Water, Electrolytes, and Body Fluids

8.1.1 Introduction

Osmoregulation is osmotic balance maintained across membranes within the body’s fluids. Osmotic balance is contributed by the electrolytes and non-electrolytes.

Electrolytes are the solutes that dissociate into ions during water dissolution, and non-electrolytes do not dissociate into ions during water dissolution. Electrolytes in living systems include zinc, sodium, potassium, magnesium, chloride, cop­per, bicarbonate, manganese, calcium, iron, phosphate, molybdenum, and chromium. Sodium, bicarbonate, phos­phate, potassium, calcium, and chloride are the major electrolytes involved in various body functions. These electrolytes perform a variety of functions in the animal body such as transmission of electrical impulses in neurons and muscles, release of hormones, stabilisation of protein structure, acid-base regulation, and also osmoregulation of body fluids. The hydrostatic pressure and osmotic pressure control the movement of water along the cell membrane. Among these two physical factors, osmosis can only be directly controlled by the movement of electrolytes. Mainte­nance of an electrical and chemical balance within and out­side the cell is accountable for an electro-chemical gradient existing between extracellular and intracellular fluids. This gradient is actually made use of in the movement of electrolytes and also in the movement of water across the cellular compartments.

Osmoconformers are organisms that maintain their inter­nal salinity same as their environment (e.g., most marine invertebrates). Osmoregulators tightly maintain body osmo­larity even after fluctuations in salt levels in the environment and are more common in the animal kingdom.

Osmosis is a physical process, by which diffusion of water occurs across a semipermeable membrane, from an area of high water potential (low solute concentration) to an area of low water potential (high solute concentration) without input of energy.

When a solution has a higher concentration of solute than a solution with a lower concentration of solute, it is referred to as hyperosmotic. If two solutions are having the same solute concentration, they are said to be isosmotic.

Tonicity is determined by the number of solutes that cannot penetrate the membrane and the effective osmotic pressure gradient. To put it another way, tonicity refers to the relative concentration of dissolved solutes in a solution that determines the direction and extent of diffusion. It describes what a solution would do to a cell’s volume at equilibrium if the cell was placed in the solution. The solutes that are unable to penetrate the cell dictate the tonicity of an infused solution. As a result, the terms isosmotic, hyperosmotic, and hyposmotic are not interchangeable with tonic, hypertonic, and hypotonic. Isosmotic refers to the osmolalities of various physiological fluids having the same value, such as plasma versus cerebrospinal fluid. The terms isotonic, hypotonic, and hypertonic are used to describe the osmolalities of solutions used in clinical practice to restore bodily fluid losses. When compared to plasma, a hypertonic solution has a higher effective osmotic pressure. A hypotonic solution has lower effective osmotic pressure compared to plasma. A solution having effective osmotic pressure identi­cal to that of plasma is called isotonic solution. Plasma has an osmolality of 0.3 Osm or 300 mOsm. 0.15 M solution of NaCl is equal to 0.3 osmol solution because NaCI ionises into two ions, Na⁺ and Cl^-; half the molar NaCI (0.15) solution contributes to 0.3 osmole. Isotonic saline solution for clinical applications is prepared with sodium chloride concentration of 9 g/L of water or 0.9% (w/v), i.e.

If water or hypotonic saline is added to extracellular fluid (ECF) or plasma, the osmotic concentration of this compart­ment is lowered and water moves into cells—this may inter­fere with normal metabolism of cells or may even lead to death of cells—this over-hydration is known as water intoxi­cation. When isotonic saline solution is given to ECF, it spreads evenly throughout the ECF but has no effect on ICF. When a hypertonic saline solution is added to ECF/plasma, the osmotic concentration of ECF rises, and water moves from within the cells (ICF) to ECF; however, the cell membrane is less permeable to sodium ions, so sodium ions accumulate within the cells, raising intracellular osmotic pressure; this is known as cellular dehydration.

8.1.2 Body Water Compartments

Water is the most important component of life and the body’s main component. The body’s water is divided into compartments separated by a selectively permeable mem­brane. The chemical composition of these compartments varies. The compartments are as follows: Intracellular fluid (ICF) is the water contained within the cells and accounts for approximately (two-thirds of body water) 65% of total water; extracellular fluid (ECF) is the water outside the cells and accounts for approximately (one-third of body water) 35% of total water. Intravascular fluid or plasma (one-fifth of ECF), interstitial fluid (four-fifths of ECF), and transcellular fluid make up extracellular fluid. The fluid that surrounds the cell is known as interstitial fluid. The fluid contained in body cavities such as cerebrospinal, peritoneal, synovial, ophthalmic fluids, and fluids in the gastrointestinal system (which is the major component in ruminants) is known as transcellular fluid (“third space,” which is generally neglected in calculations). Urine and bile are also considered as transcellular fluids.

8.1.2.1 Total Body Water (TBW)

The sum of water in intracellular and extracellular body compartments is referred to as total body water.

Out of 60% TBW, intracellular fluid accounts for 40% of total body weight, whereas extracellular fluid accounts for 20%. The amount of water in each of these compartments is controlled by the body. To keep the amount of water in each compartment generally constant, water is transported across most of the cell membranes as needed.

8.1.2.2 Water Balance

Homeostasis (coined by W. B. Cannon) is the existence and preservation of stability within the internal environment. The term internal environment or internal milieu was put forth by Claude Bernard. When daily water intake equals daily water loss, the body’s water equilibrium is maintained. In most cases, the body’s water content varies very little.

Ingestion and metabolic water (end product of cellular metabolism) provide water to the body. One gram of carbo­hydrate, fat, and protein on oxidation supplies 0.6 mL,

1.1 mL, and 0.4 mL of water, respectively. Metabolic water provides 5-10% of total body water requirements. The importance of metabolic water in many desert rats cannot be overstated. It may provide 100% of their water consump­tion, allowing them to subsist on dry food and no water. One of the examples is the kangaroo rat.

Water is lost from the body through various routes like urine, skin, expired air, faeces, and milk (lactating animals). The body’s natural regulatory mechanism regulates water losses through several routes in order to maintain equilibrium (Table 8.1).

8.1.2.2.1 Regulation of Water Intake

Water intake is intermittent, whereas water loss is continu­ous. A gradual dehydration problem is constantly present in an animal’s life. The osmolarity in all fluid compartments is almost equal. It ranges from 301.5 to 303 mOsm/kg of water in human. Water will be shifted from the cell into the ECF during gradual dehydration since the ECF is the immediate source of water loss. Water ingestion is used to replenish this water deficiency on a regular basis. Water consumption is influenced by habit or a daily routine of eating and drinking without being thirsty.

Any significant loss of bodily fluid results in a sensation of thirst as well as a behavioural desire to drink. When there is a water shortage, both thirst and the desire to drink grow. There are a number of regulating mechanisms in place to ensure that the amount of water consumed equals and corrects a bodily water deficit.

Table 8.1 Waterbalanceinacow

Dehydration causes a decrease in blood volume and blood pressure, as well as an increase in blood osmolarity. The thirst centre of hypothalamus reacts to a variety of dehydration signals, including angiotensin II (subjected to release in reac­tion to low blood pressure), vasopressin (released in response to increased blood osmolarity), and osmoreceptor cues (neurons in hypothalamus monitoring extracellular fluid osmolarity).

When the thirst centre receives the signals, it inhibits salivation by activating the sympathetic nerve supply to the salivary gland. Salivation is also reduced in dehydra­tion due to decreased capillary filtration produced by low blood pressure and high blood osmolarity. Reduced sali­vation causes the animal to feel thirsty, which leads to water consumption. Drinking water cools and moistens the mouth while also causing stomach and intestinal dis­tension. These will suppress thirst for a brief period of time.

Water consumption rehydrates the blood, lowering osmo­larity. It reduces osmoreceptor response and enhances capil­lary filtration. As a result, saliva becomes more watery and profuse. Long-term thirst inhibition is caused by water absorption from the small intestine and a decrease in blood osmolarity.

8.1.2.2.2 Regulation of Water Output

The only means by which water output can be significantly controlled is through regulation of urine volume. Antidiuretic hormone (ADH) is involved in controlling water output. In dehydration, elevated blood osmolarity stimulates the osmoreceptors in the hypothalamus. As a result of the stimulation of osmoreceptors, the posterior pituitary is stimulated to release ADH. In the kidney, ADH interacts with V₂ receptors present on the basal side of epithelial cells of late distal convoluted tubule, collecting tubule, and collecting duct. Binding of ADH with V₂ recep­tor will cause formation of second messenger cAMP. cAMP will in turn increase the number of water channels (aquaporin 2) in the epithelial cytoplasm. Aquaporin 2 is inserted on the luminal surface of the epithelium and thus increases water permeability. Water is reabsorbed till osmotic equilibrium is reached. Thus, kidney will increase water reabsorption resulting in reduced urine output. ADH helps in elevating blood volume and lowering blood osmo­larity in dehydration.

On the other hand, if blood osmolarity is very low or blood volume and blood pressure are very high, ADH release is blocked. The renal tubule’s ability to reabsorb water decreases, resulting in an increase in urine volume. This will lower the total blood water level and return it to normal.

Adjustments in sodium reabsorption are also linked to urine volume regulation. Sodium reabsorption and excretion are accompanied by a proportionate amount of water. With regard to electrolyte balance, maintaining water balance by regulating sodium excretion is better understood.

8.1.2.3 MeasurementofBodyWater

The difference in the weight of fresh carcasses and dried carcasses was used to compute the total body water at earlier times. The total body water was afterwards estimated using the dilution approach. The volume of bodily water can be determined by injecting a known-concentration indicator chemical into the bloodstream, allowing it to diffuse equally throughout the plasma, and then evaluating the amount of dilution (Table 8.2). The total body water (TBW) can be calculated from the formula given below:

Table 8.2 Different substances used to determine body fluid volume

ECF extracellular fluid, ICF intracellular fluid, RBC red blood cells

Volume of indicator solution injected ? Concentration of indicator solution injected

!B^v ⁼-------------------------------------------------------------------------------------------------------------------

Concentration of indicator solution after equilibration

An indicator solution that equally spreads in plasma and interstitial fluid but does not infiltrate the cell membrane can be used to assess the volume of extracellular fluid. Because the intracellular fluid volume cannot be directly determined, it must be calculated by subtracting the extracellular fluid volume from total body water. A material that does not readily permeate capillary membranes but persists in the circulatory system after injection is used to quantify plasma volume. Similarly to intracellular fluid volume, interstitial fluid volume cannot be measured directly. It is computed by subtracting the volume of plasma from the volume of extra­cellular fluid.

The haematocrit (the fraction of total blood volume made up of cells) can also be used to compute the blood volume using the equation below:

Another approach to estimate blood volume is to insert radioactively labelled red blood cells into the circulation. The radioactivity of a mixed blood sample can be measured after extensive mixing of these cells in circulation, and the total blood volume can be determined using the dilution principle. Radioactive chromium (⁵¹Cr), which binds firmly to red blood cells, is a common material used to identify red blood cells.

Newer non-invasive techniques using body composition have been developed to measure total body water. These techniques include bioelectrical impedance analysis, air dis­placement plethysmography, dual-energy X-ray absorptiom­etry, and nuclear magnetic resonance. Bioelectric impedance analysis is economical and simple to use. These newly devel­oped techniques measure total body water using empirical equations. These empirical equations are developed by com­paring the measurements obtained by new methods with measurements made using reference methods.

8.1.3 Electrolytes

Electrolytes play a crucial role in animal health. Chemically reactive, they have a role in metabolism. They are responsible for determining the electrical potential across the cell mem­brane. They have a significant impact on the osmolarity of body fluids and the content and distribution of body water. Because ICF and ECF have the same osmolarity, cells do not bulge or shrink, but in terms of electrolyte concentration (Table 8.3), electrolytes are more numerous than non-electrolytes; they regulate water osmosis between bodily compartments. Sodium and calcium are the predominant cations in extracellular fluid, whereas chloride and bicarbonates are the major anions. Blood plasma will contain other proteins. Potassium and magnesium are the most abun­dant cations in intracellular fluid, while phosphates, proteinates, and sulphates are the most available anions. The erythrocytes of cats, dogs, cattle, and sheep have higher sodium ions than potassium. There is a little osmotic activity difference between plasma and interstitial fluid. The concen­tration of positively charged ions in plasma is slightly higher (approximately 2% higher) than the interstitial fluid (Table 8.4).

8.1.3.1 Electrolyte Transportation

The electrolytes transfer across a cell membrane in two ways: passive and active transportation. Transportation follows a concentration gradient called passive transportation that requires no energy input. Simple diffusion, facilitated diffu­sion, filtration, and osmosis are examples of passive trans­portation. In simple diffusion, electrolytes flow across the cell membrane according to their concentration gradient, from areas of high concentration to areas of low. In facilitated diffusion, electrolytes migrate into or out of the cells down to their concentration gradient through protein channels pres­ent in the cell membrane. Molecules move across the cell membrane due to a pressure gradient in the filtration process. Hydrostatic pressure is generally applicable here. The move­ment of a solvent through a selectively permeable or semi-

Table 8.3 Osmotically active substances in human body fluid (mOsmol/kg H₂O)

Table 8.4 Plasmaconcentrations of electrolytes in dogs and cats

permeable (cell) membrane, from higher to lower, is called osmosis.

Active transportation necessitates the use of energy to transport molecules into a cell. Primary active transportation and secondary active transportation are two types of active transportation. The transport protein comprises an ATPase, which hydrolyses ATP to create the energy required for transport in primary active transportation. It may also be called as an ion pump. There is no direct coupling of ATP in secondary active transportation; instead, the potential dif­ference established by pumping ions out of the cell via primary active transport is used. Multiple electrolytes are moved across the membrane via secondary active transporta­tion, which combines the uphill movement of one electrolyte (s) with the downhill movement of the other(s). It is called symport or co-transport when electrolytes flow in the same direction and antiport or counter-transport when they move in the opposite direction. ABC transporters, P-type ATPases, and solute carrier family are the three main membrane transporters that transport electrolytes. ABC transporters are key active transporters that transfer a wide spectrum of ions. P-type ATPase enzymes are used in primary active transpor­tation to move cations. Ca²⁺-ATPases and Na⁺,K⁺-ATPases are examples of this family. Transporters in the solute carrier family use secondary active transport and facilitative diffu­sion to move solutes. The Na⁺/H⁺ exchanger is an example of the solute carrier family.

8.1.3.2 Sodium

Sodium is the primary cation in extracellular fluids. Nearly 45% of sodium in the body is present in the extracellular fluid, 45% in the bones, and the rest in the intracellular fluid. Sodium is a key solute in determining total body water volume and water distribution among fluid compartments. Sodium is responsible for 90-95% of ECF osmolarity, and it accounts for half of the osmotic pressure differential that exists between the inside of cells and their surroundings. The kidneys are primarily responsible for salt excretion. Sodium is freely filtered through the kidneys’ glomerular capillaries, and the majority of it is reabsorbed in the proximal convo­luted tubule leaving only a small amount in urine.

In ECF, sodium content is relatively constant. In animals, dietary deficiency of sodium is rare, but adequate sodium excretion by the kidney is of primary concern. Four hormones are mainly involved in the regulation of sodium; they are ADH, atrial natriuretic factor, aldosterone, and angiotensin II.

The antidiuretic hormone regulates water absorption and excretion independently of sodium excretion. Osmolarity of ECF increases when sodium concentration rises above the normal level in ECF. The osmoreceptors in the hypothalamus detect it, causing the release of ADH from the posterior pituitary. ADH increases water reabsorption from renal tubules and stimulates the thirst centre. In contrast, the release of ADH is inhibited by a drop in sodium content below normal in ECF, causing diuresis with the excretion of more water followed by the rising of sodium content in the ECF.

The hormone aldosterone (also known as the salt retention hormone) regulates the rate of sodium excretion. The adrenal cortex is directly stimulated to release aldosterone when sodium levels are reduced or potassium levels are elevated. The renin-angiotensin system promotes aldosterone secretion when blood pressure is reduced. The major cells that line the renal tubules, particularly at the later part of the convoluted tubule and collecting duct, are affected by aldosterone. The basement membrane allows aldosterone from the blood to enter the main cell. It induces gene transcription by binding to its receptors in the cytoplasm. The proteins formed cause three effects: (1) attach new sodium-potassium ATPase pumps on the basal surface of principal cells, (2) attach ENaC (epithelial sodium channels) on the luminal surface of principal cells, and (3) activate the existing sodium­potassium ATPase pump on the basal surface and sodium and potassium channels on the luminal surface. Sodium from the tubular fluid is reabsorbed into the main cell and transported to the blood via sodium-potassium ATPase pumps due to these three processes. At the same time, potas­sium from the blood enters into the principal cell via sodium­potassium ATPase pumps on the basal surface and is excreted into the tubular fluid of the renal tubule via potassium channels on the luminal surface. Sodium, from the blood, enters the principal cell via sodium-potassium ATPase pumps on the basal surface. As a result, aldosterone causes an increase in salt absorption and a decrease in potassium excre­tion. Along with sodium and water, chloride is also reabsorbed. The blood volume, blood pressure, and sodium and potassium concentration are restored to normal.

An increase of sodium with the rise in blood volume results in the release of the atrial natriuretic factor (ANF) due to distension of the heart’s atria. ANF increases salt and water excretion through the kidneys while inhibiting ADH and renin secretion. As a result, the kidneys excrete more salt and water. It aids in restoring normal blood volume and sodium levels.

Hyponatraemia is a condition in which sodium concentra­tion in the blood is lower than normal. It is mainly caused by an excess of water in the body, which dilutes the sodium. Reduced sodium intake combined with constant excretion through urine, severe sweating, vomiting, diarrhoea, and diseases that cause diuresis, such as diabetes and acidosis, causes extreme hyponatraemia. Relative hyponatraemia can occur as a result of excessive water retention in oedema or congestive heart failure.

Hypernatraemia is a condition in which blood sodium levels are abnormally high. It can be caused by the loss of water from the blood, which causes the haemo-concentration of all blood elements. It can also be caused by hormonal abnormalities involving ADH and aldosterone.

8.1.3.3 Potassium

Potassium is the most abundant as the intracellular cation, and it aids in generating action potentials and establishing the resting membrane potential after depolarisation in neurons and muscle fibres. Potassium, unlike sodium, has minimal effect on osmotic pressure. The sodium-potassium pumps in cell membranes, which maintain appropriate potassium con­centration gradients between the ICF and ECF, are responsi­ble for the low potassium levels in the blood and cerebrospinal fluid. The renal tubules, particularly at the distal convoluted tubule and collecting ducts, discharge potassium both actively and passively. Under the effect of aldosterone, potassium participates in the exchange of sodium (discussed earlier).

Aldosterone aids in the control of potassium levels in the ECF. The adrenal cortex will release aldosterone in response to a slight increase in potassium content. The tenfold increase in potassium concentration results in a threefold increase in aldosterone. Aldosterone raises potassium excretion in the urine and returns the ECF potassium concentration to normal.

Hypokalaemia is a condition in which the potassium level in the blood is abnormally low. Hypokalaemia can develop due to loss of potassium in the body or a relative reduction in potassium in the blood due to potassium redistribution. Reduced intake, which is commonly associated with famine, vomiting, diarrhoea, and alkalosis, can cause potassium loss. The redistribution of potassium causes a relative decrease in the blood in some insulin-dependent diabetic individuals. When insulin is given and glucose is taken up by cells, potassium travels through the cell membrane with the glu­cose, lowering the amount of potassium in the blood and interstitial fluid, leading to hyperpolarisation of neuron cell membranes and reduced sensitivity to stimuli.

Hyperkalaemia, or an abnormally high potassium level in the blood, can harm skeletal muscles, neurological system, and heart. Increased potassium intake in the diet can cause hyperkalaemia. Increased potassium concentration in the ECF can cause partial depolarisation (excitation) of the plasma membrane of skeletal muscle fibres, neurons, and cardiac cells and an inability to repolarise the cells. In such circumstances, the heart will not relax after a contraction, thus seizing and ceasing to pump blood, resulting in death within minutes. An individual with hyperkalaemia may have mental disorientation, numbness, and weaker respiratory muscles due to the effects on the neurological system.

8.1.3.4 Chloride

The most common extracellular anion is chloride. Chloride contributes significantly to the osmotic pressure difference between the ICF and the ECF, and it is essential for optimal hydration. Chloride maintains the electrical neutrality of the ECF by balancing cations in the fluid. Chloride ion secretion and reabsorption in the kidneys follow the same pathways as sodium ions.

Hypochloraemia, lower-than-normal blood chloride levels, occurs mainly due to faulty renal tubular absorption. Hypochloraemic dogs and cats have chloride concentrations of less than 100 mEq/L and 110 mEq/L, respectively. Hypochloraemia can also be caused by vomiting, diarrhoea, or metabolic acidosis. Dehydration, excessive ingestion of food salt (NaCl) or swallowing seawater, renal failure, renal tubular acidosis, diabetes mellitus, congestive heart failure, chronic lung disease, and other factors can cause hyperchloraemia, or higher-than-normal blood chloride levels. Pseudo-hyperchloraemia often occurs during serum examinations in the laboratory. It causes excessive loss of water and leads to chloride loss, lipemic serum, and pigments like bilirubin and haemoglobin in the serum. Injection of potassium bromide can also cause pseudo-hyperchloraemia.

8.1.3.5 Bicarbonate

The second most abundant anion in the blood is bicarbonate. Its primary role is to regulate the body’s acid-base balance by acting as a component of buffer systems. In body fluids, a small amount of CO₂ may dissolve. It leads to the production of approximately 90% of CO₂ into bicarbonate ions (HCO3^-) following the reaction as:

CO2 + H₂O $ H₂CO₃ $ HCO₃ ^- + H⁺

The bidirectional arrows indicate that depending on the concentrations of the reactants and products, the reactions can proceed either way. In tissues with a high metabolic rate, considerable volumes of carbon dioxide are generated. Car­bon dioxide converts into bicarbonate in the cytoplasm of red blood cells by the action of an enzyme known as carbonic anhydrase, and then it enters into the bloodstream. The CO₂ is regenerated from bicarbonate in the lungs, causing a reverse reaction and expelling as metabolic waste.

8.1.3.6 Calcium

Calcium, the most abundant mineral in bones and teeth (calcium reservoirs), is responsible for its hardness. Muscle contraction, enzyme function, and blood coagulation require calcium ions (Ca²⁺). Calcium also aids in the stabilisation of cell membranes and is necessary for the release of neurotransmitters and hormones from endocrine glands.

Nearly 30% of the total calcium in the bone is made up of amorphous salts that can easily be exchanged with ECF. The amount equates to around 5-10 g in total. The amorphous calcium crystals have a wide surface area that can easily absorb extra calcium when hypercalcaemia occurs. The amorphous salts are easily carried into the bloodstream if hypocalcaemia occurs. In about 70 min, any alterations in calcium concentration in the blood are restored to normal levels by this buffering mechanism. Parathyroid hormone, calcitonin, and vitamin D play a role in calcium homeostasis. These hormones regulate eucalcaemia by their effects on bone deposition and bone resorption, urinary excretion, and intestinal calcium absorption. Bone is a long-term regulator of eucalcaemia. When bone is saturated with or depleted with calcium salts, the intestine and kidney regulate eucalcaemia.

Hypocalcaemia, abnormally low blood calcium levels, is seen in hypoparathyroidism that can occur during the dys­function of the thyroid gland as four nodules of the parathy­roid gland are lodged within it. Renal illnesses, insufficient dietary calcium, vitamin D deficiency, low magnesium levels, pancreatitis, hypoparathyroidism, and certain drugs, including anticonvulsants and corticosteroids, cause hypocalcaemia. Primary hyperparathyroidism is characterised by hypercalcaemia, or unusually high calcium blood levels. Hypercalcaemia is a side effect of several cancers. Magnesium levels are closely linked to calcium levels; hence, it is common to fix and treat magnesium levels before treating calcium levels.

8.1.3.7 Phosphate

Dihydrogen phosphate (H₂PO₄^-), monohydrogen phosphate (HPO₄^2-), and phosphate (PO₄^3-) are the three ionic forms of phosphate found in the body. HPO₄^2- is the most preva­lent kind. Calcium-phosphate salts, bone, and teeth bind up 85% of the body’s phosphate. Phospholipids, such as those that make up the cell membrane, ATP, nucleotides, and buffers, all include phosphate. They play a crucial role in maintaining acid-base equilibrium by functioning as buffers.

Hypophosphataemia, or abnormally low phosphate blood levels, can occur due to excessive antacid usage or malnutri­tion. The kidneys generally conserve phosphate when faced with phosphate depletion, although this conservation is sub­stantially hampered by hunger. Hyperphosphataemia, or unusually high phosphate levels in the blood, occurs when renal function is impaired or acute lymphocytic leukaemia is present. Phosphate is a major component of the ICF; hence, any considerable cell death might result in phosphate being dumped into the ECF.

8.1.3 TranscellularFluid

The transcellular fluid is found in epithelial cell-lined bodily cavities. It includes the cerebral fluid, synovial fluid, perito­neal fluid, pleural fluid, pericardial fluid, aqueous humour, and vitreous humour of the eye, bile, and fluid from the digestive, urinary, and respiratory tracts.

8.1.4.1 Cerebrospinal Fluid

Cerebrospinal fluid (CSF) is a unique fluid found in and around the brain and spinal cord. It presents in the brain’s ventricles, the spinal cord’s central canal, and the subarach­noid region. The choroid plexus of the brain’s lateral and third ventricles produces the majority of the cerebrospinal fluid (two-thirds). Ependymal cells that line the ventricles and spinal canal create cerebrospinal fluid. The pia mater, which covers the central nervous system, produces a minor amount. A layer of pia mater and choroid epithelial cells covers the choroid plexus, which resembles a cauliflower­like proliferation of blood vessels (modified ependymal cells). Microvilli cover the apical surface of choroid epithelial cells. Many fenestrae in the capillary endothelium’s wall allow many tiny molecules to flow through. Tight connections connect adjacent choroid epithelial cells preventing water-soluble compounds from passing into the cerebrospinal fluid. The blood-cerebrospinal barrier (BCB) or blood-brain barrier (BBB) is made up of several tight junctions. Blood pressure and cerebrospinal fluid pressure both have little effect on cerebrospinal fluid secretion, which is an active process. The sodium is actively transported into the ventricles by epithelial cells. Chloride and bicarbon­ate are diffused into the ventricles to preserve electrical neutrality. As a result, the concentration of sodium chloride in the ventricles rises, causing osmosis to sip water into the ventricles. By facilitating diffusion, carrier proteins will aid in moving essential chemicals from the blood into the cere­brospinal fluid.

Table 8.5 Biochemical constituent of cerebrospinal fluid of cow

Cerebrospinal fluid is a colourless, transparent liquid. The cerebrospinal fluid has plasma’s specific gravity, pH, and osmolarity. It contains a tiny amount of protein, the same amount of plasma sodium, 15% more chloride than plasma, 40% less potassium, and 30% less glucose than plasma (Table 8.5). In comparison to plasma, cerebrospinal fluid contains less urea. Except for a few lymphocytes, the cere­brospinal fluid lacks biological components.

The cerebrospinal fluid is generated in the lateral ventricles and enters into the third ventricle through the foramen of Monro. A small volume of CSF can infuse into the third ventricle. The cerebrospinal fluid will subsequently pass through the aqueduct of Sylvius and into the fourth ventricle. A minute volume of CSF can also enter into the fourth ventricle. The fourth ventricle’s cerebrospinal fluid will enter the spinal cord’s central canal. A portion of the cerebrospinal fluid from the fourth ventricle will reach the subarachnoid space through the foramen of Luschka and the foramen of Magendie.

The cerebrospinal fluid is replaced by new cerebrospinal fluid four to five times a day. The rate of formation of the CSF varies in different species (Table 8.6). Arachnoid villi absorb the cerebrospinal fluid. Microscopic extensions of the arach­noid membrane into the dorsal sagittal sinus are known as arachnoid villi. Arachnoid granulation is a macroscopic structure formed by the aggregation of these villi. The arach­noid villi operate as a valve, allowing cerebrospinal fluid to flow quickly into the sagittal sinus while preventing back­flow. The cerebrospinal fluid pressure is 1.5 mmHg higher than that of the plasma.

Cerebrospinal fluid helps cushion the central nervous system against shock, thus protecting the brain against a blow to the head. Cerebrospinal fluid significantly lowers the brain weight by providing a buoyancy effect. It helps to maintain the consistent extracellular environment of cells of the nervous system. It is an effective waste control system that can remove potentially harmful cellular metabolites. It

Table 8.6 Rate of cerebrospinal fluid formation in various species

transports and distributes some peptide hormones and vari­ous substances of the brain into general circulation. It serves partially as nutritive media for the brain and spinal cord.

8.1.4.2 Synovial Fluid

Synovial fluid is a thick, viscous liquid found in the cavities of joints, tendon sheath, and bursae. A thin layer of synovial fluid surrounds the articular cartilage and penetrates its inte­rior regions. The synovial fluid within the auricular cartilage acts as a reserve. The reserve synovial fluid is forced out of the cartilage during joint movements to keep a fluid layer on the cartilage surface.

Synovial fluid is generated by ultrafiltration from blood plasma. The pH of synovial fluid is usually between 7.2 and 7.4. It contains proteins acquired from plasma through filtration and synthesised by synovial cavity cells. It contains small amounts of albumin, globulin, mucin, proteinase, collagenases, prostaglandins, and hyaluronic acid, but no fibrinogen. Thus, synovial fluid does not clot. Small molecules like electrolytes and glucose have similar concentrations in the synovial fluid to plasma. Large molecules are found in lower concentrations in synovial fluid than in plasma. The synovial fluid contains hyaluronic acid produced by fibroblast-like cells (type B cells) in the synovial membrane. Hyaluronan is a lubricant that enhances the viscosity and flexibility of articular cartilage. Lubricin, a glycoprotein, is secreted by chondrocytes on the surface of the articular cartilage in the synovial joint. Lubricin is involved in lubrication and helps regulate synovial cell growth.

The synovial fluid contains only a few phagocytic cells (mainly mononuclear cells). These cells remove germs and debris from the joints caused by wear and tear. Less than 10% of these cells are neutrophils, and the remaining cells present are lymphocytes, monocytes, and macrophages. The usual synovial fluid volume in dogs and cats is 0.24 mL.

Synovial fluid acts as a lubricant in the joints, reducing friction. Because of its rheopectic characteristics, it functions as a thick absorbent. It provides oxygen and nutrition to the synovial tissues, nourishing them. It gets rid of metabolic waste. In the joint, it also serves as a molecular sieve.

8.1.4.3 Peritoneal Fluid

Peritoneal fluid is present between the peritoneal layers that line the abdominal cavity. It separates the peritoneum into two layers having an odourless, non-turbid, and clear or pale yellow colour. The pH ranges between 7.5 and 8.0. Peritoneal fluid has a specific gravity of less than 1.016. It is a blood ultrafiltrate, and water is the most important component. Simple diffusion allows electrolytes and tiny compounds to enter the peritoneal cavity. Electrolyte concentrations in the peritoneal fluid are similar to those in plasma. The total protein content is less than 2.5 g/dL, and the cell count is less than 3000-5000/pL. The cells present are leukocytes and desquamated mesothelial cells. The packed cell volume of the fluid in horses is less than 1%. The volume of peritoneal fluid increases during pregnancy. Lymphatics drain perito­neal fluid from the peritoneal cavity. The drainage is propor­tionate to the rate of its production. The purpose of peritoneal fluid is to lubricate abdominal organs and reduce friction between them during digestion and movement.

8.2