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Twenty-one reasons arming Starling's law on the
capillary-interstitial uid transfer wrong and the
correct replacement is the hydrodynamic of the
porous orice (G) tube.
Ahmed N. Ghanem, MD (Urology), FRCSE Ed,
Mansoura University, Faculty of Medicine, Egypt
Retired Consultant Urologist Surgeon and Independent Investigator .
No1 President Mubarak Street, Mansoura 35511, Egypt.
Mobile Egypt: 00201150488346
Mobile UK: 00447306321589
Orcid ID orcid.org/0000-0002-1310-7080
Number of references 27
Number of photos 1
Number of tables 0
Number of pages 7
There are 21 reasons why Starling's law is wrong and the correct
replacement is the hydrodynamic of porous ori%ce (G) tube. His
hypothesis is based on Poiseuille's work in which the hydrostatic pressure causes filtration.
The oncotic pressure force of plasma albumin causes re-absorption. Starling's law is wrong on
The capillary has a pre-capillary sphincter and wide pores that allow the passage of plasma
proteins. This makes the capillary a porous orifice (G) tube with different hydrodynamic; side
pressure causes suction not filtration. The pores nullify the oncotic force in vivo. There is
evidence to show that the osmotic chemical composition of various body fluids is identical to
plasma proteins. The interstitial fluid (ISF) space has a negative pressure of -7 cm water.
Evidence on plasma protein versus Saline shows no significant difference. This affirms that
the oncotic force does not exist in vivo that partly prove Starling's law wrong. Inadequacy in
explaining the capillary–ISF transfer, has previously called for reconsideration of Starling’s
Physics and physiological research demonstrate that pressure does not cause filtration across
the wall of G tube, it causes suction. In G tube negative side pressure gradient causing suction
maximum near the inlet and turns positive maximum near the exit causing filtration.
Physiological study completed the evidence that Starling’s law is wrong as the capillary
works as G tube not Poiseuille’s tube. Both absorption and filtration are autonomous
functions of G tube thus fit to replace Starling's law. The clinical significance is discussed.
The complete evidence that Starling's law is wrong and the correct
replacement is the hydrodynamic of the porous ori%ce tube is now
reported as summarized here1: Dr, Starling2 proposed his hypothesis >80 years
prior to the discovery of the capillary ultrastructure and correct physiology as shown here. He
based his hypothesis on Poiseuille's2 work in which the hydrostatic pressure is a positive force
of the arterial pressure causing filtration3. The oncotic pressure force of plasma proteins
causes re-absorption. Starling's law is wrong on both forces because of the following reasons3
1. In the pulmonary circulation arterial pressure is less than the plasma oncotic πc
pressure. In the liver, muscles and lung interstitial fluid (ISF) has high protein
content. nThus, fluid filtration in the lungs and reabsorption in the liver and muscles
2. The capillary has a pre-capillary sphincter as reported by Rhodin in 19675 which
makes it different from Poiseuille's tube of uniform diameter as modern research
mentioned below demonstrates.
3. The capillary has porous wall of intercellular slits that allow the passage of molecules
larger than plasma proteins as shown by Karnoveski in 19676. Hence plasma proteins
cannot exert an oncotic pressure in vivo.
4. The osmotic chemical composition of various body fluids is identical to plasma
proteins as demonstrated by Hendry in 19627, Hence the oncotic pressure if it exists is
too week and too slow force to cause absorption.
5. The oncotic pressure of plasma proteins does not work as absorption force neither in
physiology as proved by Hendry in 19627 nor in clinical practice demonstrated by
Cochrane Injuries Group and other authors in 19988 and 200610.Also most recent
study using hydroxyethyl Starch (HES) as plasma substitutes for fluid resuscitation in
2020 demonstrated, like albumin, that there is no significant difference from using
6. Guyton and Coleman (1968) 12 demonstrated that the interstitial fluid (ISF) space has
a negative pressure of -7 cm water and Calnan et al (1972)13 showed that the lymph
has the same negative pressure. The pressure under the skin is negative. That cannot
be explained by Starling's law.
7. Inadequacy in explaining the capillary–ISF transfer in many parts of the body as
reported by Keele et al in 19824, particularly vital organs, has previously called for
reconsideration of Starling’s hypothesis by Renkin in 198614.
8. Recently reported evidence on plasma protein8-10 and HES11 versus Saline for
volume replacement therapy during major surgery shows no significant
difference. This affirms that the oncotic force does not exist in vivo that partly prove
Starling's law wrong.
9. Both physics15,16 and physiological17 research has demonstrated that the hydrostatic or
rather dynamic flow pressure induced by the proximal akin to arterial pressure does
not cause filtration, as proposed by Starling, across the wall of porous orifice (G)
tube. It causes suction15-16.
10. The proximal or arterial pressure induces negative side pressure gradient along the G
tube wall causing suction maximum near the inlet and turns positive maximum near
the exit causing filtration as based on physics experiments15,16 (Figure 1) and
physiological research17. Venous pressure enhances filtration and causes edema, but
arterial pressure does not- it causes absorption by suction. Both absorption and
filtration are autonomous functions of G tube making it the correct replacement for
the faulty law1.
11. The physiological study on the hind limb of sheep17 has completed the evidence that
Starling’s law is wrong as the capillary works as G tube not Poiseuille’s tube1.
12. The physiological study showed that plasma proteins versus Saline as circulation
fluid has no significant difference. First set of experiments the fluid is run through the
artery. This produced no edema formation but irrigated the limb well. Second set of
experiments the fluid is run through the vein; both plasma and saline induced edema
and accumulation of fluid under the cling membrane that replaced the skin.
13. Received thinking that elevating central venous pressure (CVP) is synonymous with
elevating arterial pressure is prevailing in current clinical practice during fluid
therapy for shock, the resuscitation of the acutely ill patients and prolonged major
surgery. This may be correct during restoration therapy for hypovolemic and
haemorrhagic shock, but vascular expansion or volumetric overload (VO) is a
different issue as it induces volumetric overload shocks (VOS)18--23 and causes the
acute respiratory distress syndrome (ARDS)23,24 that was originally reported by
Ashbaugh et al,24 in 1967.
14. Persistent attempts to elevate CVP up to levels of 18 to 22 cm water are common
received practice, but wrong,23. The normal CVP is around 0 and most textbooks
report a range of –7 to +7 cm water3,4,25 The question of: Does raising CVP up to level
of 18-22 cm water cause VOS? Has been positively answered26.
15. Clinical observations demonstrate that, in addition to the well-known effect of high
venous pressure causing oedema, arterial hypertension has no such effect, if not exact
opposite. In clinical practice, although arterial hypertension is common, ISF oedema
is unknown among its complications23.
16. In the G–C model of the physics experiments15,16, a minor increase in distal pressure
(DP), akin to venous pressure, increases fluid volume in chamber C around the G
tube (Figure 1) reverting chamber pressure (CP) from negative to positive while
slowing the G–C circulation. Increasing DP has similar effect to decreasing proximal
pressure (PP) akin to arterial pressure on the G–C circulation and CP and volume.
17. Vascular expansion of volumetric overload with hypervolaemia causes VO shocks18-
22. There is no doubt that the erroneous Starling's law is responsible for the many
errors and misconceptions prevailing on fluid therapy22 for shock, the acutely ill
patients and during major surgery which mislead physicians into giving too much
fluid that induce VOS and ause the multiple organ dysfunction syndrome (MODS) or
18. This wrong law dictates faulty rules on fluid therapy that underlies the treating
physician’s thought when embarking on the overzealous fluid infusion during the
resuscitation of shock, acutely ill and prolonged major surgery.
19. A concept based on the new hydrodynamic phenomenon of G tube is proposed to
replace Starling's law for the capillary–ISF circulation1. It explains this vital
circulation in every organ and tissue.
20. A rapid autonomous dynamic magnetic field-like G–C circulation occurs between
fluid in the G tube’s lumen and a surrounding fluid compartment C akin to ISF
around the capillaries (Figure 1).
21. The presented evidence does not only prove that Starling’s law is wrong but also
provides the correct replacement that is the hydrodynamic of the G tube explaining
the capillary-ISF circulation in every tissue and organ of the body. This is the only
way to resolve the puzzles of the transurethral resection of the prostate (TURP)
syndrome, acute dilution hyponatraemia (HN) and ARDS23,26,27.
Additional reason is the most serious experimental error
in the study that transformed Starling’ hypothesis into a
The report by Pappenheimer and Soto-Rivera in (1948)  was the main
reason for the transformation of Starling’s hypothesis into a law. These
authors thought that elevating the capillary pressure may be achieved by
elevating the venous pressure or arterial pressure alike, matching mmHg
for mmHg, and they reported this to be in support of Starling’s hypothesis.
However, this also has proved wrong, as demonstrated in the G tube and
Poiseuille’s tube experiments as well as evidence from clinical practice:
Elevating distal pressure (DP) akin to venous pressure augments %ltration
as shown in graph (Figure 11 SI) and in clinical practice causes oedema
formation while elevating proximal pressure (PP) akin to arterial pressure
or MHP does not, it enhances suction or absorption via the negative SP
maximum near the inlet of the G tube .
In support of the above fact is: High venous pressure, or obstruction, is
the main cause of the most common clinical oedema but arterial
hypertension though quite common it never causes oedema. O< course
neither Starling nor any of the authors who transferred his hypothesis into
a law were aware of the brilliant discoveries of precapillary sphincter 
and wide porous wall of intercellular clefts of the capillary that allow the
passage of plasma proteins thus nulli%es oncotic pressure in vivo  that
were discovered later in 1967. The G tube discovery demonstrate PP akin
to arterial pressure induce negative pressure gradient exerted on the
tube’s wall that is maximum near the inlet causing suction or absorption.
So, both Starling’s forces are wrong .
The same wrong conception that elevating CVP to levels of 20-22 cm H20
may elevate the arterial pressure in shock by infusing too many @uids was
prevailing in clinical practice till recently. Fortunately, such practice has
stopped now since it was realized that it induces volume kinetic shocks
[15,16] that cause ARDS [13,14,28].
Conict of interest: None declared by the author
Funds received during the studies and reports: None.
1. Ghanem AN. The Correct Replacement for the Wrong Starling’s law
is the Hydrodynamic of the Porous Ori%ce (G) Tube: The Complete
Physics and physiological Evidence with Clinical Relevance and
Signi%cance. Research Article. Cardiology: Open Access Cardio
Open, 2020 Volume 5 | Issue 1 | 7
2. Starling E. H. Factors involved in the causation of dropsy. Lancet
1886; ii: 1266–1270, 1330–1334 and 1406–1410.
3. Folkow B., Neil E. Circulation. Oxford University Press: London 1971; 1–125.
4. Keele C. A., Neil E., Joels N. Sampson Wright Applied Physiology. 13th ed.
Oxford University Press; Oxford, 1982.
5. Rhodin J. A. The ultra-structure of mammalian arterioles and pre-
capillary sphincters. J Ultrastructure Research 1967; 18:181–222.
6. Karnovesky M. J. The ultra-structural basis of capillary permeability
studied with peroxidase as a tracer. J Cell Biol 1967; 35: 213–236.
7. Hendry E. B. The osmotic pressure and chemical composition of
human body @uids. Clinical Chemistry 1962; 8(3): 246–265.
8. Cochrane Injuries Group. Human albumin administration in the
critically ill patients: systemic review of randomized controlled
trials: Why albumin may not work. BMJ 1998; 317: 235-40.
9. Finfer S. E<ect of baseline serum albumin concentration on outcome
of resuscitation with albumin or saline in patients in intensive care
units: analysis of data from the saline versus albumin @uid
evaluation (SAFE) study. BMJ; 333: 1044-6. (18 November 2006)
10.Vincent JL. Editorial. Resuscitation using albumin in critically ill
patients: Research in patients at high risk of complications is now
needed. BMJ; 333:1029-30. (18 November 2006)
11. Futier E, Garot M, Godet T, et al. E<ect of Hydroxyethyl Starch vs
Saline for Volume Replacement Therapy on Death or Postoperative
Complications Among High-Risk Patients Undergoing Major
Abdominal Surgery: The FLASH Randomized Clinical
Trial. JAMA. 2020;323(3):225–236. doi:10.1001/jama.2019.20833
12. Guyton A. C., Coleman T. G. Regulation of interstitial @uid volume and
pressure. Annals New York Academy of Sciences 1968; 150: 537–547.
13. Calnan J. S., P@ug J. J., Chisholm G. D., Taylor L. M. Lymphatic surgery.
Proceedings Royal Soc Med 1972; 65: 715–719.
14.Renkin E. M. Some consequences of capillary permeability to
macromolecules: Starling’s hypothesis reconsidered. Am J Physiol
(Heart Circ Physiol) 1986; 250, 19: H706–H710.
15.Ghanem AN. Magnetic %eld-like @uid circulation of a porous ori%ce
tube and relevance to the capillary-interstitial @uid circulation:
Preliminary report. Medical Hypotheses 2001 Mar; 56 (3): 325- 334.
2001 Mar; 56(3):325-34.
16.Ghanem KA. and Ghanem AN. 2017. The proof and reasons that
Starling’s law for the capillary- interstitial @uid transfer is wrong,
advancing the hydrodynamics of a porous ori%ce (G) tube as the
real mechanism. Blood, Heart and Circ, Volume 1(1): 1-7
doi:10.15761/BHC.1000102 Available online
17.Ghanem KA, Ghanem AN. The Physiological Proof that Starling’s Law
for the Capillary-Interstitial Fluid Transfer is wrong: Advancing the
Porous Ori%ce (G) Tube Phenomenon as Replacement. Open Acc Res
Anatomy. 1(2). OARA.000508. 2017
18.Ghanem A. N., Ward J. P. Osmotic and metabolic sequelae of
volumetric overload in relation to the TURP syndrome. Br J Urol
1990; 66: 71–78.
19.Ghanem, A.N. and Ghanem, S.A. Volumetric Overload Shocks: Why
Is Starling’s Law for Capillary Interstitial Fluid Transfer Wrong? The
Hydrodynamics of a Porous Ori%ce Tube as Alternative. Surgical
Science, 2016; 7: 245-249. http://dx.doi.org/10.4236/ss.2016.76035
20.Pindoria N, Ghanem SA, Ghanem KA and Ghanem AN, (2017)
Volumetric overload shocks in the patho-etiology of the
transurethral resection prostatectomy syndrome and acute dilution
hyponatraemia. Integr Mol Med, 2017 doi: 10.15761/IMM.1000279
21.Ghanem KA. and Ghanem AN. Volumetric overload shocks in the
patho-etiology of the transurethral resection prostatectomy
syndrome and acute dilution hyponatraemia: The clinical evidence
based on 23 case series. Basic Research Journal of Medicine and
Clinical Sciences ISSN 2315-6864 Vol. 6(4) pp. xx-xx April 2017
Available online http//www.basicresearchjournals.org
22.Ghanem SA, Ghanem KA, Ghanem A N. Volumetric Overload Shocks
in the Patho-Etiology of the Transurethral Resection of the Prostate
(TURP) Syndrome and Acute Dilution Hyponatraemia: The Clinical
Evidence Based on Prospective Clinical Study of 100 Consecutive
TURP Patients. Surg Med Open Access J. 2017: 1(1);1-7
23. Ghanem AN. The Adult Respiratory Distress Syndrome: Volumetric
Overload Shocks in Patho-Etiology Correcting Errors and
Misconceptions on Fluid Therapy, Vascular and Capillary Physiology.
Surg Med Open Acc J. 2(2). SMOAJ.000534.2018. DOI:
24.Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory
distress in adults. Lancet 1967; ii: 319-23.
25. Guyton A. C. (1986) Textbook of Medical Physiology. An HBJ International
Seventh Edn. WB Saunders Company. Philadelphia London; 19: 221.
26. Ghanem AN. Does Raising the Central Venous Pressure (CVP) in
Treating Shock with Fluids Induce Volumetric Overload Shocks
(VOS)?. Adv Card Res 1(5)- 2019. ACR.MS.ID.000120. DOI:
27.Ghanem AN. Volumetric Overload Shocks: Resolving the puzzles of the
transurethral resection of the prostate (TURP) syndrome, acute dilution
hyponatraemia (HN) and the acute respiratory distress syndrome (ARDS). Scholars
Press USA, 2018.
28.Pappenheimer JR, Soto-Rivera A. E<ective osmotic pressure of the
plasma proteins and other quantities associated with the capillary
circulation in the hind limbs of cats and dogs. Am J Physiol. 1948;
152: 471- 491.
Figure 1 shows a diagrammatic representation of the hydrodynamic of G tube based on G
tubes and chamber. This 40-years old diagrammatic representation of the hydrodynamic
of G tube in chamber C is based on several photographs. The G tube is the plastic tube
with narrow inlet and pores in its wall built on a scale to capillary ultra-structure of
precapillary sphincter and wide inter cellular cleft pores, and the chamber C around it is
another bigger plastic tube to form the G-C apparatus. The chamber C represents the ISF
space. The diagram represents a capillary-ISF unit that should replace Starling’s law in
every future physiology, medical and surgical textbooks, and added to chapters on
hydrodynamics in physics textbooks. The numbers should read as follows:
1 .The inflow pressure pushes fluid through the orifice
2 .Creating fluid jet in the lumen of the G tube.**
3 .The fluid jet creates negative side pressure gradient causing suction maximal over the
proximal part of the G tube near the inlet that sucks fluid into lu
4 .The side pressure gradient turns positive pushing fluid out of lumen over the distal
part maximally near the orifice
5 .Thus, the fluid around G tube inside C moves in magnetic field-like circulation (5)
taking an opposite direction to lumen flow of G tube.
6 .The inflow pressure 1 and orifice 2 induce the negative side pressure creating the
dynamic G-C circulation phenomenon that is rapid, autonomous, and efficient in moving
fluid and particles out from the G tube lumen at 4, irrigating C at 5, then sucking it back
again at 3,
7 .Maintaining net negative energy pressure inside chamber C.
**Note the shape of the fluid jet inside the G tube (Cone shaped), having a diameter of the
inlet on right hand side and the diameter of the exit at left hand side (G tube diameter). I lost
the photo on which the fluid jet was drawn, using tea leaves of fine and coarse sizes that runs
in the center of G tube leaving the outer zone near the wall of G tube clear. This may explain
the finding in real capillary of the protein-free (and erythrocyte-free) sub-endothelial zone in
the Glycocalyx paradigm (Woodcock and Woodcock 2012) . It was also noted that fine tea
leaves exit the distal pores in small amount maintaining a higher concentration in the
circulatory system than that in the C chamber- akin to plasma proteins.