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CS Block 3
Renal
| Question | Answer |
|---|---|
| Asymptomatic presentation of renal disease | "incidental finding;" high BUN/creatinine, microhematuria (under scope), proteinuria |
| Symptomatic presentation of renal disease | high BP, edema, gross hematuria, "bubbly urine" = proteinuria |
| Evaluation of Renal Disease | 1. estimate disease duration; 2. careful urinalysis; 3. assessment of GFR; 4. renal ultrasound |
| Acute Renal Failure stats | **potentially reversible; duration of few hours to days; acute rise in BUN & creatinine, dec GFR, usu identifiable renal insult (ex: drugs, contrast dyes, dehydration) |
| Chronic renal failure stats | *usu irreversible and progresses to end-stage renal disease (ESRD); gradual/progressive loss of renal fxn; Hx of renal dx; >3mo duration; previously documented rise in BUN & creatinine (you need another lab to compare); small kidneys via ultrasound/CT |
| Acute on CRF | acute worsening of renal function in a previously stable renal failure |
| Progressive Chronic Renal Failure | slowly worsening renal failure over time; slowly increasing BUN & creatinine; usu seen in outpt clinic |
| "aging of the kidney" | GFR reaches peak at age 40 and declines 1cc/min of GFR per year thereafter; (ex: GFR in 50yo = 90; assuming 100 is nml) |
| Stages of Chronic Kidney Disease (CKD) | 1 (damage w/nml-inc GFR >90; Tx comorbid conditions, slow progress, dec CV dx risk); 2 (damage w/mild dec GFR 60-89; estim progress); 3 (mod GFR 30-59; eval & Tx complications); 4 (severe dec GFR 15-29; prepare for transplant); 5 (failure GFR<15: replace) |
| Azotemia | asymptomatic high BUN/creatinine |
| Uremia | symptomatic; high BUN & creatinine, usu ESRD (metabolic acidosis, hyperkalemia, oliguria, nausea, vomiting, CNS (encephalopathy, altered mental status), pericarditis, indication for dialysis) |
| Nonoliguria | urine output of >400 cc/24hr; better prognosis, hyperkalemia is less severe; less likely to be put on dialysis; prone to pulmonary edema |
| Oliguria | urine output of 100-400cc/24hr; hyperkalemia (indication for dialysis); prone to pulmonary edema |
| Anuria | urine production of <100cc/24hr; hyperkalemia (indication for dialysis) |
| Urinalysis | "poor man's renal biopsy;" collect midstream in AM; use bladder catheter if menstruating; examine w/in 1hr |
| Urinalysis Findings | color (straw-dark yellow); clear-haze (ptn or UTI); specific gravity (1.003=too much fluid; 1.029=no fluid in 24hrs); ptn, glucose, ketones, bilirubin, occult blood, leukocyte esterase, nitrite, urobilinogen, WBC, RBCs, casts, bacteria, yeast, parasites |
| Hyaline casts | concentrated urine, febrile disease, after strenuous exercise, in course of diuretic therapy (not indicative of renal disease) |
| Red cell casts | indicative of glomerulonephritis |
| White cell casts | indicative of pyelonephritis, interstitial nephritis (infection or inflammation) |
| Renal tubular cell casts | indicative of tubular necrosis, interstitial nephritis |
| Coarse, granular casts | non-specific finding; can represent acute tubular necrosis |
| Broad, waxy casts | indicative of chronic renal failure d/t stasis in collecting tubule |
| Proteinuria: abnormal and neprhotic syndome levels | >150mg/24hr urine; >3.5g/24hr urine sample |
| Functional proteinuria | benign, related to exercise, stress, positional (common in peds) |
| Overflow proteinuria | overproduction of circulating, filterable plasma proteins (ex: multiple myeloma, rhabdomyolysis) |
| Glomerular proteinuria | inc filtration of normal plasma proteins (ex: nephrotic syndrome) |
| Tubular proteinuria | faulty reabsorption of normally filtered plasma proteins in proximal tubues (ex: ATN, toxic drug injury (aminoglycosides, lead), acute renal failure) |
| Assessment of Glomerular Filtration Rate | index of overall renal function; 120cc/min/1.73m2 BSA (body surface area); measured by 24hr creatinine clearance |
| Normal creatine clearance vs acute renal failure | 0.5 -1.5; if your first reading is 1 and your second result is 2, your GFR has been halved and that is acute renal failure |
| Kidney imaging studies | radionucleotide studies, ultrasound, IV urography (IVP), CT, MRI, arteriography, venography; assesses GFR/flow, split renal fxn, assesses fxnl renal tissue in mass lesions, detects obstruction, assesses renovascular disease (ex: renal a. stenosis) |
| Radionucleotide studies of kidney: assessment of GFR | 125I-iothalamate and 99mTc-DTPA (Technetium diethylentriamine petnaacetic acid) |
| Radionucleotide studies of kidney: assesment of functional renal mass | 99mTc-DMSA |
| Radionucleotide studies of kidney: assessment of renal plasma flow | radioiodinated orthoiodohippurate |
| Kidney Ultrasound | assesses size and # of kidneys, mass/cyst, obstruction, screens congenital diseases (PCKD), evaluates perirenal space, guides invasive procedures, assesses bladder for urine retention, assesses calculi |
| IV pyelography (IVP) | assesses fxn and structure of urinary tract; disadvantage is that IV contrast is NEPHROTOXIC! |
| CT scan | further test after ultrasound of IVP; expensive; sometimes uses IV contrast (nephrotoxic), useful in assessment of mass/cysts, hemorrhages (retroperitoneal) or obstruction |
| MRI | as good as CT for evaluation of cyst; *better than CT in evaluation of solid lesions/masses; MRA is sensitive for renal artery stenosis |
| 1. Arteriography and 2. venography | 1. assesses renal artery stenosis (gold standard), vasculitis, aneurysm and renal mass lesions (uses IV contrast); 2. assesses renal vein thrombosis, CT/MRI are less invasive |
| Renal biopsy indications | unexplained acute renal failure, unexplained hematuria, nephrotic or nephritic syndrome, treatment guidelines (ex: SLE); suspected renal transplant rejection |
| Renal biopsy contraindications | renal infxn, renal cancer, congenital anomalies (CPKD), coagulopathy, ESRD, uncontrolled HTN, uncooperative pts, solitary fxning kidney (relative contraindication) |
| Nocturnal Enuresis: Primary vs Secondary | if the child has experienced a minimum of 6-months of continence before the onset of bedwetting, it is considered SNE; genetic component (auto dom a/w chrom 22, 8, 12, and 16) |
| Psychological and social impact of nocturnal enuresis | PNE (psych probs are a result, not the cause); SNE (psychological probs are a possible cause); behavioral problems occur d/t emotional impact on child and family (punishment, emotional/physical abuse, anxiety, loss of self esteem, dec school performance) |
| Enuresis | dryness at night usually follows achievement of continence by day; ~4yo, child can initiate micturition even in absence of desire to void by voluntary relaxation of external urethral sphincter |
| Nocturnal Enuresis Stats | more common in males; prevalence in boys 7-10yo is 9% and 10%, compared to 6% and 3% in girls; declines during childhood 5yo>7>10>18yo |
| History taking for nocturnal enuresis | ask about fluid intake, daytime voiding freq/vol, # episodes of bed-wetting (fam may need to record this over 2wks); sleep time patterns (deep, restless, arousals, timing and # of wetting episodes); diet and intake after school, assess emotional impact |
| Causes of nocturnal enuresis | idiopath (sleep arousal, noct polyuria, small night bladder capacity), urge syndrome & dysfxnl voiding, cystitis, constipation, psychological, acquired neurogenic bladder, seizures, sleep apnea, diabetes, hyperthyroidism, heart block, urethral obstruction |
| Disorders of sleep arousal | children w/NE do not wake up normally in response to auditory signals; confirming defective arousal |
| Nocturnal polyuria | d/t fluid or food ingestion b/f bedtime, low nocturnal secretion of ADH, increased nocturnal solute excretion; this cannot be the sole cause b/c there must be a reason why child doesn't wake up from sensation of full or contracting bladder |
| Cystitis | common cause of NE and an aggravating factor of other causes; can be present at any age; causes uninhibited detrusor contractions leading to day or nighttime wetting; if only cause-treat w/antibiotics (if a/w other probs daytime symptoms don't resolve) |
| Problems a/w cystitis | urge syndrome, dysfunctional voiding, neurogenic bladder, urethral obstruction, ectopic ureter, diabetes mellitus |
| Psychological causes of NE | birth of a new sibling, parental divorse/separation, death in family, child abuse, other social dysfxn at school or home; higher rate of behavioral disorders and continuous psychosocial stress a/w SNE than PNE; |
| Constipation | can cause SNE; common aggravating factor that should be considered when other causes are present; pressure of stool in descending or sigmoid colon can trigger uninhibited detrusor contraction; usu present w/neurogenic bladder and urge/dysfxnl voiding synd |
| Neurogenic bladder-1 | can develop b/c of a lesion at any time in the nervous system (cerebral cortex, spinal cord, or peripheral nerves); up to 37% of kids w/ cerebral palsy have NE; myelomeningocele, caudal regression, tethered cord, tumors, ant spinal artery, cord trauma |
| Neurogenic bladder-2 | dysfxn of external urethral sphincter can develop after pelvic extirpative surgery, radiation for pelvic malignancy, pelvic fx, incontinence surgery; a/w sacral agenesis, imperforate anus |
| Urethral obstruction | can be congenital (post urethral valves, congen stricture, urethral diverticula) or acquired (trauma - catheter, foreign body, trauma, infectious stricture - N. gonorrhoeae); Meatal stenosis distal obstruction in circumcised males |
| Seizure disorders | SNE may be the result of an unobserved major motor convulsion in a child w/a known seizure disorder; new onset seizures rarely occur at night and therefore bed-wetting is not a manifestation of them |
| Ectopic ureter | rare congen abnormality d/t insertion of ureter in a location other than lateral angle of bladder trigone; enuresis occurs when it is distal to external urethral sphincter; 3-4x more common in girls; mc site is adjacent to external urethral meatus |
| Diabetes mellitus and NE | NE is not usually the presenting complaint w/new onset IDDM; SNE in child w/established disease may indicate poor control of nocturnal polyuria d/t hyperglycemia; disorder of arousal may also be present as well as abnormal afferent sensory pathways |
| Diabetes insipidus and NE | uncommon; may be d/t nocturnal polyuria or arousal disorder; disease may be central-pituitary (d/t intracranial tumor, head trauma, encephalitis, meningitis) or nephrogenic (renal failure, diffuse cortical or medullary damage, hypo-K, hyper-Ca, drugs |
| NE urinalysis lab workup | most important screening test; Cystitis (WBCs or bacteria; a/w urge/dyxfxnl void, urethral obst, neurogen bladder, ectopic ureter, IDDM); Urethral obstruction (RBCs), IDDM (glucose), Spec gravity >1.020 excludes dibetes insipidus |
| Ultrasound and NE | not usu indicated; check for residual volume; check bladder and kidneys of pts w/daytime voiding; avoid more invasive tests for >3mo to detect improvement of symptoms |
| Voiding cystourethrography | indicated if bladder wall is thick or trabeculated or there is significant postvoid residual vol; also for pts w/suspected neurogenic bladder (look for sacral agenesis or spinal dysraphism); also for urethral obstruction |
| Treatment-Alarm Therapy | alarm detects wetness; must have compliant family to get chid to toilet; possible improvement of NE; consider for every pt; inc noturnal bladder capacity (child may slowly stop volume voided in bed, get up or wait till morning); success 68% |
| Desmopressin acetate therapy (DDAV) | preferred medication for NE; total dryness in 38-55%; tablet or nasal spray, dec nocturnal urine production and improves arousal; check serum electrolytes; can be used in combo with alarm therapy |
| Diet and NE | restrict or minimize intake after evening meal |
| Urinary tract infections (determine why child has it) | very common kid infxn; distresses child and parents, may cause permanent kidney damage; can ID an underlying structural or neurogenic abnormality of urinary tract; location of infxn often unclear w/pyuria & signif bacteriuria w/other infxn source of fever |
| Acute pyelonephritis (upper tract infection) | febrile child w/significant bacteriuria w/ or w/o other systemic symptoms |
| Cystitis (lower tract infection) | child w/UTI and voiding symptoms, little or no fever, no systemic symptoms |
| Pathophysiology of UTI | usu ascending; disturbance of normal flora that inhabit distal urethra (urine is normally sterile in proximal urethra, urinary bladder and more proxmial sites); uropathogens must gain access to bladder (d/t impaired voiding defenses) |
| Frequency of UTI | highest rate of first-time symptomatic UTI in 1st yr of life for both sexes (M>F; acute pyelonephritis); after age 2, cystitis incidence inc in girls >> boys |
| Morbidity and Mortality a/w UTI | rare in developed countries; a/w acute pyelonephritis (fever, abdoml pain, vomit, dehydration, bacteremia, sepsis, acute cystitis?; long-term: HTN, ESRD, pregnancy probs); Acute cystitis (transient voiding probs, renal damage 2* to pyelo in long-term) |
| UTI: birth to 2 months | acute pyelonephritis not a/w with symptoms; discovered as part of evaluation for neonatal sepsis |
| UTI: 2 months to 2 years | acute pyelonephritis a/w unexplained fever; at higher risk for renal injury than older children d/t delay in identifying signs and initiation of antibiotic therapy; 3-day rule may avoid undue delay for tx (urine sample for child w/unexplained fever >3d) |
| UTI: 2 months to 2 years (less common presentation) | some infants w/acute pyelonephritis are irritable, dec oral intake, abdom pain, vomit, loose bowels; Pts 1-2yo crying on urination or fowl odor to urine w/o fever have acute cystitis |
| UTI: 2-6 years | Pyelonephritis: fever, loss of appetite, irritability, abdom/flank/back pain, w/ or w/o voiding abnormalities; Acute cystitis: voiding Sx (urgency, frequency, dysuria, incontinence) w/no fever, abdom pain and fowl odor to urine |
| UTI: older children and adolescnets | usu lower tract acute cystitis, but acute pyelonephritis is possible; similar symptoms to 2-6yo group; girls usu have recurrent UTI if they start young |
| UTI: Physical Findings | in older children: pyelonephritis may be a/w flank or costovertebral angle tenderness and Acute cystitis may have suprapubic tenderness |
| UTI: Causes | proliferation of bacteria in urinary tract; ascending; E. coli causes initial infection, but other G(-) bacilli & enterococci too; Staph saprophyticus in adolescent females; entry into bladder d/t turbulent void flow, dysfxn, catheter, sex, genital manip |
| UTI: predisposing factors | broad spectrum antibiotic use (amoxicillin, cephalexin) that can alter GI and periurethral flora; prolonged incubation of bacteria in bladder urine d/t incomplete or infrequent voiding; voiding dysfxn, constipation; (uncircumscised inc risk in 1st yr) |
| UTI: imaging studies | don't obtain until diagnosis confirmed by quantitative urine culture |
| UTI: ultrasound | indicated for all first time diagnosis of acute pyelonephritis or acute cystitis (infants); if second time infxn, only image if suspected abscess or obstruction needs to be ruled out; not necessary in children >2yo w/acute cystitis responsive to treatment |
| UTI: Voiding cystourethrogram (VCUG) | perform on pt w/acute pyelonephritis with no previous bladder imaging once bacteria is cleared from urine |
| Treatment for Acute Pyelonephritis | children require oral or parenteral fluids and antipyretics as well as antibaterials; if severe, pt may require inpatient management; suppressive antibacterial therapy for 6months+ |
| Treatment for Acute Cystitis | no special medical care needed besides appropriate antibiotics |
| Hematuria | presence of >5 RBCs in 3 consecutive specimens obtained 1wk apart; dipstick in office is often 1st indication; can be gross or microscopic; symptomatic or not; isolated or a/w proteinuria an other urinary abnormalities; common consult to ped nephrologist |
| Hematuria Pathophysiology | varied; glomerular origin (structural disruption in BM d/t inflam or immune processes), chemical toxicities of renal tubules; calculi w/mechanical erosion of mucosal surfaces in GU tract |
| Hematuria: frequency | 0.13% of children; >50% of cases have easy etiology (mc is cystitis); microscopic more common than gross; rare coexistance w/proteinuria, but indicative of significant renal disease |
| Hematuria: morbidity and mortality | if isolated, prognosis is good; if a/w HTN, proteinuria, abnml serum creatinine there are more serious probs; dependent on cause of disease process |
| Hematuria: relavent histories for differential | UTI (fever, abdom pain, dysuria, freq); Trauma (hydronephrosis); Postinfective glomerulonephritis (recent throat/skin infxn); exercise, mensturation, cather, drugs/toxins; familial dx (Alport syndrome, collagen vascular dx, stones, PCKD) |
| Hematuria: Pathology | glomerular (brown urine, RBC casts, dysmorphic-sm misshapen/fragmented RBCs, proteinuria) or non-glomerular (reddish/pink urine, passage of blood clots, eumorphic-nml biconcave RBCs) |
| Causes of Glomerular hematuria | thin basement membrane dx (benign familial hematuria), Alport syndrome, IgA nephropathy, hemolytic uremic syndrome, postinfectious GN, membranoprolif GN, lupus nephritis, anaphylactoid purpura (Henoch-Schonlein purpura) |
| Causes of Non-Glomerular hematuria | fever, strenuous exercise, mechanical trauma (masturbation), foreign bodies, UTI, hypercalciuria/stones, sickle cell dx/trait, coagulopathy, tumors, drugs/toxins, anatomy (hydronephrosis, PCKD, vascular malformations) |
| Hypercalciuria | 30% of kids w/isolated hematuria (gross or microscopic); may or may not be a/w dysuria; a history of "sandy urine" or actual passage of calculi can occur |
| IgA (Berger) Nephropathy | *most common cause of chronic glomerulonephritis in the world* usu painless intermittant gross hematuria followed by persistant microscopic; colicky abdom pain; preceded by URTI; may have HTN, proteinuria, elevated serum creatinine; presentation may vary |
| IgA Nephropathy: Incidence, Dx, Tx | less common in blacks; M>F; up to 50% progress to chronic or ESRF; elevated serum IgA is not sufficient for Dx, *must get biopsy w/characteristic IgA deposition in glomerular mesangium;* No effective Tx |
| Henoch-Schonlein Purpura | similar IgA pathophysiology to IgA nephropathy in addition to vasculitis & purpura (back/legs); peaks at 4-5yo; M>F; 30% precede w/URTI; hemat-/proteinuria; rule out SLE w/ ANA & C3 levels; self limited, no Tx |
| Henoch-Schonlein Purpura: supportive tx and possible outcome | antihypertensives to control HTN, diuretics to relieve fluid retention, CCsteroids for inflam of joints and rash intensity; If it presents w/nephritis and/or nephrotic syndrome pt may progress to chronic renal failure |
| Hemolytic uremic syndrome (HUS) | common cause of acute renal failure in children; develops thrombocytopenic microangiopathic hemolytic anemia and renal failure after preceding/bloody gastroenteritis (<2wks); usu microscopic hematuria; a/w Shiga toxin from E. coli; rare in blacks; F>M |
| Postinfectious Glomerulonephritis | mc cause of gross hematuria in kids; preceded by 1-4wk infxn w/nephritogenic strain of GAS (skin infxn or pharyngitis 1-2wks b/f onset of GN symptoms); pharyngitis in winter/spring 5-15yo; skin in summer/fall (pyoderma) in younger kids |
| Postinfectious glomerulonephritis: diagnosis | gross hematuria 25-33% (pink-dark tea color); 85% edema, HTN and oliguria; dysmorphic RBCs & RBC casts; elevated ASO (antistreptolysin-O) and dec C3 levels; anti-DNAse B in pyoderma cases; serial serum samples help |
| Postinfectious Glomerulonephritis: Treatment | mostly supportive; fluid/salt restriction to help fluid retention; HTN: (loop diuretics, vasodilators, Ca-channel blockers, b-blockers, ACE-i); C3 will normalize; gross hematuria stops, but microscopic may remain for yrs |
| Systemic Lupus Erythematous | 2/3 of affected kids have renal involvment; varied combos of gross hematuria and proteinuria (up to nephrotic range) and HTN; *degree of hematuria does NOT correlate w/severity of renal lesions* |
| SLE: renal findings | range from mild glomerulonephritis to diffuse proliferative glomerulonephritis; Tx and Px depends on histological class; drugs (steroids, alkylating agents (cyclophosphamide), animalarials, calcineurin-i, mycophenolate mofetil) |
| Tests for hematuria | urine dipstick (followed by microscopic if positive) is most sensitive (detects peroxidase activity of Hb); detects trace Hb of Mb; false positives from dyes, drugs, beets or oxalates |
| Renal and bladder sonography | detects urinary tract anomalies (hydronephrosis, hydroureter, nephrocalcinosis, urolithiasis); if obese, use CT instead |
| Other imaging studies for hematuria | spiral CT (urolithiasis), voiding cystourethrograms (detect cystitis); radionucleotide studies, IV urographyy |
| Justification for renal biopsy in pts with hematuria | symptomatic pt; simultaneous proteinuria, elevated serum creatinine, abnml complement or dsDNA; hypertension, suspicious clinical/family Hx, recurrent gross hamaturia; other imaging/lab abnormalities |
| Approach to hematuria | comprehensive history and physical; urine dipstick, microscopic review, urinalysis to confirm RBCs/casts; localization of bleeding (casts and dysmorphic cells = glomerular bleeds); urine culture and Ca-creatinine ratio |
| Hematuria of glomerular origin | low C3 (membranoproliferative GN or SLE - confirm w/ANA or dsDNA); low C3 + high ASO titer or anti-DNAseB (poststreptococcal GN) |
| Proteinuria | >30mg/d of albumin (indicative of inc glomerular permeability); usu detection on dipstick is transient, on repeat more males are confirmed than females |
| Albuminuria/microalbuminuria | >300mg/d (detectable on dipstick); 30-300mg/d need urine spot test to give microalbumin:creatinine ratio |
| Nephrotic syndrome | glomerular cause (PNS, SNS); massive loss of urinary protein (primarily albuminuria) leading to hypoproteinemia (hypoalbuminemia) and its result, edema; usu a/w hyperlipidemia, hypercholesterolemia and inc lipiduria; Watch for HTN, hematuria and azotemia |
| Secondary Nephrotic Syndrome | a/w more clearly defined diseases: anaphylactoid purpura, SLE, diabetes mellitus, sickle cell disease, syphilis... |
| Pathophysiology of Nephrotic Syndrome: Edema | natural course of hypoalbuminemia; dec in plasma oncotic pressure causes pooling in interstitial space; decreases plasma vol & dec renal perfusion stimulates Renin-angiotensin system; along w/inc antidiuretic hormone, renal tubule reabsorbs more Na/water |
| Net result of Edematous Mechanism in Nephrotic Syndrome | the combo of Starling forces, reduction in renal perfusion (GFR) and inc hormonal activity causes further reabsorption of Na and water, which leads to either maintenance or furthering edema |
| Nephrotic Syndrome Stats | Primary NS is very rare; mortality depends on the type of dx causing loss of albumin; MCNS has 70% remission rate with lower mortality than FSGS (focal segmental glomerulosclerosis) 24% remission, but 50% mortality |
| Minimal change nephrotic syndrome (MCNS) | a chronic disease that requires administration of meds a/w significant adverse effects; high rate of recurrence (>60% have relapses); potential progression to chronic renal failure |
| Minimal-change nephrotic syndrome Pathology | glomerular morphology on light microscope is nml; minimal mesangial alterations, no immunoglobluins;*electron microscopy shows flattening and fusion of epithelial cell podocytes* |
| Focal global glomerulosclerosis (FGGS) Pathology | globally sclerotic glomerulus occuring in focal areas w/remaining glomeruli nml; <5% of nml variant glomeruli may be sclerotic |
| Focal segmental glomerulosclerosis (FSGS) Pathology | lesions where some glomeruli are involved in segmental sclerosis (one lobule/section w/in single glomerulus) w/remaining nml; usu confined to juxtamedullary nephrons; IgM-complex deposits in sclerotic area on immunofluorescence |
| Mesangial proliferative glomerulonephritis (MPN) | minimal mesangial expansion; *IgM, IgG, C3 found on immunofluorescence* |
| Membranoproliferative Glomerulonephritis (MPGN) | all glomeruli involved; proliferation of cells and extensive immune deposits on immunofluorescence and electron microscopy |
| Glomerular lesion complications: NS secondary to MCNS | few complications, acute renal failure is rare, tubulointerstitial nephritis, hypertension and progression to CRF is UNCOMMON |
| Tubulointerstitial neprhitis and NS | common in all NS except MCNS; a/w glucosuria and aminoaciduria in FSGS |
| Hypertension and NS | common consequence of MPGN and FSGS |
| Progression to CRF and NS | observed with increasing frequency in MGN, FSGS, MPGN |
| Medical care for NS | treat primary causes if NS is secondary; try glucocoritcoids (prednisone or prednisolone), the other drugs (diuretics, antihypertensives, immunosuppressives) have significant side effects |
| Hypoproteinemia | massive loss of urinary ptn induces a degree of ptn malnutrition in all kids w/NS; if they fail therapy they are at a negative ptn balance and at risk for growth failure, etc; |
| Hyperlipidemia | direct result of inc hepatic production of lipids and lipoproteins and is related to degree/duration of hypoproteinemia; if chronic can lead to CV complications and progression of renal disease |
| What proteins are lost in hypoproteinemia? | mostly albumin; but other small MW anionic ptns (transferrin for Fe transport, opsonins important to avoid peritontisis; anticoagulant loss can lead to thrombosis) |
| Diabetes epidemiology | 124mill people (2.1% of pop, 97% are NIDM); most dialysis pts have diabetes; |
| Type I Diabetes | autoimmune isletitis; genetic w/possible viral trigger; usu younger pts that are very sick/brittle; aggressive diabetic probs in mid 30s include: eyes, kidneys, infxn, stroke, heart, peripheral vascular disease |
| 10yr follow up of Type I Diabetes: | 20-50% progress to proteinuria; glomerular lesions; hypertension; retinal lesions; cholesterol; stroke; amputations |
| Type II Diabetes | insulin resistance; inc blood insulin level (atherogenic mileau); usu older pts w/other problems (weight, cardiac, essential hypertension) |
| Type I vs. Type II Diabetes, what's the difference really? | **Retinopathy has very close correlation with nephropathy in TYPE I (thus, be suspicious of diagnosing nephropathy w/o retinopathy); treatment for both seems to be the same (bp, glucose, lipids, ptn); **though, 90% of diabetics on dialysis have TYPE II** |
| Advanced glycosylation end products | d/t the combo of time, temp and reactants..too much sugar for too long with cause AGEPs |
| Glycosylated hemoglobin (HbA1C) | glucose irreversibly binds to Hb depending on [blood glucose]; HbA1C reflects mean [glucose] over past 6-8wks (**best index of glycemic control**); target regresion value is 7% (~150mg/dL) to protect against renal & eye dx |
| Hyperfiltration theory | inc blood flow per nephron causes stress damage in glomerular capillary wall resultingin glomerular scarring "focal sclerosis," nonspecific may be the end stage of several initial disease processes |
| Protein restriction slows progression of diabetic nephropathy | d/t a 75% reduction in the rate of loss of glomerular filtration rate |
| The incidence of diabetic retinopathy increases over time | the percent of diabetic pts w/retinopathy correlates with nephropathy d/t similar capillary damage |
| Diabetic vascular disease | multifactorial or multifaceted (eyes, heart, kindey, brain, feet) |
| Estimate of proteinuria by spot test | get protein-creatinine ratio to estimate excretion |
| Potential causes of microalbuminuria other than diabetes mellitus | endothelial dysfxn, renin-angiotensin-aldosterone, lipid abnormality (atherosclerosis), systemic inflammtion (peridontal dx can lower glucose tolerance) |
| Normal Albuminuria | negative dipstick: <20mic/min, <30mg/24hr, <30mic/mg creatinine |
| Diabetic Nephropathy Stage I: No lesions | inc GFR (elevated glucose>GH surge, genetics, hyperfiltration, low nephron number, larger kidneys, stressed) |
| Diabetic Nephropathy Stage II | lesions present, no proteinuria, normal BP...you can do a lot at this stage to prevent progression |
| Diabetic Nephropathy: Microalbuminuria Stage II-III | special dipstick positive (more sensitive test); pt is in trouble so you need to do something; 20-200mic/min, 30-300mg/24hr, 30-300mic/mg creatinine |
| Diabetic Nephropathy: Microalbuminuria Stage III | 5+ years of diabetes, poor glycemic control (HbA1C); 400% inc risk for progression to ESRD |
| Diabetic Nephropathy: Macroalbuminuria (proteinurea) Stage III-IV | positive urine dipstic most of time (damage done-nephrologist consult); >200mic/min, >300mg/24hr, >300mic/mg creatinine |
| Diabetic Nephropathy: Stage V | *glomerular filtration is <15-20% of normal (GFR declines 1.2mL/mo)!* dialysis, coronary and other heart disease/death is high, infxn, death; 10-20yrs of diabetes; dipstic positive; HTN in 75% |
| What are the thre preventive diabetic retinopathy screening tests? | HbA1C, Lipid levels, Retinal eye exam |
| How can you protect your diabetic patients from getting nephropathy? | **Get their blood pressure down;** inhibition of the renin-angiotensin-aldosterone system, independent of blood pressure changes, decreases both micro and macrovascular complications in type 1 and type 2 diabetics |
| Increased cardiovascular risk in essential HTN and microalbuminurea (not DM) | LVH, impaired LV fxn; more severe coronary disease at angiography; thicker carotid artery wall, ischemic stroke, peripheral vascular disease |
| Strict glycemic control prevents: | microalbuminuria in pts with type I diabetes mellitus |
| Diabetic Nephropathy: Associated lesions not unique to diabetes | nephrosclerosis, atherosclerosis, emboli, interestitial nephritis, atheroocclusive diseases |
| Clinical Diabetic Proteinuria | "quiet urine" - ptn, but not many cells; HTN, retinopathy, edema, slowly worsening azotemia (urea in blood) |
| Pt does NOT have Diabetic Nephropathy if you see the following: | on urinalysis: casts (RBC/WBC), RBCs, Globulin; Recent infectious disease; Systemic illness (rheumatological); Severe anemia; |
| DDx for Diabetic Nephropathy | membranous nephropathy, myeloma, amyloid, minimal change glomerulonephritis; **diagnose before you start treatment |
| Major Causes of End-stage renal disease | Diabetes and HTN |
| How to treat diabetics with nephropathies? | **blood pressure lowering drugs (ACE-i, b-blockers, Ca-channel blockers)**, diet and exercise modification |
| Action of ACE-i (ex: captopril) | inhibits conversion of angiotensin I to angiotensin II by at level of ACE; also inhibits conversion of kinins to inactive metabolites which allows them to upregulate bradykinin B2 receptors for vasodilation; **delays progression of microalbuminuria) |
| ACE-i/ARB side effects | **contraindicated in pregnancy;** hyperkalemia (aldosterone reduced/blocked); renal failure (use caution w/CDK III), *cough* |
| Normal blood lab values: Na | 131-145 |
| Normal blood lab values: K | 3.5-5.6 |
| Normal blood lab values: Cl | 98-110 |
| Normal blood lab values: HCO3 | 22-31 |
| Normal blood lab values: BUN | 5-20 |
| Normal blood lab values: Creatinine | 0.5-1.5 |
| What does a doubling of creatinine show? | a halving of the GFR; deterioration of renal function |
| How is renal dysfunction detected? | creatinine and BUN in blood (**gold standard used to estimate GFR**; blood and protein in the urine |
| Having only one value for serum creatinine cannot indicate if pt is healthy or not, b/c: | we lose muscle mass with age, males have more muscle mass and higher SCr than females; amputations and race alter normal values |
| Estimating GFR | labs should report the MDRD back to you with the creatinine value |
| Solute reabsorption by the kidney: | Water (98-99%), Na (>99%), Cl (99%), HCO3- (~100%), K (80-95%), Urea (40-50%) |
| Major functions of the Glomerulus | forms an ultrafiltrate of plasma |
| Functions of proximal tubule | reabsorbs 60-65% of NaCL and H2O, 90% of HCO3; major site for ammonia production; reabsorbs K, PO4, Ca, Mg, urea, uric acid and most glucose/AAs; secretes urate, creatine, ptn-bound drugs/toxins |
| Majore functions of the Loop of Henle | Reabsorbs 25-35% of NaCl; countercurrent multipliers as NaCL reabsorbed in excess of water; major site of Mg excretion |
| Major functions of the Distal Tubule | reabsorbs 5% of NaCl and almost no water; major site, w/connecting segment, of active regulation of Ca excretion |
| Major functions of the Connecting Segment and Cortical Collecting Duct | principal cells reabsorb NaCl and secrete K under influence of *Aldosterone;* Intercalated cells secrete H+, reabsorb K and in metabolic alkalosis secrete HCO3; Reabsrob water in presence of *Antidiuretic Hormone* |
| Major functions of the Medullary Collecting Duct | site of final urine modification; reabsorbs NaCl; water and urea reabsobtion relative to amt of ADH; secretes H+ and NH3 (urine pH can be reduced as low as 4.5-5.0); can contribute to K balance by reabsorption OR secretion of K |
| Acute Renal Failure Defined | sudden dec in GFR occuring over hrs-days and resulting in failure of kidney to excrete nitrogenous waste products and maintain fluid/electrolyte homeostasis; Clinically recognized by doubling of SCr & inc BUN; ARF occurs in pts w/nml renal fxn or CKD |
| Distinguishing ARF from CRF | get old records for previous SCr and BUN levels; are kidneys small? does pt have anemia (erythropoeitin isn't stimulating bone marrow to produce more RBCs? --> that would be CRF |
| Mortality a/w ARF | ICU a/w respiratory failure and dialysis > ICU > hospitalized pts > following IV contrast > following cardiac surgery > following administration of amphotericin B |
| ARF: Pre-renal etiologies | 1. dec intravascular fluid vol (ECF floss or sequestration); 2. dec cardiac output (heart dysfxn, peripheral vasodilation); 3. severe renal vasoconstriction (sepsis, drugs, hepatorenal syndrome); 4. mechanical occlusion of renal aa (thrombotic occlusion) |
| ARF: Post-renal etiologies | Intrarenal (crystal deposition, protein deposition); Extrarenal (ureteric/pelvic intrinsic or extrinsic obstruction); Bladder (prostate hypertrophy; stones, clots, tumor, neurogenic, meds); Urethral, Stricture, Phimosis of foreskin |
| ARF: Intra-renal etiologies | Renal vascular disorders; Glomerulonephritis; Interstitial nephritis; Infxn; Infiltration; CT disease; Tubular necrosis |
| Pre-renal failure (oliguria, inc BUN, inc SCr): Hypovolemic states | hemorrhage, burns, dehydration, vomiting, diarrhea, diuretics, pancreatitis |
| Pre-renal failure: low cardiac output states | arrhythmias, pulmonary embolism, myocardial or valvular dx, tamponade, pulmonary HTN |
| Pre-renal failure: renal vasoconstrictive states (results in ischemia) | septicemia; liver failure - cirrhosis w/ascites, vasocosntrictive drugs (Epi, NE, cyclosporine, amphotericin B) |
| Pre-renal failure: intrinsic decrease of renal perfusion states | liver failure; cyclo-oxygenase (COX) inhibitors, ACE-i |
| Intra-renal failure: actue tubular injury/necrosis | exogenous toxins (contrast, cyclosporine, aminoglycosides, ethylene glycol, acetaminphen, metals); endogenous toxins (myoglobin, uric acid, oxalate); postpartum hemorrhage (Sheehan's pituitary necrosis); rejection of renal transplant |
| Intra-renal failure: obstruction of renal vasculature | atherosclerosis, vasculitis, disseminated intravascular coagulopathy, GN, hemolytic uremic syndrome, thrombotic thombocytic purpura, pregnancy, scleroderma, SLE |
| Intra-renal failure: interstitial nephritis | b-lactams, sulfonamides, thrimethophrim (TMP), rifampin, NSAIDs, diuretics, captopril , infxn |
| Post-renal failure: bilateral obstruction of ureters or obstruction of urethra; <5% of ARF | urolithiasis; prostatic hyperplasia; tumor obstructing bladder or ureters bilaterally; neurogenic bladder |
| Community aquired ARF: prerenal or ATN | acute systemic illness (viral/flu/diarrhea) d/t volume depletion |
| Community aquired ARF: acute poststreptococcal GN | strep pharyngitis/pyoderma leads to immune complex deposition in glomeruli |
| Community aquired ARF: rhadomyolysis | trauma, crush injury, prolonged immobilization leads to extensive muscle damage and tissue breakdown (elevated CPK) |
| Community aquired ARF: postrenal | urinary tract symptoms (difficulty voiding, incontinence, dribbling) d/t obstruction or neurogenic bladder |
| Community aquired ARF: allergic interstitial nephritis | fever and/or rash in new pt w/a new med d/t NSAIDs, antibx, diuretics for outpts |
| Community aquired ARF: ATN | accidental/intentional overdose on nephrotoxic drug w/altered mental status: heavy metals, solvents, ethylene glycol, salicylates, acetaminophen |
| Hospital aquired ARF: prerenal or ATN | excessive fluid loss from aggressive diuresis, nasogastric suction, surgical drains, diarrhea, etc; causes volume depletion |
| Hospital aquired ARF: prerenal or ATN | surgery w/ or w/o concommitant vol depletion; anesthesis causes renal vasoconstriction which reduces renal blood flow |
| Hospital aquired ARF: ATN | radiologic (contrast CT) or other procedures (coronary angiography) d/t nephrotoxic IV contrast dye |
| Hospital aquired ARF: ATN | sepsis: infxn, vol depletion, hypotension, nephrotoxic antibx (ex: aminoglycosides, NSAIDs, ARB, ACE-i) |
| Most cases of ARF are d/t: | acute tubular necrosis |
| Sequential evaluation of acute renal failure | 1. **take Hx, **urinalysis, consider bladder cath; 2. Diagnostic testing, Empirical Trials (stop drugs, vol expansion, improve cardiac fxn, relieve UT obstruction), Tissue Analysis (renal Bx, other tissue Bx) |
| Clearance | how much is cleared from the kidney in a minute |
| Fractional excretion of sodium | divide sodium clearance by creatinine clearance |
| Fractional excretion of Na: Prerenal ARF | FENa <1; kidney is still functional |
| Fractional excretion of Na: Renal ARF | FENa >2; kidney is damaged and is not fxning normally |
| Conservative treatment for acute renal failure | reverse/treat causes of ARF; improve blood volume; establish a urine output; provide nutrition, minimize use of invasive lines/procedures; monitor drug dosages; **DON'T TRY DIURETICS (they may be good for other kidney probs, just not ARF)** |
| Renal-dose dopamine | **do NOT use with ARF;**doesn't work; causes arrhythmias, necrosis of skin, doesn't change pt's outcome (only improves urine output slightly) |
| What indications are there to start dialysis in a pt with ARF | physiologic (kidney controls bp, if vol is so high you have CHF/pulm edema); Electrolytes (hyper-K+ can stop the heart); Nitrogenous waste products (uremic symptoms - nausea, vomiting, irritability); Bicarbonate (acidodic pts need it) |
| When do start dialysis? | persistent oliguria (<400mL/d); SCr >6mg/dL; BUN >100mg/dL; Pulmonary edema unresponsive to diuretics; Hyperkalemia >6.5mEq/dL; Symptomatic uremia (encephalopathy, pericarditis); Severe metabolic acidosis |
| ARF Cases: BUN/Creatine ratio of 10:1, pt recently dx w/ gout | **drug-induced by Allopurinol; this is a renal problem b/c of the ratio |
| ARF Case: total hip replacement, indwelling foley (urethral) catheter; BUN/Cr = 10:1 | exclusion of obstruction; Renal; get a fractional excretion of Na test; he's on NSAIDs...stop them |
| ARF Case: CHF, BUN/Cr is extremely high; being treated w/antidiuretics; FENa <1 | prerenal azotemia |
| ARF Case: trauma, in hosptital, BUN/Cr=10:1; we don't know creatinine on admission | CPK is normal, she had a fever and is treated w/gentamycin (aminoglycoside); REVERSIBLE |
| ARF Case: old man altered mental status; high BUN/Cr ratio | does he have enlarged prostat? uremic how long has he been sick? mo-yrs; put a catheter in...it's postrenal |
| Physiological Functions of the kidney (and complications d/t CKD) | Filter nitrogenous waste (uremia); produce EPO (anemia); regulate acid-base (acidosis); control fluid vol (CHF/pulm edema); regulate Na, K, PO4 (2* hyperparathyroidism); regulate BP (hyper-K, hyper-PO4, HTN) |
| What may be the earliest factors to indicate potential risk of CKD? | blood pressure and glycemic control |
| What is the most common measure of renal function? | Serum creatinine; normal range is .5-1.5mg/dL; significant deterioration of renal fxn can occur before significant SCr decline; therefore it is important to screen at-risk pts on a regular basis |
| What can urinalysis uncover? | indicators of kidney disease: pyuria, proteinuria, hematuria, abnromal sediment and presence of glucose; microalbuminuria is an early indicator of nephropathy (esp in pts w/diabetes) |
| Stage 1 Kidney disease | evidence of kidney damage via ptn and glucose on urinalysis; usu have hyperinflation of kidneys d/t superphysiological GFR; you need to intervene so they don't end up on dialysis |
| **Stage 3-5 kidney disease | pts need to see a nephrologist; pts go on dialysis at different times depending on if they are diabetic or not; start stage 5 diabetics w/clearance of 15 and non-diabetics w/clearance of 10 |
| What are the 2 leading causes of chronic kidney disease? | hypertension and diabetes (followed by interstitial nephritis, glomerulonephritis, and other urologic diseases); early treatment is slowing progression |
| The majority of pts with CKD have what signs and symptoms? | NONE; it is usu diagnosed by a routine blood or urine test; (stage 4/5 have lethargy, nausea, vomitine, HTN, confusion, SOB from uremia) |
| Reasons for progression in CKD | glomerular hyperfiltration can damage kidney; abnormal glomerular permeability presents w/proteinuria and that may incite "tubulointerstitial disease" ==> a prime risk factor for renal disease progression |
| General methods to slow progression of CKD | antihypertensives (target BP 130/85 w/o ptnuria or 125/75 with); ACE-i/ARB; diabetic control of HbA1c to <7%, restrict ptn, avoid nephrotoxic meds; STOP smoking; treat specific diseases (prednisone/cytotoxic or immunosuppressives for glomerulonephritis) |
| Complications a/w CKD | **anemia (must treat; can cause LVH - CHF - angina), hypertension (cause/complication; Tx w/ACE-i), CV disease (LV dysfxn --> ESRD), diabetes, osteodystrophy, malnutrition (measure w/serum albumin; need AAs), metabolic acidosis, dyslipidemia, death |
| CKD pts are more likely to die than progress to ESRD | pts diagnosed w/CKD only are 10x more likely to die than reach dialysis; pts diagnosed w/DM and CKD are 5x more likely to die than reach dialysis |
| Anemia is a critical CV risk factor for CKD pts | pts w/mild-mod impaired renal fxn not on dialysis have high prevalence of LVH early in course of dx; LVH will progress and is a/w modifiable risk factors (low Hb and high systolic bp); **the low Hb level is an independent predictor of LVH progression** |
| Prevalence of CV disease in relation to CKD | coronary heart disease, CHF and LVH are 2-3x more common in pts with mild kidney disease than those with normal SCr (Framingham heart study) b/c of associated anemia |
| Anemia compared to Diabetes | pts w/a diagnosis of CKD and anemia have same relative risk of death as pts with a diagnosis of diabetes and CHF; and CKF is an independent predictor of mortality in CHF pts |
| Elevated PTH levels are a/w | PTH >800 is severe thyroid disease; increased mortality rate; |
| What is the only chronic kidney disease where EPO cells retain their viability? | polycystic kidney disease |
| The impact of anemia and CKD on the entire body: | affects most major organ systems, resulting in reduced quality of life, need for hospitalization, and, in some cases, death; dec exercise capacity, SOB, skin vasoconst, cardiac enlargement, angina, eyes, ears, cognition, immune/GI system, sexual fxn... |
| Associated benefits of increasing Hb/Hct levels | give synthetic EPO b/c sick kidney can't do it anymore; all pts w/kidney disease should be treated for anemia to help ward off death |
| How does kidney fxn relate to synthesis of active vitamin D? | kidney produces 1-alpha hydroxylase that produces 1.25 dihydroxy-cholecalciferol (calcitrol); this is the most active form of Vit D; as kidney disease progresses active Vit D production dec w/GFR as a reflection of fxnl renal mass |
| What's up with vit D deficiency and phosphate retention? | CKD causes a deficiency of Vit D and overabundance of phosphate b/c the kidneys cannot properly eliminate the phosphate; together this mismatch contributes to dec Ca and secondary hyperparathyroidism that breaks down bone |
| Pathophysiology of Secondary Hyperparathyroidism (HPT) | **deposition of calcium along arteries, heart valves** and cause systemic toxicity, etc; loss of kidney fxn, dec prod of active vit D, phosphorus retention, levels of ionized extracellular Ca dec; the parathyroid gland releases PTH to inc [Ca]... |
| CKD-management of Vit D deficiency and phosphate retention | Tx w/supplementation of: vit D analogs (calcitriol); low phosphate diet, phosphate binders (Ca-containing, or Ca-free), Calcium |
| Normal Acid/Base Balance | food intake = 70mEq/d of acid; to compensate for influx and acid from muscle catabolism, the kidney should excrete a similar amt of acid (40mEq/d NH4 and 30mEq/d titratable acid) in steady state it is matched & balanced w/nml Serum HCO3 (24mEq/L) |
| CKD and acid/base balance | NH4 and titratable acid excretion is insufficient to compensate for inc endogenous acid production; the fall of serum bicarb is lessened by buffering of acid by limited release of alkali by bones; renal dysfxn, GI loss of alkali (diarrhea) inc morbidity |
| CKD consequences of metabolic acidosis | abnml renal handling of ions (dec tubular phosphate/Ca reabsorption and inc filtered load of Ca/phosphate) causes inc resorption of bone and inc muscle catabolism; chronic met acidosis induces Ca/Phosphate imbalance |
| Bone resorption directly occurs when: | bone is dissolved to buffer excess H+ of metabolic acidosis; |
| Acidosis also causes bone resorption indirectly by: | stimulating the release of parathyroid hormone, the activity of osteoclasts and the suppression of osteoblasts |
| Goal of treating metabolic acidosis in CKD | get serum bicarb >20mEq/L and pH >7.35; Tx by oral alkali (sodium bicarbonate or sodium citrate; don't give w/aluminum-antacids to prevent Al intoxiation); dose is dependent on initial serum HCO3 and degree of renal insufficiency |
| CKD Nutrition, Eating well and Exercise | ptn malnutrition is common in CKD b/c ptn restriction can dec complications of uremia and dec rate of loss of renal fxn which will improve long-term survival; Exercise improves physical fxning and CV health |
| Summary: How do you reduce mortality in CKD pts? | detect CKD early; treat anemia, secondary hyperparathyroidism, acidosis, BP, DM |
| Disorders of Na concentration imply: | abnormal water balance, abnml serum osmolarity, shifts of water across the cell membrane |
| Hyponatremia | Serum Na <130; ECF vol and Sosm determine etiology; usu d/t water imbalance NOT Na (vol) imbalance; *hospitalized pts treated w/hypotonic fluids are at risk* |
| Hypotonicity effects: | inhibits hypothalamic osmoreceptors; dec AVP release (renal water excretion) and dec thirst (dec water intake) ==> leads to isotonicity |
| Hypertonicity effects: | stimulates hypothalamic osmoreceptors; inc thirst (inc water intake); inc AVP release (inc renal water retention) ==> leads to isotonicity |
| Urine Na | helps distinguish renal from non-renal causes; |
| Urine Na of >20mEq/L | 'salt wasting' |
| Urine Na of <10mEq/L or FENa <1% | (unless diuretic is given) this implies Na retention by kidneys to compensate for *extrarenal* losses (diarrhea, sweating, vomiting) |
| Isotonic Hyponatremia | rule out with Sosm, glucose and lipids; seen with *hyperlipidemia and hyperproteinemia >10g/dL (IV gamma-globulin therapy) occupying a very large portion of plasma vol, but Posm is nml; [Na] in plasma is nml 'pseudohyponatremia' |
| Hypertonic Hyponatremia | mc seen in *hyperglycemia* from diabetic ketoacidosis; glucose draws water from cells to ECF; serum Na is diluted; (also seen w/mannitol - hypertonic sol'n w/osmotically active osmoles draws water to ECF) |
| Hypotonic Hyponatremia | *true hyponatremia;* **retention of electrolyt free water always occurs b/c of impaired excretion (renal failure) or inappropriate ADH secretion** |
| Hypovolemic Hypotonic Hyponatremia | hyponatremia w/dec ECF vol; renal or extrarenal vol loss; to maintian intravasc vol ADH sec inc and water is retained; *drive to maintain vol overides need to maintain nml Sosm;* Na/water los is replace w/water only; Tx: Isotonic Saline |
| Euvolemic (nml) Hypotonic Hyponatremia | syndrome of inappropriate antidiuretic secretion of ADH (SIADH); pt is euvolemic; ADH release is independent of Osm or Vol |
| Causes of SIADH | *Drugs that inc ADH production (antidepressants, neuroleptics) or Potentiate action of ADH (NSAIDs); CNS (trauma, stroke, hemorrhage); Pulmonary (cancer, pneumonia); Malignancies; pain, postop, pregnancy |
| SIADH: Reset Osmostat | ADH suppressed at lower serum osmolality; elderly, pulm disease, malnutrition, pregnancy |
| SIADH Clinical Features: Hyponatremia | **dec Sosm (<280) with inappropriately high Uosm (>150) --> it should drop when serum osmolality is low;** no cardiac, liver, or renal disease; nml thyroid fxn; natriuresis UNa >20; low BUN and uric acid |
| Hyponatremia after surgery | excessive hyptonic postoperative fluid; high ADH secondary to pain, narcotics and volume contraction |
| Hypothyroidism | inappropriately elevated ADH; impaired water excretion by kidneys |
| Psychogenic Polydipsia | "excressive thirst* H2O intake >10L/day; bursts of ADH in manic depressive pts w/high water intake; psychiatric pts often on drugs that impair free water excretion |
| Diuretics causing hyponatremia | usu Thiazide; more common in elderly to treat HTN; it affects urine dilution |
| Endurance exercise hyponatremia | excessive quantities of hypotonic fluid ingestion; continued ADH release; often worsened by NSAIDs |
| MDMA (ecstacy) abuse | enhanced ADH released by drug and its metabolites |
| symptomatic hyponatremia | serum Na <120mEq/L (goal is to get serum to 120); *central pontine myelinolysis may occur if there is overly rapid correction, therefore inc <1mEq/hr initially and dec to 0.5mEq/hr when neurologic symptoms improve (dizziness, weakness, comatose, seizures) |
| Treating symptomatic hyponatremia | hypertonic saline; 3% saline w/[Na] = 513mEq; may be combined w/loop diuretics to create hypotonic urine; monitor SNa every 4hrs |
| Treating Asymptomatic Hyponatremia | correct more slowly than symptomatic (>0.5mEq/hr); restrict water to 0.5-1L/day; demecolocycline inhibits ADH effect , but can cause renal failure; (possible selective V2 receptor agonists - ADH acts on V2 receptors in distal tubules) |
| Hypervolemic Hypotonic Hyponatremia | hyponatermia w/inc ECF; edematous state (CHF, cirrhosis, nephrotic syndrome, advanced renal failure); effective circulatin blood vol is diminished (d/t vasoconstriction); UNa <10mEq/L; |
| Treating Hypervolemic Hypotonic Hyponatremia | treat underlying condition; restrict salt and water intake; Loop diuretics; hemodialysis |
| Hypernatremia | Na >145mEq/L; inadequate water intake; Uosm helps differentiate btw renal and nonrenal causes of water loss |
| Osmoregulation: | interaction of tonicity w/thirst center and AVP release |
| Hypernatremia considerations | *excess water loss can cause hypernatremia only when adequate water intake is not possible (ex: immobilized pt)*; an intact thirst mechanism usu prevents hypernatremia; excessive salt intake is a RARE cause |
| Hypernatremia: clinical findings | *true "cellular" dehydration does not refer to vol depletion; vol depletion leads to orthostatic hypotension and oliguria; water shifts to intravascular space to protect vol status; hyperthermia, delerium, and coma a/w severe hyperosmolality |
| What happens if hypernatremia is corrected too rapidly? | water will enter brain cells and cause cerebral edema resulting in neurologic impairment |
| Choice of fluid for hypernatremia with hypovolemia: | 1st: Isotonic (0.9% saline) to restore vol deficit and treat hyperosmolality; 2nd: Hypotonic (0.45%) saline to follow |
| Choice of fluid for Hypernatremia with Euvolemia | IV D5W (5% dextrose in water); oral water drinking; stop drugs causing hypernatremia; ADH (vasopressin) analogues for CDI (central diabetes insipidus); Thiazides for NDI (neprhogenic) |
| Choice of fluid for Hypernatremia with Hypervolemia (edema) | 1st: loop diuretic (lasix) which usu fails, so follow w/ 2nd choice: Hemodyalisis if there is renal failure |
| Disorders of potassium | total body K is 50mEq/kg (95% is intracellular); *plasma K maintained in narrow range: 3.5-5.0mEq/L* |
| Internal K+ Balance Regulation | acid/base, insulin, tonicity, b2 adrenergic receptor (catecholamines) |
| External K+ Balance Regulation | *K+ secretion regulated by 'aldosterone' secretion and action of Na/K pumps*; K+ secretion is mediated by Na reabsorption and distal nephron Na delivery and concentration; |
| Hypokalemia | serum K <3.4; d/t normal total body K+ w/transcellular shift OR a decreased total body K+ |
| Normal Total Body K+ | Alkalemia (pH is high - moves K out of blood into cells); Insulin excess; High catecholamine release ('stress' from asthma attack, AMI, drugs (cocain, amphetamines), b2 adrenergic drugs, alcohol withdrawal); Hypokalemic period paralysis (thyrotoxicosis..) |
| Decreased Total Body K | dec K+ intake, inc K+ losses (GI or renal) |
| Renal K+ loss | inc aldosterone (mineralcorticoid) effect: *excess corticosteroid*; primary hyperaldo tumor, secondary hyperaldo, renovascular HTN, malignant HTN; rare: Gitelmans or Bartters sydrome, European licorice, congen abnormalities of steroid metabolism) |
| More about renal K+ loss | *increased flow in distal nephron* - diuretics, salt losing nephropathy, *IV saline*; hypomagnesemia, renal tubular acidosis |
| Extrarenal K+ loss | vomiting (K is actually lost in urine, not the vomit, causes met alkalosis); Diarrhea (K is lost in feces); laxative abuse |
| Clinical manifestations of hyokalemia | CV (arrhythmias, digoxin toxicity); neuromuscular (smooth muscle ileus, skeletal muscle weakness, paralysis, rhabdomyolysis); Renal/electrolyte (ADH resistance, inc ammonia production); Structural (renal cysts, interstitial changes) |
| Hypokalemia Diagnosis | use urine K concentration over 24hr; acid/base status; clinical picture |
| Hypokalemia with low 24hr urine (<20mEq/d); | Extrarenal losses; *metabolic acidosis: GI losses via diarrhea*; normal pH, decreased intake |
| Hypokalemia with high 24hr Urine K>20mEq/d: | Renal losses; *met alkalosis (low urine Cl (<10mEq/d) - vomit, diuretics); nml aldosterone (cushings, ccsteroid meds); Hi aldosterone (1* hyperaldo tumor); Nml/low bp: *diuretics, Barrters, Gitelmans; Variable pH: Mg depletion; Met acidosis: RTA type I/II |
| Hypokalemia Treatment | **IV K+ for severe depletion, but NEVER faster than 10mEq/hr b/c the heart will stop and pt will die**; oral K+ for mild-mid depletion; identify and treat underlying cause (ex: drugs, vomit, diarrhea, alkalosis, hypmagnesemia, etc) |
| Hyperkalemia | serum K+ >5.0mEq/L; d/t spurious, normal total body K+ transcellular shift, or increased total body K+ |
| Spurious Hyperkalemia | d/t thrombocytosis, leukocytosis, ischemic blood draw (you should treat b/f you do this) |
| Normal total body K+ transcellular shift | d/t exercise (b adrenergic blockade and mineral acidosis); non anion gap metabolic acidosis, insulin deficiency, hypertonicity, a-adrenergic receptor stimulation, tissue breakdown (rhabdomyolysis) |
| Increased total body K+ | increased K+ intake (rare w/nml renal function); decreased renal excretion of K+ |
| Decreased renal K+ excretion: Renal Failure | *acute or chronic |
| Decreased renal K+ excretion: Hyporeninemic hypoaldosteronism | *diabetic nephropathy |
| Decreased renal K+ excretion: renal secretory defects | **Type IV RTA (renal tubular acidosis)**; RTP (renal transplant), IN, SLE, SS, obstructive uropathy |
| Decreased renal K+ excretion: Drugs interfering with RAA axis | ACE-i, ARB (a2 receptor blockers), NSAIDs (renin), COXII (renin), b-blockers (renin), Trimethoprim (renin), Spirinolactone, trimetrene, amiloride, cyclosporine, heparin (aldosterone) |
| Decreased renal K+ excretion: Decreased mineralcorticoid | Addison's disease |
| Hyperkalemia: Clinical manifestations | **Cardiovascular - peaked T waves, wide QRS, prolonged PR interval, VFIB, cardiac arrest**; neuromuscular weakness; may be disporportionally greater than level of K+; rapidity of increment is important |
| Treatment Emergency: Hyperkalemia | 1st: Calcium (stabilize cell membrane; works immediately); 2nd: HCO3 (treat acidosis; moves K+ into cell); 3rd: Albuterol (b2 adrenergic receptor agonis); insulin (shift K intracellularly), Kayexalate (K exchange resin), hemodialysis |
| Hyperkalemia Treatment: nonemergent | loop diuretics, kayexalate, dialysis (ESRD); prevent hyperkalemia **(importance of diet w/pt education; recognize drugs that dec K excretion); K exchange resins |
| Acute Interstitial Nephritis | diffuse interstitial infiltrate of inflammatory cells including eosinophils |
| Acute Interstitial Neprhitis: Tubulitis | diffuse interstitial infiltrate of mononuclear cells, many actively invading tubules leading to disruption of the tubular basement membrane; white casts can be present |
| Acute Tubular Necrosis | focal loss of tubular epithelial cells and partial occlusion of tubular lumens by cellular debris |
| Acute Tubulointerstitial Nephritis | a/w acute renal failure; develops over days to weeks; d/t acute infection or delayed hypersensitivity to medicines |
| Acute Tubulointerstitial Nephritis: Clinical Symptoms | fever, rash, arthralgias, eosinophilia, eosinophiluria, UA (RBCs, WBCs, WBC casts, mild proteinuria) |
| Acute Tubulointerstitial Nephritis: Treatment | relatively good prognosis, recovery may take wks to months; dialysis may be necessary; remove causal agent; short term high dose ccsteroids |
| Chronic Tubulointerstitial Nephritis | develops over months or years; d/t infectiosn (chronic pyelonephritis, VUR) or Drugs (analgesic neprhopathy, Li, nucleoside inhibitors, calcineurin inhibitors, aristolochic acid, chemotherapy) |
| Other causes of CTIN | toxins (Pb, Cd); Heme/neoplastic (MM, lymphoprolif dx; Sickle cell); Immune-med (SLE, sjogrens, sarcoidosis); Metabolic (hypokalemia, hypercalcemia, urate nephrop); Genetics (cystinosis, 1* hyperoxaluria); Balkan nephrop, radiation, IBD, post-ATN |
| Chronic Tubulointerstitial Nephritis: Pathology | interstitial infiltrate w/lymphocytes, monocytes, PMNs, EOS, plasma cells; tubular atrophy, glomerulosclerosis, interstitial fibrosis, cast formation (MM), IF neg (except SLE, MM) |
| Chronic Tubulointerstitial Nephritis: Clinical Features | HTH less common; proteinuria usu <1.5g/d; bland UA; Anemia d/t damaged EPO cells; Metabolic acidosis (types I, II, IV); Renal papillary necrosis (DM, analgesics); Kidney stones (genetic or metabol); NDI (neph diabetes insipidus; dec urine [ ] ability&GFR |
| Main Causes of CTIN | Obstructive uropathy, vesicoureteral reflux, drugs/analgesics; heavy metals; multiple myeloma |
| Obstructive uropathy | Mc cause of CTIN; easily detected by imaging study (CT or UTZ); prostate, stones, cancer |
| Vesicoureteral Reflux | a/w CTIN; primarily a disorder of childhood; urine passes retrograde from bladder to kidneys when voiding; diagnosed in young adults w/HTN; renal failure & Hx of UTIs in childhood; VCUG (Voiding cystourethrogram) |
| Analgesic nephropathy | a/w CTIN; ingestion of combos of phenacetin, acetaminophen, ASA, and NSAIDs; synergistic toxicity of analgesics in the renal inner medulla w/centrally acting dependence producing drugs like caffeine or codeine |
| Heavy metals and nephropathy | Pb exposure is less common; Li therapy for bipolar disorder must be carefully monitored |
| CT criteria for analgesic nephropathy | Presence of a small kidney size, a bumpy contour and/or papillary calcifications |
| Drugs involved in analgesic nephropathy | Acyclic nucleoside inhibitors (cidofovir, adefovir, tenofovir used for CMV, HBV, HIV); Chronic calcineurin inhibitor toxicity (cyclosporine, tacrolimus); Aristolochic acid (in pills for wt reduction; nephrotoxic & carcinogenic) |
| Treatment for CTIN | Identify disorder; withdraw toxins (drugs or heavy metals); diagnose OBSTRUCTIOn and treat; **diagnose VUR early**; look for secondary causes; role of renal biopsy; medical management (Na, K, Ca, HCO3); Ultimately it leads to ESRD |
| Hematuria | Blood in the urine; Grossly visable (red or brown; color change can occur w/1mL); Microscopic (RBCs or Hb detected by UA or dipstick; urine sediment is gold standard; dipstics detect 1-2RBCs/HPF) |
| Causes of Heme-Negative Red Urine | Doxorubicin, chloroquine, deferoxamine, ibuprofen, iron sorbitol, nitrofurantoin, phenazopyridine, phenolphthalein, rifampin; beets, blackberries, food coloring; bile pigments, homogenistic acid, melanin, methemoglobin, porphyrin, tyrosinosis, urates |
| Approach to the pt with red or brown urine | Centrifuge (red sediment is hematuria; red supernatant can be non-blood source or myoglobin or hemoglobin if dipstick is positive for heme) |
| Initial evaluation of a patient with hematuria | Condition is not dangerous unless extraglomerular bleeding is so fast that it causes clots that obstruct the ureters; take history and exam |
| Hematuria Initial Evaluation: Historical clues | Concurrent pyuria (WBCs) & dysuria a/w UTI; Recent URTI (postinfectious glomeruloneprhitis, IgA nephropathy); Positive fam Hx of renal dx (hereditary nephritis, polycystic kidneys); Unilat flank pain from obstruction/stones; Prostate obstruction/dx |
| Hematuria Initial Evaluation: More historical clues | Recent vigorous exercise, Hx of bleeding disorders, cyclic hematuria in women during/after periods (endometriosis); meds; blk pts w/sickle cell trait/disease (papillary necrosis & hematuria) |
| Extraglomerular vs (glomerular) hematuria | Red or pink (red, smoky brown, coca-cola); clots (no clots); <500mg/day ptn (>500mg/day ptn); normal RBC morphology (dysmorphic RBCs); no RBC casts (possible RBC casts) |
| Glomerular bleeding | **RBC casts (Pathognomonic)**; ptn excretion >500mg/day; dysmorphic RBCs |
| Extraglomerular bleeding | Blood clots; normal appearing RBCs |
| Causes of Extraglomerular bleeding | Stones & obstructive dx (hypercalciuria & hyperuicosuria; common in kids); Malignancy; )); UTIs; menstruation/endometriosis; papillary necrosis (sickle cell); NSAIDs, arteriovenous malformations & fistulas, radiation cystitis, Loin-pain-hematuria syndrome |
| Extraglomerular malignancies | Malignancy of urinary tract (>50yo; 5-20% of micro – macroscopic hematuria; Renal cell carcinoma (ultrasound); Transitional cell carcinoma (urine cytology)) |
| Causes of Glomerular bleeding | a/w 50% with idiopathic hematuria disease; 86% of pts w/hematuria >4yrs had IgA nephropathy & thin basement membrane disease; others have Alport’s Syndrome (hereditary nephritis) |
| IgA Nephropathy | **IgA deposits in mesangium (pathognomonic)**; Mc cause of glomerulonephritis d/t abnml glycosylation; inc mediators of inflame (TGFbeta, NO); alt complement path; 40-50% gross hematuria, 30-40% microscopic; <10% nephritic edema/HTN/renal insufficiency |
| Causes of IgA Nephropathy | Idiopathic (mc); cirrhosis; Gluten enteropathy; Min change dx; Rare (membranous nephropathy, HIV, Wegener’s granulomatosis; Dermatitis herpetiformis, ankylosing spondylitis, Small cell carcinoma, disseminated TB, mycosis fungoides |
| Thin Basement Membrane Disease | Only finding on renal Bx is diffuse thinning of glomerular BM; often familial, incidence may be as high as 5-9%; usu benign |
| Thin Basement Membrane Disease: Genetics | Heterozygous defects in Col43A or 4A4 (genes that encode for alpha4 chains of type IV collagen); mutations in both alleles cause AR Alport syndrome; Het defects don’t provoke 2* process that results in proteinuria, impaired GFR & glomerulcosclerosis |
| Thin BM Disease: explanation of hematuria | It represents an exaggeration of the normal process of naturally occurring leaks in the GBM; the # of leaks correlates w/thickness of the GBM; does not appear to be a/w extra-renal freatures (ex: no hearing loss, ocular abnormalities, fam Hx renal failure |
| Thin BM Disease: Diagnosis | gross hematuria w/fam Hx, but no renal insufficiency; no hearing loss, no ocular abnormalities or prominent Hx or failure; Bx w/special staining for Type IV Col (antibodies against alpha3, 4, 5 chains if IV col stain positive (not w/hereditary nephritis |
| Hereditary Nephritis (Alport Syndrome) | Progressive glomerular disease often a/w neural hearing loss & ocular abnormalities; 1/50,000 lives; Primary BM disorder arising from mutations in genes encoding several type IV collagen ptns |
| Hereditary Nephritis (Alport Syndrome): Genetic Heterogenous | X-linked (80%; women carriers have hematuria, but incomplete expression of other complications); Autosomal recessive (15%); Autosomal dominant (5%) |
| Hereditary Nephritis (Alport Syndrome): Mutations | Abnml alpha3, 4, 5 chains of type IV collagen impair BM integrity in glomerulus, eye & cochlea; impairs deposition of collagen network and 2* changes in GBM composition predisposes it to glomerulosclerosis |
| Hereditary Nephritis (Alport Syndrome): Histologic changes | Earliest changes occurs in thinning of GBM; with time, changes become diagnostic (longitudinal splitting of lamina densa of GBM on EM, producing a laminated appearance; |
| Hereditary Nephritis (Alport Syndrome): Diagnosis | Family Hx of renal failure and deafness; renal failure (ESRD) in males btw 16 and 35; hearing loss initially in high tones w/progression to all frequencies; anterior lenticularis, perimacular area & corneal lesiosn |
| Summary of Hematuria | Pts <50yo: transient hematuria commonly benign w/o explanation; Pts >50yo: malignancy if unexplained; Screening in pts w/o UTI symptoms not recommended; 50% have glomerular disease; pts w/hematuria >4 yrs have IgA nephropgahy or thin BM disease |
| Glomerulonephropathies | abnml glomerular fxn d/t damage to: Epithelium (podocytes), Basement membrane, Capillary endothelium, Mesangium |
| Glomerular filtration | ultrafiltrate is produced by filtration of fluid thru capillaries of glomerulus; must cross three barriers to filtration: Endothelium (fenestration), glomerular BM, epithelial cells (podocytes w/foot processes)) |
| Barriers to filtration for macromolecules | size (fenestra 375-400A, GBM pores 40-45A, podocytes) and charge (polyanions from heparin sulfate; endothelium and GBM are negatively charged) |
| Albumin: size & charge | radius of 36A; GBM and epithelial cells restrict its passage; endothelial cells & GBM are the major sites of passage restriction d/t negative charge |
| Protein excretion & proteinuria | < 150mg daily normally; an inc glomerular permeability allows filtration of normally nonfiltered macromolecules such as albumin; a glomerular disease d/t structural injury; inc pore size & loss of charge-selectivity; loss of foot processes or cells |
| Glomerulonephropathy | damage caused to one or more of the major glomerulus components; often an inflammatory process; specific histologic pattern of injury seen on Bx |
| Possible Clinical Presentation of Glomerulonephropathy | hematuria, proteinuria, hypoalbuminemia, hyperlipidemia, edema, renal insufficiency, abnml UA |
| Classifications of Glomerulonephropathies | Asymptomatic renal disease (focal nephritic <50% of glomeruli affected); Nephritic (diffuse nephritic; most or all glomeruli affected); Nephrotic (>3.5g of ptn/day) |
| Primary versus Secondary Renal Disease | affects the kidney only; Caused by systemic illness (diabetes, systemic lupus, vasculitis) |
| Focal Nephritic (asymptomatic) | <50% of glomeruli affected; UA (dysmorphic RBC & few red cell casts); a/w asymptomatic hematuria & proteinuria found on routine exam |
| Diffuse nephritic | affects most or all of glomeruli; a/w heavy proteinuria (may be in nephrotic range); *edema, HTN, &/or renal insufficiency possible |
| Nephrotic | heavy proetinuria (>3.5g/day); Lipiduria (inc production by liver w/inc filtration across capillary wall; few cells or casts); may have edema & hyperlipidemia (full blown nephrotic syndrome) |
| Noninflammatory mechanism of glomerulonephropathy | minimal change nephrotic syndrome/focal glomerulosclerosis & membranous nephropathy (dramatic inc in glomerular permeability in a/w little or no cellular infiltration or prolif; principle target is glomerular epithelial cell or podocyte) |
| Pathogenesis of Glomerulonephropathies | results from immunological mechanisms; unknown etilogy except infectous agents like beta-strep and HCV; usu d/t infxn, drugs, toxins; immune responses may be determined genetically (ex: AI disease - loss of tolerance to self Ag) |
| Nephritogenic Immune Responses | exhibit both humoral & cell-mediated components; leads to immune complex deposition in glomeruli & infiltration of glomeruli by circulating inflam cells |
| The difference btw inflammatory and non-inflammatory pathways of glomerular damage | complement activation: Inflammatory (C5a --> PMNs/platelets); Non-inflammatory (C5b-9; glomerular epithelial cells, endothelial cells & mesangial cells) |
| Humoral immunity in glomerulonephropathies | glomerular immunoglobulin deposition along with complement components suggesting this is the principal cause of injury (post-infectious GN, IgA nephropathy, anti-GBM antibody disease, lupus nephritis, etc) |
| Antibodies which induce glomerular immune deposits are directed against: | Nml constituents of glomerulus (ex: Goodpasture antigen); Non-renal self antigens localized to glomeruli (DNA-nucleosome in SLE); Exogenous antigens localized to glomerular structures (passive trapping or local precipitation; ex: Hepatitis C) |
| Structural & Functional Consequences at site of immune deposition | Mesangium (causes mesangial cell prolif); Subendothelium (inner surface; nephritogenic; recruits PMNs & MQs as effector cells); Subepithelial (outer surface; no inflam; no access to circulating cells; comp-derived ptns moved by filtration to urinary space |
| Biological properties of immune deposition | Complement fixing IgG subtypes (cause more injury than Ab that activate comp poorly; IgA nephropathy); Immunoglobulins don't induce significant tissue injury d/t inflam mediators (comp, oxidants, proteases) cytokines, GFs, vasoactive agents |
| Cellular immunity | primary role of mononuclear cells w/o Ab deposition; causes minimal change nephrotic syndrome/focal GN & ANCA-positive GN; |
| Mechanisms of immune injury | glomerular hypercellularity (infiltrating hematopoietic cells, PMNs, MQs); Proliferating glomerular cells; Thrombosis; Necrosis; Nephritis; Nephrotic syndrome (non-inflam lesions) |
| MCNS/FGS | non-immunoglobulin circulating permeability factor is postulated; rapid reoccurance in nml kidneys transplanted into some pts w/these disorders; rapid disease resolution when MCNS kidneys are placed in nml environment |
| Causes of Minimal Change Disease | idiopatic (mc); drugs (NSAIDs, ampicillin, rifampin, interferon); Malignancy (hematologic, Hodgkins lymphoma); Chronic graft-vs-host disease; Food allergies |
| Focal Sclerosis | Primary FGS is idiopathic possibly d/t severe minimal change disease; injury to visceral epithelial cell or podocyte which attaches to glomerular BM by discrete foot processes is the primary problem |
| Causes of Focal Sclerosis (FGS) | idiopathic; nephron loss; renal vasodilation (diabetes, sickle cell anemia); obesity; healing of prior inflam injury; Heroin; reflux nephropathy |
| Membranous nephropathy | subepithelial immune deposits of IgG, C3, & complement membrane attack complex (C5b-9); induction of large changes in glomerular ptn permeability w/o significant histology changes |
| Membranous GN: Sublytic effects of C5B-9 on Podocytes | production of hydrogen peroxide; upregulation of podocyte DNA synth (TGFb2, 3, & receptors on epithelium); Overprod of ECM causing GBM thickening & "spike" formation |
| Major causes of Membranous Nephropathy | idiopathic; malignancy (solid tumors); SLE, RA, drugs (penicillamine, gold, tiopronin); HBV; syphilis; chronic renal transplant rejection; HCV; hepatosplenic schistosomiasis; |
| Inflammatory mechanism of glomerular injury | vigorous cellular response; immune deposits form in the GBM (anti-GBM disease) on the inner surface of the capillary wall (subendothelial deposits) or in the mesangium |
| Immune deposition induces multiple inflammatory processes: | Complement activation; Cytokine release; Chemoattractant generation; *they directly access the vascular space and result in infiltration of circulating inflammatory cells |
| Diseases a/w inflammatory glomerular injury | post-streptococcal GN; membranoproliferative GN; Henoch-Schonlein purpura; SLE |
| Postinfectious GN | local influx of inflam cells d/t subendothelial immune deposits & complement activation; prolif GN; active urine sediment; dec in GFR; deposits cleared by inflam cells & hematuria may resolve; subepithelial humps (ptnuria/epith cell damage like membranous |
| Membranoproliferative GN (MPGN) | HCV infxn w/ or w/o mixed cryoglobulinemia; SLE; HBV a/w mild elevation in plasma transaminase level; Subacute bacterial endocarditis or infxn of ventriculoatrial shunt |
| Inflammatory Mechanism of Glomerular Injury: Macrophages | present in RPGN, SLE, cryoglobulinemic; effectors in humoral & cell-med injury; generate oxidants/proteases; release tissue factor for fibrin deposit & **cresent formation & TGF for ECM/sclerosis |
| Rapidly Progressive Glomerulonephritis (RPGN) | extensive cresent formation (histo); clinical progression to end-stage renal disease if untreated (wks to months) |
| RPGN: Cresent Formation | non-specific response to severe injury of glomerular capillary wall; plasma products enter Bowman's space & fibrin forms; influx of MQs/Tcells release proinflam cytokines (IL-1, TNF-a); seen in immunofluorescence & Electron microscopy |
| RPGN: Type 1 | anti-GBM antibody disease |
| RPGN: Type 2 | Immune complexes not diagnostic; rare; sera/histo point to other systemic dx (ex: mesangial IgA in IgA nephropathy, anti-strep Ab & subepith humps in post-infectious GN; ANA Ab in lupus nephritis; cryglobuins/intraluminal thrombi in mixed cryoglobulinemia |
| RPGN: Type 3 | Pauci-immune; necrotizing GN w/few or no immune depositis; most w/rena-limited vasculitis are ANCA-positive w/75-80% having myeloperoxidase (MPO)-ANCA and others w/systemic symptoms of vasculitis |
| Lupus Nephritis: Minimal mesangial Class I | immunofluorescence reveals immune deposits but glomeruli are nml by light microscopy |
| Lupus nephritis: Mesangial Proliferative Class II | reveals mesangial hypercellularity or mesangial matrix expansion |
| Lupus Nephritis: Focal Class III | <50% of glomeruli on ligh microscopy have active/inactive segmental or global endocapillary or extracapillary GN as well as mesangial involvement; commonly a/w subendothelial deposits |
| Lupus Nephritis: Diffuse segmental or global Class IV | >50% of glomeruli on light microscopy have segmental or global endocapillary or extracapillary GN as well as mesangial involvement; lesions a/w subendothelial deposits |
| Lupus Nephritis: Membranous Class V | a/w subendothelial immune deposits either global or segmental or sequelae on light, immunofluor & electron microscopy; can occur w/any of the lower classes of lupus nephritis |
| Lupus Nephritis: Advanced Sclerosing Class VI | >90% of glomeruli are sclerosed globally |
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bscaryp