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First_Aid_Step1. AdvERSE EFFECTS Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, headache, angina, drug-induced lupus. Nitrates Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate. MECHANISM Vasodilate by  NO in vascular smooth muscle  in cGMP and smooth muscle relaxation. Dilate veins >> arteries.  preload. ClINICAl uSE Angina, acute coronary syndrome, pulmonary edema. AdvERSE EFFECTS Reflex tachycardia (treat with β-blockers), hypotension, flushing, headache, “Monday disease” in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend • tachycardia, dizziness, headache upon reexposure. Contraindicated in right ventricular infarction, hypertrophic cardiomyopathy, and with concurrent PDE-5 inhibitor use. Verapamil is similar to β-blockers in effect. Pindolol and acebutolol are partial β-agonists that should be used with caution in angina.


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First_Aid_Step1. Verapamil is similar to β-blockers in effect. Pindolol and acebutolol are partial β-agonists that should be used with caution in angina. MECHANISM Inhibits the late phase of inward sodium current thereby reducing diastolic wall tension and oxygen consumption. Does not affect heart rate or blood pressure. ClINICAl uSE Angina refractory to other medical therapies. AdvERSE EFFECTS Constipation, dizziness, headache, nausea. MECHANISM A neprilysin inhibitor; prevents degradation of natriuretic peptides, angiotensin II, and substance P  vasodilation,  ECF volume. ClINICAl uSE Used in combination with valsartan (an ARB) to treat HFrEF. AdvERSE EFFECTS Hypotension, hyperkalemia, cough, dizziness; contraindicated with ACE inhibitors due to angioedema. Cardiac glycosides Digoxin. MECHANISM Direct inhibition of Na+/K+ ATPase inhibition of Na+/Ca2+ exchanger. [Ca2+]i • positive inotropy. Stimulates vagus nerve  HR.


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First_Aid_Step1. Cardiac glycosides Digoxin. MECHANISM Direct inhibition of Na+/K+ ATPase inhibition of Na+/Ca2+ exchanger. [Ca2+]i • positive inotropy. Stimulates vagus nerve  HR. ClINICAl uSE HF ( contractility); atrial fibrillation ( conduction at AV node and depression of SA node). AdvERSE EFFECTS Cholinergic effects (nausea, vomiting, diarrhea), blurry yellow vision (think van Glow), arrhythmias, AV block. Can lead to hyperkalemia, which indicates poor prognosis. Factors predisposing to toxicity: renal failure ( excretion), hypokalemia (permissive for digoxin binding at K+-binding site on Na+/K+ ATPase), drugs that displace digoxin from tissue-binding sites, and  clearance (eg, verapamil, amiodarone, quinidine). ANTIdOTE Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+.


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First_Aid_Step1. ANTIdOTE Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+. Antiarrhythmics— Slow or block () conduction (especially in depolarized cells).  slope of phase 0 depolarization. Are sodium channel state dependent (selectively depress tissue that is frequently depolarized [eg, tachycardia]). blockers (class I) Class IA Quinidine, Procainamide, Disopyramide. “The Queen Proclaims Diso’s pyramid.” MECHANISM Moderate Na+ channel blockade.  AP duration,  effective refractory period (ERP) in ventricular action potential,  QT interval, some potassium channel blocking effects. ClINICAl uSE Both atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT. AdvERSE EFFECTS Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide), thrombocytopenia, torsades de pointes due to  QT interval. Class IB Lidocaine, MexileTine. “I’d Buy Liddy’s Mexican Tacos.” 0 mV


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First_Aid_Step1. Class IB Lidocaine, MexileTine. “I’d Buy Liddy’s Mexican Tacos.” 0 mV MECHANISM Weak Na+ channel blockade.  AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Phenytoin can also fall into the IB category. ClINICAl uSE Acute ventricular arrhythmias (especially post-MI), digitalis-induced arrhythmias. IB is Best post-MI. AdvERSE EFFECTS CNS stimulation/depression, cardiovascular depression. Class IC Flecainide, Propafenone. “Can I have Fries, Please.” 0 mV MECHANISM Strong Na+ channel blockade. Significantly prolongs ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration. ClINICAl uSE SVTs, including atrial fibrillation. Only as a last resort in refractory VT. AdvERSE EFFECTS Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.


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First_Aid_Step1. AdvERSE EFFECTS Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease. Antiarrhythmics— Metoprolol, propranolol, esmolol, atenolol, timolol, carvedilol. MECHANISM Decrease SA and AV nodal activity by  cAMP,  Ca2+ currents. Suppress abnormal pacemakers by  slope of phase 4. AV node particularly sensitive— PR interval. Esmolol very short acting. ClINICAl uSE SVT, ventricular rate control for atrial fibrillation and atrial flutter.


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First_Aid_Step1. ClINICAl uSE SVT, ventricular rate control for atrial fibrillation and atrial flutter. AdvERSE EFFECTS Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Metoprolol can cause dyslipidemia. Propranolol can exacerbate vasospasm in vasospastic angina. β-blockers (except the nonselective αand β-antagonists carvedilol and labetalol) cause unopposed α1-agonism if given alone for pheochromocytoma or for cocaine toxicity (unsubstantiated). Treat β-blocker overdose with saline, atropine, glucagon. Antiarrhythmics— Amiodarone, Ibutilide, Dofetilide, Sotalol. AIDS. potassium channel blockers (class III) MECHANISM  AP duration,  ERP,  QT interval. ClINICAl uSE Atrial fibrillation, atrial flutter; ventricular tachycardia (amiodarone, sotalol). Antiarrhythmics— Diltiazem, Verapamil calcium channel blockers (class IV)


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First_Aid_Step1. ClINICAl uSE Atrial fibrillation, atrial flutter; ventricular tachycardia (amiodarone, sotalol). Antiarrhythmics— Diltiazem, Verapamil calcium channel blockers (class IV) MECHANISM Decrease conduction Velocity,  ERP, • PR interval. ClINICAl uSE Prevention of nodal arrhythmias (eg, SVT), rate control in atrial fibrillation. AdvERSE EFFECTS Constipation, flushing, edema, cardiovascular effects (HF, AV block, sinus node depression). Adenosine  K+ out of cells  hyperpolarizing the cell and  ICa, decreasing AV node conduction. Drug of choice in diagnosing/terminating certain forms of SVT. Very short acting (~ 15 sec). Effects blunted by theophylline and caffeine (both are adenosine receptor antagonists). Adverse effects include flushing, hypotension, chest pain, sense of impending doom, bronchospasm. Magnesium Effective in torsades de pointes and digoxin toxicity.


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First_Aid_Step1. Magnesium Effective in torsades de pointes and digoxin toxicity. MECHANISM IVabradine prolongs slow depolarization (phase “IV”) by selectively inhibiting “funny” sodium channels (If). ClINICAl uSE Chronic stable angina in patients who cannot take β-blockers. Chronic HFrEF. AdvERSE EFFECTS Luminous phenomena/visual brightness, hypertension, bradycardia. “If you skew the endocrine system, you lose the pathways to self.” “We have learned that there is an endocrinology of elation and despair, a chemistry of mystical insight, and, in relation to the autonomic nervous system, a meteorology and even . . . an astro-physics of changing moods.” “Chocolate causes certain endocrine glands to secrete hormones that affect your feelings and behavior by making you happy.” —Elaine Sherman, Book of Divine Indulgences


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First_Aid_Step1. The endocrine system comprises widely distributed organs that work in a highly integrated manner to orchestrate a state of hormonal equilibrium within the body. Generally speaking, endocrine diseases can be classified either as diseases of underproduction or overproduction, or as conditions involving the development of mass lesions—which themselves may be associated with underproduction or overproduction of hormones. Therefore, study the endocrine system first by learning the glands, their hormones, and their regulation, and then by integrating disease manifestations with diagnosis and management. Take time to learn the multisystem connections. Thyroid diverticulum arises from floor of primitive pharynx and descends into neck. Connected to tongue by thyroglossal duct, which normally disappears but may persist as cysts or the pyramidal lobe of thyroid. Foramen cecum is normal remnant of thyroglossal duct.


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First_Aid_Step1. Most common ectopic thyroid tissue site is the tongue (lingual thyroid). Removal may result in hypothyroidism if it is the only thyroid tissue present. Thyroglossal duct cyst A presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue (vs persistent cervical sinus leading to pharyngeal cleft cyst in lateral neck). Thyroid follicular cells derived from endoderm. Superior surface of kidney Secretes FSH, LH, ACTH, TSH, prolactin, Proopiomelanocortin derivatives—β-endorphin, GH, and β-endorphin. Melanotropin (MSH) ACTH, and MSH. Go pro with a BAM! secreted from intermediate lobe of pituitary. FLAT PiG: FSH, LH, ACTH, TSH, PRL, GH. Derived from oral ectoderm (Rathke pouch). B-FLAT: Basophils—FSH, LH, ACTH, TSH. α subunit—hormone subunit common to Acid PiG: Acidophils — PRL, GH. TSH, LH, FSH, and hCG.


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First_Aid_Step1. α subunit—hormone subunit common to Acid PiG: Acidophils — PRL, GH. TSH, LH, FSH, and hCG. β subunit—determines hormone specificity. Stores and releases vasopressin (antidiuretic hormone, or ADH) and oxytocin, both made in the hypothalamus (supraoptic and paraventricular nuclei) and transported to posterior pituitary via neurophysins (carrier proteins). Derived from neuroectoderm. Adrenal cortex (derived from mesoderm) and medulla (derived from neural crest). CORTEX Zona Fasciculata ACTH, CRH Glucocorticoids Cortisol Capsule ACTH, CRHDHEA Zona Reticularis Preganglionic Catecholamines Epi, NEChroma˜n cells sympathetic fbers MEDULLA GFR corresponds with Salt (mineralocorticoids), Sugar (glucocorticoids), and Sex (androgens). “The deeper you go, the sweeter it gets.”


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First_Aid_Step1. GFR corresponds with Salt (mineralocorticoids), Sugar (glucocorticoids), and Sex (androgens). “The deeper you go, the sweeter it gets.” Sleep, hypoglycemia, stress Growth hormone IGF-1 Anterior pituitary Posterior pituitary Somatostatin Amino acid uptake Protein synthesis Amino acid uptake Protein synthesis Glucose uptake Lipolysis DNA and RNA synthesis Chondroitin sulfate Collagen Cell size and number Aging, obesity, glucose GHRH Antidiuretic hormone Also called vasopressin. soUrce Synthesized in hypothalamus (supraoptic and paraventricular nuclei), stored and secreted by posterior pituitary. FUnction Regulates b1ood pressure (V1-receptors) and serum osmolality (V2-receptors). Primary function is serum osmolality regulation (ADH  serum osmolality,  urine osmolality) via regulation of aquaporin channel insertion in principal cells of renal collecting duct. regUlAtion Plasma osmolality (1°); hypovolemia. Also called somatotropin. Secreted by anterior pituitary.


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First_Aid_Step1. regUlAtion Plasma osmolality (1°); hypovolemia. Also called somatotropin. Secreted by anterior pituitary. Stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by liver.  insulin resistance (diabetogenic). Released in pulses in response to growth hormone–releasing hormone (GHRH). Secretion  during exercise, deep sleep, puberty, hypoglycemia, CKD. Secretion  by glucose, somatostatin, somatomedin (regulatory molecule secreted by liver in response to GH acting on target tissues). Excess secretion of GH (eg, pituitary adenoma) may cause acromegaly (adults) or gigantism (children). Treatment: somatostatin analogs (eg, octreotide) or surgery. ADH level is  in central diabetes insipidus (DI), normal or  in nephrogenic DI. Nephrogenic DI can be caused by mutation in V2-receptor. Desmopressin (ADH analog) is a treatment for central DI and nocturnal enuresis.


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First_Aid_Step1. Nephrogenic DI can be caused by mutation in V2-receptor. Desmopressin (ADH analog) is a treatment for central DI and nocturnal enuresis. Thyroid hormones Thyroid produces triiodothyronine (T3) and thyroxine (T4), iodine-containing hormones that control the body’s metabolic rate.


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First_Aid_Step1. Thyroid hormones Thyroid produces triiodothyronine (T3) and thyroxine (T4), iodine-containing hormones that control the body’s metabolic rate. soUrce Follicles of thyroid. 5′-deiodinase converts T4 (the major thyroid product) to T3 in peripheral tissue (5, 4, 3). Peripheral conversion is inhibited by glucocorticoids, β-blockers, and propylthiouracil (PTU). Reverse T3 (rT3) is a metabolically inactive byproduct of the peripheral conversion of T4 and its production is increased by growth hormone and glucocorticoids. Functions of thyroid peroxidase include oxidation, organification of iodine, and coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT). Inhibited by PTU and methimazole. DIT + DIT = T4. DIT + MIT = T3. Wolff-Chaikoff effect—excess iodine temporarily turns off thyroid peroxidase  T3/T4 production (protective autoregulatory effect). FUnction Only free hormone is active. T3 binds nuclear receptor with greater affinity than T4. T3 functions —7B’s:


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First_Aid_Step1. FUnction Only free hormone is active. T3 binds nuclear receptor with greater affinity than T4. T3 functions —7B’s: Bone growth (synergism with GH) β-adrenergic effects. • β1 receptors in heart  CO, HR, SV, contractility; β-blockers alleviate adrenergic symptoms in thyrotoxicosis Basal metabolic rate  (via Na+/K+-ATPase activity  O2 consumption, RR, body temperature) Blood sugar (• glycogenolysis, gluconeogenesis) regUlAtion TRH ⊕ TSH release • ⊕ follicular cells. Thyroid-stimulating immunoglobulin (TSI) may ⊕ follicular cells in Graves disease. Negative feedback primarily by free T3/T4: Anterior pituitary  sensitivity to TRH Thyroxine-binding globulin (TBG) binds most T3/T4 in blood. Bound T3/T4 = inactive. •  TBG in pregnancy, OCP use (estrogen  TBG)  total T3/T4 •  TBG in steroid use, nephrotic syndrome TSI T3, T4


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First_Aid_Step1. TSI T3, T4 Downstream thyroid function T3 T4 T4 > T3 (to circulation) I– I– I2 Na+ MIT, DIT Thyroglobulin Oxidation + Proteases5'-deiodinase Tyrosine DITMIT DITDIT Thyroid peroxidase Thyroid peroxidase TG TG TG TG TG Endocytosis Organifcation Coupling reaction Deiodinase PTU MIT MIT DIT DIT T3 T3 T4 T3 T4 MIT PTU, methimazole soUrce Chief cells of parathyroid FUnction  free Ca2+ in the blood (1° function) 1,25-(OH)2D3 (calcitriol) production by activating 1α-hydroxylase in PCT Tri to make D3 in the PCT PTH  serum Ca2+,  serum PO43–,  urine PO43– ,  urine cAMP


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First_Aid_Step1. PTH  serum Ca2+,  serum PO43–,  urine PO43– ,  urine cAMP RANK-L (receptor activator of NF-κB ligand) secreted by osteoblasts and osteocytes; binds RANK (receptor) on osteoclasts and their precursors to stimulate osteoclasts and • Ca2+ like PTH and is commonly increased in malignancies (eg, squamous cell carcinoma of the lung, renal cell carcinoma) serum Mg2+  PTH secretion  serum Mg2+  PTH secretion Common causes of  Mg2+ include diarrhea, aminoglycosides, diuretics, alcohol abuse ˛ ionized Ca2+, ˜ PO 3– , or 1,25-(OH)2 D 1,25-(OH)2 D3 Four para-thyroid glandsFeedback inhibition of PTH synthesis Vitamin D activity ˜ Ca2+ and PO4 3–˜ PTH released into circulation 25-OH D3 Bone Intestines 1,25-(OH)2 D3 1˜-hydroxylase ˜ Ca2+ and ˜ PO4 3– ˜ Ca2+ and ˜ PO4 3– released from bone ˜ absorption of Ca2+ and PO4 3– Renal tubular cells ˜ 1,25-(OH)2 D synthesis3 Urine Ca2+ , ˜ PO4 3– Reabsorption: ˜ Ca2+ , PO4 3–˜ ˜ ˜ Calcium homeostasis Plasma Ca2+ exists in three forms:


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First_Aid_Step1. Calcium homeostasis Plasma Ca2+ exists in three forms: Ionized/free (~ 45%, active form) Bound to albumin (∼ 40%) Bound to anions (∼ 15%) pH (less H+)  albumin binds more Ca2+ • ionized Ca2+ (eg, cramps, pain, paresthesias, carpopedal spasm) • PTH Ionized/free Ca2+ is 1° regulator of PTH; changes in pH alter PTH secretion, whereas changes in albumin concentration do not soUrce Parafollicular cells (C cells) of thyroid. Calcitonin opposes actions of PTH. Not important in normal Ca2+ homeostasis FUnction  bone resorption of Ca2+. Calcitonin tones down serum Ca2+ levels and regUlAtion  serum Ca2+ • calcitonin secretion. soUrce Made by α cells of pancreas. FUnction Promotes glycogenolysis, gluconeogenesis, lipolysis, ketogenesis. Elevates blood sugar levels to maintain homeostasis when bloodstream glucose levels fall too low (ie, fasting state). regUlAtion Secreted in response to hypoglycemia. Inhibited by insulin, hyperglycemia, somatostatin.


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First_Aid_Step1. regUlAtion Secreted in response to hypoglycemia. Inhibited by insulin, hyperglycemia, somatostatin. synthesis Preproinsulin (synthesized in RER of pancreatic β cells)  cleavage of “presignal” • proinsulin (stored in secretory granules)  cleavage of proinsulin  exocytosis of insulin and C-peptide equally. Insulin and C-peptide are  in insulinoma and sulfonylurea use, whereas exogenous insulin lacks C-peptide. regUlAtion Glucose is the major regulator of insulin release.  insulin response with oral vs IV glucose due to incretins (eg, glucagon-like peptide 1 [GLP-1], glucose-dependent insulinotropic polypeptide [GIP]), which are released after meals and • β cell sensitivity to glucose. Release  by α2,  by β2 stimulation (2 = regulates insulin) closes K+ channels (target of sulfonylureas) . Voltage-gated Ca2+ channels open and stimulation of insulin exocytosis


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First_Aid_Step1. Tyrosine phosphorylationPhosphoinositide-3 kinase pathway RAS/MAPkinasepathwayVesicles Cell growth, containing GLUT4 DNAGlycogen, lipid, protein synthesis synthesis ), inducing glucose uptake (carriermediated transport) into insulin-dependent tissue and gene transcription. Anabolic effects of insulin: •  glucose transport in skeletal muscle and adipose tissue •  glycogen synthesis and storage •  triglyceride synthesis •  Na+ retention (kidneys) •  protein synthesis (muscles) •  cellular uptake of K+ and amino acids •  glucagon release •  lipolysis in adipose tissue Unlike glucose, insulin does not cross placenta. Insulin-dependent glucose transporters: • GLUT4: adipose tissue, striated muscle (exercise can also • GLUT4 expression) Insulin-independent transporters: GLUT1: RBCs, brain, cornea, placenta GLUT2 (bidirectional): β islet cells, liver, kidney, GI tract (think 2-way street) GLUT3: brain, placenta GLUT5 (Fructose): spermatocytes, GI tract


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First_Aid_Step1. GLUT1: RBCs, brain, cornea, placenta GLUT2 (bidirectional): β islet cells, liver, kidney, GI tract (think 2-way street) GLUT3: brain, placenta GLUT5 (Fructose): spermatocytes, GI tract SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine Brain prefers glucose, but may use ketone bodies during starvation. RBCs utilize glucose, as they lack mitochondria for aerobic metabolism. BRICK LIPS (insulin-independent glucose uptake): Brain, RBCs, Intestine, Cornea, Kidney, Liver, Islet (β) cells, Placenta, Spermatocytes.


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First_Aid_Step1. BRICK LIPS (insulin-independent glucose uptake): Brain, RBCs, Intestine, Cornea, Kidney, Liver, Islet (β) cells, Placenta, Spermatocytes. Cholesterol desmolase Aldosterone synthase 21-hydroxylation 11˜-hydroxylation ZONA GLOMERULOSA Mineralocorticoids ZONA FASCICULATA Glucocorticoids Adrenal cortex Peripheral tissue ZONA RETICULARIS Androgens Estrogens, DHT Cholesterol (via StARa) Pregnenolone Progesterone 11-deoxycorticosterone Corticosterone Aldosterone 17-hydroxyprogesterone 17-hydroxypregnenolone 11-deoxycortisol Cortisone Glycyrrhetinic acid Cortisol Dehydroepiandrosterone (DHEA) Anastrozole, letrozole, exemestane Finasteride Androstenedione Testosterone Dihydrotestosterone (DHT) Angiotensin II 3˜-hydroxysteroid dehydrogenase Estrone Estradiol Aromatase Aromatase 17°-hydroxylase 17,20-lyase 17,20-lyase17°-hydroxylase 5°-reductase AMetyrapone aRate-limiting step.


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First_Aid_Step1. 17α-hydroxylasea  androstenedione XY: ambiguous genitalia, undescended testes XX: lacks 2° sexual development 21-hydroxylasea  renin activity  17-hydroxy-progesterone Most common Presents in infancy (salt wasting) or childhood (precocious puberty) XX: virilization 11β-hydroxylasea  aldosterone  11-deoxycorti-costerone (results in BP)  renin activity Presents in infancy (severe hypertension) or childhood (precocious puberty) XX: virilization aAll congenital adrenal enzyme deficiencies are autosomal recessive disorders and most are characterized by skin hyperpigmentation (due to  MSH production, which is coproduced and secreted with ACTH) and bilateral adrenal gland enlargement (due to • ACTH stimulation). If deficient enzyme starts with 1, it causes hypertension; if deficient enzyme ends with 1, it causes virilization in females.


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First_Aid_Step1. If deficient enzyme starts with 1, it causes hypertension; if deficient enzyme ends with 1, it causes virilization in females. Ghrelin Stimulates hunger (orexigenic effect) and GH release (via GH secretagog receptor). Produced by stomach. Sleep deprivation, fasting, or Prader-Willi syndrome  ghrelin production. Ghrelin makes you hunghre and ghrow. Acts on lateral area of hypothalamus (hunger center) to • appetite. Leptin Satiety hormone. Produced by adipose tissue. Mutation of leptin gene  central obesity. (Obese people have  leptin due to  adipose tissue but also appear resistant to leptin’s anorexigenic effect.) Sleep deprivation or starvation • leptin production. Leptin keeps you thin. Acts on ventromedial area of hypothalamus (satiety center) to  appetite. Endocannabinoids Act at cannabinoid receptors in hypothalamus and nucleus accumbens, two key brain areas for the homeostatic and hedonic control of food intake • appetite. Exogenous cannabinoids cause “the munchies.”


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First_Aid_Step1. Signaling pathways of endocrine hormones Signaling pathways of steroid hormones Binding to receptor Steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins, which  their solubility. In men,  sex hormone–binding globulin (SHBG) lowers free testosterone gynecomastia. In women,  SHBG raises free testosterone hirsutism. estrogen (eg, OCPs, pregnancy)  SHBG. Syndrome of inappropriate antidiuretic hormone secretion Characterized by: Euvolemic hyponatremia with continued urinary Na+ excretion Urine osmolality > serum osmolality Body responds to water retention with aldosterone and  ANP and BNP  urinary Na+ secretion • normalization of extracellular fluid volume  euvolemic hyponatremia. Very low serum Na+ levels can lead to cerebral edema, seizures. Correct slowly to prevent osmotic demyelination syndrome (formerly called central pontine myelinolysis). SIADH causes include: Ectopic ADH (eg, small cell lung cancer)


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First_Aid_Step1. SIADH causes include: Ectopic ADH (eg, small cell lung cancer) Drugs (eg, SSRIs, carbamazepine, cyclophosphamide) Treatment: fluid restriction (first line), salt tablets, IV hypertonic saline, diuretics, ADH antagonists (eg, conivaptan, tolvaptan, demeclocycline). aNo water intake for 2–3 hr followed by hourly measurements of urine volume and osmolality as well as plasma Na+ concentration and osmolality. ADH analog (desmopressin) is administered if serum osmolality > 295–300 mOsm/kg, plasma Na+ ≥ 145 mEq/L, or urine osmolality does not rise despite a rising plasma osmolality. Hypopituitarism Undersecretion of pituitary hormones due to: Nonsecreting pituitary adenoma, craniopharyngioma Sheehan syndrome—ischemic infarct of pituitary following postpartum bleeding; pregnancy-induced pituitary growth  susceptibility to hypoperfusion. Usually presents with failure to lactate, absent menstruation, cold intolerance


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First_Aid_Step1. Empty sella syndrome—atrophy or compression of pituitary (which lies in the sella turcica), often idiopathic, common in obese women; associated with idiopathic intracranial hypertension Pituitary apoplexy—sudden hemorrhage of pituitary gland, often in the presence of an existing pituitary adenoma. Usually presents with sudden onset severe headache, visual impairment (eg, bitemporal hemianopia, diplopia due to CN III palsy), and features of hypopituitarism Treatment: hormone replacement therapy (corticosteroids, thyroxine, sex steroids, human growth hormone) Acromegaly Excess GH in adults. Typically caused by pituitary adenoma. Findings Large tongue with deep furrows, deep voice,  GH in children  gigantism ( linear bone large hands and feet, coarsening of facial growth). HF most common cause of death. features with aging A , frontal bossing, diaphoresis (excessive sweating), impaired glucose tolerance (insulin resistance), hypertension.  risk of colorectal polyps and cancer.


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First_Aid_Step1. A , frontal bossing, diaphoresis (excessive sweating), impaired glucose tolerance (insulin resistance), hypertension.  risk of colorectal polyps and cancer. diAgnosis  serum IGF-1; failure to suppress serum GH following oral glucose tolerance test; pituitary mass seen on brain MRI. treAtment Pituitary adenoma resection. If not cured, treat with octreotide (somatostatin analog), pegvisomant (GH receptor antagonist), or dopamine agonists (eg, cabergoline).


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First_Aid_Step1. treAtment Pituitary adenoma resection. If not cured, treat with octreotide (somatostatin analog), pegvisomant (GH receptor antagonist), or dopamine agonists (eg, cabergoline). metAbolic Cold intolerance,  sweating, weight gain Heat intolerance,  sweating, weight loss ( basal metabolic rate • calorigenesis), ( synthesis of Na+-K+ ATPase  basal hyponatremia ( free water clearance) metabolic rate • calorigenesis) sKin/hAir Dry, cool skin (due to  blood flow); coarse, Warm, moist skin (due to vasodilation); fine hair; brittle hair; diffuse alopecia; brittle nails; onycholysis ( A ); pretibial myxedema in Graves puffy facies and generalized nonpitting edema disease (myxedema) due to  GAGs in interstitial spaces  osmotic pressure • water retention Other causes Iodine deficiency (with goiter E ), goitrogens (eg, amiodarone, lithium), Wolff-Chaikoff effect (thyroid gland downregulation in response to • iodide).


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First_Aid_Step1. Other causes Iodine deficiency (with goiter E ), goitrogens (eg, amiodarone, lithium), Wolff-Chaikoff effect (thyroid gland downregulation in response to • iodide). Graves disease Most common cause of hyperthyroidism. Thyroid-stimulating immunoglobulin (IgG, can cause transient neonatal hyperthyroidism; type II hypersensitivity) stimulates TSH receptors on thyroid (hyperthyroidism, diffuse goiter), dermal fibroblasts (pretibial myxedema), and orbital fibroblasts (Graves orbitopathy). Activation of T-cells  lymphocytic infiltration of retroorbital space • cytokines (eg, TNF-α, IFN-γ)  fibroblast secretion of hydrophilic GAGs  osmotic muscle swelling, muscle inflammation, and adipocyte count  exophthalmos A . Often presents during stress (eg, pregnancy). Associated with HLA-DR3 and HLA-B8. Histology: tall, crowded follicular epithelial cells; scalloped colloid.


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First_Aid_Step1. Histology: tall, crowded follicular epithelial cells; scalloped colloid. Toxic multinodular Focal patches of hyperfunctioning follicular cells distended with colloid working independently goiter of TSH (due to TSH receptor mutations in 60% of cases).  release of T3 and T4. Hot nodules are rarely malignant. Thyroid storm Uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/ untreated and then significantly worsens in the setting of acute stress such as infection, trauma, surgery. Presents with agitation, delirium, fever, diarrhea, coma, and tachyarrhythmia (cause of death). May see  LFTs. Treat with the 4 P’s: β-blockers (eg, Propranolol), Propylthiouracil, corticosteroids (eg, Prednisolone), Potassium iodide (Lugol iodine). Iodide load  T4 synthesis  Wolff-Chaikoff effect.


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First_Aid_Step1. Jod-Basedow Iodine-induced hyperthyroidism. Occurs when a patient with iodine deficiency and partially phenomenon autonomous thyroid tissue (eg, autonomous nodule) is made iodine replete. Can happen after iodine IV contrast or amiodarone use. Opposite to Wolff-Chaikoff effect. Causes of goiter Smooth/diffuse: Graves disease, Hashimoto thyroiditis, iodine deficiency, TSH-secreting pituitary adenoma. Nodular: toxic multinodular goiter, thyroid adenoma, thyroid cancer, thyroid cyst. Thyroid adenoma Benign solitary growth of the thyroid. Most are nonfunctional (“cold”), can rarely cause hyperthyroidism via autonomous thyroid hormone production (“hot” or “toxic”). Most common histology is follicular (arrows in A ); absence of capsular or vascular invasion (unlike follicular carcinoma).


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First_Aid_Step1. Thyroid cancer Typically diagnosed with fine needle aspiration; treated with thyroidectomy. Complications of surgery include hypocalcemia (due to removal of parathyroid glands), transection of recurrent laryngeal nerve during ligation of inferior thyroid artery (leads to dysphagia and dysphonia [hoarseness]), and injury to the external branch of the superior laryngeal nerve during ligation of superior thyroid vascular pedicle (may lead to loss of tenor usually noticeable in professional voice users). Papillary carcinoma Most common, excellent prognosis. Empty-appearing nuclei with central clearing (“Orphan Annie” eyes) A , psamMoma bodies, nuclear grooves (Papi and Moma adopted OrphanAnnie).  risk with RET/PTC rearrangements and BRAF mutations, childhood irradiation. Papillary carcinoma: most Prevalent, Palpable lymph nodes. Good prognosis.


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First_Aid_Step1.  risk with RET/PTC rearrangements and BRAF mutations, childhood irradiation. Papillary carcinoma: most Prevalent, Palpable lymph nodes. Good prognosis. Follicular carcinoma Good prognosis. Invades thyroid capsule and vasculature (unlike follicular adenoma), uniform follicles; hematogenous spread is common. Associated with RAS mutation and PAX8-PPAR-γ translocations. Medullary carcinoma From parafollicular “C cells”; produces calcitonin, sheets of polygonal cells in an amyloid stroma B (stains with Congo red). Associated with MEN 2A and 2B (RET mutations). Undifferentiated/ Older patients; presents with rapidly enlarging neck mass  compressive symptoms (eg, dyspnea, anaplastic carcinoma dysphagia, hoarseness); very poor prognosis. Associated with TP53 mutation. (vitamin D defciency, ˜ Ca2+ intake, (hyperplasia, adenoma, chronic kidney disease) carcinoma) 1° hypoparathyroidism PTH-independent (surgical resection, hypercalcemia autoimmune) (excess Ca2+ intake, cancer, ° vitamin D)


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First_Aid_Step1. Due to injury to parathyroid glands or their blood supply (usually during surgery), autoimmune destruction, or DiGeorge syndrome. Findings: tetany, hypocalcemia, hyperphosphatemia. Chvostek sign—tapping of facial nerve (tap the Cheek)  contraction of facial muscles. Trousseau sign—occlusion of brachial artery with BP cuff (cuff the Triceps)  carpal spasm. Pseudohypoparathyroidism type 1A—autosomal dominant, maternally transmitted mutations (imprinted GNAS gene). GNAS1-inactivating mutation (coupled to PTH receptor) that encodes the Gs protein α subunit  inactivation of adenylate cyclase when PTH binds to its receptor  end-organ resistance (kidney and bone) to PTH. Physical findings: Albright hereditary osteodystrophy (shortened 4th/5th digits A , short stature, round face, subcutaneous calcifications, developmental delay). Labs:  PTH, • Ca2+,  PO43–.


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First_Aid_Step1. Pseudopseudohypoparathyroidism—autosomal dominant, paternally transmitted mutations (imprinted GNAS gene) but without end-organ resistance to PTH due to normal maternal allele maintaining renal responsiveness to PTH. Physical findings: same as Albright hereditary osteodystrophy. Labs: normal PTH, Ca2+, PO43–. Usually due to parathyroid adenoma or hyperplasia. Hypercalcemia, hypercalciuria (renal stones), polyuria (thrones), hypophosphatemia,  PTH,  ALP,  urinary cAMP. Most often asymptomatic. May present with bone pain, weakness, constipation (“groans”), abdominal/flank pain (kidney stones, acute pancreatitis), neuropsychiatric disturbances (“psychiatric overtones”). Osteitis fibrosa cystica—cystic bone spaces filled with brown fibrous tissue A (“brown tumor” consisting of osteoclasts and deposited hemosiderin from hemorrhages; causes bone pain). Due to  PTH, classically associated with 1° (but also seen with 2°) hyperparathyroidism.


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First_Aid_Step1. “Stones, thrones, bones, groans, and psychiatric overtones.” AcUte mAniFestAtions Polydipsia, polyuria, polyphagia, weight loss, DKA (type 1), hyperosmolar hyperglycemic state (type 2). Rarely, can be caused by unopposed secretion of GH and epinephrine. Also seen in patients on glucocorticoid therapy (steroid diabetes). chronic comPlicAtions Nonenzymatic glycation: Small vessel disease (diffuse thickening of basement membrane)  retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation), glaucoma, nephropathy. Nodular glomerulosclerosis • progressive proteinuria (initially microalbuminuria; ACE inhibitors and ARBs are renoprotective) and arteriolosclerosis (causing hypertension)  chronic kidney disease. Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, gangrene  limb loss, cerebrovascular disease. MI most common cause of death. Osmotic damage (sorbitol accumulation in organs with aldose reductase and  or absent sorbitol dehydrogenase):


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First_Aid_Step1. Osmotic damage (sorbitol accumulation in organs with aldose reductase and  or absent sorbitol dehydrogenase): Neuropathy (motor, sensory [glove and stocking distribution], and autonomic degeneration). Cataracts. ˜ muscle mass, weight loss ˛ plasma osmolality Osmotic diuresis Loss of water, Na+, and K+˛ thirst Hypovolemia Circulation failure, ˜ tissue perfusion Coma/death tissue glucose uptake ˛˛ glycogenolysis ˛ gluconeogenesis ˛ proteolysis Hyperventilation, Kussmaul respiration ˛ serum lactate ˛ lipolysis Hyperglycemia, glycosuria ˛ plasma free fatty acids ˛ ketogenesis, ketonemia, ketonuria Anion gap metabolic acidosis Vomiting Diabetic ketoacidosis Insulin absent, ketones present (• complications). Insulin noncompliance or  requirements from  stress (eg, infection)  excess fat breakdown and • ketogenesis from  free fatty acids • ketone bodies (β-hydroxybutyrate > acetoacetate). comPlicAtions Life-threatening mucormycosis, cerebral edema, cardiac arrhythmias, HF.


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First_Aid_Step1. comPlicAtions Life-threatening mucormycosis, cerebral edema, cardiac arrhythmias, HF. treAtment IV fluids, IV insulin, K+ (to replete intracellular stores) +/– glucose to prevent hypoglycemia. comPlicAtions Can progress to coma and death if untreated. treAtment IV fluids, IV insulin, and K+ (to replete intracellular stores). etiology  cortisol due to a variety of causes: Exogenous corticosteroids  ACTH  bilateral adrenal atrophy. Most common cause. Primary adrenal adenoma, hyperplasia, or carcinoma  ACTH  atrophy of uninvolved adrenal gland. ACTH-secreting pituitary adenoma (Cushing disease); paraneoplastic ACTH secretion (eg, small cell lung cancer, bronchial carcinoids) bilateral adrenal hyperplasia. Cushing disease is responsible for the majority of endogenous cases of Cushing syndrome.


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First_Aid_Step1. Findings CUSHING Syndrome: • Cholesterol, • Urinary free cortisol, Skin changes (thinning, striae A ), Hypertension, Immunosuppression, Neoplasm (a cause, not a finding), Growth retardation (in children), • Sugar (hyperglycemia, insulin resistance). Also, amenorrhea, moon facies B , buffalo hump, osteoporosis,  weight (truncal obesity), hirsutism. diAgnosis Screening tests include:  free cortisol on 24-hr urinalysis,  late night salivary cortisol, and no suppression with overnight low-dose dexamethasone test. ˜ 24-hr urine free cortisol, ˜ late night salivary cortisol, and/or inadequate suppression on 1 mg overnight dexamethasone test (consider adrenal CT to confrm) CT of the chest/abdomen/pelvis MRI of the pituitary CT of the chest/abdomen/pelvis


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First_Aid_Step1. CT of the chest/abdomen/pelvis MRI of the pituitary CT of the chest/abdomen/pelvis Nelson syndrome Enlargement of pre-existing ACTH–secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushing disease  ACTH (hyperpigmentation), mass effect (headaches, bitemporal hemianopia). Treatment: transsphenoidal resection, postoperative pituitary irradiation for residual tumor. Adrenal insufficiency Inability of adrenal glands to generate enough glucocorticoids +/− mineralocorticoids for the body’s needs. Symptoms include weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbances, sugar and/or salt cravings. Treatment: glucocorticoid/mineralocorticoid replacement.


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First_Aid_Step1. Metyrapone stimulation test ( conversion of 11-deoxycortisol to cortisol) Indeterminate cortisol results ↓AM or random cortisol, or ACTH stimulation test with ↓ peak cortisol Measure random serum ACTH Check AM or random cortisol, or ACTH stimulation test ↓/−/↑ACTH ↓↓11-deoxycortisol ↑↑ACTH ↑↑11-deoxycortisol ↑↑ACTH ↓11-deoxycortisol ↓ ACTH ↑ ACTH 2°/3° adrenal Normal response 1° adrenal 2°/3° adrenal 1° adrenal insu˜ciency to ↓ cortisol insu˜ciency insu˜ciency insu˜ciency Most common tumor of the adrenal medulla in children, usually < 4 years old. Originates from Neural crest cells. Occurs anywhere along the sympathetic chain. Most common presentation is abdominal distension and a firm, irregular mass that can cross the midline (vs Wilms tumor, which is smooth and unilateral). Less likely to develop hypertension than with pheochromocytoma (Neuroblastoma is Normotensive). Can also present with opsoclonus-myoclonus syndrome (“dancing eyes-dancing feet”).


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First_Aid_Step1. • HVA and VMA (catecholamine metabolites) in urine. Homer-Wright rosettes (neuroblasts surrounding a central lumen A ) characteristic of neuroblastoma and medulloblastoma. Bombesin and NSE ⊕. Associated with amplification of N-myc oncogene. MEN 1 Pituitary tumors (prolactin or GH) Pancreatic endocrine tumors—Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare) Parathyroid adenomas Associated with mutation of MEN1 (menin, a tumor suppressor, chromosome 11), angiofibromas, collagenomas, meningiomas MEN 2A Parathyroid hyperplasia Medullary thyroid carcinoma—neoplasm of parafollicular C cells; secretes calcitonin; prophylactic thyroidectomy required Pheochromocytoma (secretes catecholamines) Associated with mutation in RET (codes for receptor tyrosine kinase) Associated with marfanoid habitus; mutation in RET gene MEN 1 = 3 P’s: Pituitary, Parathyroid, and Pancreas MEN 2A = 2 P’s: Parathyroid and Pheochromocytoma MEN 2B = 1 P: Pheochromocytoma


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First_Aid_Step1. Associated with marfanoid habitus; mutation in RET gene MEN 1 = 3 P’s: Pituitary, Parathyroid, and Pancreas MEN 2A = 2 P’s: Parathyroid and Pheochromocytoma MEN 2B = 1 P: Pheochromocytoma Insulinoma Tumor of pancreatic β cells  overproduction of insulin • hypoglycemia. May see Whipple triad: low blood glucose, symptoms of hypoglycemia (eg, lethargy, syncope, diplopia), and resolution of symptoms after normalization of plasma glucose levels. Symptomatic patients have  blood glucose and • C-peptide levels (vs exogenous insulin use). ∼ 10% of cases associated with MEN 1 syndrome. Treatment: surgical resection. Glucagonoma Tumor of pancreatic α cells  overproduction of glucagon. Presents with 6 D’s: Dermatitis (necrolytic migratory erythema), Diabetes (hyperglycemia), DVT, Declining weight, Depression, Diarrhea. Treatment: octreotide, surgical resection.


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First_Aid_Step1. Somatostatinoma Tumor of pancreatic δ cells  overproduction of somatostatin  secretion of secretin, cholecystokinin, glucagon, insulin, gastrin, gastric inhibitory peptide (GIP). May present with diabetes/glucose intolerance, steatorrhea, gallstones, achlorhydria. Treatment: surgical resection; somatostatin analogs (eg, octreotide) for symptom control. Carcinoid tumors arise from neuroendocrine cells most commonly in the intestine or lung. Rare and does not occur if tumor is limited to the GI tract. Prominent rosettes (arrow in A ), chromogranin A ⊕ and synaptophysin ⊕). Neuroendocrine cells secrete 5-HT → recurrent diarrhea, wheezing, right-sided valvular heart disease (eg, tricuspid regurgitation, pulmonic stenosis), niacin deficiency (pellagra). 5-HT undergoes hepatic first-pass metabolism and enzymatic breakdown by MAO in the lung. Treatment: surgical resection, somatostatin analog (eg, octreotide, telotristat) for symptom control.


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First_Aid_Step1. Rule of thirds: 1/3 metastasize 1/3 present with 2nd malignancy 1/3 are multiple Rapid acting (1-hr Bind insulin receptor (tyrosine kinase activity) Hypoglycemia, lipodystrophy, hypersensitivity peak): Lispro, Aspart, Liver:  glucose storage as glycogen reactions (rare), weight gain Glulisine (no LAG) Muscle:  glycogen, protein synthesis Short acting (2–3 hr Fat:  TG storage peak): regular Cell membrane:  K+ uptake Intermediate acting (4–10 hr peak): NPH Long acting (no real peak): detemir, glargine Lispro, aspart, glulisine Regular NPH Detemir Glargine Chlorpropamide, tolbutamide Glipizide, glyburide Meglitinides “-gliNs” Nateglinide, Close K+ channels in pancreatic B cell membrane  cell depolarizes  insulin release via • Ca2+ influx. DisulFIRam-like reaction (FIRst-generation only). Rarely used. Hypoglycemia ( risk in renal insufficiency), weight gain.


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First_Aid_Step1. DisulFIRam-like reaction (FIRst-generation only). Rarely used. Hypoglycemia ( risk in renal insufficiency), weight gain. Amylin analogs • glucagon release,  gastric emptying. Hypoglycemia, nausea.  satiety (often desired). Pramlintide Thionamides Propylthiouracil, methimazole. mechAnism Block thyroid peroxidase, inhibiting the oxidation of iodide as well as the organification and coupling of iodine  inhibition of thyroid hormone synthesis. PTU also blocks 5′-deiodinase • Peripheral conversion of T4 to T3. clinicAl Use Hyperthyroidism. PTU used in first trimester of pregnancy (due to methimazole teratogenicity); methimazole used in second and third trimesters of pregnancy (due to risk of PTU-induced hepatotoxicity). Not used to treat Graves ophthalmopathy (treated with corticosteroids). AdVerse eFFects Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity. Methimazole is a possible teratogen (can cause aplasia cutis).


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First_Aid_Step1. AdVerse eFFects Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity. Methimazole is a possible teratogen (can cause aplasia cutis). Levothyroxine, liothyronine mechAnism Hormone replacement for T4 (levothyroxine) or T3 (liothyronine). clinicAl Use Hypothyroidism, myxedema. May be abused for weight loss. Distinguish exogenous hyperthyroidism from endogenous hyperthyroidism by using a combination of TSH receptor antibodies, radioactive iodine uptake, and/or measurement of thyroid blood flow on ultrasound. AdVerse eFFects Tachycardia, heat intolerance, tremors, arrhythmias. mechAnism Synthetic analog of aldosterone with little glucocorticoid effects. clinicAl Use Mineralocorticoid replacement in 1° adrenal insufficiency. AdVerse eFFects Similar to glucocorticoids; also edema, exacerbation of heart failure, hyperpigmentation. mechAnism Sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ • PTH.


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First_Aid_Step1. mechAnism Sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ • PTH. clinicAl Use 2° hyperparathyroidism in patients with CKD receiving hemodialysis, hypercalcemia in 1° hyperparathyroidism (if parathyroidectomy fails), or in parathyroid carcinoma. AdVerse eFFects Hypocalcemia. mechAnism Nonabsorbable phosphate binder that prevents phosphate absorption from the GI tract. clinicAl Use Hyperphosphatemia in CKD. AdVerse eFFects Hypophosphatemia, GI upset. “A good set of bowels is worth more to a man than any quantity of brains.” “Man should strive to have his intestines relaxed all the days of his life.” “All right, let’s not panic. I’ll make the money by selling one of my livers. I can get by with one.”


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First_Aid_Step1. When studying the gastrointestinal system, be sure to understand the normal embryology, anatomy, and physiology and how it is affected in the various pathologic diseases. Study not only what a disease entails, but also its specific findings, so that you can differentiate between two similar diseases. For example, what specifically makes ulcerative colitis different than Crohn disease? Also, it is important to understand bile metabolism and which lab values increase or decrease depending on the disease process. Be comfortable with basic interpretation of abdominal x-rays, CT scans, and endoscopic images. Ventral wall defects Developmental defects due to failure of rostral fold closure (eg, sternal defects [ectopia cordis]), lateral fold closure (eg, omphalocele, gastroschisis), or caudal fold closure (eg, bladder exstrophy). Congenital umbilical Failure of umbilical ring to close after physiologic herniation of the midgut. Small defects usually hernia close spontaneously.


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First_Aid_Step1. Congenital umbilical Failure of umbilical ring to close after physiologic herniation of the midgut. Small defects usually hernia close spontaneously. Tracheoesophageal Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is the most common (85%) anomalies and often presents as polyhydramnios in utero (due to inability of fetus to swallow amniotic fluid). Neonates drool, choke, and vomit with first feeding. TEFs allow air to enter stomach (visible on CXR). Cyanosis is 2° to laryngospasm (to avoid reflux-related aspiration). Clinical test: failure to pass nasogastric tube into stomach. In H-type, the fistula resembles the letter H. In pure EA, CXR shows gasless abdomen.


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First_Aid_Step1. Intestinal atresia Presents with bilious vomiting and abdominal distension within first 1–2 days of life. Duodenal atresia—failure to recanalize. Abdominal x-ray A shows “double bubble” (dilated stomach, proximal duodenum). Associated with Down syndrome. Jejunal and ileal atresia—disruption of mesenteric vessels (typically SMA)  ischemic necrosis of fetal intestine  segmental resorption: bowel becomes discontinuous. X-ray shows dilated loops of small bowel with air-fluid levels. Most common cause of gastric outlet obstruction in infants (1:600). Palpable olive-shaped mass in epigastric region, visible peristaltic waves, and nonbilious projectile vomiting at ∼ 2–6 weeks old. More common in firstborn males; associated with exposure to macrolides. Results in hypokalemic hypochloremic metabolic alkalosis (2° to vomiting of gastric acid and subsequent volume contraction). Ultrasound shows thickened and lengthened pylorus A .


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First_Aid_Step1. Results in hypokalemic hypochloremic metabolic alkalosis (2° to vomiting of gastric acid and subsequent volume contraction). Ultrasound shows thickened and lengthened pylorus A . Treatment: surgical incision of pyloric muscles (pyloromyotomy). Retroperitoneal Retroperitoneal structures A are posterior to structures (and outside of) the peritoneal cavity. Injuries to retroperitoneal structures can cause blood or gas accumulation in retroperitoneal space. SAD PUCKER: Suprarenal (adrenal) glands [not shown] Aorta and IVC Duodenum (2nd through 4th parts) Pancreas (except tail) Ureters [not shown] Colon (descending and ascending) Kidneys Esophagus (thoracic portion) [not shown] Rectum (partially) [not shown] Omental foramen (epiploic foramen of Winslow) Falciform ligament Liver to anterior abdominal Ligamentum teres hepatis Derivative of ventral mesentery wall (derivative of fetal umbilical vein), patent paraumbilical veins


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First_Aid_Step1. Falciform ligament Liver to anterior abdominal Ligamentum teres hepatis Derivative of ventral mesentery wall (derivative of fetal umbilical vein), patent paraumbilical veins Hepatoduodenal Liver to duodenum Portal triad: proper hepatic ligament artery, portal vein, common bile duct Derivative of ventral mesentery Pringle maneuver—ligament is compressed manually or with a vascular clamp in omental foramen to control bleeding from hepatic inflow source Borders the omental foramen, which connects the greater and lesser sacs Part of lesser omentum Esophagus Nonkeratinized stratified squamous epithelium. Upper 1/3, striated muscle; middle and lower 2/3 smooth muscle, with some overlap at the transition. Ileum Peyer patches (arrow in D ; lymphoid aggregates in lamina propria, submucosa), plicae circulares (proximal ileum), and crypts of Lieberkühn. Largest number of goblet cells in the small intestine. Colon Crypts of Lieberkühn with abundant goblet cells, but no villi E .


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First_Aid_Step1. Colon Crypts of Lieberkühn with abundant goblet cells, but no villi E . Arteries supplying GI structures are single and branch anteriorly. Arteries supplying non-GI structures are paired and branch laterally and posteriorly. Two areas of the colon have dual blood supply from distal arterial branches (“watershed regions”)  susceptible in colonic ischemia: Rectosigmoid junction—the last sigmoid arterial branch from the IMA and superior rectal artery Nutcracker syndrome—compression of left renal vein between superior mesenteric artery and aorta. Characterized by abdominal (flank) pain and gross hematuria (from rupture of thin-walled renal varicosities). Superior mesenteric artery syndrome— characterized by intermittent intestinal obstruction symptoms (primarily postprandial pain) when SMA and aorta compress transverse (third) portion of duodenum. Typically occurs in conditions associated with diminished mesenteric fat (eg, low body weight/malnutrition).


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First_Aid_Step1. Celiac trunk Branches of celiac trunk: common hepatic, splenic, and left gastric. These constitute the main blood supply of the foregut. Strong anastomoses exist between: Pathologic blood in portal HTN Flow through TIPS, re-establishing normal fow direction Varicesof gut, butt, and caput (medusae) are commonly seen with portal hypertension. Treatment with a transjugular intrahepatic portosystemic shunt (TIPS) between the portal vein and hepatic vein relieves portal hypertension by shunting blood to the systemic circulation, bypassing the liver. TIPS can precipitate hepatic encephalopathy due to  clearance of ammonia from shunting. Pectinate line Also called dentate line. Formed where endoderm (hindgut) meets ectoderm. Above pectinate line: internal hemorrhoids, adenocarcinoma. Internal hemorrhoids receive visceral innervation and are therefore not painful. Below pectinate line: external hemorrhoids, anal fissures, squamous cell carcinoma.


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First_Aid_Step1. Internal hemorrhoids receive visceral innervation and are therefore not painful. Below pectinate line: external hemorrhoids, anal fissures, squamous cell carcinoma. External hemorrhoids receive somatic innervation (inferior rectal branch of pudendal nerve) and are therefore painful if thrombosed. Anal fissure—tear in anal mucosa below Pectinate line. Pain while Pooping; blood on toilet Paper. Located Posteriorly because this area is Poorly Perfused. Innervated by Pudendal nerve. Associated with low-fiber diets and constipation. The functional unit of the liver is made up of hexagonally arranged lobules surrounding the central vein with portal triads on the edges (consisting of a portal vein, hepatic artery, bile ducts, as well as lymphatics) A . Apical surface of hepatocytes faces bile canaliculi. Basolateral surface faces sinusoids.


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First_Aid_Step1. Apical surface of hepatocytes faces bile canaliculi. Basolateral surface faces sinusoids. Kupffer cells (specialized macrophages) located in sinusoids (black arrows in B ; yellow arrows show hepatic venule) clear bacteria and damaged or senescent RBCs. Hepatic stellate (Ito) cells in space of Disse store vitamin A (when quiescent) and produce extracellular matrix (when activated). Responsible for hepatic fibrosis. Branch of hepatic artery Branch of portal vein Zone I—periportal zone: Best oxygenated, most resistant to circulatory compromise Ingested toxins (eg, cocaine) Zone II—intermediate zone: Yellow fever Zone III—pericentral vein (centrilobular) zone: High concentration of cytochrome P-450 Most sensitive to metabolic toxins (eg, ethanol, CCl4, halothane, rifampin, acetaminophen) Site of alcoholic hepatitis Stellate cell Space of Disse


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First_Aid_Step1. High concentration of cytochrome P-450 Most sensitive to metabolic toxins (eg, ethanol, CCl4, halothane, rifampin, acetaminophen) Site of alcoholic hepatitis Stellate cell Space of Disse Gallstones that reach the confluence of the common bile and pancreatic ducts at the ampulla of Vater can block both the common bile and pancreatic ducts (double duct sign), causing both cholangitis and pancreatitis, respectively. Tumors that arise in head of pancreas (usually ductal adenocarcinoma) can cause obstruction of common bile duct  enlarged gallbladder with painless jaundice (Courvoisier sign). Cholangiography shows filling defects in gallbladder (blue arrow) and cystic duct (red arrow) A . Femoral sheath Fascial tube 3–4 cm below inguinal ligament. Contains femoral vein, artery, and canal (deep inguinal lymph nodes) but not femoral nerve. Aponeurosis of external oblique muscle


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First_Aid_Step1. Femoral sheath Fascial tube 3–4 cm below inguinal ligament. Contains femoral vein, artery, and canal (deep inguinal lymph nodes) but not femoral nerve. Aponeurosis of external oblique muscle Evagination of transversalis fascia Internal (deep) inguinal ring Ductus (vas) deferens Genital branch of genitofemoral Hernias Protrusion of peritoneum through an opening, usually at a site of weakness. Contents may be at risk for incarceration (not reducible back into abdomen/pelvis) and strangulation (ischemia and necrosis). Complicated hernias can present with tenderness, erythema, fever.


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First_Aid_Step1. Direct inguinal hernia Protrudes through inguinal (Hesselbach) triangle. Bulges directly through parietal peritoneum medial to the inferior epigastric vessels but lateral to the rectus abdominis. Goes through external (superficial) inguinal ring only. Covered by external spermatic fascia. Usually occurs in older men due to acquired weakness of transversalis fascia. MDs don’t LIe: Medial to inferior epigastric vessels = Direct hernia. Lateral to inferior epigastric vessels = Indirect hernia. Femoral hernia Protrudes below inguinal ligament through femoral canal below and lateral to pubic tubercle. More common in females, but overall inguinal hernias are the most common. More likely to present with incarceration or strangulation (vs inguinal hernia).


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First_Aid_Step1. Abdominal structures enter the thorax A ; may occur due to congenital defect of pleuroperitoneal membrane or from trauma. Commonly occurs on left side due to relative protection of right hemidiaphragm by liver. Most commonly a hiatal hernia, in which stomach herniates upward through the esophageal hiatus of the diaphragm. Sliding hiatal hernia—gastroesophageal junction is displaced upward as gastric cardia slides into hiatus; “hourglass stomach.” Most gastric fundus common type. Associated with GERD. Paraesophageal hiatal hernia— gastroesophageal junction is usually normal but gastric fundus protrudes into the thorax. Goes through the internal (deep) inguinal ring, external (superficial) inguinal ring, and into the groin. Enters internal inguinal ring lateral to inferior epigastric vessels. Caused by failure of processus vaginalis to close (can form hydrocele). May be noticed in infants or discovered in adulthood. Much more common in males B .


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First_Aid_Step1. B . Follows the pathway of testicular descent. Covered by all 3 layers of spermatic fascia. Gastrin G cells (antrum of stomach, duodenum) in chronic atrophic gastritis (eg, H pylori) Intrinsic factor Parietal cells Vitamin B12–binding Autoimmune destruction (stomach A ) protein (required for B12 of parietal cells  chronic uptake in terminal ileum) gastritis and pernicious anemia. Gastric acid Parietal cells  stomach pH  by histamine, (stomach) vagal stimulation (ACh), gastrin  by somatostatin, GIP, prostaglandin, secretin Pepsin Chief cells Protein digestion  Pepsinogen (inactive) is (stomach) stimulation converted to pepsin (active) in (ACh), local the presence of H+. acid by pancreatic (stomach, and biliary the gastric epithelium. duodenum, secretion with salivary glands, secretin pancreas) and Brunner glands (duodenum)


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First_Aid_Step1. Gastrin  acid secretion primarily through its effects on enterochromaffin-like (ECL) cells (leading to histamine release) rather than through its direct effect on parietal cells. Pancreatic secretions Isotonic fluid; low flow  high Cl−, high flow  high HCO3 − . Only monosaccharides (glucose, galactose, fructose) are absorbed by enterocytes. Glucose and galactose are taken up by SGLT1 (Na+ dependent). Fructose is taken up via Facilitated diffusion by GLUT5. All are transported to blood by GLUT2. d-xylose absorption test: simple sugar that requires intact mucosa for absorption, but does not require digestive enzymes. Helps distinguish GI mucosal damage from other causes of malabsorption. Iron Absorbed as Fe2+ in duodenum Iron Fist, Bro Clinically relevant in patients with small bowel disease or after resection (eg, vitamin B12 Vitamin B Absorbed in terminal ileum along with bile salts, requires intrinsic factor Think of IgA, the Intra-gut Antibody


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First_Aid_Step1. Vitamin B Absorbed in terminal ileum along with bile salts, requires intrinsic factor Think of IgA, the Intra-gut Antibody Unencapsulated lymphoid tissue A found in lamina propria and submucosa of ileum. Contain specialized M cells that sample and present antigens to immune cells. B cells stimulated in germinal centers of Peyer patches differentiate into IgA-secreting plasma cells, which ultimately reside in lamina propria. IgA receives protective secretory component and is then transported across the epithelium to the gut to deal with intraluminal antigen. Bilirubin Heme is metabolized by heme oxygenase to biliverdin, which is subsequently reduced to bilirubin. Unconjugated bilirubin is removed from blood by liver, conjugated with glucuronate, and excreted in bile. Direct bilirubin: conjugated with glucuronic acid; water soluble (dissolves in water). Indirect bilirubin: unconjugated; water insoluble. Excreted in urine as urobilin (˜ yellow color)


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First_Aid_Step1. Excreted in urine as urobilin (˜ yellow color) Excreted in feces as stercobilin (˜ brown color of stool) Most are benign and commonly affect parotid gland (80-85%). Nearly half of all submandibular gland neoplasms and most sublingual and minor salivary gland tumors are malignant. Typically present as painless mass/swelling. Facial paralysis or pain suggests malignant involvement. Pleomorphic adenoma (benign mixed tumor)—most common salivary gland tumor A . Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or ruptured intraoperatively. May undergo malignant transformation. Mucoepidermoid carcinoma—most common malignant tumor, has mucinous and squamous components. Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal centers. Typically found in smokers. Bilateral in 10%; multifocal in 10%. “Warriors from Germany love smoking.”


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First_Aid_Step1. Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal centers. Typically found in smokers. Bilateral in 10%; multifocal in 10%. “Warriors from Germany love smoking.” Barrett esophagus Specialized intestinal metaplasia A —replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells [stained blue in B ]) in distal esophagus. Due to chronic gastroesophageal reflux disease (GERD). Associated with  risk of esophageal adenocarcinoma. Most commonly gastric adenocarcinoma; lymphoma, GI stromal tumor, carcinoid (rare). Early aggressive local spread with node/liver metastases. Often presents late, with weight loss, abdominal pain, early satiety, and in some cases acanthosis nigricans or Leser-Trélat sign. Associated with blood type A.


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First_Aid_Step1. Intestinal—associated with H pylori, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis. Commonly on lesser curvature; looks like ulcer with raised margins. Diffuse—not associated with H pylori; most cases due to E-cadherin mutation; signet ring cells (mucin-filled cells with peripheral nuclei) A ; stomach wall grossly thickened and leathery (linitis plastica). Erosions can be caused by: Especially common among alcoholics and NSAIDs—• PGE2  gastric mucosa patients taking daily NSAIDs (eg, patients with protection rheumatoid arthritis) Burns (Curling ulcer)—hypovolemia Burned by the Curling iron Brain injury (Cushing ulcer)—• vagal Always Cushion the brain stimulation  ACh  H+ production Mucosal inflammation, often leading to atrophy (hypochlorhydria • hypergastrinemia) and intestinal metaplasia ( risk of gastric cancers)


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First_Aid_Step1. Mucosal inflammation, often leading to atrophy (hypochlorhydria • hypergastrinemia) and intestinal metaplasia ( risk of gastric cancers) Hyperplasia of gastric mucosa  hypertrophied rugae (look like brain gyri A ). Causes excess mucus production with resultant protein loss and parietal cell atrophy with  acid production. Precancerous. Presents with Weight loss, Anorexia, Vomiting, Epigastric pain, Edema (due to protein loss) (WAVEE). Virchow node—involvement of left supraclavicular node by metastasis from stomach. Krukenberg tumor—bilateral metastases to ovaries. Abundant mucin-secreting, signet ring cells. Sister Mary Joseph nodule—subcutaneous periumbilical metastasis. Blumer shelf—palpable mass on digital rectal exam suggesting metastasis to rectouterine pouch (pouch of Douglas).


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First_Aid_Step1. Sister Mary Joseph nodule—subcutaneous periumbilical metastasis. Blumer shelf—palpable mass on digital rectal exam suggesting metastasis to rectouterine pouch (pouch of Douglas). Hemorrhage Gastric, duodenal (posterior > anterior). Most common complication. Ruptured gastric ulcer on the lesser curvature of stomach  bleeding from left gastric artery. An ulcer on the posterior wall of duodenum • bleeding from gastroduodenal artery. Obstruction Pyloric channel, duodenal. Perforation Duodenal (anterior > posterior). Anterior duodenal ulcers can perforate into the anterior abdominal cavity, potentially leading to pneumoperitoneum. May see free air under diaphragm (pneumoperitoneum) A with referred pain to the shoulder via irritation of phrenic nerve. ComPliCations Malabsorption/malnutrition, colorectal cancer ( risk with pancolitis).


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First_Aid_Step1. ComPliCations Malabsorption/malnutrition, colorectal cancer ( risk with pancolitis). Fistulas (eg, enterovesical fistulae, which can Fulminant colitis, toxic megacolon, perforation. cause recurrent UTI and pneumaturia), phlegmon/abscess, strictures (causing obstruction), perianal disease. intestinal maniFestation Diarrhea that may or may not be bloody. Bloody diarrhea. eXtraintestinal maniFestations Rash (pyoderma gangrenosum, erythema nodosum), eye inflammation (episcleritis, uveitis), oral ulcerations (aphthous stomatitis), arthritis (peripheral, spondylitis).


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First_Aid_Step1. Appendicitis Acute inflammation of the appendix (yellow arrows in A ), can be due to obstruction by fecalith (red arrow in A ) (in adults) or lymphoid hyperplasia (in children). Proximal obstruction of appendiceal lumen produces closed-loop obstruction  intraluminal pressure  stimulation of visceral afferent nerve fibers at T8-T10  initial diffuse periumbilical pain  inflammation extends to serosa and irritates parietal peritoneum. Pain localized to RLQ/ McBurney point (1/3 the distance from right anterior superior iliac spine to umbilicus). Nausea, fever; may perforate  peritonitis; may elicit psoas, obturator, and Rovsing signs, guarding and rebound tenderness on exam. Differential: diverticulitis (elderly), ectopic pregnancy (use hCG to rule out), pseudoappendicitis. Treatment: appendectomy. Diverticula of the GI tract Zenker diverticulum


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First_Aid_Step1. Diverticula of the GI tract Zenker diverticulum Pharyngoesophageal false diverticulum A . Esophageal dysmotility causes herniation of mucosal tissue at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor. Presenting symptoms: dysphagia, obstruction, gurgling, aspiration, foul breath, neck mass. Most common in elderly males. Elder MIKE has bad breath: Elderly Males Inferior pharyngeal constrictor Killian triangle Esophageal dysmotility Halitosis


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First_Aid_Step1. Elder MIKE has bad breath: Elderly Males Inferior pharyngeal constrictor Killian triangle Esophageal dysmotility Halitosis Meckel diverticulum True diverticulum. Persistence of the vitelline (omphalomesenteric) duct. May contain ectopic acid–secreting gastric mucosa and/or pancreatic tissue. Most common congenital anomaly of GI tract. Can cause hematochezia/ melena (less common), RLQ pain, intussusception, volvulus, or obstruction near terminal ileum. Contrast with omphalomesenteric cyst = cystic dilation of vitelline duct. Diagnosis: 99mTc-pertechnetate scan (aka Meckel scan) for uptake by heterotopic gastric mucosa. The rule of 2’s: 2 times as likely in males. 2 inches long. 2 feet from the ileocecal valve. 2% of population. Commonly presents in first 2 years of life. May have 2 types of epithelia (gastric/ pancreatic).


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First_Aid_Step1. Congenital megacolon characterized by lack of ganglion cells/enteric nervous plexuses (Auerbach and Meissner plexuses) in distal segment of colon. Due to failure of neural crest cell migration. Associated with loss of function mutations in RET. Presents with bilious emesis, abdominal distention, and failure to pass meconium within 48 hours • chronic constipation. Normal portion of the colon proximal to the aganglionic segment is dilated, resulting in a “transition zone.” Risk  with Down syndrome. Explosive expulsion of feces (squirt sign)  empty rectum on digital exam. Diagnosed by absence of ganglionic cells on rectal suction biopsy. Treatment: resection. RET mutation in the REcTum. Malrotation Anomaly of midgut rotation during fetal development  improper positioning of bowel (small bowel clumped on the right side) A , formation of fibrous bands (Ladd bands). Can lead to volvulus, duodenal obstruction.


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First_Aid_Step1. Volvulus Twisting of portion of bowel around its mesentery; can lead to obstruction and infarction. Can occur throughout the GI tract. Chronic mesenteric “Intestinal angina”: atherosclerosis of celiac artery, SMA, or IMA  intestinal hypoperfusion ischemia • postprandial epigastric pain  food aversion and weight loss. Colonic ischemia Reduction in intestinal blood flow causes ischemia. Crampy abdominal pain followed by hematochezia. Commonly occurs at watershed areas (splenic flexure, rectosigmoid junction). Typically affects elderly. Thumbprint sign on imaging due to mucosal edema/hemorrhage. Ileus Intestinal hypomotility without obstruction  constipation and  flatus; distended/tympanic abdomen with  bowel sounds. Associated with abdominal surgeries, opiates, hypokalemia, sepsis. Treatment: bowel rest, electrolyte correction, cholinergic drugs (stimulate intestinal motility).


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First_Aid_Step1. Colonic polyps Growths of tissue within the colon A . Grossly characterized as flat, sessile, or pedunculated on the basis of protrusion into colonic lumen. Generally classified by histologic type. Submucosal polyps May include lipomas, leiomyomas, fibromas, and other lesions. Malignant potential tooth” pattern of crypts on biopsy. Up to 20% of cases of sporadic CRC. A B C Polyp Polyp Cancer SessilePedunculated Lynch syndrome Previously called hereditary nonpolyposis colorectal cancer (HNPCC). Autosomal dominant mutation of mismatch repair genes (eg, MLH1, MSH2) with subsequent microsatellite instability. ∼ 80% progress to CRC. Proximal colon is always involved. Associated with endometrial, ovarian, and skin cancers. Diagnosis Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises suspicion. Screening:


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First_Aid_Step1. Diagnosis Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises suspicion. Screening: Low risk: screen at age 50 with colonoscopy (polyp seen in A ); alternatives include flexible sigmoidoscopy, fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), FIT-fecal DNA, CT colonography Patients with a first-degree relative who has colon cancer: screen at age 40 with colonoscopy, or 10 years prior to the relative's presentation Patients with IBD: distinct screening protocol “Apple core” lesion seen on barium enema x-ray B . CEA tumor marker: good for monitoring recurrence, should not be used for screening. ePiDemiology Most patients are > 50 years old. ~ 25% have a family history. Presentation Rectosigmoid > ascending > descending. Right side (cecal, ascending) associated with occult bleeding; left side (rectosigmoid) associated with hematochezia and obstruction (narrower lumen).


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First_Aid_Step1. Right side (cecal, ascending) associated with occult bleeding; left side (rectosigmoid) associated with hematochezia and obstruction (narrower lumen). Ascending—exophytic mass, iron deficiency anemia, weight loss. Descending—infiltrating mass, partial obstruction, colicky pain, hematochezia. Can present with S bovis (gallolyticus) bacteremia/endocarditis or as an episode of diverticulitis. risK FaCtors Adenomatous and serrated polyps, familial cancer syndromes, IBD, tobacco use, diet of processed meat with low fiber. Molecular Chromosomal instability pathway: mutations in APC cause FAP and most sporadic cases of CRC pathogenesis of via adenoma-carcinoma sequence; (firing order of events is “AK-53”). colorectal cancer Microsatellite instability pathway: mutations or methylation of mismatch repair genes (eg, MLH1) cause Lynch syndrome and some sporadic CRC (via serrated polyp pathway). Overexpression of COX-2 has been linked to colorectal cancer, NSAIDs may be chemopreventive.


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First_Aid_Step1. Loss of tumor suppressor Loss of APC gene KRAS mutation gene(s) (TP53, DCC) Cirrhosis—diffuse bridging fibrosis (via stellate cells) and regenerative nodules (red arrows in A ; white arrows show splenomegaly) disrupt normal architecture of liver;  risk for hepatocellular carcinoma (white arrow in B ). Etiologies include alcohol, nonalcoholic steatohepatitis, chronic viral hepatitis, autoimmune hepatitis, biliary disease, genetic/metabolic disorders. Portal hypertension— pressure in portal venous system. Etiologies include cirrhosis (most common cause in Western countries), vascular obstruction (eg, portal vein thrombosis, Budd- Chiari syndrome), schistosomiasis. Eects of portal hypertension *Due to estrogen Anorexia Nausea, vomiting Dull abdominal pain Serum markers of liver pathology Reye syndrome Rare, often fatal childhood hepatic encephalopathy.


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First_Aid_Step1. Eects of portal hypertension *Due to estrogen Anorexia Nausea, vomiting Dull abdominal pain Serum markers of liver pathology Reye syndrome Rare, often fatal childhood hepatic encephalopathy. Associated with viral infection (especially VZV and influenza) that has been treated with aspirin. Aspirin metabolites • β-oxidation by reversible inhibition of mitochondrial enzymes. Findings: mitochondrial abnormalities, fatty liver (microvesicular fatty changes), hypoglycemia, vomiting, hepatomegaly, coma. Avoid aspirin in children, except in those with Kawasaki disease. Salicylates aren’t a ray (Reye) of sunSHINE for kids: Steatosis of liver/hepatocytes Hypoglycemia/Hepatomegaly Infection (VZV, influenza) Not awake (coma) Encephalopathy


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First_Aid_Step1. Salicylates aren’t a ray (Reye) of sunSHINE for kids: Steatosis of liver/hepatocytes Hypoglycemia/Hepatomegaly Infection (VZV, influenza) Not awake (coma) Encephalopathy Alcoholic cirrhosis Final and usually irreversible form. Sclerosis around central vein (arrows in C ) may be seen in early disease. Regenerative nodules surrounded by fibrous bands in response to chronic liver injury  portal hypertension and end-stage liver disease. Nonalcoholic fatty Metabolic syndrome (insulin resistance); ALT > AST (Lipids) liver disease obesity • fatty infiltration of hepatocytes A  cellular “ballooning” and eventual necrosis. May cause cirrhosis and HCC. Independent of alcohol use. Most common 1° malignant tumor of liver in adults


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First_Aid_Step1. Most common 1° malignant tumor of liver in adults A . Associated with HBV (+/− cirrhosis) and all other causes of cirrhosis (including HCV, alcoholic and nonalcoholic fatty liver disease, autoimmune disease, hemochromatosis, Wilson disease, α1-antitrypsin deficiency) and specific carcinogens (eg, aflatoxin from Aspergillus). May lead to Budd-Chiari syndrome. Findings: jaundice, tender hepatomegaly, ascites, polycythemia, anorexia. Spreads hematogenously. Diagnosis: • α-fetoprotein; ultrasound or contrast CT/MRI B , biopsy. Hepatic adenoma Rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use; may regress spontaneously or rupture (abdominal pain and shock). Metastases GI malignancies, breast and lung cancer. Most common overall; metastases are rarely solitary.


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First_Aid_Step1. Metastases GI malignancies, breast and lung cancer. Most common overall; metastases are rarely solitary. Budd-Chiari syndrome Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis  congestive liver disease (hepatomegaly, ascites, varices, abdominal pain, liver failure). Absence of JVD. Associated with hypercoagulable states, polycythemia vera, postpartum state, HCC. May cause nutmeg liver (mottled appearance). 1-antitrypsin Misfolded gene product protein aggregates in In lungs, • α1-antitrypsin  uninhibited elastase deficiency hepatocellular ER  cirrhosis with in alveoli  elastic tissue • panacinar PAS ⊕ globules A in liver. Codominant trait. emphysema. Often presents in young patients with liver damage and dyspnea without a history of smoking. Jaundice Abnormal yellowing of the skin HOT Liver—common causes of • bilirubin and/or sclera A due to bilirubin deposition. level:


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First_Aid_Step1. Jaundice Abnormal yellowing of the skin HOT Liver—common causes of • bilirubin and/or sclera A due to bilirubin deposition. level: Hyperbilirubinemia 2° to  production Hemolysis or  clearance (impaired hepatic uptake, Obstruction conjugation, excretion). Tumor Hereditary All autosomal recessive. hyperbilirubinemias Gilbert syndrome Mildly  UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake. Asymptomatic or mild jaundice usually with stress, illness, or fasting.  unconjugated bilirubin without overt hemolysis. Relatively common, benign condition. Dubin-Johnson Conjugated hyperbilirubinemia due to defective liver excretion. Grossly black (Dark) liver due to syndrome impaired excretion of epinephrine metabolites. Benign. Similar to Dubin-Johnson syndrome, but milder in presentation without black (Regular) liver. Due to impaired hepatic uptake and excretion.


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First_Aid_Step1. Similar to Dubin-Johnson syndrome, but milder in presentation without black (Regular) liver. Due to impaired hepatic uptake and excretion. Endothelial cells Hemoglobin circulating bilirubin Kuper cell (macrophage) Obstructive jaundice (downstream) (albumin bound, unconjugated, water insoluble) Space of Disse HEPATIC SINUSOID RSTQQBILIRUBIN UPTAKE CONJUGATION INTRACELLULAR TRANSPORT UDP-glucuronosyl-transferase Unconjugated bilirubin Conjugated bilirubin (bilirubin diglucuronide, water soluble) Bile canalicular lumen Hepatocyte Bile fow Unknown cause of concentric “onion skin” bile duct fibrosis  alternating strictures and dilation with “beading” of intraand extrahepatic bile ducts on ERCP, magnetic resonance cholangiopancreatography (MRCP).


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First_Aid_Step1. Also called hepatolenticular degeneration. Autosomal recessive mutations in hepatocyte copper-transporting ATPase (ATP7B gene; chromosome 13) • copper incorporation into apoceruloplasmin and excretion into bile  serum ceruloplasmin. Copper accumulates, especially in liver, brain, cornea, kidneys;  urine copper. Presents before age 40 with liver disease (eg, hepatitis, acute liver failure, cirrhosis), neurologic disease (eg, dysarthria, dystonia, tremor, parkinsonism), psychiatric disease, Kayser-Fleischer rings (deposits in Descemet membrane of cornea) A , hemolytic anemia, renal disease (eg, Fanconi syndrome). Treatment: chelation with penicillamine or trientine, oral zinc. Liver transplant in acute liver failure related to Wilson disease.


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First_Aid_Step1. Treatment: chelation with penicillamine or trientine, oral zinc. Liver transplant in acute liver failure related to Wilson disease. Autosomal recessive. On HFE gene, located on chromosome 6; associated with HLA-A3. Leads to abnormal iron sensing and  intestinal absorption ( ferritin,  iron,  TIBC  transferrin saturation). Iron overload can also be 2° to chronic transfusion therapy (eg, β-thalassemia major). Iron accumulates, especially in liver, pancreas, skin, heart, pituitary, joints. Hemosiderin (iron) can be identified on liver MRI or biopsy with Prussian blue stain A .


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First_Aid_Step1. Presents after age 40 when total body iron > 20 g; iron loss through menstruation slows progression in women. Classic triad of cirrhosis, diabetes mellitus, skin pigmentation (“bronze diabetes”). Also causes restrictive cardiomyopathy (classic) or dilated cardiomyopathy (reversible), hypogonadism, arthropathy (calcium pyrophosphate deposition; especially metacarpophalangeal joints). HCC is common cause of death. Treatment: repeated phlebotomy, iron (Fe) chelation with deferasirox, deferoxamine, deferiprone. May present with pruritus, jaundice, dark urine, light-colored stool, hepatosplenomegaly. Typically with cholestatic pattern of LFTs ( conjugated bilirubin, • cholesterol,  ALP, • GGT). Classically in middle-aged men Associated with ulcerative with ulcerative colitis. colitis. p-ANCA ⊕.  IgM. Can lead to 2° biliary cholangitis.  risk of cholangiocarcinoma and gallbladder cancer.


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First_Aid_Step1. Classically in middle-aged men Associated with ulcerative with ulcerative colitis. colitis. p-ANCA ⊕.  IgM. Can lead to 2° biliary cholangitis.  risk of cholangiocarcinoma and gallbladder cancer. Autoimmune reaction Classically in middle-aged Anti-mitochondrial antibody ⊕, infiltrate women.  IgM. Associated with other +/– granulomas autoimmune conditions of lobular bile (eg, Hashimoto thyroiditis, ducts. rheumatoid arthritis, celiac disease). Treatment: ursodiol. Extrahepatic biliary obstruction Patients with known May be complicated by  pressure in intrahepatic obstructive lesions (gallstones, ascending cholangitis. ducts  injury/ fibrosis and biliary strictures, pancreatic bile stasis. carcinoma).  cholesterol and/or bilirubin,  bile salts, and Gender (female), Chronic hemolysis, gallbladder stasis all cause stones. age, obesity, genetics, biliary tract infection 2 types of stones:


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First_Aid_Step1.  cholesterol and/or bilirubin,  bile salts, and Gender (female), Chronic hemolysis, gallbladder stasis all cause stones. age, obesity, genetics, biliary tract infection 2 types of stones: Cholesterol stones (radiolucent with 10–20% opaque due to calcifications)—80% of stones. Associated with obesity, Crohn disease, advanced age, estrogen therapy, multiparity, rapid weight loss, Native American origin. Pigment stones A (black = radiopaque, Ca2+ bilirubinate, hemolysis; brown = radiolucent, infection). Associated with Crohn disease, chronic hemolysis, alcoholic cirrhosis, advanced age, biliary infections, total parenteral nutrition (TPN). Risk factors (4 F’s): 1. 2. 3. 4. Most common complication is cholecystitis; can also cause acute pancreatitis, ascending cholangitis. Diagnose with ultrasound. Treat with elective cholecystectomy if symptomatic.


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First_Aid_Step1. 2. 3. 4. Most common complication is cholecystitis; can also cause acute pancreatitis, ascending cholangitis. Diagnose with ultrasound. Treat with elective cholecystectomy if symptomatic. ↓cholesterol 7αhydroxylase ↑Cholesterol, ↓bile salts, gallbladder stasis ↑Unconjugated bilirubin, gallbladder stasis Supersaturation of bile with calcium bilirubinate Pigment stones Supersaturation of bile with cholesterol Cholesterol stones Choledocholithiasis Presence of gallstone(s) in common bile duct, often leading to elevated ALP, GGT, direct bilirubin, and/or AST/ALT.


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First_Aid_Step1. Cholecystitis Acute or chronic inflammation of gallbladder. Calculous cholecystitis—most common type; due to gallstone impaction in the cystic duct resulting in inflammation and gallbladder wall thickening (arrows in B ); can produce 2° infection. Acalculous cholecystitis—due to gallbladder stasis, hypoperfusion, or infection (CMV); seen in critically ill patients. Murphy sign: inspiratory arrest on RUQ palpation due to pain. Pain may radiate to right shoulder (due to irritation of phrenic nerve).  ALP if bile duct becomes involved (eg, ascending cholangitis). Diagnose with ultrasound or cholescintigraphy (HIDA scan). Failure to visualize gallbladder on HIDA scan suggests obstruction. Gallstone ileus—fistula between gallbladder and GI tract  stone enters GI lumen  obstructs at ileocecal valve (narrowest point); can see air in biliary tree (pneumobilia). Rigler triad: radiographic findings of pneumobilia, small bowel obstruction, gallstone (usually in iliac fossa).


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First_Aid_Step1. Porcelain gallbladder Calcified gallbladder due to chronic cholecystitis; usually found incidentally on imaging C . Treatment: prophylactic cholecystectomy generally recommended due to  risk of gallbladder cancer (mostly adenocarcinoma). Ascending cholangitis Infection of biliary tree usually due to obstruction that leads to stasis/bacterial overgrowth. Charcot triad of cholangitis includes jaundice, fever, RUQ pain. Reynolds pentad is Charcot triad plus altered mental status and shock (hypotension). Autodigestion of pancreas by pancreatic enzymes ( A shows pancreas [yellow arrows] surrounded by edema [red arrows]). Causes: Idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune disease, Scorpion sting, Hypercalcemia/Hypertriglyceridemia (> 1000 mg/dL), ERCP, Drugs (eg, sulfa drugs, NRTIs, protease inhibitors). I GET SMASHED.


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First_Aid_Step1. Diagnosis by 2 of 3 criteria: acute epigastric pain often radiating to the back,  serum amylase or lipase (more specific) to 3× upper limit of normal, or characteristic imaging findings. Complications: pseudocyst B (lined by granulation tissue, not epithelium), abscess, necrosis, hemorrhage, infection, organ failure (ALI/ARDS, shock, renal failure), hypocalcemia (precipitation of Ca2+ soaps). Chronic pancreatitis Chronic inflammation, atrophy, calcification of the pancreas A . Major causes include alcohol abuse and genetic predisposition (ie, cystic fibrosis); can be idiopathic. Complications include pancreatic insufficiency and pseudocysts. Pancreatic insufficiency (typically when <10% pancreatic function) may manifest with steatorrhea, fat-soluble vitamin deficiency, diabetes mellitus. Amylase and lipase may or may not be elevated (almost always elevated in acute pancreatitis).


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First_Aid_Step1. Very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular infiltration A ); often metastatic at presentation, with average survival ~ 1 year after diagnosis. Tumors more common in pancreatic head B (lead to obstructive jaundice). Associated with CA 19-9 tumor marker (also CEA, less specific). Risk factors: Jewish and African-American males Often presents with: Abdominal pain radiating to back Weight loss (due to malabsorption and anorexia) Migratory thrombophlebitis—redness and tenderness on palpation of extremities (Trousseau syndrome) Obstructive jaundice with palpable, nontender gallbladder (Courvoisier sign) Treatment: Whipple procedure (pancreaticoduodenectomy), chemotherapy, radiation therapy. HCO3 ”alkaline tide”— ˜ blood pH after gastric acid secretion (eg, after meals, vomiting) Misoprostol H+ K+ Sucralfate, bismuth


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First_Aid_Step1. HCO3 ”alkaline tide”— ˜ blood pH after gastric acid secretion (eg, after meals, vomiting) Misoprostol H+ K+ Sucralfate, bismuth Histamine-2 blockers Cimetidine, ranitidine, famotidine, nizatidine. Take H2 blockers before you dine. Think “table for 2” to remember H2. meCHanism Reversible block of histamine H2-receptors  H+ secretion by parietal cells. CliniCal Use Peptic ulcer, gastritis, mild esophageal reflux. aDVerse eFFeCts Cimetidine is a potent inhibitor of cytochrome P-450 (multiple drug interactions); it also has antiandrogenic effects (prolactin release, gynecomastia, impotence,  libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta. Both cimetidine and ranitidine  renal excretion of creatinine. Other H2 blockers are relatively free of these effects. Proton pump inhibitors Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole. meCHanism Irreversibly inhibit H+/K+ ATPase in stomach parietal cells.


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First_Aid_Step1. Proton pump inhibitors Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole. meCHanism Irreversibly inhibit H+/K+ ATPase in stomach parietal cells. CliniCal Use Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome, component of therapy for H pylori, stress ulcer prophylaxis. aDVerse eFFeCts  risk of C difficile infection, pneumonia, acute interstitial nephritis. Vitamin B12 malabsorption;  serum Mg2+ and • Ca2+ absorption (potentially leading to increased fracture risk in elderly). Antacids Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. All can cause hypokalemia. Overuse can also cause the following problems: Bismuth, sucralfate meCHanism Bind to ulcer base, providing physical protection and allowing HCO3 secretion to reestablish pH gradient in the mucous layer. Sucralfate requires acidic environment, not given with PPIs/H2 blockers.


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First_Aid_Step1. CliniCal Use  ulcer healing, travelers’ diarrhea (bismuth). Bismuth also used in quadruple therapy for H pylori gastritis. aDVerse eFFeCts Diarrhea. Contraindicated in women of childbearing potential (abortifacient). meCHanism Long-acting somatostatin analog; inhibits secretion of various splanchnic vasodilatory hormones. CliniCal Use Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors. aDVerse eFFeCts Nausea, cramps, steatorrhea.  risk of cholelithiasis due to CCK inhibition. meCHanism A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). Activated by colonic bacteria. CliniCal Use Ulcerative colitis, Crohn disease (colitis component). aDVerse eFFeCts Malaise, nausea, sulfonamide toxicity, reversible oligospermia. meCHanism Agonist at μ-opioid receptors; slows gut motility. Poor CNS penetration (low addictive potential). CliniCal Use Diarrhea. aDVerse eFFeCts Constipation, nausea.


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First_Aid_Step1. meCHanism Agonist at μ-opioid receptors; slows gut motility. Poor CNS penetration (low addictive potential). CliniCal Use Diarrhea. aDVerse eFFeCts Constipation, nausea. meCHanism 5-HT3 antagonist;  vagal stimulation. Powerful central-acting antiemetic. CliniCal Use Control vomiting postoperatively and in patients undergoing cancer chemotherapy. aDVerse eFFeCts Headache, constipation, QT interval prolongation, serotonin syndrome. meCHanism D2 receptor antagonist.  resting tone, contractility, LES tone, motility, promotes gastric emptying. Does not influence colon transport time. CliniCal Use Diabetic and postoperative gastroparesis, antiemetic, persistent GERD. aDVerse eFFeCts • parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction, Parkinson disease (due to D2-receptor blockade), • seizure threshold.


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First_Aid_Step1. meCHanism Inhibits gastric and pancreatic lipase  breakdown and absorption of dietary fats. Taken with fat-containing meals. CliniCal Use Weight loss. aDVerse eFFeCts Abdominal pain, flatulence, bowel urgency/frequent bowel movements, steatorrhea;  absorption of fat-soluble vitamins. Laxatives Indicated for constipation or patients on opiates requiring a bowel regimen. meCHanism Substance P antagonist. Blocks NK1 (neurokinin-1) receptors in brain. CliniCal Use Antiemetic for chemotherapy-induced nausea and vomiting. “You’re always somebody’s type! (blood type, that is)” “All the soarings of my mind begin in my blood.” “The best blood will at some time get into a fool or a mosquito.”


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First_Aid_Step1. “You’re always somebody’s type! (blood type, that is)” “All the soarings of my mind begin in my blood.” “The best blood will at some time get into a fool or a mosquito.” When studying hematology, pay close attention to the many cross connections to immunology. Make sure you master the different types of anemias. Be comfortable interpreting blood smears. When reviewing oncologic drugs, focus on mechanisms and adverse effects rather than details of clinical uses, which may be lower yield. Please note that solid tumors are covered in their respective organ system chapters. Fetal erythropoiesis Fetal erythropoiesis occurs in: Young Liver Synthesizes Blood. Bone marrow (18 weeks to adult) Embryonic globins: ζ and ε. Fetal hemoglobin (HbF) =αγ From fetal to adult hemoglobin: 2 2. Adult hemoglobin (HbA ) =αβ Alpha Always; Gamma Goes, Becomes Beta. 1 22.


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First_Aid_Step1. Embryonic globins: ζ and ε. Fetal hemoglobin (HbF) =αγ From fetal to adult hemoglobin: 2 2. Adult hemoglobin (HbA ) =αβ Alpha Always; Gamma Goes, Becomes Beta. 1 22. HbF has higher affinity for O2 due to less avid binding of 2,3-BPG, allowing HbF to extract O2 from maternal hemoglobin (HbA1 and HbA2) across the placenta. HbA2 (α2δ2) is a form of adult hemoglobin present in small amounts. Site of erythropoiesis 50 40 % of total 30 globin synthesis 20 Hemolytic disease of Also known as erythroblastosis fetalis. the newborn Neutrophils Acute inflammatory response cells. Numbers Hypersegmented neutrophils (nucleus has 6+  in bacterial infections. Phagocytic. lobes) are seen in vitamin B / folate deficiency.


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First_Aid_Step1. Neutrophils Acute inflammatory response cells. Numbers Hypersegmented neutrophils (nucleus has 6+  in bacterial infections. Phagocytic. lobes) are seen in vitamin B / folate deficiency. A 12 Multilobed nucleus A . Specific granules A left shift with  band cells (immature contain leukocyte alkaline phosphatase neutrophils) reflects states of  myeloid (LAP), collagenase, lysozyme, and proliferation (eg, bacterial infections, CML). lactoferrin. Azurophilic granules (lysosomes) Important neutrophil chemotactic agents: C5a, contain proteinases, acid phosphatase, IL-8, LTB4, kallikrein, platelet-activating factor. myeloperoxidase, and β-glucuronidase.


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First_Aid_Step1. Carry O2 to tissues and CO2 to lungs. Anucleate and lack organelles; biconcave A , with large surface area-to-volume ratio for rapid gas exchange. Life span of 120 days. Source of energy is glucose (90% used in glycolysis, 10% used in HMP shunt). Membranes contain Cl−/HCO3 − antiporter, which allow RBCs to export HCO3 − and transport CO2 from the periphery to the lungs for elimination. Eryth = red; cyte = cell. Erythrocytosis = polycythemia =  Hct. Anisocytosis = varying sizes. Poikilocytosis = varying shapes. Reticulocyte = immature RBC; reflects erythroid proliferation. Bluish color (polychromasia) on Wright-Giemsa stain of reticulocytes represents residual ribosomal RNA.


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First_Aid_Step1. Reticulocyte = immature RBC; reflects erythroid proliferation. Bluish color (polychromasia) on Wright-Giemsa stain of reticulocytes represents residual ribosomal RNA. Involved in 1° hemostasis. Small cytoplasmic fragments A derived from megakaryocytes. Life span of 8–10 days. When activated by endothelial injury, aggregate with other platelets and interact with fibrinogen to form platelet plug. Contain dense granules (Ca2+ , ADP, Serotonin, Histamine; CASH) and α granules (vWF, fibrinogen, fibronectin, platelet factor 4). Approximately 1⁄3 of platelet pool is stored in the spleen. in petechiae. vWF receptor: GpIb. Fibrinogen receptor: GpIIb/IIIa. Thrombopoietin stimulates megakaryocyte proliferation. Alfa granules contain vWF, fibrinogen, fibronectin, platelet factor four. Monocytes Found in blood, differentiate into macrophages Mono = one (nucleus); cyte = cell. in tissues. Large, kidney-shaped nucleus A . Extensive “frosted glass” cytoplasm.


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First_Aid_Step1. Monocytes Found in blood, differentiate into macrophages Mono = one (nucleus); cyte = cell. in tissues. Large, kidney-shaped nucleus A . Extensive “frosted glass” cytoplasm. Phagocytose bacteria, cellular debris, and senescent RBCs. Long life in tissues. Differentiate from circulating blood monocytes A . Activated by γ-interferon. Can function as antigen-presenting cell via MHC II. Important cellular component of granulomas (eg, TB, sarcoidosis). Macro = large; phage = eater. Macrophage naming varies by specific tissue type (eg, Kupffer cells in liver, histiocytes in connective tissue, Langerhans cells in skin, osteoclasts in bone, microglial cells in brain). Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock.


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First_Aid_Step1. Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock. Basophils Mediate allergic reaction. Densely basophilic Basophilic—stains readily with basic stains. granules A contain heparin (anticoagulant) Basophilia is uncommon, but can be a sign of and histamine (vasodilator). Leukotrienes myeloproliferative disorders, particularly CML. synthesized and released on demand. Dendritic cells Highly phagocytic antigen-presenting cells (APCs) A . Function as link between innate and adaptive immune systems. Express MHC class II and Fc receptors on surface. Defend against helminthic infections (major basic protein). Bilobate nucleus. Packed with large eosinophilic granules of uniform size A . Highly phagocytic for antigen-antibody complexes. Produce histaminase, major basic protein (MBP, a helminthotoxin), eosinophil peroxidase, eosinophil cationic protein, and eosinophilderived neurotoxin. Eosin = pink dye; philic = loving.


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First_Aid_Step1. Produce histaminase, major basic protein (MBP, a helminthotoxin), eosinophil peroxidase, eosinophil cationic protein, and eosinophilderived neurotoxin. Eosin = pink dye; philic = loving. Causes of eosinophilia = PACCMAN: Parasites Asthma Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) Chronic adrenal insufficiency Myeloproliferative disorders Allergic processes Neoplasia (eg, Hodgkin lymphoma) Lymphocytes Refer to B cells, T cells, and NK cells. B cells and T cells mediate adaptive immunity. NK cells are part of the innate immune response. Round, densely staining nucleus with small amount of pale cytoplasm A .


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First_Aid_Step1. A . Natural killer cells Important in innate immunity, especially against intracellular pathogens. Larger than B and T cells, with distinctive cytoplasmic lytic granules (containing perforin and granzymes) that, when released, act on target cells to induce apoptosis. Distinguish between healthy and infected cells by identifying cell surface proteins (induced by stress, malignant transformation, or microbial infections). Mediate humoral immune response. Originate from stem cells in bone marrow and matures in marrow. Migrate to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue). When antigen is encountered, B cells differentiate into plasma cells (which produce antibodies) and memory cells. Can function as an APC. B = Bone marrow.


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First_Aid_Step1. B = Bone marrow. Mediate cellular immune response. Originate from stem cells in the bone marrow, but mature in the thymus. Differentiate into cytotoxic T cells (express CD8, recognize MHC I), helper T cells (express CD4, recognize MHC II), and regulatory T cells. CD28 (costimulatory signal) necessary for T-cell activation. Most circulating lymphocytes are T cells (80%). T = Thymus. CD4+ helper T cells are the primary target of HIV. Rule of 8: MHC II × CD4 = 8; MHC I × CD8 = 8. Plasma cells Produce large amounts of antibody specific to Multiple myeloma is a plasma cell dyscrasia. a particular antigen. “Clock-face” chromatin distribution and eccentric nucleus, abundant RER, and well-developed Golgi apparatus (arrows in A ). Found in bone marrow and normally do not circulate in peripheral blood.