Session 17
Homeostasis
Group work
Total body water
1. What is the expected value for the normal total body water, expressed as fraction of body weight, in:
a. a female of average weight
b. a male of average weight
c. a new born infant
d. a male aged 70 years.
a. 50%
b. 60%
c. 75%
d. 50%
2. What may account for the differences you give?
Differences in cellular composition between the sexes and between the very young and the elderly. Adipose tissue has little water (~10%), while lean body mass has some 70 – 75% water. Differences in relative adipose tissue mass are the principal cause of the differences in the answer to question 1. However the relative extracellular fluid volume is higher, as a fraction of total body water, in neonates.
Distribution of body water
3. How is body water distributed among compartments?
The principal compartments are intracellular water (~67% in males)
extracellular fluid (~33% in males)
Extracellular fluid is divided between interstitial fluid (~80% of the ECF) and plasma (~20% of the ECF)
Cellular water is about 60% of total body water in females and about 55% in neonates.
4. How, in general, would you measure the size of these compartments?
By measuring the concentration of a known quantity of an injected marker whose distribution is limited to the particular compartment.
The dye Evan’s blue is used to measure plasma volume. It does not enter red cells and is retained within the circulation.
Inulin – a polysaccharide - or mannitol – an alcohol derived from mannose – are used to measure ECF volume.
Tritiated water or deuterium oxide is used to measure total body water.
(Note that the detail of the substances – names, chemical nature - given in this specimen answer need not be memorised.)
5. Outline the electrolyte composition of the various compartments of body fluids.
Intracellular fluid has K+ as the principal cation (~160mmol.l-1) and organic anions as the principal anions. Most organic anions are polyvalent. Haemoglobin is the principal anion of red cells. Na+, Cl-, and HCO3- are at low concentrations. Free Ca2+ (0.1mmol.l-1) and Mg2+ are at low concentrations.
Extracellular fluid has Na+ as cation (150mmol.l-1), with K+ at 4mmol.l-1. Cl- (~115mmol.l-1) and HCO3- (~25mmol.l-1) are the principal anions. Free Ca2+ is typically 1.2mmol.l-1.
6. How far do the concentrations of these components change in normal physiological conditions? What might you expect to happen in severe exercise?
They are regulated by homeostatic mechanisms, so they don’t normally change materially.
However, electrical activity does depend on ionic movements. The movements are minute for a single action potential in nerve or muscle (~10-12mol.cm-2; in terms of quantity per unit area of cell membrane.) But intense muscle activity does lead to an increase in K+ concentration in extremes of exercise. Performance athletes – distance runners for example – can double their extracellular K+ concentration, an increase that would jeopardise the normal heart beat in a resting individual.
Cellular water and interstitial fluid
7. How is an equilibrium maintained between cellular water and interstitial fluid?
Cells and the interstitial fluid are in osmotic equilibrium. Although permeant ions are not at equal concentrations inside and outside cells, equilibrium is established by the presence of impermeant anions inside cells and by the low permeance of Na+, held outside by the Na-pump of cell membranes.
Permeant ions distribute themselves according to a Donnan equilibrium:
8. In open heart surgery, a cardioplegic solution may be used to stop the heart. The composition of St Thomas’ cardioplegic solution No.2 is:
component / concentration (mmol-1)Na+ / 120
K+ / 16
Mg2+ / 16
Ca2+ / 1.2
Cl- / 160.4
HCO3- / 10
(You are not expected to remember the detail of this composition. During the CVS module you will consider how cardioplegic solutions stop the heart.)
8.1. What effect will this solution have on membrane potential of cardiac myocytes?
It will depolarise the membrane, owing to the 4× increase in [K+].
8.2 Why does cell volume increase in the heart perfused with such a cardioplegic solution?
Because the Donnan equilibrium is upset. The gradient on Cl- remains high, but that on K+ is reduced
.
The result is that K+, Cl-, and water enter the myocytes.
8.3. How might you consider altering the composition of a cardioplegic solution to prevent this increase in cell volume? (You are being asked to speculate here – there is no clear ‘correct’ answer.)
Following the answer to 8.2, you might consider maintaining the Donnan equilibrium by reducing Cl- concentration, replacing Cl- by an impermeant anion. (Someone has patented such a solution.)
Or add an osmotically active, impermeant substance to the solution to impede the movement of water into the cells.
Glucose is often added to the solutions to accelerate recovery from the cellular swelling.
9. Central neurones, exposed to low osmolality solutions, release taurine. What effect will this release have on the expected cell swelling resulting from the low osmolality of the extracellular solution?
Cells do have regulatory responses to changes of cell volume, altering membrane permeability and organic osmolyte concentrations. The release of taurine – an amino sulphonic acid - to the extracellular milieu reduces swelling. Cellular swelling is a problem in the brain, contained as it is within the rigid skull.
(You are not expected to know the details of cellular regulatory responses to changes of cell volume, of which this is an example.).
Interstitial fluid and plasma – Starling forces
10. What factors determine the equilibrium between interstitial fluid and plasma?
The equilibrium is generated at capillaries in the systemic and pulmonary circulations.
The factors are:
the hydrostatic pressure within capillaries (between 35 and 15mmHg in systemic capillaries);
the colloid osmotic pressure or oncotic pressure (25mmHg); and
the permeability of capillaries.
Gravity will affect hydrostatic pressures.
11. What will happen to this equilibrium if capillary permeability is increased, as in anaphylaxis?
The equilibrium will be shifted towards an increase in interstitial fluid – i.e. towards increased filtration, owing to reduction of the colloid osmotic pressure gradient.
12. What will happen to this equilibrium if venous hydrostatic pressures are increased, as in ventricular (heart) failure?
There will be increased filtration of fluid, owing to the increased hydrostatic pressures in capillaries. Oedema occurs in lungs and in the body, owing to changes in pressures in the systemic and pulmonary circulations, respectively.
Don’t worry about the detail of this at present; you will have a whole session on heart failure as part of the CVS module in semester 2.
13. Liver disease may result in oedema. What factor(s) lead to oedema in such conditions?
A reduction in the synthesis of plasma proteins results in a reduced oncotic pressure gradient. Oedema is a result.
Liver disease may lead to ascites - oedema of the abdominal cavity - if there are problems with drainage of the hepatic portal system into the liver as a result of disease. Here hydrostatic pressures increase in the hepatic portal system.
14. Disease of the renal glomerulus (which filters blood as the first step in urine formation) may also lead to oedema. Why should this be the case?
Filtration of plasma proteins at the glomerulus may occur in disease. These proteins are then lost in the urine at a rate faster than they are replaced by synthesis in the liver. Loss of oncotic pressure gradients results in oedema. An example is minimal change glomerular lesion, where the kidney appears normal in biopsy, yet is filtering protein into the urine.
These mechanisms will be dealt with in detail in the Urinary Tract module in semester 3.
Dehydration
15. Diarrhoeal diseases lead to loss of body water, often causing death through dehydration. What will happen to the various compartments of body water in cholera?
The extracellular compartments will be reduced in volume very significantly. Cholera stimulates the loss of salt (Na+) and water form the GI tract. But some intracellular water will also be lost.
16. What will happen to a) urine output, b) blood pressure, c) body temperature, and d) haematocrit in someone suffering from a diarrhoeal disease?
a. Urine output will fall, owing to reduced filtering at the kidney amd operation of homeostatic mechanisms that are trying to maintain normalcy.
b. The blood pressure will fall, owing to loss of circulating blood volume. Again homeostatic mechanisms will be trying to keep the blood pressure up – these mechanisms will be introduced in semester 2.
c. Body temperature will rise, owing to inability to secrete enough sweat to maintain normal body temperature.
d. Haematocrit will fall owing to the loss of plasma volume (greater than the loss of red cell volume).
17. Oral rehydration therapy was introduced ~30 years ago. Its introduction led to a world wide reduction in child deaths from diarrhoea from 4.6 million a year in 1980 to around 1.5million a year in 2000. The World Health Organisation and UNICEF recommend use of a solution with the following composition:
Na+ / 75
Cl- / 65
Glucose / 75
K+ / 20
citrate3- / 10
(You are not expected to remember the composition of this solution.)
17.1 Why does this solution contain glucose and Na+?
Glucose and Na+ are taken up by co-transport into the bloodstream from the GI tract. (Anions and) water will follow. This will help counteract the losses of salt and water stimulated in diarrhoea. Thus Na+ helps to restore the ECF volume. Glucose provides a substrate for metabolism.
17.2 By what mechanism(s) are these transported through the intestinal mucosa?
As in the answer to 17.1: co-transport of Na+ and glucose occurs in the brush border of intestinal mucosal cells (sodium glucose transport protein 1, SGLT1). Glucose is absorbed at the basal border by the glucose transporter GLUT2 and Na+by the Na+-K+ ATPase.
17.3 Why does the solution contain K+ in addition to Na+?
K+ is lost in diarrhoea and needs to be replaced. (Diarrhoeal fluid contains K+ at something like 10 – 50mmol.l-1)
17.4 By what mechanism does cholera (infection with Vibrio cholerae) generate high loss of salt and water through diarrhoea?
It stimulates adenylyl cyclase (through ADP ribosylation of Gsa - detail not required), leading to constitutive production of cAMP, which in turn stimulates secretion of salt and water from the intestine.
Hypovolaemic shock (You will learn more about shock in semester 2, so detailed understanding is not expected at this stage.)
18. What do you understand by the term hypovolaemic shock?
Shock is associated with circulatory collapse and is a medical emergency. A reduction in extracellular fluid volume will be associated with a reduction in circulating blood volume (hypovolaemia), with lower pressures in the circulation, insufficient to maintain organ perfusion.
19. Hypovolaemia may be managed by giving intravenous fluids. What do you understand by a) a crystalloid solution and b) a colloid solution? How would these solutions be distributed through the body fluid compartments?
Both are used in intravenous therapy.
a. A crystalloid solution contains only electrolyte, based around Na+ salts. It will be distributed throughout the extracellular fluid spaces (interstitial fluid and plasma).
b. A colloid solution also contains a high molecular weight osmotically active substance (e.g. albumin, dextrans) which remain in the blood stream. This will increase plasma volume.
20. 0.9% NaCl solution is often described as isotonic. What does the term isotonic denote? Show, by calculating the concentration of NaCl in mmol.l-1, that 0.9% saline is isotonic. The molecular weight of NaCl is 58.5.
0.9% NaCl contains: 9g NaCl per litre of solution
= 9/58.5 = 154mmol NaCl.l-1
NaCl is dissociated to give a total concentration of 308mOsmol.l-1.
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