1. www2.kumc.edu/ki/physiology/course/figures.htm

2. Normal Plasma Values Substance Plasma Concentration Na+
mEq/L K+
3.5 – 4.5 mEq/L
Cl-
95 – 105 mEq/L
HCO3 -
24 – 32 mEq/L
Glucose
65 – 110 mg/dl (= mmol/L)
Blood urea nitrogen (BUN)
8 – 25 mg/dl

3. Osmolarity

4. Plasma Osmolarity
Posm = 2 x [Na+(mEq/L)]p + [glucose(mg/dl)]/18 + [urea (mg/dl)]/2.8
The difference between measured and calculated plasma osmolarity is the result of unmeasured osmoles.
These include potassium, chloride and proteins, but they account for very little of the total osmolarity.

5. Sodium is responsible for about 97% of plasma osmolarity.
Plasma Osmolarity Values:
Posm = 2 x [Na+(mEq/L)]p + [glucose(mg/dl)]/18 + [urea (mg/dl)]/2.8
Posm = 2 x [140 mEq/L)]p + [90 (mg/dl)]/18 + [14 (mg/dl)]/2.8
= about 290 mOsm/kg
Sodium is responsible for about 97% of plasma osmolarity.

6. Conditions in which plasma Na+ is low, but osmolarity is normal
Usually there is another solute present.
Body responds to increase osmolarity by increasing ADH release, and water retention. This dilutes the sodium.
Eg: High glucose in diabetic patient
Eg: Ethylene glycol poisoning

7. True hypoosmolarity (low sodium and low osmolarity)
Could be due to :
Problems with ability to sense osmolarity, or to changes in set point for osmolarity
Alterations in thirst mechanism
Problems with ADH release
Problems with renal response to ADH
Drinking too much water before or during exercise

8. To consider the possible causes of hypoosmolarity, consider the components of the negative feedback loop for osmoregulation.
Sensor: osmoreceptors
Set point: normal value = about 295 mOsm/L
Responses:
Thirst (decreased in response to hypoosmolarity)
ADH release (decreased in response to hypoosmolarity)

9. Hypo-osmolarity Example: Pregnancy Lower setpoint for osmolarity - ADH release and thirst occur at a lower than normal osmolarity.
ADH
release
progesterone
Plasma osmolarity (sOsm/L)

10. Hypo-osmolarity
example:
Psychogenic
Polydipsia
Vasopressin = ADH

11. Hypo-osmolarity example: Loss of plasma volume
ADH release is triggered by decrease in plasma volume rather than an increase in osmolarity.
Note that ADH is an effector for regulating two different regulated variables.

12. Hypo-osmolarity Example: Fluid loss to interstitium
Example: Cirrhosis of the liver
Damage to liver interferes with protein production
Fluid leaks out of capillaries due to shift in Starling forces
Fluid accumulates in abdomen – ascites
Also: portal hypertension increases hydrostatic pressure, injury and inflammation increases permeability to proteins, exacerbating the condition.

13. Hyperosmolarity of plasma due to high sodium conc.
Can be caused by:
Administration of sodium salts
Loss of hypotonic fluids (vomiting diarrhea, sweating)
Extrarenal fluid loss (eg: increased ventilation as occurs in fever)
Excessive renal water loss (inability to secrete or respond to ADH)

14. Example: Diabetes insipidus
Can be due to lack of ADH production, or in the case of nephrogenic diabetes insipidus, lack of ability to generate an osmotic gradient for water reabsorption
Results in loss of large volume of hypotonic urine

15. Problems of salt regulation
Leads to generalized decrease in extracellular volume
Eg: Fluid loss from biliary obstruction and consequent pancreatitis
The common bile duct is blocked, so bile backs up into the gallbladder and liver, and digestive enzymes back up into the pancreas
The resulting pancreatitis causes local tissue degradation and inflammation. Capillaries become leaky, and fluid leaves the capillaries causing ascites fluid to build up.

16. Potassium

17. Potassium Regulation
Most (55%) of the filtered potassium is reabsorbed in the proximal tubule, another 30% is absorbed in the loop of Henle.
Depending on diet, potassium may be reabsorbed or secreted in the distal convoluted tubule and the cortical collecting duct.

18. Renal handling of potassium

19. Regulation of potassium secretion
Na+/K+/ATPase A high K+ diet enhances update of K+ into the principal cells (the ones that line the tubule)
Aldosterone increases K+ uptake into the principal cells (via Na+/K+/ATPase), and makes the luminal membrane more permeable to K+
K+ secretion is flow dependent – high urine production can lead to K+ deficiency.

21. K+ Na+ Hyperkalemia in diabetes mellitus K+ K+ Na+ K+ insulin
adrenalin
aldosterone K+
Na+ K+
Na+
acidosis
increased osmolarity
cell injury K+

22. Aldosterone alters
the expression of
this enzyme

25. Glucose

26. From: Physiology of the Kidney and Body Fluids” by R.F. Pitts.

27. From: Physiology of the Kidney and Body Fluids” by R.F. Pitts.

28. Increased urine volume in diabetes mellitus
↑plasma glucose 
↑filtered glucose
Tm exceeded
glucose remains in tubules
H2O retained osmotically
increased urine volume
if not replaced by drinking, blood volume decreases

29. Increased urine volume in diabetes mellitus
Example: Untreated diabetes mellitus (assuming no renal damage)
Increased plasma glucose i
Increase filtered glucose
Tm exceeded
Glucose remains in tubules
Water retained in tubules osmotically
Increased urine volume
Blood volume decreases (if not replaced by drinking)
Decreased blood pressure (by Frank-Starling mechanism)

30. Acid-Base Balance

31. Alterations in plasma H+ concentrations can be potentially life-threatening
Condition [H+] pH Significance
(nmol/L)
Acidosis >100 <7.0 life-threatening
clinically signif.
Normal normal
Alkalosis clinically signif.
<20 >7.7 life-threatening
from Clinical Detective Stories, Halperin and Rolleston. Portland Press 1993.)

32. Alterations in plasma H+ concentration can influence potassium balance
Acidosis (excessive H+) causes K+ to move out of cells
Alkalosis (insufficient H+) causes K+ to move into cells.
Mechanisms of these interactions is not clear.
Diabetics are at risk for hyperkalemia (plasma K+ levels too high) since they tend to develop acidosis as a result of the production of ketoacids.

33. Hydrogen Ion Balance We gain hydrogen ion through diet and metabolism
Meat eaters tend to produce more acid
Dietary hydrogen ion is consumed through metabolism, and lost through the expiration of CO2, and excreted in the urine.
Meat eaters produce a more acidic urine

34. Hydrogen Ion Balance is Maintained by Buffers
Most important is Bicarbonate (HCO3-)
Also:
Proteins
Phosphate
NH4+

36. How does hydrogen ion concentration get out of balance?
There are two basic kinds of problems
Acidosis
Alkalosis
There are two basic causes of these problems:
Metabolic
Respiratory
In addition, there are metabolic and respiratory compensations for imbalances in either system.

37. Acid-Base Imbalances Involve Shifts in This Equation:
CO2 + H2O  H2CO3 HCO3- + H+
Normal Values:
H+ = mmol/L
HCO3- = 24 mmol/L

38. Acidosis
Metabolic – results from excess acid production or loss of alkaline fluid
High lactic acid production during exercise
Prolonged diarrhea
Respiratory – results from hypoventilation
Injury that makes ventilation painful
Lung disease

39. Compensation for Acidosis
Metabolic Acidosis
Increased ventilation
Respiratory or Metabolic Acidosis
Increased excretion of H + (requires a phosphate group, which is in limited supply
Increased NH4+ production

40. Alkalosis
Metabolic – results from prolonged vomiting, which causes the loss of an acid-containing fluid, or from the ingestion of alkali fluid
Respiratory – results from hyperventilation

41. Compensation for Alkalosis
Metabolic Alkalosis
Sometimes results in decreased ventilation, but this is a relatively small response
Respiratory or Metabolic Alkalosis
Increased renal excretion of bicarbonate
NH4+ production and excretion are inhibited