University of Split

School of Medicine

Disorders of salt and water transport

Ascites
Matea Laco

Third year – Medicine

CONTENT

1. Introduction

1.1. Body fluid and electrolyte transport - physiology

1.2. Ascites generally

2. Elaboration

2.1. Pathophysiology of edema

2.2. Pathophysiology of ascites

3. Conclusion

4. Summary

5. References
1.1. Body fluid and electrolyte balance - physiology

Body fluids can be discussed in terms of their specific fluid compartment, a location that is
largely separate from another compartment by some form of a physical barrier. The
intracellular fluid (ICF) compartment is the system that includes all fluid enclosed in cells by
their plasma membranes. Extracellular fluid (ECF) surrounds all cells in the body.
Extracellular fluid has two primary constituents: the fluid component of the blood (called
plasma) and the interstitial fluid (IF) that surrounds all cells not in the blood.
Water moves freely and often rapidly between the various body fluid compartments. Two
forces determine this movement: hydrostatic pressure and osmotic pressure. Hydrostatic
pressure from pumping of the heart (and the effect of gravity on the column of blood in the
vessel) and osmotic pressure exerted by plasma proteins (oncotic pressure) are important
determinants of fluid movement across the capillary wall. By contrast, because hydrostatic
pressure gradients are not present across the cell membrane, only osmotic pressure
differences between ICF and ECF cause movement of fluid into and out of cells. Osmotic
pressure differences between ECF and ICF are responsible for movement of fluid between
these compartments. Because the plasma membrane of cells contains water channels
(aquaporins), water can easily cross the membrane. Hence, a change in the osmolality of
either ICF or ECF results in rapid movement of water between these compartments. Thus,
except for transient changes, the ICF and ECF compartments are in osmotic equilibrium. In
contrast to water, the movement of ions across cell membranes is more variable from cell to
cell and depends on the presence of specific membrane transport proteins.

The intracellular ionic composition of cells varies from tissue to tissue. For example, the
intracellular composition of neurons is different from that of muscle cells, which differs from
that of blood cells. Nevertheless, there are similar patterns. When compared with ECF, ICF is
characterized by a low [Na⁺ ] and a high [K⁺ ]. This is the result of the activity of Na⁺-K⁺ -
ATPase, which transports 3Na⁺ ions out of the cell and 2 K⁺ ions into the cell for each
molecule of ATP hydrolyzed. As will be discussed, the activity of Na⁺ - K⁺ -ATPase is not only
important for establishing the cellular Na⁺ and K⁺ gradients but is also involved in indirectly
determining the cellular gradients for many other ions and molecules. Because Na⁺ - K⁺ -
ATPase transports three cations out of the cell in exchange for two cations, it is electrogenic
and thus contributes to the establishment of membrane voltage (cell interior negative). The
Na⁺ - K⁺ -ATPase–generated ion and electrical gradients are used to drive the transport of
other ions and molecules into or out of the cell. For example the inwardly directed Na⁺
gradient drives the secondary active extrusion of H⁺ from the cell and thus contributes to the
maintenance of intracellular pH. The 3Na⁺ -1Ca⁺⁺ antiporter, along with plasma membrane
Ca⁺⁺ -ATPase, extrudes Ca⁺⁺ from the cell and thus contributes to maintenance of a low
intracellular [Ca ++ ]. Finally, the membrane voltage drives Cl¯ out of the cell through Cl¯ -
selective channels, thus lowering the intracellular concentration below that of the ECF.

1.2. Ascites generally

Ascites represents a pathologic accumulation of fluid within the peritoneal cavity. The term
“ascites” is derived from the Greek term “askos” in reference to its similar appearance to a
winebag or sac. This seems rather appropriate, both in description of presentation and as an
allusion to a main cause of cirrhosis. However, in 20% of cases, it is not linked to liver
cirrhosis. The pathophysiology is mostly different. The understanding of these
pathophysiological mechanisms can lead to etiologic diagnosis. The diagnostic approach is
mainly based on the protein concentration and albumin gradient between serum and
ascites. According to the International Ascites Club, it is classified as grade 1, 2 and 3 as far as
severity. Based on associated complications and therapeutic response, it can also be
classified as uncomplicated, complicated and refractory ascites.

2.1. Pathophysiology of edema

Alterations in sodium and water balance are closely related. Water imbalances may develop
because of changes in osmotic gradients caused by gain or loss of salt. Likewise, sodium
imbalances occur with alterations in body water volume. Generally the alterations can be
classified as changes in tonicity, or the change in concentration of electrolytes in relation to
water. Alterations can therefore be classified as isotonic, hypertonic, or hypotonic.

Edema occurs when an excessive volume of fluid accumulates in the tissues, either within
cells (cellular edema) or within the collagen-mucopolysaccharide matrix distributed in the
interstitial spaces (interstitial edema. Our focus is on swelling of the extracellular matrix or
interstitial edema, which may occur as a result of aberrant changes in the pressures
(hydrostatic and oncotic) acting across the microvascular walls, alterations in the molecular
structures that comprise the barrier to fluid and solute flux in the endothelial wall that are
manifest as changes in hydraulic conductivity and the osmotic reflection coefficient for
plasma proteins, or alterations in the lymphatic outflow system, as predicted by examination
of the Starling equation.

2.2. Pathophysiology of ascites

Cirrhotic ascites, in the setting of portal hypertension, comprises approximately 85% of all
cases. Other causes of ascites (non-cirrhotic) can be broadly defined as pre- or post-hepatic
in origin. Pre-hepatic causes might include: portal vein thrombosis, lymphoma, abdominal
lymphatic injury or obstruction, bowel perforation, renal failure, pancreatitis, peritoneal
tuberculosis, or a malignancy with peritoneal implants. Post-hepatic causes include
congestive heart failure usually associated with pulmonary hypertension, constrictive
pericarditis, the Budd-Chiari syndrome, and stricture/web formation in the inferior vena
cava (IVC).
Malignant ascites, which is found in 10% of cases, can occur as a result of any neoplastic
disease having peritoneal metastasis, but is more common with breast, bronchus, ovary,
gastric, pancreatic or colon cancer. Up to 20% of cases of malignant ascites have a tumor of
unknown origin. Most cases of malignant ascites have a high protein content. Because there
are multiple potential causes of ascites other than liver disease and/or portal hypertensive
origin, non-hepatic disease processes should be ruled out through clinical history and by
utilizing specific laboratory testing and imaging.
In the setting of portal hypertension, backflow and stasis of vasodilatory substances, (nitric
oxide), begin to accumulate. This causes, amongst other results splanchnic vasodilation with
resultant hypoperfusion (although even when globally euvolemic or hypervolemic) of the
renal system. Appropriately in this sense, the renin-angiotensin-aldosterone system (RAAS)
is activated leading to aggressive fluid retention. In brief, renin is secreted from the renal
juxtaglomerular apparatus (JGA) around the proximal nephrons in response to changes in
vascular pressures, changes in serum sodium, and from activation of the sympathetic
nervous system. It in turn will convert angiotensinogen (made in the liver) to angiotensin 
I which is further converted to angiotensin II by angiotensin converting enzyme (ACE) in the
lungs. Angiotensin II has multiple important functions that drive fluid acquisition and
retention, including stimulation of the thirst drive, release of aldosterone from the zona
glomerulosa of the adrenal cortex, and secretion of vasopressin from the posterior pituitary.
This excess retained blood volume is thought to leak-out (filtered in a sense) directly from
both the liver surface, and the mesenteric vessels. This latter mechanism is due to increased
hydrostatics and vascular wall permeability, and concurrently decreased oncotic (osmotic)
fluid retention in the form of absolute or relative hypoalbuminemia. These three
parameters, as described in the classical Starling equation, overwhelm the reabsorptive
capacity of the peritoneal surface and lymphatic system. Continued dysregulation of these
mechanisms can lead to profound ascitic fluid retention.

3.
The most common complication to chronic liver failure is ascites. The formation of ascites in
the cirrhotic patient is caused by a complex chain of pathophysiological events involving
portal hypertension and progressive vascular dysfunction. Since ascites formation represents
a hallmark in the natural history of chronic liver failure it predicts a poor outcome with a
50% mortality rate within 3 years. Patients with ascites are at high risk of developing
complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal
impairment. Adequate management of cirrhotic ascites and its complications betters quality
of life and increases survival.
4. Summary
Edema, (alternate spelling: oedema) formerly referred to as dropsy or hydropsy, is the
swelling of the body's tissues due to excess interstitial fluid retention. Edema can occur
locally, often affecting the extremities (peripheral edema), or generally, affecting the entire
body (anasarca).
In the body, there are two main compartments between which fluid is exchanged: the
intravascular and extravascular compartments. Intravascular compartments include the
cardiac chambers and the vascular system itself, whereas the extravascular compartments
include everywhere else. Fluid moves easily between these compartments, and the extent of
this movement is determined primarily by the balance between hydrostatic and oncotic
pressures.
Normally the peritoneal cavity contains only a small amount of fluid, although in women this
can vary (by 20ml, or less than an ounce) depending on the menstrual cycle. Ascites is the
term used to denote increased fluid in the peritoneal cavity, a situation that is not normal.
There are a variety of diseases that can cause the fluid to accumulate and the reasons that
the ascites occurs may be different for each disease. Cancer that spreads to the peritoneum
can cause direct leakage of fluid, while other illnesses cause an excess accumulation of water
and sodium in the body. This fluid can eventually leak into the peritoneal cavity.
Most commonly, ascites is due to liver disease.
REFERENCES

 Berne & Levy Physiology, Sixth Updated Edition

 Pathophysiology of Disease, An Introduction to Clinical Medicine 7E
 Pathophsysiology ,The Biologic Basis for Disease in Adults and Children
 Pathophysiology of Portal Hypertension, Yasuko Iwakiri, Ph.D. (Pub Med
article)