Renal
Help!
|
|
||||
|---|---|---|---|---|---|
| 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
🗑
|
Review the information in the table. When you are ready to quiz yourself you can hide individual columns or the entire table. Then you can click on the empty cells to reveal the answer. Try to recall what will be displayed before clicking the empty cell.
To hide a column, click on the column name.
To hide the entire table, click on the "Hide All" button.
You may also shuffle the rows of the table by clicking on the "Shuffle" button.
Or sort by any of the columns using the down arrow next to any column heading.
If you know all the data on any row, you can temporarily remove it by tapping the trash can to the right of the row.
To hide a column, click on the column name.
To hide the entire table, click on the "Hide All" button.
You may also shuffle the rows of the table by clicking on the "Shuffle" button.
Or sort by any of the columns using the down arrow next to any column heading.
If you know all the data on any row, you can temporarily remove it by tapping the trash can to the right of the row.
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Created by:
bscaryp