Acute Tubular Necrosis

Acute Tubular Necrosis
Presented by Dr Gagandeep K Heer, MD

* Definition: ARF is defined as an abrupt or rapid decline in the renal function.
* A rise in serum BUN or creatinine concentration, with or without decrease in urine output, usually is evidence of ARF.
* ARF is often transient and completely reversible.

Background
* The causes of ARF are divided into 3 categories:

Prerenal
Renal
Postrenal
* ATN is the most common cause of ARF in the renal category.
* ATN is the 2nd most common cause of all categories of ARF in hospitalized patients, with only prerenal azotemia occurring more frequently.
* In outpatients, obstruction (ureteric, bladder neck or urethral) is the 2nd most common cause of ARF after prerenal azotemia.
* Other causes of ARF include acute interstitial nephritis, acute glumerulonephtitis, vasculitis, HUS, TTP, DIC, accelerated HTN, radiation nephritis, acute on chronic renal failure, renovascular obstruction (bilateral or unilateral in the setting of single functioning kidney), renal allograft rejection, intratubular deposition and obstruction (myeloma proteins, urate, oxalate crystals, etc.)

Pathophysiology
* ATN usually occurs after an acute ischemic or toxic event, and it has a well-defined sequence of events.
* Initiation phase characterized by acute decrease in GFR to very low levels, with a sudden increase in serum Cr and BUN concentrations.
* Maintenance phase is characterized by sustained severe reduction in GFR and the BUN and Cr continue to rise.
* Recovery phase, in which the tubular function is restored, is characterized by an increase in urine volume (if oliguria was present) and gradual decrease in Cr and BUN to their pre-injury level.

Ischemic ATN
* Ischemic ATN is often described as a continuum of prerenal azotemia. Response to fluid repletion can help distinguish between the two: return of renal function within 24-72 hours usually indicate prerenal disease although short-lived ATN can recover within similar timeframe (e.g. self limited insult such as transient aortic clamping during suprarenal aortic aneurysm surgery).
* Initiation phase: Hypoperfusion initiates cell injury that often leads to cell death. It is most prominent in straight portion of the proximal tubules and thick ascending limb of loop of Henle. The reduction in the GFR occurs not only from reduced filtration due to hypoperfusion but also from casts and debris obstructing the lumen, causing back leak of filtrate through the damaged epithelium (ineffective filtration). In addition, ischemia leads to decreased production of vasodilators (i.e. nitric oxide, prostacyclin) by tubular epithelial cells, leading to further vasoconstriction and hypoperfusion.
* Maintenance phase is characterized by stabilization of GFR at a very low level, and it typically lasts 1-2 weeks. Uremic complications typically develop during this phase. In addition to the above mentioned mechanism of injury, tubulo-glomerular feedback also plays a role by causing constriction of afferent arterioles by the macula densa cells, which detect and increased salt load in the distal tubules.
* During Recovery phase, there is regeneration of tubular epithelial cells. An abnormal diuresis sometimes occurs, causing salt and water loss and volume depletion. The mechanism of the diuresis is not completely understood, but it may in part be due to delayed recovery of tubular cell function in the setting of increased glomerular filtration. In addition, continued use of diuretics (often administered during initiation and maintenance phases) may also add to the problem.

Nephrotoxic ATN
* Most of the pathophysiological features of ischemic ATN are shared by the nephrotoxic forms and it has the same three phases.
* Nephrotoxic injury to tubular cells occurs by multiple mechanisms including direct toxicity, intrarenal vasoconstriction, and intratubular obstruction.
* Ischemic ATN

Nephrotoxic ATN
Frequency
History
Physical Exam
* Physical exam may be unremarkable because ARF is often found incidentally during routine laboratory studies (i.e. elevated BUN and Cr).
* Look for pericardial friction rub (pt may have pericarditis), asterixis and/or excoriation marks related to uremic pruritis.
* Hypertension or edema may be noted.
* Physical findings related to the underlying disease.

Causes of ATN
Causes of Ischemic ATN
Causes of Nephrotoxic ATN
Exogenous toxins
Aminoglycosides:
Amphotericin B:
Exogenous Toxins
Radiocontrast media:
Endogenous toxins
Myoglobinuria
Hemoglobinuria
Crystals:
Workup
Lab studies
Laboratory Findings Used to Differentiate Prerenal Azotemia from ATN
Plasma BUN/Cr ratio
Imaging Studies
Renal biopsy
Complications
Prevention
Treatment
Mortality and Morbidity
Prognosis

Acute Tubular Necrosis.ppt

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Childbearing & the Pelvic Floor

Childbearing & the Pelvic Floor: A Review of the Literature
By:Nancy H. Sullivan, CNM, MS, FACNM

Types of pelvic floor disorders
* Pelvic pain
* Nerve damage
* Pelvic organ prolapse: cystocele, rectocele, enterocele, uterine prolapse
* Urinary incontinence: stress, urge, mixed
* Fecal incontinence

Prevalence of pelvic floor disorders
* Pelvic organ prolapse is common and is seen in 50% of parous women.
* Around 10% of women in the community undergo surgery at some time of their lives for the management of prolapse (Olsen et al.).
* Urinary and fecal incontinence are common and prevalence estimates vary from 9% of women over 15 (UK study) to 38% of women over 60 (US study).
* Studied 2070 women who sought care for UI or PFD at Kaiser Permanente, San Diego.
* Forty-six percent had undergone previous hysterectomy; ten percent had undergone previous anti-incontinence surgery; six percent had undergone previous anterior or posterior repair (or both).
* Median age of women seeking care was 61; half of women were from 30-60 years of age.
* Genuine stress incontinence was more common in younger patients than in older patients (78% vs 57%);
* Detrusor instability/urge incontinence was more common in older women than in younger ones (67% vs 56%);
* Mixed incontinence was common; 38% of all patients had this diagnosis.
* Pelvic organ prolapse was similar in both groups (27% vs 30%).
* Population survey in South Australia; 3010 interviews in respondent’s homes
* Prevalence of all types of incontinence in women was 35.3%.
* Pregnancy >20 weeks, regardless of mode of delivery, greatly increased the prevalence of major pelvic floor dysfunction.
* Significant increase in PFD for women with history of instrumental delivery over women with CS, but not for women with SVD over women with CS
* Other risk factors for PFD were age, obesity or increased BMI, coughing, osteoporosis, arthritis, and reduced quality of life scores.

Additional associated factors identified in the literature:
* Menopause and estrogen depletion
* However – HRT increases the risk of developing urinary incontinence in post-menopausal women, according to new data from the Nurses’ Health Study (Grodstein et al, 2004) and from the Australian Longitudinal Study of Women’s Health (Miller et al, 2003).
* This increased risk does not vary by route of administration, type of hormone, or dose taken, but is diminished upon cessation of use.
* Depression; individuals with UI more likely to be depressed- which comes first?
* Impaired mobility; relationship among UI, urinary urgency, and falling – which comes first?
* Medications, bladder irritants
* Smoking – possibly because of smoker’s cough?
* Work environment, including limited access to bathroom, heavy lifting, bending, walking, or standing.
* Chronic disease causing cognitive impairment, peripheral neuropathy or decreased mobility. Examples are Alzheimer’s Disease, stroke Parkinson’s Disease, diabetes, multiple sclerosis.
* Physical and occupational activity, especially high-impact exercise, are risk factors.
* But…there is evidence that women who have better ability to absorb impact forces (more flexibility) have less stress incontinence.
* Nygaard et al (1996) studied the relationship between urinary incontinence in elite nulliparous athletes and force absorption as assessed by foot arch flexibility, and found a significant correlation between decreased foot flexibility and stress urinary incontinence.

Childbearing is a leading cause of pelvic floor disorders.
* Research studies are heterogeneous in definition and design, controversial, and inconclusive.
* Pregnancy itself, regardless of mode of delivery, is a risk factor. However, much of the professional as well as the lay literature ignores or minimizes this and focuses the blame on the birth process.
* Significant confounding factors are age and hysterectomy; by around 60 years of age, nulliparous women have the same rate of incontinence as parous women.
* However, most studies show an increased risk with vaginal delivery or cesarean after trial of labor over elective cesarean.
* Survey by the authors reported that 61% of women in a Dublin population (n=7771) reported the onset of symptoms of urinary incontinence before or during pregnancy.
* In another study, the authors compared two groups of healthy physio-therapists, 20-28 years, one nulliparous (n=10)and one primiparous (VD only) (n=10).
* Each group was assessed with a manual digital exam, electromyography (EMG) and perineometry on one occasion only.
* Statistical analysis of digital assessment data showed significant differences between groups for all four types of assessment, with the nulliparous group scoring higher.
* Despite measured loss of pelvic floor integrity in primiparous group, none of the subjects had symptoms of urinary incontinence.
* Authors suggest program of pelvic floor exercises for all women postpartum.

Urinary incontinence after vaginal delivery or Cesarean section
* Did not investigate the effect of instrument-assisted deliveries, shown to be a major factor in other studies
* Did not look at length of second stage or pushing phase
* Found no significant difference between rate in elective CS and CS after labor, shown to be a factor in other studies
* Found no association of incontinence with mode of delivery for women over 50, consistent with other studies
* Mean age of nulliparae lowest, women who had a vaginal birth highest
* Gestational age and birthweight significantly higher in vaginally-delivered group than in cesarean group
* Concluded that an individual woman’s risk of moderate or severe incontinence would be decreased from about 10% to about 5% if she delivered all her children by CS. This decrease would apply only until 50 years of age.
* For women having had two CS, odds still lower than for women with a VD; however, by third CS, odds were the same.
* Women who performed daily antenatal pelvic floor exercises had lower rate than those who did not; women with higher BMI and parity of 5 or greater had higher rates.

The case against elective cesarean section.
* Medial episiotomy increases anal tears (up to 22-fold in one study).
* Even without extending, episiotomy is associated with 2.4 times more fecal incontinence than spontaneous second-degree lacerations.
* Three months after childbirth, primiparae with intact perineums had the strongest pelvic floors, followed by women with spontaneous tears, women with episiotomies, and, weakest of all, women whose episiotomy extended.
* Compared with nulliparity, pelvic floor dysfunction is significantly associated with cesarean section (OR 2.5), with spontaneous vaginal delivery (OR 3.4) and with at least one instrumental delivery (OR 4.3). The difference between cesarean and instrumental delivery was significant, but not the difference between CS and VD.
* Looked at elective CS vs SVD vs CS performed for obstructed labor
* Study population 363 primiparae delivering in maternity ward in Tel Aviv; interviewed them one year postpartum regarding symptoms of SUI; excluded those with SUI prior to childbirth
* Subgroups comparable with respect to age, weight/height, gestational age at delivery, Apgar scores, and use of epidural anesthesia
* Women with postpartum SUI significantly heavier, older, and had increased prevalence of SUI during pregnancy; duration of first and second stage of labor significantly longer in these women.
* Aim of study was to quantify the changes that occur in the levator ani muscles after vaginal delivery using MRI.
* Scanned 6 women one day, one, two and six weeks, and six months postpartum
* Changes noted at one day postpartum had completely returned to normal by 6 weeks postpartum in 5 out of six women, and on one side in the sixth.
* Timing of sampling is very important.
* Vaginal delivery leads to increased anterior vaginal wall mobility.
* These alterations are more marked in women with limited pelvic organ mobility prior to childbirth.
* Postpartum sampling varied from 2-5 months, a variation of 3 months during which substantial changes may be happening.
* Current advanced imaging studies can delineate clearly the musculo-fascial defects associated with vaginal birth and could enhance our understanding of post-cesarean incontinence.
* Incidence of anal incontinence similar in primiparae with elective CS and non-instrumental VD; higher in primiparae with forceps delivery; SUI more frequent after all VD than after CS.
* Prevalence of both increases with parity, but the association with UI is lost in the elderly (hence, study showing elderly nuns with SUI).
* Postpartum urinary incontinence can persist, resolve spontaneously, or symptoms can arise de novo within a 7-year period. Primagravidae who develop incontinence in the immediate postpartum period usually regain continence within three months.

Pelvic floor exercises – Can they prevent PFD? Review of the evidence.
prevents urinary incontinence during pregnancy and after childbirth.”

* 268 primigravidae with bladder neck mobility of >5mm randomized to (1)supervised PFE with PT from 20 weeks until delivery or (2) usual advice from midwives.
* Fewer women in study group reported postpartum SUI. No difference in bladder neck mobility or in pelvic floor strength.
* Difference attributed to “the knack” of contracting pelvic floor muscles prior to exertion, cough, sneeze, etc.
What else can we learn from the literature?
Counseling Women About Elective Cesarean Section

Childbearing & the Pelvic Floor.ppt

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Pelvic Floor Disorders: Evaluation and Treatment

Pelvic Floor Disorders: Evaluation and Treatment
By:Elisa Rodriguez Trowbridge, MD
Departments OB/GYN and Urology
Division of Female Pelvic Medicine and Reconstructive Surgery



3 General Categories of Disorders

* Urinary Incontinence
* Pelvic Organ Prolapse
* Anal Incontinence

Urinary Incontinence
Types of Urinary Incontinence
* Stress Incontinence
* Urge Incontinence
* Mixed Incontinence
* Overflow Incontinence

Stress Urinary Incontinence (SUI)
* Generally occurs with sudden movements or increases in intra-abdominal pressure- coughing, laughing, sneezing, or running.
Urge Incontinence
* Typically preceded by an urge to void, and can involve a trigger such as running water, opening a door, removing undergarments.
* Mixed urinary incontinence: Involuntary leakage associated with urgency and also with exertion, sneezing, or coughing (SUI).

Overactive Bladder
* Urgency- DRY
* Frequency- DRY
* Urge Urinary Incontinence (UUI)- WET

Urinary Incontinence- Evaluation
* History
* Exam
Incontinence Physical Exam
* Standing or Supine Stress Test
Post Void Residual & Urine Dipstick
Voiding Diary
* Normal Voiding
Overflow incontinence
* Obstruction of urethra
* Poor contractile bladder muscle
* Must find out PVR !!
** Must stop anticholinergics!!
Simple Cystometry (Urodynamics)
Multichannel Urodynamics
Indications:
* Uncertain diagnosis
* Fail respond to treatment
* Prior failed surgery
* Complex

Risk factors of UI
* Sex: Women are more likely than men to have stress incontinence –pregnancy, childbirth, and menopause.
* Age: As you get older, the muscles in your bladder and urethra lose some of their strength. Changes with age reduce how much your bladder can hold and increase the chances of involuntary urine release. However, getting older doesn't necessarily mean that you'll have incontinence. Incontinence isn't normal at any age — except during infancy.
* Obesity: Being overweight increases the pressure on your bladder.
* Smoking: A chronic cough can cause episodes of incontinence or aggravate incontinence that has other causes. Smokers are also at risk of developing overactive bladder.
* Other diseases: Having kidney disease or diabetes may increase risk of urinary incontinence.

Treatment Urinary Incontinence
* Lifestyle modification
* Pads
* Physical Therapy- Kegels, biofeedback
* Pessary
* Medications- eg anticholinergics (Detrol)
* Botox (OAB)
* Surgery (many!!)

Pelvic Prolapse
3 Compartments of Prolapse

* Anterior
* Middle or Apical
* Posterior
3 Compartments: Normal Support
3 Compartments of Prolapse
Cystocele (Anterior)
Symptoms: bulging, pressure, “mass”, difficulty voiding, incomplete emptying, splinting vaginal wall, difficulty inserting tampon, pain with intercourse.
Vaginal vault prolapse/ Enterocele (Middle/Apical)
Symptoms: bulging, pressure, “mass”, difficulty voiding, incomplete emptying, splinting vaginal wall, difficulty inserting tampon, pain with intercourse.
Rectocele (Posterior)
Symptoms: bulging, pressure, “mass”, difficulty defecation, incomplete defecation, splinting vaginal wall or perineum, difficulty inserting tampon.
Complete eversion (All compartments)
* Uterine Procidentia
* Complete uterine prolapse

Pelvic Organ Prolapse Quantification System (POP-Q)
* Patient straining, 6 specific sites are evaluated, at rest 3 sites measured.
* Measure each site (cm) in relation to the hymenal ring, which is a “fixed”. The hymenal ring is the zero point of reference.
* If a site is above the hymen, assigned a negative number.
* If site prolapses below the hymen, the measurement is positive.

POP-Q: Normal
* What type of prolapse
* What compartment?
Prolapse treatment options
* Expectant Management
* Physiotherapy???
* Pessary
* Surgery (Many!!)
o Abdominal
o Vaginal
o Laparoscopic
o Robotic assisted Laparoscopy
o Mesh kits
Abdominal Sacralcolpopexy
Vaginal Hysterectomy
Mesh repairs
Anal Incontinence
Anal incontinence (AI)
* Anal Incontinence is the inability to control passage of gas, liquid or solid stool from the rectum.
* Affects two to 15 percent of adults in the United States.
* This condition affects men and women of all ages, but because people are embarrassed to talk about their symptoms, many people go untreated because they are unwilling to ask for help.

Types of Anal Incontinece
* Flatal incontinence:
* Double incontinence:
* Rectovaginal fistula:

Evaluation- AI
* History
* Pelvic exam
* Transanal ultrasound: Assess integrity of external and internal anal sphincter. A probe is about the size of a finger is place in the anorectum.
* MRI: Muscles of the pelvic floor, CNS or spinal cord lesions.
* Defecography: Barium paste is placed into your rectum and vagina and patient sits in the toilet simulationg defecation.
* Anal manometry: Assessment of muscles, capacity and sensation of the anorectum. A small air-filled balloon is inserted into your rectum.

Treatment of AI
* Lifestyles modifications
* Medications
* Physical Therapy
o Electrical Stimulation
o Biofeedback
Surgery for Separated Anal Sphincter
Anal sphincteroplasty
* Performed if involuntary loss of stool is caused by an injured/separated sphincter muscle.
* Opening made between the vagina and anus. Separated muscles are identified and approximated with sutures.
Treatment AI
* There are effective treatments that can help, or even cure, the problem. However, fecal incontinence has long been a neglected subject, and for some fecal incontinence problems, we do not yet have completely effective treatments.

Pelvic Floor Disorders: Evaluation and Treatment .ppt

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