediterranean fever (FMF).

Back 1

AR

Dysfunction of neutrophils

occurs in persons of mediterranean origin.

Presents with episodes of fever and acute serosal inflammation (can mimic appendicitis, arthritis, or myocardial infarction)

High SAA- deposits of AA in tissues

Front 2

Romano-Ward syndrome

Back 2

AD

congenital long QT pure cardiac phenotype (no deafness).

Front 3

Jervell and Lange-Nielsen syndrome

Back 3

AR

congenital long QT sensorineural deafness

Front 4

Brugada syndrome

Back 4

AD

Most common in Asian males.

ECG pattern of pseudo-right bundle branch block and ST elevations in V1-V3.

Risk of ventricular tachyarrhythmias and sudden cardiac death.

Prevent SCD with implantable cardioverter-defibrillator (ICD).

Front 5

Wolff-Parkinson-White syndrome

Back 5

Most common type of ventricular preexcitation syndrome.

Abnormal fast accessory conduction pathway from atria to ventricle (bundle of Kent),

Delta wave with widened QRS complex and shortened PR interval on ECG.

May result in reentry circuit--supraventricular tachycardia.

Front 6

1st degree Heart Block

Back 6

The PR interval is prolonged (> 200 msec)

Front 7

Mobitz type I (Wenckebach) heart block

Back 7

Type 2 heart block. Progressive lengthening of PR interval until a beat is “dropped”(a P wave not followed by a QRS complex)

Front 8

Mobitz type II Heart block

Back 8

Type 2 heart block. 2:1. Dropped beats that are not preceded by a change in the length of the PR interval

Front 9

3rd degree (complete) heart block

Back 9

The atria and ventricles beat independently of each other.

Front 10

Tricuspid atresia

Back 10

Absence of tricuspid valve and hypoplastic RV

Requires both ASD and VSD for viability. (bypasses RV and pulmonary circuitry

Front 11

Tetralogy of Fallot

Back 11

Most common cause of early childhood cyanosis.

Pulmonary stenosis (mostimportant determinant for prognosis)

Right ventricular hypertrophy (RVH)— boot‑shaped heart on CXR

Overriding aorta

VSD

Front 12

Eisenmenger syndrome

Back 12

Uncorrected left-to-right shunt (VSD, ASD, PDA)-- increased pulmonary blood flow—pulmonary arterial hypertension. RVH occurs to compensate---shunt becomes right to left.

Causes late cyanosis, clubbing, and polycythemia

Front 13

Coarctation of the aorta

Back 13

Aortic narrowing near insertion of ductus arteriosus (“juxtaductal”).

Associated with Turner syndrome.

Hypertension in upper extremities and weak, delayed pulse in lower extremities (brachial-femoral delay).

Notched ribs on CXR

Front 14

Dressler syndrome

Back 14

Autoimmune phenomenon resulting in fibrinous pericarditis (several weeks post-MI).

Front 15

Löffler syndrome

Back 15

Endomyocardial fibrosis with a prominent eosinophilic infiltrate

Front 16

Angiosarcoma

Back 16

Rare blood vessel malignancy typically occurring in the head, neck, and breast areas.

Usually in elderly, on sun-exposed areas.

Associated with radiation therapy and chronic postmastectomy lymphedema.

Hepatic angiosarcoma associated with vinyl chloride and arsenic exposures.

Very aggressive and difficult to resect due to delay in diagnosis. Express CD 31/ PECAM-1

Front 17

Bacillary angiomatosis

Back 17

Benign capillary skin papules found in AIDS patients.

Caused by Bartonella henselae infections.

Frequently mistaken for Kaposi sarcoma, but has neutrophilic infiltrate.

Front 18

Cherry hemangioma

Back 18

Benign capillary hemangioma of the elderly. Does not regress.

Front 19

Cystic hygroma

Back 19

Cavernous lymphangioma of the neck.

Associated with Turner syndrome.

Front 20

Glomus tumor

Back 20

Benign, painful, red-blue tumor under fingernails.

Arises from modified smooth muscle cells of the thermoregulatory glomus body- constrict blood vessels in fingers when cold

Front 21

Kaposi sarcoma

Back 21

Endothelial malignancy most commonly of the skin, but also mouth, GI tract, and respiratory tract.

Associated with HHV-8 and HIV.

Front 22

Pyogenic granuloma

Back 22

Polypoid capillary hemangioma that can ulcerate and bleed.

Associated with trauma and pregnancy.

Front 23

Strawberry hemangioma

Back 23

Benign capillary hemangioma of infancy.

Grows rapidly and regresses spontaneously by 5–8 years old.

Front 24

Temporal (giant cell) arteritis

Back 24

Unilateral headache (temporal artery), jaw claudication.

May lead to irreversible blindness.

Focal granulomatous inflammation

Increased ESR.

Tx: corticosteroids

Front 25

Takayasu arteritis

Back 25

Usually Asian females < 40 years old.

“Pulseless disease” (weak upper extremity pulses), fever, night sweats, arthritis, myalgias, skin nodules, ocular disturbances.

Granulomatous thickening and narrowing of aortic arch

Increased ESR.

Tx: corticosteroids.

Front 26

Polyarteritis nodosa

Back 26

Associated with Hepatitis B.

Fever, weight loss, malaise, headache. abdominal pain, melena.

Hypertension, neurologic dysfunction, cutaneous eruptions, renal damage.

Involves renal and visceral vessels, SPARES pulmonary arteries.

Immune complex- transmural inflam of arterial wall w/ fibrinoid necrosis. bead-like aneurysm formation (rosary)

Front 27

Kawasaki disease

Back 27

Asian children < 4 years old.

Conjunctival injection, Rash( desquamating), Adenopathy (cervical), Strawberry tongue (oral mucositis), Handfoot changes (edema, erythema), fever.

May develop coronary artery aneurysms.

Tx with ASPIRIN

Front 28

Buerger disease (thromboangiitis obliterans)

Back 28

Heavy smokers, males < 40 years old. Intermittent claudication may lead to gangrene.

Front 29

Granulomatosis with polyangiitis (Wegener)

Back 29

Perforation of nasalseptum, chronic sinusitis, otitis media, hemoptysis, hematuria, red cell casts.

Triad: Focal necrotizing vasculitis, necrotizing granulomas in lung, necrotizing glomerularnephritis.

C-ANCA, anti-proteinase 3.

Front 30

Microscopic polyangiitis

Back 30

Necrotizing vasculitis commonly involving lung, kidneys, and skin with pauci-immune glomerulonephritis and palpable purpura.

No granulomas.

MPO-ANCA/p-ANCA H (antimyeloperoxidase)

Front 31

Churg- Strauss

Back 31

Asthma, sinusitis, skin nodules or purpura, peripheral neuropathy (e.g., wrist/foot drop).

Granulomatous, necrotizing vasculitis with eosinophilia.

MPO-ANCA/p-ANCA, increased IgE level.

Front 32

Henoch-Schönlein purpura

Back 32

Most common childhood systemic vasculitis.

Often follows URI.

Classic triad: palpable purpura on buttocks/legs; Arthralgias; abdominal pain.

Vasculitis 2° to IgA immune complex deposition.

Associated with IgA nephropathy (Berger disease).

Front 33

Addison disease

Back 33

chronic adrenal insufficiency due to adrenal atrophy or destruction (autoimmune, TB, metastasis). Sx: weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbances, sugar and/or salt cravings, hyperkalemia, metabolic acidosis, skin and mucosal hyperpigmentation (due to MSH increase from byproduct of ACTH).

Front 34

Conn syndrome

Back 34

Primary hyperaldosteronism. Hypertension, hypokalemia, metabolic alkalosis, low plasma renin. (normal Na+ due to aldosterone escape mechanism).

Front 35

Waterhouse-Friderichsen syndrome

Back 35

acute 1° adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitidis), DIC, endotoxic shock.

Front 36

Neuroblastoma

Back 36

Most common tumor of the adrenal medulla in children, usually < 4 years old. Originates from neural crest cells; Homer-Wright rosettes characteristic. Homovanillic acid (HVA; a breakdown product of dopamine). Bombesin and neuron enolase positive. N-myc oncogene. Brown tumor.

Front 37

Pheochromocytoma

Back 37

Most common tumor of the adrenal medulla in adults. Derived from chromaffin cells (arise from neural crest). Episodic hypertension, headache, palpitations, pallor. Associated with neurofibromatosis type 1, von Hippel-Lindau disease, MEN 2A and 2B. Increased catecholamines, metanephrines and VMA(in urine).

Front 38

Hashimoto thyroiditis

Back 38

Antithyroid peroxidase, antimicrosomal and antithyroglobulin antibodies. Associated with HLA-DR5. Increased risk of non-Hodgkin lymphoma. May be hyperthyroid early due to thyrotoxicosis. Histologic findings: Hürthle cells, lymphoid aggregate with germinal centers. Moderately enlarged, nontender thyroid.

Front 39

Congenital hypothyroidism (cretinism)

Back 39

Severe fetal hypothyroidism due to maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis. Sx: Pot-bellied, Pale, Puffy-faced child, umbilical hernia, enlarged tongue, and Poor brain development (need TH for brain development).

Front 40

Subacute thyroiditis (de Quervain)

Back 40

Self-limited following a flu-like illness. Histology: granulomatous inflammation. Findings: increased ESR, jaw pain, early inflammation, very tender thyroid. Young female, tender thyroid.

Front 41

Riedel thyroiditis

Back 41

Thyroid replaced by fibrous tissue (hypothyroid). Fibrosis may extend to local structures. Considered a manifestation of IgG4-related systemic disease. Findings: fixed, hard (rock-like), painless goiter.

Front 42

Graves disease

Back 42

Autoantibodies (IgG) stimulate TSH receptors on thyroid, retro-orbital fibroblasts (exophthalmos), and dermal fibroblasts (pretibial myxedema b/c also have TSH receptors. Scalloped colloid and chronic inflammation.

Front 43

Toxic multinodular goiter

Back 43

Focal patches of hyperfunctioning follicular cells independently of TSH due to mutation in TSH receptor. increased release of T3 and T4.

Front 44

Thyroid storm

Back 44

Stress-induced catecholamine surge seen as a serious complication of thyrotoxicosis. Presents with agitation, delirium, fever, diarrhea, coma, and tachyarrhythmia (cause of death). May see increased ALP

Front 45

Jod-Basedow phenomenon

Back 45

Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete.

Front 46

Papillary carcinoma of the thyroid

Back 46

Most common, excellent prognosis. Empty-appearing nuclei with central clearing (“Orphan Annie” eyes), psammoma bodies, nuclear grooves. Lymphatic invasion common. RET and BRAF mutations, ionizing radiation.

Front 47

Follicular carcinoma

Back 47

Good prognosis, invades thyroid capsule (unlike follicular adenoma), uniform follicles.

Front 48

Medullary carcinoma

Back 48

From parafollicular “C cells”; produces calcitonin, sheets of cells in an amyloid stroma. Associated with MEN 2A and 2B (RET mutations). Decreased Ca2+, amyloid.

Front 49

Undifferentiated/ anaplastic carcinoma

Back 49

Older patients; invades local structures, very poor prognosis.

Front 50

Hypoparathyroidism

Back 50

Due to accidental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome. Findings: hypocalcemia, tetany. Chvostek sign—tapping of facial nerve (tap the Cheek) increased contraction of facial muscles. Trousseau sign—occlusion of brachial artery with BP cuff causes carpal spasm.

Front 51

Primary Hyperparathyroidism

Back 51

Usually due to parathyroid adenoma or hyperplasia. Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia, increased PTH, increased ALP, increased cAMP in urine. Most often asymptomatic. Stones, bones, groans, psychiatric overtones.

Front 52

SIADH

Back 52

Syndrome of inappropriate antidiuretic hormone secretion: Excessive free water retention, Euvolemic hyponatremia with continued urinary Na+ excretion, Urine osmolality > serum osmolality. Small cell lung cancer!

Front 53

Sheehan syndrome

Back 53

ischemic infarct of pituitary following postpartum bleeding; usually presents with failure to lactate, absent menstruation, cold intolerance

Front 54

Empty sella syndrome

Back 54

atrophy or compression of pituitary, often idiopathic, common in obese women

Front 55

Pituitary apoplexy

Back 55

sudden hemorrhage of pituitary gland, often in the presence of an existing pituitary adenoma

Front 56

Carcinoid syndrome

Back 56

Carcinoid tumors (neuroendocrine cells), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT). Not seen if tumor is limited to GI tract Results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right-sided valvular disease. 5-hydroxyindoleacetic acid (5-HIAA) in urine, niacin deficiency (pellagra).

Front 57

Zollinger-Ellison syndrome

Back 57

Gastrin-secreting tumor (gastrinoma). Acid hypersecretion causes recurrent ulcers in duodenum and jejunum. Positive secretin stimulation test: gastrin levels remain elevated after administration of secretin. May be associated with MEN 1.

Front 58

MEN 1

Back 58

Parathyroid tumors, Pituitary tumors (prolactin or GH), Pancreatic endocrine tumors—Zollinger- Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare). Associated with mutation of MEN1 gene (menin, a tumor suppressor) “Diamond”

Front 59

MEN 2A

Back 59

Parathyroid hyperplasia, Pheochromocytoma, Medullary thyroid carcinoma (secretes calcitonin). Associated with marfanoid habitus; mutation in RET gene (codes for receptor tyrosine kinase). “Square”

Front 60

MEN 2B

Back 60

Pheochromocytoma, Medullary thyroid carcinoma (secretes calcitonin) Oral/intestinal ganglioneuromatosis: mucosal neuromas. Associated with marfanoid habitus; mutation in RET gene. “triangle”

Front 61

Li-Fraumeni syndrome

Back 61

1 mutated p53 gene- characterized by the propensity to develop multiple types of carcinomas and sarcomas)

Front 62

Familial retinoblastoma

Back 62

1 Rb is mutated; characterized by bilateral retinoblastoma and osteosarcoma.

Front 63

IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

Back 63

Autoimmune production of IgG against platelet antigens (e.g., GPIIb/llla) produced by plasma cells of spleen. Acute form in children weeks after a viral infection or immunization; self-limited. Chronic in adults, usually secondary to SLE. Decreased platelet count, normal PT/ PTT, increased megakaryocytes. Tx: corticosteroids, IVIG if severe, splenectomy.

Front 64

MICROANGIOPATHIC HEMOLYTIC ANEMIa

Back 64

Pathologic formation of platelet microthrombi in sma11 vessels. Seen in thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)

Front 65

TTP

Back 65

due to decreased ADAMTS13, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation. Large, uncleaved multimers leading to abnormal platelet adhesion--- microthrombi. CNS predominance Skin and mucosal bleeding, MAHA, Fever. Thrombocytopenia, shear cells, increased BT, PT/PTT normal (b/c coag cascade isn’t activated)

Front 66

HUS

Back 66

endothelial damage by drugs or infection by E coli O157;H7. E coti verotoxin damages endothelial cells resulting in platelet microthrombi. Predominant renal symptoms. Skin and mucosal bleeding, MAHA, Fever. Thrombocytopenia, shear cells, increased BT, PT/PTT normal (b/c coag cascade isn’t activated)

Front 67

Bernard-Soulier syndrome

Back 67

genetic GPfb deficiency; platelet adhesion is impaired. Blood smear shows mild thrombocytopenia with enlarged platelets (immature platelets- Big Suckers)

Front 68

Glanzmann thrombasthenia

Back 68

genetic GPHb/llla deficiency; platelet aggregation is impaired.

Front 69

Congenital pyloric stenosis

Back 69

hypertrophy of the pylorus- olive mass in epigastric region, nonbilous projectile vomiting at 2-6 weeks old.

Front 70

Pleomorphic adenoma of salivary gland

Back 70

(benign mixed tumor)—most common salivary gland tumor. Presents as painless, mobile mass. Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or ruptured intraoperatively.

Front 71

Mucoepidermoid carcinoma of salivary gland

Back 71

most common malignant tumor, has mucinous and squamous components. Typically presents as painless, slow-growing mass.

Front 72

Warthin tumor of salivary gland

Back 72

(papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal centers.

Front 73

Achalasia

Back 73

Failure of relaxation of LES due to loss of myenteric (Auerbach) plexus. Bird beak. Risk of esophageal squamous cell carcinoma.

Front 74

Chagas disease

Back 74

(T. cruzi infection)- can cause achalasia

Front 75

Boerhaave syndrome

Back 75

Transmural, usually distal esophageal with pneumomediastinum (arrows) A due to violent retching; surgical emergency.

Front 76

Eosinophilic esophagitis

Back 76

Infiltration of eosinophils in the esophagus in atopic patients. Food allergens causing dysphagia,Unresponsive to GERD therapy.

Front 77

Esophageal strictures

Back 77

Associated with lye ingestion and acid reflux.

Front 78

Esophagitis

Back 78

Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane; HSV-1: punched-out ulcers; CMV: linear ulcers), or chemical ingestion.

Front 79

Mallory-Weiss syndrome

Back 79

Mucosal lacerations at the gastroesophageal junction due to severe vomiting. Leads to hematemesis. Usually found in alcoholics and bulimics.

Front 80

Plummer-Vinson syndrome

Back 80

Triad of Dysphagia, Iron deficiency anemia, and Esophageal webs. May be associated with glossitis. esophageal squamous cell carcinoma

Front 81

Sclerodermal esophageal dysmotility

Back 81

Esophageal smooth muscle atrophy leading to decreased LES pressure and dysmotility. acid reflux and dysphagia, stricture, Barrett esophagus, and aspiration. Part of CREST syndrome.

Front 82

Acute gastritis (erosive)

Back 82

Disruption of mucosal barrier--inflammation. Can be caused by: NSAIDs, PGE2. Burns (Curling ulcer). Brain injury (Cushing ulcer)—increased vagal stimulation. Increased ACh, increased H+ production

Front 83

Chronic gastritis (nonerosive)

Back 83

Type A (fundus/body)-(chronic autoimmune gastritis) Autoantibodies to parietal cells, pernicious Anemia, and Achlorhydria. Associated with other autoimmune disorders. First part of stomach (fundus/body). Type B (antrum)- (chronic H. pylori) Most common type. Caused by H. pylori in the stomach (antrum). increased risk of MALT lymphoma.

Front 84

Ménétrier disease

Back 84

Gastric hyperplasia of mucosa, hypertrophied rugae, parietal cell atrophy, increased mucous cells. Precancerous. Rugae look like brain gyri.

Front 85

Intestinal stomach cancer

Back 85

associated with H. pylori, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis. Commonly on lesser curvature; looks like ulcer with raised margins. Metastasizes to Virchow node (left supraclavicular) or Sister-mary joseph (periumbilical)

Front 86

Diffuse stomach cancer

Back 86

not associated with H. pylori; signet ring cells (mucin-filled cells with peripheral nuclei); stomach wall grossly thickened and leathery (linitis plastica). Metastasizes to Virchow node (left supraclavicular) or krunkenberg tumor (ovaries)

Front 87

Celiac disease

Back 87

Autoimmune-mediated intolerance of gliadin HLA-DQ2, HLA-DQ8, dermatitis herpetiformis, Findings: anti-endomysial, anti-tissue transglutaminase, and anti-gliadin antibodies; blunting of villi; and lymphocytes in lamina propria

Front 88

Pancreatic insufficiency

Back 88

Due to cystic fibrosis, obstructing cancer, chronic pancreatitis. Causes malabsorption of fat and fat-soluble vitamins, B12. Increased neural fat in stool

Front 89

Tropical sprue

Back 89

Similar findings as celiac sprue (affects small bowel), but responds to antibiotics.

Front 90

Whipple disease

Back 90

Infection with Tropheryma whipplei (gram positive); PAS ⊕ foamy macrophages in intestinal lamina propria, mesenteric nodes. Cardiac symptoms, Arthralgias, and Neurologic symptoms are common. Most often occurs in older men.

Front 91

Crohn Disease

Back 91

Th1, transmural inflammation. noncaseating granulomas and lymphoid aggregates.

Front 92

Ulcerative colitis

Back 92

Th2, crypt abscesses and ulcers. Sclerosing cholangitis, toxic megacolon, colorectal carcinoma. Bloody diarrhea. P-ANCA

Front 93

Zenker diverticulum

Back 93

Pharyngoesophageal false diverticulum. Herniation of mucosal tissue at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor. Presenting symptoms: dysphagia, obstruction, foul breath from trapped food particles (halitosis).

Front 94

Meckel diverticulum

Back 94

True diverticulum. Persistence of the vitelline duct. May contain ectopic acid–secreting gastric mucosa and/or pancreatic tissue.

Front 95

Intussusception

Back 95

telescoping, currant jelly stools

Front 96

Familial adenomatous polyposis (FAP)

Back 96

AD mutation of APC tumor suppressor gene on chromosome 5q. 100% progress to CRC unless colon is resected. always involves rectum.

Front 97

Gardner syndrome

Back 97

FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium, impacted/supernumerary teeth.

Front 98

Turcot syndrome

Back 98

FAP + malignant CNS tumor. Turcot = Turban.

Front 99

Peutz-Jeghers syndrome

Back 99

AD featuring numerous hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands, genitalia. Associated with risk of colorectal, breast, stomach, small bowel, and pancreatic cancers.

Front 100

Juvenile polyposis syndrome

Back 100

AD in children (typically < 5 years old) featuring numerous hamartomatous polyps in the colon, stomach, small bowel. increased risk of CRC.

Front 101

Acute mesenteric ischemia

Back 101

Critical blockage of intestinal blood flow (often embolic occlusion of SMA) small bowel necrosis, abdominal pain out of proportion to physical findings. May see red “currant jelly” stools.

Front 102

Adhesion Fibrous

Back 102

band of scar tissue; commonly forms after surgery; most common cause of small bowel obstruction. Can have well-demarcated necrotic zones.

Front 103

Angiodysplasia

Back 103

Tortuous dilation of vessels hematochezia. Most often found in cecum, terminal ileum, ascending colon. More common in older patients. Confirmed by angiography.

Front 104

Duodenal atresia

Back 104

Causes early bilious vomiting with proximal stomach distention (“double bubble” on X-ray) because of failure of small bowel recanalization. Associated with Down syndrome.

Front 105

Ileus

Back 105

Intestinal hypomotility without obstruction. constipation and flatus; decreased abdomen with bowel sounds. Associated with abdominal surgeries, opiates, hypokalemia, sepsis.

Front 106

Ischemic colitis

Back 106

Reduction in intestinal blood flow causes ischemia. Pain after eating weight loss. Commonly occurs at watershed areas (splenic flexure, distal colon). Typically affects elderly.

Front 107

Meconium ileus

Back 107

In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth.

Front 108

Necrotizing enterocolitis

Back 108

Seen in premature, formula-fed infants with immature immune system. Necrosis of intestinal mucosa (primarily colonic) with possible perforation.

Front 109

Reye syndrome

Back 109

Rare, often fatal childhood hepatic encephalopathy. Findings: mitochondrial damage, fatty liver (microvesicular fatty change), hypoglycemia, vomiting, hepatomegaly, coma. Associated with viral infection (especially VZV and influenza B) that has been treated with aspirin. Decreased beta- oxidation

Front 110

Hepatic steatosis

Back 110

Macrovesicular fatty change

Front 111

Alcoholic hepatitis

Back 111

requires sustained, long-term consumption. Swollen and necrotic hepatocytes with neutrophilic infiltration. Mallory bodies (intracytoplasmic eosinophilic inclusions of damaged keratin filaments)

Front 112

Alcoholic cirrhosis

Back 112

Final and irreversible form. Micronodular, irregularly shrunken liver. Sclerosis around central vein (zone III). Mediator= stellate cells. TGF-beta

Front 113

Hepatocellular carcinoma/hepatoma

Back 113

Most common 1° malignant tumor of liver in adults. Associated with HBV, all other causes of cirrhosis (including HCV, alcoholic and non-alcoholic fatty liver disease, autoimmune disease, hemochromatosis, α1-antitrypsin deficiency, Wilson disease) and aflatoxin from Aspergillus. May lead to Budd-Chiari syndrome. Alpha- fetoprotein.

Front 114

Cavernous hemangioma

Back 114

Common, benign liver tumor; typically occurs at age 30–50 years. Biopsy contraindicated because of risk of hemorrhage.

Front 115

Hepatic adenoma

Back 115

Rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use

Front 116

Angiosarcoma

Back 116

Malignant tumor of endothelial origin; associated with exposure to arsenic, vinyl chloride.

Front 117

Budd-Chiari syndrome

Back 117

Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis-- congestive liver disease (hepatomegaly, varices, abdominal pain, eventual liver failure). Absence of JVD. Associated with hypercoagulable states, polycythemia vera, postpartum state, HCC. May cause nutmeg liver (mottled appearance).

Front 118

α1-antitrypsin deficiency

Back 118

Misfolded gene product protein aggregates in hepatocellular ER cirrhosis with PAS+ globules in liver. Codominant trait. In lungs, increased α1-antitrypsin--uninhibited elastase in alveoli-- decreased elastic tissue—Panacinar emphysema

Front 119

Physiologic neonatal jaundice

Back 119

At birth, immature UDP-glucuronosyltransferase --unconjugated hyperbilirubinemia-- jaundice/ kernicterus (bilirubin deposition in brain, particularly basal ganglia). Tx: Phototherapy- unconjugated bilirubin to water-soluble form).

Front 120

Gilbert syndrome

Back 120

Mildly decreased UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake. Seen during fasting/ stress.

Front 121

Crigler-Najjar syndrome, type I

Back 121

Absent UDP-glucuronosyltransferase. Presents early in life; patients die within a few years. Findings: jaundice, kernicterus (bilirubin deposition in brain), increased unconjugated bilirubin.

Front 122

Dubin-Johnson syndrome

Back 122

Conjugated hyperbilirubinemia due to defective liver excretion. Grossly black liver. Benign.

Front 123

Rotor syndrome

Back 123

is similar but even milder than Dubin-Johnson and does not cause black liver.

Front 124

Wilson disease

Back 124

hepatolenticular degeneration.Inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmin. Leads to copper accumulation, In kidneys- Fanconi syndrome, and joints. AR chromosome 13. Copper normally excreted into bile by hepatocyte copper transporting ATPase (ATP7B gene). Treatment includes chelation with penicillamine or trientine, oral zinc. Decreased ceruloplasmin, cirrhosis, corneal deposits (Kayser-Fleischer rings), hemolytic anemia, asterixis, dementia, dyskinesia, dysarthria.

Front 125

Hemochromatosis

Back 125

Hemosiderosis is the deposition of hemosiderin (iron), which stains blue; hemochromatosis is the disease caused by this iron deposition. Classic triad of micronodular cirrhosis, Diabetes mellitus, and skin pigmentation—“bronze” diabetes. Heart failure, testicular atrophy, increased HCC. HFE gene.

Front 126

Secondary biliary cirrhosis

Back 126

Extrahepatic biliary obstruction pressure in intrahepatic ducts---injury/ fibrosis and bile stasis. Patients with known obstructive lesions (gallstones, biliary strictures, pancreatic carcinoma). May be complicated by ascending cholangitis.

Front 127

Primary biliary cirrhosis

Back 127

Autoimmune reaction--lymphocytic infiltrate + granuloma—destruction of intralobular bile ducts. Classically in middle-aged women. Anti-mitochondrial antibody+, including IgM. autoimmune conditions

Front 128

Primary sclerosing cholangitis

Back 128

Unknown cause of concentric “onion skin” bile duct fibrosis alternating strictures and dilation with “beading” of intra- and extrahepatic bile ducts. young men with IBD. Hypergammaglobulinemia (IgM). MPO-ANCA/p- ANCA+. Associated with ulcerative colitis. Cholangiocarcinoma.

Front 129

Cholecystitis

Back 129

Acute or chronic inflammation of gallbladder. Usually from cholelithiasis (gallstones). Increased ALP.

Front 130

Porcelain gallbladder

Back 130

calcified gallbladder due to chronic cholecystitis. Treatment: prophylactic cholecystectomy due to high rates of gallbladder carcinoma.

Front 131

Acute pancreatitis

Back 131

Autodigestion of pancreas by pancreatic enzymes. Labs: amylase, lipase (higher specificity). Can lead to DIC, ARDS, diffuse fat necrosis, hypocalcemia (Ca2+ collects in pancreatic Ca2+ soap deposits), pseudocyst formation (granulation tissue, not epithelium).

Front 132

Chronic pancreatitis

Back 132

Chronic inflammation, atrophy, calcification of the pancreas. Major causes are alcohol abuse and idiopathic, cystic fibrosis. Can cause chronic pancreatic insufficiency.

Front 133

HEMOPHILIA A

Back 133

X-linked recessive, de novo usually though. Factor 8 deficiency. deep tissue, joint, and postsurgical bleeding, increased PTT; normal PT. Tx: reecombinant FVIII.

Front 134

HEMOPHILIA B (CHRISTMAS DISEASE)

Back 134

Factor 9 deficiency. Same presentation as Hemophilia A.

Front 135

COAGULATION FACTOR INHIBITOR

Back 135

Acquired antibody against a coagulation factor resulting in impaired factor function. Usually anti- Factor 8. Presents like hemophilia A but PTT does not correct upon mixing study

Front 136

VON W1LLEBRAND DISEASE

Back 136

Genetic vWF deficiency- most common inherited coagulation disorder. Mild mucosal and skin bleeding; low vWF impairs platelet adhesion--- Increased bleed time. Isn’t there to stabilize Factor 8- increased PTT. Abnormal ristocetin- makes platelets aggregate. Tx: Desmopressin--- increases release of vWF from Weibel Palade bodies from endothelial cells.

Front 137

VITAMIN K DEFICIENCY

Back 137

Vitamin K is activated by epoxide reductase in the liver. Activated vitamin K gamma carboxvlates Factors 2, 7, 9, 10, and proteins C and S; gamma carboxylation is necessary for factor function.

Front 138

HEPARIN-INDUCED THROMBOCYTOPENIA

Back 138

Ab formation against the heparin- platelet factor 4 complex that forms-- platelet destruction – thrombocytopenia. Worried about fragments of destroyed platelets may activate remaining platelets, leading to thrombosis. Don’t give warfarin b/c can get Warfarin skin necrosis!!

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DISSEMINATED INTRAVASCULAR COAGULATION

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Pathologic activation of the coagulation cascade. Microthrombi+ consumption of platelets and factors results in bleeding, especially from IV sites and mucosal surfaces. ALWAYS secondary to something (Obstetric complications—Tissue thromboplastin in the amniotic fluid, Sepsis (especially with E.Coli or N meningitidis)—Endotoxins from the bacterialwall and cytokines (e.g., TNF and IL-1) induce endothelial cells to make tissue factor, Adenocarcinoma—Mucin activates coagulation, Acute promyelocytic leukemia—Primary granules (auer rods) activate coagulation, Rattlesnake bite—Venom activates coagulation. MAHA, increased D-Dimer!! (decreased platelets, increased PT/PTT)

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Disorders of fibrinolysis

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radical prostectomy- urokinase activates plasmin, Cirrhosis of'liver—reduced production of a2-antiplasmin. Looks like DIC but NO D-DIMER!!

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Cystathionine beta synthase (CBS) deficiency

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results in high homocysteine levels with homocystinuria,. CBS converts homocysteine to cystathionine; enzyme deficiency leads to homocysteine buildup. Sx: vessel thrombosis, mental retardation, lens dislocation, and long slender fingers.

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Protein C or S deficiency

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AD decreases negative feedback on the coagulation cascade. Proteins C and S normally inactivate factors V and VIII. Increased risk for warfarin skin necrosis

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Factor V Leiden

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Mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S. Most common inherited cause of hypercoagulable state

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Prothrombin 20210A

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Point mutation in prothrombin that results in increased gene expression, increased thrombin, promoting thrombus formation.

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ATIII deficiency

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decreases the protective effect of heparin-like molecules produced by the endothelium, increasing the risk for thrombus. In AT3 deficiency- PTT does not rise with standard heparin dosing b/c heparin binds to AT3

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Lead poisoning

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Lead inhibits ferrochelatase and ALA dehydratase, decreased heme synthesis and but increased protoporphyrin. Also inhibits rRNA degradation---basophilic stippling. Sx: (LEAD) Lead Lines on gingivae (Burton lines) and on metaphyses of long bones. Encephalopathy and Erythrocyte basophilic stippling. Abdominal colic and sideroblastic Anemia. Wrist and foot Drop. Tx: Dimercaprol and EDTA. Succimer used for chelation

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Sideroblastic anemia

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Defect in heme synthesis. Hereditary: X-linked defect in δ-ALA synthasegene. Acquired: deficiency, copper deficiency, isoniazid. Ringed sideroblasts (Prussian blue–stained mitochondria) myelodysplastic syndromes, alcohol is most common, also lead, vitamin B6 seen in bone marrow. Increased iron, decreased TIBC, increased ferritin.

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Orotic aciduria

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AR Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase. Sx: failure to thrive, developmental delay, and megaloblastic anemia refractory to folate and B12. No hyperammonemia.

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Intravascular hemolysis

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Findings: decreased haptoglobin, increased LDH, schistocytes and increased reticulocytes on blood smear. Characteristic hemoglobinuria, hemosiderinuria, and urobilinogen in urine. Notable causes are mechanical hemolysis (e.g., prosthetic valve), paroxysmal nocturnal hemoglobinuria, MAHA. MANY CAUSES

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Extravascular hemolysis

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Findings: macrophages in spleen clear RBCs. Spherocytes in peripheral smear, increased LDH, no hemoglobinuria/hemosiderinuria, increased unconjugated bilirubin, which can cause jaundice. MANY CAUSES

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Anemia of chronic disease

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Inflammation increases hepcidin (Acute Phase reactant- released by liver) binds ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport. Decreased iron, decreased TIBC, increased ferritin, decreased EPO production, increased FEP.

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Aplastic anemia

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Caused by failure or destruction of myeloid stem cells due to: radiation and drugs, viral agents (parvovirus B19, EBV, HIV, HCV), Fanconi anemia (DNA repair defect), Idiopathic.

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Hereditary spherocytosis (E)

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Defect in proteins interacting with RBC membrane skeleton and plasma membrane (e.g., ankyrin, band 3, protein 4.2, spectrin). small, round RBCs with less surface area and no central pallor (increased MCHC, increased red cell distribution width)--premature removal by spleen. Splenomegaly, aplastic crisis (parvovirus B19 infection). Labs: osmotic fragility test +. Treatment: splenectomy.

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G6PD deficiency (I/E)

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X-linked recessive. Defect in G6PD-- decreased. Hemolytic anemia following oxidant stress (e.g., sulfa drugs, antimalarials, infections, fava beans).

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Pyruvate kinase deficiency (E)

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AR. Defect in pyruvate kinase- decreased ATP-- rigid RBCs.

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HbC defect (E)

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Glutamic acid–to-lysine mutation in β-globin. HbC crystals

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Paroxysmal nocturnal hemoglobinuria (I)

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complement-mediated RBC lysis- lack of GPI anchor for decay-accelerating factor (DAF and MIRL) that protects RBC membrane from complement). Mild acidosis during sleep causes complement activation and hemolysis. Coombs negative. Hemolytic anemia, pancytopenia, venous thrombosis. CD55/59 negative (DAF/ MIRL). Tx: Eculizumab.

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Sickle Cell Complications

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Aplastic crisis (due to parvovirus B19).Autosplenectomy (Howell- Jolly bodies), risk of infection by encapsulated organisms, Splenic infarct/sequestration crisis, Salmonella osteomyelitis, Painful crises (vaso-occlusive): dactylitis, acute chest syndrome, avascular necrosis, stroke.Renal papillary necrosis (decreased Po2 in papilla) and microhematuria (medullary infarcts).

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Autoimmune hemolytic anemia

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Warm agglutinin (IgG)—chronic anemia seen in SLE and CLL and with certain drugs (e.g., α-methyldopa) (“warm weather is Great”). Cold agglutinin (IgM)—acute anemia triggered by cold; seen in CLL, Mycoplasma pneumonia infections, and infectious Mononucleosis (“cold weather is MMMiserable”). Many warm and cold AIHAs are idiopathic in etiology.

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Acute intermittent porphyria

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Porphobilinogen deaminase deficiency. Increased Porphobilinogen, δ-ALA, coporphobilinogen (urine). Symptoms: Painful abdomen, Port wine–colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs (e.g., cytochrome P-450 inducers), alcohol, starvation. Treatment: glucose and heme, which inhibit ALA synthase.

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Porphyria cutanea tarda

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Uroporphyrinogen decarboxylase def. Uroporphyrin (teacolored urine) Blistering cutaneous photosensitivity. Most common porphyria

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Iron poisoning

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High mortality rate with accidental ingestion by children (adult iron tablets may look like candy). Cell death due to peroxidation of membrane lipids. SYM PTOMS /SIGNS Nausea, vomiting, gastric bleeding, lethargy, scarring leading to GI obstruction. TREATMENT Chelation (e.g., IV deferoxamine, oral deferasirox) and dialysis.

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Bernard-Soulier syndrome

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Defect in adhesion Large platelets. decreased GpIb-- defect in platelet adhesion. No agglutination on ristocetin cofactor assay.

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Glanzmann thrombasthenia

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Defect in aggregation GpIIb/IIIa deficiency-- defect in platelet-to-platelet aggregation. Labs: blood smear shows no platelet clumping. Agglutination with ristocetin cofactor assay.

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Immune thrombocytopenia

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Anti-GpIIb/IIIa antibodies (IgG)-- splenic macrophage consumption of platelet‑antibody complex. Commonly due to viral illness. Labs: increased megakaryocytes on bone marrow biopsy. Treatment: steroids, intravenous immunoglobulin.

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Thrombotic thrombocytopenic purpura

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Deficiency of ADAMTS 13 (vWF metalloprotease) Which cleaves vWF multimers. Pathogenesis: large vWF multimers— increased platelet adhesion—increased platelet aggregation and thrombosis. Labs: schistocytes, increased LDH, normal bleeding time. Symptoms: pentad of neurologic, fever, thrombocytopenia, and microangiopathic hemolytic anemia. Treatment: plasmapheresis, steroids.

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Hemolytic uremic syndrome

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predominant in the kidneys. Caused by infection of E. coli O157:H7. Produces verotoxin—damages endothelial cells—decreased ADAMTS13+ microthrombi, MAHA.

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von Willebrand disease

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AD. decreased vWF- not platelet adhesion. Increased PTT b/c vWF acts to carry/protect factor VIII. Mild but most common inherited bleeding disorder. Diagnosed in most cases by ristocetin cofactor assay (decreased agglutination is diagnostic). Treatment: desmopressin, which releases vWF stored in endothelium.

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Hodgkin’s Lymphoma

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Reed-Sternberg cells. “owl eyes”. RS cells are CD 20-, CD15+ and CD30+ B-cell origin. Subtypes: nodular sclerosing, lymphocyte rich, lymphocyte poor, mixed. Better prognosis with reaction against RS cells. Nodular sclerosing form most. Lymphocyte-rich form has best prognosis. Lymphocyte mixed or depleted forms have worse prognosis.

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Burkitt lymphoma

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Mature B cell Non-Hodgkins lymphoma t(8;14)—translocation of c-myc (8) and heavy-chain Ig (14)“Starry sky” appearance. Associated with EBV. Jaw lesion B in endemic form in Africa; pelvis or abdomen in sporadic form.

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Diffuse large B-cell lymphoma

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Mature B cell Non-Hodgkins lymphoma Usually older adults, Most common type of non-Hodgkin lymphomain adults. Can transform from follicular

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Follicular lymphoma

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Mature B cell Non-Hodgkins lymphoma Adults t(14;18)—translocation of heavy-chain Ig (14) and BCL-2 (18) Indolent course; Bcl-2 inhibits apoptosis. Presents with painless “waxing and waning. Lymphadenopathy. CD20+, no normal architecture, no macrophages. Tx: Rituximab.

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Mantle cell lymphoma

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Mature B cell Non-Hodgkins lymphoma Older males t(11;14)—translocation of cyclin D1 (11) and heavy-chain Ig (14). CD5+

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Marginal zone

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Mature B cell Non-Hodgkins lymphoma. Chronic inflammation- Hashimoto’s thyroiditis, sjogren, h. pylori-- MALToma

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Adult T-cell lymphoma

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Mature T cell lymphoma. Adults Caused by HTLV1 (IV drugs). Adults present with cutaneous lesions; especially affects populations in Japan, West Africa, and the Caribbean. Lytic bone lesions, hypercalcemia.

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Mycosis fungoides/ Sézary syndrome

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Mature T cell lymphoma. Adults. Skin patches/ plaques (cutaneous T-cell lymphoma),characterized by atypical CD4+ cells with “cerebriform” nuclei. May progress to Sezary syndrome (T-cell leukemia).

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Multiple myeloma

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Monoclonal plasma cell (“fried egg”appearance) cancer, increased susceptibility to infection. Primary amyloidosis (AL). Punched-out lytic bone lesions on x-ray, M spike on SPEP, Ig light chains in urine (Bence Jones protein). Rouleaux formation, Numerous plasma cells C with “clock‑face” CRAB- Hypercalcemia, renal insufficiency, anemia, bone lytic lesions, Back pain.

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Waldenström macroglobulinemia

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M spike = IgM. hyperviscosity syndrome (e.g., blurred vision, Raynaud phenomenon); no “CRAB”findings

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Monoclonal gammopathy of undetermined significance (MGUS)

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monoclonal expansion of plasma cells, asymptomatic, may lead to multiple myeloma. No “CRAB” findings.

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Acute lymphoblastic leukemia/lymphoma (ALL)

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B or T >20% blasts. Age: < 15 years. T-cell ALL can present as mediastinal mass (presenting as SVC-like syndrome). Associated with Down syndrome. TdT+ (marker of pre-T and pre-B cells), CD10+, 19+, 20+ (pre-B cells only). May spread to CNS and testes. t(12;21) better prognosis. T(9;22)- worse prognosis.

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Small lymphocytic lymphoma (SLL)/ chronic lymphocytic leukemia (CLL)

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Naïve B cells CD5+, CD20+. Adults. Smudge cells. Often asymptomatic, progresses slowly; autoimmune hemolytic anemia. SLL same as CLL except CLL has increased peripheral blood lymphocytosis or bone marrow involvement.

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Hairy cell leukemia

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Mature B-cell tumor in the elderly. Marrow fibrosis-- dry tap on aspiration. TRAP+ (tartrate-resistant acid phosphatase). Splenomegaly due to red pulp sequestration (instead of white pulp) Treatment: cladribine, pentostatin

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Acute myelogenous leukemia (AML)

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Auer rods; MPO+. Adults. AML; increased circulating myeloblasts on peripheral smear. Risk factors: prior exposure to alkylating chemotherapy, radiation, myeloproliferative disorders, Down syndrome. t(15;17)= M3 AML subtype responds to all-trans retinoic acid (vitamin A), inducing differentiation of myeloblasts; DIC is a common presentation.

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Chronic myelogenous leukemia (CML)

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Elderly 64 years. Defined by the Philadelphia chromosome (t[9;22], BCR-ABL) tyrosine kinase activity; myeloid stem cell proliferation; presents with increased neutrophils, metamyelocytes, basophils ; transformation to AML or ALL“blast crisis”. Very low Alk phos (LAP) as a result of low activity in mature granulocytes (vs. leukemoid reaction, in which LAP is INCREASED). Tx: imatinib.

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Langerhans cell histiocytosis

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Dendritic (Langerhans) cells. Presents in a child as lytic bone lesions (present with bone fracture) and skin rash or as recurrent otitis media with a mass involving the mastoid bone. Do not effectively stimulate primary T cells via antigen presentation. Cells express S-100 (mesodermal origin) and CD1a. Birbeck granules (“tennis rackets” or rod shaped on EM) are characteristic. Subtype: Letterer-Siwe (Malignant <2 y.o.), Eosinophilic granuloma (benign). Hand-Schuller- Christian Disease (Malignant >3 y.o.).

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Polycythemia vera

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Disorder of increased hematocrit, JAK2 mutation. May present as intense itching after hot shower (due to increased basophils). Erythromelalgia (severe, burning pain and red-blue coloration) due to episodic blood clots in vessels of the extremities. Decreased EPO

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Essential thrombocytosis

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Overproduction of abnormal platelets-- bleeding, thrombosis. Enlarged megakaryocytes

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Myelofibrosis

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Obliteration of bone marrow due to increasd fibroblast activity, increased megakaryocytes—PDGF—marrow fibrosis. Teardrop RBCs, massive splenomegaly.

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Leukocyte adhesion deficiency

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AR; defect of integrins (CD18 suhunit). Clinical features include delayed separation of the umbilical cord (no blood-ischemia- neutrophils come in to get rid of it), increased circulating neutrophils (due to impaired adhesion of marginated pool in lungs of leukocytes), and recurrent bacterial infections that lack pus formation.. Increased neutrphil count due to loss of margination attachments

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Chediak-Higashi syndrome

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AR microtubule deficiency- impaired phagolysosome formation. Can’t bring phagosome to lysosome. Sx: Increased risk of pyogenic infections, neutropenia (neutrophils can’t divide propery), giant granules in leukocytes (pile up near b/c can’t move Golgi apparatus), defective primary hemostasia (platelet granules pile up), albinism (melanin isn’t handed-off), peripheral neuropathy (can’t move NT)

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Chronic granulomatous disease (CGD)

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X-linked or AR; no O.-dependent killing due to NADPH oxidase defect. Leads to recurrent infection and granuloma formation with catalase-positive organisms, particularly (S. aureus, Pseudpmonas cepacia, Serratia marcescens, Nocardia, and Aspergillus)**. Nitroblue tetrazolium test remains colorless.

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MPO deficiency

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Can’t produce bleach, can’t convert H2O2 to HOCl; usually asymptomatic, but increased risk for Candida infections; NBT is normal, respiratory burst is intact.

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DIGEORGE SYNDROME

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No 3rd and 4th pharyngeal pouches; 22qll microdeletion; Presents with T-cell deficiency {lack of thymus); hypocalcemia (lack of parathyroids); and abnormalities of heart, great vessels, and face

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SEVERE COMBINED IMMUNODEFICIENCY (SCID)

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Defective cell-mediated and humoral immunity No T and B cells; Etiologies: Adenosine deaminase (ADA) deficiency—ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products; buildup of adenosine and deoxyadenosine is toxic to lymphocytes. Cytokine receptor defects—Cytokine signaling is necessary for proliferation and maturation of B and Tcells , MHC class II deficiency—M HC class II is necessary for CD4+ helper T cell activation and cytokine production. Sx fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines

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X-UNKED AGAMMAGLOBULINEMIA

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X-linked . Lack of immunoglobulin due naive B cells cannot mature to plasma cells. Due to mutated Bruton tyrosine kinase; after 6 months of life with recurrent bacterial, enterovirus (e.g., polio and coxsackievirus), and Giardia lamblia infections (no IgA= mucosal infection with enterovirus, giardia)

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COMMON VARIABLE IMMUNODEFICIENCY (CVID)

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Low immunoglobulin due to B-cell or helper T-cell defects; Increased risk for bacteria], enterovirus, and Giardia lamblia infections, usually in late childhood. Increased risk for autoimmune disease and lymphoma

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IgA DEFICIENCY

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Low serum and mucosal IgA; most common immunoglobulin deficiency, increased risk tor mucosal infection, especially viral

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HYPER-lgM SYNDROME

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Characterized by elevated IgM; Due to mutated CD40L (on helper T cells) or CD40 receptor (on B cells)—can’t class switch; Low IgA, IgG, and IgE result in recurrent pyogenic infections (due to poor opsonization/ IgG), especially at mucosal sites.

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WISKOTT-ALDRICH SYNDROME

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; X-linked. Characterized by thrombocytopenia, eczema, and recurrent infections {defective humoral and cellular immunity); due to mutation in the WASP gene. B (pyogenic organisms- n. meningitidis, h. flu, s. pneumoniae) and T (PCP, herpesviridae) lymphocyte disorder. Tx: bone marrow transplant

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C5-C9 deficiencies

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Increased risk for Neisseria infection (Ngonorrhoeae and N meningitidis)

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CI inhibitor deficiency

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overactivation of complement-results in hereditary angioedema, which is characterized by edema of the skin (especially periorbital and mucosal surfaces

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Autoimmune polyendocrine syndrome

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AIRE mutation- allows self-reactive T cells to escape: hypoparathyroid, adrenal failure, candida infection.

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Autoimmune lymphoproliferative syndrome

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Fas apoptosis pathway mutation. Causes survival of self-reactive lymphocytes (due to lack of peripheral tolerance); Sx: anemia, thrombocytopenia, lymphadenopathy, hepatosplenomegaly. Risk for lymphoma

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IPEX syndrome

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Immune dysregulation, polyendocrinopathy, Enteropathy, X-linked

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SLE

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Type III (antigen-antibody complex) hypersensitivity. Complement components are used up. Abs directed against self-nuclear material; Fever and weight loss; Malar 'butterfly' rash/ discoid rash- circular, erythematous with scarring; oral/ nasopharyngeal ulcers; Arthritis; Pleuritis and pericarditis (involvement of serosal surfaces); CNS psychosis/ seizures; Renal damage—Diffuse proliferative glomerulonephritis, membranous glomerulonephritis; Endocarditis, myocarditis, or pericarditis (can affect any 1 aver of the heart); Libman-Sacks endocarditis (small vegetations on both sides of valve); Anemia, thrombocytopenia, or leukopenia (HSR2). Anit-d.s.DNA and anti-smith (speficic), ANA. (Anti-d.s.DNA prognosis and active disease). Antiphospholipid Ab (anticardiolipin- false VDRL/RPR, lupus anticoagulant- false PTT elevation, anti-Beta2-glycoprotein 1)

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Antiphospholipid syndrome

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Autoantibody against proteins bound to phospholipids, hypercoaguable state. Results in arterial and venous thrombosis including deep venous thrombosis, hepatic vein thrombosis, placental thrombosis (recurrent pregnancy loss), and stroke. Requires lifelong anticoagulation

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Sjogren syndrome

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autoimmune destruction of lacrimal and salivary glands. Lymphocytic sialadenitis (salivary gland biopsy). Most commonly associated with RA. RF positive. ANA. Anti-ribonucleoprotein (Anti-SSA (Ro), and Anti-SSD (La)). Anti-SSA can cross placenta and cause neonatal lupus and congenital heart block**. Increased risk for B-cell lymphoma (of parotid glands)

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Scleroderma

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autoimmune destruction of mesenchyme. CREST- limited type. Calcinosis, Anti-Centromere abs**, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangectasias. Diffuse type- early visceral involvement: vessels, interstitial fibrosis of lung, kidneys- sclerodema and renal crisis) Anti-DNA topoisomerase 1 (anti-Scl-70)**

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MIXED CONNECTIVE TISSUE DISEASE

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Autoimmune-mediated tissue damage with mixed features of SLE, systemic sclerosis, and polymyositis. Abs against U1 ribonucleoprotein** and ANA

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Cushing syndrome

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increased cortisol due to a variety of causes; Hypertension, weight gain, moon facies, truncal obesity A , buffalo hump, skin changes (thinning, striae), osteoporosis, hyperglycemia (insulin resistance), amenorrhea, immunosuppression.

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Trousseau syndrome

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tumor associated release of procoagulants- thought to be responsible for migratory thrombophlebitis in disseminated cancers.

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Achondroplasia

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activating mutation of FGFR3. Turns on- inhibits cartilage growth/ proliferation.

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Osteopetrosis (marble bone disease)

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Failure of normal bone resorption due to defective osteoclasts. Thickened, dense fracture easily. Bone fills marrow space--pancytopenia, extramedullary hematopoiesis. Often b/c of carbonic anhydrase II mutation- osteoclast can’t generate acidic environment necessary for bone resorption. Can result in cranial nerve impingement, renal tubular acidosis (b/c of decreased carbonic anhydrase).

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Osteomalacia/rickets

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Vitamin D deficiency. osteomalacia in adults; rickets in children. Due to defective mineralization/calcification of osteoid. soft bones that bow out. Hyperactivity of osteoblasts means increased ALP (osteoblasts require alkaline environment). Kids- pigeon breasting, frontal bossing, Rosary ribs, bowing of legs. Adults- weak bone

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Paget Disease

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increased Alk phos only. Sporadic bones. Hearing loss, lion-like facies, hat size changes. Mosaic pattern- sclerotic and woven bone. Tx: calcitonin and bisphosphonates- inhibits OC function. Can cause AV shunts in bone (high output cardiac failure) and osteosarcoma.

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Casseon’s disease

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gaseous emboli

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Osteoporosis

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no change in serum markers. Trabecular (spongy) bone loss- porous

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Osteitis fibrosa cystica

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due to primary or secondary hyperparathyroidism“Brown tumors” due to fibrous replacement of bone, subperiosteal thinning. Secondary- Often as compensation for ESRD (decreased PO4 excretion and decreased production of activated vitamin D)

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Osteomyelitis

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infection

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Giant cell tumor of bone

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Epiphyseal end of long bones (usually knee) benign. “Osteoclastoma.””Soap bubble” appearance. Multinucleated giant cells.

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Osteochondroma

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Most common benign tumor. Lateral projection of metaphysis. Mature bone with cartilaginous (chondroid) cap.

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Osteosarcoma

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2nd most common 1° malignant bone tumor (after multiple myeloma). Bimodal distribution. Predisposing factors: Paget disease of bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome. Metaphysis of long bones, often around knee. Codman triangle (lesion drags periosteum off bone) or hazy sunburst pattern on x-ray. Aggressive. Large pleomorphic cells, lots of w/ lots of pink osteoid.

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Ewing sarcoma

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Boys < 15 years old. Neuroectoderm. Diaphysis of long bones inside medulla. Anaplastic small blue cell malignant tumor. “Onion skin” layering of periosteum. Associated with t(11;22) translocation causing fusion protein EWS-FLI 1.

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Chondrosarcoma

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cartilaginous tumor. Arise in medulla of axial skeleton/ pelvis.

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Rheumatoid arthritis

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spares DIPs. RF positive- anti Fc portion of IgG), MORE SPECIFIC- anti- CCP. HLA-DR4. Synovitis with pannus formation and granulation tissue. Pannus have blood vessels, fibroblasts, myofibroblasts.

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Sjogren’s syndrome

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Anti-nuclear abs. SS-A (anti-Ro) and SS-B (anti-La). Ab destruction of exocrine glands. Parotid gland enlargement.

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Infectious arthritis

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S. aureus, strep, n. gonnorhea (migratory arthritis). Single joint. Increased ESR. Treat quickly.

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Psoriatic arthritis

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Seronegative Spondyloarthropathies HLA-B27 + (MHC 1). Joint pain and stiffness associated with psoriasis. Dactylitis (“sausage fingers”), “pencil-in-cup” deformity on x-ray B . Axial and peripheral joints- DIP

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Ankylosing spondylitis

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Seronegative Spondyloarthropathies HLA-B27 + (MHC 1). Chronic inflammatory disease of spine and sacroiliac joints ankylosis (stiff spine due to fusion of joints), uveitis-, redness of eye, blurry vision, aoritis-weakening of aortic walls- aortic regurgitation.

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Inflammatory bowel disease

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Seronegative Spondyloarthropathies HLA-B27 + (MHC 1). Crohn disease and ulcerative colitis are often accompanied by ankylosing spondylitis or peripheral arthritis.

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Reactive arthritis (Reiter syndrome)

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Seronegative Spondyloarthropathies HLA-B27 + (MHC 1). Classic triad. Conjunctivitis and anterior uveitis, Urethritis, Arthritis “Can’t see, can’t pee, can’t bend my knee.” Post-GI (Shigella, Salmonella, Yersinia, Campylobacter) or Chlamydia infections.

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Systemic lupus erythematosus

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Rash (malar A or discoid), Arthritis, Soft tissues/serositis, Hematologic disorders (e.g., cytopenias), Oral/nasopharyngeal ulcers, Renal disease, Raynaud phenomenon, Photosensitivity, Positive VDRL/RPR. Antinuclear antibodies, Immunosuppressants, Neurologic disorders (e.g. seizures, psychosis). Antinuclear antibodies (ANA)- Sensitive, not specific; Anti-dsDNA antibodies- Specific, poor prognosis (renal disease); Anti-Smith antibodies- Specific, not prognostic (directed against snRNPs); Antihistone antibodies- Sensitive for drug-induced lupus; decreased C3, C4, due to immune complex formation.

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Antiphospholipid syndrome

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1° or 2° autoimmune disorder (most commonly in SLE). Sx: history of thrombosis (arterial or venous) or spontaneous abortion along. Labs: lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein antibodies. Treat with systemic anticoagulation. Anticardiolipin antibodies and lupus anticoagulant can cause false-positive VDRL and prolonged PTT.

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Sarcoidosis

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Immune-mediated, widespread noncaseating granulomas, elevated serum ACE level and increased hypercalcemia, and elevated CD4+/CD8+ ratio. Often asymptomatic except for enlarged lymph nodes. CT: extensive hilar and mediastinal adenopathy. Associated with restrictive lung disease (interstitial fibrosis), erythema nodosum, lupus pernio, Bell palsy, epithelioid granulomas containing microscopic Schaumann and asteroid bodies, uveitis, hypercalcemia (due to increased 1α-hydroxylase–mediated vitamin D activation in macrophages)

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Polymyalgia rheumatic

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Pain and stiffness in shoulders and hips, often with fever, malaise, weight loss. Does not cause muscular weakness. Associated with temporal (giant cell) arteritis. Increased ESR, increased CRP, normal CK. Tx: steroids

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Polymyositis

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increased CK, ANA+, + anti-Jo-1, + anti-SRP, + anti-Mi-2 antibodies. characterized by endomysial inflammation with CD8+ T cells. Only muscles Progressive symmetric proximal muscle weakness

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Dermatomyositis

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increased CK, ANA+, + anti-Jo-1, + anti-SRP, + anti-Mi-2 antibodies. Perimysial inflammation and atrophy with CD4+ T cells. Muscles+ skin. Similar to polymyositis, but also involves malar rash (similar to SLE), Gottron papules, heliotrope (erythematous periorbital) rash- rash on upper eyelids, “shawl and face” rash. “mechanic’s hands.”associated with underlying gastric cancer.

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Myasthenia gravis

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Autoantibodies to postsynaptic ACh receptor. Ptosis, diplopia, weakness. Worsens with muscle use. ASSOCIATED WITH Thymoma, thymic hyperplasia. Tensilon test (AChEi= better)

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Lambert-Eaton myasthenic syndrome

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Autoantibodies to presynaptic Ca2+ channel. Decreased ACh release. Proximal muscle weakness, autonomic symptoms (dry mouth, impotence) Improves with muscle use. ASSOCIATED WITH Small cell lung cancer

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X-linked muscular dystrophy (Duchenne/ Becker)

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replacement of skeletal muscle with fat. Dystrophin gene (largest gene in body). Increased creatinine kinase

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Scleroderma (Diffuse)

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Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis. widespread skin involvement, rapid progression, early visceral involvement. Associated with anti- Scl-70 antibody (anti-DNA topoisomerase I antibody).

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Scleroderma (Limited)

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Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis. limited skin involvement confined to fingers and face. Also with CREST involvement: Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. Associated with anti-centromere antibody.

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Molluscum contagiosum

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Umbilicated papules caused by a poxvirus. While frequently seen in children, it may be sexually transmitted in adults.

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Hairy leukoplakia

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Irregular, white, painless plaques on tongue that cannot be scraped off. EBV mediated. Immunocompromised. Not thrush (scrapable) and leukoplakia (precancerous).

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Pemphigus vulgaris

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HSR2. IgG antibody against desmoglein (component of desmosomes). Flaccid intraepidermal bullae caused by acantholysis (keratinocytes in stratum spinosum are connected by desmosomes); oral mucosa also involved. Immunofluorescence- tombstone appearance, reticular (net-like) pattern. Positive Nikolsky sign (separation of epidermis upon manual stroking of skin).

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Bullous pemphigoid

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Less severe than pemphigus vulgaris. IgG antibody against hemidesmosomes (epidermal basement membrane; antibodies are “bullow” the epidermis). Tense blisters containing eosinophils affect skin but NOT oral mucosa. Immunofluorescence- linear pattern at epidermal-dermal junction. Don’t get bigger when rubbed.

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Erythema multiforme

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Associated with infections (e.g., Mycoplasma pneumoniae, HSV), drugs (e.g., sulfa drugs, β-lactams, phenytoin), cancers, autoimmune disease. Presents with multiple types of lesions— macules, papules, vesicles, target lesions (look like targets with multiple rings and dusky center showing epithelial disruption).

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Stevens-Johnson syndrome

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Fever, bullae formation and necrosis, sloughing of skin, high mortality rate. Targetoid skin lesions may appear, as seen in erythema multiforme. Usually associated with adverse drug reaction.

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Toxic Epidermal necrolysis (TEN)

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A more severe form of Stevens-Johnson syndrome (SJS) with > 30% of the body surface area involved is. 10–30% involvement denotes SJS-TEN.

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Acanthosis nigricans

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Epidermal hyperplasia causing symmetric, hyperpigmented thickening of skin, especially in axilla or on neck. Associated with hyperinsulinemia (e.g., diabetes, obesity, Cushing syndrome). If appear rapidly- THINK Gastric adenocarcinoma.

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Actinic keratosis

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Premalignant lesions caused by sun exposure. Small, rough, erythematous papules or plaques. Risk of squamous cell

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Erythema nodosum

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Painful inflammatory lesions of subcutaneous fat, usually on anterior shins. Often idiopathic, but can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, streptococcal infections, leprosy, Crohn disease.

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Lichen Planus

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Hep C! Pruritic, Purple, Polygonal Planar Papules and Plaques are the 6 P’s of lichen Planus. Mucosal involvement manifests as Wickham striae (reticular white lines). Sawtooth infiltrate of lymphocytes at dermal-epidermal junction. Associated with hepatitis C.

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Pityriasis rosea

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“Herald patch” followed days later by other scaly erythematous plaques, often in a “Christmas tree” distribution. Self-resolving in 6–8 weeks.

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Basal cell carcinoma

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Most common skin cancer. Rarely metastasizes. Pink, pearly nodules, commonly with telangiectasias, rolled borders, central crusting or ulceration. Palisading nuclei

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Squamous cell carcinoma

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Second most common skin cancer. Associated with excessive exposure to sunlight, immunosuppression, and occasionally arsenic exposure. Commonly appears on face, lower lip, ears, hands. Locally invasive, may spread to lymph nodes, and will rarely metastasize. Ulcerative red lesions with frequent scale. Associated with chronic draining sinuses. Histopathology: keratin “pearls”

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Melanoma

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Common tumor with significant risk of metastasis. S-100 tumor marker. Often driven by activating mutation in BRAF kinase. BRAF V600E mutation may benefit from vemurafenib, BRAF kinase inhibitor. Subtypes: lentigo maligna- radial growth, superficial spreading- most common dominant radial growth. Nodular- early vertical growth. Acral lentiginous- palms and soles of dark skinned- not related to UV light.