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Gallstone Ileus and Gallbladder Carcinoma

Gallstone enters and obstructs the small intestine

Due to cholecystitis with fistula formation between the gallbladder and small intestine

As the stone advances it may cause intermittent "tumbling" obstruction with diffuse abdominal pain and vomiting

Vomiting, pneumobilia (air in the biliary tree), hyperactive bowel sounds, and dilated loops of bowels

Until finally lodging in the ileum, the narrowest section of the bowels, several days later

Diagnosis: abdominal CT scan which reveals gallbladder wall thickening, pneumobilia, and an obstructing stone

Treatment is surgical and involves removal of the stone and either simultaneous or delayed cholecystectomy

In addition to experiencing colicky pain and vomiting, patients may report distension and inability to pass flatus or stool

May show signs of hypovolemia (eg, hypotension, tachycardia)

Adenocarcinoma arising from the glandular epithelium that lines the gallbladder

Risk factors: gallstones and especially when also combined with porcelain gallbladder

Presents as cholecystitis in elderly women

Poor Prognosis

U. Right Upper Quadrant pain, thickened gallbladder, patchy uniform calcification

Biliary Colic

Waxing and waning right upper quadrant pain

Due to gallbladder contracting against a stone lodged in the cystic duct

Relieved with stone passing

Common bile duct obstruction may result in acute pancreatitis or obstructive jaundice

Associated with nausea/vomiting

Neurohormonal activation (eg, by CCK after a fatty meal) triggers contraction of gallbladder

Labs are normal, ultrasound shows cholelithiasis

Features that distinguish biliary colic from cholecystitis are pain resolution within 4-6 hours and absence of abdominal tenderness, fever, and leukocytosis

Chronic Cholecystitis

Chronic inflammation of the gallbladder

Due to chronic chemical irritation from longstanding cholelithiasis with or without superimposed bouts of acute cholecystitis

Characterized by herniation of gallbladder mucosa into the muscular wall (Rokitansky-Aschoff sinus)

Presents with vague right upper quadrant pain, especially after eating

Porecelain gallbladder is a late complication

Shrunken, hard gallbladder due to chronic inflammation, fibrosis and dystrophic calcification

Increased risk of carcinoma

Treatment: cholecystectomy, especially if porcelain gallbladder is present

Plain x-rays can show a rimlike calcification, CT scan typically reveals a calcified rim in the gallbladder wall with a central bile-filled dark area

Cholecystectomy considered for porcelain gallblad der, particularly if symptomatic or have incomplete mural calcification

Prophylactic cholecystectomy if they have symptoms of gallbladder disease (eg, biliary colic) or if punctate calcifications are present

Curvilinear gallbladder calcifications minimally increase cancer risk and generally do not require intervent ion

Leukocytosis

Bacterial infection, tissue necrosis - causes early release from bone marrow (left shift)

Left shift - decreased Fc receptors (CD16)

Increased neutrophil precursors, such as band cells and metamyelocytes

High cortisol states - impairs adhesion of a marginated pool of neutrophils in pulmonary vasculature

Chronic inflammatory (autoimmune and infectious), malignancy

Allergic reactions (type 1 hypersensitivity), parasitic infection, Hodgkin's lymphoma

Due to eosinophilic chemotactic factor

Chronic myeloid leukemia (CML)

Viral infections, B. pertussis (lymphocytosis promoting factor - blocks lymphocytes from entering lymph nodes)

Coagulation Factor Inhibitor and Disorders of Fibrinolysis

Antibody against coagulation factor; anti-FVIII most commonly

Mimics hemophilia A

PTT does not correct upon mixing studies

In hemophilia A, mixing studies corrects PTT

Excess plasmin activity leading to excessive fibrinogen cleavage

Radical prostatectomy - Release of urokinase which activates plasmin

Cirrhosis of the liver - reduced production of a2-antiplasmin

Mimics DIC: Increased PT/PTT and bleeding time

Differentiated by DIC because increased fibrinogen split products without increased D-dimer

Treatment: aminocaproic acid (blocks plasminogen activation)

Chronic Rheumatic Heart Disease

Valve scarring that arises as a consequence of rheumatic fever

Mitral valve - results in stenosis with a classic 'fish-mouth' appearance

Almost always involves the mitral valve; leads to thickening of chordae tendineae and susps

Occasionally involves the aortic valve; leads to fusion of the commissures; effectively causing aortic stenosis

Other valves are less commonly involved

Complications include infectious endocaritis

Due to repeat exposure to group A B-hemolytic streptoccoi results in relapse of the acute phase --> chronic disease

III—Dysbetalipoproteinemia FA 17 90

Autosomal recessive

Defective ApoE3 and ApoE4

Increased Chylomicron/VLDL remnants

Premature atherosclerosis

Tuberoeruptive xanthomas

Xanthoma striatum palmare

Lymph node 190

A 2° lymphoid organ that has many afferents, 1 or more efferents

Encapsulated, with trabeculae

Functions are nonspecific filtration by macrophages, storage of B and T cells, and immune response activation

Site of B-cell localization and proliferation

In outer cortex; 1° follicles are dense and dormant; 2° follicles have pale central germinal centers and are active

Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses

Medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages

Houses T cells

Region of cortex between follicles and medulla

Contains high endothelial venules through which T and B cells enter from blood. Not well developed in patients with DiGeorge syndrome

Paracortex enlarges in an extreme cellular immune response (eg, viral infection)

Thymoma 229

Benign neoplasm of thymus

Pure red cell aplasia - Anemia with low reticulocytes

Good syndrome - Hypogammaglobulinemia

Myasthenia gravis - Antibodies against postsynaptic ACh receptors at NMJ

Superior vena cava syndrome

Cortex is dense with immature T cells

Medulla is pale with mature T cells and Hassall corpuscles containing epithelial reticular cells

Dopamine 246

D1 = D2 > β > α

Unstable bradycardia, HF, shock

Inotropic and chronotropic effects at lower doses due to β effects

Vasoconstriction at high doses due to α effects

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Allopurinol

Anticonvulsants

Antibiotics

Vancomycin

Sulfa drugs

Potentially fatal delayed hypersensitivity reaction

Latency period (2–8 weeks) followed by fever, morbilliform skin rash, and frequent multiorgan involvement

Withdrawal of offending drug, corticosteroids

Familial Mediterranean Fever

Genetic disease with dysfunction of neutrophils that causes systemic amyloidosis

Usually seen in people of Mediterranean origin

High SAA that deposits as AA amyloid

Acute fever

Serosal inflammation (serosal inflammation of heart might mimic MI, of gut may mimic appendicitis, arthritis)

Occurs in episodes

Chondroma and Osteoid Osteoma

Benign tumor of cartilage

Arises in the medulla of small bones of the hands and feet

Benign tumor of osteoblasts (produces osteoid) surrounded by a rim of reactive bone

Young adults <25 years of age (more common in males)

Arises in cortex of long bones on the diaphysis

Bone pain (often worst at night) that resolves with aspirin

Imaging reveals a bony mass (<2cm) with a radiolucent core (osteoid)

Osteoblastoma is similar in disease course but is larger than 2cm, arises in vertebra and presents with bone pain not relieved by aspirin

Serial examination and x-rays every 4-5 months to monitor the lesion

NSAIDs for pain, surgical resection is typically reserved for patients with refractory symptoms,

Most lesions spontaneously resolve over several years

Angiotensin II 540

Acts at angiotensin II receptor, type 1 (AT1) on vascular smooth muscle

Vasoconstriction

Increase BP

Constricts efferent arteriole of glomerulus

Increases FF to preserve renal function (GFR) in low-volume states (ie, when decreased RBF)

Aldosterone release (adrenal cortex)

Increses Na+ channel insertion and activity of Na+/K+ pump

Enhances K+ and H+ excretion by way of principal cell K+ channels and α-intercalated cell H+ ATPases

Creates favorable Na+ gradient for Na+ and H2O reabsorption

ADH release (posterior pituitary)

Increased aquaporin insertion in principal cells

H2O reabsorption

Increased PCT Na+/H+ activity

Na+, HCO3 –, and H2O reabsorption (can permit contraction alkalosis)

Stimulates hypothalamus (thirst)

Spleen 191

Located in LUQ of abdomen, anterior to left kidney, protected by 9th-11th ribs

Sinusoids are long, vascular channels in red pulp (red arrows) with fenestrated “barrel hoop” basement membrane

T cells are found in the periarteriolar lymphatic sheath (PALS) within the white pulp (white arrows)

B cells are found in follicles within the white pulp

The marginal zone, in between the red pulp and white pulp, contains macrophages and specialized B cells

Where antigenpresenting cells (APCs) capture blood-borne antigens for recognition by lymphocytes

Macrophages found nearby in spleen remove encapsulated bacteria

Decreased IgM causes decreased complement activation causing decreased C3b opsonization

Increases susceptibility to encapsulated organisms

Howell-Jolly bodies (nuclear remnants)

Target cells

Thrombocytosis (loss of sequestration and removal)

Lymphocytosis (loss of sequestration)

Vaccinate patients undergoing splenectomy against encapsulated organisms (pneumococcal, Hib, meningococcal)

Feared long-term complication is sepsis with encapsulated bacteria, most commonly Streptococcus pneumoniae

Daily oral penicillin prophylaxis for three to five years following splenectomy or until adulthood (for pediatric patients)

Tyramine

Normally degraded by monoamine oxidase (MAO)

Levels increase in patients taking MAO inhibitors who ingest tyramine-rich foods (eg, aged cheese, wine, pepperoni, pickled foods and soy sauce).

Overripe fruits

Excess tyramine enters presynaptic vesicles and displaces other neurotransmitters (eg, NE)

Increased active presynaptic neurotransmitters

Increased diffusion of neurotransmitters into synaptic cleft increasing sympathetic stimulation

Classically results in a hypertensive crisis

Nasal Polyps, Angiofibroma and Nasopharngeal Carcinoma

Protrusion of edematious, inflamed nasal mucosa

Secondary to repeated bouts of rhinitis; occurs in cystic fibrosis and aspirin-intolerant asthma, kartagener

Aspirin-intolerant asthma consists of asthma, aspirin-induced bronchospasms, nasal polyps

Surgery often temporary relief, polyps recur; ultimate treatment should be management of underlying etiology

Not just aspirin, any NSAIDs

Can do aspirin desensitization if aspirin is required

Treatment includes management of the patient's underlying asthma and chronic rhinosinusitis

Avoidance of NSAIDs, and desensitization if NSAID use is required

Leukotriene inhibitors (zileuton) and leukotriene antagonists (montelukast) --> improved resp/nasal symptoms

Considered a pseudoallergy

Benign tumor of nasal mucosa composed of large blood vessels and fibrous tissue; classically seen in adolescent males

Profuse epistaxis

Can cause nasal obstruction and nasal drainage

Malignant

EBV association; classically African children/Chinese Adults

Risk is thought to be higher in these locations due to diet (salt-cured food, early exposure to salted fish) and genetic predisposition

Pleomorphic keratin-positive epithelial cells (poorly differentiated squamous cell carcinoma) in a background of lymphocytes

Often presents with cervical lymph node involvement

EBV assays are often used to monitor treatment response and disease relapse

Invades adjacent tissues --> congestion, epistaxis, headache, CN palsy, serous otitis media (eustachian obstruction)

Nasal congestion with epistaxis, headache, cranial nerve palsies (eg , facial numbness), serous otitis media (eustachian tube obstruction)

Early metastatic spread to the cervical lymph nodes may cause a nontender neck mass

Nasopharyngeal endoscopy should be considered

Growth hormone (Somatotropin) 311

Secreted by anterior pituitary

Stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by liver

Increased insulin resistance (diabetogenic)

Released in pulses in response to growth hormone–releasing hormone (GHRH)

Secretion increased during exercise, deep sleep, puberty, hypoglycemia, ghrelin

Secretion inhibited by glucose and somatostatin release via negative feedback by somatomedin

Anatomy of the Heart 265

SA node is supplied by branches of the RCA

The AV nodal artery is usually derived from the dominant Coronary artery ie the one that gives rise to the PDA

Supplies right ventricle

Supplies AV node, posterior 1/3 of interventricular septum, 2/3 posterior walls of ventricles, and posteromedial papillary muscle

Inferior wall of left ventricle

Supplies anterior 2/3 of interventricular septum, anterolateral papillary muscle, and anterior surface of left ventricle

Supplies lateral and posterior walls of left ventricle, anterolateral papillary muscle

Diagonal branches from the LAD artery also run downward to supply the anterolateral wall of the left ventr icle

The right coronary supplies the right ventric le and inferoposterior walls of the left ventricle

Peroxisome and Related Disorders 43

Membrane-enclosed organelle involved in catabolism of:

Very-long-chain fatty acids (through β-oxidation), branched-chain fatty acids, amino acids, and ethanol

Peroxisomal disorders commonly lead to neurologic diseases due to deficits in synthesis of plasmalogens

Important phospholipids in myelin

P. Contains catalase which breaks down H2O2 into H2O

Hypotonia, seizures, hepatomegaly, early death

Scaly skin, ataxia, cataracts/night blindness, shortening of 4th toe, epiphyseal dysplasia

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