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First_Aid_Step1. (retroperitoneal). Gynecologic procedures (eg, ligation of  ureteral obstruction or leak. (in female) Bladder contraction compresses the intravesical ureter, preventing urine reflux. Blood supply to ureter: Middle—gonadal artery, aorta, common and internal iliac arteries 3 common points of ureteral obstruction: ureteropelvic junction, pelvic inlet, ureterovesical junction. Body mass: 70 kg HIKIN’: HIgh K+ INtracellularly. 60–40–20 rule (% of body weight for average 60% of body mass = 42 kg 42 L 40% of body mass = 28 kg person): 40% ICF, mainly composed of K+, Mg2+, organic phosphates (eg, ATP) 20% ECF, mainly composed of Na+, Cl–, Extracellular fuid (ECF)~ 14 kg (20% of 70 kg) Intracellular fuid (ICF)~ 28 kg (40% of 70 kg) Interstitial fuid = 75% ECF 10.5 L 10.5 kg Blood volume 6 L Plasma = 25% ECF 3.5 L 3.5 kg RBC volume 2.8 L HCO3–, albumin Normal Hct = 45% Plasma volume can be measured by Hct (%) 3 [Hb] in g/dL radiolabeling albumin.


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First_Aid_Step1. HCO3–, albumin Normal Hct = 45% Plasma volume can be measured by Hct (%) 3 [Hb] in g/dL radiolabeling albumin. or mannitol. Serum osmolality = 285–295 mOsm/kg H2O. Plasma volume = TBV × (1 – Hct). Glomerular filtration Responsible for filtration of plasma according to Charge barrier—all 3 layers contain ⊝ charged barrier size and charge selectivity. glycoproteins that prevent entry of ⊝ charged Composed of: Basement membrane with type IV collagen chains and heparan sulfate Visceral epithelial layer consisting of podocyte foot processes (FPs) molecules (eg, albumin). Size barrier—fenestrated capillary endothelium (prevents entry of > 100 nm molecules/blood cells); podocyte foot processes interpose with glomerular basement membrane (GBM); slit diaphragm (prevents entry of molecules > 50–60 nm). Glomerular filtration Inulin clearance can be used to calculate GFR 14 rate because it is freely filtered and is neither reabsorbed nor secreted. 12


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First_Aid_Step1. Glomerular filtration Inulin clearance can be used to calculate GFR 14 rate because it is freely filtered and is neither reabsorbed nor secreted. 12 Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR because 2 creatinine is moderately secreted by renal tubules. coefficient). Normal GFR ≈ 100 mL/min. Filtration Filtration fraction (FF) = GFR/RPF. GFR can be estimated with creatinine Normal FF = 20%. clearance. Filtered load (mg/min) = GFR (mL/min) RPF is best estimated with PAH clearance. × plasma concentration (mg/mL). Prostaglandins Dilate Afferent arteriole (PDA). Angiotensin II Constricts Efferent arteriole (ACE). Prostaglandins preferentially dilate aƒerent arteriole Bowman capsule GFR, so no ˜ FF) (parietal layer) RPF, RPF, GFR, so Calculation of Filtered load = GFR × P. reabsorption and Excretion rate = V × Ux.


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First_Aid_Step1. RPF, RPF, GFR, so Calculation of Filtered load = GFR × P. reabsorption and Excretion rate = V × Ux. secretion rate Reabsorption rate = filtered – excreted. Secretion rate = excreted – filtered. FeNa = fractional excretion of sodium. Glucose clearance Glucose at a normal plasma level (range 60–120 mg/dL) is completely reabsorbed in proximal convoluted tubule (PCT) by Na+/glucose cotransport. In adults, at plasma glucose of ∼ 200 mg/dL, glucosuria begins (threshold). At rate of ∼ 375 mg/min, all transporters are fully saturated (Tm). Normal pregnancy is associated with  GFR. With  filtration of all substances, including glucose, the glucose threshold occurs at lower plasma glucose concentrations  glucosuria at normal plasma glucose levels. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (eg, -flozin drugs) result in glucosuria at plasma concentrations < 200 mg/dL. Glucosuria is an important clinical clue to diabetes mellitus.


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First_Aid_Step1. Glucosuria is an important clinical clue to diabetes mellitus. Splay phenomenon—Tm for glucose is reached gradually rather than sharply due to the heterogeneity of nephrons (ie, different Tm points); represented by the portion of the titration curve between threshold and T . Early PCT—contains brush border. Reabsorbs all glucose and amino acids and most HCO3–, Na+, Cl–, PO43–, K+, H2O, and uric acid. Isotonic absorption. Generates and secretes NH3, which enables the kidney to secrete more H+. PTH—inhibits Na+/PO43– cotransport •• PO43– excretion. AT II—stimulates Na+/H+ exchange •• Na+, H2O, and HCO3− reabsorption (permitting contraction alkalosis). 65–80% Na+ and H2O reabsorbed. Thin descending loop of Henle—passively reabsorbs H2O via medullary hypertonicity (impermeable to Na+). Concentrating segment. Makes urine hypertonic. Mg2+, Ca2+ Interstitium blood Diusion down the electrochemical gradient


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First_Aid_Step1. Mg2+, Ca2+ Interstitium blood Diusion down the electrochemical gradient Thick ascending loop of Henle—reabsorbs Na+, K+, and Cl−. Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through ˜ lumen potential generated by K+ backleak. Impermeable to H2O. Makes urine less concentrated as it ascends. 10–20% Na+ reabsorbed. Early DCT—reabsorbs Na+, Cl−. Impermeable to H2O. Makes urine fully dilute (hypotonic). PTH—• Ca2+/Na+ exchange •• Ca2+ reabsorption. 5–10% Na+ reabsorbed. Collecting tubule—reabsorbs Na+ in exchange for secreting K+ and H+ (regulated by aldosterone). Aldosterone—acts on mineralocorticoid receptor • mRNA • protein synthesis. In principal cells: • apical K+ conductance, • Na+/K+ pump, • epithelial Na+ channel (ENaC) activity • lumen negativity • K+ secretion. In ˜-intercalated cells: lumen negativity •• H+ ATPase activity •• H+ secretion •• HCO3−/Cl− exchanger activity.


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First_Aid_Step1. ADH—acts at V2 receptor • insertion of aquaporin H2O channels on apical side. 3–5% Na+ reabsorbed. Renal tubular defects Order: Fanconi’s BaGeLS Gitelman syndrome Bartter syndrome Liddle syndrome, SAME Syndrome of Apparent Mineralocorticoid Excess Treatment: K+-sparing diuretics (• mineralocorticoid effects) or corticosteroids (exogenous corticosteroid • endogenous cortisol production • mineralocorticoid receptor activation) 0% 25% 50% 75% 100% % Distance along PCT length PAH Creatinine Inulin clearance = GFR Urea Cl−Glucose Amino acids HCO3 – K+ Osmolarity, Na+ 1.90 1.85 when solute is reabsorbed less quickly 1.80 Tubular inulin  in concentration (but not amount) along the PCT as a result of water reabsorption. Cl− reabsorption occurs at a slower rate than Na+ in early PCT and then matches the rate of Na+ reabsorption more distally. Thus, its relative concentration  before it plateaus.


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First_Aid_Step1. Renal cells ↑BP ↑activity Na+ , HCOƒ , and H⁄O H+ secretion ↑receptor type I Vasoconstriction ↑FF arteriole Na+ reabsorption H⁄O reabsorption secretion pituitary) Preserves GFR (when RBF ) PCT cell α-intercalated cell Principal cell Na+/K+ ATPase, and ENaC activity) Renin Secreted by JG cells in response to  renal perfusion pressure (detected by renal baroreceptors in afferent arteriole),  renal sympathetic discharge (β1 effect), and • NaCl delivery to macula densa cells. AT II Helps maintain blood volume and blood pressure. Affects baroreceptor function; limits reflex bradycardia, which would normally accompany its pressor effects. ANP, BNP Released from atria (ANP) and ventricles (BNP) in response to  volume; inhibits renin-angiotensinaldosterone system; relaxes vascular smooth muscle via cGMP  GFR, • renin. Dilates afferent arteriole, promotes natriuresis.


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First_Aid_Step1. ADH Primarily regulates serum osmolality; also responds to low blood volume states. Stimulates reabsorption of water in collecting ducts. Also stimulates reabsorption of urea in collecting ducts to maximizes corticopapillary osmotic gradient. Aldosterone Primarily regulates ECF volume and Na+ content;  release in  blood volume states. Responds to hyperkalemia by  K+ excretion. contraction alkalosis) activity) ( K+ conductance, JGA maintains GFR via renin-angiotensinaldosterone system. In addition to vasodilatory properties, β-blockers can decrease BP by inhibiting β1-receptors of the JGA  renin release. Calciferol (vitamin D) PCT cells convert 25-OH vitamin D to 1,25-25-OH D (OH)2 vitamin D3 (calcitriol, active form). (calcidiol) 1˜-hydroxylase (calcitriol) 1,25-(OH) D Secreted in response to ° atrial pressure. Causes ° GFR and ° Na+ fltration with no compensatory Na+ reabsorption + loss and volume loss.


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First_Aid_Step1. Synthesized in response to reabsorption in proximal and distal nephron. Net e˜ect: BP. Causes e˜erent arteriole˜ ° GFR and ° FF but with compensatory Na+ preservation of renal function (° FF) in low-volume state with simultaneous Na+ reabsorption (both proximal and distal) to maintain circulating volume. Glomerulus Proximal convoluted tubule Loop of Henle Ascending limb, loop of Henle (permeable to salts) Collecting duct convoluted tubule Cortex Medulla Sugars Amino acids Na+ Na+ K+ 2CI– Ca2+ Mg2+ Mg2+ Na+ CI– H Ca2+ Parathyroid hormone Secreted in response to ˜ plasma [Ca2+], ° plasma [PO43–], or ˜ plasma 1,25-(OH)2 D3. Causes ° [Ca2+] reabsorption (DCT), ˜ [PO43–] reabsorption (PCT), and ° 1,25-(OH)2 D3 production (° Ca2+ and PO43– absorption from gut via vitamin D). Aldosterone Secreted in response to ˜ blood volume (via AT II) and ° plasma [K+ ]; causes ° Na+ reabsorption, ° K+ secretion, ° H+ secretion. ADH (vasopressin) Secreted in response to ° plasma osmolarity and ˜ blood


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First_Aid_Step1. in response to ˜ blood volume (via AT II) and ° plasma [K+ ]; causes ° Na+ reabsorption, ° K+ secretion, ° H+ secretion. ADH (vasopressin) Secreted in response to ° plasma osmolarity and ˜ blood volume. Binds to receptors on principal cells, causing ° number of aquaporins and ° H2O reabsorption. ° reabsorption of urea in collecting ducts to maximize corticopapillary osmotic gradient. K+ H+ Na+


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First_Aid_Step1. Features of renal disorders Key: • = compensatory response. [HCO3 −]Henderson-Hasselbalch equation: pH = 6.1 + log 0.03 P2 Predicted respiratory compensation for a simple metabolic acidosis can be calculated using the Winters formula. If measured Pco2 > predicted Pco2  concomitant respiratory acidosis; if measured Pco2 < predicted Pco2 • concomitant respiratory alkalosis: Pco2 = 1.5 [HCO3–] + 8 ± 2 Acidosis and alkalosis Check arterial pH pH < 7.35 Pco2 > 44 mm Hg HCO3 – < 20 mEq/L Acidemia Respiratory acidosis Metabolic acidosis Hypoventilation Airway obstruction Acute lung disease Chronic lung disease Opioids, sedatives Weakening of respiratory muscles •Anion gap MUDPILES: Normal anion gap Check anion gap Methanol (formic acid) Uremia Diabetic ketoacidosis Propylene glycol Iron tablets or INH Lactic acidosis Ethylene glycol (oxalic acid) Salicylates (late) HARDASS:= Na+ – (CI + HCO3 )– _


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First_Aid_Step1. Anxiety/panic attack Hypoxemia (eg, high altitude) Salicylates (early) Tumor Pulmonary embolism pH > 7.45 6.97.0 7.17.2 7.37.4 7.57.6 7.77.8 7.9 Renal tubular Disorder of the renal tubules that causes normal anion gap (hyperchloremic) metabolic acidosis. acidosis Distal renal Inability of > 5.5 • Amphotericin B toxicity,  risk for calcium tubular acidosis α-intercalated cells to analgesic nephropathy, phosphate kidney (type 1) secrete H+  no new congenital anomalies stones (due to  urine HCO3 is generated (obstruction) of urinary pH and  bone • metabolic acidosis tract, autoimmune turnover related to diseases (eg, SLE) buffering) Defect in PCT > 5.5 when HCO3 reabsorption resorptive  excretion of threshold


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First_Aid_Step1. Defect in PCT > 5.5 when HCO3 reabsorption resorptive  excretion of threshold Urine can be acidified by exceeded; α-intercalated cells in < 5.5 when collecting duct, but not HCO3 enough to overcome depleted • Fanconi syndrome,  risk for multiple myeloma, hypophosphatemic carbonic anhydrase rickets (in Fanconi inhibitors syndrome) (eg, diabetic hyporeninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency) or aldosterone resistance (eg, K+-sparing diuretics, nephropathy due to obstruction, TMP-SMX) Casts in urine Presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin. Bladder cancer, kidney stones  hematuria, no casts. Acute cystitis  pyuria, no casts. A Glomerulonephritis, hypertensive emergency. B Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection.


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First_Aid_Step1. A Glomerulonephritis, hypertensive emergency. B Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection. Nomenclature of glomerular disorders Glomerular diseases  GBM damage  loss of RBCs into urine • hematuria Hematuria, RBC casts in urine  oliguria, azotemia, release, HTN Proteinuria often in the subnephrotic range (< 3.5 g/ day) but in severe cases may be in nephrotic range Massive proteinuria (> 3.5 g/ day) with hypoalbuminemia, edema Frothy urine with fatty casts Associated with hypercoagulable state due to antithrombin III loss in urine and  risk of infection (loss of IgGs in urine and soft tissue compromise by edema) May be 1° (eg, direct podocyte damage) or 2° (podocyte damage from systemic process):


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First_Aid_Step1. Kidney Can lead to severe complications such as hydronephrosis, pyelonephritis, and acute kidney injury. Obstructed stones stone presents with unilateral flank tenderness, colicky pain radiating to groin, hematuria. Treat and prevent by encouraging fluid intake. Calcium Calcium Radiopaque Radiopaque Shaped like oxalate: envelope Calcium Radiopaque Radiopaque Wedge-phosphate: shaped • pH prism Calcium stones most common (80%); calcium oxalate more common than calcium phosphate stones. Can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia (associated with  urine pH), malabsorption (eg, Crohn disease). Treatment: thiazides, citrate, low-sodium diet. Treatment: low-sodium diet, thiazides. B Account for 15% of stones. Caused by infection magnesium with urease ⊕ bugs (eg, Proteus mirabilis, phosphate Staphylococcus saprophyticus, Klebsiella) (struvite) that hydrolyze urea to ammonia  urine alkalinization. Commonly form staghorn calculi


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First_Aid_Step1. C . Treatment: eradication of underlying infection, surgical removal of stone. D About 5% of all stones. Risk factors:  urine visible or rosettes volume, arid climates, acidic pH. Strong association with hyperuricemia (eg, gout). Often seen in diseases with  cell turnover (eg, leukemia). Treatment: alkalinization of urine, allopurinol. opaque radiopaque which Cystine-reabsorbing PCT transporter loses function, causing cystinuria. Transporter defect also results in poor reabsorption of Ornithine, Lysine, Arginine (COLA). Cystine is poorly soluble, thus stones form in urine. Usually begins in childhood. Can form staghorn calculi. Sodium cyanide nitroprusside test ⊕. “SIXtine” stones have SIX sides. Treatment: low sodium diet, alkalinization of urine, chelating agents (eg, penicillamine) if refractory.


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First_Aid_Step1. “SIXtine” stones have SIX sides. Treatment: low sodium diet, alkalinization of urine, chelating agents (eg, penicillamine) if refractory. Hydronephrosis Distention/dilation of renal pelvis and calyces A . Usually caused by urinary tract obstruction (eg, renal stones, severe BPH, congenital obstructions, cervical cancer, injury to ureter); other causes include retroperitoneal fibrosis, vesicoureteral reflux. Dilation occurs proximal to site of pathology. Serum creatinine becomes elevated if obstruction is bilateral or if patient has an obstructed solitary kidney. Leads to compression and possible atrophy of renal cortex and medulla. Urinary incontinence Mixed incontinence has features of both stress and urgency incontinence.


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First_Aid_Step1. Urinary incontinence Mixed incontinence has features of both stress and urgency incontinence. Acute cystitis Inflammation of urinary bladder. Presents as suprapubic pain, dysuria, urinary frequency, urgency. Systemic signs (eg, high fever, chills) are usually absent. Risk factors include female sex (short urethra), sexual intercourse, indwelling catheter, diabetes mellitus, impaired bladder emptying. Causes: Staphylococcus saprophyticus—seen in sexually active young women (E coli is still more common in this group) Proteus mirabilis—urine has ammonia scent Labs: ⊕ leukocyte esterase. ⊕ nitrites (indicate gram ⊝ organisms). Sterile pyuria (pyuria with ⊝ urine cultures) could suggest urethritis by Neisseria gonorrhoeae or Chlamydia trachomatis. Treatment: antibiotics (eg, TMP-SMX, nitrofurantoin).


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First_Aid_Step1. Acute pyelonephritis Neutrophils infiltrate renal interstitium A . Affects cortex with relative sparing of glomeruli/vessels. Presents with fevers, flank pain (costovertebral angle tenderness), nausea/vomiting, chills. Causes include ascending UTI (E coli is most common), hematogenous spread to kidney. Presents with WBCs in urine +/− WBC casts. CT would show striated parenchymal enhancement B . Risk factors include indwelling urinary catheter, urinary tract obstruction, vesicoureteral reflux, diabetes mellitus, pregnancy. Complications include chronic pyelonephritis, renal papillary necrosis, perinephric abscess, urosepsis. Treatment: antibiotics.


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First_Aid_Step1. Also called tubulointerstitial nephritis. Acute interstitial renal inflammation. Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity (eg, diuretics, NSAIDs, penicillin derivatives, proton pump inhibitors, rifampin, quinolones, sulfonamides). Less commonly may be 2° to other processes such as systemic infections (eg, Mycoplasma) or autoimmune diseases (eg, Sjögren syndrome, SLE, sarcoidosis). Associated with fever, rash, hematuria, pyuria, and costovertebral angle tenderness, but can be asymptomatic. Remember these 5P’S: Acute tubular necrosis Most common cause of acute kidney injury in hospitalized patients. Spontaneously resolves in many cases. Can be fatal, especially during initial oliguric phase.  FENa. Key finding: granular casts (often muddy brown in appearance) A . 3 stages: 1. 2. Maintenance phase—oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, uremia 3.


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First_Aid_Step1. 2. Maintenance phase—oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, uremia 3. Recovery phase—polyuric; BUN and serum creatinine fall; risk of hypokalemia and renal wasting of other electrolytes and minerals Can be caused by ischemic or nephrotoxic injury: Ischemic—2° to  renal blood flow (eg, hypotension, shock, sepsis, hemorrhage, HF). Results in death of tubular cells that may slough into tubular lumen B (PCT and thick ascending limb are highly susceptible to injury). Nephrotoxic—2° to injury resulting from toxic substances (eg, aminoglycosides, radiocontrast agents, lead, cisplatin, ethylene glycol), crush injury (myoglobinuria), hemoglobinuria. Proximal tubules are particularly susceptible to injury. Diffuse cortical Acute generalized cortical infarction of both Associated with obstetric catastrophes (eg, necrosis kidneys. Likely due to a combination of abruptio placentae), septic shock. vasospasm and DIC.


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First_Aid_Step1. Renal papillary Sloughing of necrotic renal papillae A • gross Associated with: Sickle cell disease or trait, necrosis hematuria and proteinuria. May be triggered Acute pyelonephritis, Analgesics (NSAIDs), by recent infection or immune stimulus. Diabetes mellitus (SAAD papa with papillary necrosis). Consequences of renal failure Decline in renal filtration can lead to excess retained nitrogenous waste products and electrolyte disturbances. Consequences (MAD HUNGER): Uremia—clinical syndrome marked by: Na+/H2O retention (HF, pulmonary edema, hypertension) 2 forms of renal failure: acute (eg, ATN) and chronic (eg, hypertension, diabetes mellitus, congenital anomalies). Incremental reductions in GFR define the stages of chronic kidney disease.


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First_Aid_Step1. Incremental reductions in GFR define the stages of chronic kidney disease. Renal osteodystrophy Hypocalcemia, hyperphosphatemia, and failure of vitamin D hydroxylation associated with chronic kidney disease  2° hyperparathyroidism  3° hyperparathyroidism (if 2° poorly managed). High serum phosphate can bind with Ca2+  tissue deposits  serum Ca2+. • 1,25-(OH)2D3  intestinal Ca2+ absorption. Causes subperiosteal thinning of bones. Autosomal recessive Cystic dilation of collecting ducts B . Often presents in infancy. Associated with congenital polycystic kidney hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter sequence. Concerns disease beyond neonatal period include systemic hypertension, progressive renal insufficiency, and portal hypertension from congenital hepatic fibrosis.


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First_Aid_Step1. Autosomal dominant Also called medullary cystic kidney disease. Causes tubulointerstitial fibrosis and progressive renal tubulointerstitial insufficiency with inability to concentrate urine. Medullary cysts usually not visualized; smaller kidney disease kidneys on ultrasound. Poor prognosis. Renal cell carcinoma Polygonal clear cells A filled with accumulated lipids and carbohydrate. Often golden-yellow B due to • lipid content. Originates from PCT  invades renal vein (may develop varicocele if left sided)  IVC • hematogenous spread  metastasis to lung and bone. Manifests with hematuria, palpable masses, 2° polycythemia, flank pain, fever, weight loss. Treatment: surgery/ablation for localized disease. Immunotherapy (eg, aldesleukin) or targeted therapy for metastatic disease, rarely curative. Resistant to chemotherapy and radiation therapy. C . Most common in men 50–70 years old, • incidence with smoking and obesity.


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First_Aid_Step1. C . Most common in men 50–70 years old, • incidence with smoking and obesity. Associated with paraneoplastic syndromes, eg, PTHrP, Ectopic EPO, ACTH, Renin (“PEAR”-aneoplastic). Clear cell (most common subtype) associated with gene deletion on chromosome 3 (sporadic, or inherited as von Hippel-Lindau syndrome). RCC = 3 letters = chromosome 3. Benign epithelial cell tumor arising from collecting ducts (arrows in A point to well-circumscribed mass with central scar). Large eosinophilic cells with abundant mitochondria without perinuclear clearing B (vs chromophobe renal cell carcinoma). Presents with painless hematuria, flank pain, abdominal mass. Often resected to exclude malignancy (eg, renal cell carcinoma). Also called Wilms tumor. Most common renal malignancy of early childhood (ages 2–4). Contains embryonic glomerular structures. Presents with large, palpable, unilateral flank mass A and/or hematuria and possible HTN.


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First_Aid_Step1. “Loss of function” mutations of tumor suppressor genes WT1 or WT2 on chromosome 11. May be a part of several syndromes: WAGR complex—Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, mental Retardation/intellectual disability (WT1 deletion) Denys-Drash syndrome—Wilms tumor, Diffuse mesangial sclerosis (early-onset nephrotic syndrome), Dysgenesis of gonads (male pseudohermaphroditism), WT1 mutation Beckwith-Wiedemann syndrome—Wilms tumor, macroglossia, organomegaly, hemihyperplasia (WT2 mutation), omphalocele Urothelial carcinoma Also called transitional cell carcinoma. Most of the bladder common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters, and bladder) A B . Can be suggested by painless hematuria (no casts). Associated with problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, and Cyclophosphamide.


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First_Aid_Step1. Associated with problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, and Cyclophosphamide. Diuretics site of action 5Glomerulus A°erent Mannitol Acetazolamide Loop diuretics Thiazide diuretics K+ sparing diuretics Proximal convoluted tubule Loop of Henle Descending limb, loop of Henle (permeable to water) Ascending limb, loop of Henle (permeable to salts) Collecting duct Distal convoluted tubule Cortex Medulla 1234Sugars Amino acids Na+ Na+ K+ 2CI– Ca2+ Mg2+ Na+ CI– Na+ Na+ HCO3 – Ca2+ 34K+ H+ 5521E°erent H2O mEChANism Osmotic diuretic.  tubular fluid osmolarity  urine flow,  intracranial/intraocular pressure. CLiNiCAL UsE Drug overdose, elevated intracranial/intraocular pressure. ADVERsE EFFECts Pulmonary edema, dehydration, hypoor hypernatremia. Contraindicated in anuria, HF. mEChANism Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and  total body HCO3 − stores. Alkalinizes urine.


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First_Aid_Step1. mEChANism Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and  total body HCO3 − stores. Alkalinizes urine. CLiNiCAL UsE Glaucoma, metabolic alkalosis, altitude sickness, idiopathic intracranial hypertension. ADVERsE EFFECts Proximal renal tubular acidosis, paresthesias, “Acid”azolamide causes Acidosis. NH3 toxicity, sulfa allergy, hypokalemia. Promotes calcium phosphate stone formation (insoluble at high pH). Furosemide, bumetanide, torsemide mEChANism Sulfonamide loop diuretics. Inhibit cotransport system (Na+/K+/2Cl−) of thick ascending limb of loop of Henle. Abolish hypertonicity of medulla, preventing concentration of urine. Associated with  PGE (vasodilatory effect on afferent arteriole); inhibited by NSAIDs.  Ca2+ excretion. Loops Lose Ca2+. CLiNiCAL UsE Edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia. CLiNiCAL UsE Diuresis in patients allergic to sulfa drugs.


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First_Aid_Step1. CLiNiCAL UsE Edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia. CLiNiCAL UsE Diuresis in patients allergic to sulfa drugs. ADVERsE EFFECts Similar to furosemide, but more ototoxic. Loop earrings hurt your ears. Thiazide diuretics Hydrochlorothiazide, chlorthalidone, metolazone. mEChANism Inhibit NaCl reabsorption in early DCT  diluting capacity of nephron. • Ca2+ excretion. CLiNiCAL UsE Hypertension, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis. ADVERsE EFFECts Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. Sulfa allergy. HyperGLUC. Potassium-sparing Spironolactone, Eplerenone, Amiloride, Keep your SEAT diuretics Triamterene. mEChANism Spironolactone and eplerenone are competitive aldosterone receptor antagonists in cortical collecting tubule. Triamterene and amiloride block Na+ channels at the same part of the tubule.


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First_Aid_Step1. mEChANism Spironolactone and eplerenone are competitive aldosterone receptor antagonists in cortical collecting tubule. Triamterene and amiloride block Na+ channels at the same part of the tubule. CLiNiCAL UsE Hyperaldosteronism, K+ depletion, HF, hepatic ascites (spironolactone), nephrogenic DI (amiloride), antiandrogen. ADVERsE EFFECts Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (eg, gynecomastia, antiandrogen effects). Diuretics: electrolyte changes Urine NaCl  with all diuretics (strength varies based on potency of diuretic effect). Serum NaCl may decrease as a result. Urine Ca2+  with loop diuretics:  paracellular Ca2+ reabsorption  hypocalcemia.  with thiazides: enhanced Ca2+ reabsorption.


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First_Aid_Step1. Urine Ca2+  with loop diuretics:  paracellular Ca2+ reabsorption  hypocalcemia.  with thiazides: enhanced Ca2+ reabsorption. Angiotensin-Captopril, enalapril, lisinopril, ramipril. converting enzyme inhibitors mEChANism Inhibit ACE  AT II  GFR by preventing constriction of efferent arterioles.  renin due to loss of negative feedback. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator. CLiNiCAL UsE Hypertension, HF, proteinuria, or chronic kidney disease (eg, diabetic nephropathy) with intolerance to ACE inhibitors (eg, cough, angioedema). ADVERsE EFFECts Hyperkalemia, • GFR, hypotension; teratogen. mEChANism Direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I. Aliskiren Kills Renin. CLiNiCAL UsE Hypertension. ADVERsE EFFECts Hyperkalemia, • GFR, hypotension, angioedema. Relatively contraindicated in patients already taking ACE inhibitors or ARBs and contraindicated in pregnancy.


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First_Aid_Step1. ADVERsE EFFECts Hyperkalemia, • GFR, hypotension, angioedema. Relatively contraindicated in patients already taking ACE inhibitors or ARBs and contraindicated in pregnancy. “Artificial insemination is when the farmer does it to the cow instead of the bull.” Make no mistake about why these babies are here they are here to replace us. “Whoever called it necking was a poor judge of anatomy.” “See, the problem is that God gives men a brain and a penis, and only enough blood to run one at a time.” The reproductive system can be intimidating at first but is manageable once you organize the concepts into the pregnancy, endocrinologic, embryologic, and oncologic aspects of reproduction. Study the endocrine and reproductive chapters together, because mastery of the hypothalamic-pituitary-gonadal axis is key to answering questions on ovulation, menstruation, disorders of sexual development, contraception, and many pathologies.


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First_Aid_Step1. Embryology is a nuanced subject that covers multiple organ systems. Approaching it from a clinical perspective will allow for better understanding. For instance, make the connection between the presentation of DiGeorge syndrome and the 3rd/4th pharyngeal pouch, and between the Müllerian/Wolffian systems and disorders of sexual development. As for oncology, don’t worry about remembering screening or treatment guidelines. It is more important to know how these cancers present (eg, signs and symptoms) and their associated labs, histopathology, and risk factors. In addition, some of the testicular and ovarian cancers have distinct patterns of hCG, AFP, LH, or FSH derangements that serve as helpful clues in exam questions. Important genes of embryogenesis Types of errors in morphogenesis Deformation Extrinsic disruption (eg, multiple gestations  crowding  foot deformities); occurs after embryonic period. Malformation Intrinsic disruption; occurs during embryonic period (weeks 3–8).


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First_Aid_Step1. Malformation Intrinsic disruption; occurs during embryonic period (weeks 3–8). Sequence Abnormalities result from a single 1° embryologic event (eg, oligohydramnios  Potter sequence). Teratogens Most susceptible in 3rd–8th weeks (embryonic period—organogenesis) of pregnancy. Before week 3, “all-or-none” effects. After week 8, growth and function affected. ACE inhibitors Renal failure, oligohydramnios, hypocalvaria. Lithium Ebstein anomaly. Methimazole Aplasia cutis congenita (congenital absence of skin, particularly on scalp). Alcohol Fetal alcohol syndrome. Iodine (lack or excess) Congenital goiter or hypothyroidism (cretinism). Maternal diabetes Caudal regression syndrome, cardiac defects (eg, VSD), neural tube defects, macrosomia, neonatal hypoglycemia (due to islet cell hyperplasia), polycythemia. Methylmercury Neurotoxicity. Highest in swordfish, shark, tilefish, king mackerel.


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First_Aid_Step1. Methylmercury Neurotoxicity. Highest in swordfish, shark, tilefish, king mackerel. Vitamin A excess Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac). X-rays Microcephaly, intellectual disability. Minimized by lead shielding. One of the leading preventable causes of intellectual disability in the US. Newborns of mothers who consumed alcohol during any stage of pregnancy have  incidence of congenital abnormalities, including preand postnatal developmental retardation, microcephaly, facial abnormalities A (eg, smooth philtrum, thin vermillion border, small palpebral fissures), limb dislocation, heart defects. Heart-lung fistulas and holoprosencephaly in most severe form. One mechanism is due to impaired migration of neuronal and glial cells. Twinning Dizygotic (“fraternal”) twins arise from 2 eggs that are separately fertilized by 2 different sperm (always 2 zygotes) and will have 2 separate amniotic sacs and 2 separate placentas (chorions).


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First_Aid_Step1. Monozygotic (“identical”) twins arise from 1 fertilized egg (1 egg + 1 sperm) that splits in early pregnancy. The timing of cleavage determines chorionicity (number of chorions) and amnionicity (number of amnions) (SCAB): Cleavage 0–4 days: Separate chorion and amnion Cleavage 4–8 days: shared Chorion Cleavage 8–12 days: shared Amnion Cleavage 13+ days: shared Body (conjoined) 2 eggs, 1 egg, 1 sperm 2 sperm Placenta 1º site of nutrient and gas exchange between mother and fetus. Decidua basalis Derived from endometrium. Maternal blood in lacunae. Branch villus Umbilical vein (O2 rich) Umbilical arteries (O2 poor) Endometrial vein Maternal circulation Chorionic plate Maternal blood Amnion Maternal circulation Fetal circulation CO2 H2O Urea, waste products Hormones Endometrial artery Decidua basalis Endothelial cell Syncytiotrophoblast Cytotrophoblast O2 H2O, electrolytes Nutrients Hormones IgG Drugs Viruses


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First_Aid_Step1. Urachus Allantois forms from hindgut and extends into urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and umbilicus. Failure of urachus to involute can lead to anomalies that may increase risk of infection and/or malignancy (eg, adenocarcinoma) if not treated. Obliterated urachus is represented by the median umbilical ligament after birth, which is covered by median umbilical fold of the peritoneum. Vesicourachal Slight failure of urachus to obliterate  outpouching of bladder. diverticulum Vitelline duct 7th week—obliteration of vitelline duct (omphalomesenteric duct), which connects yolk sac to midgut lumen. Vitelline fistula Vitelline duct fails to close  meconium discharge from umbilicus. Meckel diverticulum Partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum, white arrow in B ). May be asymptomatic. May have heterotopic gastric and/or pancreatic tissue  melena, hematochezia, abdominal pain.


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First_Aid_Step1. Aortic arch derivatives Develop into arterial system. 1st Part of maxillary artery (branch of external 1st arch is maximal carotid) 3rd Common Carotid artery and proximal part of C is 3rd letter of alphabet internal Carotid artery 4th On left, aortic arch; on right, proximal part of 4th arch (4 limbs) = systemic right subclavian artery 6th Proximal part of pulmonary arteries and (on left only) ductus arteriosus 6th arch = pulmonary and the pulmonary-tosystemic shunt (ductus arteriosus) Pharyngeal apparatus Composed of pharyngeal clefts, arches, CAP covers outside to inside: pouches. Clefts = ectoderm Pharyngeal clefts—derived from ectoderm. Also Arches = mesoderm + neural crest called pharyngeal grooves. Pouches = endoderm Pharyngeal arches—derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage). Pharyngeal pouches—derived from endoderm. • Maxilla, zygoMatic  Mandible, Malleus and incus, sphenoMandibular ligament


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First_Aid_Step1. • Maxilla, zygoMatic  Mandible, Malleus and incus, sphenoMandibular ligament Reichert cartilage: Stapes, Styloid process, leSSer horn of hyoid, Stylohyoid ligament Muscles of Mastication (temporalis, Masseter, lateral and Medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, anterior 2/3 of tongue, tensor veli palatini Muscles of facial expression, Stapedius, Stylohyoid, platySma, posterior belly of digastric CN V3 chew Pierre Robin sequence— micrognathia, glossoptosis, cleft palate, airway obstruction


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First_Aid_Step1. CN VII (facial • craniofacial expression) abnormalities (eg, smile zygomatic bone and mandibular hypoplasia), hearing loss, airway compromise 3rd pharyngeal Greater horn of hyoid Stylopharyngeus (think CN IX (styloarch of stylopharyngeus pharyngeus) innervated by swallow stylishly glossopharyngeal nerve) 4th and 6th Arytenoids, Cricoid, pharyngeal Corniculate, arches Cuneiform, Thyroid (used to sing and ACCCT) 4th arch: most pharyngeal 4th arch: CN Arches 3 and 4 form constrictors; cricothyroid, X (superior posterior 1/3 of tongue levator veli palatini laryngeal branch) Arch 5 makes no 6th arch: all intrinsic simply swallow major developmental muscles of larynx except 6th arch: CN contributions cricothyroid X (recurrent/ inferior laryngeal branch) speak aSensory and motor nerves are not pharyngeal arch derivatives. They grow into the arches and are derived from neural crest (sensory) and neuroectoderm (motor).


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First_Aid_Step1. When at the restaurant of the golden arches, children tend to first chew (1), then smile (2), then swallow stylishly (3) or simply swallow (4), and then speak (6). 1st pharyngeal pouch Middle ear cavity, eustachian 1st pouch contributes to Ear, tonsils, bottom-to-top: tube, mastoid air cells endoderm-lined structures 1 (ear) of ear 2 (tonsils) 3 dorsal (bottom for inferior 2nd pharyngeal pouch Epithelial lining of palatine 3rd pharyngeal pouch Dorsal wings • inferior 3rd pouch contributes to 3 parathyroids structures (thymus, left and (C) cells of thyroid Cleft lip and cleft Distinct, multifactorial etiologies, but often occur together. palate Cleft lip Due to failure of fusion of the maxillary and merged medial nasal processes (formation of 1° palate). Cleft palate Due to failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelf with the nasal septum and/or 1° palate (formation of 2° palate).


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First_Aid_Step1. Cleft palate Due to failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelf with the nasal septum and/or 1° palate (formation of 2° palate). Intermaxillary segment Roof of mouth (1° palate) Nasal septum Maxillary prominence Palatine shelves (2° palate) Female Default development. Mesonephric duct degenerates and paramesonephric duct develops.


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First_Aid_Step1. Female Default development. Mesonephric duct degenerates and paramesonephric duct develops. Metanephric kidney Ureter Uterus Vagina Vas deferens Degenerated paramesonephric duct Degenerated mesonephric duct Oviduct Urinary bladder Testis Ovary Epididymis Testis-determining factor Androgens MIF Gubernaculum Mesonephros Paramesonephric duct Mesonephric duct Urogenital sinus No androgens (Müllerian) duct fallopian tubes, uterus, upper portion of vagina (lower portion from urogenital sinus). Male remnant is appendix testis. Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome)—may present 2° sexual characteristics (functional ovaries). (Wolffian) duct prostate)—Seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens (SEED). Female remnant is Gartner duct. determining factor • testes development. Sertoli cells secrete Müllerian inhibitory factor (MIF, also called antimullerian hormone) that suppresses development of paramesonephric ducts.


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First_Aid_Step1. determining factor • testes development. Sertoli cells secrete Müllerian inhibitory factor (MIF, also called antimullerian hormone) that suppresses development of paramesonephric ducts. Leydig cells secrete androgens that stimulate development of mesonephric ducts. Paramesonephric Develops into female internal structures— as 1° amenorrhea (due to a lack of uterine development) in females with fully developed Absence of Sertoli cells or lack of Müllerian inhibitory factor  develop both male and sexual differentiation. Sertoli Shuts down female (internal) sexual differentiation. genitalia, ambiguous external genitalia until In the testes: Leydig Leads to male (internal and external) Septate uterus Common anomaly vs normal uterus A . Incomplete resorption of septum B .  fertility and early miscarriage/pregnancy loss. Treat with septoplasty. Opening of sinus Scrotum Opening of Anus


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First_Aid_Step1. Opening of sinus Scrotum Opening of Anus Hypospadias Abnormal opening of penile urethra on ventral Hypospadias is more common than surface of penis due to failure of urethral folds epispadias. Associated with inguinal hernia, to fuse. cryptorchidism, chordee (downward or upward bending of penis). Hypo is below. Can be seen in 5α-reductase deficiency. Epispadias Abnormal opening of penile urethra on dorsal Exstrophy of the bladder is associated with surface of penis due to faulty positioning of Epispadias. genital tubercle. When you have Epispadias, you hit your Eye when you pEE. Descent of testes and ovaries Adnexal torsion Twisting of ovary and fallopian tube around infundibulopelvic ligament and ovarian ligament  compression of ovarian vessels in infundibulopelvic ligament  blockage of lymphatic and venous outflow. Continued arterial perfusion  ovarian edema  complete blockage of arterial inflow  necrosis, local hemorrhage.


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First_Aid_Step1. Associated with ovarian masses. Presents with acute pelvic pain, adnexal mass, nausea/vomiting. Vagina Stratified squamous epithelium, nonkeratinized Ectocervix Stratified squamous epithelium, nonkeratinized Uterus Simple columnar epithelium with long tubular glands in proliferative phase; coiled glands in secretory phase Pathway of sperm during ejaculation— SEVEN UP: Seminiferous tubules Epididymis Vas deferens Ejaculatory ducts (Nothing) Urethra Penis Autonomic innervation of male sexual response Occurs almost exclusively in men. Suspect if blood seen at urethral meatus. Urethral catheterization is relatively contraindicated. If Buck fascia is torn, urine escapes into perineal space Blood at urethral meatus and scrotal hematoma Blood at urethral meatus and high-riding prostate Erection—Parasympathetic nervous system (pelvic splanchnic nerves, S2-S4): NO  cGMP  smooth muscle relaxation  vasodilation  proerectile.


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First_Aid_Step1. Erection—Parasympathetic nervous system (pelvic splanchnic nerves, S2-S4): NO  cGMP  smooth muscle relaxation  vasodilation  proerectile. antierectile. Emission—Sympathetic nervous system (hypogastric nerve, T11-L2). Expulsion—visceral and Somatic nerves (pudendal nerve). Point, Squeeze, and Shoot. S2, 3, 4 keep the penis off the floor. PDE-5 inhibitors (eg, sildenafil)  cGMP breakdown. local levels of testosterone Produce MIF Tight junctions between adjacent Sertoli cells  inhibin B with  temperature Line seminiferous tubules Non-germ cells Convert testosterone and androstenedione to estrogens via aromatase Sertoli cells are inSide Seminiferous tubules, Support Sperm Synthesis, and inhibit FSH Homolog of female granulosa cells  temperature seen in varicocele, cryptorchidism Leydig cells Secrete testosterone in the presence of LH; Interstitium temperature Homolog of female theca interna cells


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First_Aid_Step1. Leydig cells Secrete testosterone in the presence of LH; Interstitium temperature Homolog of female theca interna cells Spermatogenesis Begins at puberty with spermatogonia. Full “Gonium” is going to be a sperm; “Zoon” is development takes 2 months. Occurs in “Zooming” to egg. seminiferous tubules. Produces spermatids Tail mobility impaired in ciliary dyskinesia/ that undergo spermiogenesis (loss of Kartagener syndrome  infertility. cytoplasmic contents, gain of acrosomal cap) Tail mobility normal in cystic fibrosis (in CF, to form mature spermatozoa. Spermatogonium 1° spermatocyte 2° spermatocyte Diploid Diploid Haploid (2N, 2C) (2N, 4C) (1N, 2C) absent vas deferens  infertility). Mature spermatozoon Haploid Haploid (1N, 1C) (1N, 1C) SOURCE Ovary (17β-estradiol), placenta (estriol), adipose Potency: estradiol > estrone > estriol. tissue (estrone via aromatization).


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First_Aid_Step1. Mature spermatozoon Haploid Haploid (1N, 1C) (1N, 1C) SOURCE Ovary (17β-estradiol), placenta (estriol), adipose Potency: estradiol > estrone > estriol. tissue (estrone via aromatization). FUNCTION Development of genitalia and breast, female fat distribution. Growth of follicle, endometrial proliferation,  myometrial excitability. Upregulation of estrogen, LH, and progesterone receptors; feedback inhibition of FSH and LH, then LH surge; stimulation of prolactin secretion.  transport proteins, SHBG;  HDL;  LDL. Pregnancy: 1000-fold  in estriol (indicator of fetal wellbeing) Estrogen receptors expressed in cytoplasm; translocate to nucleus when bound by estrogen. SOURCE Corpus luteum, placenta, adrenal cortex, testes. Fall in progesterone after delivery disinhibits FUNCTION During luteal phase, prepares uterus for implantation of fertilized egg: Stimulation of endometrial glandular secretions and spiral artery development Production of thick cervical mucus


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First_Aid_Step1. FUNCTION During luteal phase, prepares uterus for implantation of fertilized egg: Stimulation of endometrial glandular secretions and spiral artery development Production of thick cervical mucus Prevention of endometrial hyperplasia •  body temperature •  estrogen receptor expression •  gonadotropin (LH, FSH) secretion During pregnancy: • Maintenance of pregnancy •  myometrial excitability  contraction frequency and intensity •  prolactin action on breasts prolactin  lactation.  progesterone is indicative of ovulation. Progesterone is pro-gestation. Prolactin is pro-lactation. Oogenesis 1° oocytes begin meiosis I during fetal life and complete meiosis I just prior to ovulation. Meiosis I is arrested in prOphase I for years until Ovulation (1° oocytes). Meiosis II is arrested in metaphase II until fertilization (2° oocytes). “An egg met a sperm.” If fertilization does not occur within 1 day, the 2° oocyte degenerates.


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First_Aid_Step1. Oogonium 1° oocyte 2° oocyte Ovum Diploid Diploid Haploid Haploid (2N, 2C) (2N, 4C) (1N, 2C) (1N, 1C) N = ploidy C = # of chromatids Menstrual cycle Follicular phase can vary in length. Luteal phase is 14 days. Ovulation day + 14 days = menstruation. Follicular growth is fastest during 2nd week of the follicular phase. Estrogen stimulates endometrial proliferation. Progesterone maintains endometrium to support implantation.  progesterone • fertility. Abnormal uterine Characterized as either heavy menstrual Terms such as dysfunctional uterine bleeding, bleeding bleeding (AUB/HMB) or intermenstrual menorrhagia, oligomenorrhea are no longer bleeding (AUB/IMB). recommended. These are further subcategorized by PALM COEIN: Structural causes (PALM): Polyp, Adenomyosis, Leiomyoma, or Malignancy/ hyperplasia Non-structural causes (COEIN): Coagulopathy, Ovulatory, Endometrial, Iatrogenic, Not yet classified


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First_Aid_Step1. COEIN: Structural causes (PALM): Polyp, Adenomyosis, Leiomyoma, or Malignancy/ hyperplasia Non-structural causes (COEIN): Coagulopathy, Ovulatory, Endometrial, Iatrogenic, Not yet classified Pregnancy Fertilization most commonly occurs in upper end of fallopian tube (the ampulla). Occurs within 1 day of ovulation. Implantation within the wall of the uterus occurs 6 days after fertilization. Syncytiotrophoblasts secrete hCG, which is conception. Gestational age—calculated from date of last menstrual period. Physiologic adaptations in pregnancy: Weeks of pregnancy •  GFR  BUN and creatinine, Placental hormone secretion generally increases  glucosuria threshold over the course of pregnancy, but hCG peaks at • • cardiac output (• preload,  afterload, 8–10 weeks. Anemia ( plasma, • RBCs) •  lipolysis and fat utilization (due to maternal hypoglycemia and insulin resistance)  preserves glucose and amino acids for utilization by the fetus


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First_Aid_Step1. Anemia ( plasma, • RBCs) •  lipolysis and fat utilization (due to maternal hypoglycemia and insulin resistance)  preserves glucose and amino acids for utilization by the fetus SOURCE Syncytiotrophoblast of placenta. FUNCTION Maintains corpus luteum (and thus progesterone) for first 8–10 weeks of pregnancy by acting like LH (otherwise no luteal cell stimulation  abortion). After 8–10 weeks, placenta synthesizes its own estriol and progesterone and corpus luteum degenerates. Used to detect pregnancy because it appears early in urine (see above). Has identical α subunit as LH, FSH, TSH (states of  hCG can cause hyperthyroidism). β subunit is unique (pregnancy tests detect β subunit). hCG is  in multiple gestations, hydatidiform moles, choriocarcinomas, and Down syndrome; hCG is  in ectopic/failing pregnancy, Edwards syndrome, and Patau syndrome. Human placental Also called chorionic somatomammotropin. lactogen SOURCE Syncytiotrophoblast of placenta.


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First_Aid_Step1. Human placental Also called chorionic somatomammotropin. lactogen SOURCE Syncytiotrophoblast of placenta. FUNCTION Stimulates insulin production; overall  insulin resistance. Gestational diabetes can occur if maternal pancreatic function cannot overcome the insulin resistance. Assessment of newborn vital signs following delivery via a 10-point scale evaluated at 1 minute and 5 minutes. Apgar score is based on Appearance, Pulse, Grimace, Activity, and Respiration. Apgar scores < 7 may require further evaluation. If Apgar score remains low at later time points, there is  risk the child will develop long-term neurologic damage. Milestone dates are ranges that have been approximated and vary by source. Children not meeting milestones may need assessment for potential developmental delay. Cruises, takes first steps (by = age (yr) × 3 Cutlery—feeds self with fork and spoon (by 20 mo) Kicks ball (by 24 mo)


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First_Aid_Step1. Cruises, takes first steps (by = age (yr) × 3 Cutlery—feeds self with fork and spoon (by 20 mo) Kicks ball (by 24 mo) Defined as < 2500 g. Caused by prematurity or intrauterine growth restriction (IUGR). Associated with  risk of sudden infant death syndrome (SIDS) and with  overall mortality.


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First_Aid_Step1. Lactation After parturition and delivery of placenta, rapid  in progesterone disinhibits prolactin • initiation of lactation. Suckling is required to maintain milk production and ejection, since  nerve stimulation  oxytocin and prolactin. Prolactin—induces and maintains lactation and  reproductive function. Oxytocin—assists in milk letdown; also promotes uterine contractions. Breast milk is the ideal nutrition for infants < 6 months old. Contains maternal immunoglobulins (conferring passive immunity; mostly IgA), macrophages, lymphocytes. Breast milk reduces infant infections and is associated with  risk for child to develop asthma, allergies, diabetes mellitus, and obesity. Guidelines recommend exclusively breastfed infants get vitamin D and possibly iron supplementation. Breastfeeding  maternal risk of breast and ovarian cancer and facilitates mother-child bonding. Menopause Diagnosed by amenorrhea for 12 months.


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First_Aid_Step1. Menopause Diagnosed by amenorrhea for 12 months. • estrogen production due to age-linked decline in number of ovarian follicles. Average age at onset is 51 years (earlier in smokers). Usually preceded by 4–5 years of abnormal menstrual cycles. Source of estrogen (estrone) after menopause becomes peripheral conversion of androgens,  androgens  hirsutism.  FSH is specific for menopause (loss of negative feedback on FSH due to  estrogen). Hormonal changes:  estrogen,  FSH,  LH (no surge),  GnRH. Causes HAVOCS: Hot flashes, Atrophy of the Vagina, Osteoporosis, Coronary artery disease, Sleep disturbances. Menopause before age 40 suggests 1° ovarian insufficiency (premature ovarian failure); may occur in women who have received chemotherapy and/or radiation therapy. Androgens Testosterone, dihydrotestosterone (DHT), androstenedione. SOURCE DHT and testosterone (testis), AnDrostenedione Potency: DHT > testosterone > (ADrenal) androstenedione. FUNCTION Testosterone:


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First_Aid_Step1. SOURCE DHT and testosterone (testis), AnDrostenedione Potency: DHT > testosterone > (ADrenal) androstenedione. FUNCTION Testosterone: Differentiation of epididymis, vas deferens, seminal vesicles (internal genitalia, except prostate) Growth spurt: penis, seminal vesicles, sperm, muscle, RBCs Deepening of voice Closing of epiphyseal plates (via estrogen converted from testosterone) Libido DHT: Early—differentiation of penis, scrotum, prostate Late—prostate growth, balding, sebaceous gland activity Testosterone is converted to DHT by 5α-reductase, which is inhibited by finasteride. In the male, androgens are converted to estrogen by cytochrome P-450 aromatase (primarily in adipose tissue and testis). Aromatase is the key enzyme in conversion of androgens to estrogen.


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First_Aid_Step1. In the male, androgens are converted to estrogen by cytochrome P-450 aromatase (primarily in adipose tissue and testis). Aromatase is the key enzyme in conversion of androgens to estrogen. Androgenic steroid abuse—abuse of anabolic steroids to  fat-free mass, muscle strength, and performance. Suspect in men who present with changes in behavior (eg, aggression), acne, gynecomastia,  Hb and Hct, small testes (exogenous testosterone • hypothalamic-pituitary-gonadal axis inhibition • intratesticular testosterone  testicular size,  sperm count, azoospermia). Women may present with virilization (eg, hirsutism, acne, breast atrophy, male pattern baldness). Tanner stages of sexual development Tanner stage is assigned independently to genitalia, pubic hair, and breast (eg, a person can have Tanner stage 2 genitalia, Tanner stage 3 pubic hair). Earliest detectable secondary sexual characteristic is breast bud development in girls, testicular enlargement in boys.


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First_Aid_Step1. Coarsening of pubic Coarse hair across pubis, Coarse hair across pubis and Flat-appearing chest with (pubarche) hair Breast enlarges, raised adult size (thelarche), mound forms areola, mound on mound Adult breast contour, areola fattens Pre-pubertal ~ 811.5 years ~ 11.5–13 years ~ 13–15 years Usually > 15 years Precocious puberty Appearance of 2° sexual characteristics (eg, adrenarche, thelarche, menarche) before age 8 years in girls and 9 years in boys.  sex hormone exposure or production  linear growth, somatic and skeletal maturation (eg, premature closure of epiphyseal plates  short stature). Types include: Central precocious puberty ( GnRH secretion): idiopathic (most common; early activation of hypothalamic-pituitary gonadal axis), CNS tumors.


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First_Aid_Step1. Central precocious puberty ( GnRH secretion): idiopathic (most common; early activation of hypothalamic-pituitary gonadal axis), CNS tumors. Peripheral precocious puberty (GnRH-independent;  sex hormone production or exposure to exogenous sex steroids): congenital adrenal hyperplasia, estrogen-secreting ovarian tumor (eg, granulosa cell tumor), Leydig cell tumor, McCune-Albright syndrome. Sex chromosome Aneuploidy most commonly due to meiotic nondisjunction. disorders Klinefelter syndrome Male, 47,XXY. Dysgenesis of seminiferous tubules Testicular atrophy, eunuchoid body shape,  inhibin B  FSH. tall, long extremities, gynecomastia, female Abnormal Leydig cell function  testosterone A . May present with  LH  estrogen. developmental delay. Presence of inactivated X chromosome (Barr body). Common cause of hypogonadism seen in infertility work-up.


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First_Aid_Step1. A . May present with  LH  estrogen. developmental delay. Presence of inactivated X chromosome (Barr body). Common cause of hypogonadism seen in infertility work-up. Double Y males 47, XYY. Phenotypically normal (usually undiagnosed), very tall. Normal fertility. May be associated with severe acne, learning disability, autism spectrum disorders. Female, 45,XO. Short stature (associated with SHOX gene, preventable with growth hormone therapy), ovarian dysgenesis (streak ovary), shield chest B , bicuspid aortic valve, coarctation of the aorta (femoral < brachial pulse), lymphatic defects (result in webbed neck or cystic hygroma; lymphedema in feet, hands), horseshoe kidney, high-arched palate, shortened 4th metacarpals. Most common cause of 1° amenorrhea. No Barr body. Menopause before menarche.


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First_Aid_Step1. Most common cause of 1° amenorrhea. No Barr body. Menopause before menarche.  estrogen leads to  LH, FSH. Sex chromosome (X, or rarely Y) loss often due to nondisjunction during meiosis or mitosis. Meiosis errors usually occur in paternal gametes  sperm missing the sex chromosome. Mitosis errors occur after zygote formation  loss of sex chromosome in some but not all cells  mosaic karyotype (eg. 45,X/46XX). (45,X/46,XY) mosaicism associated with increased risk for gonadoblastoma. Pregnancy is possible in some cases (IVF, exogenous estradiol-17β and progesterone). • Defective androgen receptor • Testosterone-secreting tumor, exogenous ⊕⊝ Hypergonadotropic hypogonadism (eg, Turner syndrome, genetic mosaicism, pure gonadal dysgenesis) Hypogonadotropic hypogonadism (eg, CNS lesions, Kallmann syndrome)


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First_Aid_Step1. Kallmann syndrome Failure to complete puberty; a form of hypogonadotropic hypogonadism. Defective migration of neurons and subsequent failure of olfactory bulbs to develop  synthesis of GnRH in the hypothalamus; hyposmia/anosmia;  GnRH, FSH, LH, testosterone. Infertility (low sperm count in males; amenorrhea in females). Abruptio placentae Premature separation (partial or complete) of placenta from uterine wall before delivery of infant. Risk factors: trauma (eg, motor vehicle accident), smoking, hypertension, preeclampsia, cocaine abuse. Presentation: abrupt, painful bleeding (concealed or apparent) in third trimester; possible DIC (mediated by tissue factor activation), maternal shock, fetal distress. May be life threatening for mother and fetus. Complete abruption with Partial abruption (blue arrow) concealed hemorrhage with apparent hemorrhage (red arrow)


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First_Aid_Step1. Complete abruption with Partial abruption (blue arrow) concealed hemorrhage with apparent hemorrhage (red arrow) Defective decidual layer  abnormal attachment and separation after delivery. Risk factors: prior C-section or uterine surgery involving myometrium, inflammation, placenta previa, advanced maternal age, multiparity. Three types distinguishable by the depth of penetration: Placenta accreta—placenta attaches to myometrium without penetrating it; most common type. Placenta increta—placenta penetrates into myometrium. Placenta percreta—placenta penetrates (“perforates”) through myometrium and into uterine serosa (invades entire uterine wall); can result in placental attachment to rectum or bladder (can result in hematuria). Presentation: often detected on ultrasound prior to delivery. No separation of placenta after delivery  postpartum bleeding (can cause Sheehan syndrome).


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First_Aid_Step1. Presentation: often detected on ultrasound prior to delivery. No separation of placenta after delivery  postpartum bleeding (can cause Sheehan syndrome). Placenta previa Attachment of placenta over internal cervical os. Risk factors: multiparity, prior C-section. Associated with painless third-trimester bleeding. A “preview” of the placenta is visible through cervix. Low-lying placenta (< 2 cm from internal cervical os, but not over it) is managed differently from placenta previa. Implantation of fertilized ovum in a site other Isthmus (highest riskInterstitium than the uterus, most often in ampulla of Fallopian tube of tubal rupture) fallopian tube A . Suspect with history of amenorrhea, lower-than-expected rise in hCG based on dates, and sudden lower abdominal pain; confirm with ultrasound, which may show extraovarian adnexal mass. Often clinically mistaken for appendicitis. Pain +/− bleeding. Risk factors: History of infertility


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First_Aid_Step1. Pain +/− bleeding. Risk factors: History of infertility Hydatidiform mole Cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast). Presents with vaginal bleeding, emesis, uterine enlargement more than expected, pelvic pressure/ pain. Associated with hCG-mediated sequelae: early preeclampsia (before 20 weeks), theca-lutein cysts, hyperemesis gravidarum, hyperthyroidism. Treatment: dilation and curettage and methotrexate. Monitor hCG. Rare; can develop during or after pregnancy in mother or baby. Malignancy of trophoblastic tissue A (cytotrophoblasts, syncytiotrophoblasts); no chorionic villi present.  frequency of bilateral/ multiple theca-lutein cysts. Presents with abnormal • hCG, shortness of breath, hemoptysis. Hematogenous spread to lungs B . Treatment: methotrexate. Incidence (US)—endometrial > ovarian > cervical; cervical cancer is more common worldwide due to lack of screening or HPV vaccination.


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First_Aid_Step1. B . Treatment: methotrexate. Incidence (US)—endometrial > ovarian > cervical; cervical cancer is more common worldwide due to lack of screening or HPV vaccination. Prognosis: Cervical (best prognosis, diagnosed < 45 years old) > Endometrial (middleaged, about 55 years old) > Ovarian (worst prognosis, > 65 years). CEOs often go from best to worst as they get older. Bartholin cyst and Due to blockage of Bartholin gland duct causing accumulation of gland fluid. May lead to abscess abscess 2° to obstruction and inflammation A . Usually in reproductive-age females. Lichen sclerosus Thinning of epidermis with fibrosis/sclerosis of dermis. Presents with porcelain-white plaques with a red or violet border. Skin fragility with erosions can be observed B . Most common in postmenopausal women. Benign, but slightly increased risk for SCC.


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First_Aid_Step1. Lichen simplex Hyperplasia of vulvar squamous epithelium. Presents with leathery, thick vulvar skin with chronicus enhanced skin markings due to chronic rubbing or scratching. Benign, no risk of SCC. Neoplastic Vulvar carcinoma Carcinoma from squamous epithelial lining of vulva C . Rare. Presents with leukoplakia, biopsy often required to distinguish carcinoma from other causes. HPV-related vulvar carcinoma—associated with high-risk HPV types 16, 18. Risk factors: multiple partners, early coitarche. Usually in reproductive-age females. Non-HPV vulvar carcinoma—usually from long-standing lichen sclerosus. Females > 70 years old. Imperforate hymen Incomplete degeneration of the central portion of the hymen. Accumulation of vaginal mucus at birth  self-resolving bulge in introitus. If untreated, leads to 1° amenorrhea, cyclic abdominal pain, hematocolpos (accumulation of menstrual blood in vagina  bulging and bluish hymenal membrane).


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First_Aid_Step1. Vaginal squamous cell Usually 2° to cervical SCC; 1° vaginal carcinoma rare. carcinoma Disordered epithelial growth; begins at basal layer of squamocolumnar junction (transformation zone) and extends outward. Classified as CIN 1, CIN 2, or CIN 3 (severe, irreversible dysplasia or carcinoma in situ), depending on extent of dysplasia. Associated with HPV-16 and HPV-18, which produce both the E6 gene product (inhibits TP53) and E7 gene product (inhibits pRb) (6 before 7; P before R). Koilocytes A are pathognomonic of HPV infection. May progress slowly to invasive carcinoma if left untreated. Typically asymptomatic (detected with Pap smear) or presents as abnormal vaginal bleeding (often postcoital). Risk factors: multiple sexual partners, HPV, smoking, early coitarche, DES exposure, immunocompromise (eg, HIV, transplant).


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First_Aid_Step1. Risk factors: multiple sexual partners, HPV, smoking, early coitarche, DES exposure, immunocompromise (eg, HIV, transplant). Invasive carcinoma Often squamous cell carcinoma. Pap smear can detect cervical dysplasia before it progresses to invasive carcinoma. Diagnose via colposcopy and biopsy. Lateral invasion can block ureters • hydronephrosis • renal failure. Most common causes Pregnancy, polycystic ovarian syndrome, obesity, HPO axis abnormalities/immaturity, premature of anovulation ovarian failure, hyperprolactinemia, thyroid disorders, eating disorders, competitive athletics, Cushing syndrome, adrenal insufficiency, chromosomal abnormalities (eg, Turner syndrome). Also called exercise-induced amenorrhea. Severe caloric restriction,  energy expenditure, and/or stress  functional disruption of pulsatile GnRH secretion  LH, FSH, estrogen. Pathogenesis includes  leptin (due to  fat) and  cortisol (stress, excessive exercise).


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First_Aid_Step1. Associated with eating disorders and “female athlete triad” ( calorie availability/excessive exercise,  bone mineral density, menstrual dysfunction). Hyperinsulinemia and/or insulin resistance hypothesized to alter hypothalamic hormonal feedback response • LH:FSH,  androgens (eg, testosterone) from theca interna cells,  rate of follicular maturation  unruptured follicles (cysts) + anovulation. Common cause of • fertility in women. Enlarged, bilateral cystic ovaries A ; presents with amenorrhea/oligomenorrhea, hirsutism, acne,  fertility. Associated with obesity, acanthosis nigricans.  risk of endometrial cancer 2° to unopposed estrogen from repeated anovulatory cycles. Treatment: cycle regulation via weight reduction ( peripheral estrone formation), OCPs (prevent endometrial hyperplasia due to unopposed estrogen); clomiphene (ovulation induction); spironolactone, finasteride, flutamide to treat hirsutism.


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First_Aid_Step1. Primary dysmenorrhea Painful menses, caused by uterine contractions to  blood loss • ischemic pain. Mediated by prostaglandins. Treatment: NSAIDs. TyPE mAlIgNANT? CHARACTERISTICS arrow in E ). Tumor marker: AFP. Endometriosis Endometrium-like glands/stroma outside endometrial cavity, most commonly in the ovary (frequently bilateral), pelvis, peritoneum (yellow-brown “powder burn” lesions). In ovary, appears as endometrioma (blood-filled “chocolate cysts” [oval structures above and below asterisks in A ]). May be due to retrograde flow, metaplastic transformation of multipotent cells, transportation of endometrial tissue via lymphatic system. Characterized by cyclic pelvic pain, bleeding, dysmenorrhea, dyspareunia, dyschezia (pain with defecation), infertility; normal-sized uterus. Treatment: NSAIDs, OCPs, progestins, GnRH agonists, danazol, laparoscopic removal.


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First_Aid_Step1. Endometritis Inflammation of endometrium B associated with retained products of conception following delivery, miscarriage, abortion, or with foreign body (eg, IUD). Retained material is nidus for bacteria from vagina or GI tract. Chronic endometritis shows plasma cells on histology. Treatment: gentamicin + clindamycin +/− ampicillin. Commonly postmenopausal. Often presents as a palpable hard mass A most often in the upper outer quadrant. Invasive cancer can become fixed to pectoral muscles, deep fascia, Cooper ligaments, and overlying skin  nipple retraction/skin dimpling. Usually arises from terminal duct lobular unit. Amplification/overexpression of estrogen/ progesterone receptors or c-erbB2 (HER2, an EGF receptor) is common; triple negative (ER ⊝, PR ⊝, and HER2/neu ⊝) form more aggressive.


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First_Aid_Step1. Risk factors in women:  age; history of atypical hyperplasia; family history of breast cancer; race (Caucasians at highest risk, African Americans at  risk for triple ⊝ breast cancer); BRCA1/BRCA2 mutations;  estrogen exposure (eg, nulliparity); postmenopausal obesity (adipose tissue converts androstenedione to estrone);  total number of menstrual cycles; absence of breastfeeding; later age of first pregnancy; alcohol intake. In men: BRCA2 mutation, Klinefelter syndrome. Axillary lymph node metastasis most important prognostic factor in early-stage disease. Invasive ductal Firm, fibrous, “rock-hard” mass with sharp margins and small, glandular, duct-like cells in desmoplastic stroma. aAll types of invasive breast carcinoma can be either of tubular subtype (well-differentiated tubules that lack myoepithelium) or mucinous subtype (abundant extracellular mucin, seen in older women).


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First_Aid_Step1. Peyronie disease Abnormal curvature of penis A due to fibrous plaque within tunica albuginea. Associated with erectile dysfunction. Can cause pain, anxiety. Consider surgical repair or treatment with collagenase injections once curvature stabilizes. Distinct from penile fracture (rupture of corpora cavernosa due to forced bending). Ischemic priapism Painful sustained erection lasting > 4 hours. Associated with sickle cell disease (sickled RBCs block venous drainage of corpus cavernosum vascular channels), medications (eg, sildenafil, trazodone). Treat immediately with corporal aspiration, intracavernosal phenylephrine, or surgical decompression to prevent ischemia. Squamous cell Seen in the US, but more common in Asia, Africa, South America. Precursor in situ lesions: carcinoma Bowen disease (in penile shaft, presents as leukoplakia “white plaque”), erythroplasia of Queyrat


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First_Aid_Step1. B (carcinoma in situ of the glans B , presents as erythroplakia “red plaque”). Bowenoid papulosis (carcinoma in situ of unclear malignant potential, presenting as reddish papules). Associated with uncircumcised males and HPV. Cryptorchidism Descent failure of one A or both testes; impaired spermatogenesis (since sperm develop best at temperatures < 37°C); can have normal testosterone levels (Leydig cells are mostly unaffected by temperature); associated with  risk of germ cell tumors. Prematurity  risk of cryptorchidism.  inhibin B,  FSH,  LH; testosterone  in bilateral cryptorchidism, normal in unilateral. Most cases resolve spontaneously; otherwise, orchiopexy performed before 2 years of age.


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First_Aid_Step1.  inhibin B,  FSH,  LH; testosterone  in bilateral cryptorchidism, normal in unilateral. Most cases resolve spontaneously; otherwise, orchiopexy performed before 2 years of age. Testicular torsion Rotation of testicle around spermatic cord and vascular pedicle. Commonly presents in males 12–18 years old. May occur after an inciting event (eg, trauma) or spontaneously. Characterized by acute, severe pain, high-riding testis, and absent cremasteric reflex. Treatment: surgical correction (orchiopexy) within 6 hours, manual detorsion if surgical option unavailable in timeframe. If testis is not viable, orchiectomy. Orchiopexy, when performed, should be bilateral because the contralateral testis is at risk for subsequent torsion.


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First_Aid_Step1. Varicocele Dilated veins in pampiniform plexus due to  venous pressure; most common cause of scrotal enlargement in adult males; most often on left side because of  resistance to flow from left gonadal vein drainage into left renal vein; can cause infertility because of • temperature; diagnosed by standing clinical exam/Valsalva maneuver (distension on inspection and “bag of worms” on palpation; augmented by Valsalva) or ultrasound A ; does not transilluminate. Treatment: consider surgical ligation or embolization if associated with pain or infertility. Extragonadal germ cell Arise in midline locations. In adults, most commonly in retroperitoneum, mediastinum, pineal, and tumors suprasellar regions. In infants and young children, sacrococcygeal teratomas are most common. Scrotal masses Benign scrotal lesions present as testicular masses that can be transilluminated (vs solid testicular tumors).


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First_Aid_Step1. Scrotal masses Benign scrotal lesions present as testicular masses that can be transilluminated (vs solid testicular tumors). Congenital hydrocele Common cause of scrotal swelling A in infants, Transilluminating swelling. due to incomplete obliteration of processus vaginalis. Most spontaneously resolve within 1 year. Germ cell tumors account for ∼ 95% of all testicular tumors. Arise from germ cells that produce sperm. Most often occur in young men. Risk factors: cryptorchidism, Klinefelter syndrome. Can present as a mixed germ cell tumor. Do not transilluminate. Usually not biopsied (risk of seeding scrotum), removed via radical orchiectomy. Sex cord stromal tumors develop from embryonic sex cord (develops into Sertoli and Leydig cells of seminiferous tubules, theca and granulosa cells of follicle) derivatives. 5% of all testicular tumors. Mostly benign.


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First_Aid_Step1. Orchitis Inflammation of testis. Presents with testicular pain and swelling. Mumps orchitis  infertility risk. Rare in boys < 10 years old. Prostatitis Characterized by dysuria, frequency, urgency, low back pain. Warm, tender, enlarged prostate. Acute bacterial prostatitis—in older men most common bacterium is E coli; in young men consider C trachomatis, N gonorrhoeae. Chronic prostatitis—either bacterial or nonbacterial (eg, 2° to previous infection, nerve problems, chemical irritation). Common in men > 50 years old. Characterized by smooth, elastic, firm nodular enlargement (hyperplasia not hypertrophy) of periurethral (lateral and middle) lobes, which compress the urethra into a vertical slit. Not premalignant. Often presents with  frequency of urination, nocturia, difficulty starting and stopping urine stream, dysuria. May lead to distention and hypertrophy of bladder, hydronephrosis, UTIs.  free prostate-specific antigen (PSA).


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First_Aid_Step1.  free prostate-specific antigen (PSA). Treatment: α1-antagonists (terazosin, tamsulosin), which cause relaxation of smooth muscle; 5α-reductase inhibitors (eg, finasteride); PDE-5 inhibitors (eg, tadalafil); surgical resection (eg, TURP, ablation). Control of reproductive hormones Goserelin, leuprolide mECHANISm GnRH analogs. When used in pulsatile Leuprolide can be used in lieu of GnRH. fashion act as GnRH agonists. When used in continuous fashion first transiently act as GnRH agonists (tumor flare), but subsequently act as GnRH antagonists (downregulate • LH). ClINICAl USE Uterine fibroids, endometriosis, precocious puberty, prostate cancer, infertility. ADVERSE EFFECTS Hypogonadism,  libido, erectile dysfunction, nausea, vomiting. mECHANISm GnRH antagonist. No start-up flare. ClINICAl USE Prostate cancer. ADVERSE EFFECTS Hot flashes, liver toxicity. Estrogens Ethinyl estradiol, DES, mestranol. mECHANISm Bind estrogen receptors.


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First_Aid_Step1. ClINICAl USE Prostate cancer. ADVERSE EFFECTS Hot flashes, liver toxicity. Estrogens Ethinyl estradiol, DES, mestranol. mECHANISm Bind estrogen receptors. ClINICAl USE Hypogonadism or ovarian failure, menstrual abnormalities (combined OCPs), hormone replacement therapy in postmenopausal women. ADVERSE EFFECTS  risk of endometrial cancer (when given without progesterone), bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero,  risk of thrombi. Contraindications—ER ⊕ breast cancer, history of DVTs, tobacco use in women > 35 years old. Raloxifene Antagonist at breast, uterus; agonist at bone;  risk of thromboembolic events (especially with smoking) but no increased risk of endometrial cancer (vs tamoxifen); used primarily to treat osteoporosis. Aromatase inhibitors Anastrozole, letrozole, exemestane. mECHANISm Inhibit peripheral conversion of androgens to estrogen. ClINICAl USE ER ⊕ breast cancer in postmenopausal women.


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First_Aid_Step1. Aromatase inhibitors Anastrozole, letrozole, exemestane. mECHANISm Inhibit peripheral conversion of androgens to estrogen. ClINICAl USE ER ⊕ breast cancer in postmenopausal women. mECHANISm Bind progesterone receptors,  growth and  vascularization of endometrium, thicken cervical mucus. ClINICAl USE Contraception (forms include pill, intrauterine device, implant, depot injection), endometrial cancer, abnormal uterine bleeding. Progestin challenge: presence of withdrawal bleeding excludes anatomic defects (eg, Asherman syndrome) and chronic anovulation without estrogen. Antiprogestins Mifepristone, ulipristal. mECHANISm Competitive inhibitors of progestins at progesterone receptors. ClINICAl USE Termination of pregnancy (mifepristone with misoprostol); emergency contraception (ulipristal). mECHANISm Produces local inflammatory reaction toxic to sperm and ova, preventing fertilization and implantation; hormone free.


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First_Aid_Step1. mECHANISm Produces local inflammatory reaction toxic to sperm and ova, preventing fertilization and implantation; hormone free. ClINICAl USE Long-acting reversible contraception. Most effective emergency contraception. ADVERSE EFFECTS Heavier or longer menses, dysmenorrhea. Risk of PID with insertion (contraindicated in active pelvic infection). Tocolytics Medications that relax the uterus; include terbutaline (β2-agonist action), nifedipine (Ca2+ channel blocker), indomethacin (NSAID). Used to  contraction frequency in preterm labor and allow time for administration of steroids (to promote fetal lung maturity) or transfer to appropriate medical center with obstetrical care. mECHANISm Synthetic androgen that acts as partial agonist at androgen receptors. ClINICAl USE Endometriosis, hereditary angioedema. ADVERSE EFFECTS Weight gain, edema, acne, hirsutism, masculinization,  HDL levels, hepatotoxicity, idiopathic intracranial hypertension.


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First_Aid_Step1. ClINICAl USE Endometriosis, hereditary angioedema. ADVERSE EFFECTS Weight gain, edema, acne, hirsutism, masculinization,  HDL levels, hepatotoxicity, idiopathic intracranial hypertension. Testosterone, methyltestosterone mECHANISm Agonists at androgen receptors. ClINICAl USE Treat hypogonadism and promote development of 2° sex characteristics; stimulate anabolism to promote recovery after burn or injury. ADVERSE EFFECTS Masculinization in females;  intratesticular testosterone in males by inhibiting release of LH (via negative feedback)  gonadal atrophy. Premature closure of epiphyseal plates. • LDL, • HDL. Finasteride 5α-reductase inhibitor ( conversion of Testosterone DHT (more potent). testosterone to DHT). Used for BPH and male-pattern baldness. Adverse effects: gynecomastia and sexual dysfunction. Tamsulosin α -antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α receptors (found on prostate) vs vascular α1B receptors.


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First_Aid_Step1. Tamsulosin α -antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α receptors (found on prostate) vs vascular α1B receptors. mECHANISm Direct arteriolar vasodilator. ClINICAl USE Androgenetic alopecia (pattern baldness), severe refractory hypertension. “There’s so much pollution in the air now that if it weren’t for our lungs, there’d be no place to put it all.” “Freedom is the oxygen of the soul.” “Whenever I feel blue, I start breathing again.” —L. Frank Baum “Life is not the amount of breaths you take; it’s the moments that take your breath away.” —Will Smith, Hitch Group key respiratory, cardiovascular, and renal concepts together for study whenever possible. Know obstructive vs restrictive lung disorders, V˙/Q˙ mismatch, lung volumes, mechanics of respiration, and hemoglobin physiology. Lung cancers and other causes of lung masses are high yield. Be comfortable reading basic chest x-rays, CT scans, and PFTs.


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First_Aid_Step1. Club cells Nonciliated; low columnar/cuboidal with secretory granules. Located in bronchioles. Degrade toxins; secrete component of surfactant; act as reserve cells. Type I pneumocytes Squamous. 97% of alveolar surfaces. Thinly line the alveoli (two black arrows in A ) for optimal gas exchange. A . 2 (surface tension) 2 functions: radius A . (≥ 2 is healthy; < 1.5 predictive of NRDS), foam Risk factors: prematurity, maternal diabetes (due stability index, surfactant-albumin ratio. to  fetal insulin), C-section delivery ( release Persistently low O2 tension  risk of PDA. of fetal glucocorticoids; less stressful than vaginal delivery). Treatment: maternal steroids before birth; exogenous surfactant for infant. Retinopathy of prematurity, Intraventricular hemorrhage, Bronchopulmonary dysplasia (RIB).


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First_Aid_Step1. Treatment: maternal steroids before birth; exogenous surfactant for infant. Retinopathy of prematurity, Intraventricular hemorrhage, Bronchopulmonary dysplasia (RIB). Conducting zone Large airways consist of nose, pharynx, larynx, trachea, and bronchi. Airway resistance highest in the largeto medium-sized bronchi. Small airways consist of bronchioles that further divide into terminal bronchioles (large numbers in parallel  least airway resistance). Warms, humidifies, and filters air but does not participate in gas exchange  “anatomic dead space.” Cartilage and goblet cells extend to the end of bronchi. Pseudostratified ciliated columnar cells primarily make up epithelium of bronchus and extend to beginning of terminal bronchioles, then transition to cuboidal cells. Clear mucus and debris from lungs (mucociliary escalator). Airway smooth muscle cells extend to end of terminal bronchioles (sparse beyond this point).


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First_Aid_Step1. Respiratory zone Lung parenchyma; consists of respiratory bronchioles, alveolar ducts, and alveoli. Participates in gas exchange. Mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli. Cilia terminate in respiratory bronchioles. Alveolar macrophages clear debris and participate in immune response. Right lung has 3 lobes; Left has Less Lobes (2) and Lingula (homolog of right middle lobe). Instead of a middle lobe, left lung has a space occupied by the heart A . Relation of the pulmonary artery to the bronchus at each lung hilum is described by RALS—Right Anterior; Left Superior. Carina is posterior to ascending aorta and anteromedial to descending aorta B . Right lung is a more common site for inhaled foreign bodies because right main stem bronchus is wider, more vertical, and shorter than the left. If you aspirate a peanut: While supine—usually enters superior segment of right lower lobe.


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First_Aid_Step1. While supine—usually enters superior segment of right lower lobe. While lying on right side—usually enters right upper lobe. While upright—usually enters right lower lobe. Structures perforating diaphragm: At T8: IVC, right phrenic nerve At T10: esophagus, vagus (CN 10; 2 trunks) At T12: aorta (red), thoracic duct (white), azygos vein (blue) (“At T-1-2 it’s the red, white, and blue”) Diaphragm is innervated by C3, 4, and 5 (phrenic nerve). Pain from diaphragm irritation (eg, air, blood, or pus in peritoneal cavity) can be referred to shoulder (C5) and trapezius ridge (C3, 4). Number of letters = T level: T8: vena cava (IVC) T10: (O)esophagus T12: aortic hiatus I ate (8) ten eggs at twelve. C3, 4, 5 keeps the diaphragm alive. Other bifurcations: The common carotid bifourcates at C4. The trachea bifourcates at T4. The abdominal aorta bifourcates at L4. Lung volumes Note: a capacity is a sum of ≥ 2 physiologic volumes. 6.0


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First_Aid_Step1. The common carotid bifourcates at C4. The trachea bifourcates at T4. The abdominal aorta bifourcates at L4. Lung volumes Note: a capacity is a sum of ≥ 2 physiologic volumes. 6.0 Tidal volume Air that moves into lung with each quiet inspiration, typically 500 mL 2.7 2.2 1.2 FRC Determination of physiologic dead space VD = physiologic dead space = anatomic dead space of conducting airways plus alveolar dead space; apex of healthy lung is largest contributor of alveolar dead space. Volume of inspired air that does not take part in gas exchange. VT = tidal volume. Paco2 = arterial Pco2. Peco = expired air Pco 2 2. Taco, Paco, Peco, Paco (refers to order of variables in equation) Physiologic dead space—approximately equivalent to anatomic dead space in normal lungs. May be greater than anatomic dead space in lung diseases with V˙/Q˙ defects. Minute ventilation Total volume of gas entering lungs per minute Normal values: VE = VT × RR Respiratory rate (RR) = 12–20 breaths/min


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First_Aid_Step1. Minute ventilation Total volume of gas entering lungs per minute Normal values: VE = VT × RR Respiratory rate (RR) = 12–20 breaths/min Alveolar ventilation Volume of gas that reaches alveoli each minute T V = 150 mL/breath Elastic recoil Tendency for lungs to collapse inward and chest wall to spring outward. At FRC, airway and alveolar pressures equal atmospheric pressure (called zero), and intrapleural pressure is negative (preventing atelectasis). The inward pull of the lung is balanced by the outward pull of the chest wall. System pressure is atmospheric. Pulmonary vascular resistance (PVR) is at a minimum. 0.5 0.0 +2 Compliance Change in lung volume for a change in pressure (ΔV/ΔP). Inversely proportional to wall stiffness and increased by surfactant. 6 •  compliance = lung easier to fill (eg, emphysema, aging) •  compliance = lung harder to fill (eg, 4 pulmonary fibrosis, pneumonia, ARDS, pulmonary edema)


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First_Aid_Step1. Hysteresis Lung inflation follows a different pressure-2 volume curve than lung deflation due to need to overcome surface tension forces in inflation. Hemoglobin Oxygen content of blood O2 content = (1.34 × Hb × Sao2) + (0.003 × Pao2) Hb = hemoglobin concentration; Sao2 = arterial O2 saturation Pao2 = partial pressure of O2 in arterial blood Normally 1 g Hb can bind 1.34 mL O2; normal Hb amount in blood is 15 g/dL. O2 binding capacity ≈ 20 mL O2/dL of blood. With  Hb there is  O2 content of arterial blood, but no change in O2 saturation and Pao2. O2 delivery to tissues = cardiac output × O2 content of blood. ODC has sigmoidal shape due to positive cooperativity (ie, tetrameric Hb molecule can 100 bind 4 O2 molecules and has higher affinity for each subsequent O2 molecule bound). 80 Myoglobin is monomeric and thus does 70 not show positive cooperativity; curve lacks 60 sigmoidal appearance.


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First_Aid_Step1. Shifting ODC to the right  Hb affinity for O2 (facilitates unloading of O2 to tissue)  P50 (higher Po2 required to maintain 50% saturation). Shifting ODC to the left  O2 unloading compensatory erythrocytosis. Fetal Hb (2 α and 2 γ subunits) has higher affinity for O2 than adult Hb (due to  affinity for 2,3-BPG)  dissociation curve is shifted left, driving diffusion of O2 across the placenta from mother to fetus. Cyanide vs carbon Both inhibit aerobic metabolism via inhibition of complex IV (cytochrome c oxidase)  hypoxia monoxide poisoning that does not fully correct with supplemental O2 and  anaerobic metabolism. Both can lead to pink or cherry red skin (usually postmortem finding), seizures, and coma. SOURCE Byproduct of synthetic product combustion, Odorless gas from fires, car exhaust, or gas ingestion of amygdalin (cyanogenic glucoside heaters. found in apricot seeds) or cyanide. TREATmENT Hydroxocobalamin (binds cyanide 100% O2, hyperbaric O2.


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First_Aid_Step1. TREATmENT Hydroxocobalamin (binds cyanide 100% O2, hyperbaric O2. • cyanocobalamin • renal excretion). Nitrites (oxidize Hb • methemoglobin  binds cyanide • cyanomethemoglobin  less toxicity). Sodium thiosulfate (• cyanide conversion to thiocyanate • renal excretion). SIgNS/SYmPTOmS Breath has bitter almond odor; cardiovascular Headache, dizziness. collapse. Multiple individuals may be involved (eg, family with similar symptoms in winter). Classically associated with bilateral globus pallidus lesions on MRI A , although rarely seen with cyanide toxicity as well. normal initially. Left shift in curve  affinity for O2  O2 unloading in tissues. Binds competitively to Hb with 200× greater affinity than O2 to form carboxyhemoglobin • %O2 saturation of Hb. O2 bound to Hb (mL O2 /100 mL)


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First_Aid_Step1. Binds competitively to Hb with 200× greater affinity than O2 to form carboxyhemoglobin • %O2 saturation of Hb. O2 bound to Hb (mL O2 /100 mL) Normally a low-resistance, high-compliance system. A  in Pao2 causes a hypoxic vasoconstriction that shifts blood away from poorly ventilated regions of lung to well-ventilated regions of lung. Perfusion limited—O2 (normal health), CO2, N2O. Gas equilibrates early along the length of the capillary. Exchange can be  only if blood flow . Diffusion limited—O2 (emphysema, fibrosis, exercise), CO. Gas does not equilibrate by the time blood reaches the end of the capillary. A consequence of pulmonary hypertension is cor pulmonale and subsequent right ventricular failure. P – P Diffusion: V˙ gas = A × Dk × 1 2 where Δ A = area, Δ x = alveolar wall thickness, Dk = diffusion coefficient of gas, P1 – P2 = difference in partial pressures. A  in emphysema. Δ x  in pulmonary fibrosis.


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First_Aid_Step1. A = area, Δ x = alveolar wall thickness, Dk = diffusion coefficient of gas, P1 – P2 = difference in partial pressures. A  in emphysema. Δ x  in pulmonary fibrosis. DLCO is the extent to which CO passes from air sacs of lungs into blood. Ventilation/perfusion Ideally, ventilation is matched to perfusion (ie, mismatch V˙/Q˙ = 1) for adequate gas exchange. Lung zones: V˙/Q˙ at apex of lung = 3 (wasted ventilation) Q V˙/Q˙ at base of lung = 0.6 (wasted perfusion) Both ventilation and perfusion are greater at the base of the lung than at the apex of the lung. With exercise ( cardiac output), there is vasodilation of apical capillaries  V˙/Q˙ ratio approaches 1. Certain organisms that thrive in high O2 (eg, TB) flourish in the apex.


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First_Aid_Step1. With exercise ( cardiac output), there is vasodilation of apical capillaries  V˙/Q˙ ratio approaches 1. Certain organisms that thrive in high O2 (eg, TB) flourish in the apex. V ˜˜ V˙/Q˙ = 0 = “oirway” obstruction (shunt). In Q shunt, 100% O2 does not improve Pao2 (eg, foreign body aspiration). V˙/Q˙ = ∞ = blood flow obstruction (physiologic dead space). Assuming < 100% dead space, 100% O2 improves Pao2 (eg, pulmonary embolus). CO2 is transported from tissues to lungs in 3 forms: HCO3 − (70%). Carbaminohemoglobin or HbCO2 (21–25%). CO2 bound to Hb at N-terminus of globin (not heme). CO2 favors deoxygenated form (O2 unloaded). Dissolved CO2 (5–9%). In lungs, oxygenation of Hb promotes dissociation of H+ from Hb. This shifts equilibrium toward CO2 formation; therefore, CO2 is released from RBCs (Haldane effect). In peripheral tissue,  H+ from tissue metabolism shifts curve to right, unloading O2 (Bohr effect). Majority of blood CO2 is carried as HCO3 − in the plasma.


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First_Aid_Step1. In peripheral tissue,  H+ from tissue metabolism shifts curve to right, unloading O2 (Bohr effect). Majority of blood CO2 is carried as HCO3 − in the plasma. Response to high altitude sickness. Chronic  in ventilation. erythropoietin  Hct and Hb (due to chronic hypoxia). 2,3-BPG (binds to Hb causing rightward shift of the ODC so that Hb releases more O2). Cellular changes ( mitochondria). renal excretion of HCO3 − to compensate for respiratory alkalosis (can augment with acetazolamide). Chronic hypoxic pulmonary vasoconstriction results in pulmonary hypertension and RVH. Response to exercise  CO2 production.  O2 consumption. Right shift of ODC. ventilation rate to meet O2 demand. V˙/Q˙ ratio from apex to base becomes more uniform. pulmonary blood flow due to  cardiac output. pH during strenuous exercise (2° to lactic acidosis). No change in Pao2 and Paco2, but  in venous CO2 content and  in venous O2 content.


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First_Aid_Step1. pulmonary blood flow due to  cardiac output. pH during strenuous exercise (2° to lactic acidosis). No change in Pao2 and Paco2, but  in venous CO2 content and  in venous O2 content. Obstruction of sinus drainage into nasal cavity  inflammation and pain over affected area. Typically affects maxillary sinuses, which drain against gravity due to ostia located superomedially (red arrow points to fluid-filled right maxillary sinus in A ). Superior meatus—drains sphenoid, posterior ethmoid; middle meatus—drains frontal, maxillary, and anterior ethmoid; inferior meatus—drains nasolacrimal duct. Most common acute cause is viral URI; may lead to superimposed bacterial infection, most commonly H influenzae, S pneumoniae, M catarrhalis. Paranasal sinus infections may extend to the orbits, cavernous sinus, and brain, causing complications (eg, orbital cellulitis, cavernous sinus syndrome, meningitis).


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First_Aid_Step1. Paranasal sinus infections may extend to the orbits, cavernous sinus, and brain, causing complications (eg, orbital cellulitis, cavernous sinus syndrome, meningitis). Head and neck cancer Mostly squamous cell carcinoma. Risk factors include tobacco, alcohol, HPV-16 (oropharyngeal), EBV (nasopharyngeal). Field cancerization: carcinogen damages wide mucosal area • multiple tumors that develop independently after exposure. Blood clot within a deep vein  swelling, redness A , warmth, pain. Predisposed by Virchow triad (SHE): Stasis (eg, post-op, long drive/flight) Hypercoagulability (eg, defect in coagulation cascade proteins, such as factor V Leiden; oral contraceptive use; pregnancy) Most pulmonary emboli arise from proximal deep veins of lower extremity. d-dimer lab test used clinically to rule out DVT in low-to-moderate risk patients (high sensitivity, low specificity). Imaging test of choice is compression ultrasound with Doppler.


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First_Aid_Step1. d-dimer lab test used clinically to rule out DVT in low-to-moderate risk patients (high sensitivity, low specificity). Imaging test of choice is compression ultrasound with Doppler. Use unfractionated heparin or low-molecular weight heparins (eg, enoxaparin) for prophylaxis and acute management. Use oral anticoagulants (eg, rivaroxaban, apixaban) for treatment and long-term prevention.


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First_Aid_Step1. Pulmonary emboli V˙/Q˙ mismatch, hypoxemia, respiratory alkalosis. Sudden-onset dyspnea, pleuritic chest pain, tachypnea, tachycardia. Large emboli or saddle embolus A may cause sudden death due to electromechanical dissociation (pulseless electrical activity). CT pulmonary angiography is imaging test of choice for PE (look for filling defects) B . May have S1Q3T3 abnormality on ECG. Lines of Zahn C are interdigitating areas of pink (platelets, fibrin) and red (RBCs) found only in thrombi formed before death; help distinguish preand postmortem thrombi. Types: Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor. An embolus moves like a FAT BAT. Fat emboli—associated with long bone fractures and liposuction; classic triad of hypoxemia, neurologic abnormalities, petechial rash. Air emboli—nitrogen bubbles precipitate in ascending divers (caisson disease/decompression sickness); treat with hyperbaric O2; or, can be iatrogenic 2° to invasive procedures (eg, central line placement).


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First_Aid_Step1. bubbles precipitate in ascending divers (caisson disease/decompression sickness); treat with hyperbaric O2; or, can be iatrogenic 2° to invasive procedures (eg, central line placement). Amniotic fluid emboli—typically occurs during labor or postpartum, but can be due to uterine trauma. Can lead to DIC. Rare, but high mortality.


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First_Aid_Step1. Mediastinal pathology Normal mediastinum contains heart, thymus, lymph nodes, esophagus, and aorta. Mediastinal masses Some pathologies (eg, lymphoma, lung cancer, abscess) can occur in any compartment, but there are common associations: Anterior—4T’s: Thyroid (substernal goiter), Thymic neoplasm, Teratoma, “Terrible” lymphoma. Middle—esophageal carcinoma, metastases, hiatal hernia, bronchogenic cysts. Posterior—neurogenic tumor (eg, neurofibroma), multiple myeloma. Mediastinitis Inflammation of mediastinal tissues. Commonly due to postoperative complications of cardiothoracic procedures (≤ 14 days), esophageal perforation, or contiguous spread of odontogenic/retropharyngeal infection. Chronic mediastinitis—also known as fibrosing mediastinitis; due to  proliferation of connective tissue in mediastinum. Histoplasma capsulatum is common cause. Clinical features: fever, tachycardia, leukocytosis, chest pain, and sternal wound drainage.


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First_Aid_Step1. Pneumomediastinum Presence of gas (usually air) in the mediastinum (black arrows show air around the aorta, red arrow shows air dissecting into the neck A ). Can either be spontaneous (due to rupture of pulmonary bleb) or 2° (eg, trauma, iatrogenic, Boerhaave syndrome). Ruptured alveoli allow tracking of air into the mediastinum via peribronchial and perivascular sheaths. Clinical features: chest pain, dyspnea, voice change, subcutaneous emphysema, ⊕ Hamman sign (crepitus on cardiac auscultation). Emphysema (“pink puffer”) Normal Centriacinar emphysema Panacinar emphysema Findings: barrel-shaped chest D , exhalation through pursed lips (increases airway pressure and prevents airway collapse). Centriacinar—affects respiratory bronchioles while sparing distal alveoli, associated with B . Frequently in upper lobes (smoke rises up). Panacinar—affects respiratory bronchioles and alveoli, associated with α1-antitrypsin deficiency. Frequently in lower lobes.


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First_Aid_Step1. B . Frequently in upper lobes (smoke rises up). Panacinar—affects respiratory bronchioles and alveoli, associated with α1-antitrypsin deficiency. Frequently in lower lobes. Enlargement of air spaces recoil, • compliance, from destruction of alveolar walls (arrow in C ) and  blood volume in pulmonary capillaries. Imbalance of proteases and antiproteases • elastase activity  loss of elastic fibers • lung compliance. CXR: • AP diameter, flattened diaphragm, • lung field lucency. Asthma Findings: cough, wheezing, tachypnea, dyspnea, hypoxemia, • inspiratory/ expiratory ratio, pulsus paradoxus, mucus plugging E . Triggers: viral URIs, allergens, stress. Hyperresponsive bronchi • reversible bronchoconstriction. Smooth muscle hypertrophy and hyperplasia, Curschmann spirals F (shed epithelium forms whorled mucous plugs), and Charcot-Leyden crystals G (eosinophilic, hexagonal, double-pointed crystals formed from breakdown of eosinophils in sputum). DLCO normal or .


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First_Aid_Step1. F (shed epithelium forms whorled mucous plugs), and Charcot-Leyden crystals G (eosinophilic, hexagonal, double-pointed crystals formed from breakdown of eosinophils in sputum). DLCO normal or . Type I hypersensitivity reaction. Diagnosis supported by spirometry and methacholine challenge. NSAID-exacerbated respiratory disease is a combination of COX inhibition (leukotriene overproduction • airway constriction), chronic sinusitis with nasal polyps, and asthma symptoms. TYPE PRESENTATION PAThOlOgY OThER Bronchiectasis Findings: purulent sputum, recurrent infections (most often P aeruginosa), hemoptysis, digital clubbing. Chronic necrotizing infection of bronchi or obstruction permanently dilated airways. Associated with bronchial obstruction, poor ciliary motility (eg, smoking, Kartagener syndrome), cystic fibrosis H , allergic bronchopulmonary aspergillosis. A B C D E G HF