1. AIMST UNIVERSITY
PHYSIOLOGY UNIT
DR.P.SUNITHA

2. REGULATION OF FLUID VOLUME AND OSMOLARITY

3. Definition: Keeping the internal environment in a Steady state
Homeostasis
Definition: Keeping the internal environment in a Steady state
It is controlled by Negative Feedback Mechanism

4. Body Fluids Fluid compartments Body Water Healthy adult 2 main ones
Male = 60%
Female = 50%
Babies = 75%
Elderly = 45%
Calculation:
1 Kg = 1 L water volume
150# = 70Kg
60% of 70Kg
= approx 40Kg
40Kg = 40L
Fluid compartments
2 main ones
ICF = 2/3 volume of fluid in body
ECF = 1/3 volume of fluid in body
Plasma = 20%
Interstitial fluid = 80%
Calculation:
40L = fluid volume
2/3 = 25L of ICF
1/3 = 15L of ECF
NB: Blood = 3-4% of weight

6. Fluid and Electrolytes
60% of body consists of fluid
Intracellular space [2/3]
Extracellular space [1/3]
Electrolytes are active ions: positively and negatively charged

7. Solution = Solute + Solvent
Solution = the fluid compartment (ICF or ECF)
Solvent = water
Solutes:
Electrolytes
Charged ions
They dissolve in water
They can conduct an electric current
Major cations:
ECF = sodium ICF = potassium
Major anions:
ECF = chloride, bicarbonate ICF = proteins w/ neg charge
Non-electrolytes
Polar =those that are water soluble (sugars, proteins)
Non-polar = those that are water insoluble (lipids)

8. Note: Insensible loss = 1000 cc/day
Fluid balance
Important in IV daily maintenance
Intake & output ( I &O )
Note: Insensible loss = 1000 cc/day

9. Basic concepts relating to regulation of fluid & electrolytes
Water moves passively in response to changes in solute concentration
Key = water follows salt
Thus, regulation of fluid balance & electrolyte balance are intertwined
Fluid shifts occur between ICF & ECF in response to changes only in ECF
Key to equilibrium is maintaining solute concentration (osmolality = # solute particles in one liter of solution & is the ability of that solution to cause osmosis) between ICF & ECF
If change to hypertonic ECF, then water into ECF
If change to hypotonic ECF, then water into ICF

10. Regulation of Body Fluid Compartments
Osmosis is the diffusion of water caused by fluid gradient

11. Regulation of Body Fluid Compartments
Diffusion is the movement of a substance from area of higher concentration to one of lower
concentration
“Downhill
Movement”

12. Regulation of Body Fluid Compartments
Osmolality reflects the concentration of fluid that affects the movement of water between fluid compartments by osmosis

13. Regulation of Body Fluid Compartments
Osmotic pressure is the amount of hydrostatic pressure needed to stop the flow of water by osmosis

14. Control of Volume
Kidneys maintain constant volume and composition of body fluids
Filtration and reabsorption of Na
Regulation of water excretion in response to ADH
Water is freely diffusible
Movement of certain ions and proteins between compartments restricted

15. Volume Control osmoreceptors - day to day control
baroreceptors - respond to pressure change
neural and hormonal efferents
hormonal mediators

16. Baroreceptors Hormonal mediators aldosterone renin ANP dopamine
Hormonal effect  ECF  Na and water reabsorption

17. Baroreceptors
Neural mechanism
Autonomic nervous system

19. Osmolarity
Osmolality
Osmolarity is the № of osmoles per liter of solution
Eg. plasma.
Osmolality is the № of osmoles per kg of water
Affected by volume of the various solutes in the solution & temperature
Not affected

20. Osmoregulation osmolality 289 mOsm/kg H20
osmoreceptor cells in paraventricular/ supraoptic nuclei
osmoreceptors control thirst and ADH
small changes in Posm - large response

21. Osmoregulation Excess free water (Posm 280) thirst inhibited
ADH declines
urine dilutes to Uosm 100

22. Osmoregulation Decreased free water (Posm 295) thirst increased
ADH increases
urine concentrates to Uosm 1200

23. Factors affecting ECF & ICF volumes
Infusion of water
Dehydration
Intravenous infusion of different types of
solutions
Loss of large amounts of water from GIT
by sweating
through the kidney

24. The control of fluid balance
What is monitored: Volume & Osmolality (osmotic pressure via solute conc.)
Mechanisms:
ADH (antidiuretic hormone) , osmoreceptors, & thirst mechanism
Osmoreceptors in hypothalamus regulates secretion of ADH from posterior pituitary
The higher the osmolality, the more ADH secreted
ADH causes: (1) thirst center to be stimulated
(2) kidneys to conserve water
Aldosterone
Secreted by adrenal cortex
Causes kidneys to retain sodium (nb: water follows salt)
Stimulated by: increase potassium, falling sodium, & renin-angiotensin
Atrial natriuretic peptide (ANP)
Released by distended atrial walls of heart
Secretion caused by increased pressure and/or volume
Antagonistic to aldosterone

25. ADH secretion Synthesis: SON & PVN,
Stored & Released from Posterior pituitary
Stimulus: Plasma Osmolarity Blood volume Surgical stress
Site of action:-DCT & collecting ducts adenylcyclase - c-AMP  aquaporins open Water reabsorption

26. Antidiuretic hormone
Stimulates reabsorption of water by the kidneys.

27. Mechanism of action of ADH
ADH binds to V2 receptors in the DCT, & CD epithelia  formation of c-AMP activates protein kinases  stimulates the movement of an intracellular protein called Aquaporin-2 to the luminal side of the cell membranes

28. Mechanism of action of ADH
The molecules of AQP2 cluster together & fuse with the cell membrane by exocytosis form water channels that permit rapid diffusion of water through the cells. The AQP-3, AQP-4 in the basolateral side provide a path for water to leave the cell

29. Renin-angiotensin Renin secreted when drop BP
drop Na delivery to kidney
increased sympathetic tone

30. Aldosterone Release stimutlated by Effect Angiotensin II increased K
ACTH
Effect
Na and water absorption
in distal tubular segments

32. Atrial Natriuretic Peptide
A. Source:- Secretory granules on Atrial muscle & ventricular muscle
B. Site of action:- Kidney tubules.
C. Action:- a. Slight increase in GFR
b. Inhibit sodium reabsorption in
collecting ducts.
c. Increases excretion of sodium
D. Stimulus:- Stretching of atrial muscles by
a. Inc. in central venous pressure
b. High sodium in blood

33. Plasma volume
Activity of renal sympathetic nerves
Arterial pressure
GFR & flow to macula densa
Renal juxta glomerular cells
NaCl delivery to macula densa
Plasma renin
Plasma angiotensin II
Adrenal cortex Aldosterone secretion
Plasma aldostrone
Cortical collecting ducts Na+ & H2O reabsorption
Na+ & H2O excretion

35. Water deficit
Osmoreceptor-ADH feedback mechanism for regulating ECF osmolarity in response to a water deficit
Extracellular osmolarity
+ Osmoreceptors
ADH secretion
(Posterior pituitary)
Plasma ADH
H2O permeability in distal tubules,& collecting ducts
H2O reabsorption
H2O excreted

36. Juxtaglomerular apparatus
Decreased delivery of Na+ and Cl- to the distal tubules is associated with increased renin secretion.
Juxtaglomerular apparatus

37. Mechanisms of glomerulotubular balance and tubuloglomerular feedback
Renal arteriolar pressure
Glomerular capillary pressure
GFR
Solute reabsorption in PCT
Solute reabsorption in thick ascending limb
Salt & fluid delivery to the distal tubule
Glomerulo tubular balance
Tubulo
glomerular
feed back
Mechanisms of glomerulotubular balance and tubuloglomerular feedback

38. Osmoregulation (Water & Mineral salts)
After having a very salty meal
produce concentrated urine to remove excess salts in solution form
extra water is needed to be excreted along with the excess salts
sensation of thirst (drink more water to compensate for the water loss)

39. Reabsorption of Salt and Water

40. The Homeostatic Regulation of Normal Sodium Ion Concentrations in Body Fluids
Figure 27.4

42. Electrolytes & Their Imbalances Sodium (Na+)
Sodium balance
Sodium = major cation in extracellular fluid (ECF)
Sodium = most common problem with electrolyte balance
Key to balance: ingestion via G-I tract = excretion via kidney
Aldosterone controls sodium levels via the kidney
Remember aldosterone’s antagonist = ANP
Sodium contributes to resting membrane potential
Sodium rushing into cell via open channels causes depolarization of nerves and muscles

43. Potassium K+ Most abundant cations in ICF
Key role in establishing resting membrane potential in neurons and muscle fibers
Also helps maintain normal ICF fluid volume
Helps regulate pH of body fluids when exchanged for H+
Controlled by aldosterone – stimulates principal cells in renal collecting ducts to secrete excess K+

44. 5. Potassium reabsorption and secretion

45. Clinical implications – Diabetes insipidus
Sites of lesions that cause deficiency of ADH secretion
Symptoms: Polyuria- large volume of dilute urine,
Polydipsia,
Intact thirst mechanism is important

46. Signs of sodium imbalance
hyponatremia hypernatremia
Weakness & fatigue weakness & agitation
G-I: anorexia, nausea, cramps G-I: thirst, dry mucosa
Hypotension hypertension & edema
Mental confusion & ? Seizures
(from fluid shift into brain cells)
Causes of hyponatremia
Excess sweating, vomiting, diarrhea
Diuretics
Renal failure
Excess water intake (water intoxication)
Hormonal imbalances
Causes of hypernatremia
Watery diarrhea
Long periods of rapid respiration
Loss of thirst mechanism

47. Hyponatremia Sodium level less than 135 mEq/L
May be caused by vomiting, diarrhea, sweating, diuretics, etc.

48. Fluid Volume Disturbances
Fluid Volume Deficit (Hypovolemia)

49. After Sweating Concentrated Blood
Concentrated Urine
is produced
Concentrated Blood
Normal Water Content in Blood
Larger proportion of water is reabsorbed

50. Smaller proportion of water is reabsorbed
After Drinking
Diluted Blood
Diluted Urine is produced
Normal Water Content in Blood
Smaller proportion of water is reabsorbed

51. Fluid Volume Deficit Mild – 2% of body weight loss
Moderate – 5% of body weight loss
Severe – 8% or more of body
weight loss

52. Fluid Volume Deficit 2 Clinical manifestations Acute weight loss
Decreased skin turgor

53. Fluid Volume Disturbances 2
Fluid Volume Excess (Hypervolemia)

54. Fluid Volume Excess 2
Clinical manifestations – edema, distended neck veins, crackles, tachycardia, increased blood pressure, increased weight

56. HAVE A HEALTHY KIDNEY
HAVE A NICE DAY

57. Learning objectives
Role of kidneys in regulation of osmolality of body fluids:
the need to regulate osmolality of body fluids; osmoreceptors; humoral mechanisms affecting renal excretion of water – special reference to the role of antidiuretic hormone.

58. Learning outcomes
Describe the release, mechanism of action & functions of ADH.
Explain how the body fluid osmolarity is regulated.
Describe the disorders of ADH secretion