Reviewer's report
Title:Quantitative Modeling of the Physiology of Ascites in Portal Hypertension
Version: 3Date:15 February 2012
Reviewer: Tony Bruns
Reviewer's report:
In this communication, the authors provide a qualitative and quantitative
pathophysiological model for the development of ascites due to portal
hypertension. Notably, this model only considers the difference of liver pressure
and abdominal pressure and the rate of lymph drainage from the abdominal
cavity but does not include systemic changes due to renal sodium retention,
mesenteric vasodilatation and hyperdynamic changes.
The model bases on certain assumptions:
1) There is a critical difference of liver pressure and abdominal pressure that
allows leaking of protein from the liver to the abdominal cavity via the (ruptured)
liver capsule or (ruptured) lymphatics.
2) The mesothelium has similiary properties as capillaries and is not highly
permeable for protein.
3) The lymphatic flow from the peritoneal cavity (linearly) increases with
increasing abdominal pressure/ascitic fluid volume.
Although some of the assumptions are controversial, the model provided here is
consistent in itself and offers a recently neglected perspective on the
development of ascites. Furthermore, it allows to estimate effects of
pharmaceutical interventions on ascitic fluid (AF) volume.
Minor Essential Revisions:
1) Transfer some of the evidence from the literature for weeping from liver
surface (Add. File 1D) to the main manuscript to support this concept without
looking into the supplementary files.
2) In their model, diuretics decrease ascites volume by lower central venous
pressure. Please provide evidence that ascitic fluid reduces in patients with
ascites that are refractory to diuretics or anuric (body weight would not be a
sufficient measure, since AF should be redistributed to the venous
compartiment). How much ascites could be mobilized in an anuric patient with
gross ascites without a change in HPVG?
3) The model and Figure 1 does not consider hepato-venous shunts in patients
with decompensated cirrhosis. Please discuss how the presence of a certain
shunt volume would change the critical pressure for protein weeping from the
liver (PL-PA).
4) Figure 2 provides AF protein as a function of HPVG. Ascitic protein
concentration is provided as colloid-osmotic pressure (COP) and varies between
7 and 11 mmHg. In clinical practice AF protein concentrations between 5 and 20
g/l are ususally found. Please provide the corresponding concentrations (g/l) of
AF protein COP (mmHg) in Figure 2 and discuss the narrow range observed by
the quantitative model.
Discretionary Revisions
1) Please insert a step in eq. 15 to allow easier understanding, i.e.
PL-PA=(Phv+Ppv)/2-Phv=(Pwedge-Pfree)/2
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Quantitative Modeling of the Physiology of Ascites in Portal Hypertension
Version: 3Date:15 February 2012
Reviewer: Tony Bruns
Reviewer's report:
In this communication, the authors provide a qualitative and quantitative
pathophysiological model for the development of ascites due to portal
hypertension. Notably, this model only considers the difference of liver pressure
and abdominal pressure and the rate of lymph drainage from the abdominal
cavity but does not include systemic changes due to renal sodium retention,
mesenteric vasodilatation and hyperdynamic changes.
The model bases on certain assumptions:
1) There is a critical difference of liver pressure and abdominal pressure that
allows leaking of protein from the liver to the abdominal cavity via the (ruptured)
liver capsule or (ruptured) lymphatics.
2) The mesothelium has similiary properties as capillaries and is not highly
permeable for protein.
3) The lymphatic flow from the peritoneal cavity (linearly) increases with
increasing abdominal pressure/ascitic fluid volume.
Although some of the assumptions are controversial, the model provided here is
consistent in itself and offers a recently neglected perspective on the
development of ascites. Furthermore, it allows to estimate effects of
pharmaceutical interventions on ascitic fluid (AF) volume.
Minor Essential Revisions:
1) Transfer some of the evidence from the literature for weeping from liver
surface (Add. File 1D) to the main manuscript to support this concept without
looking into the supplementary files.
2) In their model, diuretics decrease ascites volume by lower central venous
pressure. Please provide evidence that ascitic fluid reduces in patients with
ascites that are refractory to diuretics or anuric (body weight would not be a
sufficient measure, since AF should be redistributed to the venous
compartiment). How much ascites could be mobilized in an anuric patient with
gross ascites without a change in HPVG?
3) The model and Figure 1 does not consider hepato-venous shunts in patients
with decompensated cirrhosis. Please discuss how the presence of a certain
shunt volume would change the critical pressure for protein weeping from the
liver (PL-PA).
4) Figure 2 provides AF protein as a function of HPVG. Ascitic protein
concentration is provided as colloid-osmotic pressure (COP) and varies between
7 and 11 mmHg. In clinical practice AF protein concentrations between 5 and 20
g/l are ususally found. Please provide the corresponding concentrations (g/l) of
AF protein COP (mmHg) in Figure 2 and discuss the narrow range observed by
the quantitative model.
Discretionary Revisions
1) Please insert a step in eq. 15 to allow easier understanding, i.e.
PL-PA=(Phv+Ppv)/2-Phv=(Pwedge-Pfree)/2
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Quantitative Modeling of the Physiology of Ascites in Portal Hypertension
Version: 3Date:15 February 2012
Reviewer: Tony Bruns
Reviewer's report:
In this communication, the authors provide a qualitative and quantitative
pathophysiological model for the development of ascites due to portal
hypertension. Notably, this model only considers the difference of liver pressure
and abdominal pressure and the rate of lymph drainage from the abdominal
cavity but does not include systemic changes due to renal sodium retention,
mesenteric vasodilatation and hyperdynamic changes.
The model bases on certain assumptions:
1) There is a critical difference of liver pressure and abdominal pressure that
allows leaking of protein from the liver to the abdominal cavity via the (ruptured)
liver capsule or (ruptured) lymphatics.
2) The mesothelium has similiary properties as capillaries and is not highly
permeable for protein.
3) The lymphatic flow from the peritoneal cavity (linearly) increases with
increasing abdominal pressure/ascitic fluid volume.
Although some of the assumptions are controversial, the model provided here is
consistent in itself and offers a recently neglected perspective on the
development of ascites. Furthermore, it allows to estimate effects of
pharmaceutical interventions on ascitic fluid (AF) volume.
Minor Essential Revisions:
1) Transfer some of the evidence from the literature for weeping from liver
surface (Add. File 1D) to the main manuscript to support this concept without
looking into the supplementary files.
2) In their model, diuretics decrease ascites volume by lower central venous
pressure. Please provide evidence that ascitic fluid reduces in patients with
ascites that are refractory to diuretics or anuric (body weight would not be a
sufficient measure, since AF should be redistributed to the venous
compartiment). How much ascites could be mobilized in an anuric patient with
gross ascites without a change in HPVG?
3) The model and Figure 1 does not consider hepato-venous shunts in patients
with decompensated cirrhosis. Please discuss how the presence of a certain
shunt volume would change the critical pressure for protein weeping from the
liver (PL-PA).
4) Figure 2 provides AF protein as a function of HPVG. Ascitic protein
concentration is provided as colloid-osmotic pressure (COP) and varies between
7 and 11 mmHg. In clinical practice AF protein concentrations between 5 and 20
g/l are ususally found. Please provide the corresponding concentrations (g/l) of
AF protein COP (mmHg) in Figure 2 and discuss the narrow range observed by
the quantitative model.
Discretionary Revisions
1) Please insert a step in eq. 15 to allow easier understanding, i.e.
PL-PA=(Phv+Ppv)/2-Phv=(Pwedge-Pfree)/2
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant