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Myasthenia Gravis

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Medical treatment Hepatorenal syndrome was recalcitrant to medical therapy for so many years that it is still perceived by many physicians as untreatable. – PowerPoint PPT presentation

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Title: Myasthenia Gravis


1
(No Transcript)
2
Learning objectives
  • To understand the pathophysiologic basis for
    vasoactive therapies for HRS
  • To become familiar with the diagnostic criteria
    for HRS
  • To learn about therapeutic options for patients
    with HRS

3
  1. Sinusoidal portal hypertension, in the presence
    of severe hepatic decompensation
  2. Leads to splanchnic and systemic
    vasodilatation-role of NO
  3. Decreased effective arterial blood volume
  4. Activation of systemic vasoactive factors, such
    as the renin-angiotensin system, the sympathetic
    nervous system, and vasopressin aimed at
    restoring arterial filling pressure.
  5. Renal vasoconstriction increases concomitantly
    (leukotrienes and endothelins), counterbalanced
    by the intrarenal hyperproduction of vasodilating
    prostaglandins. When this balance is lost renal
    hemodynamics worsens, and hepatorenal syndrome
    develops

4
39-year-old man with a history of heavy alcohol
abuse and cirrhosis but no other significant past
medical problems was admitted for treatment of
increasing ascites. He had no known history of
kidney disease He had jaundice, tense ascites,
severe leg edema, and mild to moderate
encephalopathy. He had no signs of fluid loss,
such as bleeding or diarrhea. The patient was
not taking any nephrotoxic medications.
5
His AST and ALT were 202 U/L and 68 U/L,
respectively, and his initial serum creatinine
level was 62 micromoles/L and Na 123. Results
of serologic testing for antibody to hepatitis C
virus, hepatitis B surface antigen, IgM antibody
to hepatitis A virus, antinuclear antibodies, and
antibody to Sm nuclear antigen were negative.
The patient had no detectable paracetamol level,
and his ceruloplasmin level was normal.
6
Between day 5 and day 14 of the patient's
hospitalization, his serum creatinine level
increased from 230 micromoles/L. No improvement
in renal function after volume expansion with
1.5L isotonic saline solution Microscopic
examination of his urine revealed fewer than 50
red blood cells per high-power field. Urine and
serum osmolality values were 354 mOsm/kg H2O and
246 mOsm/kg H2O Urine protein excretion was 246
mg/24 hr, and spot urine sodium level was 7
mmol/L. Renal ultrasound was normal.
Serum-ascites albumin gradient was 2.1 g/dL,
and PMN count 2
7
International Ascites Club diagnostic criteria
for HRS
  • Major criteria
  • Chronic or acute hepatic disease and liver
    failure with portal hypertension
  • Serum creatinine level gt133 micromoles/L or 24-hr
    creatinine clearance lt40 mL/min
  • Absence of shock, ongoing bacterial infection,
    recent use of nephrotoxic drugs, excessive fluid
    or blood loss
  • No sustained improvement in renal function after
    volume expansion with 1.5 L isotonic saline
    solution
  • Proteinuria lt500 mg/day and no ultrasonographic
    evidence of renal tract or parenchymal disease
  • Minor criteria
  • Urine volume lt500 mL/day
  • Urine sodium lt10 mEq/L
  • Urine osmolality greater than plasma osmolality
  • Urine red blood cell count lt50 per high-power
    field
  • Serum sodium lt130 mEq/L

8
Types of HRS
  • Type I HRS is the more serious type
  • defined by a rise in creatinine level to over
    221 micromoles/L in less than 2 weeks (or at
    least a 50 percent lowering of the creatinine
    clearance to a value below 20 mL/min) median
    survival of 2 weeks
  • Type II HRS is defined as less severe renal
    insufficiency than that observed with type I
    disease it is principally characterized by
    ascites that is resistant to diuretics. median
    survival of 3-6 months.

9
Other Problems to be Excluded
  • Prerenal azotemia from volume depletion(diuretic/G
    I bleed/LVP)
  • Systemic infection/SBP(HRS type 1 develops in 15
    )
  • Drug-induced nephrotoxicity aminoglycosides,
    diuretics, iodine-containing contrast agents, and
    nonsteroidals. ACE inhibitors, demeclocycline,
    and dipyridamole.
  • Postrenal azotemia from outflow obstruction
  • Renal vascular disease
  • Glomerulonephritis, nonstreptococcal
    postinfectious

10
PRERENAL HRS ATN
SPOT Na lt10 lt10 gt30
Urine sediment Nil Nil Positive
Fluid challenge Responds Nil Nil
11
  • HEPATORENAL SYNDROME

12
Incidence
  • HRS occurs in approximately 4 of patients with
    cirrhosis who are decompensated,
  • With a cumulative probability of 8 per year,
    which increases to 39 at 5 years.
  • In hospitalized patients with ascites, the
    incidence rate is 7-15.

13
Assessing renal perfusion
  • Creatinine production may be substantially
    reduced in this setting, due to the liver disease
    and to decreased muscle mass and protein and meat
    intake.
  • Creatinine clearance value obtained in patients
    with renal insufficiency will tend to
    overestimate the true GFR due to increased
    creatinine secretion
  • Noninvasive techniques to assess the degree of
    renal vasoconstriction duplex Doppler
    ultrasonography.A high resistive index ( 0.70) is
    indicative of renal vasoconstriction.

14
Treatment options
  • OLT
  • Haemodialysis
  • TIPSS
  • Vasoactive Medical treatment

15
OLT
  • Liver transplantation carries the best chance for
    long-term survival, but the rapid deterioration
    associated with type 1 HRS means that many
    patients die before an organ becomes available.
  • The systemic and neurohumoral abnormalities
    associated with HRS also resolve in the first
    postoperative month.
  • The hepatorenal syndrome is a prerenal disease,
    as the kidneys are normal histologically

16
Dialysis
  • This is used most commonly in patients who are
    awaiting liver transplantation, as dialysis
    improves the priority score for the transplant.
  • Acute and potentially reversible hepatic insult
    may benefit from dialysis, since renal function
    will recover in parallel with improving hepatic
    function.
  • Hemodialysis is frequently difficult to perform
    in patients with hepatorenal syndrome since
    decompensated hepatic function is associated with
    hemodynamic instability.

17
TIPSS
  • The transjugular intrahepatic portosystemic shunt
    (TIPS) has been used in the treatment of
    refractory ascites. When used in this setting,
    there may also be a delayed improvement in renal
    function
  • There is much less information on the use of TIPS
    in patients who fulfill criteria for the
    hepatorenal syndrome
  • Overall, these results suggest that, in selected
    patients with hepatorenal syndrome, TIPSS may
    provide short-term benefit. Given the risks
    associated with this procedure (particularly the
    high incidence of encephalopathy), it should be
    considered only as a last resort in patients who
    are not a candidate for or are awaiting liver
    transplantation.

18
Medical treatment
  • Hepatorenal syndrome was recalcitrant to medical
    therapy for so many years that it is still
    perceived by many physicians as untreatable.
  • Clearly, new therapies have significantly
    brightened the short-term outlook for patients
    with type 1 hepatorenal syndrome, and improvement
    in short-term survival rates may lead to
    increased opportunity for definitive therapy (ie,
    liver transplantation).

19
Vasoactive therapy
  • Midodrine- octreotide- albumin regime
  • Terlipressin plus albumin

20
  • Midodrine and octreotide Growing data suggest
    that combination therapy with midodrine (a
    selective alpha-1 adrenergic agonist) and
    octreotide (a somatostatin analog) may be highly
    effective and safe.
  • The rationale is midodrine (systemic
    vasoconstrictor) and octreotide (inhibitor of
    endogenous vasodilator release)will reverse the
    pathophysiology

Angelie et al Hepatology 1999 Pomier-Layrargues
et al Hepatology 2003
21
  1. Sinusoidal portal hypertension, in the presence
    of severe hepatic decompensation
  2. Leads to splanchnic and systemic
    vasodilatation-role of NO
  3. Decreased effective arterial blood volume
  4. Activation of systemic vasoactive factors, such
    as the renin-angiotensin system, the sympathetic
    nervous system, and vasopressin aimed at
    restoring arterial filling pressure.
  5. Renal vasoconstriction increases concomitantly
    (leukotrienes and endothelins), counterbalanced
    by the intrarenal hyperproduction of vasodilating
    prostaglandins. When this balance is lost renal
    hemodynamics worsens, and hepatorenal syndrome
    develops

22
Midodrine- octreotide- albumin regime
  • Midodrine (7.5 mg by mouth every 8 hours)
  • Octreotide (100 mg subcutaneously every 8 hours)
  • Albumin (25 mg intravenously per day)

23
Terlipressin plus albuminregime
  • Terlipressin bolus(0.5mg/4h)-increase every 3
    days if no response to 1-2mg/4h
  • Given until creatinine normalizes or for 15 days
  • Albumin 1g/kg on day1,20-60g/d thereafter

Uriz et al J Hepatol 2000
24
  • In one prospective, nonrandomized study 21
    patients were treated with terlipressin plus
    albumin compared with terlipressin alone.
  • The group treated with terlipressin and albumin
    had a 3-month survival rate of 50, compared to
    10 for the terlipressin-only group.

Ortega et al hepatology 2002
25
  • A small cohort of nine patients with cirrhosis
    and HRS were given Terlipressin and albumin until
    the reversal of hepatorenal syndrome or for a
    maximum of 15 days
  • Seven of the nine patients showed a reversal of
    hepatorenal syndrome. There was also a marked
    improvement in MAP. Plasma renin activity and
    plasma norepinephrine decreased

Uriz et al J Hepatol 2000
26
PREVENTION
  • In patients with spontaneous bacterial
    peritonitis, the administration of intravenous
    albumin (1.5 g/kg) at the time of diagnosis of
    infection and another dose of albumin (1.0 g/kg)
    on day three of antibiotic treatment may reduce
    the incidence of both renal impairment and
    mortality during hospitalization and at three
    months
  • Pentoxifylline (400 mg PO TID) may be preventive
    in patients with severe alcoholic hepatitis

27
  • Thank you
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