1. Essentials of Clinical Medicine
Session 17 Lecture 2
Homeostasis
Peter Stanfield

2. The concept of homeostasis and the internal environment
Set point
Comparator
Often the nervous system
Often the nervous or endocrine systems
Sensor
Effector
Controlled quantity

3. Water and salt loads are distributed differently and dealt with by different mechanisms
changes osmolality
changes volume of ECF
and Na+ balance
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 28.1

4. 28 10 3 1 Water and salt loads are distributed differently
Saline will expand the ECF volume
Extracellular fluid (ECF) 14
Interstitial fluid
Plasma
Secretions
Intracellular fluid (ICF) 28 10 3 1
Water is distributed through these compartments
Total body water 42

5. Two classes of mechanism are required for homeostasis of body fluids
1. To deal with a water load – which will lower the osmolality of all compartments – need to sense and to regulate this quantity (osmolality).
To deal with a saline load – which will expand ECF volume – need to sense and to regulate:
ECF volume – plasma volume that is sensed
Na+ load of the body
In both cases, nervous and endocrine systems are involved in regulation. Renal excretion is regulated to restore the internal environment. Thirst and sodium appetite are also regulated.

6. The response to a water load

7. A water load will lead to cellular swelling.
Since water will distribute among all fluid compartments, all will be increased in volume.
The cellular compartment will thus swell slightly owing to movement of water into cells.
This swelling is sensed
- particularly in the brain – and in osmoreceptors of the hypothalamus.

8. Osmoreceptors in the hypothalamus
Hypothalamus is part of the forebrain – part of the diencephalon - linking nervous and endocrine function – through its connections to the pituitary
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 6.3

9. Osmoreceptors in the hypothalamus
Neurones acting as osmoreceptors controlling secretion of vasopressin from posterior pituitary
↓osmolality
/Anti-diuretic hormone (ADH)
↓secretion of ADH
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 12.6

10. Vasopressin - alias anti-diuretic hormone - has two principal physiological effects
Vasopressin – has effects on the circulation, constricting blood vessels.
It also has effects on the kidney, regulating the volume and the dilution/concentration of urine

11. Vasopressin/ADH targets kidney
The kidney excretes urine, the composition of which is varied according to physiological need.
Vasopressin increases water reabsorption in the renal tubule – altering the osmolality of urine
In response to a water load, vasopressin secretion is reduced and copious dilute urine of low osmolality is excreted.
(Though note that electrolyte – especially NaCl will also be also be lost.)

12. The renal tubule filters blood and then works on the filtrate
The glomerulus forms a filtrate
Vasopressin acts here – increasing water permeability – to concentrate the urine that is finally produced.
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 17.10
Details will be given in the urinary tract module (semester 3)

13. The renal tubule filters blood and then works on the filtrate
An increase in water load gives ↓Vasopressin secretion, reducing water permeability →copious dilute urine
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 17.10
Details will be given in the urinary tract module (semester 3)

14. The concept of homeostasis and the internal environment
Set point
Paraventricular and supraoptic nuclei
Comparator
Often the nervous system
Altered secretion of vasopressin (ADH), acting to alter water excretion
Osmoreceptors in anterior hypothalamus
Often the nervous or endocrine systems
Sensor
Effector
Osmolality of body fluids
Controlled quantity

15. The response to dehydration
Dehydration will lead to an increase in osmolality – the sensing of this increase will lead to an increase in vasopressin secretion.
Vasopressin will increase the reabsorption of water in the renal tubule.
Leading to production of a low volume of hypertonic urine.
Since water is still lost – need to increase water intake to restore water balance.
Thirst is also stimulated as a result of sensing the increased osmolality in the hypothalamus.

16. Dehydration Dehydration
Is usually associated with loss of both salt and water.
Changes in excitability – muscle cramps
Collapse of the circulation
Lack of vasopressin
Leads to diabetes insipidus – damage to pituitary or loss of receptors for vasopressin in the kidney.
Inappropriately copious dilute urine, so that fluid must be replaced by copious drinking.

17. Hypersecretion of vasopressin
Water intoxication
Hypersecretion of vasopressin
For example from a pituitary tumour – leads to a reduced tonicity of body fluids, yet a hypertonic urine.
Water intoxication
Uncommon and usually associated with disease
Cellular swelling in brain leads to:
Headache
Fits
Coma

18. The response to an increase in extracellular fluid volume

19. Water and salt loads are distributed differently and dealt with by different mechanisms
changes volume of ECF
and Na+ balance
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 28.1

20. Isotonic saline increases both ECF volume and the Na+ load of the body
An increase in ECF volume will be distributed between the plasma and interstitial fluid.
If plasma – and therefore blood – volume increases, pressures in the vasculature will increase, and the heart will have to do more work*.
Correction will involve sensing of:
1. the volume of the ECF
sensed as blood volume
2. the sodium load of the body
sensed in the kidney
Two interrelated processes
* This will be explained in the CVS module; it is why there are health recommendations about salt intake

21. Atrial natriuretic peptide is released in response to an increase in plasma volume

22. The heart is an endocrine organ as well as a pump
The plasma (blood) volume is sensed in volume receptors in the great veins & atria
An increase in volume stretches the atria.
In response to stretch, atrial myocytes enhance the secretion of a hormone:
atrial natriuretic peptide (ANP)
Left
Right
The heart is an endocrine organ as well as a pump

23. Atrial natriuretic peptide increases the excretion of NaCl and water.
Increased stretch of atrial myocytes
Increased secretion of ANP
Correction of the increased ECF volume
Increased loss of Na+ (and water) in urine

24. ANP increases filtering of blood, by increasing filtration into the renal tubule
ANP acts to increase filtration
Increased filtration leads to natriuresis and diuresis.
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 17.10
Details will be given in the urinary tract module (semester 3)

25. The kidney responds to an increased Na+ load.
The roles of renin, angiotensin, and aldosterone

26. The amount of Na+ handled by the kidney is sensed in the renal tubule
Na+ load in distal part of the renal tubule is sensed
In juxtaglomerular apparatus, where distal tubule contacts glomerulus
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 17.10
Details will be given in the urinary tract module (semester 3)

27. The amount of Na+ sensed regulates the secretion of a hormone, renin
Renin is a proteolytic enzyme, released into blood stream
angiotensinogen
renin catalyses
angiotensin I
angiotensin converting enzyme* catalyses
angiotensin II
An increased Na+ load reduces the secretion of renin, and hence inhibits this cascade occurring in the blood stream.
A fall in Na+ stimulates secretion.
* on inner lining of blood vessels

28. Angiotensin II has important physiological actions
Vasoconstriction throughout the vasculature
angiotensin II
Acts on hypothalamus to stimulate thirst
stimulate vasopressin release
Stimulates the secretion of the hormone aldosterone from adrenal cortex
Aldosterone increases reabsorption of Na+ in the kidney, reducing its output in urine

29. Aldosterone is a steroid hormone from the adrenal cortex (zona glomerulosa)
adrenal cortex – steroid hormones
r. adrenal
r. kidney
adrenal medulla – adrenaline and noradrenaline
From: Abrahams et al (2005) Illustrated Clinical
Anatomy Fig 8.9
Outermost part of adrenal cortex is the zona glomerulosa

30. The action of aldosterone and the reversal of its action take time.
Aldosterone is a steroid hormone – with a cytoplasmic receptor
It affects transcription of genes involved in Na+ transport in the renal tubule, including:
Na+-K+ ATPase
Epithelial Na+ channel (ENaC)
These responses take time – and the response to a reduction in aldosterone also takes time
Response to a Na+ load is relatively slow

31. Excessive salt intake becomes difficult to counteract:
A result of long term action of aldosterone – a saline load takes time to clear: high intake of salt will override homeostatic control.
Excessive salt intake becomes difficult to counteract:
high salt diet is a risk factor for hypertension .
changes volume of ECF
and Na+ balance
From: G Pocock & CD Richards Human Physiology – The Basis of Medicine 3rd Edition 2006 Fig 28.1

32. The amount of Na+ sensed regulates the secretion of a hormone, renin
Isotonic saline, added to the body fluids
Reduced secretion of renin
Reduced levels of angiotensin II
correcting
Reduced reabsorption of Na+; ie increased Na+ loss in urine
Reduced levels of aldosterone

33. The amount of Na+ sensed regulates the secretion of a hormone, renin
increased secretion of renin
Deficit of Na+
Defending body Na+ and ECF volume
increased levels of angiotensin II
Increased reabsorption of Na+; ie increased Na+ loss in urine
Increased levels of aldosterone

34. Renin release is also stimulated by:
1. A reduction in blood pressure, sensed within the kidney
Na+ load will increase and a Na+ deficit will reduce blood volume and hence blood pressure;
Renin secretion is reduced or increased, respectively.
2. Nervous - sympathetic (autonomic nervous system) - stimulation of kidney
If the atrial volume receptors sense a reduction in volume, reflex stimulation of renin release occurs through sympathetic innervation of the kidney.

35. Addison’s disease
Addison’s disease is associated with the loss of adrenal cortical hormones, including aldosterone.
Result in a loss of Na+ and retention of K+ - resulting in progressive weakness owing to effects on excitability of nerve and muscle.
Excessive dehydration, owing to loss of Na and water from kidney, is associated with reduced blood pressure
Patients have a high salt appetite

36. Aldosteronism
Conn’s syndrome associated with increased secretion of aldosterone. Increased renin also increases aldosterone secretion.
Result in a retention of Na+ and loss of K+.
Expansion of the extracellular fluid volume (and the vascular effects of angiotensin II) is associated with hypertension.

37. Two hormonal pathways act in antagonism to each other
Altered secretion of ANP
ANP → loss of Na+
A change in Na+ load
Altered secretion of aldosterone
aldosterone → retention of Na+
Such hormonal mechanisms, working in opposition to each other, are a common feature of homeostasis

38. In summary
Threats to body fluid balance are dealt with by hormonal responses regulating the excretion of water and Na+, the principal cation of the extracellular fluid.
Vasopressin – increases osmolality of the urine
Atrial natriuretic peptide – accelerates the loss of Na+.
Aldosterone – causes retention of Na+.
Regulation of aldosterone release is complex – through the renin- angiotensin-aldosterone system.