✅ Lytes, Acid-Base, Injury, Vasculitis Flashcards

Question

Hyperthyroidism

Answer 1

Hypercalcemia is a frequent incidental finding in hyperthyroidism, which results from direct stimulation of osteoclasts by thyroxine or triiodothyronine. Low PTH?

Answer 2

Constitutive overexpression of the calcium-sensing receptor gene. Dx: Elevated calcium, low phosphate, and a calcium-creatinine clearance ratio \<0.01 [calculated as (Urine calcium ÷ Serum calcium) × (Serum creatinine ÷ Urine creatinine)]. Normal PTH?

Answer 3

Calcium normally **9-10.5** mg/dL Causes * **Neck surgery** (parathyroidectomy) * Pancreatitis * Sepsis * Tumor lysis syndrome * Acute alkalosis * Chelation: blood (citrate) transfusion, EDTA (ethylenediaminetetraacetic acid), foscarnet Clinical features * **Muscle cramps** * Chvostek & Trousseau signs * **Paresthesias** * Hyperreflexia/tetany * Seizures Treatment * IV calcium gluconate/chloride **Decreased _{👨🏽‍🔬}PTH production** **_ⓂHypomagnesemia** causes **decreased** production of _{👨🏽‍🔬}**PTH** as well as decreased end-organ response to the hormone. 🍻 **Alcohol** causes **increased urinary losses of magnesium** which then leads to the mentioned effects on PTH and ultimately to hypocalcemia. Hypomagnesemia alone would ^🅿**increase phosphorus** by decreasing parathormone effect. **_⚪Hypoalbuminemia** Approximately 40% of circulating calcium is bound to proteins (predominantly albumin). **Hypoalbuminemia will lower the total serum calcium level;** therefore, **measured calcium levels are corrected upward** based on the extent of hypoalbuminemia. Conversely, hyperalbuminemia is associated with an increase in total calcium. The **serum calcium** concentration **INCREASES** by **0.8** mg/dL for every **1** g/dL **decrease** in serum **albumin**; the corrected calcium level can be calculated using the following formula: **Corrected calcium** = (measured total calcium) + 0.8 × (4.0 g/dL − serum albumin in g/dL) "**Add 0.8 mg/dL to the observed calcium** level **for every 1 g reduction in the albumin level** (from **4** used as normal)" An **ionized calcium** level is consistent and accurate regardless of the albumin level of a patient. Direct measurement of ionized calcium is performed in many clinical laboratories, but it requires special handling and may not be readily available. Plasma calcium exists in 3 forms: **ionized calcium (45%), albumin-bound calcium (40%), and calcium bound to inorganic and organic anions (15%).** Homeostasis of these forms is significantly influenced by the extracellular pH level. An increased extracellular pH (due to respiratory alkalosis ) causes hydrogen ions to dissociate from albumin molecules, thereby freeing up the albumin to bind with calcium. This increase in the affinity of albumin for calcium leads to decreased levels of ionized calcium. Ionized calcium is the only physiologically active form, which means that a decrease in ionized calcium can result in the clinical manifestations of **hypocalcemia (eg, crampy pain, paresthesias, carpopedal spasm)** even though total calcium is unchanged. * **Chvostek sign** * **Trousseau sign** **🍊 Citrate** in **transfused blood** binds **ionized calcium**, which is the biologically active fraction (total calcium levels will not be significantly affected). Hypocalcemia is uncommon following blood transfusion in patients with normal liver function as citrate is rapidly metabolized by the liver; however, 🐄 **hepatic dysfunction** can. Other infused substances that can chelate calcium in the blood include lactate, foscarnet, and sodium ethylenediaminetetraacetic acid (EDTA). **Tx:** **Oral calcium (carbonate or citrate) supplementation**. **Intravenous calcium guconate/chloride** more rapidly increases the serum calcium level and may be indicated in patients with very low (\< 7.5 mg/dL) calcium levels or more significant clinical findings associated with the hypocalcemia, such as severe musculoskeletal weakness, tetany, or electrocardiographic conduction abnormalities. **Recombinant form of parathyroid hormone (teriparatide)** is available, although its primary use is in the treatment of advanced osteoporosis in selected patients. Although teriparatide holds promise as a potential therapy for chronic hypoparathyroidism, its safety and long-term effectiveness for this indication have not been established, and it does not have Food and Drug Administration approval for treatment of acute hypoparathyroidism.

Answer 4

Hypophosphatemia is defined as a serum phosphorus concentration **less than 2.5 mg/dL** and is most common in patients with a **history of chronic 🍻 alcohol use, critical illness, or malnutrition.** **Respiratory alkalosis** is one of the commonest causes of hypophosphatemia; it results from shift of phosphate from the extracellular to the intracellular space. **Dx:** Most patients with hypophosphatemia are **asymptomatic**, but symptoms of **weakness** may manifest at serum phosphorus levels \< 2.0 mg/dL. Levels less than 1.0 mg/dL may result in respiratory muscle weakness, hemolysis, rhabdomyolysis or tumor lysis. Serum uric acid \>15 mg/dL suggests rhabdomyolysis or TLS. **🍗Refeeding syndrome** is caused by an **intracellular shift of _🅿phosphorus**; calories provided to a patient after a prolonged period of starvation serve as a stimulus for **cellular growth**, which **consumes phosphorus** in the form of phosphorylated intermediates such as **adenosine triphosphate.** **Hx:** Persons who chronically 🍻**abuse alcohol** frequently may develop refeeding syndrome, largely because of underlying **poor nutrition.** The syndrome may also be the result of intravenous infusion **IV** of **glucose** in malnourished patients. Such patients have clear clinical evidence of malnutrition. In addition, malnutrition almost always causes hypoalbuminemia. **Tx:** If the refeeding syndrome occurs, **the level of nutritional support should be reduced**, and the hypophosphatemia, hypokalemia, and hypomagnesemia should be corrected. Moderately to severely ill patients with marked edema or a serum phosphorus level less than 2.0 mg/dL should be hospitalized for intravenous therapy to correct electrolyte deficiencies. Continuous telemetry may also be needed to monitor cardiopulmonary physiology.

Answer 5

**Tx:** Restrict dietary potassium, ensure adequate hydration, and use loop diuretics as necessary. Severe hyperkalemia (\>6.0 meq/L [6.0 mmol/L]) is associated with life-threatening cardiac dysrhythmias; patients with severe hyperkalemia require emergent hospitalization for medical management. **Stabilize** (Cacl) **Temporize** (Insulin, NaHCO3, beta-agonist); decrease total body K+ (loop Diuretics, kayexylate, **dialysis**) **Calcium gluconate** Raises threshold for depolarization (myocardial membrane stabilization) **Sodium bicarbonate** Shifts potassium intracellularly. Patients with severe kidney disease or hypervolemic states, such as CHF, may not tolerate alkalinization or the associated sodium load. Ideally, the serum bicarbonate and creatinine should be checked before intravenous sodium bicarbonate is administered. **Insulin/glucose** Shifts potassium intracellularly. In euglycemic patients, a combination of insulin (**10U**) and glucose (**25g**) is typically administered concomitantly to decrease the risk of hypoglycemia (can lower the serum potassium level by 0.5 to 1.0). In hyperglycemic patients insulin alone should be given. **β-Agonists (eg, inhaled albuterol)** Shifts potassium intracellularly. Probably more effective than IV sodium bicarbonate. It Measures to promote potassium loss from the body (Kayexalate, furosemide, or dialysis) take time to work. **Loop diuretics** Increases renal excretion of potassium. Depending on the patient’s kidney function and volume status, may be considered, but they take hours to work and should not take the place of immediate therapy. **Sodium polystyrene sulfonate (kayexelate)** Ion exchange resin binding potassium in the gut; may be no more effective than laxatives and has been associated with intestinal necrosis; ; need good bowel function. The delayed onset of action of this drug prevents this from being the best initial intervention. **Dialysis** Extracorporeal removal of potassium .1 for every 10 mEq

Answer 6

* **Surreptitious vomiting** * ****Physical findings that are characteristic of surreptitious vomiting are scars/calluses on the dorsum of the hands, and **dental erosions**. The dorsal scars result from repeated chemical/mechanical injury as the patient uses his/her hands to induce vomiting. Dental erosions result due to increased exposure to gastric acid. Surreptitious vomiting may also result in hypovolemia and hypochloremia, which in turn lead to a low urine chloride concentration. * Diuretic abuse (Potassium-wasting diuretics) * Bartter syndrome * Gitelman's syndrome * Hypokalemia, alkalosis and normotension, but their **urine chloride concentrations are high.** * Diarrhea **Hx:** In some patients, clinically significant hypokalemia can result, causing **muscle weakness, arrhythmias, and EKG changes**. Other common side effects of beta-2 agonists include tremor, headache and palpitations. Symptoms of hypokalemia depend on the severity of the imbalance, but can include weakness, fatigue, and muscle cramps. Flaccid paralysis, hyporeflexia, tetany, rhabdomyolysis, and arrhythmias may occur with severe hypokalemia (serum concentration \<2.5 mEq/L). An ECG will show **broad flat T waves**, U waves, ST depression, and premature ventricular beats. Atrial fibrillation, torsades de pointes, and ventricular fibrillation can occur. **Beta-2 agonists** like albuterol reduce serum potassium levels by driving potassium into cells.

Answer 7

**Increased serum anion gap:** * Ketoacidosis (**DKA**, Alcohol Abuse, starvation) * **L**actic acidosis (ischemia, sepsis, shock, drugs) * Exogenous substances (**M**ethanol, **E**thylene glycol, **S**alicylates, toluene) **Salicilates:** Aspirin stimulates central respiratory drive (medullary respiratory center) to cause tachypnea and respiratory alkalosis. In addition, aspirin causes an anion gap metabolic acidosis due to increased production and decreased renal elimination of organic acids (eg, lactic acid, ketoacids)[suppression of oxidative phosphorylation]. • Chronic kidney disease (**U**remia) Isoniazid/**Iron (poisoning)** classically presents in children age \<6 due to unintentional ingestion of prenatal vitamins or concentrated ferrous sulfate tablets. Iron causes direct mucosal damage to the intestinal tract, leading to abdominal pain, vomiting, diarrhea, and bleeding (hematemesis, melena). **Normal serum anion gap** (hyperchloremic): Common causes include renal tubular acidosis, bicarbonate loss owing to **diarrhea****. HARDASS (H**yperalimnetation,**A**ddisons (mineralocorticoid [Adrenal] deficiency),**R**TA, 💩**D**iarrhea,**A**cetazolamide,**S**pronolactone,**S**aline Infusion). Toluene inhalation (glue sniffing)? • ➕ **Positive** 🚽 **urine anion gap**: Metabolic acidosis of kidney origin related to the inability to excrete acid and the resulting a positive UAG related to minimal urine ammonium excretion. ○ **Type I RTA (normo- or hypokalemic),** caused by **impaired _distal_ tubule acidification**, (The kidney's **ability to excrete hydrogen ions in response to acidemia is impaired**) should be considered in patients with a normal anion gap acidosis, **hypokalemia**, a positive urine anion gap, and a urine **pH \>5.5 🔵 alkali)** in the setting of systemic acidosis; serum bicarbonate concentration may be as low as **≅10 mEq/L** (10 mmol/L). **Hx:** Autoimmune disorders such as Sjögren syndrome, systemic lupus erythematosus, or rheumatoid arthritis; drugs such as lithium or amphotericin B; hypercalciuria; and hyperglobulinemia; The persistently increased pH encourages the development of kidney stones (nephrolithiasis and nephrocalcinosis). ○ **Type IV RTA** **(hyperkalemic),** should be suspected in patients with a normal anion gap metabolic acidosis associated with 🍌 **hyperkalemia** and a slightly positive urine anion gap. Type 4 RTA occurs most often in patients with 🍭**diabetes** who have mild to moderate kidney insufficiency. The disorder is caused by **hyporeninemic hypoaldosteronism**, which is characterized by deficient angiotensin II production caused by both decreased renin production and an intraadrenal defect leading to aldosterone deficiency. urine pH \<5.5 **Normal** 🚽 **urine anion gap** ○ **Type II RTA (normo- or hypokalemic)**, caused by **reduced proximal tubule bicarbonate reabsorption** 🏎 (defect in regenerating bicarbonate in the proximal tubule) and should be suspected in patients with a normal anion gap metabolic acidosis, a normal urine anion gap, **hypokalemia**, and an intact ability to acidify the urine to a **pH of \<5.5** while in a steady state. serum [HCO3] **≅ 16–18 mEq/L** (16-18 mmol/L) **Glycosuria**, phosphaturia, uricosuria, aminoaciduria, and tubular proteinuria (Fanconi syndrome). Proximal RTA is associated with glycosuria, phosphaturia, and aminoaciduria (**Fanconi syndrome**). • ➖ **Negative** 🚽 **urine anion gap**: Metabolic acidosis of extrarenal origin (usually gastrointestinal) caused by **significantly increased urine ammonium excretion**, which is used as a measure of the kidney's ability to excrete acid. ○ Patients with increased **gastrointestinal (GI) losses of bicarbonate and potassium** have intact renal tubular function that results in a compensatory increase in urine ammonium production, indicating increased acid secretion by the kidney; ureterosigmoidostomy. ○ Ingestion of acid

Answer 8

* **Respiratory center depression** **(stroke**, **infection**, **tumor**, **opiates**, **COPD**, **OHS**, post-ictal, **drug overdose** causing **hypoventilation**) * **Neuromuscular failure** (muscular dystrophy, ALS, Guillain-Barré syndrome, myasthenia gravis) * **Decreased respiratory system compliance** (kyphoscoliosis, **interstitial lung disease ((ILD/DPLD)**) * **Increased airway resistance** or **obstruction (asthma, COPD, OHS)** * **Increased dead space** or ventilation–perfusion mismatch **(pulmonary embolism, COPD, OHS)** **COPD** Chronic retention of carbon dioxide. **Renal compensation** for persistent hypercapnia results from stimulation of secretion of protons at the level of the distal nephron. Dx: The **urine pH decreases**, and excretion of urine ammonium, titratable acid, and chloride is enhanced. Consequently, the **reabsorption of bicarbonate** throughout the nephron is enhanced. **OHS** Patients with OHS **"can't breathe"** (due to excess weight and altered lung mechanics) and **"won't breathe"** (due to decreased chemosensitivity to hypercapnia from persistent nocturnal hypoventilation). **Hx:** Daytime **hypercapnia (PaCO2 \>45 mm Hg)** in an obese patient (BMI \>30 kg/m2, often \>40 kg/m2) without another explanation for the hypercapnia. Most patients have coexisting obstructive sleep apnea with frequent apneic events and daytime hypersomnolence. Other features of OHS include dyspnea, polycythemia, **respiratory acidosis with compensatory metabolic alkalosis**, pulmonary hypertension, and cor pulmonale. Obesity **reduces chest wall and lung compliance**, leading to a decrease in tidal volumes and total lung capacity and an increase in airway resistance. As a result, higher levels of ventilatory drive are required to maintain normocapnia, but there is an inability to exhale excess CO2 during the day (due to persistent restriction). This leads to CO2 accumulation overnight, with subsequent chronic respiratory acidosis. Renal bicarbonate excretion is decreased as a compensatory mechanism; this blunts the ventilatory response to the increased CO2 and contributes to hypoventilation.

Answer 9

* **🤮Vomiting/**Nasogastric suctioning * **Thiazide and loop diuretic therapy** * Contraction alkalosis * Exogenous bicarbonate in the setting of kidney dysfunction * Low cardiac output (low effective arterial blood volume) **Saline-responsive metabolic alkalosis** **Hx:** Patients typically develop volume depletion (eg, hypotension, orthostasis) and low serum Cl- due to chloride loss in the gastric secretions. The ECF loss leads to **increased renal mineralocorticoid levels,** increased renal sodium and chloride reabsorption, and increased urinary H+ and K+ excretion. The end result is **decreased urine chloride, _🍌hypokalemia, and metabolic alkalosis.** **Tx:** Usually corrects with **isotonic saline infusion** alone and restores both ECF volume and low serum Cl-. **Chloride unresponsive (urine [chloride] \>15 meq/L** * Elevated mineralocorticoid activity (primary hyperaldosteronism, **Cushing syndrome**) * Exogenous mineralocorticoid * Bartter, Gitelman, Liddle syndromes (genetically based tubular disorder) * Some forms of **congenital adrenal hyperplasia** * Severe hypokalemia * Chronic licorice ingestion **Hx:** Patients can have expanded extracellular fluid (ECF) with hypervolemia (eg, primary hyperaldosteronism, Cushing syndrome, excessive black licorice ingestion) or appear hypo/euvolemic (eg, Bartter syndrome, Gitelman syndrome). **Tx:** **Saline-unresponsive** typically presents with a higher level of urinary chloride (\>20 mEq/L). These conditions require treatment of the **underlying disorder**; the metabolic alkalosis is not corrected by saline infusion alone.

Answer 10

* **CNS stimulation** (stroke, infection, tumor, fever, **pain**) * **Drugs** (**aspirin**, progesterone, theophylline, caffeine) * **Hyperventilation 💨** (😰**Anxiety**, psychosis, Pregnancy) * **Pulmonary Hypertension, Pulmonary Embolism 🔴** * **Pulmonary parenchymal Disease** (Pneumonia, pulmonary fibrosis) * **Hypoxemia** (🗻low atmospheric oxygen, severe anemia, lung disease, right-to-left shunt, heart failure, sepsis) REBREATHING AIR **Plasma calcium** exists in 3 forms: ionized calcium (45%), albumin-bound calcium (40%), and calcium bound to inorganic and organic anions (15%). Homeostasis of these forms is significantly influenced by the extracellular pH level. An increased extracellular pH (due to **respiratory alkalosis**) causes **hydrogen ions to dissociate from albumin molecules**, thereby **freeing up the albumin to bind with calcium**. This increase in the affinity of albumin for calcium leads to **decreased levels of ionized calcium.** Ionized calcium is the only physiologically active form, which means that a decrease in ionized calcium can result in the **clinical manifestations of hypocalcemia** (eg, crampy pain, paresthesias, carpopedal spasm) even though total calcium is unchanged. Thus, patients can experience signs and symptoms of hypocalcemia due to respiratory alkalosis likely caused by hyperventilation, as may be seen in pulmonary embolism.

Answer 11

Acute kidney injury (AKI) develops over hours to days and is usually diagnosed in hospitalized patients or following a procedure. * **Stage 1** (risk) Creatinine Increase of ≥150%–200% Urine output \<0.5 mL/kg/h for \>6 h * **Stage 2** (injury) Creatinine Increase of ≥200%–300% Urine output \<0.5 mL/kg/h for \>12 h * **Stage 3** (failure) Creatinine Increase of \>300% or \>4 mg/dL (353.6 µmol/L) with acute increase ≥0.5 mg/dL (44 µmol/L) Urine output \<0.3 mL/kg/h for \>24 h or anuria for 12 h **Intrinsic AKI** is divided into oliguric (≤400 mL/24 h) and nonoliguric (\>400 mL/24 h) forms. **Prerenal** * BUN/creatinine ratio * Typically \>20 * Urine sodium * \<20 mEq/L * Fractional excretion of sodium * \<1% * Urine osmolality * \>500 mOsm/kg * Urine specific gravity * \>1.020 * Microscopy * Bland AKI can be categorized as prerenal (eg, low urine sodium [eg, \<20 mEq/L], elevated blood urea nitrogen (BUN)/creatinine ratio [eg, \>20]), postrenal (eg, hydronephrosis on ultrasound), or intrinsic.

Answer 12

Significant proteinuria suggests glomerular disease. **Hematuria:** **No erythrocytes** suggests rhabdomyolysis. **I****somorphic, normal-appearing erythrocytes**and the absence of proteinuria = nonglomerular bleeding. In a patient age younger than age 40 years, greater than**3 erythrocytes/high-power field on two or more occasions constitutes hematuria** and is a common finding on urinalysis. A single episode in older patients or in those at risk ( smoking history, occupational exposure to chemicals or dyes, age older than 40 years, a history of gross hematuria, a urologic disorder, irritative voiding symptoms, urinary tract infection, analgesic abuse, or pelvic irradiation) should initiate a full evaluation of the upper and lower urinary tract. **Dysmorphic erythrocytes** suggest acute glomerulonephritis. Glomerular hematuria also is characterized by the presence of dysmorphic erythrocytes or acanthocytes, which are erythrocytes that retain a ring shape but have “blebs” protruding from their membrane, giving them a characteristic shape (compared with acanthocytes in the blood, in which the membrane protrusions appear to have a “spiked” shape). **Urine pH** may range between 4.5 and 8.0. **Specific gravity** ranges between 1.003 and 1.035, with the specific gravity of normal serum being approximately 1.010. Excretion of urine with a persistently **low specific gravity** (\<1.007) is called hyposthenuria and may indicate a loss of concentrating ability (eg, diabetes insipidus). High urine specific gravity may reflect an appropriate response to water loss or dehydration or may indicate a pathologic state of fluid retention (eg, heart failure). The detection of **proteinuria** implies an albumin excretion rate (AER) of ≥300 mg/24 h. However, the detection of lesser but still abnormal degrees of albuminuria (albumin excretion rates of 30–300 mg/24 h) requires other quantitative methods. The dipstick protein indicator is insensitive to **tubular proteins** and **immunoglobulins**; identification of the latter (eg, Bence-Jones proteins secondary to multiple myeloma) is best accomplished by a **24-hour urine collection for total protein** with protein electrophoresis and immunofixation. Lysed neutrophils and macrophages release indoxyl esterase, which can be detected by multireagent dipstick technology (leukocyte esterase positive). A positive reaction for urine **nitrite** may indicate the presence of bacteria that reduce nitrate, most commonly gram-negative pathogens. Whereas a positive result for both urine **leukocyte esterase** and urine nitrites is 68% to 88% sensitive for urinary tract infection, **Eosinophils** may be seen in the urine of patients with AKI caused by drug-induced interstitial nephritis and in a variety of other conditions, including rapidly progressive glomerulonephritis, prostatitis, renal atheroemboli, and small-vessel vasculitis. Renal tubular **epithelial cell casts** may be produced by desquamation of epithelial cells associated with acute tubular necrosis, proliferative glomerulonephritis, or interstitial nephritis. Hyaline casts are composed of Tamm-Horsfall glycoprotein and normally may be seen in increased numbers in concentrated urine specimens. Granular casts are hyaline casts containing aggregated filtered proteins and may be seen in patients with albuminuria and proteinuria. Degenerated cellular casts may appear granular and upon further degeneration are described as waxy casts.

Answer 13

Decrease in ECF volume: Decrease in RBF Altered intrarenal hemodynamics BUN/creatinine ratio: Typically \>20 Urine sodium: \<20 mEq/L Fractional excretion of sodium: \<1% Urine osmolality: \>500 mOsm/kg Urine specific gravity: \>1.020 Microscopy: Bland

Answer 14

**GI losses; Hemorrage** **Hx:** volume loss (eg, vomiting, diarrhea), the presence of orthostatic symptoms, decreased urine volume, or urine that appears more concentrated. **Px:** Signs of hypovolemia, such as tachycardia, a postural pulse rate increase of \>30/min, dry axillae, flat neck veins, and dry oral mucosa. Elevated jugular venous pressure, an S3 gallop, and pulmonary crackles on lung examination. **Dx:** Low urine flow is associated with reabsorption of urea along the nephron, and patients with prerenal failure frequently have a **BUN–creatinine ratio \>20:1**, urine sodium \<10 mEq/L (10 mmol/L) or FENa \> 1% suggests ATN. FENa ≤ 1% suggests prerenal azotemia (when oliguria is present) and AGN; bland urine sediment, and urine specific gravity \>1.018 (high urine specific gravity) may reflect an appropriate response to water loss or dehydration or may indicate a pathologic state of fluid retention. Prerenal disease is associated with a normal urinalysis. **Spot urine sodium:** Volume depletion leads to activation of hormonal systems aimed at conserving salt and water and is characterized by high urine osmolality and low urine sodium concentration (\<10 meq/L), with a fractional excretion of sodium of \<1%. **Tx:** Treat volume depletion with normal saline; if severe anemia is present, transfuse packed red blood cells. If the serum albumin level is extremely low or if a patient has portal hypertension and ascites, albumin may be beneficial as a volume expander in select patients.

Answer 15

Heart Failure, Renal artery stenosis **Hx:** Heart failure, liver disease, and the nephrotic syndrome, which are other conditions associated with decreased effective circulating volume. **Px:** Spider telangiectasia, jaundice, and ascites support a diagnosis of liver disease. **Dx:** CT angiography (renal artery stenosis, or renal vascular lesion). High urine specific gravity may reflect an appropriate response to water loss or dehydration or may indicate a pathologic state of fluid retention (eg, heart failure). **Tx:** Treat volume depletion with normal saline; if severe anemia is present, transfuse packed red blood cells. If the serum albumin level is extremely low or if a patient has portal hypertension and ascites, albumin may be beneficial as a volume expander in select patients.

Answer 16

NSAIDS, Calcineurin Inhibitors, ACE, ARBs, Sepsis, Hypercalcemia, Cirrhosis/hepatorenal syndrome, abdominal compartment syndrome **Hx:** Medications that can alter effective circulating volume, such as NSAIDs, ACE inhibitors, ARBs, diuretics, and vasodilators. **Px:** Increases in intraabdominal pressure from massive ascites or edematous bowel can lead to abdominal compartment syndrome, which limits both renal arterial perfusion and renal venous outflow. A distended, tense abdomen supports a diagnosis of abdominal compartment syndrome, which can be confirmed by placing a pressure transducer into the bladder. **Tx:** Treat volume depletion with normal saline; if severe anemia is present, transfuse packed red blood cells. If the serum albumin level is extremely low or if a patient has portal hypertension and ascites, albumin may be beneficial as a volume expander in select patients

Answer 17

Atheroembolic and thromboembolic disease Intrarenal vascular disease Acute glomerulonephritis Acute tubular necrosis Acute interstitial nephritis Intrarenal tubular obstruction Renal vein obstruction Hepatorenal Syndrome vasculature (vasculitis, microangiopathic hemolytic anemia).

Answer 18

**Hx:** Recent invasive vascular procedures that may result in atheroembolic kidney disease (eg, angiography, aortic stenting, aneurysm repair). Fever, joint pain, fatigue, rashes, and jaundice. Atrial fibrillation or recent myocardial infarction may be associated with thromboembolic disease. **Px:** Clues to vasculitis include palpable purpura, petechiae, joint swelling, and skin rashes. The presence of a fine, reticular (netlike) red to purple rash (livedo reticularis) or blue toes (“blue toe syndrome”) suggests atheroembolic disease. **Dx:** Atheroembolic disease characterized by urinary eosinophils.

Answer 19

Renal infarctions occur from a variety of etiologies (eg, atrial fibrillation, renal artery trauma, hypercoagulability). Renal infarctions typically manifest with acute flank pain, nausea, and vomiting; fever may also occur. Urinalysis classically demonstrates hematuria and proteinuria without casts. A rise in serum creatinine may occur but is more common with bilateral or very large, unilateral infarction. Other characteristic laboratory abnormalities include an elevated lactate dehydrogenase level, leukocytosis, and elevation in C-reactive protein. A contrast-enhanced CT scan or MRI demonstrating a **wedge-shaped cortical infarction** is diagnostic.

Answer 20

**Hx:** Vasculitis (i.e., PAN), malignant hypertension, or TTP-HUS. **Dx:** Characterized by hematuria with erythrocyte or granular casts, mild proteinuria, and leukocytes. Look for schistocytes and decreased platelets on peripheral smear, which imply a thrombotic microangiopathy, such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. If present, confirm hemolysis with serum lactate dehydrogenase and haptoglobin concentrations. **Tx:** Begin renal replacement therapy (dialysis) in all patients with uremic signs or symptoms (nausea, vomiting, altered mental status, seizures, pericarditis) as well as patients who have hyperkalemia, metabolic acidosis, or volume overload that cannot be easily managed with medication.

Answer 21

Primary glomerular damage leads to decreased glomerular filtration rate with eventual development of significant volume overload (eg, pulmonary edema, distended neck veins, **anasarca**). Abnormal urinary sediment (red blood cells, red blood cell casts) and variable degrees of proteinuria are present on urinalysis. Serum creatinine can also be elevated. The increased volume also leads to hypertension. Significant proteinuria (3+) eventually leads to hypoalbuminemia, which further contributes to the edema. Glomerular diseases present with proteinuria and sometimes an active urinary sediment (dysmorphic red cells, white blood cells, and red cell casts). **⚪ Nephrotic syndrome** is characterized by heavy proteinuria (**\>2+ protein** by dipstick, urine **P:C \>3.5 g/d**)[3+ (300 mg/dL) or 4+ (1000 mg/dL)] and a relatively bland urine sediment, which may contain hyaline or hyaline-granular casts, lipids, and none to moderate numbers of erythrocytes. Other proteins (eg, Bence-Jones proteins, myoglobin) can cause severe proteinuria, but, since they do not cause albumin loss in the urine, they do not cause the nephrotic syndrome. **C**haracterized by high-grade **proteinuria** ( \>3.5 g/24 h), **hypoalbuminemia, hyperlipidemia, and edema**. Usually “Bland” urine sediment; Hyaline casts; Lipiduria; oval fat bodies; Hypercoagulability. Hypoalbuminemia can cause significant peripheral edema but usually does not cause pulmonary edema. Alveolar capillaries have a higher permeability to albumin at baseline (reducing oncotic pressure difference) and greater lymphatic flow than skeletal muscle, protecting the lungs from edema. **Membranous Nephropathy (common)** cause of idiopathic nephrotic syndrome in adults. 🍭 **Diabetic nephropathy** (common in adults) **Dx:** Biopsy Noninflammatory **📏 Minimal change disease (common in kids)** While it often presents as primary renal disease, it is also seen in association with other conditions like NSAID use with concomitant interstitial nephritis and Hodgkin disease. Clinically, patients present as described with sudden onset of edema, nephrotic syndrome, and amorphous urinary sediment on the urinalysis. **Tx:** Trial of 🌑 corticosteroids precedes renal biopsy. [cyclophosphamide, chlorambucil, or mycophenolate mofetil.] **Focal segmental glomerulosclerosis (FSGS):** **Hx:** More common in intravenous drug users with HIV. **Tx:** Fairly responsive to corticosteroid and cytotoxic therapy. Amyloid **🔴 Nephritic syndrome** is characterized by varying degrees of proteinuria and an active urine sediment, which may contain granular casts, moderate to large numbers of dysmorphic erythrocytes, and erythrocyte casts. **C**haracterized by **hematuria**, variable proteinuria, and hypertension, often with other systemic manifestations. Common causes include **postinfectious glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis.** Proteinuria (UPCR): Variable; may be \<3.5 g/g **Urine sediment:** Dysmorphic RBCs, RBC casts, Granular casts **🥧 Postinfectious glomerulonephritis:** Acute glomerulonephritis usually occurs a week or two after the sore throat (ie, to give enough time for vigorous antibody production against the streptococcal antigens). **Poststreptococcal** GN is now a rare condition in the adult population of developed nations. Inflammatory Diffuse proliferative glomerulonephritis **Membranoproliferative glomerulonephritis (MPGN):** Depressed C3 is caused by an autoantibody that directly activates the third component of complement. A progressive clinical course and erratic response to therapy are typical. **IgA nephropathy (common) (Berger):** Berger disease is associated with IgA deposits in the mesangium. Patients with IgA nephropathy often have an exacerbation of their hematuria with intercurrent **respiratory illnesses**. **Anti-glomerular basement membrane (anti-GBM) disease** causes a nephritic picture with hematuria and rapidly progressive renal insufficiency. Light microscopy often reveals crescent formation, and immunofluorescence shows linear **IgG** staining of the GBM. **❗ Rapidly progressive glomerulonephritis (RPGN)** is a clinical syndrome characterized by a swift loss of kidney function, hematuria, proteinuria, and glomerular **crescent formation**. The syndrome may be caused by many primary or secondary glomerular diseases, including those previously listed. **Px:** Some patients with the nephritic syndrome have dermal inflammation that manifests as palpable purpura, necrosis, ulcers, or nodules. Renal–dermal syndromes (SLE, Henoch-Schönlein purpura, antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and cryoglobulinemia). **Dx:** **Dysmorphic erythrocytes** suggest acute glomerulonephritis. Glomerular hematuria also is characterized by the presence of dysmorphic erythrocytes (especially erythrocytes with blebs, termed acanthocytes). Assays for anti–glomerular basement membrane antibody, **ANCA**, and markers for immune complex diseases (eg, antinuclear antibodies (ANA), anti–double-stranded DNA antibodies, cryoglobulins, antibodies to hepatitis B or C virus, complement concentrations [MPGN]) may further refine the diagnosis; low complement concentrations suggest lupus nephritis, postinfectious and membranoproliferative glomerulonephritis, and mixed cryoglobulinemia (Hep C). **Tx:** Begin **renal replacement therapy (dialysis)** in all patients with uremic signs or symptoms (nausea, vomiting, altered mental status, seizures, pericarditis) as well as patients who have hyperkalemia, metabolic acidosis, or volume overload that cannot be easily managed with medication. **Cx:** SLE commonly affects the kidneys and may cause nephritic or nephrotic syndrome. A kidney biopsy often is needed to make a specific diagnosis and to guide therapy. To prevent irreversible kidney damage, early treatment with a **high-dose glucocorticoid** is indicated for patients whose condition raises strong suspicion for lupus nephritis

Answer 22

Clinical features * Can be asymptomatic * If symptomatic: * Gross hematuria (tea- or **cola-colored urine**) * **Edema** (periorbital, generalized) * Hypertension Laboratory findings * Urinalysis: + protein, + blood, ± red blood cell casts * Serum: * ↓ **C3** & possible ↓ C4 * ↑ Serum creatinine * ↑ Anti-DNase B & ↑ AHase (antihyaluronidase) * ↑ ASO & ↑ anti-NAD (from preceding pharyngitis) Acute poststreptococcal glomerulonephritis (APSGN) is an immune-mediated disease that occurs approximately 1-4 weeks after group A streptococcal (GAS) **pharyngitis** **OR impetigo**. Pathogenesis involves the postinfectious formation of nephritogenic-specific streptococcal antigens and antibody complexes. These immune complexes are then deposited within the glomerular basement membraneand mesangium, causing activation of the complement system and accumulation of complement component C3 in the glomerular deposits. Therefore, laboratory findings include decreased C3 levels with possible elevation in serum creatinine. Symptomatic patients with APSGN may develop hematuria, edema, and hypertension several weeks after GAS skin or throat infection. Urinalysis typically reveals red blood cells with or without protein and red blood cell casts. Most patients recover with supportive care (eg, blood pressure management).

Answer 23

Goodpasture syndrome is a progressive glomerulonephritis accompanied by pulmonary disease (ie, alveolar hemorrhage); biopsy reveals **linear IgG deposition in the GBM**. * Pulmonary symptoms

Answer 24

Mesangial IgA deposition IgA nephropathy typically presents with hematuria 1–2 days after the onset of an **upper respiratory tract infection**, and serum complement levels are normal. Patients have concomitant gross hematuria and **upper respiratory symptoms (eg, rhinorrhea, sore throat)**.

Answer 25

Pathogenesis * Inherited (most commonly X-linked) * **Mutation of type IV collagen** Clinical findings * Nephropathy * **Hematuria** (microscopic or gross) * Progressive **renal insufficiency** * ± Proteinuria * ± Hypertension * **Bilateral sensorineural hearing loss** * Anterior lenticonus (lens protrusion) Diagnosis * Molecular genetic testing * Renal biopsy: **longitudinal splitting of GBM** Alport syndrome is an inherited, progressive disease affecting type IV collagen in the glomerular basement membrane (GBM), cochlea, and eye. The typical patient is a **boy age \<10** with gross **hematuria** after a recent upper respiratory infection. Asymptomatic, microscopic hematuria often precedes gross hematuria, which recurs periodically and may be accompanied by hypertension, proteinuria, and chronic renal failure. Mutated collagen in the cochlea and eye results in **sensorineural hearing loss** and **anterior lenticonus** (conical lens protrusion), respectively. Most cases are X-linked, and patients often have a family history of chronic kidney disease. History may also reveal hereditary hearing loss. Laboratory results may demonstrate elevated serum creatinine and **normal complement levels**. Diagnosis is confirmed by renal biopsy, with electron microscopy showing a **lamellated GBM due to longitudinal splitting of the lamina densa.** Genetic testing can also screen patients with a family history of Alport syndrome or confirm the diagnosis in a symptomatic patient. Management is **supportive** and may include transplant in patients with end-stage renal disease.

Answer 26

Dense intramembranous deposits that stain for C3 is a characteristic microscopic finding for membranoproliferative glomerulonephritis, type 2 (also called **dense deposit disease)**. This condition is unique among glomerulopathies, because it is caused by **IgG antibodies (termed C3 nephritic factor) directed against C3 convertase** of the alternative complement pathway. These antibodies reacting with C3 convertase lead to persistent complement activation and kidney damage.

Answer 27

Common etiologies * **IV Acyclovir** * Sulfonamides * Methotrexate * Ethylene glycol * Protease inhibitors * Uric acid (tumor lysis syndrome) Clinical presentation * Usually asymptomatic * AKI \<7 days of starting drug * UA: Hematuria, pyuria & crystals * Increased risk with volume depletion, CKD Management * Discontinuation of drug * Volume repletion * Loop diuretic The kidney rapidly excretes acyclovir into the urine, but the drug has low urine solubility. As a result, it easily **precipitates in renal tubules, causing intratubular _obstruction_** and direct renal tubular toxicity. Crystal-induced AKI is more common with large intravenous doses of acyclovir and occurs only rarely with oral acyclovir. Intravenous acyclovir less commonly causes AKI through acute tubular necrosis or acute interstitial nephritis. Risk factors for crystal-induced AKI include underlying volume depletion or chronic kidney disease. Most patients develop AKI within 24-48 hours after drug exposure and can be asymptomatic or develop nonspecific symptoms (eg, nausea, flank/abdominal pain). Urinalysis can show hematuria, pyuria, and crystals visualized with a polarizing microscope. Treatment involves discontinuing the drug and providing volume repletion. Administration of intravenous fluids for adequate hydration while giving the drug can also prevent AKI.

Answer 28

FSGS is a common cause of NS in adults and adolescents. **HIV** is the most commonly associated infection.

Answer 29

Universal vaccination has dramatically reduced rates of **hepatitis B virus-associated membranous nephropathy (HBVMN)**, and unvaccinated children who have immigrated from endemic areas should be screened for hepatitis B. Positive for **HBsAg** and **HBeAg** and negative for anti-HBsAg antibody are findings consistent with active hepatitis B infection. The pathogenesis of HBVMN may involve deposition of HBeAg or its corresponding antibody in the glomeruli.

Answer 30

Acute tubular necrosis * BUN/creatinine ratio: Typically normal (~10-15) * Urine sodium: \>40 mEq/L * Fractional excretion of sodium: \>2% * Urine osmolality: ~300 mOsm/kg * Urine specific gravity: \<1.020 * Microscopy: Muddy brown casts Common causes include ischemia (eg, shock), drugs (eg, radiocontrast), and other nephrotoxins. **Tubular damage limits reabsorptive capacity, resulting in a high urine sodium** (typically \>40 mEq/L) and fractional excretion of sodium (\>2%). Creatinine, which varies inversely with glomerular filtration, is elevated, but the BUN/creatinine ratio is normal at ~10-15:1, in contrast to prerenal AKI (where passive urea reabsorption leads to an elevated BUN/creatinine ratio). Renal injury usually causes **hypocalcemia** due to reduced phosphorus clearance leading to calcium phosphate salt formation. **Hx:** **Radiocontrast agents** [contrast-induced nephropathy (CIN)], drugs (**aminoglycosides**, **amphotericin B, cisplatin**), and episodes of **hypotension**. Patients who are using cocaine or who are found comatose from drug ingestion may develop **rhabdomyolysis**. Patients with **lymphoma** or **leukemia** who develop tumor lysis after chemotherapy **Initiation phase** of ATN corresponds with the original ischemic or toxic insult and lasts about **36 hours**. During this phase, there is only a slight decrease in urine output as renal tubular cell damage begins. **Maintenance phase**, tubular damage is fully established and patients commonly have **oliguria**, **fluid overload,** and electrolyte abnormalities (🍌**hyperkalemia**, **metabolic acidosis**). This second phase of ATN usually lasts **1-2 weeks**, during which the glomerular filtration rate (GFR) stabilizes at a level well below normal with a rise in serum creatinine. **Recovery phase** of ATN is characterized by re-epithelization of tubules. It manifests with vigorous **diuresis** (sometimes \> 3 L/day), but because the renal tubules cannot yet function fully, electrolyte balance is still altered. A high volume, hypotonic urine may lead to decreased serum concentrations of K, Mg, PO4, and Ca. **Hypokalemia** is one of the most serious complications of the recovery phase of ATN. The majority of patients eventually experience complete restoration of renal function. **Dx:** **Muddy brown cast**s, tubular epithelial cell casts, high urine sodium concentration (\>20 mEq/L), and FENa \>1%. Increased CPK, myoglobin, a renal tubular toxin. Severe hyperphosphatemia suggests acute rhabdomyolysis or TLS. Serum uric acid \>15 mg/dL suggests rhabdomyolysis or TLS. In patients with multiple myeloma, immunoglobulin light chains can precipitate within the renal tubules. **Tx:** In patients who require contrast studies, use of low osmolar contrast agents and **hydration** (intravenous 0.9% saline)[with bicarbonate]s to promote urine flow and avoid volume contraction has been shown to decrease the risk for CIN. **Cx: MM-induced 🥛hypercalcemia** is due to osteoclast activating factors and can cause AKI (vasoconstriction, tubular calcium deposition). Light chains reabsorbed by the proximal tubules are directly toxic. Intratubular light chain casts form if the resorptive capacity is overwhelmed, worsening tubular damage. Glassy light chain casts are often present; however, the urinalysis may be bland if cast formation has not yet occurred. Urine dipstick typically demonstrates mild proteinuria (only detects albumin); however, a quantitative 24-hour protein assay will demonstrate elevated protein excretion (Bence-Jones proteinuria)

Answer 31

**Hx:** Use of combined analgesics (e.g., 🧯 **aspirin** and **naproxen**). It is generally seen after cumulative ingestion of 2-3 kg (4.4-6.6 lbs) of the index drug. Allergic reaction to antibiotics, particularly **beta-lactams** and **sulfa** derivatives. Pyuria and **eosinophiluria** are usually present. Patients can also develop painless and prominent hematuria due to papillary ischemia from analgesic-induced vasoconstriction of medullary blood vessels (vasa recta). Significant **papillary necrosis** and sloughing may cause **renal colic**. **Dx:** Polyuria and **sterile pyuria (WBC casts** may also be seen) are early manifestations; Urine eosinophils, and nephritic-range proteinuria (in the case of drug- or **NSAID**-induced minimal change disease). **Papillary necrosis** and chronic tubulointerstitial nephritis are the most common pathologies seen. **Px:** 🤡 Rash **Tx:** Discontinue any unnecessary or suspicious medications. Begin renal replacement therapy (dialysis) in all patients with uremic signs or symptoms (nausea, vomiting, altered mental status, seizures, pericarditis) as well as patients who have hyperkalemia, metabolic acidosis, or volume overload that cannot be easily managed with medication.

Answer 32

**DDx:** Consider rhabdomyolysis, TLS, or multiple myeloma. **Dx:** Thrombotic microangiopatihies - Characterized by coarse tubular casts (including muddy brown granular casts), crystalluria, and urinary light chains. Serum and urine protein electrophoresis can identify the types and relative quantities of urine proteins. Obtain in the setting of AKI, anemia, or hypercalcemia, especially in patients age \>60 y or when serum anion gap is low to diagnose multiple myeloma. In proteinuria of glomerular origin, albumin constitutes 60% to 90% of the total urine protein. In tubular proteinuria, low-molecular-weight proteins typically predominate, and this may indicate either impaired tubular protein reabsorption or overproduction and filtration of low-molecular-weight proteins (eg, multiple myeloma).

Answer 33

Development of kidney failure in patients with portal hypertension and normal renal tubular function. Intense renal vasoconstriction leads to a syndrome of acute kidney dysfunction characterized by increased renal sodium avidity, a relatively normal urine sediment, and oliguria in some patients. **Hx:** Spontaneous bacterial peritonitis, vigorous diuretic therapy, paracentesis without volume expansion, and gastrointestinal bleeding also may precipitate hepatorenal syndrome. **Tx:** In addition to albumin administration, measures to increase mean arterial pressure, including norepinephrine or midodrine plus octreotide, may improve renal function in these patients. The most effective treatment is **liver transplantation.**

Answer 34

Urinary tract obstruction

Answer 35

Urinary tract obstruction **DDx:** Consider nephrolithiasis, ureteral stones, malignancy, granuloma, pregnancy, hematoma, radiation, neurogenic bladder, benign prostatic hypertrophy, or retroperitoneal fibrosis. Calcium oxylate crystals (ethylene glycol poisoning), Drugs (indinavir, methotrexate) **Hx:** **Flank pain** (renal capsular distension) and poor urine output (mechanical obstruction to urine outflow). Intermittent episodes of high-volume urination can occur when the obstruction is overcomeby a large volume of retained urine (**post-obstructive diuresis**). Excessive diuresis may lead to potassium wasting and dehydration, both of which can cause weakness. Pelvic tumors or irradiation, congenital urinary tract abnormalities, kidney stones, genitourinary infections, various procedures or surgeries. Most common in **elderly men with prostatic hypertrophy**, children with a history of congenital urinary tract abnormalities, and patients with a history of pelvic malignancy. **Hematuria** (gross or microscopic) is present in most patients with symptomatic stones. **Px:** Prostatic enlargement, suprapubic fullness, or an abdominal or pelvic mass suggests urinary obstruction. **Dx:** Urine sediment is **bland** (**No leukocytes**, erythrocytes, or erythrocyte casts). **🥇Noncontrast abdominal helical CT:** The most frequently used method for diagnosing kidney stones. This study identifies urinary tract obstruction with hydronephrosis, detects stones as small as 1 mm in diameter, and helps evaluate other potential causes of abdominal pain and hematuria. **_Renal Ultrasound_:** Because of the lack of definitive symptoms on presentation, kidney imaging, typically ultrasonography, should be considered for all ❗ **patients with AKI,** particularly when risk factors for obstruction are present. Radionuclide kidney clearance scanning (**GFR scanning**): GFR estimation, urinary tract obstruction, kidney infarction **Tx:** 90% of stones **\< ✋🏽5 mm** pass **spontaneously**. * **Increased oral fluid intake** (\>2-2.5 L/day) is recommended to ensure adequate flow of dilute urine. * Strain urine for stone composition analysis (not by itself an indication for hospitalization). **Medical expulsive therapy:** using agents such as a **α-blocker** **(such as tamsulosin)** or a **Calcium channel blocker (such as nifedipine)** is common practice for patients with stones less than 10 mm and well-controlled symptoms. Stones that are more than 10 mm are unlikely to pass without intervention. **Evidence of urinary obstruction:** Place a **urinary catheter** to relieve bladder outlet obstruction; if the obstruction is above the bladder, either retrograde or antegrade a **nephrostomy tube** will be necessary. **Cx: ❗Urosepsis** fever, tachycardia, anuria; acute kidney injury; or refractory pain require urgent urologic consultation for possible **percutaneous nephrostomy** or **ureteral stent insertion**. In addition, those with large stones that are unlikely to pass spontaneously (≥10 mm), or those whose stones do not pass within 4-5 weeks, also warrant urologic evaluation (eg, in the outpatient setting) to consider more aggressive interventions (eg, lithotripsy, ureteroscopic intervention). **Utersocopy:** Stones located in the distal ureter are usually accessible by directed therapy guided by ureteroscopy. During ureteroscopy, **“intracorporeal” lithotripsy** can be performed using lasers, ultrasonography, or other techniques. **Rx:** **Calcium stones:** Dietary oxalate forms complexes with calcium in the intestinal lumen and is eliminated in the feces. If intestinal concentrations of calcium are low (eg, **low-calcium diet**, fat malabsorption), **absorption of free oxalate is increased**; the increased oxalate load is filtered by the kidneys and can cause **calcium oxalate stones.** **_Hydrochlorothiazide (HCTZ)_** promotes proximal tubular calcium reabsorption; May inhibit bone resorption. Use in patients with hypercalciuria. Sodium restriction maximizes effectiveness. Most patients require concomitant treatment with **potassium citrate** because of hypokalemia or decreased citrate excretion. **🍊Potassium citrate** forms soluble complexes with calcium. Citrate increases urine pH after metabolism to bicarbonate by the liver, which dissolves uric acid crystals and makes cystine soluble. May cause hyperkalemia, heartburn, and nausea. **Tx: Increased sodium intake enhances calcium excretion (hypercalciuria),** and low sodium intake promotes sodium and calcium reabsorption through its effect on the medullary concentration gradient. Reabsorption of sodium and calcium is coupled via complex mechanisms involving the calcium-sensing receptor in the thick ascending limb. If these patients continue to develop renal stones, their urine sodium levels may be checked to evaluate adherence to a **sodium-restricted diet.** **Uric acid stones:** Risk factors * Increased uric acid excretion: **Gout, myeloproliferative disorders** * Increased urine concentration: **Hot, arid climates; dehydration** * Low urine pH: Chronic diarrhea (GI bicarbonate loss), metabolic syndrome/diabetes mellitus Risk factors for uric acid stones include **gout**, obesity, diabetes mellitus/metabolic syndrome, chronic diarrhea (due to intestinal bicarbonate loss and compensatory acidification of the urine), and increased systemic uric acid production (eg, **myeloproliferative disorders, TLS,** hemolytic anemia). Pathophysiology * **Acidic urine** favors formation of uric acid (insoluble) over urate (soluble) * Supersaturation of urine with uric acid precipitates crystal formation Clinical characteristics * **Radiolucent** stones (not visible on x-ray) * Uric acid crystals on urine microscopy * **Urine pH usually \<5.5** Patients often report passage of small crystals ("sand") in the urine, but this is not a specific symptom. Treatment **Dx:** 💎Diamond shaped **Tx:** Alkalinization of the urine with **potassium citrate** **🍊**or **potassium bicarbonate** effectively dissolves the stones, and interventional efforts to clear the stones (eg, ureteroscopic extraction) are usually unnecessary. **Allopurinol** is a Xanthine oxidase inhibitor that reduces urinary uric acid excretion. Adjunct to potassium citrate for treating uric acid stones because urinary alkalinization appears to be more important. **Hyperoxaluria** is caused by increased gastrointestinal absorption of oxalate, whereas secondary hyperoxaluria is usually caused by increased intake of oxalate-rich foods such as rhubarb, peanuts, spinach, beets, and chocolate. Therefore, dietary restriction of oxalate-rich foods would decrease risk of recurrent calcium oxalate stones. Furthermore, oxalate binds to urine calcium as it is eliminated by the kidneys, which results in calcium oxalate stone formation. With a high-calcium diet, the calcium binds to oxalate in the gut and prevents its absorption and ultimate filtration at the level of the kidneys. **["Magnesium-ammonium-Phosphate (MAP)"] (second most common) _Struvite stones_** / **Staghorn calculi** are caused by **urease-producing organisms (eg, Proteus, Klebsiella)**. Hydrolysis of urea yields **ammonia**, which alkalinizes the urine and facilitates the precipitation of struvite crystals. **Coffin Lid** ⚰ appearance Because of the large quantities of urea excreted in urine, these stones can grow very rapidly and fill the renal calyces **(🦌staghorn calculi)**. The large size of these calculi prevents them from passing into the ureter, so patients typically have symptoms related to associated recurrent infections rather than acute renal colic. If left untreated, the stones can seed further infections, and chronic infection and obstruction can lead to loss of kidney function. Eradication of staghorn calculi is difficult; antibiotics alone do not eliminate the source of the infection because bacteria grow within the stone matrix. **Stone removal (eg, percutaneous nephrolithotomy)** is typically recommended, and **nephrectomy** may be required for patients with a chronically infected, nonfunctioning kidney. Cx:

Answer 36

RVTs most commonly occur in the setting of nephrotic syndrome (due to urinary loss of anticoagulant proteins and alteration of hemostatic balance) but can also occur with acquired hypercoagulability associated with malignancy or trauma. Laboratory analysis typically demonstrates **hematuria** (with an otherwise bland urinalysis) and **elevated lactate dehydrogenase (LDH)** levels (possibly related to necrosis in the setting of thrombosis); acute kidney injury (AKI) may occur but is more typical in the setting of bilateral RVTs. Renal ultrasound with Doppler and abdominal CT scan have a low sensitivity and may demonstrate only an enlarged kidney, although a Doppler ultrasound may show a reversal of diastolic flow. The diagnosis is confirmed by **CT or MR angiography or renal venography**. Management depends on the presence of AKI, which, if present, requires urgent clot removal (eg, **thrombolysis, thrombectomy**); otherwise, **anticoagulation** alone is appropriate.

Answer 37

**Subacute kidney injury** defines a presentation that develops more slowly than AKI but generally results in worsening creatinine in less than three months. **Chronic kidney disease (CKD)** is defined by an elevated creatinine, or other evidence of kidney damage, that is relatively stable for **greater than three months.** **Dx:** **(CKD-EPI) equation** will best estimate this patient's glomerular filtration rate (GFR) **Creatinine clearance:** Because creatinine is secreted by renal tubules **overestimates GFR.** The **Cockcroft-Gault equation** was developed to predict creatinine clearance (CCr [mL/min]) using the serum creatinine, age, and weight, adjusted for gender: **CCr = (140 − age [y]) × weight [kg] / (SCr × 72) × 0.85 [if female]** **Serum creatinine:** Reduction of muscle mass, as occurs in amputees and patients with malnutrition or muscle wasting, can result in a lower serum creatinine level without a corresponding change in GFR. Younger persons, men, and black persons often have higher muscle mass and higher serum creatinine levels at a given level of GFR compared with older persons with decreased muscle mass. Patients with advanced liver disease produce lower concentrations of precursors of serum creatinine and often have muscle wasting, with a correspondingly lower serum creatinine level at a particular level of GFR. Finally, serum creatinine concentration overestimates kidney function in elderly persons, especially women. Spot urine albumin–creatinine ratio **Urine protein-creatinine ratio:** Normal ratio is **\<30** mg/g; **30–300 mg/g** is defined as moderately increased albuminuria (**microalbuminuria**); a value of **\>150 mg/g is abnormal;** a ratio **\>3.5 g/g is classified as nephrotic-range proteinuria.** First morning urine specimens are preferred, but random specimens are acceptable. Patients with two or more positive quantitative test results 1–2 wk apart are diagnosed with persistent proteinuria and must undergo further evaluation and management. **Urinalysis:** Hematuria, proteinuria, casts, and leukocytes are some of the abnormalities seen in CKD. **24-hour urine collection:** The gold standard for measuring urine protein excretion. However, this test is cumbersome and unreliable if not collected correctly. **Electrolytes:** Hyponatremia, hyperkalemia, hyperphosphatemia, and metabolic acidosis (because of a fall in plasma bicarbonate) generally occur in later stages of kidney disease. **NAGMA (❗Acute HD indication)**. The kidneys handle the obligatory acid genesis that occurs as part of daily metabolism. Loss of functional nephrons results in the inability to properly buffer and excrete this acid load, resulting in **non–anion gap metabolic acidosis**. Metabolic acidosis is linked to malnutrition, accelerates renal osteodystrophy, suppresses albumin synthesis, and causes a premature decline in overall renal function. **Tx: 🧁**Use **oral sodium bicarbonate** to maintain serum carbon dioxide levels within the range of 22 to 26 meq/L (22–26 mmol/L). **Hypocalcemia (❗Acute HD indication)** can be seen in patients with CKD. Corrected total calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × (4 − Serum albumin [g/dL]). Circulating **parathyroid hormone (PTH)** levels **increase** with declining glomerular filtration rate (GFR), and the magnitude of PTH elevation usually correlates with severity of renal failure. **Secondary hyperparathyroidism** is the body's response to normalize serum calcium, phosphorus, and calcitriol in renal failure. Phosphate retention begins early with decreasing GFR and decreased renal phosphate excretion. Phosphate binds to circulating calcium and also interferes with renal production of **1,25 dihydroxyvitamin D (calcitriol)**. Decreased calcitriol leads to decreased intestinal calcium absorption. **Secondary hyperparathyroidism** may result in renal **osteodystrophy**, a mixture of multiple bone pathologies that includes osteitis fibrosa cystica, osteoporosis, osteomalacia, and adynamic bone disease. Secondary hyperparathyroidism also promotes vascular calcification, resulting in increased cardiovascular morbidity and mortality. **Dx: PTH level** is used to detect secondary hyperparathyroidism. Measure PTH in patients with stage 3 or higher CKD. **Tx:** Multiple medications aimed at lowering serum phosphorous, correcting vitamin D deficiency, and suppressing parathyroid hormone **Albumin:** Serum albumin level is a marker of nutritional status and an independent predictor of mortality in patients on dialysis. **Lipid profile:** Patients with CKD are at high risk for cardiovascular disease. **Complete blood count:** If the hemoglobin level is \<11 g/dL, check erythrocyte indices, iron stores, reticulocyte count, and stool for occult blood to evaluate the need for iron replacement or an ESA. **Renal ultrasonography:** often the first imaging choice to assess kidney disease because it is safe, not dependent upon kidney function, noninvasive, and relatively inexpensive. Because it does not require contrast dye, ultrasonography does not place patients at risk for contrast-induced nephropathy. Hydronephrosis may be found on ultrasonography in patients with urinary tract obstruction or vesicoureteral reflux. The presence of multiple discrete macroscopic cysts suggests **autosomal dominant (APCKD) or recessive polycystic kidney disease**. Increased cortical echogenicity and small kidney size are nonspecific indicators of CKD. **Autosomal dominant polycystic kidney disease (ADPKD):** Affected patients begin developing asymptomatic kidney cysts early in life. By age 30-40, the cystic changes have often progressed to the point that disease manifestations become clinically apparent. The most common early disease manifestations include flank pain, hematuria, and hypertension. **Hypertension** typically precedes any clinically detectable renal dysfunction and its progression correlates with the cystic structural derangement of the kidneys. It is believed the hypertension results from cyst expansion leading to localized renal ischemia and consequent **increased ☔renin release**. The increased activation of the renin-angiotensin-aldosterone system (RAAS) in effect leads to **secondary hyperaldosteronism**. Due to their inhibition of RAAS, ACE inhibitors (eg, lisinopril) are the drugs of choice for treating hypertension in ADPKD. Most patients progress to end-stage renal disease despite meticulous blood pressure control with ACE inhibitors or angiotensin receptor blockers. About **10%** of patients with adult PCK disease harbor **berry aneurysms** in the circle of Willis. APCKD patients also have an increased incidence of **abdominal and thoracic aneurysms** as well as **diverticulosis**. The abnormal gene, on chromosome 16 in 85% of patients, appears to encode a structural protein that helps keep the renal tubules open and unobstructed. This same protein provides strength to the walls of arteries and other epithelial structures (pancreatic ductules, bile ductules, colon). **Other imaging studies:** IVP, CT, MRI, or nuclear medicine scanning can be used for specific situations, such as stone disease, renal artery stenosis, or obstruction. **Tx:** Agents that interfere with the renin–angiotensin–aldosterone axis (RAAS), specifically 🃏**angiotensin-converting enzyme (ACE) inhibitors** and **angiotensin receptor blocking agents (ARBs**), are of particular clinical benefit in patients with CKD because of their **antihypertensive** and **antiproteinuric** effects. They have been shown to slow the progression of CKD are considered to be **renoprotective**. Target blood pressure of **less than 140/90** mm Hg for patients with kidney disease. CKD patients tend to have volume-sensitive hypertension; diuretic therapy, particularly **loop diuretics,** may be helpful in achieving appropriate hypertension targets. Ensure medications are dosed appropriately for the eGFR. If administration of **iodinated contrast** is essential, give **sodium bicarbonate** or **isotonic saline** intravenously and consider using N-acetylcysteine before and after the procedure, closely monitoring fluid and electrolyte status to decrease the risk of contrast-induced nephropathy. ✖ Gadolinium, a contrast agent used with magnetic resonance imaging scanning, is contraindicated in patients when eGFR is \<30 mL/min/1.73 m2 because of an increased risk of nephrogenic systemic fibrosis (NSF). NSF causes thickening and hardening of the skin over the extremities and trunk but may also involve other organ systems and is associated with a high mortality rate. There is no treatment for NSF. **Dietary Modification:** Limit sodium intake to \<2.4 g/day Limit potassium intake to \<2 g/day in patients with hyperkalemia Limit phosphorous intake to \<1 g/day when serum phosphorous is \>4.6 mg/dL (1.49 mmo/L) Limit protein intake to \<0.8 g/kg/day with stage 4 and 5 CKD Avoid laxatives containing magnesium or phosphorus, NSAIDs, and cyclooxygenase-2 (COX-2) inhibitors. **EPO** **Cx: 🍽 Platelet dysfunction:** The pathogenesis is multifactorial, but the major defect involves platelet-vessel wall and platelet-platelet interaction. Several uremic toxins have been implicated in the pathogenesis of platelet dysfunction seen in chronic renal failure (CRF), the chief among which is **guanidinosuccinic acid.** Activated partial thromboplastin (**aPTT**), prothrombin (**PT**), and thrombin times (**TT**) are generally **normal**. ❗**Bleeding time (BT)** is reflective of platelet function, and is usually prolonged. The **platelet count is normal,** but there is platelet dysfunction that causes bleeding. **Tx:** A number of agents such as **desmopressin (DDAVP),** cryoprecipitate, and conjugated estrogens have been used to correct the coagulopathy in uremic patients. DDAVP increases the release of factor VIII:von Willebrand factor multimers from endothelial storage sites. **Hypoproliferative anemia** due to inadequate production of erythropoietin by the kidneys. **Erythropoiesis-stimulating agents (ESAs),** such as recombinant **erythropoietin** and darbepoetin, stimulate red blood cell production and are the treatment of choice in CKD-related anemia. All patients with significant renal failure and a hemoglobin \<10 g/dL are candidates for ESAs after iron deficiency has been ruled out. Up to 30% of patients on erythropoietin therapy develop new or ♨ **worsening hypertension,** which typically occurs 2-8 weeks after treatment initiation. Hypertension is generally mild but can be severe, leading to end-organ damage (eg, encephalopathy, seizures). Large doses of erythropoietin or rapidly rising hemoglobin soon after administration increase the risk of hypertension. Therefore, patients started on erythropoietin require close blood pressure monitoring.

Answer 38

Diabetic kidney disease is the leading cause of CKD in the United States. **Px:** A thorough physical examination may identify important clinical consequences and comorbidities. Look for signs of prolonged hypertension or volume overload, such as a cardiac gallop or lower extremity edema. The funduscopic examination is important for the detection of hypertensive or diabetic retinopathy. Check for signs of uremia, such as asterixis, or a pericardial friction rub. **Dx:** To screen for nephropathy, it is recommended that all patients with T1DM and T2DM be tested for **urine albumin excretion** with a **spot urine** sample for **albumin-creatinine ratio.** Follows a characteristic course, manifesting first as moderately increased albuminuria (microalbuminuria) followed by clinical proteinuria, hypertension, and declining GFR. Diabetic nephropathy often is accompanied by diabetic retinopathy, particularly in type 1 diabetes. In patients with type 2 diabetes, the presence of retinopathy strongly suggests coexisting diabetic nephropathy. Even in the absence of retinopathy, diabetic nephropathy is likely, but an evaluation for other causes of proteinuria is reasonable. **Tx:** The presence of moderately increased albuminuria (approximately 30-300 mg/g) should prompt initiation of an **angiotensin-converting enzyme inhibitor (ACE) or angiotensin-receptor blocker (ARB) for its renoprotective effects.**

Answer 39

Patients generally have a bland or relatively normal urinalysis but may have proteinuria, a concentrating defect, pyuria, casts, or radiologic abnormalities. Analgesic nephropathy, lead nephropathy, chronic obstruction, and reflux nephropathy are examples.

Answer 40

Patients can have normal findings on urinalysis. Diagnosis usually is made by imaging techniques and family history. **Simple renal cysts** are common, particularly in older persons. Autosomal dominant polycystic disease types I and II are the most common forms. Features suggesting **malignancy** include irregular or multilocular structure with multiple septations, heterogeneous content, and contrast enhancement on CT or MRI. Incidentally discovered cysts with benign features require no additional follow-up evaluation or imaging, and the patient may be reassured.

Answer 41

CKD in a renal transplant recipient may be due to chronic rejection, drug toxicity, or recurrence of native kidney disease. A careful history and serum drug levels and often a kidney biopsy are required for diagnosis.

Answer 42

Protein excretion that increases during the day but decreases at night during recumbency. Protein excretion may vary based on time of collection and, in a small percentage of children and young adults, may also vary with changes in posture. **Dx: Split urine collection:** Established by comparing the urine protein excretion during the day with findings from a separate urine collection obtained during the night. **An 8-hour nighttime urine collection containing ≤50 mg of protein is required for diagnosis.** Typically, urine protein excretion in patients with orthostatic proteinuria is less than 1 g/24 h but can rarely be greater than 3 g/24 h. **Tx:** Orthostatic proteinuria is **benign** and has not been associated with long-term kidney disease. Other benign causes of transient or isolated proteinuria include **febrile illnesses** and **rigorous exercise**. Because transient or isolated proteinuria is typically benign, **further evaluation is NOT warranted.**

Answer 43

TTP is closely related to **hemolytic uremic syndrome (HUS**). Both cause MAHA and thrombocytopenia. Unlike TTP, HUS is typically associated with Escherichia coli O157:H7 and is primarily a disorder of the renal system; neurologic findings and fever are uncommon. **Thrombotic thrombocytopenic purpura (TTP)** is a life-threatening disorder of the microvasculature characterized by the formation of small vessel thrombi that consume platelets, shear red blood cells, and cause end organ damage. Classically, TTP is marked by the pentad of: Thrombocytopenia Microangiopathic hemolytic anemia (MAHA) Renal insufficiency Neurologic changes (eg, headache, confusion, coma, stroke) Fever TTP is caused by a deficiency of plasma protease ADAMTS13 (due to the formation of an autoantibody). In the absence of this protease, long chains of von Willebrand factor accumulate on the endothelial wall, trapping platelets and generating thrombi in areas of high shearing force (eg, arterioles, capillaries). The diagnosis is based largely on clinical and laboratory findings; evidence of MAHA on peripheral blood smear (schistocytes/red blood cell fragments) is an important diagnostic finding. Laboratory markers of coagulation (eg, prothrombin time [PT]) are normal in TTP (unlike in disseminated intravascular coagulation [DIC]). **Tx:** TTP is life threatening and must be treated emergently with **plasma exchange (PEX)**. PEX removes the patient's plasma and replaces it with donor plasma. This replenishes ADAMTS13 and removes the autoantibodies. Without emergent PEX, the mortality rate is approximately 90%.

Answer 44

HTN-related symptoms * Resistant HTN (uncontrolled despite 3-drug regimen) * Malignant HTN (with end-organ damage) * Onset of severe HTN (\>180/120 mm Hg) after age 55 * Severe HTN with diffuse atherosclerosis * Recurrent flash pulmonary edema with severe HTN Supportive evidence * Physical examination * Asymmetric renal size (\>1.5 cm) * Abdominal bruit * Laboratory results * Unexplained rise in serum creatinine (\>30%) after starting ACE inhibitors or ARBs * Imaging results * Unexplained atrophic kidney Renovascular hypertension is the most common correctable cause of secondary hypertension. Renal artery stenosis (RAS) is present in ~1% of patients with mild hypertension and in 25%-35% of patients with peripheral arterial disease. A **systolic-diastolic abdominal bruit** can be heard in ~40% of patients; this finding has very high specificity for RAS. The diagnosis is confirmed by noninvasive assessment with **renal duplex Doppler ultrasonography, CT angiography, or magnetic resonance angiography.**

Answer 45

**Large vessel vasculitis:** Giant cell arteritis (GCA)/polymyalgia rheumatica (PMR) Takayasu arteritis **Variable vessel vasculitis:** Behçet disease Cogan syndrome **Medium vessel vasculitis:** Polyarteritis nodosa Kawasaki disease **Small vessel vasculitis:** ANCA-associated vasculitis Granulomatosis with polyangiitis (Wegener) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) Microscopic polyangiitis **Immune-complex mediated vasculitis:** Anti-glomerular basement membrane (Goodpasture) disease IgA vasculitis (Henoch-Schönlein purpura) Cryoglobulinemic vasculitis Cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis) Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)

Answer 46

Granulomatosis with polyangiitis (Wegener) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) Microscopic polyangiitis

Answer 47

One of the most common **Hx:** Upper airway (otitis media, nasal ulcers, **saddle-👃🏽nose deformity,** **sinusitis**), lower respiratory tract (pulmonary infiltrates, cavitary lesions and nodules, hemoptysis). Constitutional symptoms include fever and weight loss. **🍇Pulmonary manifestations** include hemoptysis, cough, fleeting pulmonary infiltrates and bilateral, occasionally cavitary, pulmonary nodules. Limited GPA refers to the absence of renal involvement. **Renal:** Glomerulonephritis occurs in up to 80% of patients and is suggested by the findings of urine red blood cell casts, hematuria, and proteinuria. Up to 40% of patients ultimately develop chronic renal insufficiency **Dx:** Positive **c-ANCA** (cytoplasmic antineutrophil cytoplasmic antibody)[associated with antibodies against **proteinase 3**] (95% specific); dx is best established by lung or kidney biopsy. **Tx:** Combination of **glucocorticoids** and daily oral **cyclophosphamide**. Newer studies have shown efficacy of **rituximab** as an alternative to cyclophosphamide. **Plasma exchange** is used as adjunctive therapy with life-threatening disease. Although about 90% of patients achieve remission, up to 30% will relapse, requiring maintenance therapy with an immunosuppressant.

Answer 48

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing small vessel vasculitis with eosinophilic infiltration. **Hx: Asthma**, **allergic rhinitis and** **sinusitis**. **Dx:** Migratory pulmonary infiltrates, mononeuritis multiplex, necrotizing crescentic glomerulonephritis, palpable purpura, cardiomyopathy and gastrointestinal disease. Peripheral **eosinophilia** occurs in the prodromal stages. Also see crescentic glomerulonephritis, pulmonary infiltrates, mononeuritis multiplex. Only 40% of patients will be **p-ANCA**-positive; therefore, biopsy is frequently necessary. **Tx:** Limited cases respond well to **glucocorticoid therapy** alone, but addition of **cyclophosphamide** is needed with kidney involvement (azotemia, proteinuria \>1 g/day), cardiomyopathy, gastrointestinal disease, or neurologic manifestations.

Answer 49

**Microscopic polyangiitis (MPA)** is a necrotizing vasculitis **Hx:** Presents with rapidly progressive glomerulonephritis and pulmonary capillaritis. Similar to other ANCA-associated vasculitides, arthralgias, myalgias, and fever are common, along with palpable purpuric skin lesions. **🍇Pulmonary manifestations** range from mild dyspnea and anemia to massive **alveolar hemorrhage**, with patchy to diffuse infiltrates noted on chest radiography. Small-vessel (ie, glomerular) renal involvement **Dx:** Positive p-ANCA; dx best made by biopsy of skin, kidney, or lung lesions. **Tx:** Combined therapy with **glucocorticoids** and **cyclophosphamide** (or rituximab) is used to induce remission,

Answer 50

Polyarteritis nodosa Kawasaki disease

Answer 51

**Macroscopic polyarteritis nodosa** is a vasculitis of medium-sized blood vessels that causes renal artery aneurysms (severe hypertension), abdominal aneurysms (abdominal pain), and ischemic damage to skin and peripheral nerves. Patients are most commonly older males and anyone who is hepatitis B surface antigen-positive. **Hx:** Abdominal pain, new onset hypertension. **Dx:** Renal insufficiency, mononeuritis multiplex, cutaneous lesions, aneurysms on **angiography**.

Answer 52

**Hx:** Mostly in children, but also in HIV-infected adults; arthritis, acute coronary syndrome, aneurysms. **Px:** Conjunctivitis, strawberry tongue, erythematous rash, cervical lymphadenopathy,

Answer 53

Giant cell arteritis (GCA)/polymyalgia rheumatica (PMR)

Answer 54

Giant cell arteritis (GCA) is the most common systemic vasculitis in adults, frequently affecting adults aged \>50 years. **Polymyalgia rheumatica (PMR)** is a condition closely related to GCA that presents with hip and shoulder girdle stiffness and pain and elevated inflammatory markers. Although PMR may occur independently from GCA and is not considered a vasculitis, it shares many features with GCA, including the same inflammatory cytokines and associations with age, ethnicity, and HLA class II alleles. **Hx:** **GCA:** New-onset headache, with temporal artery tenderness or enlargement, jaw claudication, transient ischemic attacks or stroke and fever and malaise. scalp tenderness (GCA), and noncranial ischemia (such as arm claudication). **Visual symptoms**, including diplopia and loss of vision, may be irreversible and reflect occlusive arteritis of the posterior ciliary artery. **PMR:** Arthralgias and myalgias involving the proximal limb and axial musculature and tendinous attachments; fever is uncommon and malaise and weight loss are frequent. Pain is worse with movement, but muscle strength is preserved. **Dx: GCA and PMR:** Elevated **erythrocyte sedimentation rate,** seen in 96% of patients. A mild normocytic anemia may be seen. **GCA** requires a temporal artery biopsy, which has a sensitivity of 90% to 95%. In some patients a contralateral second biopsy is necessary. Inflammation with lymphocytic infiltration affects extracranial branches of the **aorta** in a segmental fashion, with the presence of multinucleated giant cells seen in half of biopsy specimens. **Tx: CGA:** Given the risk of irreversible vision loss in patients with GCA, prompt initiation of glucocorticoid therapy (1 mg/kg/day of prednisone) is warranted. Up to 4 weeks of steroid therapy is needed until symptoms and laboratory abnormalities resolve, followed by a slow taper. **PMR:** In the absence of symptoms or clinical findings consistent with GCA, a trial of glucocorticoid therapy is indicated, as PMR typically responds dramatically to this therapy. Patients with PMR tend to respond to 10 to 20 mg/day of prednisone, with rapid improvement in musculoskeletal pain and stiffness.

Answer 55

Systemic symptoms * Fever, fatigue, malaise, weight loss Localized symptoms * Headaches: Located in temporal areas * Jaw claudication: Most specific symptom of GCA * PMR * Arm claudication: Associated bruits in subclavian or axillary areas * Aortic wall thickening or aneurysms * CNS: TIAs/stroke, vertigo, hearing loss Visual symptoms * Amaurosis fugax: Transient vision field defect progressing to monocular blindness * **Anterior ischemic optic neuropathy (AION):** Most common ocular manifestation Anterior ischemic optic neuropathy is the most common ocular manifestation and is detected on funduscopy by the presence of a swollen and pale disc with blurred margins. Laboratory results * Normochromic anemia * Elevated ESR & CRP * **Temporal artery biopsy** Treatment * PMR only: Low-dose oral glucocorticoids (eg, prednisone 10-20 mg daily) * GCA: Intermediate- to high-dose oral glucocorticoids (eg, prednisone 40-60 mg daily) * GCA with vision loss: Pulse **high-dose IV glucocorticoids (eg, methylprednisolone 1,000 mg daily) for 3 days** followed by intermediate- to high-dose oral glucocorticoids Giant cell (temporal) arteritis produces inflammatory changes that affect branches of the external carotid, cervical internal carotid, posterior ciliary, extracranial vertebral, and intracranial arteries Occurs almost exclusively in patients aged **\>50 y.** Associated with tenderness of the scalp and temporal artery, **jaw claudication** (muscular pain due to inadequate blood flow), and **visual changes (red flag).** **Px:** May show tender, nodular, or pulseless temporal arteries. **Dx:** Laboratory findings include an increased erythrocyte sedimentation rate and evidence of vascular stenosis or occlusion on angiography or color duplex ultrasonography.

Answer 56

**Hx:** Young Asian women **Px:** Limb claudication, vascular bruits, aortic regurgitation, **Dx:** Vascular stenosis/occlusion/aneurysm on CT angiography

Answer 57

Behçet disease Cogan syndrome

Answer 58

Behçet's is a chronic multisystem disease commonly found in Asians and people of Mediterranean origin. Painful oral and genital ulcerations, uveitis, skin lesions, gastrointestinal or CNS involvement, and oligoarthritis. **Cutaneous manifestations** include erythema nodosum, pyoderma gangrenosum, Sweet syndrome-like lesions or pustules. Pathergy, the appearance of a pustule or papule 48 hours after the skin is pricked with a 20- to 21-gauge needle, is present in some patients. **Ocular involvement**, including uveitis and hypopyon (purulent exudate in the anterior chamber), is common. Treatment includes topical, intraocular or systemic glucocorticoid, and addition of immunosuppressive agents when severe. **Px:** Oral and genital ulcers, uveitis, pathergy, cutaneous lesions.

Answer 59

**Hx:** Aortic aneurysm or regurgitation, interstitial keratitis, sensorineural hearing loss

Answer 60

Anti-glomerular basement membrane (Goodpasture) disease IgA vasculitis (Henoch-Schönlein purpura) Cryoglobulinemic vasculitis Cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis) Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)

Answer 61

Anti-glomerular basement membrane (GBM) disease is a vasculitis caused by the deposition of autoantibodies reactive against type IV collagen found in basement membranes of the glomerular and pulmonary capillaries. **Hx:** Necrotizing glomerulonephritis, pulmonary hemorrhage, anemia, rash. **Dx:** Circulating anti-GBM antibodies in serum or detection of linear IgG deposits to GBM on kidney biopsy. **Tx:** Treatment involves plasma exchange and use of immunosuppressants.

Answer 62

Small-vessel vasculitis that most commonly occurs in children under 5; the syndrome may affect adults with greater severity. **Hx:** Presenting features include a purpuric rash predominantly affecting the distal lower extremities, arthritis, abdominal pain, and **hematuria**. **Antecedent** (occuring before) **upper respiratory infection**, abdominal pain, palpable purpura, arthralgias, glomerulonephritis. **Dx:** Biopsy shows a predominance of IgA deposition on immunofluorescence. **Normal platelet count** **Tx:** The disease can be self-limited when mild. When kidney involvement is present, aggressive immunosuppressive therapy including systemic glucocorticoids and **cyclophosphamide** is prescribed.

Answer 63

**Cryoglobulins** are immunoglobulins (IgG or IgM). When plasma is refrigerated at 4ºC for up to 72 hours, proteins may precipitate (cryoprecipitate). If refrigerated serum and plasma both form a precipitate, then the precipitated proteins are referred to as cryoglobulins (CGs). If, however, precipitation develops after refrigeration of plasma but does not occur in cold serum, the plasma precipitate is referred to as **cryofibrinogen** (CF). **Type I cryoglobulinemia** is associated with an isolated _monoclonal immunoglobulin_ most often due to an underlying B cell proliferative disorder such as Waldenström macroglobulinemia (IgM) or multiple myeloma (usually IgG). **Hx:** Hyperviscosity and thrombosis, but vasculitic symptoms can occur. **Type II cryoglobulinemia:** Is associated with both a _polyclonal IgG_ (which may either act as an antigen or be directed against an antigen) and a _monoclonal IgM_ rheumatoid factor directed against the IgG. About 90% are associated with hepatitis C infection. When type II cryoglobulinemia is not associated with hepatitis C, the disease is called essential mixed cryoglobulinemia. **Essential mixed cryoglobulinemia** can cause palpable purpura, nephritis, and neuropathy. Although 30% of patients with SLE have mildly elevated aminotransferase levels, these findings should lead to a search for hepatitis B or C in which this disorder frequently occurs. **Hx:** Triad of arthralgias, myalgias, and palpable purpura. Involvement of medium-sized vessels results in cutaneous ulcers, digital ischemia, and fixed livedo reticularis. Severe involvement leads to membranoproliferative glomerulonephritis and mononeuritis multiplex. **Tx:** Based on suppression of viral replication **Type III cryoglobulinemia** is characterized by the presence of _polyclonal IgG_ and _polyclonal IgM_. **Hx:** Frequently seen in patients with chronic infections, Sjögren syndrome, and systemic lupus erythematosus. Triad of arthralgias, myalgias, and palpable purpura. Involvement of medium-sized vessels results in cutaneous ulcers, digital ischemia, and fixed livedo reticularis. Severe involvement leads to membranoproliferative glomerulonephritis and mononeuritis multiplex. **Hx:** Arthralgias, myalgias, palpable purpura, common in hepatitis C infection. **Dx:** Membranoproliferative glomerulonephritis, mononeuritis multiplex, low C3 and C4 levels, presence of serum cryoglobulins, positive rheumatoid factor Laboratory abnormalities include high titers of **rheumatoid factor,** a **low serum complement C4** level **(out of proportion to the decreased C3 level)**, and the detection of **serum cryoglobulins.** **Tx:** Patients with severe involvement, such as mononeuritis and glomerulonephritis, require immunosuppressive therapy (glucocorticoids and rituximab) and plasma exchange to reduce circulating cryoglobulins.

Answer 64

This disease is defined by exposure to an offending agent, usually a medication or infectious agent. **Px:** Palpable purpura and/or maculopapular rash. No systemic involvement **Dx:** Biopsy shows neutrophilic infiltration around a blood vessel. **Tx:** Discontinuation of the medication, with systemic **glucocorticoids** used only when disease is extensive.

Answer 65

**Hx:** Painful urticarial lesions, glomerulonephritis, arthritis, COPD, uveitis. **Dx:** Positive ANA, positive C1q precipitin, low C3 and C4 levels

Answer 66

Etiology * Skeletal muscle lysis/necrosis due to: * Crush injury or prolonged immobilization * Intense muscle activity (eg, seizure, exertion) * Drug/medication toxicity (eg, statins) Clinical features * Muscle pain and weakness * Dark urine (myoglobinuria/pigmenturia) * + blood on urinalysis & no RBCs on microscopy * ↑ serum K and PO4, ↓ serum Ca, ↑ AST \> ALT * Acute kidney injury Diagnosis * Serum creatine kinase \>1,000 U/L * Consistent clinical features Management * Aggressive intravenous fluid resuscitation * Sodium bicarbonate in some cases A key component of rhabdomyolysis is the release of **myoglobin**, a **skeletal muscle O2-storage protein** that contains heme pigment, into the bloodstream. In the kidneys, myoglobin is degraded and releases heme into the renal tubules; this can cause renal tubular obstruction and tubular epithelial cell injury, resulting in **acute tubular necrosis** (eg, renal insufficiency). Potassium and phosphorus are also released from lysed muscle cells, causing hyperkalemia and hyperphosphatemia. Rhabdomyolysis most commonly develops after exposure to myotoxic drugs, infection, excessive exertion, or prolonged immobilization. Diagnosis should be considered in patients with a serum creatine kinase level above 5000 U/L who demonstrate blood on urine dipstick testing in the absence of significant hematuria. **Cx:** Complications of rhabdomyolysis include hypocalcemia, hyperphosphatemia, hyperuricemia, metabolic acidosis, acute muscle compartment syndrome, and limb ischemia. **Tx:** Treatment consists of aggressive **fluid resuscitation**; fluids should be adjusted to maintain an hourly urine output of at least 300 mL until the urine is negative for myoglobin. Acute kidney injury resulting from acute tubular necrosis occurs in approximately one third of patients.

Answer 67

Hypovolemia and Renin... The kidneys respond by releasing renin from the juxtaglomerular cells. Renin converts angiotensinogen to angiotensin I, which is then converted into angiotensin II by ACE. Angiotensin II has the following systemic effects: **Vasoconstriction: Increases 📗🚶🏾‍♀️Efferent and systemic arteriolar resistance**, which improves glomerular filtration rate and blood pressure Sodium and water reabsorption: Directly increases proximal tubule sodium reabsorption Aldosterone secretion: Increases sodium and water reabsorption in the distal tubule **Decreased renal perfusion seen in 💔CHF** and subsequent RAAS activation lead to increased angiotensin II levels. Angiotensin II causes numerous effects including: * **Vasoconstriction** of both the **afferent AND efferent** glomerular arterioles, leading to an increase in renal vascular resistance and a net decrease in renal blood flow. * **Preferential vasoconstriction of 🚶🏾‍♀️📗Efferent renal arterioles**, which increases intraglomerular pressure in an attempt to maintain adequate glomerular filtration rate (GFR). * Direct stimulation of sodium resorption in the proximal tubules and increased secretion of aldosterone from the adrenal glands, which in turn promotes further sodium resorption in the cortical collecting tubule. These actions lead to decreased sodium delivery to the distal tubule and an increase in extracellular fluid volume.

Answer 68

is the most common of the hereditary nephritis conditions, frequently leading to end-stage renal disease. In 85% of patients with Alport syndrome, an X-linked dominant form of inheritance is found; about 15% are autosomal recessive. All cause hematuria and progressive nephritis. Other findings include deafness and ocular defects.

Answer 69

The nonspecific findings of anorexia, polydipsia and polyuria, vomiting, and unexplained fevers, along with the more specific laboratory abnormalities of glucosuria but normal blood sugar, abnormally high urine pH in the face of mild or moderate serum hyperchloremic metabolic acidosis, and mild albuminuria in the presence of normal serum protein and albumin, suggest Fanconi syndrome (also called global proximal tubular dysfunction). Fan-coni syndrome can be hereditary or acquired; hereditary forms are usually secondary to a genetic abnormality such as cystinosis, galactosemia, Wilson disease, and some mitochondrial abnormalities. A number of agents can cause Fanconi syndrome, including gentamicin (or other aminoglyco-sides), outdated tetracycline, cephalothin, cidofovir, valproic acid, strepto-zocin, 6-mercaptopurine, azathioprine, cisplatin, ifosfamide, heavy metals (eg, lead, mercury, cadmium, uranium, platinum), paraquat, maleic acid, and toluene (from sniffing glue). The mechanism of action of these agents is through acute tubular necrosis, alteration of renal blood flow, intratubu-lar obstruction, or allergic reactions within the kidney itself. Many of these toxic effects are reduced or eliminated with removal of the offending agent. Renal tubular acidosis (RTA) type 1 is a distal RTA, and has a positive urine anion gap, as does RTA type 4. Type 3 is not a recognized type of RTA. Congenital nephrotic syndrome is a rare version of nephrotic syndrome, characterized by edema early in infancy, with hypoalbuminemia.

Answer 70

While renal stones in children are relatively uncommon in the United States and are usually related to metabolic abnormalities (where they are twice as common in boys), they are endemic in southeast Asia and related to diet. Symptoms of a stone in the renal pelvis, calyx, or ureter cause obstruction and the symptoms presented in the case. A stone in the distal ureter results in symptoms of dysuria, urgency, and frequency. Once in the bladder the stone is asymptomatic unless it moves into the urethra, then dysuria and voiding difficulties may arise. While some stones may be visible via plain abdominal radiograph, the non-contrast spiral CT scan will accurately diagnose the number and location of the stone as well as assist in confirming if the affected kidney is hydronephrotic. Once the child’s condition has stabilized (the stone passed or retrieved), a metabolic evaluation is undertaken in an attempt to identify the cause of the stone.

Answer 71

Urinary tract infections (UTIs) are common in children, particularly in girls and uncircumcised boys during infancy. Escherichia coli is the most common etiology, followed by other gram-negative bacteria (eg, Klebsiella, Proteus). UTIs often present with vague symptoms in infants and should be suspected in a child with fever (especially temperature ≥39 C [102.2 F]), fussiness, and poor feeding. Positive **nitrites** (specific for Enterobacteriaceae) and **leukocyte esterase** (produced by white blood cells) on urinalysis are highly suggestive of a UTI. Bacteriuria on **urine culture** confirms the diagnosis. **Tx:** When a UTI is suspected based on clinical presentation and urinalysis, **empiric antibiotics** are recommended because a delay in therapy increases the risk of renal complications (eg, scarring, hypertension). Children are typically treated with a **third-generation cephalosporin, such as cefixime**, to cover the most common pathogens. Antibiotics may be modified based on the urine culture results. Symptoms generally improve by 48 hours of appropriate antibiotic therapy. **Cx: Persistent fever** and **costovertebral tenderness** despite oral antibiotic therapy is concerning for renal infection, either pyelonephritis or renal abscess. The next steps in management are to broaden antibiotics to cover a resistant organism and to obtain a **renal and bladder ultrasound**. A 🔊 **renal ultrasound** should be obtained following an **initial UTI in any child** and can be repeated in case of **recurrent febrile UTI**; it may detect hydronephrosis suggestive of VUR but is not sensitive for the diagnosis. Therefore, a **voiding cystourethrogram (VCUG)** is often obtained in children with UTI in whom VUR should be excluded. Indications for VCUG include: **≥2 febrile UTIs**; **abnormal renal ultrasound; fever ≥39 C (102.2 F) with bacteria other than E coli; signs of chronic kidney disease (ie, poor growth, hypertension).** **VOIDING CYSTOURETHROGRAM (VCUG):** A radiographic study in which a catheter is placed in the bladder and contrast is instilled. Upon voiding, the urethra is visualized and, in cases of vesicoureteral reflux, the ureters are outlined. The preferred methods of urine collection include **bladder catheterization** and suprapubic bladder aspiration. Infants and children with VUR receive prophylactic antimicrobial therapy and close monitoring for infection with urinalysis and urine culture at 3- to 4-month intervals. Sulfamethoxazole-trimethoprim, trimethoprim alone, and nitrofurantoin are commonly used for antimicrobial prophylaxis, VUR is graded from I to V based on the degree of reflux. Higher-grade reflux is less likely to resolve spontaneously and is more likely to result in renal damage. The higher the reflux into the renal system, especially if the renal pelvis is dilated, the more likely it is for renal damage to occur; the grading system is based upon these radiographic observations. **Grade I VUR** is reflux of urine into an undilated ureter. Reflux into the ureter and collecting system without dilatation is called grade II. **Grade III** lesions have dilatation of the ureter and collecting system without blunting of the calyces. Grade IV lesions are characterized by blunting of the calyces, and **grade V** lesions demonstrate even more dilatation and tortuosity of the ureter. While somewhat controversial, low-grade lesions (grade I and grade II) usually are conservatively managed with close observation, daily low-dose antibiotics, and urinalyses and cultures every 3 to 4 months. **Grade V** lesions (and some grade IV lesions) require surgical reimplantation of a ureter if the findings persist. Lesions in between these two extremes are treatment dilemmas. Neither a diet low in protein nor early toilet training would likely affect the VUR.

Answer 72

is in the middle of the spectrum between pyelonephritis and renal abscess. Patients have prolonged fever curves despite appropriate antibiotics. A CT scan is most useful in diagnosing nephronia, but a renal ultrasound can identify the process as well. Treatment is prolonged IV and then PO antibiotics. Shorter courses like the typical treatment for pyelonephritis can lead to recurrence and renal abscess. Surgery and biopsy are not necessary, and a DMSA scan, while identifying alterations in flow consistent with pyelonephritis, would not add to the patient’s care.

Answer 73

Pathogenesis * Inherited (most commonly X-linked) * Mutation of type IV collagen Clinical findings * Nephropathy * **Hematuria** (microscopic or gross) * Progressive renal insufficiency * ± Proteinuria * ± Hypertension * Bilateral sensorineural hearing loss * Anterior lenticonus (lens protrusion) Diagnosis * Molecular genetic testing * Renal biopsy: longitudinal splitting of GBM Alport syndrome is an inherited, progressive disease affecting type IV collagen in the glomerular basement membrane (GBM), cochlea, and eye. The typical patient is a boy age \<10 with gross hematuria after a recent upper respiratory infection, as in this case. Asymptomatic, microscopic hematuria often precedes gross hematuria, which recurs periodically and may be accompanied by hypertension, proteinuria, and chronic renal failure. Mutated collagen in the cochlea and eye results in sensorineural hearing loss and anterior lenticonus (conical lens protrusion), respectively. Most cases are X-linked, and patients often have a family history of chronic kidney disease, such as the renal transplant in this patient's uncle. History may also reveal hereditary hearing loss. Laboratory results may demonstrate elevated serum creatinine and normal complement levels. Diagnosis is confirmed by renal biopsy, with electron microscopy showing a lamellated GBM due to longitudinal splitting of the lamina densa. Genetic testing can also screen patients with a family history of Alport syndrome or confirm the diagnosis in a symptomatic patient. Management is supportive and may include transplant in patients with end-stage renal disease.

Answer 74

**Bartter syndrome** (also known as juxtaglomerular hyperplasia) is an autosomal recessive condition that causes hypokalemia, hypercalciuria, alkalosis, hyperaldosteronism, and hyperreninemia; blood pressure is usually normal. Clinical presentations occurring frequently between 6 and 12 months of age include failure to thrive with constipation, weakness, vomiting, polyuria, and polydipsia. Treatment is aimed at preventing dehydration, providing nutritional support, and returning the potassium level to normal.

Answer 75

Defined as a ventrally displaced urethral opening. This embryologic defect results from failure of the **urethral folds** to fuse during early fetal development. In addition, incomplete ventral foreskin closure leads to a dorsal hooded foreskin, . Penile curvature (chordee) may also be seen in patients with hypospadias. Diagnosis is clinical, and further workup is not required in cases of isolated hypospadias. The first step in management of hypospadias is **urologic evaluation** as most cases require surgical correction. Circumcision is deferred until after evaluation because the foreskin may be required in future hypospadias repair. In addition, placement of conventional circumcision devices over asymmetric foreskin may be unsafe.

Answer 76

A tortuous dilation of the pampiniform plexus of spermatic veins. Varicoceles are very common and occur in up to 20% of males. The left testis (which frequently hangs lower than the right) and hemiscrotum are often affected due to drainage of the left spermatic (gonadal) vein into the left renal vein, which is subject to compression between the superior mesenteric artery and the aorta. The increased pressure and retrograde blood flow results in venous dilation and the classic "bag of worms" appearance that typically decreases with recumbency. The diagnosis is typically made clinically but can be confirmed with ultrasound. Clinical presentation * Soft scrotal mass **("bag of worms")** * **↓ In supine position🛌🏿** * **↑ With standing/Valsalva maneuvers** * **Subfertility** * Testicular atrophy Ultrasound findings * Retrograde venous flow * Tortuous, anechoic tubules adjacent to testis * Dilation of pampiniform plexus veins Treatment * Gonadal vein ligation (boys & young men with testicular atrophy) * Scrotal support & NSAIDs (older men who do not desire additional children) **Cx: ❗ Infertility** Although most patients are asymptomatic, varicoceles are associated with decreased fertility in males, likely due to mildly **increased scrotal temperatures**. This can result in testicular atrophy, reduced sperm production, and impaired spermatic motility. Patients who desire fertility but have abnormal semen parameters or evidence of testicular atrophy are candidates for **surgical venous ligation or embolization**, which is associated with improved pregnancy rates. Older patients who do not desire fertility may be conservatively managed with nonsteroidal anti-inflammatory medications and scrotal support. However, **younger men** should be followed for signs of testicular atrophy or changes in semen analysis; abnormal findings generally warrant surgical intervention. When intervention is indicated, surgical venous ligation can improve **fertility**.

Answer 77

Epidemiology * Young & middle-aged men * ↑ Risk with diabetes, smoking, urinary tract procedure Pathogens * Coliforms enter from urethra via intraprostatic reflux * Escherichia coli causes \>75% of cases Presentation * Recurrent urinary tract infection (with the same organism) * +/- Prostatic tenderness & swelling (often absent) * **💥Pain with ejaculation** * History of antibiotic treatment → transient improvement Diagnosis * Pyuria and bacteriuria on urinalysis * Bacteria in prostatic fluid \> bacteria in urine Treatment * Fluoroquinolones (eg, ciprofloxacin) for 6 weeks Most cases arise in young or middle-aged men who smoke or have diabetes mellitus. Coliform bacteria (eg, Escherichia coli) cause the majority of cases and generally gain access to the prostate from the urethra via the intraprostatic reflux of urine. Manifestations are often subtle, but many patients have ≥1 of the following: * Symptoms of recurrent urinary tract infections (eg, dysuria, frequency, suprapubic tenderness, pyuria, bacteriuria) that transiently improve with short courses of antibiotic therapy * Pain with ejaculation (discharge of prostatic fluid is irritative) * Prostatic swelling and tenderness; however, notably, the prostate examination is often normal The diagnosis is generally made clinically, but confirmation requires prostatic massage followed by examination of prostatic fluid (prostatic fluid bacteria \> urine bacteria prior to prostatic massage). Eradication of the pathogen usually requires at least 6 weeks of antibiotic therapy (eg, fluoroquinolone).

Answer 78

A fluid-filled cyst of the head of the epididymis that **transilluminates**. It presents as a painless mass at the superior pole of the testis. A spermatocele does not change in size with positioning or Valsalva maneuvers.

Answer 79

Peritoneal fluid collections between the parietal and visceral layers of the tunica vaginalis. Although communicating hydroceles can change size with positioning, the fluid within a hydrocele is easily **transilluminated**.

Answer 80

A common disorder characterized by fibrotic narrowing of the urethra and occurs most frequently in the bulbar portion. Strictures are commonly idiopathic, but secondary causes include urethral trauma (eg, pelvic fracture, iatrogenic instrumentation), infection (eg, sexually transmitted urethritis), and radiotherapy. In some cases, the inciting cause is temporally remote and may not be immediately remembered by the patient. Urethral strictures can lead to acute urine retention, recurrent urinary tract infection, bladder stones, or, rarely, hydronephrosis and renal insufficiency. Patients typically have obstructive-type voiding symptoms (eg, weak urine stream, urinary spraying), although dysuria can occur. The diagnosis is suggested by an **elevated postvoid residual volume**. Urethrography (eg, voiding cystourethrogram) or cystourethroscopy can confirm the diagnosis. In addition to voiding problems, complications can include bladder stones, hydronephrosis, and fistulas. Mild strictures may be observed cautiously, but significant strictures typically require correction with either urethral dilation or surgical urethroplasty.

Answer 81

Epidemiology * Most common in adolescents Clinical features * Testicular, inguinal, abdominal pain * Nausea, vomiting * Horizontal testicular lie with elevated testicle * **Absent cremasteric reflex** * Swollen, erythematous scrotum Imaging * No blood flow on scrotal ultrasound with Doppler Management * Surgical detorsion & fixation with exploration of the * contralateral side * Manual detorsion (if immediate surgery is not available) Acute-onset scrotal pain and edema occurring after trauma has a broad differential diagnosis (eg, scrotal contusions, hematoma, testicular rupture). However, testicular torsion is an underrecognized diagnosis that can occur after testicular trauma and should be considered in any patient with significant scrotal pain and swelling. Although the diagnosis of testicular torsion is often made clinically, a **Doppler ultrasound of the scrotum** is the imaging of choice to evaluate scrotal contents and can confirm torsion in those without a clear diagnosis or evaluate other causes of scrotal pain. Ultrasound findings of reduced or absent blood flow or twisting of the spermatic cord are suggestive of torsion. Testicular torsion occurs due to insufficient attachment of the testicle to the tunica vaginalis, allowing for testicular hypermobility; mild trauma or exercise can induce twisting of the testis on the spermatic cord, leading to testicular ischemia. Spontaneous torsion can also occur. Other classic findings of torsion include absent cremasteric reflex (elevation of the testicle with stroking of the inner thigh) and scrotal pain unrelieved by elevation of the testicle (negative Prehn sign), although this test cannot reliably rule out torsion. Testicular torsion is a surgical emergency; up to 80% of patients with untreated torsion develop a nonviable testicle within 12 hours.

Answer 82

Epidemiology * Age 15-35 * Risk factors: family history, cryptorchidism Types * Germ cell tumors (95%): seminomatous or nonseminomatous (embryonal carcinoma, yolk sac, choriocarcinoma, teratoma, mixed) * **Nonseminomatous germ cell tumors typically also produce AFP**, which is not produced by seminomas * Sex cord–stromal tumors: Sertoli cell, Leydig cell Manifestations * Unilateral, painless testicular mass * Dull ache in lower abdomen Diagnosis * Examination: firm, ovoid mass * Elevated tumor markers (AFP, β-hCG, LDH) * Scrotal ultrasound Most cases present with a unilateral testicular nodule that is generally painless but may be associated with a dull ache in the lower abdomen or perineum. Subsequent bimanual examination of the testes usually reveals a hard, ovoid mass within the tunica albuginea. Because testicular cancer spreads primarily through regional lymphatics, the **retroperitoneal lymph nodes** are often initially affected. Bulky retroperitoneal lymphadenopathy may compress adjacent structures (nerve roots, psoas muscle) and lead to **lumbar back pain**. Solid organ metastatic disease to the lungs and liver are also common. Lung metastases (nodules) may result in cough or dyspnea. Prompt diagnostic workup and treatment is required to provide the best chance for cure. This generally includes: * **Scrotal ultrasound**, which usually reveals a solid, hypoechoic lesion (seminoma) or a lesion with cystic areas and calcifications (nonseminomatous germ cell tumor [NSGCT]). * **Serum tumor markers such as β-hCG, alpha-fetoprotein,** and lactate dehydrogenase, which are often elevated (particularly with NSGCTs). * **❗Radical inguinal orchiectomy**, which is performed t**o confirm the diagnosis histologically and provide definitive treatment.**

Answer 83

Etiology * Age \<35: sexually transmitted (chlamydia, gonorrhea) * Age \>35: bladder outlet obstruction (coliform bacteria) Manifestations * Unilateral, **posterior testicular pain** * Epididymal edema * Pain **improved with testicular elevation ☝🏽** * Dysuria, frequency (with coliform infection) Diagnosis * NAAT for chlamydia & gonorrhea * Urinalysis/culture Most cases arise when pathogens from the urethra travel in a retrograde fashion through the ejaculatory duct to the ductus deferens and epididymis. The likely underlying pathogen differs based on the age of the patient: * 👦🏾Age \<35 – most cases are caused by **sexually transmitted infections,** particularly Neisseria **gonorrhoeae** or **Chlamydia** trachomatis. Patients often have minimal urinary symptoms (eg, dysuria, frequency, urethral discharge) and mild or no pyuria. * **👴🏿Age \>35** – most cases are associated with bladder outlet obstruction (eg, benign prostatic hypertrophy) and are caused by **coliform bacteria (eg, Escherichia coli).** Patients generally have urinary symptoms and significant pyuria on urinalysis. Epididymitis is often suspected when physical examination reveals posterior testicular swelling and tenderness that **improves with elevation of the testes (Prehn sign)**. Confirmation requires urinalysis/urine culture and nucleic acid amplification testing for N gonorrhoeae and C trachomatis. **Tx:** Treatment with **ceftriaxone** plus **doxycycline** (for N gonorrhoeae or C trachomatis) or **levofloxacin** (for enteric pathogens) is generally curative.

Answer 84

Germ cell (95%) * **Seminoma** * Retain features of spermatogenesis * β-hCG, AFP usually **negative** * Nonseminoma * ≥1 partially differentiated cells: yolk sac, **embryonal** carcinoma, teratoma, and/or **choriocarcinoma** * **β-hCG, AFP usually positive** Choriocarcinoma, teratoma, and yolk sac tumors are nonseminomatous germ cell tumors. They typically present with a painless, firm testicular mass. However, they often produce β-hCG (particularly choriocarcinoma) or AFP (particularly yolk sac tumors) Stromal (5%) * **Leydig** * Often produces excessive **estrogen (gynecomastia)** **OR testosterone (acne)** * Can cause precocious puberty Leydig cells are the primary source of testicular **testosterone** but are **also capable of generating estrogen**. Therefore, Leydig cell tumors often present with endocrine manifestations due to excessive estrogen (eg, **gynecomastia, loss of libido, erectile dysfunction)** or testosterone (eg, acne, hirsutism). Examination frequently reveals a testicular mass, which is typically confirmed by bilateral scrotal ultrasound. In contrast to many germ cell tumors, Leydig cells do not generally produce serum tumor markers such as β-hCG or alpha-fetoprotein (AFP). However, the generation of estrogen or testosterone often leads to **FSH and LH suppression.** * Sertoli * Rare * Occasionally associated with excessive estrogen secretion (eg, gynecomastia)

Answer 85

A common condition (affecting ~5% of men) that arises due to repetitive blunt trauma to the penis during sexual intercourse with subsequent aberrant wound healing. It is characterized by the formation of **fibrous plaques** (due to transforming growth factor-1 upregulation) in the tunica albuginea, which reduce tissue elasticity and expansion during erections. Manifestations generally include penile pain, curvature, and dorsal nodules or plaques. Distortion of the penis during erection may make sexual intercourse difficult or impossible, leading to body image and relationship issues. Most cases are diagnosed based on clinical findings, but ultrasound is sometimes necessary. In many individuals, the pain and deformity resolve spontaneously over 1-2 years. However, those with active or progressive PD often require nonsteroidal anti-inflammatory drugs for pain; pentoxifylline to reduce fibrosis; and/or intralesional injections of collagenase. Surgery may be indicated in refractory cases.

Answer 86

An undescended testis, is due to failure of in utero testicular descent from the abdomen into the scrotum. Risk factors include prematurity, small for gestational age, and low birth weight (\<2.5 kg). At birth, boys with cryptorchidism typically have an empty, poorly rugated scrotum. The testis may be palpable in the inguinal canal, or undetectable. Because the cryptorchid testis often descends spontaneously in the first few months of life, monitoring for testicular descent is appropriate. However, testes that have not descended by age **6 months** are unlikely to descend and require **surgical intervention**. **Orchiopexy** (surgical pinning of the testis) is performed, ideally **before age 1**, to reduce complications associated with cryptorchidism such as **testicular torsion, infertility, and testicular malignancy.**

Answer 87

Erectile dysfunction (ED) is common in patients with cardiovascular disease due to decreased penile blood flow, endothelial dysfunction, and vasoactive medications. First-line treatment for most patients with ED, including those with cardiovascular disease, is a **phosphodiesterase-5 (PDE-5) inhibitor (eg, sildenafil).** These medications are **safe** and effective in treating ED in low-risk patients with cardiovascular disease. However, PDE-5 inhibitors are contraindicated in patients taking nitrates as concomitant use can cause a precipitous drop in blood pressure, leading to syncope. Coadministration of alpha blockers with PDE-5 inhibitors can also cause severe hypotension. Other common side effects of PDE-5 inhibitors include headaches and disturbances in vision and hearing.

Answer 88

Etiology * Male \> female * Urethral trauma (eg, catheterization) * Urethritis * Radiotherapy Symptoms * Weak or spraying stream * Incomplete emptying * Irritative voiding (eg, dysuria, frequency) Complications * Acute urine retention * Recurrent urinary tract infection * Bladder stones Diagnosis * Postvoid residual, uroflowmetry * Urethrography * Cystourethroscopy Management * Dilation * Urethroplasty Urethral stricture is a common disorder characterized by fibrotic narrowing of the urethra and occurs most frequently in the bulbar portion. Strictures are commonly idiopathic, but secondary causes include urethral trauma (eg, pelvic fracture, iatrogenic instrumentation), infection (eg, sexually transmitted urethritis), and radiotherapy. In some cases, the inciting cause is temporally remote and may not be immediately remembered by the patient. Urethral strictures can lead to **acute urine retention**, recurrent urinary tract infection, bladder stones, or, rarely, hydronephrosis and renal insufficiency. Patients typically have obstructive-type voiding symptoms (eg, weak urine stream, urinary spraying), although dysuria can occur. The diagnosis is suggested by an elevated postvoid residual volume. Urethrography (eg, voiding cystourethrogram) or cystourethroscopy can confirm the diagnosis. In addition to voiding problems, complications can include bladder stones, hydronephrosis, and fistulas. Mild strictures may be observed cautiously, but significant strictures typically require correction with either urethral dilation or surgical urethroplasty.

Answer 89

Rheumatoid arthritis * RF: 70-80 * Anti-CCP: 95 Systemic lupus erythematosus * ANA: 95 * Anti-dsDNA/anti-Sm: 96 Drug-induced lupus * ANA: 95 * Antihistone: 95 Diffuse systemic sclerosis * ANA: 95 * Anti–Scl-70 (anti–topoisomerase I): 99 Limited systemic sclerosis * ANA: 95 * Anticentromere: 97 Polymyositis/dermatomyositis * ANA: 75 * Anti–Jo-1: 99

Answer 90

Uncomplicated cystitis * **Nitrofurantoin** for 5 days (avoid in suspected pyelonephritis or creatinine clearance \<60 mL/min) * **Trimethoprim-sulfamethoxazole for 3 days** (avoid if local resistance rate \>20%) * Fosfomycin single dose * **Fluoroquinolones** only if above options cannot be used * Urine culture needed only if initial treatment fails Complicated cystitis\* * **🌼Fluoroquinolones**\*\* (5-14 days), extended-spectrum antibiotic (eg, ampicillin/gentamicin) for more severe cases * Obtain sample for urine culture prior to initiating therapy & adjust antibiotic as needed Pyelonephritis * Outpatient: 🌼**Fluoroquinolones** (eg, ciprofloxacin, levofloxacin) * Inpatient: Intravenous antibiotics (eg, fluoroquinolone, aminoglycoside ± ampicillin) * Obtain sample for urine culture prior to initiating therapy & adjust antibiotic as needed **Uncomplicated pyelonephritis** Patients with uncomplicated pyelonephritis usually develop symptoms of cystitis (dysuria, frequency, urgency, suprapubic pain, and/or hematuria) along with flank pain, abdominal or pelvic pain, nausea, vomiting, fever (\>38 C), or costovertebral angle tenderness. Bacteria typically ascend the bladder, invade the ureters, and can enter the bloodstream to cause Gram-negative sepsis. Patients should have urine culture and receive empiric oral antibiotics against Gram-negative organisms (eg, fluoroquinolone). Hypotensive patients require hospitalization and blood cultures to determine the causative organism, evaluate for bacteremia, and check for drug-resistant organisms. These patients also need aggressive resuscitation with intravenous fluids and empiric intravenous antibiotics. Uncomplicated pyelonephritis does not require routine urological imaging (eg, CT of abdomen/pelvis), especially if the patient is improving clinically. **Imaging is typically reserved for patients with persistent clinical symptoms despite 48-72 hours of therapy, history of nephrolithiasis, or unusual urinary findings** (eg, gross hematuria, suspicion for urinary obstruction). **Complicated pyelonephritis** Involves progression of the initial pyelonephritis to **renal corticomedullary abscess, perinephric abscess, emphysematous pyelonephritis, or papillary necrosis**. Patients can develop sepsis with multiorgan failure, shock, and renal failure. Complicated pyelonephritis occurs more commonly in patients with conditions such as diabetes, kidney stones, immunosuppression, or other anatomic abnormalities of the urinary tract. These patients usually require imaging to evaluate for these complications, urological evaluation, and prompt therapy (medical/surgical).

Answer 91

**Urethral injury** (eg, blood at the urethral meatus, high-riding prostate). **Anterior urethral injury: penile trauma** (eg, laceration, contusion) is often visible. Bulbomembranous junction (junction of the anterior and posterior urethra) is the most common site of urethral injury. **Posterior urethral injury** (eg, membranous urethral injury) and bulbomembranous transection, digital rectal examination may reveal a high-riding prostate. **Extraperitoneal bladder injury (EPBI)** may consist of either contusion or rupture of the **neck, anterior wall, or anterolateral wall** of the bladder. In the case of rupture, extravasation of urine into adjacent tissues causes localized pain in the lower abdomen and pelvis. Pelvic fracture is almost always present in EPBI, and sometimes a bony fragment can directly puncture and rupture the bladder. **Gross hematuria** is also usually present, and urinary retention (evidenced by suprapubic fullness in this patient) may occur, especially in the case of injury to the bladder neck. **Anterior bladder wall** and the bladder neck are extraperitoneal structures. A tear in these locations is almost always accompanied by **pelvic fracture** and causes extraperitoneal leakage of urine, leading to localized lower abdominal pain. **Dome of bladder** Spillage of blood, bowel contents, bile, pancreatic secretions, or urine into the peritoneal cavity can cause **acute chemical peritonitis ❗**, which is evidenced by diffuse abdominal pain and guarding. The superior and lateral surfaces of the bladder compose the dome of the bladder and are bordered by the peritoneal cavity. Therefore, **rupture of the dome of the bladder** causes urine to spill into the peritoneum, leading to peritonitis. Bladder rupture after blunt trauma is due to a sudden increase in intravesical pressure and most likely occurs following a blow to the lower abdomen when the bladder is full and distended. In addition, irritation of the peritoneal lining of the right or left hemidiaphragm may cause **referred pain to the ipsilateral shoulder (Kehr sign)** as sensory innervation to the shoulder originates from the C3 to C5 spinal roots; these roots are also the origin of the phrenic nerve innervating the diaphragm.

Answer 92

Abrupt upward shifting of the bladder and prostate can lead to urethral tearing, which most commonly affects the membranous urethra at the bulbomembranous junction (dividing point between the anterior and posterior urethra). Findings consistent with PUI include blood at the urethral meatus, inability to void, perineal or scrotal hematoma, and a **high-riding prostate** on digital rectal examination. **Dx:** In patients with suspected urethral injury, a **retrograde urethrogram** should be performed. This diagnostic test involves an x-ray of the lower genitourinary tract obtained during the injection of radiopaque contrast into the urethra. A normal study demonstrates contrast entering the bladder uninterrupted. Extravasation of contrast from the urethra or inability of contrast to reach the bladder is diagnostic of urethral injury.

Answer 93

The first step in evaluation for endocrine causes of ED is a morning testosterone and prolactin level. Free testosterone is more specific but much more expensive. A **testosterone** level **above 350** effectively excludes hypogonadism. Levels between 200 and 350 are equivocal and should either be repeated or be followed by a free testosterone. If the testosterone level is low, **gonadotrophin** **levels** will help determine if the cause is **central (low LH)** or **peripheral (ie, testicular failure** with high gonadotrophin level). An elevated prolactin level or evidence of central hypogonadism in a young or middle-aged man should prompt a search for a pituitary tumor.