Renal Flashcards

Question

Acute interstitial nephritis: casues

Answer 1

Allergic reaction in kidney Typically due to medications: - NSAIDs - PPI

Answer 2

History: - Drug hypersensitivity - Eosinophil > 10% in periphery Urine WBCs with negative culture (no infection) - Casts with no pyelonephritis - No urinary obstruction/inflammation of kidneys on imaging Gold standard diagnosis: kidney biopsy

Answer 3

Inflammation of glomeruli, typically auto-immune Urine sediment: - Dysmorphic RBCs - RBC casts, WBC casts - Proteinuria ``` Causes: Acute post-infectious glomerulonephritis Autoimmune diseases: - SLE - Polyarteritis nodosa - Henoch-Schonlein purpura - Goodpastures syndrome ANCA vasculitis (most common cause in hospital) ```

Answer 4

Small atheromatous crystals flecking off arterial wall--> kidney - After manipulation of arteries (post-embolization) - Loss of kidney function after 1-2 weeks - Urine bland, maybe eosinophilia - PE may show emboli (fingertips) - No specific treatment

Answer 5

1. Pre-renal: - replace fluid - CHF: treat arrhythmias, inotropes, reduce load 2. Post-renal: - Remove cause/bypass obstruction (EMERGENCY when creatinine begins to elevate) 3. Acute tubular necrosis: - No interventions will improve renal function after onset of acute tubular necrosis

Answer 6

1. Intravascular volume (overloaded): - low salt diet, water restriction - diuretic use 2. Hyponatremia: - restrict free water, avoid D5W in IVF???? 3. Hyperkalemia: - Renal diet, eliminate K/K-sparing diuretics - K-binding ion exchange resin in colon - Glucose/insulin, 50-100 mEq NaHCO3, albuterol, Ca-gluconate 4. Metabolic acidosis: - Sodium bicarb to maintain HCO3 > 15 5. Hyperphosphatemia, hypermagnesemia, hypocalcemia - Phosphate-binding agents - Avoid milk - Discontinue Mg-containing antacids (malox, mylanta) - Ca-gluconate, Ca-carbonate

Answer 7

1. Pre-renal: recovery complete if perfusion restored 2. Post-renal: almost complete recovery with fast resolution of obstruction (within 1 week) 3. ATN: - Mild injury: complete recovery - Prolonged oliguria: decreased recovery - > 50% mortality in ICU patients with ATN and HD support (Hemodialysis) 4. AIN: complete recovery after agent withdraw 5. Renal arteroemboli: rare recovery

Answer 8

(24 x age x ideal weight(kg))/ (72x (serum creatinine))

Answer 9

``` Based on creatinine clearance: Stage 1: normal GFR with signs of kidney disease Stage 2: GFR 60-99 (mild impairment) Stage 3: GFR 30-59 (moderate impairment) Stage 4: GFR 15-29 (severe impairment) Stage 5: GFR <15 Stage 6: renal replacement therapy ```

Answer 10

Mild: minimal fatigue, salt and H2O retention (edema, HTN) Moderate dysfunction: more fatigue and edema, mildly impaired cognition, appetite preserved Severe dysfunction: fatigue, loss of appetite (nausea, vomiting) - Symptoms= UREMIC

Answer 11

Asterixis Seizures Pericardial friction rub: serosanguinous pericardial fluid Lab abnormalities: - prolonged bleeding time (platelet dysfunction) - profound anemia - low calcium and high phosphate- sometimes with subperiostial bone resorbtion on x-ray - high alkaline phosphotase (secondary hyperparathyroidism) - low bicarbonate (metabolic acidosis) - high potassium

Answer 12

Treated with medical management: - Anemia (Hg 9-10: avoid transfusion) - Pulmonary edema - Vascular calcification (bone disease) - Severe acidosis - Bone disease Treated with renal dialysis/replacement: - Peripheral nervous system dysfunction - Pericarditis - Malnutrition

Answer 13

Renal disease tends to be progressive, even if an insult is recognized and eliminated Concept of progressive glomerular damage Hyperfiltration injury Efferent vs. afferent vasoconstriction Physician uses anti-hypertensives to preserve renal function (ACE-I, ARB) by lowering GFR - See slight elevations in creatinine (demonstrative benefit)

Answer 14

Type 1 diabetics: First 20 years: diabetes result in overt proteinuria in 15-20% of cases (if no proteinuria by 30 years, home free) - All who develop proteinuria also have retinopathy and/or neuropathy - Nephrotic range proteinuria (3+ g/day) - Followed by end-stage renal disease in 5 years Type 2 diabetics: - Less predictable (onset unknown) - May or may not include retinopathy/neuropathy - Same pathology

Answer 15

- Microalbuminuria = >30 mg albumin daily - Overt nephropathy > 300mg/day (nephrotic syndrome approximately 3,000 mg/day * * Routine urinalysis can’t detect microalbuminuria * * Microalbunuria portends nephropathy

Answer 16

- Controlling BP to less than 130/80 - Utilizing ACE inhibitors and ARB’s - Diuretics - Disrupt RAAS - Very tight blood sugar control - Type 2 outcome less predictable because of comorbidities like hypertensive renal disease, atherosclerosis, obesity * Now overt proteinuria =5%, ESRD= 0.8%

Answer 17

Begins with GFR < 60 ml/min - Progressive hemoglobin decline as GFR falls further - Major cause = erythropoeitin deficiency Treatment: - Recombinant erythropoeitin injections - Iron supplementation * Target Hgb 9-10 grams- NOT TO NORMAL Why correct anemia? - Increased feeling of well being - Reversal of LVH - Improved cognition - Improved cognition - Improved life expectancy - Forestall dialysis ?

Answer 18

- Desmopressin – increased multimeric form of factor VIII vonWillebrand factor (increases platelet “stickiness”) * * Tachyphylaxis after 2nd dose - Cryoprecipitate - Conjugated estrogen – delayed onset, longer effect - PRCB to hct > 30%

Answer 19

Cause= fall in serum bicarbonate Symptoms: - Normal anion gap, then high anion gap - Bicarb < 16 is symptomatic Treatment: - Oral bicarbonate or citrate: 30-40 meq daily usually does the trick

Answer 20

Renal osteodystrophy--> elevated PTH--> Osteitis fibrosa (cystica) Low bone turn over disease (osteoporosis) Osteomalacia

Answer 21

- High PTH due to: hypocalcemia, hyperphosphetemia, low calcitriol level, - Low calcium due to low calcitriol level - High phosphate due to decreased GFR - Result of increased PTH: too rapid bone turnover, abnormal bone (woven vs. trabecular) Management: - Maintain PTH at 2-3 times normal value (uremic bone resistance to PTH)-target varies with GFR (keep endogenous PTH low- Cinacalcet) - Begin measuring PTH in stage 3 kidney disease - Raise calcium to normal (vitD analogs, calcium carbonate, calcium acetate, calcitriol) - Keep phosphate below 5 (phosphate binder= calcium acetate, calcium carbonate, sevelamer,or lanthanum carbonate with meals) - Keep C X P < 55 - Kidney transplantation

Answer 22

High calcium X phosphate product; Low PTH - May result from overzealous management of PTH with phosphate binders containing calcium Result: vascular calcification, valvular calcification ** Most ESRD patients develop coronary calcifications

Answer 23

Historically iatrogenic Heavy metal (aluminum) deposits at calcification front in bone Don’t use aluminum hydroxide as a phosphate binder

Answer 24

Protein restriction: malnutrition vs. minimal renal preservation effect Potassium: 2 gram restriction. Usually clearance less than 25 ml/min Low phosphate with stage 3-4 CKD Sodium restriction: from day one Fluid – variable

Answer 25

Hemodialysis: thrice weekly for 4 hours per treatment in center - Short daily hemodialysis-home? - Nocturnal hemodialysis-home? - Peritoneal dialysis: at home, often at night * * Dialytic mortality: 24% annually

Answer 26

``` Deceased donor: - 95% one year patient survival - 90% one year graft survival - half-life 8-10 years - 4-6 year wait Live donor: - 98% one year pt - 94% one year graft survival - half-life 17 years ``` Donor issues: cadaver and live organ “quality” Recipient issues: age and comorbidity

Answer 27

- Surgical-bleed/hematoma/lymphocoele/MI - Immunosuppression risk = meds - Induction meds: IL2 receptor bockers, antithymocyte globulin - Calcineurin inhibitors-cyclosporine, tacrolymus - Antimetabolite = sirolimus, mycophenolic acid - Corticosteroids

Answer 28

2 x {Na+} + Glu/18 + Urea/2.8 * Can be directly measured by lab

Answer 29

"Effective osmoles"= Tonically active osmoles are confined to one side of cell membrane or the other - Water moves across ICF and ECF to maintain equal tonicity between compartments (since Na and K cannot move) Effective= Na, K, Cl, Mannitol Ineffective= urea, ethanol * Glucose can be effective or ineffective (depending on insulin) * Can NOT be directly measured by lab

Answer 30

RAAS responds to effective vascular volume (total body Na) Hypothalamus responds to tonicity (amount of water in spaces= concentration of Na) - Secretes ADH and stimulates sensation of thirst * 10% reduction in effective vascular volume overrides tonicity and stimulates hypothalamic secretion of ADH + thirst

Answer 31

Na is major osmole of ECF - Total body Na determines ECF volume - Stable hemodynamics is dependent on stable ECF volume (maintained by Na balance) Na Intake (dietary) = Na Output (renal and extrarenal) - Renal excretion of Na is the major way of regulate Na content in body * Extrarenal Na loss can outpace Na intake under certain conditions (diarrhea, burns, blood loss) leading to total body Na loss and abnormally low ECF volume (hypovolemia)

Answer 32

Abnormalities in total body sodium content - Normal total body sodium=euvolemia - Too little sodium=volume depletion/ hypotension - Too much sodium=volume overload/ edema

Answer 33

Abnormalities in sodium concentration= abnormalities of water balance - Too much water (relative to sodium) =hyponatremia - Too little water (relative to sodium) =hypernatremia

Answer 34

IVF used to give NaCl--> Isotonic Saline - Often called “normal saline” - Tonicity is comparable to the aqueous portion of blood IVF used to give water--> 5mg/dl dextrose - Often called “D5W” - Giving pure water IV would lyse red cells 5mg/dl dextrose is close to iso-osmolar initially, but the dextrose gets metabolized - This leaves behind water

Answer 35

Glomerulus: Na is freely filtered - Daily Na filtered= GFRxPna=180Lx140meq/L=25,200meq - Kidneys have an enormous capacity for Na excretion Tubules: >99% of filtered Na is reabsorbed - Daily Na intake 80 to 250 meq - Changes in daily Na intake only require very small adjustments in the rate of Na reabsorption - Increased renin/AngII/aldo activity leads to increased Na reabsorption

Answer 36

CAI (acetazolamide)= proximal tubule Furosemide= loop of henle Thiazide= Distal tubule Amiloride= Collecting duct

Answer 37

``` Decreased venous return to heart--> decreased CO--> decreased BP--> increased baroreceptor stimulation--> increased sympathetic tone--> increased renin secretion--> 1. Angiotensin II formation--> vascular constriction and Na reabsorption 2. Angiotensin II--> aldosterone--> Na reabsorption ```

Answer 38

insert water channels into collecting duct luminal surface to increase water reabsorption Medullary collecting tubule= water impermeable (without ADH) * Need high osmotic gradient between medullary lumen and interstitium - Allows for water to exit out of lumen down concentration gradient--> reabsorption Maximal urinary concentration= determined by osmotic gradient in medulla and ADH secretion (max 1200 osmol)

Answer 39

Osmole intake = 600-1000 mOsmol per day - Na, K, and protein (majority of osmol intake in western diet--> converted to urea) Osm intake must = osmol output - If ADH level fixed, Osm intake determines Urine volume (ex: Urine osm= 300 msosm/L, Osm intake= 600 mosm; urine volume= 2 liters (600/300))

Answer 40

- Hypertonicity - Habit (For normal people, drinking “8 glasses of water daily” has no proven health benefit!) - Dry mouth - Social conventions - True volume depletion - Effective volume depletion

Answer 41

Psychogenic polydipsia or compulsive water drinking - Normal individuals can excrete 12-15 liters/day of free water - Psychiatric illness or drugs for its treatment can interfere with water excretion Decreased water intake - Physical disability limiting access to fluids - Primary hypodipsia from lesions of the thirst center (rare) - Geriatric hypodipsia (common)

Answer 42

> 3 L of urine daily - Water diuresis: inability to concentrate urine: Uosm300 - “Mixed” diuresis: Uosm 150-300

Answer 43

``` High serum osmol: hyperglycemia Normal serum osmol: hyperlipid, protein Low serum osmol: everything else - Hypo-osmolar hyponatremia: to develop patient must have: 1. Fluid intake (IV/PO) 2. [Osm] of fluid in< [Osm] fluid out ```

Answer 44

1. Is kidney doing right thing? - tonicity too low - ADH should be absent (test for ADH with urine osmolality--> urine should be < 100 mosmol) * A low urine osmol that is NOT < 100 (ie there is still ADH or urine is not maximally diluted) when the plasma osmol is low means there is: - inappropriate ADH secretion OR - > 10% effective intra-vascular volume depletion (blood loss) - kidney damage (v. common) Urine Osm < 100 mosmol: - RARE conditions: psychogenic polydipsia, beer potomania (tea and toast diet), osmostat reset, or "you fixed it" hyponatremia

Answer 45

1. Evaluate volume states (hypo-, hyper-, eu-volemic) - History - Orthostatic vitals (HR)- change of > 10% when sitting--> standing - Urine [Na] < 20 mEq/L (volume depleted) - Rule out diuretcs, kidney disease, etc.

Answer 46

Determined by Extra-cellular fluid volume CHF Cirhosis Nephrosis

Answer 47

``` GI losses Sweating Thiazides Cerebral Na wasting Aldosterone deficiency ```

Answer 48

SIADH Glucocorticoid deficiency (glucocorticoids prevent fluid overload) Hypothyroidism Reset Osmostat (hypothalamus damaged--> fluid balance reset at new level causing fluid overload)

Answer 49

``` Idiopathic Drugs (ADH release enhanced): - TCA, amitrptyline, haldol, morphine, vincristine, cyclophosphamide Drugs promoting ADH action: - ASA, NSAIDs Cancers: SCLC (paraneoplastic syndrome Brain damage Meningitis Infections Hypothyroidism ```

Answer 50

Normal saline Indications: 1. Dangerous hypovolemia (organ dysfunction, unstable vitals) --> bolus regardless of effect on hyponatremia 2. Mild-moderate hyponatremia and: - Clearly due to volume depletion - SIADH with urine electrolyte content < Saline (Electrolyte content = 2 x (U[Na] + U[K]), Can lower urine electrolyte content by giving Lasix) - Benefit: Less risk of over-correction, Easier to fix volume status (since you can give more) - Risks: 1. Can worsen hyponatremia in SIADH 2. If urine electrolyte content > saline electrolyte content, then water from saline will be retained in body 3. Over-correction still possible especially in hypovemic hyponatremia: - Volume status restored before resolution of hyponatremia --> ADH drops to zero. Brisk water diuresis ensues--> rapid over-correction. - Important example of “You fixed it” hyponatremia Hypertonic saline * only used in severe cases (CNS symptoms; Na < 120 mEq/L; unsure if SIADH vs volume depletion, but don't want drop in [Na]) - Benefit: Increases Na regardless of cause of hyponatremia - Risk: Can over-correct, and delays restoration of volume status in patient with undetected volume depletion

Answer 51

Fluid restriction: +/- Hypertonic Saline (+/- Lasix) +/- Vaptan (largely experimental- blocks ADH effect) +/- NaCl or Urea tablets (chronic management) +/- Demeclocycline (chronic management)

Answer 52

Fluid restriction Lasix +/- Vaptan (largely experimental)

Answer 53

If [Na] > 120, probably not an emergency If [Na] < 120, then need to guess how well-compensated patient is: - How quickly did this happen? (prior serum [Na]?) - The faster the change, the more dangerous - Is patient symptomatic? Mild: Nausea, Headache Moderate: Mental Status Change (can be subtle) Severe: Seizure, Coma, Death * Reversing disorder needs to be done gradually (over a couple of days) to avoid other complications of disrupting homeostasis - Order FREQUENT LABS for serum [Na] and admit to ICU for close monitoring

Answer 54

``` Osmotic demyelination: Signs/Symptoms: - Dysarthria/Dysphagia - Weakness/paresis - Seizures - Lethargy/confusion/obtundation/coma - Often irreversible Occurs 2-6 days after over-correction ``` * Incidence: Unknown (Probably not that frequent) High risk groups: - Overcorrection: >12 mEq [Na] over 24 hours - Females who have not had menopause - Alcoholism - Malnutrition, liver disease, hypokalemia

Answer 55

Water! - Give isotonic solution as bolus to avoid tonicity disorder Do NOT bring serum [Na] down by more than 12 mEq/day

Answer 56

* Cannot reach urine osmol of 600 or more Central: no ADH secretion - Should be corrected by dDAVP - Treatment: dDAVP (or excess water intake) Nephrogenic: kidneys don't respond to ADH - Will not correct with dDAVP - Treatment: discontinue offending meds, administer thiazide diuretics (paradoxical), NSAIDs, Na-restriction

Answer 57

Congenital anomalies of the kidney and urinary tract (CAKUT) due to: - Malformation of renal parenchyma resulting in failure of normal nephron development--> renal dysplasia, renal agenesis, renal tubular dysgenesis, and polycystic renal diseases. - Abnormalities of embryonic migration of the kidneys as seen in renal ectopy (eg, pelvic kidney) and fusion anomalies, such as horseshoe kidney. - Abnormalities of the developing urinary collecting system as seen in duplicate collecting systems, posterior urethral valves, and UPJ obstruction Kidneys are variable in size but most are smaller - Discovered during routine antenatal screening.(increased echogenicity as a result of abnormal renal parenchymal tissue, poor corticomedullary differentiation, and parenchymal cysts.) - By 20 weeks gestation, fetal urine accounts for 90 percent of the amniotic volume. Oligohydramnios is a clue . - Associated urological findings- abnormalities of the renal pelvis and calyces (congenital hydronephrosis) and ureters (duplicating collecting system), megaureter, ureteral stenosis, and vesicoureteral reflux (VUR). - Symptomatic presentation due to urinary tract infection, hematuria, fever, and abdominal pain Clinical: Important Contributor to ESRD in children (Especially in bilateral disease) - In past, thought was that progressive loss of renal function was due to associated collecting system abnormality leading repeated bouts of pyleonephritis - Modern belief is that parenchymal abnormalities are the cause of progressive decline in renal function Management: - Medical prophylaxis of UTI versus surgical correction of collecting system abnormalities - No convincing evidence that surgery is superior - Severe reflux with very frequent and/or severe UTI’s is nevertheless often managed surgically. - The rate of spontaneous resolution is dependent upon age, grade of reflux, and whether the reflux is unilateral or bilateral.

Answer 58

Types: - Autosomal dominant polycystic kidney disease - Autosomal recessive polycystic kidney disease - Medullary sponge - Mdullary cystic disease/nephronophthisis - Simple renal cysts- few, no disease - Acquired cystic disease of renal failure

Answer 59

AKA—Adult Polycystic Kidney Disease - Common congenital disease—1/1000 births - Accounts for 5% of all adult renal failure - Initial symptoms occur between 30 & 50 yrs - Back pain is most common complaint - Half of all ADPKD pts will require transplantation or dialysis Symptoms: - Typically asymptomatic until the fourth decade of life - loin “fullness” - Palpable flank masses in adults - Hematuria (gross clots) - Azotemia - Uremia Pathogenesis: - 85% of cases show mutation in PKD 1 gene on chromosome 16 (40s-50s, worse outcome) » Protein = polycystin-1 – 15% of cases show mutation in PKD 2 gene on chromosome 4 (70s-80s, better prognosis) » Protein = polycystin-2 – Both proteins reside in tubular cell cilia » Defects affect calcium signaling » Mutations result in abnormal renal tubular growth Gross pathology: - Bilateral Enlargement - Up to 4500 g - Distorted shape - Multiple cysts of varying sizes filled with clear, straw-colored fluid Histo: - Simple cysts lined by flattened cuboidal and columnar epithelium - Arise from proximal and distal tubules as well as from the collecting ducts - Normal renal parenchyma can be present between the cysts Associated path: - Hepatic Cysts—33% of cases - Splenic Cysts—10% of cases - Pancreatic Cysts—5% of cases - Cerebral Aneurysms—No Family history- 6 % prevalence, family history -21% prevalence. - Diverticular Disease of the colon often seen

Answer 60

``` Supportive Care – Monitor Creatinine – Aggressive blood pressure control » ACEI, especially if there is evidence of proteinuria. » Avoid caffeine, DASH diet ``` Future therapies: – Vaptans (ADH antagonists) have been effective in animal studies in preventing progression – Human Studies are ongoing Antibiotics: - Some drugs do not penetrate cysts well. - Fluoroquinolones, TMP- sulfa, chloramphenicol best for cyst penetration. - Do not adjust dose for UTI in renal insufficiency.

Answer 61

AKA—Infantile Polycystic Kidney Disease - Rare—1/10,000 to 1/50,000 births - 75% of affected infants die perinatally - Rare cases can manifest in older children Clinical correlates: - Results in Oligohydramnios (decreased amniotic fluid as fetal kidneys can't properly filter blood, produce urine) - Causes Pulmonary Hypoplasia due to mass effects - See Associated Hepatic and Pancreatic Cysts - Infants often have biliary dysgenesis and hepatic fibrosis Pathogenesis: Mutations in the PKHD1 gene - Protein = fibrocystin - Fibrocystin is involved in cell proliferation and adhesion - Fibrocystin is found in the kidneys, liver, and pancreas Pathology: - Disease is Bilateral - Enlarged Kidneys (often impede delivery) - Fusiform Cysts of Collecting Ducts – Affects cortical and medullary ducts - Cysts Arranged Radially, Perpendicular to renal capusule - Accompanying interstitial fibrosis and tubular atrophy (due to compression)

Answer 62

``` Nephrocalcinosis with hypercalemia and hypercalciuria: associated with systemic problems: - Primary hyperparathyroidism – Sarcoidosis - Vitamin D therapy - Milk alkali syndrome ``` Nephrocalcinosis without hypercalcemia but presence of hypercalciuria- not systemic problem – Distal RTA - Medullary sponge kidney - Premature infant with lasix usage

Answer 63

Unknown pathogenesis: Epidemiology: - Sex predilection-slight male predominance - Symptomatic cases usually emerge at 30-60 yrs - Nonhereditary Symptoms: - flank pain, dysuria, hematuria, gravel sized stones. - Hypercalciuria in 50% of symptomatic pts Clinical course: - Increased risk of kidney stones and urinary tract infection - Excellent long-term prognosis – progressive disease very rare Pathology: - May be associated with hemihypertrophy - bilateral in 75% of patients - Cysts involve the branches of collecting ducts and papillae - Glomeruli are normal if secondarily affected by distal obstruction - Kidneys are not enlarged and are symetrical - Discovered in work-ups of nephrolithiasis Microscopic – Flattened cuboidal or transitional epithelium – Intracystic calcifications – Associated intersitial inflammation

Answer 64

- Acute tubular injury due to hypotension/ sepsis - Staphylococcal pyelonephritis with abcess formation. - Obstructive uropathy - Prerenal from volume depletion (febrile)

Answer 65

Etiology: - Ischemic - Toxic - Inflammatory - Immunologic - Atrophy - Viral Management: - Keep Mean arterial pressure>65 - No nephrotoxins - Adjust Antibiotics dosage - Once euvolemic, cautiously give IVF based on insensible losses and urine output - Assess need for renal replacement therapy based on daily labs and clinical picture.

Answer 66

Infectious causes - A recently (within last 2 weeks) treated UTI - Chlamydial urethritis - Prostatitis - Appendicitis – if appendix lies close to ureter or bladder - Renal tract tuberculosis - Adenovirus, BK,rejection – in immunocompromised patients Non infection related - Recent cystoscopy and urinary tract surgery - Urinary tract stones - Urinary tract neoplasm - Interstitial nephritis - Polycystic kidneys - Interstitial cystitis-( cystoscopy shows inflammation with ulceration) - SLE and other systemic inflammatory diseases, Kawasaki disease

Answer 67

Causes: - DRUGS: NSAIDS, PCN, cephalosporins, rafampin, cimetidine, ciprofloxacin, allopurinol - Infections: legionella, mycobacteria, streptococcus, CMV, BK polyoma etc - Idiopathic- 8%  Autoimmune disorders-SLE, sarcoidosis, Sjögren's syndrome. - TINU (tubulo-interstital nephritis and uveitis) syndrome- flank pain, sterile pyuria, hematuria, proteinuria (usually subnephrotic range) and uveitis. Histo: - Key is eosinophilic infiltrate in interstitium - Variable amount of interstitial edema - Can see “spill-over” effects on glomerulus - Interstitial fibrosis is dependent on duration of disease.

Answer 68

Path: - Acute inflammation of tubules - Secondary tubular damage - Spill-over into interstitium - Neutrophilic casts in tubular lumens - Casts may be seen in urine Symptoms: - Cystitis- dysuria,frequency,urgency, suprapubic pain, and/or hematuria. - Pyelonephritis consist of the above symptoms (symptoms of cystitis may or may not be present) plus fever (>38oC), chills, flank pain, costovertebral angle tenderness, and nausea/vomiting Management: * Untreated cases can lead to chronic pyelonephritis 1. Complicated Cystitis: - oral fluoroquinolone such as ciprofloxacin (500 mg orally twice daily or 1000 mg extended release once daily) - levofloxacin (750 mg orally once daily) for 7 to 14 days. - Avoid moxifloxacin.. 2. Complicated Pyelonephritis — should be managed initially as inpatients. Use broad spectrum antibiotics while awaiting susceptible testing 3. Underlying urinary tract anatomic or functional abnormalities (such as obstruction or neurogenic bladder) should be addressed in consultation with an urologist. Complications requiring hospitalization: Diabetes - Pregnancy - History of acute pyelonephritis in the past year - Symptoms for seven or more days before seeking care - Broad-spectrum antimicrobial resistant uropathogen - Renal failure - Urinary tract obstruction - Presence of an indwelling urethral catheter, stent, nephrostomy tube or urinary diversion - Recent urinary tract instrumentation, Renal transplantation, Immunosuppression

Answer 69

Histo - tubular atrophy - interstitial fibrosis - tubular protein casts - Lymphocytes and plasma cells in interstitium - Pathology is dependent on chronicity of inflammation - Secondary Glomerular changes occur - Uncommon cause of interstitial disease

Answer 70

``` Bicarb= 25 mmol/L pCO2= 40 mmHg pH= 7.42= 6.1 + log[25/(0.03x40)]= 6.1 + log(20.8) ```

Answer 71

``` Monobasic-dibasic phosphate HPO42-/H2PO4- = pK 6.8 Ammonium-ammonia NH4+/NH3= pK 9.2 Lactic acid-lactate = pK 3.9 Deoxygenated hemoglobin= pK 7.9 Oxygenated hemoglobin= pK 6.7 Serum proteins (albumin, immunoglobulins) ```

Answer 72

1. Addition of H+ ions to the body from endogenous (e.g., lactic acid) or exogenous (e.g., salicylic acid) sources. 2. Loss of HCO3- from body fluids via GI tract (diarrhea) or the kidneys (renal tubular acidosis). 3. Decrease in the ability of the kidneys to excrete acid (acute or chronic renal failure). 4. Rapid dilution of the extracellular fluid with a non- HCO3- solution (so-called dilutional acidosis). * In simple metabolic acidosis, serum HCO3 is ALWAYS lower than 25 (normal value)

Answer 73

``` Anion Gap (AG)= Na+ - (Cl- + HCO3-) Normal AG= 10-12 ``` * Adding any acid to blood (besides HCl)--> anion gap > 10 Causes: - Lactic acidosis - Ketoacidosis - Toxins (salicylate, methanol, ethylene glycol) - Renal failure - Rhabdomyolysis - Toxic shock

Answer 74

Hyperchloremic non-Anion Gap Acidosis: - Add HCl to blood- buffer 10 meq of H+ with 10 mEq HCO3- - Simultaneously, 10 mEq Cl- is added (part of anion gap equation) - Anion gap does not change, but acid was added to blood Causes: - GI losses of bicarb due to: diarrhea, panreatic drainage, anion exchange resins - Expansion acidosis (inappropriate fluid replacement with large volumes of isotonic saline---> dilutes HCO3, raises Cl-) - Proximal Renal Tubular Acidosis: kidney can't resorb bicarb (also seen withcarbonic anhydrase inhibitors) - Distal Renal Tubular Acidosis: Impaired H+ ion secretion (renal insufficiency, distal RTA) - Hypoaldosteronism (hyperkalemia--> decreased kidney production--> decreased NH4Cl excretion) - Parenteral hyperalimentation, addition of HCl, recovery from ketoacidosis

Answer 75

Administration of too much bicarb--> imbalance between bicarb and pCO2 1. patient attempts to increase pCO2: 2. Stops breathing to increase pCO2 * NO benefit in giving NaHCO3 to patients in severe DKA, regardless of pH * Unsure about giving bicarb for shock-induced severe lactic acidosis

Answer 76

Respiratory: Kussmaul’s breathing (blowing off CO2) Cardiac: decreased contractility, hypotension. Increased ionized Ca2+: - H+ and Ca+2 compete for binding to albumin. - Increased H+ (acidosis)--> unbound Ca+2 - If a patient is already hypocalcemic (low ionized Ca2+) while he is suffering from metabolic acidosis, correction of metabolic acidosis (without first or concomitantly correcting hypocalcemia) will worsen hypocalcemia and precipitate tetany. Systemic arterial vasodilatation: hypotension. Demineralization of skeleton (chronic metabolic acidosis); - H+ is buffered by bone. - In distal renal tubular acidosis, filtered PO42- and SO42- require cations for excretion since H+ excretion is not adequate--> Ca2+ and Mg2+ are lost in urine.

Answer 77

1. Always try to treat underlying cause: fluids, vasopressors, antibiotics for septic shock; IABP, inotropes, etc., for cardiogenic shock; fluids and insulin for diabetic ketoacidosis. 2. Calculate HCO3- deficit: if you decide to give NaHCO3, then calculate HCO3- deficit as follows: - Total Body Water = Body Weight x 0.6 Liters - HCO3- deficit = (25 – [HCO3-]) x TBW - e.g., 70 Kg man, serum [HCO3-] = 10 meq/L - HCO3- deficit = (25 –10)meq/L x 42L = 630 meq. 3. Replace ½ of HCO3- deficit in 1st 24 hours, and the remaining ½ in next 48 hours. - e.g., in above case, want to give 315 meq HCO3- in 1st 24 hours. - Put 3 amps (150 meq total) NaHCO3 in 1L of D5W. 2L of this fluid will give 300 meq of NaHCO3. Rate of IV infusion = 2000ml/24 hr = 83 ml/hr. 4. Don’t forget to correct hypocalcemia if present.

Answer 78

Proximal tubule: 1. Carbonic anhydrase present in lumen (nowhere else) 2. H+ secreted by Na+/H+ exchanger in apical membrane 3. H+ combines with HCO3- to form H2CO3 4. Carbonic anhydrase: H2CO3--> H2O and CO2 5. Carbonic anhydrase: CO2--> proximal tubular cell--> HCO3--> reabsorbed (80-90%) Distal tubule/collecting duct (intercalated cells): 1. H+ secreted by H-ATPase--> forms H2C)# in lumen--> dissociates to H2O and CO2 (slowly reabsorbed) - 5% in loop of Henle, 3% in distal tubule, 1-2% in collecting duct

Answer 79

Loop, thiazide diuretics Inadequate intake GI losses, sweating Diabetic ketoacidosis Hypomagnesemia Alkalosis Hyperaldosteronism Congenital: - Bartter's syndrome - Gitelman's syndrome - Liddle's syndrome

Answer 80

1. Increased Na+ reabsorption : Proximal tubular H+ secretion is linked to Na+ entry. In the distal tubule, enhanced Na+ reabsorption increases lumen electronegativity. 2. Mineralocorticoids: Increased Na+ reabsorption in the distal nephron (increased ENaC channels), increased H+-ATPase activity. 3. Increased pCO2: Increased intracellular acidosis. 4. Hypokalemia: increased ammoniagenesis. * * With volume contratction, renal blood flow decreases--> 1. Decrease GFR : decrease filtered NaCl, NaHCO3 and H2O. 2. Increase Proximal Reabsorption of both Na+ and HCO3-. 3. Increase renin/angiotensin II/aldosterone: enhance distal Na+ reabsorption and H+-ATPase, leading to increased HCO3- reabsorption.

Answer 81

Due to: 1. Volume contratction (decreased effective circulatory volume) 2. Persistant Hypokalemia 3. Both Causes: - Vomiting/gastric drainag - Diuretic therapy inhibiting NaCl reabsorption (Furosemide, ethacrynic acid, metolzone, bumetanide, thiazides) - Sudden relief of chronic hypercapnia - Congenital chloridorrhea (diarrhea) - Administration of alkali - Resistance to chloride (excess mineralocorticoids, Bartter's syndrome, Severe K+ depletion)

Answer 82

1. decreased ionized Ca2+: paresthesias, carpopedal spasm. 2. decreasedrespiratory drive: decreased pO2, increased pCO2. Important if you are trying to wean your patient from the ventilator. 3. decreased K+: polyuria, polydipsia, muscle weakness

Answer 83

Acute: - Airway obstruction (aspiration, laryngospasm, bronchospasm) - Circulatory catastrophes - CNS depression - NM impairment - Ventilatory restriction Chronic: - COPD - NM diseases - Ventilatory restriction - CNS disorders

Answer 84

- Hypoxia (high altitude, V/Q mismatch, hypotension) - CNS - Drugs/hormones (salicylates, nicotine, dinitrophenol, xanthines, pressor hormones, progesterone) - Pulmonary diseases (interstitial fibrosis, pneumonia, pulmonary edema, embolism) - Other (pregnancy, hepatic failure, gram-neg septicemia, heat) - Mechanical overventilation

Answer 85

1. Respiratory acidosis: Acute: ^HCO3= 0.1^(pCO2) - or 1 mEq increase in HCO3 for 10 mm Hg increase in PCO2 Chronic: ^HCO3= 0.3^(pCO2) - or 3.5 mEq increase in HCO3 for 10 mm Hg increase in PCO2 2. Respiratory alkalosis Acute: ^HCO3 = 0.2 ^pCO2 - or 2 mEq drop in HCO3 for 10 mm Hg drop in pCO2 Chronic: ^HCO3= 0.4 ^pCO2 - or 5 mEq drop in HCO3 for 10 mm Hg drop in PCO2 ^= delta (change in value)

Answer 86

1. pCO2= 1.5 x HCO3- +8 +/- 2 (Winter's formula) 2. pCO2= 15 + HCO3- 3. pCO2= last 2 digits of pH

Answer 87

Specific gravity of water= 1.000 Specific gravity of urine= 1.0XX (higher= more dehydrated) pH of urine= 5-6.5 ``` Contents of blood: Protein in blood: - Red blood cells (heme) - Myoglobin Heme Nitrites (Nitrate breakdown from UTI) Ketones (low sugar diet--> ketogenesis) Glucose (diabetes) ```

Answer 88

Kidneys develop in utero; issues with development can be clinically important 1. Single kidney (can survive without awareness of absent kidney) 2. Kidney malrotation and duplication - Collecting system faces laterally, passes over anatomic structures - Can develop uro-pelvic junction obstruction (painful, UTIs, hydronephrosis) 3. Horseshoe kidney: - Common malformation in Turner's (45X) 4. Polycystic kidneys 5. Potter syndrome: - Congenital absence of kidneys - Oligohydramnios--> less fluid in sac--> abnormal limb development - Dies from lung failure due to inadequate fluid in amniotic sac 6. Multiple ureters, can be attached to various structures 7. Uretocele: obstructs ureters from emptying into bladder 8. Vesicoureteral reflux: on urination, moves back up toward kidney - Scale of 1-5 (5= worst, more UTIs, hydronephrosis) 9. "Prune belly syndrome"- no abdominal musculature, organ malformation

Answer 89

``` Asymptomatic UTIs Hematuria Renal insufficiency/hypertension Obstruction Wilm's tumor ```

Answer 90

GFR: Increases with age- comparable to adult levels at 2-3 years Osmolarity: increased ability to concentrate urine Capacity: increases with age - 2 ounces at birth - 1 ounce per year until adulthood Decreased ability to reabsorb bicarbonate - Lower serum bicarb in children than adults (19 vs 24) - Children compensate with higher respiratory rate

Answer 91

Concentrated urine Bile Medications (rifampin, coumadin, flagyl) Urate

Answer 92

Blood (RBCs, hemoglobin) Myoglobin Medications (phenothiazines, dilantin) Food (beets, blackberries, red dye)

Answer 93

Medications (amitryiptyline, methylene blue, indomethacin) | Pseudomonas infection

Answer 94

Hemoglobinuria Hematuria (renal, extrarenal) Glomerular: casts, red cell morphology, concurrent proteinuria, cola colored, concurrent hypertension and edema - Vasculitis (Henoch Schonlein purpura, HUS) - Glomerulonephritis - Recurrent hematuria syndrome Non-glomerular: - UTI - Trauma - Nephrolithiasis, hypercaciuria - Hemoglobinopathies - Renal malformations - Medications - Tumors

Answer 95

Normal 70 Kg man= 3500 mEq of K - 98% distributed in intracellular compartment - 75% in muscle - 2% in extracellular fluids ``` Body distribution of K: RBC (250 mEq) Muscle (2635 mEq) Liver (250 mEq) Bone (300 mEq) ``` Body fluid K: - Normal serum K = 3.5 to 5 meq/L - Extracellular K is freely filterable. - Normal intracellular K = 120 to 150 meq/L Excretion: - Urine< 20-25 mEq/day - Stool= 5-10 mEq/day

Answer 96

Location: collecting duct Main job= moving potassium out of kidney (Pee K out) Tubular lumen: - Na channel (move Na in) - K channel (move K out) Capillary side: - ATPase (Na out of cell into blood, K into cell) - Aldosterone Receptor: opens Na channel on luminal side)--> electronegative gradient set up in lumen--> K moves out

Answer 97

Absorbs potassium (keep K In) Tubular lumen: - H+ ATPase: pumps H+ out - K/H+ ATPase: K+ in, H+ out Capillary side: - Cl- moves into cell, HCO3- moves out (into blood)

Answer 98

Resting membrane potential (Em) is greatly influenced by shifts in extracellular potassium (Ke) - Will lead to dramatic changes in cardiac rhythm, NM function

Answer 99

Decrease: - Insulin - Beta-2 stimulation - Alkalosis - Anabolism Increase: - Mineral acidosis (H shifts into cells, K out) - increased tonicity - Beta-blockade - alpha-stimulation

Answer 100

Promotes entry of K into skeletal and hepatic cells by increasing Na-K ATPase - Also causes hyperpolarization--> passive entry * Remember that patients with severe hyperglycemia are already K-deprived--> treating with insulin can worsen this

Answer 101

Beta-agonists--> increased aldosterone (hypokalemia) Alpha-agonists/ beta-blockers--> decreased aldosterone (hyperkalemia) MOA: - Beta-2-adrenergic agonists activates Na-K-ATPase --> increased K uptake in liver and muscle. - Beta-adrenergic receptors in muscle also activates Na-K-2Cl cotransporter, (1/3 of K uptake response to catecholamines) - Beta-adrenergic agonists impair the ability to buffer increases in K due to IV loading or exercise. The cellular mechanism is unknown. * Propranolol (Beta blocker, non selective)--> decreased aldosterone--> can cause hyperkalemia * Chronic digitalis use can increase risk of hypokalemia * atenolol (beta 1 blocker, selective)= will not effect K levels

Answer 102

Acute acidemia shifts H into cells and K out of cells. - Acute acidemia also inhibits distal tubular secretion of K. - In general, a 0.1 unit decrease in pH will increase serum K by 0.5 to 0.6 meq/L - Metabolic acidosis causes a more pronounced increase in serum K than respiratory acidosis. * More commonly caused by mineral acidosis

Answer 103

Hyperglycemia is clinically the most common cause of hypertonicity. - Other causes: hypertonic mannitol, hypernatremia - Hypertonicity shifts K and water out of cells. * * Important cause of hyperkalemia in diabetic patients, especially in hyperosmolar nonketotic coma. * * In diabetic ketoacidosis, hyperkalemia is not as marked because of associated severe K deficiency.

Answer 104

Small increases in plasma K stimulates aldosterone release--> distal K excretion 1. Elevated plasma K--> increased aldosterone 2. Aldosterone--> Na absorption via EnaC channel--> electronegative lumen 3. Increase transport of Na out, K in via Na K ATPase pump on capillary side--> increased intracellular K conc. 4. Increased intracellular K--> Opens up ROMK channels for K excretion.

Answer 105

Na enters the cell via amiloride-sensitive ENaC, resulting in the generation of lumen-negative potential in the cortical collecting duct. - This negative lumen potential drives K exit via ROMK (small K) and Ca-activated K (maxi-K) channels. - Increases in distal Na delivery, increase in K secretion. - When luminal Na is < 8 meq/L, K secretion ceases

Answer 106

Aldosterone increases ENaC activity: 1. re-distributes ENaC from cell interior to plasma membrane 2. Decreases ENaC ubiquitination and degradation (aldosterone activates serum glucocorticoid-induced kinase 1 (SGK-1) which phosphorylates Nedd4-2. Phosphorylated Nedd4-2 cannot bind to the PPxY motif of ENaC, resulting in failure to ubiquitinate ENaC). 3. Increases open probability of ENaC (channel activating protease 1 or CAP-1). - Increases ENaC activity results in increased apical Na entry, making the lumen more negative, favoring K secretion via ROMK and Maxi-K channels. - Aldosterone also increases expression of Na-K-ATPase in CCD

Answer 107

- Increase in distal flow rate, increased K secretion. - This is because lower tubular fluid K concentration due to K free fluid from more proximal segments and therefore high concentration gradient maintained. - Most likely mediated by Ca-activated K channel (Maxi-K) channels.

Answer 108

Acute metabolic/repsiratory acidosis: decrease K secretion by decreasing apical Na/K channel conductances in CCD Chronic metabolic acidosis: increases K secretion by inhibiting proximal tubule Na and fluid reabsorption, thereby increasing distal Na delivery. Acute metabolic or respiratory alkalosis: increases K secretion by increasing channel open probability.

Answer 109

Increased filtration fraction (due to low blood levels): 1. Increased proximal Na reabsorption--> Decreased distal Na delivery--> 2. RAAS activation--> increased aldosterone--> * BUT, no Na to be reabsorbed in distal tubule--> K is not dumped - Hypokalemia will not ensue

Answer 110

Decreased filtration fraction: 1. Decreased proximal Na reabsorption--> Increased distal Na delivery 2. decreased JG activity--> decreased renin--> decreased aldosterone * Aldosterone decreases (decreasing Na reabsorption--> potential hyperkalemia) BUT Na reabsorbed in distal tubule--> more K dumped - No hyperkalemia

Answer 111

- Cell injury (rhabdo, tumor lysis, massive hemolysis, ischemia) - toxins, drugs (digoxin, succinylcholine) - DKA (hypertonicity--> solvent drag moves K out with water), non-ketotic hyperosmolar states - Hyperkalemic periodic paralysis

Answer 112

Inorganic (mineral acids like HCl): causes K shifts - H moves in (without Cl)--> K must move out Organic acidosis examples: - DKA (insulin deficiency, hypertonicity) - Lactic acidosis (cell ischemia) - Epsilon aminocaproic acid, IV lysine/arginine

Answer 113

- Decrease in mineralocorticoid activity (no Na channel activation, K does not go out) - Decreased distal sodium delivery: oliguric ARF, glomerulonephritis, CHF, hepatorenal - Abnormal cortical collecting duct (drugs, tubulo-interstitial disease, urinary obstruction--> backward pressure in collecting ducts--> electronegative charge in lumen disrupted--> impeded secretion)

Answer 114

Diabetics: microvascular disease of JG cells; hyperrenin, hyperaldosterone NSAIDs: inhibits renin release (due to decreased prostaglandin synthesis) Beta blockers: propanolol predisposes to hyperkalemia, block adrenergic system--> hyporeninism hypoaldosteronism Cyclosporin: suppress renin release ACE-I: prevent Angiotensin-I going to angiotensin II ARBs: Angiotensin II can't produce aldosterone Heparin: inhibit aldosterone biosynthesis in adrenal gland Azole antifungals: inhibit aldosterone synthesis (ketoconazole> diflucan) Spironolactone/eplerinone: prevent aldosterone from binding Drugs inhibitng ENaC channel (amiloride, triamterine, rifampin, amiloride

Answer 115

TdP, arrhythmias

Answer 116

Ca gluconate: prevent arrhythmias Glucose-insulin: move K back into cells (with glucose to prevent hypoglycemia, except in diabetics Beta-agonists (higher concentrations): stimulate Na/K ATPase NaHCO3: temporary measure Kayexalate: dump K from body - Oral (4 hours- binds more K in intestine) or rectal (2 hours) Dialysis: physically remove K from blood - Diffusion of K out of body

Answer 117

Stop offending meds Low K diet (70 mEq/day) Assess volume, BP status - Can use florinef (mineralocorticoid--> stimulate aldosterone receptors) - Loop diuretics (dump K) - NaHCO3 Kayexalate: can cause GI ulceration (don't give in post-op ileus, bowel obstruction)

Answer 118

Caused by: - Cellular shifts: insulin, -adrenergic agonists, anabolism - Inadequate dietary intake: alcoholism or anorexia nervosa - GI losses: NG suction, vomiting, diarrhea (villous adenoma of colon), laxative use * * LOWER GI losses cause hypokalemia; upper GI losses (NG suction)--> alkalosis--> hypokalemia - Hypokalemic periodic paralysis: mutated L-type Ca channel. - Renal K wasting. - Ureterosigmoidostomy: secretion of K and HCO3 in exchange for Na and Cl in colon.

Answer 119

AML: metabolically active cells take up K with marked leukocytosis (test tube phenomenon) - Prevent by storing blood at 4 degrees C

Answer 120

- Anabolism: Rx of pernicious anemia, TPN, rapidly growing leukemia and lymphomas. - Hypothermia (K moves intracellularly- don't aggressively correct K as it will move back out as they warm up) * * QRS prolonged, PR prolonged, brady, amplitude decreases, giant osbrone wave or j wave - Barium and chloroquine intoxication (RARE- poisons Na/K pump) - Hypokalemic periodic paralysis

Answer 121

Intermittent acute attacks of muscle weakness with low K and often low phos and low Mg. Triggered by large CHO meals, rest post exercise; two forms: 1. AD, mutation in alpha 1 subunit of DHP sensitive Ca channel 2. Thyrotoxicosis: Asians and Mexicans - Only K replacement for acute attack and then stop (episodic) - Long term management: B2 blockade (propanolol- moves K extracellularly, prevents thyrotoxicosis (T3-T4 conversion), acetazolamide, low carb diet, Rx hyperthyroidism

Answer 122

Most common finding: Urinary K renal K loss due to alkalosis from loss of stomach HCl - Clay ingestion: (binds K in GI tract, also see low Fe); but red clay associated with hyperkalemia (contains K). - Chloridorrhea, villous adenoma, chronic laxative abuse (colon effect) - High volume profuse diarrhea involving small bowel.

Answer 123

Laxative effect on colon---> K depletion--> 1. Intracellular acidosis--> Increased renal NH3 production (to deplete H overload)-->Increased urinary excretion of NH4Cl 2. Increased intercalated cell H+/K ATPase activity ** Generates metabolic alkalosis

Answer 124

Urinary K > 20 mEq/day with no history of diarrhea - Coupling of increased distal sodium delivery, increased mineralocorticoid activity Increased EABV--> decreased Na reabsorption (Na dumping) + high K in urine asdfasdf what??

Answer 125

Primary hyperrrenism: - Elevated renin, aldosterone - Saline suppression test - Differential diagnosis: malignant HTN (50% hypokalemic due to pressure natriuresis), RAS (15% hypokalemic) Primary Hyperaldosteronism: - Elevated aldo, depressed renin - Differential: Conn's syndrome, bilateral adrenal cortical hyperplasia ``` Increase in non-aldo mineralocorticoid: - Depressed renin and aldosterone Differential: - Cushing's - Congenital adrenal hyperplasia (11-beta hydroxylase deficiency= virilization, 17-alpha hydroxylase deficiency= decreased sex hormones) - Liddle syndrome ```

Answer 126

Non-responsiveness to aldosterone: Mutation causing Na channel to be open all the time (not responsive to aldosterone) - Leads to Na retention, K loss Symptoms: - Hypertension - Hypokalemia - Metabolic alkalosis-like hyperaldosteronism, decreased renin, aldosterone Treatment: - Na restriction - Drugs blocking Na channel: triamterene, amiloride

Answer 127

Diuretics (acting on proximal collecting duct) - Causes volume depletion--> high aldosterone--> hypokalemia Magnesium deficiency - Mg deficiency inhibits thick ascending limb Na absorption - important cofactor for ATP production; TAL uses ATP--> depletion--> less Na reabsorption (more K dumping) - Similar to 10 mg lasix dose Non-reabsorbable anions: - Sodium dragged distally due to nonreabsorbable anion - Aldosterone+ sodium coupled--> K wasting - DKA, carbenicillin, ticarcillin can also drag Na distally Bartter's syndrome: - Like being on Lasix: Cl-channel mutation (type 3- only type that survives to adulthood- Also seen in inner ear (deafness)) - Treat with K replacement, K-sparing diuretics - Ca-wasting seen--> hypercalciuria, Mg wasting - Increased secretion of prostaglandins prevents HTN Gitelman’s syndrome - Similar to thiazide diuretics: NaCl co-transporter inactivating mutation - Hypokalemia, hypomagnesemia, hypocalciuria (retaining Ca in blood) - Asymptomatic- see symptoms in adolescence (cramps, muscle weakness)

Answer 128

Cardiac: - decreases excitability, increases conduction. - Arrhythmias (atrial fibrillation). - Potentiates digitalis toxicity (K and digoxin competes for binding sites in the Na-K-ATPase). - U-wave after T-wave with increased amplitude Neuromuscular: - ascending muscle weakness, - respiratory failure, - rhabdomyolysis, - paralytic ileus. Renal: - Impaired concentrating ability(decreases aquaporin 2 expression in collecting duct) - Increased renal ammoniagenesis - Increased bicarbonate and Na reabsorption( increased exporession of Na-H exchanger in proximal tubule (increased Na and HCO3 reabsorption) - Hypokalemic nephropathy - Elevation in blood pressure

Answer 129

Replace KCl IV or PO - drop from 4-3 meq/L--> loss of 200-400 mEq of K - KCl used to replete Cl as well - IV repletion should be non-dextrose

Answer 130

70 kg man= 1.3 kg calcium 99% in bone, teeth 1% soft tissues 0.15% in extracellular fluid Body fluid calcium: - Concentration= 8.5 to 10.5 mg/dl - 50%= ionized form (BIOLOGICALLY ACTIVE form). Normal ionized calcium is 4.5 to 5.1 mg/dl - 40%= bound to serum proteins (albumin, globulins) and not ultrafiltrable - At pH 7.4, 1 g/dl of albumin binds 0.8 mg/dl of calcium - 10% is complexed to organic anions (citrate, phosphate, acetate, bicarbonate) and ultrafiltrable

Answer 131

Normal intake= 1 gm per day. - 20 to 30% is absorbed in the duodenum and jejunum and ileum= 300 mg absorbed and 150 mg gets secreted. - Net uptake= approximately 150 -200 mg - No net gain or loss of calcium from the skeleton. - To maintain calcium balance, the kidneys must excrete 150 – 200 mg of calcium per day

Answer 132

PTH: secreted from parathyroid gland - Synthesized as 115 aa polypeptide (pre-pro PTH)--> 90 aa (pro-PTH)--> 81 aa (cleaved based on body needs) - decreased plasma Ca2+ --> PTH--> 1. Bone: resorption--> Ca release 2. Kidneys: increased phosphate excretion (decreased phosphate), increase calcium reabsorption, increased calcitriol (Vit D) formation to increase intestinal CaHPO4 absorption

Answer 133

Cholecalciferol converted to calcitriol in Kidneys (after PTH stimulation due to low serum Ca) Causes: 1. Ca and Phosphate uptake by small intestines 2. Mobilizes Ca from bone by increasing bone resorption 3. Decreases Calcium and phosphate excretion at the level of the kidney.

Answer 134

1. Secretion stimulated by Ca. 2. Inhibits osteoclastic bone resorption 3. Promotes renal excretion of Ca *Neither athyroid patients (calcitonin-deficient) nor patients with medullary thyroid cancer (excess calcitonin production) have alterations in Ca homeostasis.

Answer 135

Calcium + Phosphate hydroxyapatite Therefore, decrease in phosphate--> increased calcium (won't form hydroxyapatite)

Answer 136

Parallels Na reabsorption: 1. PCT: 60% 2. Descending limb: 10% 3. TAL: 20-25% 4. DCT: 5-10% 5. Collecting duct: 0.5%

Answer 137

1. Extracellular volume depletion: increased Na reabsorption, increased Ca reabsorption. 2. PTH: increased Ca reabsorption in cortical thick ascending limb, distal convoluted tubules and connecting tubules, independent of Na reabsorption. 3. Thiazide diuretics: volume contraction, increased proximal Ca reabsorption. Also direct effect on distal tubule reabsorption. 4. Metabolic alkalosis: increased Ca reabsorption in distal tubule.

Answer 138

1. Extracellular volume expansion: decreased Na reabsorption, decreased Ca reabsorption. 2. Hypercalcemia: increased Ca excretion in proximal tubule, decreased Ca reabsorption in coritical and medullary thick ascending limb. 3. Loop diuretics: decreased Na reabsorption in loop, decreased Ca reabsorption. 4. Metabolic acidosis: H displaces Ca from bound albumin, increases ionized Ca, increased filtered Ca load. H inhibits distal tubular Ca reabsorption.

Answer 139

1. Primary hyperparathyroidism - Ambulatory patients: MEN-1, MEN-2; - can be seen in 1 gland (85%) or all 4 glands (15%)) 2. Malignancies (hospitalized patients) - osteolytic hypercalcemia= cytokine production (breast, myeloma, NSCLC, lymphoma) - humoral hypercalcemia= PTHrP; (squamous cell lung, head/neck, renal, ovarian) - tumoral calcitriol (Hodgkin's/non-Hodgkin's) 3. Dissolution of bones: - post-renal transplant (autonomous PTH) - Immobilization - Thyrotoxicosis (osteoclast activity inc.) - Familial hypocalciuric hypercalcemia= mutation in CaSR

Answer 140

1. Milk-alkali syndrome: hypercalcemia, alkalemia, nephrocalcinosis, renal failure 2. Hypervitaminosis D: alpha-hydroxylase in macrophages autonomously converts Vit D 3. Granulomatous diseases (sarcoidosis, TB, leprosy)

Answer 141

Thiazide diuretics lower urinary calcium excretion, an effect that is useful in the treatment of patients with hypercalciuria and recurrent calcium nephrolithiasis.

Answer 142

Li Rx- mild hypercalcemia, most likely due to increased secretion of PTH due to an increase in set point at which calcium suppresses PTH release. Pheo: It can be due to concurrent hyperparathyroidism (in MEN, type II) or to the pheochromocytoma itself due to tumoral production of PTH-related protein. Rhabdo: during the diuretic phase of acute renal failure, most often in patients with rhabdomyolysis due to the mobilization of calcium that had been deposited in the injured muscle.

Answer 143

"Groans, bones, moans, and stones" CNS: psychiatric (irritability, depression, psychosis), confusion, lethargy, proximal muscle weakness, cranial nerve abnormalities, obtundation, coma. Cardiac: hypertension, arrhythmias, heart block, shortened QT on EKG. GI: anorexia, nausea, vomiting, pancreatitis, peptic ulcer disease (Ca stimulates gastrin secretion). GU: polyuria (nephrogenic diabetes insipidus), nephrocalcinosis, nephrolithiasis, acute renal failure. Neuromuscular: hyporeflexia, myalgia, arthralgia. Skeletal: bone pain Metastatic calcification

Answer 144

History: medications, family history, malignancies, anemia. Blood tests: - iPTH (high in hyperparathyroidism, low in malignancies); - PTHrP (malignancies); - phosphate (low in hyperpara); - 1,25-(OH)2-Vitamin D3 (increased in sarcoidosis, granulomatous diseases); - 25-(OH)-Vitamin D3 (increased in hypervitaminosis D); - ionized Ca; - serum protein immunoelectrophoresis (multiple myeloma); - thyroid function tests. 24h urine Ca excretion (highest in malignancy, high in hyperpara, normal to low in familial hypocalciuric hypercalcemia). X-rays: metastases, osteitis fibrosa cystica, chondrocalcinosis, nephrolithiasis Sestamibi scanning: detects solitary parathyroid adenoma in >90% of patients.

Answer 145

1. Discontinue Ca supplements and Vitamin D. 2 Volume expansion with saline 3. Loop diuretics (only after volume expansion) 4. Bisphosphonates.(with normal renal function- prevent Ca leeching from bones) 5. Calcitonin (works in the short term) 6. Dialysis in patients with renal failure. 7. Avoid IV phosphate as it can cause metastatic calcification.

Answer 146

1. Surgical ablation or post-irradiation 2. Infiltrative diseases: tumor, amyloid, Wilson’s diseases, hemochromatosis. 3. Hypomagnesemia: impaired PTH secretion. 4. Idiopathic hypoparathyroidism 5. Polyglandular autoimmune syndrome Type 1: hypoparathyroidism, primary adrenal insufficiency, chronic mucocutaneous candidiasis

Answer 147

end-organ resistance to PTH, circulating PTH is elevated. Classic phenotype is short stature, obesity, bradydactyly, mental retardation (Albright’s hereditary osteodystrophy) . Albright's hereditary osteodystrophy= absent third knuckle

Answer 148

1. Dietary: elderly, malnourished alcoholics(Mg def) 2. Malabsorption(small bowel disease) 3. Impaired bile salt formation: cholestyramine 4. Anti-convulsant drugs: phenobarbital, phenytoin(impaired 25 hydroxylation in liver) 5. Chronic renal insufficiency 6. Vitamin D dependent rickets

Answer 149

1. Hyperphosphatemia 2. Nephrotic syndrome (loss of Vit. D binding protein) 3. Drugs: bisphosphonates, loop diuretics, amphotericin B, aminoglycosides, cis-platinum, phenobarbital, phenytoin 4. Acute pancreatitis (deposition of Ca) 5. Hungry bone syndrome (total parathyroidectomy--> no bone resorption--> bones eat all ECF calcium) 6. Rhabdomyolysis: deposition of calcium in injury phase (released during degradation phase) 7. Massive blood transfusion: citrated blood 8. Use of MRI contrast (Gadolinum)- spurious hypocalcemia- no Rx.

Answer 150

``` Acute: NM irritability: - Paresthesias - Muscle twitching - Carpopedal spasm - Trousseau's sign (inflate BP cuff--> hand spasm) - Chvostek's sign (tap facial nerve--> twitch) - Seizures - Laryngospasm - Bronchospasm ``` Cardiac: - Prolonged QT interval - Hypotension - Heart failure - Arrhythmia Papilledema Chronic: - Ectopic calcification - Extrapyramidal signs - Parkinsonism - Dementia - Subcapsular cataracts - Abnormal dentition - Dry skin

Answer 151

Blood tests: - ionized Ca (pseudohypocalcemia:hypoalbuminemia ) - Mg (hypomagnesemia) - iPTH - 1,25-(OH)2-Vitamin D3 - 25-(OH) -Vitamin D3 Most hypocalcemia patients with hyperphosphatemia and normal renal function will have hypoparathyroidism (idiopathic, acquired or pseudohypoparathyroidism)

Answer 152

1. Acute: 10-20 ml of Ca gluconate (90 mg elemental Ca/ 10 ml) in 50 – 100 ml of D5W IV over 10 minutes. Needs cardiac monitoring because serious cardiac arrhythmias may occur. 2. Intermediate (for recurrent and symptomatic hypocalcemia): Ca gluconate (10 – 15 mg/Kg) over 6 – 8 hours. 3. Chronic: Ca supplements (1-2 g elemental Ca per day), thiazide diuretics, rocaltrol (0.5 to 1.5 g/day). 4. Mg deficiency: empirical Rx. estimate 1-2 meq/Kg deficit. Replace 1x deficit over 1st day, and 1x deficit over remaining 2-4 days. - 4 ml of 50% MgSO4 (16 meq) IM q4-6h - 12 ml of 50% MgSO4 (49 meq) in 1L D5W IV over 3h - 4 ml of 50% MgSO4 in 100 ml D5W IV over 10 min in generalized seizures

Answer 153

``` Heavy proteniuria Free fat droplets Oval fat bodies Fatty casts Variable hematuria ```

Answer 154

Red cells Red cell casts Variable proteinuria Frequent white cell and white cell casts

Answer 155

Nephrotic syndrome---> Nephritic syndrome: 1. Minimal change glomerulopathy 2. Membranous glomerulopathy 3. Focal segmental glomerulosclerosis 4. Mesangioproliferative glomerulopathy 5. Membranoproliferative glomerulonephritis 6. Proliferative glomerulonephritis 7. Acute diffuse proliferative glomerulonephritis 8. Crescentic glomerulonephritis

Answer 156

Present with: - Edema - Dyspnea - Hypertension 1. Proteinuria > 3 grams/24 hours: - Patient can have nephrotic proteinuria WITHOUT nephrotic syndrome 2. Hypoalbuminemia ( edema - ANP - Increased activity in Na/K ATPase in basolateral membrane 4. Hyperlipidemia/Thromboembolism: - High cholesterol and triglycerides - Increased hepatic lipoprotein synthesis - Impaired catabolism of triglycerides - Impaired clearance from circulation - Increased risk of atherosclerosis Other complications of nephrotic syndrome: - Arterial/venous thromboembolism: renal vein thrombosis - Protein malnutrition - Acute renal failure due to hypovolemia- (esp. with very low serum albumin level) - Infection - Iron deficiency, Vit D deficiency, altered pharmacokinetics of protein bound drugs

Answer 157

Primary diseases of kidney: - Minimal change disease: common in kids, steroid responsive - Membranous nephropathy: associated with malignancy, thrombosis - Focal segmental glomerulosclerosis: most common cause of idiopathic nephrotic syndrome in adults, particularly blacks; treated with prolonged high dose steroids - Membranoproliferative glomerulonephritis Systemic diseases: - Diabetes - Plasma cell dyscrasias - SLE

Answer 158

ALL patients recieve: - ACE/ARB: decrease protein excretion, improve blood pressure (lower GFR) - Lipid lowering therapy: statins - Diuretics: manage symptoms

Answer 159

``` Pattern of Glomerular Tuft Involvement - Peripheral (basement membranes vs. Mesangial Character of Deposits - Granular vs. Linear (Goodpasture's) Type of Deposits - Ig species (IgG and IgA) and Complement Components Intensity of Deposits Blood Vessel and Tubular Deposits ```

Answer 160

- Epithelial cell foot process fusion - Subepithelial electron dense deposits - Endothelial cell swelling or proliferation - Subendothelial electron dense deposits - Character of capillary basement membranes - Mesangial cellularity and/or dense deposits - Fibril deposition - Tubular basement membranes or cellular inclusions

Answer 161

"Nil" disease= Proteinuria with epithelial cell foot processes fusion Most common cause of nephrotic syndrome in children Prognosis: - Progression to renal failure v. rare - Responsive to steroids - 50-65% of adults relapse (have steroid dependence) - Good prognosis in children Pathogenesis: - Probably immunologic basis - More prevalent in certain HLA haplotypes - Proposed Immune dysfunction: Circulating cytokine (IL-13) that damages epithelial cells; innate T cell dysregulation (cmyb pathway) Treatment: directed at T cells - Prednisone (first-line) - Cyclophosphamide or cyclosporine (relapsing or steroid resistant) - Mycophenolate mofetil (relapsing or steroid-resistant), rituximab, tacrolimus

Answer 162

Clinical course: - 1/3 with spontaneous complete remission - 1/3 with persistent proteinuria - 1/3 with progression to ESRD Treatment: - ACE/ARB for tight BP control - Immune-suppression for those at high risk of ESRD: 1. elevated creatinine at presentation 2. proteinuria > 8g/dL for 6 months after conservative treatment (ACE/ARB) 3. worsening kidney function 4. Refractory manifestations of nephrosis Immune suppression: - Cyclophosphamide or calcineurin inhibitor + Corticosteroids - Alternate Agents- Rituximab (NIH clinical trials)

Answer 163

- Autoimmune Disease – IgG4 linked to certain MHC loci - Production of autoantibody to M-type phospholipase A2 receptor - Immune complexes are formed in situ: C5b-C9 attack complex that injures epithelial cells

Answer 164

- Chronic circulating immune complexes of a specific size are trapped (IgG mediated) - Antigen-antibody complex activate complement attack complex, causing epithelial and BM injury Causes: 1. Systemic lupus erythematosus (WHO Class V) 2. Drugs: - Penicillamine - Bucillamine - Gold salts - Anti-TNF therapy - Tiopronin - NSAIDs 3. Hepatitis B virus/ Hepatitis C virus 4. Malignancy 5. Hematopoietic cell transplant / GVHD Status post renal transplantation 6. Sarcoidosis 7. Treponema, 8. Thyroglobulin

Answer 165

Electron-dense subepithelial deposits Granular deposition of IgG deposits Granular characteristic of basement membrane on silver stain

Answer 166

AKA: Focal Sclerosis Two Major Clinical Forms: 1. Primary or Idiopathic (includes familial/genetic forms) 2. Secondary - Virus (HIV, Parvovirus B19) - Drugs (Heroin, Interferon, Lithium) - Adaptive functional response (obesity, loss of one kidney) Multiple Histologic Subtypes: 1. Classic 2. Perihilar 3. Cellular 4. Tip Variant 5. Collapsing (Associated with HIV)

Answer 167

Light microscopy: - Mesangial cell proliferation - Focal process: not all glomeruli involved - Segmental process: only tufts involved - Trichrome stain: expansion of mesangium Immunofluorescence: - Trapping of IgM within mesangium ``` Electron microscopy: Epithelial Cell Injury - Foot process fusion - Detachment from underlying basement membrane Mesangial Changes - Fibrosis - Mesangial Matrix Increase - Insudative deposition of IgM and C3 - Lipid vacuoles ```

Answer 168

1. Primary event is Epithelial Cell injury induced by circulating factor (SuPAR) - Can see return of proteinuria within 24 hr's after transplant - Candidate circulating factor has been tentatively identified 2. Subsequent loss of GBM integrity 3. Glomerular structure becomes hyper permeable 4. See secondary extracellular matrix depositions and insudative trapping of IgM in the mesangium Genetic predisposition: - Polymorphisms/mutations in: Nephrin gene, Podocin gene Injury: Angio-poietin-like-e--> alters slit diaphragm between podocyte processes--> loss of GBM integrity--> proteinuria

Answer 169

35-40% cases of nephrotic syndrome in adults - 50% of cases of NS in blacks - only 20% of nephrotic syndrome cases in children Clinical course/prognosis: - Immunosuppressive therapy only for primary FSGS - 50% will have partial or complete remission with treatment - Poor prognostic factors- proteinuria >10 grams/day; histology (collapsing), renal failure at presentation, poor response to therapy, black race Treatment: - Immunosuppression if nephrotic at preserved GFR - Prolonged/high dose steroids - 1 mg/kg for at least 6 months - If unable to tolerate steroids – cyclosporine - If GFR may recur immediately post-kidney transplant

Answer 170

1. Hematuria with varying proteinuria 2. Decreased renal function 3. Hypertension 4. Edema Urinalysis: - Red cells - Red cell casts - Variable proteinuria - Frequent white cell/white cell casts

Answer 171

Primary renal disorders: - IgA nephropathy - Post-strep glomerulonephritis - Membranoproliferative glomerulonephritis (MPGN)

Answer 172

Immune complex glomerulonephritis involving intense deposition of dimeric and polymeric forms of IgA1 within the mesangium of the glomerulus - There is a defect in IgA metabolism - The O-glycosylation pattern of serum IgA1 is abnormal - The precise mechanism responsible for this aberrant glycosylation is not established. - Genetic deficiency in the enzymatic machinery mediating O-glycosylation of IgA1 (galactosyltransferase) Begins with infection--> excess IgA--> kidney can't clear IgA from blood--> deposition

Answer 173

Light microscopy: Capillary lumens open Proteinuria generally swells epithelium (not a lot of swelling here) Too many cells in section of mesangium= mesangial hypercellularity and increase in matrix = mesangial proliferation RBCs in mesangial space Immunofluorescence: IgA deposition Electron microscopy: - Mesangial Expansion and increased mesangial cellularity - Finely granular electron dense deposits are present along mesangial reflections

Answer 174

Most common cause of GN worldwide** - Young age (15-30 years of age) - Asian** Variable clinical presentation: - 40%-”Synpharyngitic” gross hematuria (pharyngitis with hematuria) - 40%-Microscopic hematuria with mild proteinuria (asymptomatic - 10%-Nephrotic proteinuria - 10%-RPGN (rapid progressive glomerulonephritis) Prognosis: - Good prognosis if minimal proteinuria (<500mg/day) - Worse outcome if elevated Cr, HTN or moderate/nephrotic proteinuria

Answer 175

- Observation if mild disease - If proteinuria >500mg/day – ACEI/ARBs + fish oil - Nephrotic or RPGN – Steroids +/- cyclophosphamide - Severe disease may require maintenance rx with azathioprine or mycophenolate

Answer 176

Immune complex mediated disease * *Follow group A beta-Hemolytic Strep infection** - See elevated antibody titers to strep Ag’s - Antigenic component not well characterized - ? endostreptosin or cationic protein related to streptokinase - Complexes lodge in glomerulus

Answer 177

Light microscopy: - Glomerular tuft enlarged, small urinary space - Capillary lumens congested - Segmented neutrophils - Peripheral inflammatory glomerulonephritis Immunofluorescence: - Coarse Granular Pattern - Capillary wall mainly but some mesangial IgG and C3 Electron microscopy: - Coarse Electron Dense Deposits (cross-react with streptococcal antigens) - Subepithelial and Mesangial Location - Epithelial and Mesangial Cell Proliferation - Some Foot Process Fusion

Answer 178

Diagnosis: - Often a clinical diagnosis - Latent period of 10-21 days from infection to nephritis - Low Complement (C3) levels - Elevated titers of antistreptolysin O, antihyaluronidase and Anti-DNAase B antibodies Clinical course: - Due to: Nephritogenic group A streptococcipharyngitis or impetigo - More common in children - Usually self-limited, renal function normalizes in 3-4 weeks

Answer 179

Treatment is supportive only Dietary sodium restriction Loop diuretics for edema

Answer 180

Primary and Secondary forms - Both involve activation of classic and alternative complement pathways 1. Stimulating Antigen in Primary form is not known (truly idiopathic) 2. Secondary Type I MPGN associated with antigens from: - SLE, Hep B, Hep C, HIV, Endocarditis, CLL, - Alpha 1-antitrypsin deficiency

Answer 181

Light microscopy: - Small urinary space, enlarged glomerulus - Lobular proliferation of tuft (vs diffuse in post-strep) - NO neutrophils (not actively inflammatory) - PAS stain (glycoproteins): see basement membrane duplication/splitting Immunofluorescence: - IgG, C3 (low in serum--> ends up in glomerulus), C1q located in subendothelium (vs epithelial) Electron microscopy: - Focal foot process fusion - Capillary Basement membrane duplication - Subendothelial electron dense deposits - Mesangial electron dense deposits

Answer 182

- Uncontrolled activation of alternative complement pathway - Loss of control secondary to an inherited deficiency of factor H (Factor H normally inactivates the C3bBb complex) - Without inactivation, continuous cleavage of C3 leading to the formation of abundant C3bC3bBb (the C5 convertase) - -> C3b dimer deposition along the GBM

Answer 183

Light microscopy (same as Type 1): - Small urinary space, enlarged glomerulus - Lobular proliferation of tuft (vs diffuse in post-strep) - NO neutrophils (not actively inflammatory) - PAS stain (glycoproteins): see basement membrane duplication/splitting Immunofluorescence (same as type 1): - IgG, C3 (low in serum--> ends up in glomerulus), C1q located in Basement membrane (vs subendothelium) Electron microscopy: - band-like dense deposits in basement membrane

Answer 184

Underlying pathology= Hypocomplementemia Two major types: 1. Type I – most common form, idiopathic. Clinical features= - Infections – HCV (circulating cryoglobulins/systemic vasculitis), HBV, IE, malaria, endocarditis - Autoimmune - Lupus, Sjogren’s, RA - Other: Cryoglobulinemia (without HCV), Sickle Cell, Lymphoma 2. Type II – dense deposit disease, children. Clinical features: - Partial lipodystrophy - Retinal drusen * Recurs in > 90% of kidney transplants

Answer 185

Treat underlying condition (e.g. HCV) Idiopathic, nephrotic - Corticosteroids Antiplatelets? Cyclosporine? *Relapse is common

Answer 186

- Angiotensin blockade - Lipid-lowering rx - If elevated C3 nephritic factor – plasma exchange - Eculizumab may be an interesting option

Answer 187

Most common cause of end stage renal disease in the U.S. Occurs in both Type I and Type II DM Hyperglycemia results in: - Activated protein kinase C pathway - Polyol pathway - Oxygen radical production - Increase in system wide glycation of proteins Events due to hyperglycemia cause: - General accumulation of hyperglycosylated proteins - Glomerular hypertrophy - Mesangial expansion - Basement membrane thickening - Hyperfiltration injury (related to obesity)

Answer 188

- Nodular and diffuse forms - PAS positive mesangial expansion - Basement membrane thickening - Hilar vessel sclerosis - Histology is the same for types I & II Histo: Light microscopy: - Nodular diffuse nephropathy: - Acellular, PAS, glycosylated proteins deposited in glomerular tuft - Start in mesangium and spread to rest of glomerulus, compress capillaries Immunofluorescence: - Pseudo-linear peripheral IgG and Albumin - Nodular mesangial deposition of IgM and C3 - Insudative Vascular deposition of IgM and C3, especially in hilar vessels Electron microscopy: - Thickened GBM and TBM, >600nm - Fused epithelial foot processes - Mesangial expansion, nodular, by the deposition of amorphous ground substance - Insudative electron dense deposits in mesangium and blood vessels

Answer 189

Early: - Increased GFR - Glomerular hypertrophy - Increased kidney size - Microalbuminuria Late: - GFR decreases - Macroalbuminuria--> proteinuria Treatment: - Blood sugar control (HbA1c~7%) - Screen for microalbuminuria - if present treat with ACEI or ARBs - Tight control of blood pressure (500-1000 mg/g creatinine)

Answer 190

A collection of diseases sharing a common feature: - common feature = Extracellular deposition of pathologic insoluble fibrillar proteins - Protein deposition impairs normal function Multiple organs and tissues can be involved Virchow coined the term amyloid, meaning starch like Renal dialysis--> alpha-2-beta globulin deposition

Answer 191

Light microscope: - Amorphous deposition of pink material around glomeruli, afferent, efferent arterioles - Congo red positive, Not PAS positive Immunofluorescence: - Non-specific staining with Ig reagents Characteristics of protein: - Many precursor proteins - Abnormal folding - Beta pleated sheet configuration - Appear as fibrils by EM, 8-10nm in diameter, indefinite length - Appears “apple green” with Congo red stain under polarized light

Answer 192

Plasma cell dyscrasia with fragment of light chains forming amyloid fibrils Treatment: chemo +/- bone marrow transplant

Answer 193

chronic inflammatory states (e.g. RA, IBD, CF, psoriasis) with acute phase reactant serum amyloid A forming fibrils Causes: - Rheumatoid arthritis - Ankylosing spondylitis - Psoriatic arthritis - Chronic infections (e.g. bronchiectasis, TB, osteomyelitis) - Inflammatory bowel disease - Cystic Fibrosis - Malignancy (e.g. RCC, NHL) - Familial Mediterranean Fever Treatment: treat underlying inflammatory disorder

Answer 194

- Immune Complex Mediated Glomerulonephritis - Secondary to a Variety of Autoantigens - Associated with Systemic Lupus Erythematosus

Answer 195

1. Class I and II: Mesangial electron-dense deposits 2. Class III and IV –Mesangial and subendothelial deposits with endocapillary proliferation 3. Class V – Subepithelial deposits - resembles idiopathic membranous glomerular nephritis Activity index: - Leukocyte infiltration - Hyaline deposition - Necrosis - Cellular crescents - Interstitial inflammation Chronicity index: predictive of rapid renal decline - Glomerular sclerosis - Fibrous crescents (epithelial cell proliferation compressing tuft) - Tubular atrophy - Interstitial fibrosis

Answer 196

Lupus nephritis ressembles many diseases--> plastic disease (nothing specific!) Light microscopy: - Mesangial cell proliferation Immunofluorescence: - See deposition of all immunoglobulins, complement proteins - Peripheral and mesangial deposition, granular - IgM, IgG, IgA, C3, C1q Electron microscopy: - Presence of Ig detected

Answer 197

Many factors play a role when deciding treatment: - Pathology (activity and chronicity indexes) - Symptoms (asymptomatic or full blown nephrotic syndrome) - Risk factors for worse prognosis (AA race, males, low socioeconomic status, higher creatinine at presentation, high grade proteinuria) - Compliance Meds: 1. ACEI/ARB Rx 2. Immunosuppressive Rx for Classes III-V - III and IV: Steroids + Cyclophosphamide or MMF - IV and V: FK+MMF+steroids - V alone (similar to membranous): Steroids+CYA or CsA 3. No immunosuppression for Stage VI 4. Rarely recurs after kidney transplant

Answer 198

Rapid loss of kidney function over 3 months 1. Anti-Glomerular basement membrane (GBM) antibody: - Goodpasture's 2. Immune complex - SLE - Post-infectious - etc. 3. Pauci-immune (+ANCA): - Wegener's - Microscopic polyarteritis ** Nephrology emergency

Answer 199

ANCA-positive= | Antineutrophil cytoplasmic autoantibody (ANCA)-mediated glomerulonephritis

Answer 200

Light microscopy: - Proliferation of crescent-shaped cells compressing glomerular capillaries--> decreased GFR - Lose nuclei with fibrinous material (necrosis) Immunofluorescence: - Negative for all reagents (Pauci-immune) - NOT mixed connective tissue disease - Must be vasculitis (Wegener's, microscopic polyarteritis, etc.) Electron microscopy: - No electron dense deposits, fibril deposits - No specific cellular injury

Answer 201

- Spare of the upper respiratory tract (vs Wegener's granulomatosis) - Pulmonary infiltrates/hemorrhage - RPGN - Crescentic GN with no immune deposits/negative immunostaining (Pauci immune) - Positive P-ANCA (vs C-ANCA in Wegener's) Rx: immunosuppression (Cytoxins and steroids) + plasmapheresis in severe renal dysfunction.

Answer 202

- Upper/lower respiratory tract disease (sinusitis) including pulmonary hemorrhage - RPGN - Crescentic GN with no immune deposits/negative immunostaining (Pauci immune) - Positive C-ANCA (vs P-ANCA in polyarteritis) Rx: Immunosuppression (CTX and steroids) + plasmapheresis in severe renal dysfunction.

Answer 203

- Can develop at any age - Pulmonary hemorrhage/glomerulonephritis - Circulating anti-GBM antibody - Antigen-alpha-3 chain type IV collagen Rx: plasmapharesis/immunosuppression

Answer 204

Type 1 Renal Tubular Acidosis: Failure of distal alpha intercalated cells to excrete H+ ``` Leads to: - Elevated blood H+ - Inability to acidify urine (pH > 5.3) - Elevated Chloride - Elevated K Hyperchloremic non-anion gap acidosis ```

Answer 205

Type 2 Renal Tubular Acidosis Failure of proximal tubular cells to reabsorb bicarb Leads to: - Elevated blood H+ - CAN acidify urine (excrete H+)- ph < 5.3 Seen in Fanconi's anemia

Renal Flashcards

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