1. Urine Luck! (Part II) Renal slides by Dan Cushman Donations accepted and strongly encouraged

2. Presidential Election 2008… You have a choice. Kupin for President!

3. TestValue Serum [Na + ]140 mEq/L Serum [Cl - ]103 mEq/L Serum [K + ]4.5 mEq/L pCO 2 40 mmHg Serum [HCO 3 - ]24 mEq/L Serum [Ca 2+ ]9.4 mEq/dL Anion Gap13 Hematocrit~0.45 Serum [Hb]15 g/dL Normal values

4. TestValue BUN16 mg/dL Serum [Cr]0.7 – 1.4 mg/dL Serum [uric acid]5 mg/dL BUN/Cr16 Urine specific gravity1.002 – 1.030 Plasma specific gravity1.010 Urine pH5-7 Urine proteinTrace Serum glucose100 Normal values (continued)

5. Laboratory Evaluation of ARF Pre- renal Azotemia GlomerulonephritisATN RBCs------Dysmorphic----- WBCs------+++----- RBC cast------++++----- Granular cast------+++++++

6. Raise or lower plasma creatinine level

7. Raise or lower BUN level

8. ConditionATNPRA Recovery2-3 weeksRapid Cell death?YesNo Urine sodiumHigh (>40)Low (<20) FENaHigh (>3%)Low (<1%) Ur. Spec. Grav.Iso (1.010)High (>1.015) Ur. OsmolalityNormal (280)High (>500) RBCs in urineAbsent Plasma [K + ]High Granular castsPresentNo, sir ATN vs. Pre-renal Azotemia

9. Raise or lower BUN:Cr ratio How? Impairs Creatinine secretion How?

10. Cockroft and Gault formula Which variables go on each side of the equation? Cr [Na + ] Sex GFR Age [K + ] (140- )* / (72 * ) = Wgt (Adjust by 0.85 with )

11. HRS

12. Drugs inducing ATN (4) 1.Aminoglycosides 2.Amphotericin 3.IV contrast 4.Cisplatinum 1.Proximal tubule 2.Distal tubule 3.Proximal tubule 4.Distal & proximal Which parts of the kidney do these affect?

13. Match the Correct Response and Substance PGEAT IIConstrictionDilation

14. Midodrine ADH Octreotide NE Match the drug with its action α1-agonists Glucagon antagonism V1 agonists SomatostatinOrnipressin What do all of these drugs do? Splanchnic vasoconstriction

15. Which region is most likely to be affected by ARF? Outer Medulla

16. Hyperkalemia What happens to the T-wave? Peaked The P wave? Decreased amplitude How does trimethoprim cause hyperkalemia? Impairs distal tubule K + secretion And NSAIDs? Decreased PGE  decreased aldosterone  decreased K + secretion (same with ACEIs and ARBs) Hyperkalemia is treated with? Insulin/glucose, β 2 -agonists, Calcium chloride, kayexalate

17. ConditionAcuteChronic Renal Size (cm)>10cm<9cm [Ca 2+ ]No correlation EchogenicityNormalIncreased OsteodystrophyAbsentPresent AcidosisNo correlation CastsBland, GranularWaxy AnemiaNo correlation [K + ]IncreasedNo correlation? [phosphorous]No correlation Acute vs. Chronic Kidney Disease

18. TIPS What’s the point of TIPS? Reduce portal hypertension, as HRS is a reversible phenomena of a functional nature, not structural damage What veins are involved? *Little known fact: Due to the large proportion of alcoholic cirrhotic patients undergoing TIPS, Dr. Eugene Esmerald coined the phrase “tipsy,” referring to his future patients. * Totally made that all up.

19. Phases of Acute Renal Failure 1.Initiating – exposure 2.Oliguric – 10-14 days, <400cc/day 3.Diuretic – no change in renal function 4.Recovery – 3-12 months

20. Chinese Herb Nephropathy What herb is associated with it? Fangchi If you said Fang Ji, you need to work on your Herbology; that’s remedial. Fangchi contains which toxic agent? Aristolic acid Which does what physiologically? Inhibits protein reabsorption in the proximal tubules and covalently binds to DNA This causes what? Weight loss! (And cortical interstitial fibrosis) (And transitional cell cancer)

21. Herbal nephropathy Name the four pathophysiologic effects of Sheng Fu Chui (also known as Willowroot, Tonguebait, Snifflewood, or Tree tamer’s juice) I made all that up. (Sounds real, though, doesn’t it?)

22. St. John’s Wort What is SJW used for? Depression Does it work? Shut up. I hate you. How can SJW be harmful if taken as a complementary medicine? It induces the CYP450 and intestinal P-glycoprotein/MDR1 enzymes Will the plasma concentration of penicillin be increased or decreased when given with St. John’s Wort? Neither, penicillin doesn’t use the CYP450 excretion pathway. What about if you took an oral contraceptive (that had the same CYP450 excretion) with SJW? (And you thought you were depressed before…)

23. Grapefruit juice Why shouldn’t you drink it if you’re taking medications? It inhibits the CYP450 pathway, which increases plasma levels of the other medications Why should you drink it if you’re not taking medications? It’s refreshing

24. Starfruit What component of starfruit is dangerous to the kidney? High levels of oxalate How is this bad? Kidney stones What should you do to your “pickled sour juice” to make it safer? Dilute it. I have no idea what pickled sour juice is, I’m just reading off the slide.

25. Ephedra Ephedra is also known as what (the Chinese name)? Minh Hoang What renal issues can it cause? Ephedra stones, hypertension I mean Ma Huang

26. Licorice Spell the active ingredient in licorice (hint: the second word is “Gabra”) Z LA Y R I H G C Y R

27. Licorice What does glycyrrhizic acid bind directly to? 11 β-hydroxysteroid dehydrogenase What is the normal job of 11 β-hydroxysteroid dehydrogenase? Degrade cortisol Why? Cortisol binds to aldosterone receptors Where is this important? Principal cells What condition comes from this? Apparent Mineralocorticoid Excess (AME)

28. Heavy Metals How do heavy metals get reabsorbed in the kidney? Through the DMT1 channel in the proximal tubule What happens? ↓ reabsorption of other divalent cations, ↑ serum levels of toxic metals What does lead lead to? (The first “lead” is Pb) CKD, plus the triad: hypertension, renal failure, gout What about Cadmium? Irreversible damage, including osteoporosis and hypertension

29. Heavy Metals

30. Autoregulation Curve What are the labels on the axes? RBF or GFRSystolic blood pressure What happens to the curve upon administration of NSAIDs? It shifts to the right! (The same blood pressure doesn’t allow for a large enough GFR)

31. Kidney in pregnancy ? ? ?

32. Kidney in pregnancy (cont)

33. Preeclampsia ? ? ? ? ? ?

34. Severe preeclampsia ? ? ? ? ?

35. Preeclampsia

36. Pregnancy sucks What causes gestational diabetes insipidus? Vasopressinases in placenta ↓ ADH Why are pregnant patients often hyponatremic? The osmostat is decreased, resulting in a reduced [Na + ] by 5mEq/L Are they acidotic or alkalotic? Generally alkalotic Due to what? What is the resultant [HCO 3 - ] level in the serum? Progesterone → Hyperventilation → respiratory alkalosis; Low [HCO 3 - ] in the serum *Little known fact: Babies can suck the life out of you. At least according to a Swedish survey from 1997 (JASA, Hortenz et. al, 1997) * Totally made that all up.

37. What am I? Preeclampsia

38. TypeSystolic BPDiastolic BPOther factor Gestational>140>90NO Proteinuria, after week 20 Preeclampsia>140>90Proteinuria >300mg/d, new-onset Chronic HTN>140>90Onset before week 20 possible Hypertension in pregnancy What is the pathophysiology of preeclampsia? The cytotrophoblastic tissue of the fetus does not invade into the maternal placenta, thus not allowing for dilation of the spiral arteries and results in placental ischemia. That’s bad. Should the blood pressure be lowered? Yes (for the mother’s sake), though it won’t cure preeclampsia

39. Drugs (not the fun kind) What is the equation for bioavailability? Bioavailability (AUC) o (AUC) iv = Do IV drugs experience the first-pass effect? No If you were administering an IV drug, will you need to administer more or less of the equivalent oral drug? More Name the three sites of first-pass metabolism 1.CYP450 enzymes in the small intestine 2.CYP450 enzymes in the liver 3.P-Glycoprotein in the small intestine

40. Drugs (not the fun kind) Drug’s effect on body Pharmacokinetics Pharmacodynamics Body’s effect on drug Which is smaller – the lag time (t lag ) or the time at C max (t max ) ? t lag will always be smaller Name the four factors that will reduce bioavailability of an oral drug 1.Destruction in gut 2.Lack of absorption 3.Destruction by gut wall 4.Destruction by liver Match

41. Drugs (not the fun kind) If patient D has diabetes mellitus and patient N is normal, who will more likely require a higher dose of a dose- dependent drug? Patient D, because he/she may have diabetic gastroparesis Which patient will take more time to have effects of the drug? Patient D What will happen to the t lag and C max of patient D? Increased t lag and decreased C max What’s the importance of phosphate binders? They are antacids that reduce the absorption of some drugs (fluoroquinolones) What does CKD do to CYP450 metabolism? I have no idea how, but CKD itself reduces the potency of CYP450 and P-glycoprotein *Little known fact: The DARE program has saved a grand total of 3 children from a life of drugs. In 1998, police officer Greg Partroy accidentally backed over a group of schoolchildren in rural Indiana with his DARE van. Thus, they never did drugs after that. The War on Drugs is a winning proposition! * Totally made that all up.

42. Volume of Distribution What is the equation for Volume of Distribution? V d = Dose / [drug] plasma What would CKD do specifically that could affect V d (4 things)? 1.Decreased albumin levels 2.Decreased protein binding 3.Decreased tissue binding 4.Volume overload How does CKD lower albumin binding? Uremic toxins displace drug from albumin How much phenytoin (dilantin) is protein bound? With and without CKD. 90% without, 75% with CKD Which of the two are measured in serum drug concentrations? Bound Unbound Both!

43. Kinetics What order am I? Is this what the body usually does? First-order Yup Where is the majority of kidney drug metabolism localized? The proximal tubule What ways does the kidney remove drugs (4)? Filtration, secretion, absorb & destroy, pH How much insulin is removed by the kidney? 30% – kidney failure can result in higher-than-normal levels of insulin What will dialysis remove? Small, unbound drug

44. Osmolarity [Na] in hyponatremia<135 mEq/L [Na] in severe hyponatremia<120 mEq/L ADH decreases with pain?No – it increases Site of hypothalamic volume control Supraoptic nucleus Site of hypothalamic tonicity control Paraventricular nucleus ↑ plasma osmolarity = ? ADHIncrease More powerful – volume or tonicity Volume

45. More sensitive – volume or tonicity Tonicity (2% vs. 10%) Body protects volume or tonicity more? Volume Idiogenic molecule for osmotic force Myoinositol Is BUN part of osmolarity calculation? Yes Urine [Na + ] in CHF<20 mEq/L (due to ↑ renin) ↑/↓ water excretion in CHF?Decreased (due to ADH) ↑/↓ ADH levels from pain/surgery? Increased Osmolarity (continued)

46. I don’t have a good title for this Osmolarity Number of particles that exist in a fluid environment Number of particles existing in a fluid environment that have the potential to exert water movement Tonicity Match Which of the following two conditions causes most clinical complications? Hypertonic hyponatremia Hypotonic hyponatremia Equation 1: Tonicity = ?Equation 2: Osmolarity = ? T = 2[Na] + [Glu] / 18O = 2[Na] + [Glu] / 18 + BUN / 3

47. Calculate HyperglycemiaUremia Glucose90090 Na130 BUN30120 Osmolality (2*130)+(900/18)+(30/3) 320 (2*130)+(90/18)+(120/3) 305 Tonicity (2*130)+(900/18) 310 (2*130)+(90/18) 265 DiagnosisHypertonicHypotonic

48. CauseSerum osmolalityVolume status HyperglycemiaHypertonicHypovolemic? GI LossHypotonicHypovolemic PseudohyponatremiaIsotonic? CHFHypotonicHypervolemic SIADHHypotonicIsovolemic Renal losses – diureticsHypotonicHypovolemic CirrhosisHypotonicHypervolemic K + lossesHypotonicIsovolemic Kidney failureHypotonicHypervolemic Reset osmostatHypotonicIsovolemic Third-space lossesHypotonicHypovolemic Impaired adrenal functionHypotonicIsovolemic Hypertonic infusionHypertonic? Hyponatremia

49. SIADH What does it stand for?Syndrome of Inappropriate Antidiuretic Hormone Good kidney function? Sure What’s the urine concentration like? >100 mosm/L, typically >300 mosm/L And the urine [Na + ]? Also high, >30 mEq/L (without Na restriction) Is the plasma hypo- or hyperosmolar? Hypoosmolar Is the plasma hypo- or hypertonic? Hypotonic What malignancy is it associated with? Small-cell carcinoma

50. Evaluation of hyponatremia Proves existence of hypotonic hyponatremia Increased value suggests SIADH Match Free water clearance affected by [ADH] Proves existence of pseudohyponatremia Decreased value suggests hypovol. hyponatremia Identifies polydypsia Urine osmolality Plasma osmolality Urine Sodium

51. Hyponatremia What types of cells are particularly sensitive to rapid volume changes? Oligodendrocytes What occurs when they are re-salted quickly during treatment for hyponatremia? Osmotic Demyelinating Syndrome How long does it take for this become clinically apparent? 2-6 days What correction rate should be used for hyponatremic patients to avoid ODS? 1-2 mEq/L/hr, not exceeding 12 mEq/L increase per 24h Or… what should be a safe level to increase the [Na] to? [Na] = 120mEq/L Or, just use aquaretics

52. Polyuria Greater than 3L per day What urine osmolality separates water diuresis from osmotic diuresis? 300 mosm/L What is the diagnosis if there is a polyuric patient with a low serum [Na]? Primary polydypsia And if it’s a high serum [Na]? Diabetes insipidus or osmotic diuresis

53. Diabetes Insipidus Central – tell me about it Deficient secretion of ADH; treat with exogenous ADH And nephrogenic? Renal resistance to the action of ADH, no response to exogenous ADH What drug is notorious for causing nephrogenic DI? Lithium That’s a really good Nirvana song. What are the first lyrics? I’m so happy/cuz today I found my friends/in my head… Anyway, what else is associated with nephrogenic DI (2)? Hypercalcemia, hypokalemia (inhibition of TALH Na-K ATPase)

54. More common in heat or cold? Heat Two most common types of stone? Calcium Oxalate > Struvite More common in men or women? Men More commonly bilateral? No – unilateral Location of stone formationThat rhymed. Tip of renal papillae. Most common etiology of CaOx stones Hypercalciuria … which is exactly what level? > 4mg/kg/day Kidney Stones

55. Most common causes of hypercalciuria? Renal leak, increased absorption Does hypercalciuria = stones?No, most clinically silent Intake of what electrolyte → stones? Na What type of stones from ↑ PTH? CaPO >> CaOx Main source of dietary oxalate Vitamin C Relationship between urate and CaOx crystals ↑ urinary Urate → ↑ CaOx crystals What is epitaxy? Increased growth of one type of a crystal due to presence of another type Kidney Stones

56. Preferred pH of CaOx stones (↑/↓)? ↓ Dietary source of urine urateAnimal protein What else does that contribute to (3)?Hypercalciuria, hypocitraturia, ↓pH urine 3 stone inhibitorsCitrate, Mg, Phosphorous 2 influences on citrate levelsAge (↓), acidity (↓) Does ↑ water intake = ↓ stones? Yes – take that, Dr. Barrett. Does ↓ Ca intake = ↓ stones?No, the opposite is true Kidney Stones Why?It binds to oxalate, decreasing its absorption in the intestine

57. Stones What contributes to hypercalciuria (8)? 1. Renal Leak 2. Increased absorption (Vit D receptor) 3. Idiopathic 4. Increased sodium 5. Hyperparathyroidism 6. Too much animal protein 7. Reduced calcium intake 8. Loop diuretics (thiazides actually help increase Ca reabsorption) Cystinuria treament? Alkalanize urine, D-penicillinamine, diamox, captopril

58. Triple-Phosphate Stones What are the three cations that phosphate binds to in a triple-phosphate stone? Ammonia, Magnesium, Calcium How do UTI’s predispose someone to these stones? There is a production of urease by bacteria → more ammonium More common in men or women? Women. Ha ha. What specific population is more likely to develop one of these? Spinal cord injury patients What is the pH of the urine like?>7.2

59. TypeX-raypH Calcium oxalateOpaqueAcidic EphedraTranslucent? Uric AcidTranslucentAcidic Triple PhosphateOpaqueBasic CystineOpaqueAcidic Calcium PhosphateOpaqueBasic Kidney Stones Notice that all the high-pH stones have “phosphate” in their name! Notice that all the radio-opaque stones contain calcium or cystine

60. Match the stones! Calcium oxalateTriple PhosphateCystine RollingUric acid

61. Match the stones! Calcium oxalateTriple PhosphateCystine Past tenseUric acid

62. Acid-Base Diabetic/alcoholic ketoacidosis Renal Tubule Acidosis Methanol ingestion Diuretics Diarrhea Lactic (& D-lactic) acidosis Ethylene glycol ingestion Vomiting Primary hyperaldosteronism Early renal failure Massive IV fluids Gittleman’s/Bartter’s syndromes High-AG metabolic acidosis Metabolic acidosis High-AG metabolic acidosis Metabolic alkalosis Metabolic acidosis High-AG metabolic acidosis Metabolic alkalosis Metabolic acidosis Metabolic alkalosis

63. Renal Tubular Acidosis Where does type I occur? The distal tubule What is the pathogenesis? DT can not secrete protons sufficiently Does this result in an acidosis or alkalosis? Read the name of the disorder, Einstein. Where does type II occur The proximal tubule What is the pathogenesis? Is the urine in type II more or less acidic than type I? PT can not reabsorb HCO 3 - sufficiently The urine is more acidic because the DT is working normally Is there an associated hypo- or hyperkalemia? Hypokalemia

64. Glomerulus ? ? Which is which? EndotheliumEpithelium *Little known fact: The Scanning Electron Microscope once saved an obviously guilty physicist who had been arrested for lewd behavior. The physicist’s defense was that his PhD was in SEM, meaning that his sado- masochistic fantasies were merely research. * Totally made that all up.

65. Proteinuria Max normal protein excretion Major normal protein type in urine % of urine that is albumin Trace amount of albumin on dipstick Microalbuminuria (amt in urine) Macroalb. shows on dipstick? Microalb. shows in urine protein? What dipstick level is pathologic? Protein/Cr ratio = ? Protein/Cr ratio of 1.0 = ? Fatty casts signify…? RBC casts signify…? 150mg/day Tamm-Horsfall (50%) 15% 10-20mg/dL (not mg/day) <300 mg/day Yes Not necessarily 2+ (1 could be due to conc. urine) 24hr urine proteinuria 1.0g/day Nephrotic syndrome Glomerulonephritis Note: proteinuria itself is a risk factor for CKD with increased BP – what should be the goal BP of a patient with proteinuria? Less than 125/175! What about severely restricting protein intake? Doesn’t do much – moderate protein restriction is the general recommendation What other condition (beside proteinuria) should require a more aggressive blood pressure reduction strategy? Diabetic nephropathy

66. ACE Inhibitors Are they good for prevention of renal disease? Yes! And their benefit seems to stem from more than just a decrease in systemic blood pressure What do ACE inhibitors do to mesangial deposition of macromolecules? …to the release of TGF- β ? Decreases both Do ACE inhibitors increase or decrease procollagen formation? Decrease If a patient is taking an ACE inhibitor, what should you monitor in the blood? Check for hyperkalemia

67. Proteinuria Why is specific gravity important when measuring proteinuria? A concentrated urine can show a falsely high urine albumin level What about if there’s an infection? Inflammation  plasma exudation  ↑ albumin Hematuria? Red cells pull in albumin as well; dipstick value will never be higher than the true value What are the 4 clinical findings involved in Nephrotic Syndrome? Hypoalbuminuria, hypercholesterolemia, edema, >3.5g protein/day What neoplasms can be associated with NS? Membranous nephropathy = adenocarcinoma, minimal change = lymphoma

68. Proteinuria Dysmorphic RBCs signify…? Leukocytes, PMNs signify…? Eosinophils, leukocytes…? Oval fat bodies…? Most common adult cause of NS Most common childhood cause of NS Proteinuria level for diagnosis of NS Diabetes + nephrotic proteinuria = ? Glomerulonephritis Infection. Duh. Interstitial nephritis Nephrotic syndrome (NS) Focal Sclerosis Minimal Change Disease >3.5 g/protein/day Advanced renal disease

69. Combined Hematuria and Proteinuria Importance of RBC Morphology Dysmorphic RBCs Non- Dysmorphic RBCs Proteinuria Glomerular Glomerular / Urologic Glomerular / Urologic 1.?2.? 4.? 3.?

70. Proteinuria How do you diagnose orthostatic proteinuria? Daytime specimen vs. nighttime specimen What makes you suspect transient proteinuria? Fever, CHF, strenuous exercise

71. NormalTubularOverflowOrthostaticGlomerular Proteinuria (mg or g) 150 mg0.5 – 2 g0.5 to > 3 g0.5 – 2 g> 3.5 g Type of proteinuria Tamm Horsfall B-2 microglobulin, Albumin Light chains (Kappa /Lambda) Albumin HTN ------- ---------- -----------+ + Renal Failure --------++ ----------- + + Hematuria -------- ---------- -----------+ Proteinuria 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Use SSA test to look for non- albumin proteins

72. What am I and what am I associated with? Oval fat bodies – nephrotic syndrome Cholesterol crystals – nephrotic syndrome

73. What am I and what am I associated with? Normal red blood cells – vampires Dysmorphic RBCs – glomerular filtration problem

74. AG Metabolic Acidosis M U D P I L E S ethanol remia iabetic/alcoholic ketoacidosis araldehyde ron actic acidosis thylene glycol alicylate overdose (aspirin)

75. Non-AG Metabolic Acidosis R E D enal tubular acidosis (RTA) arly renal failure iarrhea ilution

76. Metabolic Alkalosis H D T V yperaldosteronism (primary or secondary) iuretics he unimportant syndromes omiting What are those? Gitelman syndrome Bartter syndrome What drugs do they mimic? Thiazides Loop-acting Will they present with HTN? No (aldo is normal)

77. ECFV Characteristic↑ or ↓ Edema↑ Rales↑ Orthostatic hypotension↓ BUN/Cr > 20↓ [Na + ] > 40Doesn’t matter ↑ weight↑ High urine osm↓ JVD↑ Poor skin turgor↓

78. Proteinuria 12 345

79. Immune complexes DescriptionType CirculatingIII In SituII Induction of abnormal host response IV

80. HIVAN What is the histologic presentation of HIVAN? (Collapsing) Focal segmental glomerulosclerosis What is the microscopic pathogenesis of this? HIV infects podoctyes, resulting in hypertrophy and hyperplasia, with tubuloreticular inclusion bodies What happens to the tubules? They undergo microcystic dilation Who does it affect? What’s their blood pressure like? What’s a tubuloreticular inclusion body? Aggregation of proteins from IFN production Predominantly AA males; BP is normotensive due to cytokine response How do you treat it? HAART – for the rest of the patient’s life

81. What am I? (Normal)HIVAN (Collapsing FSGS)

82. What am I? HIVAN

83. Hepatitis C What is the main disease associated with Hep C? Cryoglobulinemic GN What is the microscopic appearance of this? Membranoproliferative GN What two Ig’s are involved in this cryoglobulinemia? IgM is directed against IgG [to be exact, anti-HCV (e2) IgG] How often does a HepC patient present with cryoglobulinemia? 50% of the time, but 2-3% are symptomatic What cells does HepC infect? Liver and B-cells How does Hep C enter the cell? LDLR (E1) and CD81 (E2) Why are B cell infections important? ↓ threshold for B-cell activation →cryoglobulinemia, B-cell lymphoma

84. Hepatitis C vs. HRS

85. Hepatitis B Do most people survive HepB? Yes – immune response is sufficient for most people What kind of virus is it? Hepadna What are its main antigens? eAg, sAg, cAg What is the main type of histologic presentation with HepB? Membranoproliferative GN (I & III) What immune complexes (ICs) can be formed? IgG – HepB eAg Which type of ICs – circulating, in-situ, or direct- effect? Circulating More boy or girl instances of hepB? Boys (80%) – no preference in adults Where do the ICs “land” in the kidney? They have single deposits on the basement membrane

86. Incidence of Acute Interstitial Nephritis ? What three hormones are associated with the interstitium? EPO, Prostaglandins, Vit D hydroxylation What are the two main cells located in the interstitium? Monocytes and fibroblasts …and the molecular composition? Glycoproteins, glycosaminoglycans, and collagen

87. Acute Interstitial Nephritis What am I? What are the two main cells types that infiltrate the interstitium? T-cells and eosinophils (not PMNs!) What are the two types of AIN? Infectious and allergic What is the clinical presentation of someone with an acute allergic interstitial nephritis? Triad: rash, fever, eosinophilia; plus proteinuria <2g How long does it take to develop? 2-3 weeks, except for NSAIDs (6mo) What’s the pathogenesis? Drug has Ag site similar to body’s HLA; T-cell-mediated response → podocyte change (minimal change disease)

88. Allergic Interstitial Nephritis What quantity of eosinophilia must be present to diagnose AIN? 5%

89. Acute Interstitial Nephritis vs. GN

90. Acute pyelonephritis What am I? What is the main infiltrate in pyelonephritis? PMNs Do you get granular casts? Yes WBC casts? Yes Eosinophiluria? Nope RBCs? Yes

91. Chronic Interstitial Nephritis What am I? How can it develop (3)? AIN → CIN, Directly, or part of a primary glomerular disease What is the most effective treatment? No treatment available What kind of casts are present? Waxy What kind of infiltrate is present? There actually isn’t much of an infiltrate What happens to the tubules? They atrophy and dilate What drug can directly cause this? Daily combination of acetaminophen and other analgesics, plus caffeine or nicotine (for many years)

92. AIN vs. CIN What do the two types of interstitial nephritis look like in ultrasound? AIN = normal/large CIN = small

93. Minutiae break!!!!!! When was complement first discovered? Who cares!! Phosphatidylserine has a key role in what? Who cares!!

94. Ag:Ab complexes What happens when you’re stuck at this point? High levels of Ag:Ab complexes → GN Is IgG high-level/high- affinity or low- level/low-affinity? High-level/high-affinity

95. Stuff you’ll forget ↑What am I?↑ What pathway do I lead to? Where in the glomerulus can these Ag:Ab complexes end up? Mesangium → inflammation → GN Histones are an example of what kind of IC formation? In situ Which complement protein is a molecular adjuvant? C3d

96. Complement The complement cascade is similar to which other cascade? Coagulation cascade How are they linked?Complement activation often simultaneously activates the coagulations cascade; activates platelets; modifies mast cells & basophils; initiates Tissue Factor coagulation pathway Is that local or systemic? Local Whew.I know. Be more specific, how are the two linked…? (hint: one coagulation molecule joins with one complement molecule) C5 + thrombin → C5a + C5b

97. Complement Which complement pathway requires a microbial surface to start the cascade? All of them What is important about C3a?It’s an anaphylatoxin Which pathway(s) includes C3? All of them What is important about C3d?It’s an adjuvant, and therefore a link between the humoral and innate immune systems *Little known fact: the character C3PO in the “Star Wars” science fiction movie trilogy was originally named C3d because director George Lucas’s neighbor did research at nearby UCSF on opsonization. Because the neighbor was so flamboyantly homosexual, Lucas cast C3d as a gay robot in his friend’s honor. The movie’s financial backer (Peter Ordwell) actually turned out to be homophobic, and a closet homosexual, so he gave Lucas the choice of increasing the manliness of the robot or changing the name to C3PO, after his own initials. Lucas went with the gay robot. * Totally made that all up. What is the relationship between complement and RBCs? RBCs have C3b receptors, allowing complement-bound Ag:Ab complexes to bind to them, allowing them to be phagocytized

98. Four Secondary GN diseases with low complement levels 1.Post-infectious GN 2.Membranoproliferative GN (Hep C) 3.Cryoglobulinemia 4.Lupus Nephritis

99. Immune complexes Where do ICs generally deposit (4)? 1. Joints 2. Glomeruli 3. Choroid plexus 4. Small vessels of the skin What would a granular IHC pattern represent? Ag:Ab complex-mediated disease And a linear deposition? Anti-basement membrane Ab- mediated disease Scant deposition Pauci-immune disease How would you treat IC diseases? Corticosteroids, immunosuppressants, plasmapheresis

100. Cryoglobulins What’s the big deal with cryoglobulins? They can activate complement → systemic inflammation What are the three types?Monoclonal and Mixed Ig of 1 single isotype and 1 single light-chain class (e.g. IgG-κ) 2 or 3 Ig isotypes (usually IgM) with mono- or polyclonal components Which one is associated with RhF? Type IType II/III Which one is more common? Which one is found in multiple myeloma? …and Hep C? Type II

101. Cryoglobulins IgGIgM Is this a type I, II, or III? Type II or III How would you differentiate between the two? Type II is a monoclonal Ab (against polyclonal Ig), while type III is a polyclonal Ab (against polyclonal Ig) What would Type I look like? Or (Light chain)

102. Complement (High/low for each)

103. Complement What does a high complement level indicate? An acute response Decreased levels?That there are excess IC’s in the serum (production has been exceeded by consumption) What are the three most commonly measured complement proteins? C3, C4, and CH50 CH50 – what’s that? A marker that measures all components of complement (C1-C9) Which pathways use C4? Classical, Lectin Which pathways use C3?All of them Which pathways use C1?Classical

104. Tubular/Interstitial Pathology Which process is reversible? Tubulointerstitial nephritis Which process results in polyuria and nocturia? ATN Which process results in a metabolic acidosis? Which process usually results from ischemia? What is the most common cause of pyelonephritis? Ascending infection By which bacteria?E. coli What could cause a vesicoureteral reflux? Short ureter, spinal cord injury * Totally made that all up. *Little known fact: Fortunately, the word structure still fits, but vesicoureteral reflux was originally coined by Dr. Frank Barrows in 1882. Dr. Barrows was known for his urology center in downtown Philadelphia, and his theory of medicine involved the “Quick Draw” as he called it. Historians differ on the exact maneuver, but Dr. Barrows made his patients create a “vesicoureteral reflex.” This routinely caused damage to the vesicular portion of the ureter, not allowing compression during voiding. Later physicians changed his “reflex” to “reflux” based on the ensuing patient condition.

105. What am I? Acute Pyelonephritis What cells are present? PMNs

106. What am I? Acute Pyelonephritis Is this associated with diabetes?Yes - ↑ susceptibility to infection Sudden or insidious onset?Sudden Clinical presentationCVA tenderness, fever, dysuria, pyuria What’s in the urine?WBC casts

107. What am I? Chronic Pyelonephritis What cells are present? Leukocytes (Note normal glomeruli!)

108. What am I? Chronic Pyelonephritis Is this associated with hypertension? Yes What are the two types?Reflux nephropathy, chronic obstructive pyelonephritis Clinical presentation? Insidious or repeated acute bouts of pyelonephritis What’s in the urine? Waxy casts

109. What am I? Acute Tubular Necrosis

110. What am I? Acute Tubular Necrosis What happens to urine output?It decreases (<400mL/day) What is the most common etiology? Ischemia > toxic injury What happens to tubular epithelial cells? Because they are susceptible to ischemia, they lose cell polarity Which leads to…?Abnormal ion transport → ↑ Na delivery to distal tubule → vasoconstriction → ↓ GFR What happens to detached injured tubular cells? They create an obsruction The point of all this?DECREASED GFR Oh – how bad is the inflammation? Virtually absent?

111. QuestionAnswer PathogenesisDrugs act as haptens during secretion by tubules Hypersensitivity Reaction types Type I (IgE) and IV (cell-mediated) Clinical signs(2wks post-drug) Fever, rash, eosinophilia ↑/↓ Cr serum ↑ (Analgesic) Lcation of necrosis Renal papillae PathogenesisAcetominophen covalently binds to tubular cells Acute drug-induced interstitial nephritis

113. What am I? Hydronephrosis

114. What am I? Uterovesicular obstruction Note the bilateral hydronephrosis and hydroureters

115. What am I? Minimal Change Disease Affects which population? Children Nephrotic or Nephritic Syndrome? Nephrotic Responsive to steroids? Yes Immune complex-mediated? No

116. What am I? Focal Segmental Glomerulosclerosis Affects which population? African-American adults Nephrotic or Nephritic Syndrome? Nephrotic, usually (or nephrotic-range proteinuria) Immune complex-mediated? No

117. What am I? Diabetic Nephropathy How the hell can you tell that? Nodular appearance How should this be screened (2)? GFR, microalbuminuria Treatment? No cure, but BP and glycemic control greatly reduce risk of acquiring it in the first place

118. What am I? Crescentic GN What is this indicative of? Rapidly-Progressive GN What makes the crescent? Proliferating cells push in the rest of the glomerulus Does this result in polyuria or oliguria? Oliguria (Umbrella term)

119. What am I? IgA Nephropathy Affects which populations? Asian, Hispanic Clinical presentation Hematuria (intermittent gross or micro-) What usually exists in history? Respiratory illness 5 days prior How long does hematuria last? Recurrent/persistent for years

120. What am I? Post-strep GN When did infection occur? Respiratory – 10 days prior Nephrotic or Nephritic Syndrome? Nephritic What happens with complement levels? ↓ acutely, ↑ as disease resolves Where do the IC’s deposit? Subepithelial Note humps in SEM * Totally made that all up. *Little known fact: Famed televangelist Pat Robertson once called the Streptococcus genus “the evil genus” and suggested that his followers help him “Step on Strep” in a two-hour tirade. The blasphemy, he stated, partially came from the “humps” in the Scanning Electron Microscope view of post-streptococcal glomerulonephritis. The main reason for the source of evil, Robertson claimed, was that the actual name of the genus involved “coccus.” Inside sources claimed that he also did not approve of enterococcus.

121. What am I? Goodpasture’s Syndrome What is the pathophysiology? Ab’s directed against BM What is a related disease? Anti-GBM disease (no lung involvement) Rapid or progressive development? Rapid How is it treated? Plasmapheresis, corticosteroids, immunosuppressants What else do you need to remember? Transplant patients with Alport Syndrome may develop Ab’s against new collagen

122. What am I? Amyloidosis What is primary amyloidosis? Light chains (mostly from multiple myeloma) – AL Secondary? Serum amyloid or other abnormal protein – AA Nephritic or Nephrotic? Nephrotic What stain do you use? (Congo Red) + (hint)

123. What am I? Membranoproliferative GN What is the pathophysiology? Two words: Hep C What is the major microscopic pathologic finding? Cryoglobulins! What clinical sign is easily visible? Palpable purpura, possibly Nephrotic or Nephritic Synd. And what happens with complement? It stays persistently low Are there sub-endothelial or sub-epithelial deposits? Sub-endothelial

124. What am I? HIV-Associated Nephropathy

125. What am I? Membranous GN Affects which population? Caucasians over 40 Nephrotic or Nephritic Syndrome? Nephrotic What is the pathophysiology? Immune-complex-mediated Where do the IC’s deposit? Subepithelial Responsive to steroids? No

126. What am I? Pheochromocytoma Hemorrhages present? Yes, why else would I have asked that question? * Totally made that all up. *Little known fact: Pheochromocytomas derive their name from the character Pheo Huxtable (played by Malcolm-Jamal Warner), who played the son of actor Bill Cosby in the 80’s TV show “The Cosby Show.”

127. What am I? Fanconi Syndrome What type of light chain causes this? Kappa (kills) What’s special about these κ-LC? They’re resistant to lysosomal degradation What is the clinical presentation? B U T G A P icarbonaturia ricosuria ubular proteinuria lucosuria minoaciduria hosphaturia What type of RF can these create? ATN

128. What am I? Cast nephropathy What type of light chain causes this? Kappa (kills) What’s special about these κ-LC? It has a special attraction to Tamm-Horsfall proteins ↑ or ↓ cast nephropathy? Characteristic↑ or ↓ High pH↓ High flow rate↓ ↑ tubular Ca 2+ ↑ Infection↑ NSAIDs↑ ?? What can this lead to? Tubular pressure → interstitial nephritis Treatment? Increase urine output, alkalize urine, and chemotherapy

129. What am I? Amyloidosis What form of amyloid will show from multiple myeloma? Amyloid L What is its special property? It is thermodynamically unstable and unfolds easily What are some of the special presentations for MM-related amyloidosis? Hard liver, no retinopathy How would you diagnose it? Superficial abdominal fat bad biopsy, UPEP What 2⁰ structure do the proteins create? Β-pleated sheet What is amyloid A? A liver protein produced in response to inflammatory cytokines – it is associated with chronic inflammation …And amyloid Aβ2M? A normally-present protein that accumulates in dialysis patients (in joints, usually) How do you treat it? It’s tough… mostly treat the underlying symptoms; dialysis

130. What am I? Multiple Myeloma What cells proliferate? B cells What is needed for diagnosis? Bone marrow generation of clonal plasma cells (10% BM), monoclonal protein in serum What’s the clinical presentation? CRAB – hyperCalcemia, Renal insufficiency, Anemia, Bone pain Is monoclonal IgG always present in serum? No, 10-20% only make light chains Note that this can’t be detected by SPAP – a urine electrophoresis test is required What are the symptoms of this? Lethargy, confusion, polyuria, renal insufficiency

131. What am I? Monoclonal Deposition Disease (MCDD) What is the special property of this LC? It induces change in other cells What does this resemble? Diabetic nephropathy Where are the deposits? Outer aspect of the basement membrane of the tubules

132. What am I? A kidney What happens with the cortex? It is decreased in size With benign nephrosclerosis How often does it occur with HTN? 15% of the time What happens to the arteries? Hyaline arteriosclerosis or fibromuscular hyperplasia What about the tubules and interstitium? Tubules → atrophy, interstitial fibrosis

133. What am I? Fibromuscular hyperplasia What is that? A proliferation of myointimal cells and deposition of collagen & glycosaminoglycans

134. What am I? Malignant hypertension What is that? A proliferation of myointimal cells leading to lumenal narrowing What is present histologically in the kidney? Necrotizing arteriolitis and fibrinoid necrosis What does the kidney look like grossly? It has pinpoint petechial hemorrhages due to ruptured capillaries

135. DiseaseLightSEMIHC Minimal Change None Diffuse effacement of the foot processes None FSGS Not all glomeruli, focal mesangial hypercellularity Diffuse effacement of the foot processes Mild IgM Membranous GN Thickening of BM without hypercellularity Subepithelial deposition of immune complexes Granular Ig + complement present along BM Membranoproliferative GN Lobular appearance, BM thickened, cellular prolif. Subendothelial deposits Granular deposition of IgG and C3 along membranes Post-streptococcal GN Crescentic glomerulitis with cellular proliferation Humps, large subepithelial deposits Granular deposits along BM Goodpasture’s Crescents, hypercellular glomeruli Breaks in BMLinear deposition on BM Pauci-Immune GN Crescents, hypercellular glomeruli Swollen endothelia, fibrin thrombi None Chronic RF Advanced scarring, glomerular balls Dense collagen depositionN/A Amyloidosis Congo red stains apple green Amyloid fibersN/A Under the microscope ??

137. Minimal Change Disease (Normal) ??

138. Membranous GN

139. Membranoproliferative GN

140. Match the definitions Pulmonary-renal vasculitic syndrome CRF Rapidly-progressive GN Asymptomatic proteinuria Asymptomatic hematuria Intermittent gross hematuria Microhematuria with the same characteristics as in the Nephritic Syndrome, but patient lacks the other features Macrohematuria with the same characteristics as in the Nephritic Syndrome, but patient lacks the other features Proteinuria without the additional features of the nephrotic syndrome Relentless loss of renal function within weeks or months (creatinine doubles in < 3 months), may have either of the features 1 - 5 Vasculitis with involvement of the lungs and the kidney. Usually presents with hematuria. Chronic kidney problems

141. Three immune mechanisms of glomerular Injury 1.Antibody-mediated injury 2.Cell-mediated injury 3.Activation of alternate complement pathway

142. Match the definitions Diffuse Focal Global Segmental Subepithelial Subendothelial Located between basement membrane and foot processes Located between basement membrane and endothelial cell Involving a portion of one glomerulus Involving the entire glomerulus Involving all of the glomeruli Involving some of the glomeruli

143. Glomerulopathies – primary or secondary? Disease1⁰1⁰2⁰ Polyarteritis Goodpasture’s Membranous GN Membranoproliferative GN Diabetes Mellitus SLE FSGS IgA Nephropathy Minimal Change Amyloidosis

144. What am I? Waxy Cast Present in Nephrotic or Nephritic Syndrome? Nephrotic

145. Glomerulopathies – Nephrotic Syndrome (NoS) or Nephritic Syndrome (NiS)? DiseaseNoSNiS Membranoproliferative Crescentic Minimal Change FSGS Acute Diffuse Proliferative Proliferative Membranous Diabetic glomerulosclerosis Amyloidosis (Can also be NiS) (Can also be NoS) (Can also be NiS)

146. Clinical Presentations – Nephrotic Syndrome (NoS) or Nephritic Syndrome (NiS)? Sign/SymptomNoSNiS Hematuria Hyperlipidemia Hyperalbumenemia Oliguria Edema Hypoalbuminemia Pyuria Proteinuria Azotemia Neither How much?>3.5g/day How much?<3gms/100mL

147. Lupus Nephritis Main lab finding?ANA-positive Mostly affects which population? Young women What is the renal presentation? Can look like any glomerular clinicopathologic syndrome What does it look like under the light microscope? What about IMF? “Full house” – all of them Treatment?ACEI/ARB, Corticosteroids, immunosuppressants

148. Systemic Vasculites What do these have to do with the kidney? They can result in a crescentic, pauci-immune GN Name 3 of these diseases (there are actually 4) Wegener’s granulomatosis Churg-Strauss Microscopic polyangitis Isolated pauci-immune GN What size of vessels are affected? Small What type of antibodies are present? ANCA What do ANCAs do?Activate neutrophils → vasculitis Treatment?ACEI/ARB, Corticosteroids, immunosuppressants

149. ANCA What type of Ig is it? Usually IgG What are the two types? Perinuclear ANCA Cytoplasmic ANCA What does p-ANCA target? Myeloperoxidase, mainly …and c-ANCA? Proteinase 3 (PR3) Name three diseases and their associated ANCA 1. Wegener’s – c-ANCA 2. Microscopic polyangitis – p-ANCA 3. Glomerulonephritis – p-ANCA (Note: the diseases that contain the letter “p” have p-ANCA) Are ANCAs pathogenic? Yes

150. Wegener’s Granulomatosis Who’s it named after? Joe P. Granulomatosis What’re the main clinical presentations? Chronic sinusitis Oral/nasal mucosal ulcerations Arthralgias Nephritic syndrome Main lab finding? ANCA-positive What other vasculitis is similar? Microscopic polyangitis (the same thing, without granulomas) – Kidding What other vasculitis is similar? Isolated pauci-immune GN (same thing, just limited to kidney)

151. Henoch-Schönlen Purpura What does it resemble? IgA Nephropathy How is it different? ANCA–negative Systemic vasculitis

152. Plasma Cells Do they make more heavy chains or light chains? An excess of light chains How can they lead to renal dysfunction (2)? Size Special properties of AA sequence Which is larger – IgG or Albumin? IgG Are there light chains in the urine? Yes, some How do they get cleared? They’re transported into the tubules where they are degraded by lysosomes Does a dipstick show light chains? No, its “protein” value only refers to albumin Then how do you verify their presence? Urine electrophoresis

153. Small vessel vasculitis ANCA-positive: Granuloma present? YesNo Asthma and eosinophilia present? Microscopic polyangiitis YesNo Churg-Strauss Syndrome Wegener’s Granulomatosis ANCA-negative IgA-dominant immune deposit? YesNo Cryoglobulin present? YesNo CryoglobulinemiaOthers, e.g., inflammatory bowel disease-asscoiated vasculitis Henoch-Schönlein purpura

154. Primary Aldosteronism What causes it? Nobody knows What are the two types? Solitary adenoma Bilateral hyperplasia What are the three main findings? HTN, hypokalemia, metabolic alkalosis What is the PAC/PRA ratio (↑/↓)? High (PAC ↑, PRA↓) How do you confirm the diagnosis after obtaining a high ratio? Challenge ‘em with NaCl – aldosterone should normally decrease in a high-salt diet How would you treat the bilateral hyperplasia? Spironolactone or eplerenone

155. Pheochromocytoma Which portion of the adrenal gland is affected? The adrenal medulla Where else can they appear? Sympathetic ganglia What are the clinical symptoms? Triad: Sweating, headache, tachycardia (all episodic) Is the HTN paroxysmal or sustained? Yes – it depends on the patient How is it diagnosed?Check the plasma metanephrines What can throw off metanephrine levels? Drugs, alcohol, physical stress

156. Normal Prehypertension Stage 1 HTN Stage 2 HTN Blood Pressure Classification What happens to systolic BP with age? To diastolic? Systolic increases, diastolic decreases How does each one respond to vascular stiffness and resistance? ↑R, ↑Stiffness = ↑SBP ↑R, ↓Stiffness = ↑DBP ↑R, ↑Stiffness = ↑SBP ↑R, ↓Stiffness = ↑DBP What does a hypertensive headache feel like? There is no proven link between HTN and headaches

157. Renovascular HTN What is the cause of renovascular HTN? Renal artery stenosis → renal ischemia What are the 2 clinical presentations? Atherosclerosis (men), fibromuscular dysplasia (women) Which portions of the renal artery are affected for each? Athero. = proximal 2cm, FMD = distal /branches Which group is younger? FMD (younger women) Does this cause an acute or insidious rise in BP? Acute What’s the treatment? Anti-hypertensives or percutaneous angioplasty (not ACEI/ARB)

158. Hypertension How can CKD lead to hypertension? ↓ GFR → ↑ Na retention; ↑ peripheral resistance What is the recommended treatment? ACEI or ARB, of course (not if patient has renal stenosis, though) What is GRA (glucocorticoid- remediable aldosteronism)? Familial hyperaldosterism type I (a rare AD disorder) What age patient gets it? Younger (<21 usually) What’s the treatment? Glucocorticoids What’s the pathophysiology? Genetic mutation causes ACTH-dependent formation of aldo in the zona fasciculata

159. Apparent Mineralocorticoid Excess Syndromes Which age group is generally affected? Juvenile (it’s an AR disorder) What is the pathophysiology? Deficiency in 11-β hydroxysteroid dehydrogenase type II What happens to the serum potassium level? It decreases, also giving a metabolic alkalosis And the plasma aldosterone? Low What about the urinary free cortisol to cortisone ratio? Very high (10x normal) What’s the therapy? Mineralocorticoid blockade, Na-channel block, dexamethasone

160. Adrenal gland Which region produces aldosterone? What about people with GRA? Which region produces cortisol? How is ATII related to all this? ATII stimulates aldosterone synthase in ZG What enzyme creates cortisol? 11-β-hydroxylase Would renin be ↑ or ↓? Decreased How is it diagnosed? Test the effects of Dexamethasone (which suppresses ACTH)

161. Hypertension – label the lines Control ACE Inhibition Angiotensin II What are the three ways ATII raises BP? 1. Smooth muscle cell proliferation 2. Aldosterone release, sodium reabsorption 3. Direct vasoconstriction 3. Direct vasoconstriction What is the effect of ATII on NO (2)? 1.ATII → AT 2 R → ↑NO 2.ATII → ↑O 2 - → ↓NO 1.ATII → AT 2 R → ↑NO 2.ATII → ↑O 2 - → ↓NO

162. Hypertension Drugs

164. Hypertension If you had normal BP at 55, how likely is it that will you have normal BP the rest of your life? If you had normal BP at 55, how likely is it that will you have normal BP the rest of your life? 10% chance (!) What percentage of adults in the US have hypertension? What percentage of adults in the US have hypertension? 46% (well, 22% pre-hypertensive + 24% hypertensive) What percentage of adults with HTN are actually treated? What percentage of adults with HTN are actually treated? 60% And what percentage are controlled? And what percentage are controlled? 33% What is the pathologic hallmark of uncontrolled HTN? What is the pathologic hallmark of uncontrolled HTN? Accelerated atherosclerosis

165. Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. With Compelling Indications Lifestyle Modifications Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. Stage 2 Hypertension (SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Without Compelling Indications ?? ?? ?? ?? Algorithm for Treatment of Hypertension

166. Churg-Strauss Syndrome Nephritic or Nephrotic? Nephritic What’re the main clinical presentations? Worsening asthma Rash Peripheral nephropathy Gastroenteritis Main lab finding? ANCA-positive What special finding is visible on biopsy? Eosinophilia

167. What am I? + O+ A cryogoblin, obviously (nerd)

168. Hypersensitivities Type I –Delayed or immediate? –Mediated by what Ig? Example ? Type II –What is it? Example? Type III –Involves what two factors? Type IV –Delayed or immediate? –Involves what cells? –Example? Type I –Immediate –IgE –Pollen binds to IgE on mast cells and immediately releases histamine/inflammatory mediators leading to rhinitis / asthma Type II –Ab directed to Ag’s on your own cells Anti-GBM Type III –Immune complex deposition and complement activation Type IV –Delayed –T cells stimulated by antigen release cytokines due to prior exposure Interstitial nephritis

169. TypeBenign or malignant? Wilms tumorMalignant AngiomyolypomaBenign ReninomaBenign OncocytomaBenign RCCMalignant AdenomaBenign Transitional carcinomaMalignant LymphomaMalignant HemangiomaBenign Tumors of the kidney

170. What am I? How do you know (3)? Simple cyst 1. Anechoic (black) 2. Smooth-walled 3. Posterior enhancement What’s the treatment? Just observation

171. What am I? ?? ?? ?? ?? ?? Cysts

172. Benign tumors Epithelial Tissue type? Treatment? Observe if <3cm, otherwise excise or ablate Defining feature in CT?Stellate central scar Looks similar to…?Renal Cell Carcinoma Well-defined or diffuse edges?Well-defined TreatmentExcision Made of…?Fat, muscle, vascular tissue Associated with…?Tubular sclerosis Stereotypical patient?Female with massive hematuria and bilateral solid masses

173. What am I? Renal Cell Carcinoma More common in men or women? Men (2:1), usually ~40-50 years old Can it be familial? Yes, and don’t smoke. What are the main originating cells? Clear cells of the proximal CT What are the top 4 presentations? Hematuria, constitutional, anemia, flank pain ?? ?? ?? ?? ?? ?? ??

174. Renal Cell Carcinoma Hypercalcemia (specific) 1. PTH → 2. Renin →Hypertension (specific) 3. EPO →Anemia (non-specific), erythrocytosis (specific) Also…?Diabetes (specific) Cushings (specific) ESR, Hepatic dysfunction, fever, neuropathy (non-specific) Treatment?Radical/partial nephrectomy Most common locations of metastasis? Lungs, liver, adrenal glands, brain Treatment of metastases?Surgical excision, immunotherapy

175. Urinary system anatomy What separates the upper urinary tract from the lower? The vesicoureteral junction Who has a higher resistance to flow – men or women? Men Does the PS or symp. nerv. system innervate the lower UT? Both What type of muscle is in the internal sphincter? Smooth muscle What does the detrusor muscle do? Empties the bladder What level of the spinal cord does the pudendal come from? S2 – S4 What about the pelvic nerve? S2 – S4 What nerve is responsible for voluntary urine control? Pudendal What type of receptors are responsible for bladder contraction? M2, M3 What type of receptors are responsible for pelvic floor contraction? nAChR Will an α-agonist promote urinary retention or voiding? Retention Would a β 2 -blocker promote urinary retention or voiding? Voiding What do the pelvic nerves innervate? The bladder

176. Voiding Dysfunction – describe 3. Static/dynamic retention – often due to BPH 1. Stress incontinence – due to weak pelvic floor muscles 2. Urge incontinence – due spastic/overactive bladder muscles 4. Inactive bladder muscles – often due to nerve damage (S2 – S4) What types of therapies can help? Kiegel exercises, α- agonists Anti-muscarinic agents (oxybutynin, tolterodine), Botox Cytoscopy, urinalysis, α-blockers, prostate therapy (α 1 - antagonists, 5-α- reductase inhibitors) Repair damage if possible, otherwise intermittent catheterization

177. Urodynamics – name the condition Pressure Flow 1. Urge incontinence 2. Stress incontinence 3. Obstruction 4. Non-functioning bladder Pressure Volume Pressure Volume Leak Abdominal Strain

178. Is there a correlation between absolute levels of BUN & Cr and the development of uremic symptoms? No

179. BPH What is the most common region for BPH? The transition zone What about prostate cancer? The peripheral zone What’s the difference between clinical and histological BPH? Clinical BPH has LUTS & BOO in addition to enlargement of the prostate *LUTS = Lower Urinary Tract Symptoms; BOO = Bladder Outlet Obstruction Will prostate removal relieve irritative symptoms? (Reference to Kazakhstan BPH autopsy study) Probably not; the long- standing bladder dysfunction → OAB regardless of BOO What else will prostate surgery do? Retrograde ejaculation 80% of the time What’s the point of an AUA questionnaire? It helps to quantify the amount of LUTS Sorry – I can’t stop thinking about how horrible retrograde ejaculation must be

180. BPH What’s flomax? An α 1a -specific antagonist What happens to the prostate with age? It steadily increases in size What does a 5-α-reductase inhibitor do? Decreases the conversion of testosterone → DHT, reducing prostate enlargement What’s the quickest accurate way to measure prostate size? (Reference to Kazakhstan BPH autopsy study) Ultrasound is preferred What’s terazosin? An α 1 -specific antagonist Why wouldn’t you use a 5-α-R inhibitor with an α-blocker? Cuz you’re an idiot. I would use a combination therapy like that if it was required.

181. PTH 1 2 3 Off-topic… does anemia occur early or late in renal disease? Early! Does Vitamin D increase or decrease serum [Ca 2+ ]? Increases it Name three functions of Vitamin D with respect to calcium (hint: bones, small intestine, kidney) Bone: increases Ca (and PO) release SI: Increases Ca absorption Kidney: Decreases Ca excretion Which rises with CKD – serum phosphate or serum Ca? Phosphate – keep in mind that increased serum phosphate corresponds with increased mortality How does the body respond to an elevated serum phosphate level? It increases its release of PTH How can an elevated PTH affect the bones? What disease does it lead to? Osteitis Fibrosa Cystica How can that be prevented? Decrease serum phosphorous – dietary restriction, Vitamin D supplementation, and phosphate binders

182. Overactive Bladder Symptoms One or more symptoms: –Frequency ( >8 micturitions/24 hours; Nocturia >2 times) –Urgency ( Strong desire to void at low bladder volumes) –Urge incontinence ( Strong desire to void plus involuntary urine loss) How many people with OAB have incontinence? –57%

183. Erectile Dysfunction

184. Prostate Where are most of the glands? Where does BPH occur? What is felt in a digital rectal exam? How many men will be diagnosed with prostate cancer? 1/6

185. Prostate cancer Where is PSA usually found? It is secreted by the prostate into the semen What is it?Prostate-Specific Antigen; a serine protease Is it more specific or sensitive of a test? More sensitive, less specific What are your chances of having prostate cancer with a PSA of 15? >50% What else could you measure? Percent Free PSA Who should be screened (3)?Men > 50, AA Men > 40, family history >40 How is the diagnosis performed?Rectal biopsy of prostate How is prostate cancer staged (3)?Gleason score, PSA, digital exam To where does it like to spread? LN, bone, local extension

186. Prostate cancer What happens when it metastasizes to bone? It produces osteoblastic activity in the bone What’s the prognosis for a T2 tumor? Potentially curable What about a T3? Probably uncurable What are the 3 treatment options? Radical prostatectomy, radiation therapy, watchful waiting How would metastatic PC be treated? Androgen deprivation therapy – not a cure What does castration accomplish?Decreases testosterone formation → ↓ proliferation of some cancer cells What is the main side effect?Hot flashes

187. Prostate cancer Is there a genetic component?Yes – 10% of cases 1q24-25 Monoclonal or polyclonal?Polyclonal Where is the first spread of the cancer, usually? Hematogenous → bone How many layers in the glands of an adenocarcinoma? One Which Gleason grade is highly- differentiated? Low score (~1) Which Gleason score is the cutoff for a good prognosis and a bad? 6 (>6 = bad, ≤6 = good) What are two microscopic features of malignancy? Perineural and capsular invasion What test would verify the presence of a malignant lymphoma? CD20 IHC

188. TypeCell originAssoc. gene Conventional RCC Proximal CTVHL Papillary RCC Distal part of PCTc-MET Chromophobe RCC Intercalated cells Collecting Duct Carc Collecting duct Medullary Carc Collecting duct Oncocytoma Intercalated cells Renal Cell Neoplasms 1.More common – familial or sporadic? 2.Appearance of cytoplasm? 3.Papillary or non-papillary in appearance? 4.Associated with what disease? 5.VHL gene performs what function? 6.Treatment? 1.More common – familial or sporadic? 2.Appearance of cytoplasm? 3.Papillary or non-papillary in appearance? 4.Associated with what disease? 5.VHL gene performs what function? 6.Treatment? 1.Sporadic 2.Granular or clear 3.Non-papillary 4.Von-Hippel Lindau Syn. 5.Suppressor gene 6.Tyrosine Kinase Inhibitors 1.Sporadic 2.Granular or clear 3.Non-papillary 4.Von-Hippel Lindau Syn. 5.Suppressor gene 6.Tyrosine Kinase Inhibitors 1.What is the center of the pap. structure? 2.Function of c-MET? 3.Treatment? 1.What is the center of the pap. structure? 2.Function of c-MET? 3.Treatment? 1.Fibromuscular core 2.Oncogene 3.Tyrosine Kinase Inhibitors 1.Fibromuscular core 2.Oncogene 3.Tyrosine Kinase Inhibitors 1.Prognosis? 2.Looks similar to what other neoplasm? 1.Prognosis? 2.Looks similar to what other neoplasm? 1.Excellent 2.Oncocytoma 1.Excellent 2.Oncocytoma 1.What marker is associated with this? 2.Slow-growing or aggressive? 3.Similar to what other carcinoma? 1.What marker is associated with this? 2.Slow-growing or aggressive? 3.Similar to what other carcinoma? 1.LMW and HMW keratin 2.Aggressive 3.Urothelial carcinoma 1.LMW and HMW keratin 2.Aggressive 3.Urothelial carcinoma 1.Associated with what disease? 2.Slow-growing or aggressive? 1.Associated with what disease? 2.Slow-growing or aggressive? 1.Sickle cell trait 2.Aggressive 1.Sickle cell trait 2.Aggressive 1.Arises from what tissue type? 2.Main macroscopic feature? 3.Comprises what percent of all renal neoplasms? 1.Arises from what tissue type? 2.Main macroscopic feature? 3.Comprises what percent of all renal neoplasms? 1.Epithelial 2.Stellate central scar 3.5% 1.Epithelial 2.Stellate central scar 3.5%

189. Prostatitis Most common cause of acute? E. coli PMNs or lymphocytes?PMNs = acute Most common cause of chronic? Abacterial > E. coli

190. BPH Which portions undergo hyperplasia? All of them Physically, what is the first symptom? Compression of the urethra How many layers are present in the glands? Two What is the main gross feature? Nodules

191. Bladder cancer More frequent in men or women?Men Associated with what disease?Schistosomiasis Is there a genetic component? Yes, in some cases Associated with smoking? Of course What do transitional cell carcinomas look like macroscopically? Papillary or flat What is the prognosis for a grade I urothelial carcinoma? Very good – it’s seldom invasive What do they look like microscopically? Pretty much the same as normal transitional epithelium Where do high-grade carcinomas metastasize to? Lymph nodes Which type of bladder cancer is associated with schistosomiasis? Which type of bladder cancer is associated with schistosomiasis? Squamous cell carcinoma of the bladder Squamous cell carcinoma of the bladder Which is more common – urothelial carcinoma or adenocarcinoma of the bladder? Which is more common – urothelial carcinoma or adenocarcinoma of the bladder? Urothelial carcinoma Urothelial carcinoma

192. What am I? AD Polycystic Kidney Disease What is the pathophysiology? Two-hit hypothesis → fluid movement, cell prolif, BM What are the main associated renal findings (4)? HTN, infection, hematuria, ESRD Who is the stereotypical patient? AA man with HTN & hematuria before 35yo What are the main associated extra-renal findings (3)? Liver cysts, MV prolapse, Berry aneurysms Which tubules are affected? All of them What imaging technique is used for diagnosis? Ultrasound, CT How many cysts are required for diagnosis? 15-29 yo: 2 cysts in one/both kidneys 30-59 yo: 2 cysts in each kidneys > 60yo: 4 cysts in each kidney 15-29 yo: 2 cysts in one/both kidneys 30-59 yo: 2 cysts in each kidneys > 60yo: 4 cysts in each kidney Uni- or bilateral? Always bilateral Develop early or late in life? Later in life What is the most commonly responsible gene? PKD1 (16p13.3) Main cause of death CVD > Other/infection

193. What am I? AR Polycystic Kidney Disease What is the pathophysiology? In utero: fusiform dilation of tubules Are the kidneys large or small? Large Is this a systemic disease? No What do the cysts look like? Elongated and radially distributed (perpendicular to the cortex) What happens to the liver? Which tubules are affected? Just the collecting ducts How do the infants die? Pulmonary hypoplasia → respiratory failure Portal fibrosis What shape do the kidneys develop into ? (They’re the normal bean shape)

194. Cystic kidney diseases What is the incidence of MSK?1:200 (common!) Usual presentation of MSK Asympt > hematuria, RTA, stones Prognosis of MCD? Will progress to ESRD Presentation of MCD? Uremia in 2 nd /3 rd decade, gout, sodium wasting What’s the genetic basis of AS? X-linked > AR, AD Pathophysiology of AS?Disorder of collagen IV (BM type) Renal consequences of AS?Microhematuria → proteinuria & HTN → ESRD Non-renal consequences of AS? Deafness, ocular defects, leiomyocytosis of esophagus MSK = Medullary Sponge KidneyMCD = Medullary Cystic DiseaseAS = Alport Syndrome How do you diagnose AS? Biopsy → IHC for collagen type IV α chains (NEGATIVE) What is the treatment for AS? Transplantation But… You can develop AGBM disease from the new collagen

195. What am I? Wilms’ Tumor Off-topic: What is the most common benign renal tumor? Congenital mesoblastic nephroma What is the histologic precursor to Wilms’ Tumor? Nephrogenic rests How old are patients diagnosed? Between 2 and 5yo Arises from what tissue? Primitive blastema Unilateral or bilateral? Both (bilateral 5-10%) Whats a stage I? Stage V? I = intact capsule (epithelial) ; V = bilateral Treatment? Chemotherapy What’s an anaplastic Wilms’ tumor? A highly responsive version with underlying p53 mutations Which three syndromes are associated with WT? WAGR, Denys-Drash, and Beckwith-Wiedemann

196. TypeAge of onsetUni- or bilateral? Wilms tumor2-5Uni > Bi AD PKDLater in lifeBi AR PKDBirth – juvenileBi Renal agenesisIn uteroBi Renal hypoplasiaIn uteroUni > Bi Cystic Renal DyspIn uteroBoth Congenital Tumors of the kidney