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General Principles of Pathophysiology n The Cellular Environment n Fluids & Electrolytes n Acid-base Balance & Maintenance n The Cellular Environment n Fluids & Electrolytes n Acid-base Balance & Maintenance
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TopicsTopics n Describe the distribution of water in the body n Discuss common physiologic electrolytes n Review mechanisms of transport –osmosis, diffusion, etc n Discuss hemostasis & blood types n Discuss concepts of acid-base maintenance n Describe the distribution of water in the body n Discuss common physiologic electrolytes n Review mechanisms of transport –osmosis, diffusion, etc n Discuss hemostasis & blood types n Discuss concepts of acid-base maintenance
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Distribution of Water n Total Body Weight/ Total Body Water n Intracellular - ICF (45%/75%) n Extracellular - ECF (15%/25%) –Intravascular (4.5%/7.5%) –Interstitial (10.5%/17.5%) n Total Body Weight/ Total Body Water n Intracellular - ICF (45%/75%) n Extracellular - ECF (15%/25%) –Intravascular (4.5%/7.5%) –Interstitial (10.5%/17.5%)
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Intra-cellular45% 31.5 kg Intra-cellular45% Interstitial 10.5 % 7.35 kg Interstitial 10.5 % 7.35 kg Intra-vascular4.5% 3.15 kg Intra-vascular4.5% Total Body Weight Fluid Distribution Extracellular Cell Membrane Capillary Membrane
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Fluid Distribution Intra-cellular75% 31.5 L Intra-cellular75% Interstitial 17.5 % 7.35 L Interstitial 17.5 % 7.35 L Intra-vascular7.5% 3.15 L Intra-vascular7.5% Total Body Water Extracellular Cell Membrane Capillary Membrane
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Total Body Weight
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Total Body Water
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EdemaEdema n Fluid accumulation in the interstitial compartment n Causes: –Lymphatic ‘leakage’ –Excessive hydrostatic pressure –Inadequate osmotic pressure n Fluid accumulation in the interstitial compartment n Causes: –Lymphatic ‘leakage’ –Excessive hydrostatic pressure –Inadequate osmotic pressure
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Fluid Intake Water from beverages: 1600 ml (64%) Water from food: 700 ml (28%) Water from metabolism: 200 ml (8%)
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Fluid Output Water from skin: 550 ml (25%) Water from feces: 150 ml (5%) Water from lungs: 300 ml (11%) Water from urine: 1500 ml (59%)
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Osmosis versus Diffusion n Osmosis is the net movement of water from an area of LOW solute concentration to an area of HIGHER solute concentration across a semi- permeable membrane. n diffusion of water –in terms of [water] n Osmosis is the net movement of water from an area of LOW solute concentration to an area of HIGHER solute concentration across a semi- permeable membrane. n 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.
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Silly definition stuff n Osmolarity = osmoles/L of solution n Osmolality = osmoles/kg of solution Where an osmole is 1 mole (6.02 x 10 23 particles) The bottom line? Use them synonymously! The bottom line? Use them synonymously!
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TonicityTonicity n Isotonic n Hypertonic n Hypotonic n Isotonic n Hypertonic n Hypotonic
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Isotonic Solutions n Same solute concentration as RBC n If injected into vein: no net movement of fluid n Example: 0.9% sodium chloride solution –aka Normal Saline n Same solute concentration as RBC n If injected into vein: no net movement of fluid n Example: 0.9% sodium chloride solution –aka Normal Saline
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Hypertonic Solutions n Higher solute concentration than RBC n If injected into vein: –Fluid moves INTO veins n Higher solute concentration than RBC n If injected into vein: –Fluid moves INTO veins
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Hypotonic Solutions n Lower solute concentration than RBC n If injected into vein: –Fluid moves OUT of veins n Lower solute concentration than RBC n If injected into vein: –Fluid moves OUT of veins
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Affects of Hypotonic Solution on Cell Cell Swelling Cell Swollen Cell RupturedCell n The [solute] outside the cell is lower than inside. n Water moves from low [solute] to high [solute]. n The cell swells and eventually bursts! n The [solute] outside the cell is lower than inside. n Water moves from low [solute] to high [solute]. n The cell swells and eventually bursts!
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Affects of Hypertonic Solution on Cell Cell n The [solute] outside the cell is higher than inside. n Water moves from low [solute] to high [solute]. n The cell shrinks! n The [solute] outside the cell is higher than inside. n Water moves from low [solute] to high [solute]. n The cell shrinks! Shrinking Cell Shrunken Cell
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n Infusion of hypertonic solution into veins n No fluid movement n Fluid movement into veins n Fluid movement out of veins n Infusion of isotonic solution into veins n Infusion of hypotonic solution into veins
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Ion Distribution 0 50 100 150 50 100 150 mEq/L Na + K+K+K+K+ Cl - PO 4 - Protein - Cations Anions Extracellular Intracellular
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Example of Role of Electrolytes n Nervous System –Propagation of Action Potential n Cardiovascular System –Cardiac conduction & contraction n Nervous System –Propagation of Action Potential n Cardiovascular System –Cardiac conduction & contraction
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Cardiac Conduction / Contraction
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Composition of Blood n 8% of total body weight n Plasma: 55% –Water: 90% –Solutes: 10% n Formed elements: 45% –Platelets –Erythrocytes n 8% of total body weight n Plasma: 55% –Water: 90% –Solutes: 10% n Formed elements: 45% –Platelets –Erythrocytes
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HematrocritHematrocrit n % of RBC in blood n Normal: –37% - 47% (Female) –40% - 54% (Male) n % of RBC in blood n Normal: –37% - 47% (Female) –40% - 54% (Male)
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Blood Components n Plasma: liquid portion of blood n Contains Proteins –Albumin (60%) contribute to osmotic pressure –Globulin (36%): lipid transport and antibodies –Fibrinogen (4%): blood clotting n Plasma: liquid portion of blood n Contains Proteins –Albumin (60%) contribute to osmotic pressure –Globulin (36%): lipid transport and antibodies –Fibrinogen (4%): blood clotting
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Blood Components n Formed Elements –Erythrocytes –Leukocytes –Thrombocytes n Formed Elements –Erythrocytes –Leukocytes –Thrombocytes
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ErythrocytesErythrocytes n ‘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 ‘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!
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LeukocytesLeukocytes n Most work done in tissues n 5,000 - 6,000/mm 3 –Neutrophils (60-70%) –Basophils (Mast Cells) (<1%) –Eosinophils (2-4%) –Lymphocytes (20-25%) –Monocytes (Macrophages) (3-8%) n Most work done in tissues n 5,000 - 6,000/mm 3 –Neutrophils (60-70%) –Basophils (Mast Cells) (<1%) –Eosinophils (2-4%) –Lymphocytes (20-25%) –Monocytes (Macrophages) (3-8%)
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ThrombocytesThrombocytes n Platelets n Cell fragments n 250,000 - 500,000/mm 3 n Form platelet plugs n Platelets n Cell fragments n 250,000 - 500,000/mm 3 n Form platelet plugs
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HemostasisHemostasis n The stoppage of bleeding. n Three methods –Vascular constriction –Platelet plug formation –Coagulation n The stoppage of bleeding. n Three methods –Vascular constriction –Platelet plug formation –Coagulation
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CoagulationCoagulation n Formation of blood clots n Prothrombin activator n Prothrombin Thrombin n Fibrinogen Fibrin n Clot retraction n Formation of blood clots n Prothrombin activator n Prothrombin Thrombin n Fibrinogen Fibrin n Clot retraction
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CoagulationCoagulation ProthrombinActivatorProthrombinActivator ProthrombinProthrombin ThrombinThrombin FibrinogenFibrinogen FibrinFibrin ClotClot
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FibrinolysisFibrinolysis n Plasminogen n tissue plasminogen activator (tPA) n Plasmin n Plasminogen n tissue plasminogen activator (tPA) n Plasmin
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Blood Types n Agglutinogens (Blood Antigens) n Agglutinins (Blood Antibodies) n Agglutination (RBC clumping) n ABO n Rh Antigens n Agglutinogens (Blood Antigens) n Agglutinins (Blood Antibodies) n Agglutination (RBC clumping) n ABO n Rh Antigens
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Type A Blood
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Type B Blood
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Type AB Blood
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Type O Blood
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Rh Antigens
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Bottom line of Acid-Base n Regulation of [H+] –normally about 1/3.5 million that of [Na + ] –0.00004 mEq/L (4 x 10 -8 Eq/L) n Dependent upon –Kidneys –Chemical Buffers n Precise regulation necessary for peak enzyme activity n Regulation of [H+] –normally about 1/3.5 million that of [Na + ] –0.00004 mEq/L (4 x 10 -8 Eq/L) n Dependent upon –Kidneys –Chemical Buffers n Precise regulation necessary for peak enzyme activity
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pH Effects on Enzyme Activity pH Enzyme Activity activity Peak Activity activity
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Acid Base n Acids release H + –example: HCl -> H + + Cl - n Bases absorb H + –example: HCO 3 - + H + -> H 2 CO 3 n Acids release H + –example: HCl -> H + + Cl - n Bases absorb H + –example: HCO 3 - + H + -> H 2 CO 3
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pH is logarithmic n pH = log 1/[H + ] n = - log [H + ] n = - log 0.00000004 Eq/L n pH = 7.4 n Think of pH as ‘power of [H + ] n pH = log 1/[H + ] n = - log [H + ] n = - log 0.00000004 Eq/L n pH = 7.4 n Think of pH as ‘power of [H + ]
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pH is Logarithmic pH is inversely related to [H+] pH is inversely related to [H+] Small pH mean large [H + ] Small pH mean large [H + ] as [H+] pH as [H+] pH as [H+] pH as [H+] pH & pH 7.4 = 0.00000004 pH 7.1 = 0.00000008 (it doubled!) pH 7.4 = 0.00000004 pH 7.1 = 0.00000008 (it doubled!)
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Buffers Resist pH Changes n Weak acid & conjugate base pair n H 2 CO 3 HCO 3 - + H + n Conjugate Acid conjugate base + acid n Weak acid & conjugate base pair n H 2 CO 3 HCO 3 - + H + n Conjugate Acid conjugate base + acid
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Henderson-Hasselbalch Equation n pH = pK a + 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 ) n pH = pK a + 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 )
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pH Scale n 0 : Hydrochloric Acid n 1: Gastric Acid n 2: Lemon Juice n 3: Vinegar, Beer n 4: Tomatoes n 5: Black Coffee n 6: Urine n 6.5: Saliva n 0 : Hydrochloric Acid n 1: Gastric Acid n 2: Lemon Juice n 3: Vinegar, Beer n 4: Tomatoes n 5: Black Coffee n 6: Urine n 6.5: Saliva n 7: Blood n 8: Sea Water n 9: Baking Soda n 10: Great Salt Lake n 11: Ammonia n 12: Bicarbonate n 13: Oven Cleaner n 14: NaOH
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Acid Base Compensation n Buffer System n Respiratory System n Renal System n Buffer System n Respiratory System n Renal System
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Buffer System n Immediate n CO 2 + H 2 0 H 2 CO 3 H + + HCO 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 Immediate n CO 2 + H 2 0 H 2 CO 3 H + + HCO 3 - n Equilibrium: 20 HCO 3 - to 1 CO 2 (H 2 CO 3 ) n Excessive CO 2 acidosis n Excessive HCO 3 - alkalosis Simplified: CO 2 H + Simplified: CO 2 H +
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Question...Question... Is the average pH of the blood lower in: a) arteries b) veins Is the average pH of the blood lower in: a) arteries b) veins Veins!Why? Because veins pick up the byproducts of cellular metabolism, including… CO 2 ! Because veins pick up the byproducts of cellular metabolism, including… CO 2 !
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Respiratory System n Minutes n CO 2 H + n Respiration : CO 2 : H + n Respiration : CO 2 : H + n Minutes n CO 2 H + n Respiration : CO 2 : H + n Respiration : CO 2 : H +
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Renal System n Hours to days n Recovery of Bicarbonate n Excretion of H + n Excretion of ammonium n Hours to days n Recovery of Bicarbonate n Excretion of H + n Excretion of ammonium
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DisordersDisorders n Respiratory Acidosis n Respiratory Alkalosis n Metabolic Acidosis n Metabolic Alkalosis n Respiratory Acidosis n Respiratory Alkalosis n Metabolic Acidosis n Metabolic Alkalosis
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Respiratory Acidosis n CO 2 + H 2 0 H 2 CO 3 H + + HCO 3 Simplified: CO 2 H + Simplified: CO 2 H +
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Respiratory Alkalosis n CO 2 + H 2 0 H 2 CO 3 H + + HCO 3 Simplified: CO 2 H + Simplified: CO 2 H +
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Metabolic Acidosis n H + + HCO 3 H 2 CO 3 H 2 0 + CO 2 Simplified: Producing too much H + Simplified: Producing too much H +
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Metabolic Alkalosis n H + + HCO 3 H 2 CO 3 H 2 0 + CO 2 Simplified: Too much HCO 3 Simplified: Too much HCO 3
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Normal Values n pH: 7.35 - 7.45 n PCO 2 : 35 - 45 n pH: 7.35 - 7.45 n PCO 2 : 35 - 45
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Abnormal Values
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All Roads Lead to Rome! Respiratory Opposes Metabolic Equals (or doesn’t oppose) Metabolic Equals (or doesn’t oppose)
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Example:Example: n pH = 7.25 n PCO 2 = 60 n pH = 7.25 n PCO 2 = 60 RespiratoryAcidosis!RespiratoryAcidosis!
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Example:Example: n pH = 7.50 n PCO 2 = 35 n pH = 7.50 n PCO 2 = 35 MetabolicAlkalosis!MetabolicAlkalosis!
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Example:Example: n pH = 7.60 n PCO 2 = 20 n pH = 7.60 n PCO 2 = 20 RespiratoryAlkalosis!RespiratoryAlkalosis!
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Example:Example: n pH = 7.28 n PCO 2 = 38 n pH = 7.28 n PCO 2 = 38 MetabolicAcidosis!MetabolicAcidosis!
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ResourcesResources 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/acid.html 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/acid.html
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