1. Fluid, Electrolyte, and Acid-Base Balance

2. The ECF and the ICF are two distinct fluid compartment
Fluids in the body are compose of water and solutes
There are 2 distinct fluid compartments
Intracellular fluid (ICF)
The cytosol of cells
Makes up about two-thirds of the total body water
Extracellular fluid (ECF)
Major components include the interstitial fluid, plasma and lymph
Minor components include all other extracellular fluids (water in dense CT, bone, fluid between visceral and parietal membranes etc.)

3. Functions of water in human physiology1
All chemical reactions occur in the medium. 2
It is crucial in regulating chemical and bioelectrical distributions within cells. 3
Transports substances such as hormones and nutrients. 4
O2 transport from lungs to body cells. 5
CO2 transport in the opposite direction. 6
Dilutes toxic substances and waste products and transports them to the kidneys and the liver. 7
Distributes heat around the body

4. Composition of fluid compartments - solutes
Water serve as universal solvent
Solutes can be divided into
Nonelectrolytes – do not dissociate in the water – no electrical charge
Most are organic molecules (ex. – glucose, lipids)
Electrolytes – dissociate into ions – electrical charge
Osmotic power of electrolyte is greater because they contribute more molecules to the solution by dissociating

5. Main electrolyte in body fluid compartments
Extracellular fluids have relatively high concentrations of sodium (Na+), chloride (Cl-), and bicarbonate (HCO3-) ions.
Intracellular fluid has relatively high concentrations of potassium (K+), magnesium (Mg+2), and phosphate (PO4-3) ions.

6. Cations and Anions in Body Fluids
Figure 27.2

7. Definitions
Osmolarity – the number of solutes particles dissolved in 1 liter of water – reflect the solution ability to cause osmosis
Determined by the number of particles and not their type or nature
The osmotic activity of 10 sodium ions is equal to that of 10 glucose or amino acid molecules in the same volume of solution
Osmol – one mole of substrate in 1 L of water

8. Acids and bases definition
Acids: defined as any compound, which forms hydrogen ions in solution.
For this reason acids are sometimes referred to as "proton donors".
Bases: a compound that combines with hydrogen ions in solution.
Therefore, bases can be referred to as "proton acceptors".
Strong Acids - a compound that ionizes completely in solution to form hydrogen ions and a base.
Weak Acids and Bases - compounds that are only partially ionized in solution.

9. Acid-Base Balance Normal pH of body fluids Arterial blood is 7.4
Venous blood and interstitial fluid is 7.35
Intracellular fluid is 7.0
Alkalosis or alkalemia – arterial blood pH rises above 7.45
Acidosis or acidemia – arterial pH drops below 7.35

10. pH and enzyme function
Hydrogen ion concentration has a widespread effect on the function of the body's enzyme systems.
The hydrogen ion is highly reactive and will combine with bases or negatively charged ions at very low concentrations.
Proteins contain many negatively charged and basic groups within their structure.
Thus, a change in pH will alter the degree ionization of a protein, which may in turn affect its functioning.
At more extreme hydrogen ion concentrations a protein's structure may be completely disrupted (the protein is then said to be denatured).

11. Sources of Hydrogen Ions
Most hydrogen ions originate from cellular metabolism
Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF
Anaerobic respiration of glucose produces lactic acid
Fat metabolism yields organic acids and ketone bodies
Transporting carbon dioxide as bicarbonate releases hydrogen ions

12. Types of acids in the body
Volatile acid comes from carbohydrate and fat metabolism
Can leave solution and enter the atmosphere (e.g. carbonic acid – H2CO3)
Breaks in the lungs to carbon dioxide and water
In the tissues CO2 reacts with water to form carbonic acid, which dissociate to give hydrogen ions and bicarbonate ions
This reaction occurs spontaneously, but happens faster with the presence of carbonic anhydrase (CA)
PCO2 and pH are inversely related
CO2 + H20  H2CO3  HCO3- + H+

13. Types of acids in the body
Fixed acids
Acids that do not leave solution (e.g. sulfuric and phosphoric acids – produced during catabolism of amino acids)
Eliminated by the kidneys
Organic acids
by-products of aerobic metabolism such as lactic acid, ketone bodies

14. Buffers
Buffers - compound that limits the change in hydrogen ion concentration (and so pH) when hydrogen ions are added or removed from the solution.

15. Buffer systems Two types of buffer in the body Chemical buffers
Bicarbonate, phosphate and protein systems
Substance that binds H+ and remove it from the solution if its concentration rises or release it if concentration decreases
Fast reaction within seconds
Physiological
respiratory (fast reaction – few minutes) or urinary (slow reaction – hours to days)
Regulates pH by controlling the body’s output of bases, acids or CO2

16. Chemical Buffer Systems
Three major chemical buffer systems
Bicarbonate buffer system
Phosphate buffer system
Protein buffer system
Any drifts in pH are resisted by the entire chemical buffering system

17. Bicarbonate Buffer System
A mixture of carbonic acid (H2CO3) and its salt, sodium bicarbonate (NaHCO3) (potassium or magnesium bicarbonates work as well)
If strong acid is added:
Hydrogen ions released combine with the bicarbonate ions and form carbonic acid (a weak acid)
The pH of the solution decreases only slightly
If strong base is added:
It reacts with the carbonic acid to form sodium bicarbonate (a weak base)
The pH of the solution rises only slightly
This system is the only important ECF buffer
CO2 + H2O  H2CO3  H+ + HCO3¯

18. Phosphate Buffer System
Nearly identical to the bicarbonate system
Its components are:
Sodium salts of dihydrogen phosphate (H2PO4¯), a weak acid
Monohydrogen phosphate (HPO42¯), a weak base
This system is an effective buffer in urine and intracellular fluid

19. Protein Buffer System
Plasma and intracellular proteins are the body’s most plentiful and powerful buffers
Some amino acids of proteins have:
Free organic acid groups (weak acids)
Groups that act as weak bases (e.g., amino groups)
Amphoteric molecules are protein molecules that can function as both a weak acid and a weak base

20. Buffer Systems in Body Fluids
Figure 27.7

21. Physiological Buffer Systems
The respiratory system regulation of acid-base balance is a physiological buffering system
The respiratory buffering system takes care of volatile acids – by-products of glucose and fat metabolism
There is a reversible equilibrium between:
Dissolved carbon dioxide and water
Carbonic acid and the hydrogen and bicarbonate ions
CO2 + H2O  H2CO3  H+ + HCO3¯

22. Physiological Buffer Systems
During carbon dioxide unloading, hydrogen ions are incorporated into water
When hypercapnia or rising plasma H+ occurs:
Deeper and more rapid breathing expels more carbon dioxide
Hydrogen ion concentration is reduced
Alkalosis causes slower, more shallow breathing, causing H+ to increase

23. Renal Mechanisms of Acid-Base Balance
Chemical buffers can tie up excess acids or bases, but they cannot eliminate them from the body
The lungs can eliminate carbonic acid by eliminating carbon dioxide
Only the kidneys can excrete the body of metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis
The ultimate acid-base regulatory organs are the kidneys

24. Renal Mechanisms of Acid-Base Balance
The kidney takes care of the non-volatile acid products
By-products of protein metabolism and anaerobic respiration
The kidneys must prevent the loss of bicarbonate ions (re-absorb) that is being constantly filtered from the blood.
Both tasks are accomplished by secretion of hydrogen ions
The majority of the hydrogen ions that are secreted will be used to help re-absorb the bicarbonate ions
Only about 10% of the hydrogen ions secreted will be excreted
As a result of the H+ excretion the urine is usually acidic

25. Reabsorption of Bicarbonate
In a person with normal acid-base balance all the HCO3- in the tubular fluid is consumed by neutralizing H+ - no HCO3- in the urine
HCO3- molecules are filtered by the glomerulus and than reabsorbed and appear in the peritubular capillary (most in the PCT).
The re-absorption is not direct – the luminar surface of the tubular cells can not absorb HCO3-
The kidney cells can also generate new HCO3- if needed

26. Reabsorption of Bicarbonate
1. Carbon dioxide combines with water in tubule cells, forming carbonic acid
2. Carbonic acid splits into hydrogen ions and bicarbonate ions
3. For each hydrogen ion secreted, a sodium ion enters the tubule cell and a bicarbonate ion enters the peritubular capillary
4. Secreted hydrogen ions form carbonic acid; thus, bicarbonate disappears from filtrate at the same rate that it enters the peritubular capillary blood
5. Carbonic acid formed in filtrate dissociates to release carbon dioxide and water
6. Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ion secretion

27. Respiratory Acidosis and Alkalosis
Result from failure of the respiratory system to balance pH
PCO2 is the most important indicator of respiratory inadequacy
PCO2 levels
Normal PCO2 fluctuates between 35 and 45 mm Hg
Values above 45 mm Hg signal respiratory acidosis
Values below 35 mm Hg indicate respiratory alkalosis

28. Respiratory Acidosis and Alkalosis
Respiratory acidosis is the most common cause of acid-base imbalance
Occurs when a person breathes shallowly, or gas exchange is slowed down by diseases such as pneumonia, cystic fibrosis, or emphysema
Respiratory alkalosis is a common result of hyperventilation

29. Metabolic Acidosis
Metabolic acidosis is the second most common cause of acid-base imbalance
All pH imbalances except those caused by abnormal blood carbon dioxide levels
Can be a result of:
Failure of the kidney to excrete metabolic acids
Renal acidosis is either the inability of kidney to excrete H+ or to re- absorb bicarbonate ion
Diarrhea – most common reason of metabolic acidosis
Loss of large amounts of sodium bicarbonate in the feces (which is normal component of the feces)
Diabetes mellitus – results in breakdown of fat that releases acids
Ingestion of acids
Acetylsalicylic acid (aspirin)
Methyl alcohol (forms acid when metabolized)

30. Metabolic Alkalosis
Rising blood pH and bicarbonate levels indicate metabolic alkalosis
Typical causes are:
Vomiting of the acid contents of the stomach
Intake of excess base (e.g., from antacids)
Constipation, in which excessive bicarbonate is reabsorbed