Principal Cells 

• reabsorbs Na and H2O
• secretes K
• aldosterone inc Na reabsorption and inc K secretion
• ADH inc H2O permeabiity by directing the insertion of H2O channels in the lminal membrane
• K sparing diuretics: dec k secretion

Alpha intercalated Cells

• secrete H by an H ATPase, which is stimulated by aldosterone
• Reabsorbs K by an H, K-ATPase (H-K antiporter)
• reabsorbs bicarb by HCO3/Cl exchanger

Beta Intercalated Cells

• secrete HCO3 by a Cl/HCO3 exchanger
• reabsorb H by a H-ATPase 

Treating hyponaremia

• if volume depleted -> NS
• if renal salt retaining state (CHF, cirrhosis, nephrotic syndrome) -> Lasix, salt/water restriction, V2 receptor antagonist
• If SIADH -> fluid restriction, lasix, demeclocycline, V2 receptor antagonist

Vaprisol (conivaptan)

• Vw and V1A (vascular smooth muscle) receptor blocker
• available IV
• indicated for treatment of euvolemic hyponatremia (SIADH) in hospitalized patients
• NOT approved for CHF

Hypokalemia Symptoms

• muscle weakness/paralysis (including ileus)
• arrhythmias, rhabdomyolysis
• renal dysfunction: impaired concentrating (less ADH sensitive), impaired urinary acidification, tubulointerstitial disease

Fractional Excretion of Sodium

(FeNa)

• Fe_Na = (UNa/PNa) / (Ucr/Pcr)
• high > 1% : acute tubular necrosis, chronic renal failure, interstitial nephritis
• Low < 1% : volume depleteion, CHF, acute GN

Stages of Chronic Kidney Disease

• Stage 1: kidney damage with normal or inc GFR
• Stage II: kidney damage with small dec in GFR
• Stage III: Kidney damage with moderate dec in GFR
• Stage IV: kdiney damage wiht large dec in GFR
• Stage V: kidney failure iwth need for dialysis (end stage renal disease; ESRD)
• noraml GFR around 90-100

Epithelial Cells: Urinalysis

• originate from anywhere in the urinary tract
• Renal tubule cells: pathologic renal d/o: acture tubular necrosis, pyelonephritis, nephrotic syndrome
• 1.5 x the size of WBC, round, large nucleus

Casts

• Hyaline: conc urine, diuretics
• RBC: glomerulonephritis, vasculitis
• WBC: acute pyelonephritis, tubule interstitial dz, glomerular disorders
• Epithelial: ATN, acute glomerulonephritis
• Fatty: degeneration fo cells w/i epithelial casts, Maltese cross of chol esters and chol
• Granular: degen cellular casts, aggregated proteins, pigmented granular (muddy brown) = ATN
• Waxy: last stage of degenerating granular casts =  advanced renal disease

Carbonic Anhydrase (CA) Inhibitors

• Acetazolamide, dichlorphenamide, methazolamide, dorsolamide
• Sites of action in proximal tubule
• Carbonic anhydrase: localized to PCT epithelial cells
• in lumen of urine CA normally converts H2CO3 to H20 and CO2 which both diffuse into PCT cells -> in cells goes back to H2CO3 and then to H and HCO3
• CA-I inc excretion of HCO3, Na, H2O and K (distal)
• therapeutic use: rarely used as diuretic, most common use is glaucoma; also metabolic alkalosis, to alkalinize urine and epilepsy
• Adv Effects: hyperchloremic metabolic acidosis, alkaline urine, hypersensitivity (sulfonamides), hypokalemia, RE- caution renal insufficiency

Loop Diuretics

• Furosemide, ethacrynic acid, bumetanide, torsemide
• inhibits NKCC co transporter, also inc syn of renal PGE2 ( inc RBF and dec left vent filling presure)
• most efficacious class of diuretics
• uses: edematous conditions, hypercalcemia, acutre renal failure, HTN (low GFR)
• ADv effects: dehydration, hypokalemic metabolic alkalosis, hypnatremia, hypomagn, hyperuricemia, hyperglycemia, hypocalcemia
• also can cause ototoxicity (etharcrynic especially)
• drug interactions: digitalis, antiarrythmics, aminoglycosides (enh ototoxic), NSAIDs and probenecid (anti gout)

Thiazide Diuretics 

(NaCl transporter inhibitor)

• hydrochlorothiazide, chlorothiazide, indapamide, metolazone, polythiazide (all sulfa drugs)
• inc excreteion of Na, H2O and K
• dec excretion of uric acid and Ca2 
• uses: HTN, HF/edema, nephrogenic diabetes, hypercalciuria (used in kidney stones)
• adv efects: hypercalcemia (only one that has this), hypokalemic metabolic alk, hyponatremia, hypomagn, hyperuricemia, hyperglycemia
• drug interactions: digitalis, antiarrhythmics, aminoglycosides (enh ototoxic), NSAID, probenecid (gout drug)
• caution in elderly and diabetes  

K Sparring Diuretics

• ENaC inh: Amiloride, triamterene: dec Na reabsorption and K secretion
• Aldosterone antagonists: Spironolactone, epleronone: comp antag aldosterone at mineralcorticoid rec, dec Na reabsorption and dec K secretion
• Uses: offsets k loss of other diuretics, states of hyperaldosteronism (spironolactone), lithium induced NDI (amiloride)
• adv effects: hyperkalemia, metabolic acidosis, kidney stones (triamterene)

Osmotic Diuretics

• mannitol, urea, glycerol, isosrbide
• MOA: freely filtered, not reabsorbed; inc osm pressure in tubule to retain water (H2O> Na excret)
• uses: acutre renal failure, reduce intracranial pressure (does not cross BBB), reduce intraocular pressure, eliminate toxic substances
• adv effect, oral mannitol causes diarrhea, rapid IV infusion can inc ECF volume (risk for pulm edema, in ie, CHF), hyper/hyponatremia

Antihypertensive Drug Effects

• Reduce PVR: RA system inhibitors, sympatholytics (beta and alpha blockers), vasodilators
• Reduce CO: beta blockers, CCBs, Sympatholitics, reduce plasma volume (diuretics, RA system inhibitors)

ACE Inhibitors

• captopril, enalapril, lisinopril
• major effect is Dec PVR, first line antihypertensive
• less effect in african americans then thiazides
• indications: diabetes (slows nephropaty), chronic kidney disease, CHF, post MI
• adv effects, fetopathic potential, dry cough, renal failure, hyperkalemia and angioedema
• NSAIDs blunt effects

Direct Renin Inhibitors

• aliskiren is the first and only DRI
• MOA: binds catalytic site of renin
• use: mono/combination (ARB, diuretic)
• adverse: diarrhea, vertigo, dizziness, cough less than ACE-I
• avoid: pregnancy, co-admin cyclosporins, combination ACE-I/ARB in diabetics

Calcium Chanel Blockers

(anti-hypertensives)

• DHPs: nifedipine, amlodipine, felodipine, isradipine
• Non DHPs: verapamile, diltiazem
• MOA: inhibit L type Ca channel on arterial smooth muscle and cardiac myocyte: leads to dec PVR and CO
• have greatest effect on phase 0 of SA node
• efffective in blacks and isolated systolic HTN (elderly)
• nifedipine (DHP) safe in pregnancy
• adve effects: short acting DHPs (inc mortality), hypotension (all), cardiac depression (non DHPs)

Hydralazine

• direct arteriodilator, moa not understode
• not a first choice in essential HTN (used in multidrug regime, refractory HTN (modest-severe)
• used in pregnancy
• adv effects: positive ANA-lupus (reversible), hypotension, prominent reflex (co-admin beta blocker, diuretic)

Minoxidil

• direct vasodilator, prodrug - active minoxidil sulfate
• MOA: opens K channels -> preferential arteriodilation
• prominent reflex: co admin beta blocker and diuretic
• used in refractoyr HTN
• not first choice in HTN emergency
• other uses: alopecia
• adv effects: relfex symptoms, hypertrichosis

Parenteral Vasodilators

• major use: hypertensive emergencies
• Diazoxide: K channel opener (arteriodilation), can induce hyperglycemia and used rarely
• Fenoldopam: D1 dopamine rec agonist: arteriodilation, undergoes rapid metabolism (1/2 life 10 mins)
• Nitroprusside: source of NO, GC activation: equal arerio and venodilation, 1/2 life of mins, IV only, drug of choice and can cause cyanide toxicity

Beta Blockers

• non selective: propranolol
• cardioselecive: metoprolol, betaxolol, nebivolol
• intrinsic sympathomimetic act: acebutolol, pindolol
• mixed blockers: carvedilol, labetalol
• dec CO, dec renin, and dec PVR (with ISA or alphaant
• less effective in african americans
• uses: post MI, chronic stable angina, atrial tachyarrythmia, essential tremor, hyperthyroidism
• Adv effects: bronchospasm, dec contractility, HR, conduction; diabetes caution and sexual dysfunction
• cardioselective agents for diabetes

Alpha Blockers

• nonselective blockers: phentolamine, phenoxybenzamine, pheochromocytoma, assoc w/ prominent reflex tachycardia
• A1 rec antagonists: prazosin, terazosin, doxasin: dec PVR, but have first dose syncope
• not for chronic monotherapy (risk of CHF)
• use adj with diuretics, beta blockers, vasodilators
• consider: benign prostatic hyperplasia

Centrally Acting Alpha 2 Agonists

• clonidine, methyldopa, guanabenz, guanfacine
• MOA: reduce sympathetic outflow: reduce BP, CO, reduce renin
• Usually used as djunctive therapy
• methyldopa: drug of choice for pregnancy
• Adv effects: CNS sedation, depresssion, dry mouth, coomb's test, rebound HTN

Anti-Hypertensive Selection

• Elderly: diuretic, ACE-I, ARB, CCB
• African: diuretic, CCB, labetalol (add diuretic to ACE-I/ARB, beta blockers)

Clinical Clues to AG Metabolic Acidosis

• Uremia: anorexia, nausea, vomiting, dyspnea, orthopnea, inability to conc, mentalchanges, azotemia
• Ketoacidosis: ketotoic breath, sick diabetic, homeless
• lactic acidosis: shock
• Intoxicants: salicylates (combo w/ resp alkalosis), methanol, ethylene glycol 

Metabolic Alkalosis

• ingestion of alkali can cause it 
• if not ingestion, look at urine chloride 
• <20 mEq/L: chloride responsive
• >20 mEq/L: chloride non responsive
• central Nervous system: letharg, confusion, stpor, agitation, disorientation, irrational behavior
• pulmonary: hypoxia secondary to hypoventilation
• assoc lab findings: hypokalemia

Acute Kidney Injury

• Stage 1: Risk: dec in GFR of 25%: inc 0.3 serum Cr
• Stage 2: Injury: dec in GFR by 50%: inc 0.5 serum Cr
• Stage 3: Failure: dec in GFR by 75%: inc 300% serum Cr
• Loss: persistent renal failure for > 4wks
• ESRD: persistent renal failure for > 3 motnhs 

Acute Tubular Necrosis

• associated with parenchymal
• initiation: cellular injury resulting in metabolic derangement: ATP depletion, oxygen free radical generation, lipid peroxidation, cytoskeleton dysfunction
• Maintenance phase: backleak of glomerular filtrate through exposed tubular basement membrane, tubular obstruction from sloughed cells, can inc intratubular pressures threefold. 
• Recovery phase: remaining viable cells must rapidly proliferate for recovery. epidermal growth facor and insulin like growth factor

Glomerulonephritis

• Azoemia, oliguria, HTN, hematuria with RBC casts, proteinuria
• rapid loss of renal function if not treated early
• Histo: see glomerular cellular proliferation and influx of various blood born cells resulting in crescent formation

Acute Interstitial Nephritis

• 10-15% of cases of ARF
• immune mediated response  that results in interstitial infiltration, or an amplification of a nonimmue interstitial injury (chol embolic disease, phosphate nephropaty)
• Clinically: azotemia, oliguria, fever, rash
• urine: pyuria and WBC casts
• FeNa > 1%

Acute Tubular Necrosis

• most common form of parenchymal damage
• hypoperfusion: affects proximal tubule
• Rhabdomyolisis
• contrast nephropathy: initial injur is vasoconstriction followed by distal tubule injury: good prognosis with 90% recovery
• aminoglycoside accumulate within proximal tubule and cochlear hiar cell, normal peak and through levels do not exclude diagnosis
• history of prolonged hypotension or exposure to nephrotoxins

Indications for Dialysis

• Volume overload
• hyperkalemia
• symptoms of uremia, pericarditis, encephalopathy, bleeding due to platelet dysfunction
• presence of toxic substance that is dialyzable
• prophylactic

Metabolic Abnormalities in Calcium Stones

• hypercalciuria
• hyperuricosuria
• hypocitraturia: like metabolic acidosis
• hyperoxaluria (2nd most common stone constitute)
• Primary hyperparathyroidism

Uric Acid Stone

• crystals are plomorphic, most often appearing as rhombic plates or rosettes 
• they are yellow or reddish brown and form only in an acid urine
• almost exclusively in men, radiolucent stones 
• hyperuricemia without gout, or primary gout (5-6%)
• tumor lysis
• seen in chronic diarrhea (UC, chrohms, JL bypass) due to low volume, acidic urine with inc uric acid concentration

Struvite Stones (MgNH4O4)

• coffin lid magnesium ammonium phsophate crystals which form only in an alkaline urine
• infection with urea splitters produce high amounts of ammonium in alkaline urine, precipitate out PO4
• disastrous: stones grow rapidly, can fill renal pelvis in a year, very difficult to eradicate once established, obstruct kidney
• proteus, klebsiella, pseudomonas, enterbacter

Xanthine Stones

• less than 1% of all stones
• autosomal recessive deficiency of xanthine oxidase leads to inc urine xanthine and hpoxanthine, with very low serum and urine uric acid
• radiolucent stones in about half of patients 
• reported in patients with overproduction of UA treated with allopurinol
• urine pH has little effect: high pKa 7.7 and 10.6

Stones Due to Drugs

• triamterene: up to 1/2 pts develop crystalluria, but stone formation rare, usually combined with calcium oxalate, but can be pure tramterene stones, more commonly a problem with pre-existing stone disease, faintly radiopaque
• allopurinol: xanthine stones
• indinavir
• others include ceftriaxone, sulfonamides, TMP-SMX blah blah blah

Suspect Renovascular Hypertension

• young and old w/ recent onset of HTN. Abrupt onset
• Refractory or accelerating HTN
• HTN w/ an abdominal bruit (or evidence of occlusive vascular dz elsewhere)
• unexplained deterioration of renal fxn or pulmonary edema during Tx w/ ACE inhibitors: ACE inhibitors make process worse

HTN Treatment Goals

• the ultimate goal of antihypertensive therapy is to reduce CV and renal morbidity and mortality
• treat all pts w/ stages 1 and 2 HTN: < 140/90 for most pts and < 13/80 for pts with diabtetes or renal disease
• lifestyle modifications for all pts including 

Hypertensive emergencies

• generally occur at bp > 180/120
• failure of auto regulation results in fibrinoid necrosis of small vessels and tissue ischemia
• Acute severe HTN (malignant HTN): retinal hemorrhages, papilledema, ± malignant nephrosclerosis (AKI, hematuria, proteinuria)
• Hypertensive encephalopathy: cerebral edema

Most Common Causes of Secondary HTN

• Renal Parenchmal Disease
• Renovascular Disease: atherosclerotic, Fbriomuscular
• Primary Aldosteronism: solitary adrenal adenoma, bilateral adernal hyperplasia
• Thyroid: hyperthyroidism, hypothyroidism
• Cushing's syndrome/disease
• pheochromocytoma
• coarctation of the aorta
• obesity
• obstructive sleep apnea

Parenchymal Kidney Disease

• parenchymal kidney disease of any type can lead to difficult to control HTN
• any of the causes of kidney dz (glomerulonephritis, interistitial nephritis, vasculitis obstruction) can lead to HTN
• most common cause of secondary HTN
• untreated HTN can also lead to further renal dmg
• HTN ay be the presenting sign of kidney disease
• elevated BUN/Creatinine, proteinuria
• treat specific causes of kidne disease, ACE-I, ARBs, diuretics

Primary Aldosteronism

• solitary adrenal tumor: Conn's Syndrome
• Bilateral adrenal hyperplasia
• autonomous sec of aldosterone with sesultant suppresion of renin 
• fatigue/muscle weakness, unprovoked hypokalemia or excessive hypokalemia on a diuretic, mild hypernatremia, mild metabolic acidosis
• aldo-renin ration (ARR) > 30:1 or use AER
• CT/MRI
• therapeutics: mineralcorticoid antagonists: aldactone, epleronene or surgery

Cushing's Syndrome

• excess cortisol prod from unrergulated sec of ACTH from the anterior pituitary (cushing dz) or autonomous sec of cortisol from an adrenal tumor or ectopic sec of ACTH resulting in cortisol excess
• Cushing syndrome secondary to adrenal tumor1/100k
• examethasone suppression testing to differentiate among various types, as well as treatment approaches

Pheochromocytoma

• NE sec: see more alpha vasoconstriction with inc diastolic pressure
• Epi sec: see more bet mediated cardiac stimulation w/ predom systolic bp rise, achycardia, sweating, flushing, tremulousness, headache
• Dopa: may not see HTN at all 
• all three of the above may occur in paroxysms and most have headaches, sweating and palpitations
• biochemical readings and localizaiton with scans
• surgery after pretreatment with alpha blockade, phenoxybenzamine

Hypothyroidism

• HTN is cauded by inc in total body Na and PVR, 
• also caused by higher plasma catecholamine levels
• diagnosed: elevated throid sitmulating hormone (TSH)
• Treatment: thyroid hormone replacement

Hyperthyroidism

• HTN  caused from: inc CO, inc myocardial contractility, tachycardia, and expanded blood volume
• diagnosis: dec thyroid stimulating hromone, elevated T3 and T4 levels
• treatment: beta blockers, treatment of underlying causes of thyroid disease 

Obesity and HTN

• Aprox 60-70% of the risk of HTN is related to obesity
• visceral adipositiy seen as a potent predictor for HTN
• visceral adiposity bears a strong relationship to insulin resistance and endothelial dysfunction
• mechanism: Na retentino, inc SNS activity (from inc leptin), inc RAA activity, inc oxidative stress
• treatment multifaceted: reversal of obesity, meds which impact SNS, volume and the RAA systematics are the most effective

Characterics of Proteinuria 

• hyaline casts
• oval fat bodies (maltese cross in polarized light)

Congenital Nephrotic Syndrome

• congenital nephrotic syndrome has its onset in utero or infancy
• char by heavy proteinuria, lipiduria, hypoproteinemia and hyper lipidemia (fatty casts in urine)
• infant is usually markedly edematous
• abnormalities of the slit pore diaphragm lead to proteinuria: slit diaphragm btw the two podocyte foot process

Podocytopathy 

(podocyte injury)

• no change in podocyte number and minimal changes on history: Minimal change disease
• Podocyte detachment/death: segmental sclerosis: focal segmental glomerularsclerosis (FSGS)
• Low podocyte proliferation: mesangial sclerosis: diffuse mesangial sclerosis (DMS)
• High podocyte proliferation: capillary collapse: colapsing glomerulopathy

Focal Segmental Glomerulosclerosis

• most common cause of nephrotic syndrome in hispanics and african americans
• primary idopathic form: specific cause unk; mediated by circ permeability factors
• Secondary forms: familial, virus assoc, drug induced, adaptive (conditions w/ or w/o initially norm renal mass
• foot process effacement -> podocyte detachment -> segmental sclerosis w/ podocyte loss -> fsgs w/ parietal cell coverage
• poor response to steroids; progress to chronic renal failure
• histologic subtupe: NOS (most common, others can progress to this), perihilar , cellular, tip

Perihlar FSGS

• perihllar hyalinosis and sclerosis involving the maj of glomeruli with segmental lesions
• perihilar lesions are located at the glomerular vascular pole
• in adaptive FSGS, there is usually glomerular hypertrophy (glomerulomegaly)
• foot process efacement is relatively mild and focal
• common in adaptive FSGS assoc with obesity, elevated lean body mass, reflux nephropathy, hypertensive nephrosclerosis, sickle cell anemia, and renal ageness
• predisp for vascular pole is probably due to normally inc filtration pressures at the proximal afferent end of glom capillary bed, which are heightened under conditions of compensator demand and vasodilation of the afferent arteriole

Cellular FSGS

• expansile segmental lesions with endocapillary hypercellularity often including foam cells and infiltrating leukocytes, with variable glomerular epithelial cell hyperplasia
• there is usually severe foot process effacement
• usually primary, but also seen in a variety of secondary forms
• this is the least comon variant
• it is thought to represent an early stage in the evolution of sclerotic lesions

Tip FSGS

• segmental lesion involving the tubular pole, wiht either adhesion to tubular outlet or confluence of podocytes and tubular epithelial cells
• compared with other variants, it has the least tubular atrophy and interstitial fibrosis
• there is usually severe foot process effacement
• used primary probably mediated by physical stresses on the paratubular segment owing to the convergence of protein rich filtrate on the tubular pole, causing shear stress and possible prolapse

Diffuse Mesangial Sclerosis

• congenital and acquired forms
• steroid resistant nephrotic syndrome
• IgM trapping in expanded mesangia often preent
• at one point viewed as a transitional entitiy btw minimal change and FSGS

Collapsing Glomerulopathy

(type of FSGS)

• implosive glomerular tuft collapse with hypertrophy and hyperplasia of the overlying visceral epithelial cells
• hyperplastic lgomerular epithelial clels may fill the urinary space, resembling crescents
• sever tubular injury and tubular microcysts are common
• there is usually severe foot process effacement
• primary or secondary to viruses: HIV-1, parovirus, B19, SV40, EBV, CMV, hemophagocyti syndrome
• drugs: pamidronate and interferon
• vaso-occlusive disease: athero-emboli, calcineurin inh nephrotoxicity, and chronic allograft nephropathy

Diabetic Nephropathy

• kimmelstiel-Wilson (K-W) nodules and thickened capilary loops: caused by sclerois of the mesangium (diabetes nephropathy eventually) progresses to nephrotic syndrome
• Diabetes- most common cause ESRD
• mesangial nodule and thick loops and albumin trapping glycosylation of the vascular basement membrane resulitng hyaline arterioloscleroiss
• glomerular efferent arteriole is more affected than the afferent arteriole, leading to the high glomerular filtration pressure 
• hyperfiltration injuryleads to microabluminuria (ACEI can slow down hyperfiltration damage by dec ang II evels that normal constrict efferent artioles) 

Primary Syndromes of Hematuria

• Alport Syndrome (hereditary nephritis) and Thin basement membrane
• IgA Nephropathy (Berger's Syndrome and HSP)
• Membranoproliferative Glomerulonephritis

Alport Syndrome and Thin basement membrane

• primary syndrome of hematuria (alport is hereditary nephritis)
• Both Alports and Thin BM syndrome have heritable abnormalities of type 4 collagen
• Hematuria assoc with abnormal ealsity breached BM
• results in thinning and splititng of the glomerular BM
• presents as isolated hematuria, sensory hearing loss and ocular disturbances (these key features and family history used for dx)

Membranoproliferative Glomerulonephritis

• can cause both nephritic and nephrotic syndrome
• lobular papearance iwth onc mesangial cells, splitting of Basement membrane in Jones stain
• thick glomerular BM on H&E, often with tram track appearance:due to immune complex deposition
• Type I - subendo deposits: assoc with HBV and HCV
• Type II - intramembran: assoc with C3 nephritic factor (MPGN or dense deposit disease)
• Secondary MPGN - example of a case assoc with monoclonal gammopathy
• poor response to steroidsl progress to Chronic renal failure

Secondary Syndromes of Hematuria

• Acue proliferative (post streptococcal) Glomerulonephritis (PSGN)
• Embolic Glomerulonephritis: assoc with SNE, line infections
• Lupus Cryoglobins (on another card)

Lupus Cryoglobins

• Lupus causes hematuria syndormes (secondary) - many patterns - mesangial or diffuse proliferative or membranous
• ANA positive; C3 often low; IgG, IgA, C and C1q in IF
• Class I: normal glomeruli (by light mic, IF and EM)
• Class II: purely Mesangial Disease: 
• Class III: Focal Proliferative glomerulonephritis (<50%)
• Class IV: diffuse proliferative glomerulonephritis >50%)
• Class V: membranous glomerulonephritis
• Cryoglobulinemia and renal disease

Rapidly Progressive Glomerulonephritis

• nephritic syndrome that progreses to renal failure in wks to months
• char by crescents in bowmans space (compr of fibrin and macrophages)
• Linear Crescents (antibasement mem): good pasture synd
• Granular Crescents: PSGN or diffuse proliferative lgomerulonephritis
• Negative IF: wegner granulomatosis, microscopic polyangitis and churgh-strauss syndrome
• causes: anti g bm disease, antineutrophil
• causes in pts with normal complement: IgA nephropahy, henoch-schonlein pupura, fibrially glomerulonephritis
• causes in pts with low complement: SLE, PSGN, membranoprolif glomnephritis: infection (HCV, HBV, HIV), gentic, collagen vasc disease (SLE, sjogrens synd)

Cystitis

• ifnection can be limited to lower tract
• white cells (neutrophils) but no white cell casts
• presents as dysuria, urinary freq, urgency and suprapubic pain; no systemic signs
• urinalysis (cloudy urine w/ >10 WBCs, dipstick (positive leukocyte esterase adn nitrites(bacteria convert nitrates to nitrites), culture 
• eosinophilic cystitis: unk etiology, young women, UTIlke symptoms
• etiology: ecoli, staph,klebsiella, proteus mirabilis
• sterile puria is the presence pyuira

Pyelonephritis

• intratubular acute inflam (neutrophils in tubules)
• abscess and scars can result
• presents with fever, flank pain WBC casts and leukocytosis in addition to symptoms of cystitis
• most common pathogens are: ecoli, enterococcus faecalis, klebsiella spec

Chronic Pyelonephritis

• interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
• due to vesicoureteral reflux (child) or obstruction (BPH or servical carcinoma)
• leads to cortical scarring with blunted calyces; scaring at upper and lower poles is char of vesicoureteral reflux
• atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles (thyroidization of the kidney); waxy casts may be seen in urine

Interstitial Nephritis

• diffuse inflammation btw tubules with many eosinophils: eosinophil granules look red when stained
• Sarcoid is a cause of granulomatous interstitial nephritis: tubules way far apart and intestinal granules everywhere
• Acute interstitial nephritis usually caused by drug overdose
• chronic tubulointerstitial injury: IgG4 related is a type of chronic tubulointersittial disease (rare entity); heavy metals and drugs cause interstitial fibrosis with modest inflammation

Obstructive Cystic Disease

• obstruction during development can lead to this
• can range from subcorical cysts to complete relpacement by cysts
• long standing in utero obstruction can lead to cystic dysplasia: babies will also hay hypoplastic lung, can see cartilage (points towards sporadic event and not an inherited thing
• Nephron mass of 30% less than normal means you are doomed to chronic kidney failure: get wedge biopsy to see if they wille ventually need a transplant or will be fine 

Medullary Sponge Kidney

• acquired cystic dilation of medullary collecting tubules: cortex pretty free of cysts
• Associated with stone formaiton (15-20% of pts with stones will demonstrate)
• usually do not become that destructive 
• no one knowns why it happens but does not appear to be heritable

Nephronophtisis

• corticomedullary ycsts that cause tubular obstruction: damage everyting in the cortex above them
• intersittial fibrosis and protein accumlation in tubules
• Jeune, joubert, mechel and bardet-beidl: syndroms of enal cystic disease, polydactyly and abnormalities of retinal and cerebellar development that have a spectrum of mutations in teh same games as the various nephronophthisis

Papillary Renal Carcinoma

• involves MET oncogene activation: generates hepatic growth actor
• seen in all familial forms and demonstrable in 15% of sporadic forms
• trisomy 7 is cytogenic char
• much more granular gross appearce histology looks like cuboidal cells with a stroma of connective tissue cells and cascular structures
• better progrnosis than celar cell
• IHC is positive for pan-keratin, EMA and CD117

Papillary or Flat Forms

(tumors of the collecting systems, ureters and Bladder)

• grade by differentation and layer of tumor cells and depth of invasion into the bladder
• Flat: develops as a high grade flat tumor and then invades assoc with early p53 mutation
• Papillary-develops as a low grade papillary tumor that progresses to a high grade papillary tumor and than invades; not assoc with early p53 mutation

Childhood Renal Tumors

• Nephroblastoma: derived from persistent nephrogenic rests, embyronal tumor: favorable histology (no anaplasia 80%) and unfavorable histo (anaplasia 5%)
• Mesoblastic Nephroma: benign mesenchymal tumor of infancy-5% all you see see is stromal tissue
• Clear cell sarcoma - often spreads to bone 4%: histo looks like nest of cells surrounded by chicken wire, not related to clear cell renal carcinoma
• rhabdoid tumor - often in infants, assoc with CNS tumors, very poor prognosis - 3%
• Metanphric tumors: mix of adenoma and fibroma
• Renal cell carcinoma, often with TEF3 translocaiton (x chromosome) seen in adolescents

Nephroblastoma

• arises from persistent nephrogenic rests in the perilobar or intralobar location
• affects 1 in 8000 to 10k children, 6.3% of childhood malignancies (80% of kidney tumors), mean age for unilateral 42-47 months
• 10% of cases assoc with phenotypic syndrome
• 2% of caes have familial tumors assoc with FWT1 nad FWT2

Rhabdomyosarcoma

• Pediatric rhabdoymosarcoma: occur assoc with testis, prosate and in the vagina, often effect the bladder; most common sarcoma of young children - is an embryonal tumor of skeletal muscle
• Embryonal RMS: submucosal has botryoid appearance
• Spindle Cell RMS: rare, best prognosis
• Make diagnosis with myogen and desmin staining, shows that it is striated muscle stem cell making the rhabdomyosarcoma
• can also show contractile units in electromicroscopy

Renovascular HTN Imaging

• Captopril Renal Scan is the main way (ACEI scan)
• 90% selective and specific, ACEI removes phsyiologic adaptive mech at the glomerular efferent arteriole
• do pre and post captopril scans
• affected side has persistent activity in the involved kidney: still holds on to its urine longer then other side
• Can also use angiography - conventional, CT or MRI

Imaging of Ureteral Obstruction

• pelvicalictasis - prominence of renal pelvis and calices
• hydroureter (large ureter)
• Perinephric/periuretral standing
• delayed enhancement: if obstructed kidney contrast enhancement could be delayed
• renal edema and swelling

Rectal Exam for Incontinence

• testing sensation in the saddle area tests afferent loop for micturation arch
• contracting anal sphincter assesses S2-S4 motor component
• anal wink
• patulous anus suggests chronic distension 

Provoked Full Bladder Test

• cough in sitting and standing position
• confirms stress incontinence
• if delayed urge incontinence