pH, Water, and Ion balance

% of body fluids that is Intracellular

65%

% of body fluids that is Extracellular

35% of body fluids 

1. 25% interstitial fluid 

2. 8% plasm and lymph 

3. 2% other 

Water Balance Barriers

1. Cell membranes 

2. Capillary walls 

3. Water moves easily across these barriers 

   1. Osmosis, facilitated osmosis, filtration, reabsorption 

Fluid gain per day

1. Gain (2,500ml/day)

   1. Ingested 

      1. Drink (1600ml/day) 

      2. Food (700ml/day) 

   2. Metabolic water (200ml/day) 

Fluid loss per day

1. Urine 

   1. 1500 ml/day 

2. Cutaneous transpiration 

   1. 400 ml/day

3. Sweat 

   1. 100 ml/day

4. Expired 

   1. 300 ml

5. Feces 

   1. 200ml/day

What does low water levels cause

1. Increase in blood osmolarity 

2. Decrease in blood pressure 

Hypothalamus influence on water gain

Thirst Center

1. Osmoreceptors respond to high osmolarity and to angiotensin II 

   1. Send signals to other cells of hypothalamus to release ADH 

   2. Send signals to cerebral cortex to increase conscious sense of thirst 

   3. Send signals to sympathetic nervous system and reduces saliva production (dry mouth increases thirst)

Kidneys influence on water gain

1. Detect decreased blood pressure 

2. Release renin and therefore increases angiotensin II 

3. Angiotensin II stimulates thirst center in hypothalamus

Baroreceptors in heart and blood vessels influence on water gain

1. Detect low blood pressure 

2. Stimulate thirst centers

Regulation of Water Loss

1. Affected by the hormones regulating ion levels (more to come later) 

2. Primarily regulated by Antidiuretic Hormone (ADH) 

   1. Released by cells of hypothalamus in response to high blood osmolarity 

   2. Increases aquaporins in cell membranes of collecting duct 

      1. Increases water reabsorption as collecting duct passes through the highly concentrated extracellular fluid of the renal medulla 

Volume depletion (hypovolemia)

1. Loss of water AND sodium 

2. Osmolarity unchanged 

3. Causes: 

   1. Hemorrhage 

   2. Severe burns 

   3. Vomiting or diarrhea 

   4. Hyposecretion of aldosterone (Addison disease) reduces Na+ and water reabsorption in kidneys

Dehydration (negative water balance)

1. Loss of water, but retention of sodium 

2. Osmolarity increases 

3. Can cause cells to crenate 

4. Causes: 

   1. Lack of ingestion of water (dementia, mobility issues, access

   2. Overuse of diuretics (medical, caffeine, alcohol) 

   3. Profuse sweating 

   4. Diabetes mellitus 

   5. Diabetes insipidus (lack of ADH function)

Volume Excess

1. Both water and sodium are retained 

2. Osmolarity is not changed 

3. Causes: 

   1. Renal failure 

   2. Hypersecretion of aldosterone 

Hypotonic hydration (water intoxication, positive water balance)

1. More water than sodium is retained 

2. Osmolarity decreases 

3. Can cause cell swelling and edema 

4. Causes: 

   1. Replacing fluid large amounts of lost as sweat or urine with pure water 

   2. ADH hypersecretion

Functions of ions

1. Control osmosis between compartments 

2. Carry electrical current (Na+, K+, Ca2+) 

3. Cofactors for some enzymes (Mg2+) 

4. Maintain acid-base balance (H+ and HCO3-)

Extracellular v intracellular fluids

1. Plasma (300 mOsm/L) 

   1. Na+ Cl- most abundant 

2. Intracellular (300 mOsm/L) 

   1. K+ and Phosphates are most abundant ions

Sodium Functions

1. Electrically excitable cells 

2. Hold water in cartilage to increase cushioning function 

3. Cotransport of other ions

Sodium Homeostasis

1. Need to ingest 0.5g/day (US diet average 3-7g/day) 

2. Aldosterone 

   1. Release stimulated by: 

      1. RAA system 

      2. Direct stimulation of adrenal cortex (hyponatremia and hyperkalemia) 

   2. Stimulates kidney to increase sodium reabsorption

      1. Increases synthesis of Na+/K+ pumps in ascending limb of nephron loop, distal convoluted tubule, and collecting duct (cortical portions) 

      2. Promotes Na+, water, and Cl- reabsorption 

      3. Has little effect on Na+ concentration 

3. ADH 

   1. reabsorption of water is separate from reabsorption of Na+ 

4. ANP (and other natriuretic peptides) 

   1. Decreases Na+ and sodium reabsorption

   2. released when blood pressure is high

Hypernatremia

1. Caused by: IV saline administration 

2. Can lead to: 

   1. Water retention 

   2. Edema 

   3. Hypertension 

   4. agitation/convulsions 

   5. Crenation of cells

Hyponatremia

1. Caused by: 

   1. Excess water 

   2. Can lead to hypotonic hydration (water poisoning) 

2. Can lead to: 

   1. Muscle weakness 

   2. Dizziness, headache, mental confusion, coma 

   3. Tachycardia 

   4. Hypotension 

Potassium Functions

1. Electrically excitable cells 

2. Helps regulate pH (exchanged for H+) 

3. Cofactor for protein production

Potassium Homeostasis

1. Distal convoluted tubule and cortical portions of collecting duct 

   1. Secrete more when K+ levels are high, less when K+ levels are low 

2. Aldosterone 

   1. Rise in K+ will stimulate release from adrenal cortex 

   2. Stimulates K+ secretion and Na+ reabsorption 

Hyperkalemia

1. Rapid onset 

   1. Caused by: 

      1. Ruptured cells (crush injury, hemolysis) 

      2. Transfusion with outdated blood (more hemolysis) 

   2. Can lead to: 

      1. Overexcitability of cells 

         1. Nausea, vomiting, diarrhea 

         2. Cardiac arrest 

2. Slower onset 

   1. Caused by: 

      1. Aldosterone hyposecretion 

      2. Renal failure 

      3. Acidosis 

   2. Can lead to: 

      1. Lower excitability of cells 

         1. Muscle weakness 

         2. Depressed reflexes 

         3. Fatigue 

         4. Arrhythmia

Hypokalemia

1. Caused by: 

   1. Inadequate intake in folks with depressed appetites/starvation

   2. Heavy sweating, vomiting, diarrhea 

   3. Aldosterone hypersecretion 

   4. Alkalosis 

2. Can lead to:

   1. Lower excitability of cells 

      1. Muscle weakness 

      2. Depressed reflexes 

      3. Fatigue 

      4. Arrhythmia

Calcium Functions

1. Blood clotting 

2. Exocytosis : ie. neurotransmitter release 

3. Muscle contraction 

4. Membrane potential 

5. Second messenger for some hormones and neurotransmitters

6. Build skeleton

Calcium Homeostasis

1. Levels of free Ca+2 in cell cytosol needs to be kept low so it does not form crystals with phosphates 

   1. Pumped out 

   2. Sequestered in smooth endoplasmic reticulum (binds calsequestrin  protein) 

2. Levels are regulated by hormones 

   1. Parathyroid hormone 

      1. Released by parathyroid glands when blood calcium levels are low 

      2. Increases osteoclast activity 

      3. Reduces osteoblast activity 

      4. Increases calcium reabsorption at kidneys (DCT) 

   2. Calcitonin 

      1. Released by kidneys when blood calcium levels are elevated 

      2. Reduces osteoclast activity 

      3. Stimulates osteoblast activity

Hypercalcemia

1. Caused by: 

   1. Alkalosis 

   2. Overproduction of PTH 

   3. Underproduction of calcitonin 

2. Can lead to: 

   1. Lower excitability of cells 

      1. Muscle weakness 

      2. Depressed reflexes 

      3. Arrhythmia 

Hypocalcemia

1. Caused by: 

   1. Vitamin D/calcitriol deficiency 

   2. Diarrhea 

   3. Pregnancy 

   4. Lactation 

   5. Acidosis 

   6. Low PTH production 

   7. overproduction of calcitonin 

2. Can lead to: 

   1. Overexcitability of cells 

   2. Tetany 

      1. Suffocation 

Normal blood pH

7.4 (7.35-7.45)

pH determined by concentration of free H

1. Low pH = high concentration of H+ 

2. High pH = low concentration of H+ 

Three Ways to Control pH

Buffers
Phosphate

Protein

Combination of a weak acid and a weak base

1. Weak acid can release H+ when pH is too high 

2. Weak base can bind H+ when pH is too low 

3. Resist changes to pH when other acids or bases are added to the solution 

4. Acts very rapidly! 

Carbonic Acid Bicarbonate

1. H₂CO₃ ↔ HCO₃^- + H⁺ 

2. When acids are added and there is more H+ 

   1. H+ binds to HCO3- (weak base) and there is a  shift to the left 

3. When bases are added (or acids removed) there is less H+ and a shift to the right 

   1. H2CO3 (weak acid) releases H+ and there is a shift to the right 

Phosphate

1. Important INTRAcellular buffer 

2. H₂PO₄- ↔ HPO₄^2- + H⁺ 

   1.  H₂PO₄-  (weak acid) 

      1. If pH increases, it releases  H⁺ 

   2. HPO₄^2-

      1. (weak base) 

      2. If pH decreases, it binds H⁺ 

Protein

1. Most abundant buffer in plasma and intracellular fluid 

   1. - COOH ↔ COO^- +  H⁺

      1. COOH is weak acid, can release H+ when pH is low 

      2. COO- is a weak base, can bind H+ when pH is high 

   2. - NH₂ + H⁺  ↔ NH₃⁺

      1. NH2 is weak base, can bind H+ when pH is low 

      2. NH3+ is a weak acid, can release H+ when pH is high 

   3. Many “R” groups can also serves as buffers 

Respiratory control

1. H₂O + CO₂ ↔H₂CO₃ ↔ HCO₃^- + H⁺ 

2. Can affect pH in minutes 

3. Increasing pulmonary ventilation 

   1. Exhale more CO2 

   2. Decreasing CO2 causes a shift to the left  

   3. Reduces H+, increases pH 

Decreasing pulmonary ventilation 

1. Exhale less CO2 

2. Increasing CO2 causes a shift to the right 

3. Increases H+, decreases pH

How is Respiratory control Regulated by Negative Feedback

1. Decrease in pH detected by chemoreceptors in medulla oblongata, aorta, and carotid sinus 

   1. Simulates inspiratory areas 

   2. Increases rate and depth of breathing 

   3. Increased release of CO2 

   4. pH returns to normal 

2. An increase in pH will reduce this signalling 

Renal Control 

1. Takes longer 

2. Only mechanism actually removing H+ from the body (others just bind it)  

   1. Na+/H+ antiporters on apical surface (secondary active transport) 

      1. Relies on Na+/K+ pumps on basolateral membrane (primary active transport) 

   2. HCO3- leaves basolateral surface (facilitated diffusion) 

Acidosis

<7.35 

1. Depresses CNS activity, disorientation, coma, death

Alkalosis

>7.45 

1. Over-exciatability of nervous and muscle cells 

   1. Nervousness, muscle spasms, convulsions, death

Acid/Base Imbalance Compensation

1. Response to acid-base imbalance that acts to normalize pH 

   1. “compensated”: pH stays within normal range 

   2. “uncompensated”: pH falls outside normal range 

2. Respiratory compensation 

   1. Occurs within minutes, reaches maximum within for a few hours 

   2. hyper/hypoventilation alter CO2 release 

3. Renal compensation 

   1. Begins in minutes, reaches maximum in days 

   2. Alter secretion/reabsorption of H+ and HCO3- 

Respiratory acidosis

1. High pCO2 

2. Caused by lack of gas exchange (obstructive and restrictive disorders, damage to respiratory centers, muscle weakness) 

3. Renal compensation 

   1. Secrete H+ 

   2. Reabsorb HCO3- 

Respiratory alkalosis 

1. Low pCO2 

2. Caused by excess gas exchange (stroke, anxiety, low O2 environment) 

3. Renal Compensation 

   1. Decrease H+ release 

   2. Increase HCO3_ reabsorption

metabolic acidosis

1. Low HCO3- levels 

2. Causes: 

   1. loss of HCO3- (diarrhea, renal dysfunction) 

   2. Accumulation of other acids (ketoacids) 

   3. Failure of kidneys to excrete H+ 

3. Respiratory compensation 

   1. Hyperventilation 

      1. Remove CO2 

      2. Shift carbonic acid/bicarbonate to the left 

Metabolic alkalosis 

1. High HCO3- levels 

2. Causes: 

   1. Loss of acid 

      1. Vomiting 

   2. Excessive intake of alkaline medications 

3. Respiratory compensation 

   1. Hypoventilation 

      1. Holds CO2 

      2. Shift carbonic acid/bicarbonate to the right