1. Homeostasis The Interstitial Fluid is the environment of the cells, and life depends on the constancy of this internal sea. Homeostatic Mechanisms : Maintain within a narrow range.  Tonicity  Volume  Specific ion concentration Defence of Tonicity  Vasopressin secretion  Thirst Mechanism

2. Homeostasis Defence of Volume:  ECF Na + - Most important  Renin-Angiotensin- Aldosterone System  Vasopressin Secretion: Volume stimuli override osmotic regulation  ANP & BNP Angiotensinogen Renin Angiotensin I ACE Angiotensin II AldosteroneVasopressin Adrenal Cortex Brain Kidney Na Retention Water Retention Blood Vessel Vasoconstriction Thirst

3. Homeostasis Defence of Specific Ionic Concentration:  Glucose  Na + & K +  Ca ++ - Mainly by Parathyroid & Calcitonin  Mg ++ - Incompletely understood mechanisms Also dependent on H + ion pH is maintained within a narrow range.

4. Acid Base Equilibrium Acid Base Equilibrium is all about Maintenance of H + ion concentration of the ECF. Source of H + ion in Body: CO 2 from metabolism H + load from AA metabolism Strenuous Exercise  Lactic Acid Diabetic KA Ingestion of NH 4 Cl, CaCl 2 Failure of Kidneys to Excrete PO4 --, SO4 --

5. Acid Base Equilibrium: CO 2 in Water:  Can Dissolve in water  Can form - Carbonic Acid  - Bicarbonate ion  - Carbonate ion CO 2(gas) CO 2(dissolved) Rate of Forward Reaction = K f * PCO 2 Rate of Reverse reaction = K r *[CO 2(dissolved) ] => [CO 2(dissolved) ] = K f /K r *PCO 2 K f /K r = SCO 2 (Solubility of CO 2 ) = 0.03mEq/L/mm Hg at 37 0 C } All these reactions have equilibrium Constants and can be solved at equilibrium.

6. Acid Base Equilibrium: CO 2 + H 2 O H 2 CO 3 => [CO 2 ][H 2 O] = K*[H 2 CO 3 ] => [H 2 CO 3 ] = K’*PCO 2 H 2 CO 3 H + + HCO 3 - Henderson Equation: [H + ] = K 1 [H 2 CO 3 ]/[HCO 3 - ] Modified Henderson Equation: [H + ][HCO 3 - ] = K 2 [CO 2 ][H 2 O] [H + ][HCO 3 - ] = K 3 [CO 2 ] [H + ] = K*PaCO 2 /[HCO 3 - ]

7. Acid Base Equilibrium: The Henderson-Hasselbalch Equation: CO 2 + H 2 O H + + HCO 3 - => [H + ] = K’a * [CO 2 ]/[HCO 3 - ] Rearranging: =>1/[H + ] = 1/K’a*[HCO 3 - ]/[CO 2 ] Taking Logarithm on both sides & Rearranging: => pH= pK’a + log 10 [HCO 3 - ]/0.03*PCO 2 Significance:  Includes components of both Met & Resp Acid base disorders  Value of any one variable can be determined if other two known. Mostly HCO 3 - is calculated  pH determined by ratio of [HCO 3 - ]/PCO 2. Maintained at 20. Increase=> alkalosis, Decrease => Acidosis

8. Clinical Concepts: Base Excess: Amount of Acid or Alkali required to return plasma in vitro to normal pH under standard conditions. Standard BE: BE calculated for Anaemic Blood (Hb = 5Gm%).  Since Hb effectively buffers plasma & ECF to a large extent.  Quantity of Acid or Alkali required to return plasma in-vivo to a normal pH under standard conditions Anion Gap:  AG = [Na + ] + [K + ] - {[HCO 3 - ] + [Cl - ]}  Normal Value: 8-12mEq/L,  Unmeasured Anion: Albumin, Phosphate, sulphate, organic anions  AG decreases by 2.5mEq/L for every 1mEq/L decrease in Plasma albumin  AG>16 ==> Ketones, lactate, salicylate, antifreeze, methanol

9. Clinical Concepts: Base Excess: Amount of Acid or Alkali required to return plasma in vitro to normal pH under standard conditions. Standard BE: BE calculated for Anaemic Blood (Hb = 5Gm%).  Since Hb effectively buffers plasma & ECF to a large extent.  Quantity of Acid or Alkali required to return plasma in-vivo to a normal pH under standard conditions Anion Gap:  AG = [Na + ] + [K + ] - {[HCO 3 - ] + [Cl - ]}  Normal Value: 8-12mEq/L,  Unmeasured Anion: Albumin, Phosphate, sulphate, organic anions  AG decreases by 2.5mEq/L for every 1mEq/L decrease in Plasma albumin  AG>16 ==> Ketones, lactate, salicylate, antifreeze, methanol

14. Acid Base Disorders  Metabolic Acidosis  Metabolic Alkalosis  Respiratory Acidosis  Respiratory Alkalosis  Metabolic: Primarily affects Bicarbonate  Respiratory: Primarily affects PaCO 2 DisorderPrimary Change Compensatory Change Metabolic Acidosis HCO 3 _ PaCO 2 Metabolic Alkalosis HCO 3 _ PaCO 2 Respiratory Acidosis PaCO 2 HCO 3 _ Respiratory Alkalosis PaCO 2 HCO 3 _

15. cause of respiratory acidosis

16. cause of respiratory alkalosis

17. cause of metabolic alkalosis

18. cause of ketoacidosis in type 1 diabetes