General Principles of Pathophysiology n The Cellular Environment

General Principles of Pathophysiology n. The Cellular Environment n. Fluids & Electrolytes n. Acid-base Balance & Maintenance

Topics Describe the distribution of water in the body n Discuss common physiologic electrolytes n Review mechanisms of transport n – osmosis, diffusion, etc Discuss hemostasis & blood types n Discuss concepts of acid-base maintenance n

Distribution of Water Total Body Weight/ Total Body Water n Intracellular - ICF (45%/75%) n Extracellular - ECF (15%/25%) n – Intravascular (4. 5%/7. 5%) – Interstitial (10. 5%/17. 5%)

Fluid Distribution Interstitial 10. 5 % 7. 35 kg Total Body Weight Capillary Membrane Intracellular 45% 31. 5 kg Cell Membrane Extracellular Intravascular 4. 5% 3. 15 kg

Fluid Distribution Interstitial 17. 5 % 7. 35 L Total Body Water Capillary Membrane Intracellular 75% 31. 5 L Cell Membrane Extracellular Intravascular 7. 5% 3. 15 L

Total Body Weight

Total Body Water

Edema Fluid accumulation in the interstitial compartment n Causes: n – Lymphatic ‘leakage’ – Excessive hydrostatic pressure – Inadequate osmotic pressure

Fluid Intake Water from metabolism: 200 ml (8%) Water from food: 700 ml (28%) Water from beverages: 1600 ml (64%)

Fluid Output Water from feces: 150 ml (5%) Water from skin: 550 ml (25%) Water from lungs: 300 ml (11%) Water from urine: 1500 ml (59%)

Osmosis versus Diffusion n n Osmosis is the net movement of water from an area of LOW solute concentration to an area of HIGHER solute concentration across a semipermeable membrane. diffusion of water – in terms of [water] n Diffusion is the net movement of solutes from an area of HIGH solute concentration to an area of LOWER solute concentration.

Silly definition stuff n Osmolarity = osmoles/L of solution n Osmolality = osmoles/kg of solution Where an osmole is 1 mole (6. 02 x 1023 particles) The bottom line? Use them synonymously!

Tonicity Isotonic n Hypertonic n Hypotonic n

Isotonic Solutions Same solute concentration as RBC n If injected into vein: no net movement of fluid n Example: 0. 9% sodium chloride solution n – aka Normal Saline

Hypertonic Solutions Higher solute concentration than RBC n If injected into vein: n – Fluid moves INTO veins

Hypotonic Solutions Lower solute concentration than RBC n If injected into vein: n – Fluid moves OUT of veins

Affects of Hypotonic Solution on Cell n n Swollen Ruptured Swelling Cell n The [solute] outside the cell is lower than inside. Water moves from low [solute] to high [solute]. The cell swells and eventually bursts!

Affects of Hypertonic Solution on Cell n n Shrinking Shrunken Cell n The [solute] outside the cell is higher than inside. Water moves from low [solute] to high [solute]. The cell shrinks!

n Infusion of isotonic solution into veins n No fluid movement n Infusion of hypertonic solution into veins n Fluid movement into veins n Infusion of hypotonic solution into veins n Fluid movement out of veins

Ion Distribution Anions Cations 150 Extracellular m. Eq/L 100 50 Na+ Cl- 0 Protein- 50 100 150 K+ PO 4 Intracellular

Example of Role of Electrolytes n Nervous System – Propagation of Action Potential n Cardiovascular System – Cardiac conduction & contraction

Cardiac Conduction / Contraction

Composition of Blood 8% of total body weight n Plasma: 55% n – Water: 90% – Solutes: 10% n Formed elements: 45% – Platelets – Erythrocytes

Hematrocrit % of RBC in blood n Normal: n – 37% - 47% (Female) – 40% - 54% (Male)

Blood Components Plasma: liquid portion of blood n Contains Proteins n – Albumin (60%) contribute to osmotic pressure – Globulin (36%): lipid transport and antibodies – Fibrinogen (4%): blood clotting

Blood Components n Formed Elements – Erythrocytes – Leukocytes – Thrombocytes

Erythrocytes ‘biconcave’ disc n 7 -8 mcm diameter n Packed with hemoglobin n 4. 5 - 6 million RBC/mm 3 (males) n Anucleate n 120 day life span n 2 million replaced per second! n

Leukocytes Most work done in tissues n 5, 000 - 6, 000/mm 3 n – Neutrophils (60 -70%) – Basophils (Mast Cells) (<1%) – Eosinophils (2 -4%) – Lymphocytes (20 -25%) – Monocytes (Macrophages) (3 -8%)

Thrombocytes Platelets n Cell fragments n 250, 000 - 500, 000/mm 3 n Form platelet plugs n

Hemostasis The stoppage of bleeding. n Three methods n – Vascular constriction – Platelet plug formation – Coagulation

Coagulation Formation of blood clots n Prothrombin activator n Prothrombin Thrombin n Fibrinogen Fibrin n Clot retraction n

Coagulation Prothrombin Activator Clot Prothrombin Thrombin Fibrinogen Fibrin

Fibrinolysis Plasminogen n tissue plasminogen activator (t. PA) n Plasmin n

Blood Types Agglutinogens (Blood Antigens) n Agglutinins (Blood Antibodies) n Agglutination (RBC clumping) n ABO n Rh Antigens n

Type A Blood

Type B Blood

Type AB Blood

Type O Blood

Rh Antigens

Bottom line of Acid-Base n Regulation of [H+] – normally about 1/3. 5 million that of [Na+] – 0. 00004 m. Eq/L (4 x 10 -8 Eq/L) n Dependent upon – Kidneys – Chemical Buffers n Precise regulation necessary for peak enzyme activity

Enzyme Activity p. H Effects on Enzyme Activity Peak Activity activity p. H

Acid Base n Acids release H+ – example: HCl -> H+ + Cl- n Bases absorb H+ – example: HCO 3 - + H+ -> H 2 CO 3

p. H is logarithmic p. H = log 1/[H+] n = - log 0. 00000004 Eq/L n p. H = 7. 4 n n Think of p. H as ‘power of [H+]

p. H is Logarithmic p. H is inversely related to [H+] Small p. H mean large [H+] as [H+] p. H & as [H+] p. H 7. 4 = 0. 00000004 p. H 7. 1 = 0. 00000008 (it doubled!)

Buffers Resist p. H Changes Weak acid & conjugate base pair n H 2 CO 3 HCO 3 + H+ n Conjugate Acid conjugate base + acid n

Henderson-Hasselbalch Equation n p. H = p. Ka + log [base]/[acid] – Ex: • = 6. 1 + log 20/1 • = 6. 1 + 1. 3 • = 7. 4 n Key ratio is base: acid – HCO 3 - : CO 2 (standing in for H 2 CO 3)

p. H Scale n n n n 0 : Hydrochloric Acid 1: Gastric Acid 2: Lemon Juice 3: Vinegar, Beer 4: Tomatoes 5: Black Coffee 6: Urine 6. 5: Saliva n n n n 7: Blood 8: Sea Water 9: Baking Soda 10: Great Salt Lake 11: Ammonia 12: Bicarbonate 13: Oven Cleaner 14: Na. OH

Acid Base Compensation Buffer System n Respiratory System n Renal System n

Buffer System Immediate + + HCO n CO 2 + H 20 H 2 CO 3 H 3 n Equilibrium: 20 HCO 3 to 1 CO 2 (H 2 CO 3) n Excessive CO 2 acidosis n Excessive HCO 3 alkalosis n Simplified: CO 2 H+

Question. . . Is the average p. H of the blood lower in: a) arteries Because veins pick up the Veins! byproducts of cellular metabolism, b) veins including… Why? CO 2!

Respiratory System Minutes n CO 2 H+ n Respiration : CO 2 : H+ n

Renal System Hours to days n Recovery of Bicarbonate n Excretion of H+ n Excretion of ammonium n

Disorders Respiratory Acidosis n Respiratory Alkalosis n Metabolic Acidosis n Metabolic Alkalosis n

Respiratory Acidosis n CO 2 + H 20 H 2 CO 3 H+ + HCO 3 • Simplified: • CO 2 H+

Respiratory Alkalosis n CO 2 + H 20 H 2 CO 3 H+ + HCO 3 • Simplified: • CO 2 H+

Metabolic Acidosis n H+ + HCO 3 H 2 CO 3 H 20 + CO 2 • Simplified: • Producing too much H+

Metabolic Alkalosis n H+ + HCO 3 H 2 CO 3 H 20 + CO 2 • Simplified: • Too much HCO 3

Normal Values p. H: 7. 35 - 7. 45 n PCO 2: 35 - 45 n

Abnormal Values

All Roads Lead to Rome! Respiratory Opposes Metabolic Equals (or doesn’t oppose)

Example: p. H = 7. 25 n PCO 2 = 60 n Respiratory Acidosis!

Example: p. H = 7. 50 n PCO 2 = 35 n Metabolic Alkalosis!

Example: p. H = 7. 60 n PCO 2 = 20 n Respiratory Alkalosis!

Example: p. H = 7. 28 n PCO 2 = 38 n Metabolic Acidosis!

Resources n A Continuing Education article on Acid. Base disturbances is available on our web site at: n http: //www. templejc. edu/ems/resource. htm n A great online tutorial at: n http: //www. tmc. tulane. edu/departments/anesthesi ology/acid. html