1. Section II: Disorders of Water and Sodium Metabolism

2. 一、 Classification 3.Normonatremia with changes of volume
According to the changes of volume:
1. Dehydration
2. Overhydration
According to the changes of [Na+]e:
1. Hypernatremia
2. Hyponatremia
3.Normonatremia with changes of volume

3. According to the clinic importance:
(1) Dehydration
1) Hypertonic dehydration
2) Hypotonic dehydration
3) Isotonic dehydration
(2) Overhydration
1) Hypertonic overhydration
2) Hypotonic overhydration (Water intoxication)
3) Isotonic overhydration (Edema)

4. 二、Dehydration

5. Dehydration脱水 (Hypovolemia)
Concept: The volume of body fluid decreases below the normal range after the loss of body fluid.
In dehydration the [Na+]e may be in three manifestations:
Dehydration [Na+] Osmotic pressure
(mmol/L) (mOsm/L)
Hypertonic > > 310
Hypotonic < < 280
Isotonic ~ ~ 310

6. 1 Hypertonic Dehydration
(1) Concept
(2) Causes
(3) Adaptive (compensatory) responses of the
body
(4) Characteristic effects
(5) Principle of treatment

7. 1 Hypertonic Dehydration
(1) Concept
Both water and sodium are lost (hypovolemia), but the water loss is in excess of salt loss.
Then the volume of ECF is reduced,
the [Na+] is over 150 mmol/L,
the plasma osmotic pressure is over 310 mOsm/L.

8. (2) Causes 1) Decreased water intake can be seen in:
① No water during navigation or in desert.
② No sense of thirst due to brain injury or coma,
③ Severe vomiting
④ Difficulty in swallowing because of esophageal diseases.
⑤ Underdose of infusion in treatment of patients
At the same time, pure water loss from lung (300ml/d) and skin (500ml/d) is not avoidable, even increased.

9. 2) Increased loss of water ①via skin ②via respiration
③via gastrointestinal tract
④via kidney,
gains (ml/day) loss (ml/day)
drink lung
food skin
metabolic feces
water urine
total

10. ① via skin:
Normally 500 ml of pure water will be lost by insensible evaporation from skin each day.
When the environmental or body temperature is increased, the evaporation (insensible loss) will increase from skin.
Elevation of 1℃(celsius) will increase loss of 500 ml pure water by evaporation each day.
Since sweat is hypotonic (0.2%NaCI), there will be more water loss than salt loss during sweating.
If water replenish is not enough.

11. ② via respiration:
Since the expired air contains water vapour, the water loss from lung is 300 ml of pure water each day.
The pure water loss is increased to 1300ml/day. during hyperventilation.
(metabolic acidosis, bronchitis, fever)
If water replenish is not enough.

12. ③ via gastrointestinal tract
Vomiting and diarrhea will lose a lot of body fluid.
Gastric juice is isotonic, loss of gastric juice with the loss of pure water from skin and lung may lead to hypertonic dehydration.
The [Na+] of watery stool is about 60 mmol/L (hypotonic fluid).
If water replenish is not enough.

13. ④ via kidney:
When the ADH secretion is reduced, such as diabetes insipidus. Increased water loss occurs.
Patients with diabetes also have increased urinary water loss due to the osmotic diuresis.
Tube feeding with a high concentration of protein is used to unconscious (coma) patients.
The urea will increase in the urine, which causes osmotic diuresis.
If water replenish is not enough.

14. (3) Adaptive (compensatory) responses of the body
1) Drink more water because of severe thirst
Hyperosmolarity and hypovolemia stimulate the sense of thirst.
Diminished saliva and the dry mucous membranes lead to the sense of thirst.
Obvious thirst occurs at early stage of hypertonic dehydration. If possible, the patient may drink water until the patient has again normal osmolarity and normal volume of ECF.

15. thirst center (anterior hypothalamus)
increase of ECF osmolality (1~2%)
elevated angiotensin II vasoconcentration
dryness of
mouth
hypovolemia
osmoreceptor (anterior hypothalamus)
volume receptor
in venae cavae and atrium
thirst center (anterior hypothalamus)
sense of thirst and drink of water
decrease of ECF osmolality
increase of ECF volume
decrease of angiotensin concentration II
disappear of dryness of mouth
no thirst

16. 2) Increased water reabsorption by increased ADH
ADH release is stimulated by the hyperosmolarity of the ECF and the hypovolemia.
ADH increases the reabsorption of water in kidneys. The volume of ECF will increase. The high osmolarity will decrease to normal.

17. increase of ECF osmolality (1~2%) via osmoreceptor
hypovolemia via volume receptor
synthesis and release of ADH
increases the reabsorption of water in kidneys
increase volume of ECF
decrease osmolality of ECF

18. 3)Shift of water
Increase of blood volume by shift of water from intracellular space.
ECF
ICF

19. (4) Characteristic effects of hypertonic dehydration on the body
1) Thirst occurs at the early stage of hypertonic dehydration.
2) Oliguria occurs at the early stage of hypertonic dehydration. (<400~500 ml/day).
Metabolic wastes like urea and uric acid are retained in the body because of the oliguria.
Urea and uric acid are harmful to the body. (azotemia)
Urine specific gravity is increased.
Na+ in urine???

20. renin release from the juxtaglomerular cells
renal
blood flow
[Na+] in macula densa
excitement of
sympathetic nerve
renin release from the juxtaglomerular cells
increase of angiotensin II releases
[K+], [Na+]
blood flow in plasma
aldosterone secretion from adrenal cortex
Na+ reaborption in renal tubules
K + and H + excretion from kidneys

21. 3) Fever
Fever may be present because water is necessary to regulate the body temperature.
Fever is more severe in infants because of the dysfunction of thermoregulatory center, which is called infantile dehydration fever.

22. 4) Intracellular dehydration
Water will shift from ICF to ECF because the ECF is hypertonic. All the cells will shrink.

23. Brain cell dehydration produces brain dysfunction like lethargy (weakness, apathy, absence of interest), which may progresses to coma (unconsiousness) when the water deficient is severe.
Increased irritability (muscular twitch, delirium) may occur, especially in children.
Twitch: uncontrollable sudden, quick movement of muscle
Delirium: violent mental disturbance accompanied by wild talk (wild excitement)
Subarachnoid hemorrhage

24. 6) blood concentration (hemoconcentration)
5) loss of body weight
Loss of body weight occurs within short period of time, which is useful in diagnosis of severity of dehydration.
6) blood concentration (hemoconcentration)
Count of WBC ↑
Count of RBC ↑
Hb (hemoglobin) ↑(in total blood, RBC)
Hematocrit ↑(percentage of RBC in total blood)
use in diagnosis?

25. (5) Principle of treatment
1) Treat the primary disease, such as diarrhea.
2) Replace firstly with 5% glucose solution to reduce the hyperosmolarity and to increase the volume of ECF.
3) Add small amount of 0.9% NaCl after infusion of 5% glucose solution.

26. 4) How to decide the volume of fluid replacement?
Degree Volume of water loss clinic manifestation
(% of body weight)
Mild ~5% thirst, oliguria
Moderate ~10% severe thirst
fever
dryness of mucosa
Severe ~15% delirium, stupor,
coma

27. 3 . Hypotonic Dehydration
(1) Concept
There is loss of both water and sodium (hypovolemia), the Na+ loss is in excess of water loss,
The ECF is hypotonic ([Na+]<130 mmol/L), the osmolarity is lower than 280mOsm/L.

28. (2) Causes
1) Replace of water only to the patients with dehydration caused by vomiting, diarrhea, gastric suction and excessive sweating lost.
2) Adrenocortical insufficiency (Addison’s disease) can cause excessive renal loss of sodium because the secretion of aldosterone is reduced.
3) Some diuretics (e.g. Furosemide速尿) inhibit the Na+ reabsorption in renal tubules.

29. (3) Adaptive responses
Aldosterone secretion is stimulated by the low sodium concentration, except in the case of adrenocortical insufficiency.

30. (4) Characteristic effect of hypotonic dehydration on the body
1) Urine volume
Urine volume is variable (low, normal, high) depending on the ADH secretion.
At the early stage of hypotonic dehydration, decreased osmolarity is the superior change, which inhibits ADH secretion, the urine is increased.
At the late stage, severe hypovolemia is the superior change, which increase the ADH release . the urine volume is decreased.

31. 2) Water shifts into the cells from ECF.
Severe hypovolemia
(Compare with hypertonic dehydration.)
ICF
ECF

32. 3) Hypotension
The blood pressure may decrease. Postural hypotension and shock will occur because the decreased blood volume. (increased urine and water shifts into the cells)

33. 4) Severely reduced interstitial fluid
Low protein concentration and colloid osmotic pressure in interstitial space.
The reduce of skin elasticity
Eyeball tension is decreased, the eyeballs are soft and sunken.

34. 5) Intracellular overhydration
Water will shift from ECF to ICF because the ICF is relatively hypertonic. The cell will swell.
Brain cell overhydration produces brain dysfunction. (Cranial cavity is fixed)
(severe headache, high brain pressure)

35. 5) There is no obvious thirst at early stage because of the low crystal osmotic pressure.
6) Blood concentration
Counts of WBC and RBC ?
Hematocrit ?
Plasma protein concentration ?
Hb in plasma ?
Hb concentration in RBC ?

36. (5) Principles of treatment
Replacement of isotonic saline (0.9%NaCl) .
Replacement of hypertonic fluid may lead to hypertonic state.
Pure water is easy to loss via skin and lung.
Hyperosmotic fluid are seldom used, except in urgent state of brain edema. 

37. 4. Isotonic Dehydration (1) Concept
There is loss of fluid (dehydration), the water loss is equal to salt loss. The ECF in the body is isotonic,
the [Na+] is 130~150 mmol/L,
the osmolarity is 280~310 mOsm/L.

38. (2) Causes
1) Loss of fluid is caused by vomiting, diarrhea, hemorrhage and from the burned area.
2) The isotonic dehydration can be induced from hypertonic and hypotonic dehydration by the renal regulation.

39. (3) Adaptive responses
The main change in isotonic dehydration is the reduced volume of ECF.
1) It stimulates the thirst, so that the patient will ask to drink water to replace the volume of ECF. (not as strong as hypertonic dehydration)
2) ADH release is stimulated, so that the water reabsorption will increase to replace the volume of ECF.(not as much as hypertonic dehydration)
3) Secretion of aldosterone is increased due to hypovolemia.(not as much as hypotonic dehydration)

40. (4) Effect on the body
1) Urine volume is diminished because of the decreased GFR, increased ADH and aldosterone secretion.
2)Thirst
3) Poor skin elasticity and sunken eyeball, because of the reduction of interstitial fluid.
4) No water shift and related symptoms and signs.

41. Turn into hypertonic dehydration ( loss pure water) or
to hypotonic dehydration (replacement of water only).

42. (5) Principle of treatment
Hypotonic saline is needed to replace the fluid deficiency.
Isotonic NaCl first.

43. Case Discussion No.1 The laboratory results were: Arterial blood:
A 36-year-old man was hospitalized with a 3-day history of fever and watery diarrhea. His blood pressure was 90/60 mmHg, the pulse was 112/min, temperature is 38.0℃. The abdomen was distended with low skin elasticity.
The laboratory results were:
Arterial blood:
pH=7.21, PaCO2=26 mmHg
PaO2= 108 mmHg [Na+]=135 mmol/L
[K+] =3.0 mmol/L [HCO3-] = 16 mmol/L
Urine: pH=5.0, Specific gravity= 1.028 

44. The patient’s problems were:
(1)isotonic dehydration
(2)metabolic acidosis
(3)hypokalemia.

45. 2. 病例分析
患婴，3个月，入院前1天开始发热。呕吐，水样便每日20余次。伴烦躁、烦渴。查体：39.8℃, 嗜睡，醒后烦躁，皮肤干热，明显腹胀。治疗：抗菌素，输入生理盐水1200ml。次日病情加重，极烦渴，呼吸深，惊厥，昏迷，并发肠麻痹死亡。

46. 三、 Overhydration According to the [Na+] concentration:
Hypertonic overhydration
(2) Hypotonic overhydration
(Water intoxication)
(3) Isotonic overhydration (Edema)

47. 1. Water intoxication
(1) Concept
Excessive fluid in the body is called overhydration.
Excessive hypotonic fluid in the body is called hypotonic overhydration (water excess, dilutional hyponatremia ).
Severe water excess causes a serial of symptoms and signs, and is called water intoxication.

48. (2) Causes
The main causes are excessive water intake and less loss of water.
1) Excessive water intake
①Excessive venous infusion of 5% glucose solution.
②Excessive water intake of psychotic disturbances (e.g. schizophrenia) may cause water intoxication.

49. Excessive water intake only can not lead to the water intoxication .
Chicago Daily News Aug. 9, 1958 reported that the world’s water drinking champion (1935) drank 20 L of water within 30 min, and was awarded a “hose”.
  It is obvious that this champion is healthy (without water intoxication).
Excessive water intake only can not lead to the water intoxication .
The reason is ???

50. At the same time, the kidneys cannot eliminate the excessive water.

51. 2) Decreased water output
① Oliguria due to low renal blood flow ( in congestive heart failure,cirrhosis).
② Oliguria due to excessive secretion of ADH
Several factors can stimulate the ADH secretion, like fear, stress, anesthesia, pain and some drugs (e.g. morphine and meperidine),

52. ③ Syndrome of inappropriate secretion of ADH (SIADH)
Causes of SIADH are:
pulmonary diseases (viral and bacterial pneumonias, tuberculosis, fungal infection, lung abscess),
diseases of central nervous system ( brain tumor, brain abscess, encephalitis and meningitis),
tumors of lung, pancreas, thymus and duodenum (ectopic ADH synthesis)
At the same time, fluid intake (intravenous or oral) is not carefully controlled.

53. (3) Effects on the body (a) Dilutional hyponatremia
Low serum protein concentration.
Low serum osmosity
Increased blood volume.
(b) A rapid weight gain in acute water intoxication,
(c) Cellular overhydration of central nervous system.
Anorexia, nausea, vomiting
Muscular weakness and twitching
Mental disturbances, convulsive seizures, stupor, and coma.
(d) Peripheral and pulmonary edema

54. 5) Principle of treatment
(a) Restriction of water intake
(b) Diuretics to excrete the excessive water
(c) Hypertonic saline (3%NaCl) for severe case, to raise the osmolarity of ECF quickly, to start the movement of water from the cells into extracellular space, then excretion from kidneys.

55. Case discussion
  A 25-year-old male has a head injury and unable to eat. He received 4~5 L of 5%glucose per day to replace his fluid losses and for nutritional purposes. On the 5th day he experienced convulsions and coma. The followings are his laboratory findings.

56. (1)What is the problem (pathological process) he had?
Day Body weight Plasma[Na+] Plasma osmolarity
(Kg) (mmol/L) (mOsm/L) O
Questions:
(1)What is the problem (pathological process) he had?
(2) Is this the normal response to intravenous infusion of
5%GS?
(3)What is the reason of convulsion and coma?