1	General Principles of Pathophysiology The Cellular Environment Fluids & Electrolytes Acid-base Balance & Maintenance
2	Topics Describe the distribution of water in the body Discuss common physiologic electrolytes Review mechanisms of transport osmosis, diffusion, etc Discuss hemostasis & blood types Discuss concepts of acid-base maintenance
3	Distribution of Water Total Body Weight/ Total Body Water Intracellular - ICF (45%/75%) Extracellular - ECF (15%/25%) Intravascular (4.5%/7.5%) Interstitial (10.5%/17.5%)
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5	Fluid Distribution
6	Total Body Weight
7	Total Body Water
8	Fluid Intake
9	Fluid Output
10	Osmosis versus Diffusion 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. diffusion of water in terms of [water] Diffusion is the net movement of solutes from an area of HIGH solute concentration to an area of LOWER solute concentration.
11	Osmosis
12	Tonicity Isotonic Hypertonic Hypotonic
13	Isotonic Solutions Same solute concentration as RBC If injected into vein: no net movement of fluid Example: 0.9% sodium chloride solution aka Normal Saline
14	Hypertonic Solutions Higher solute concentration than RBC If injected into vein: Fluid moves INTO veins
15	Hypotonic Solutions Lower solute concentration than RBC If injected into vein: Fluid moves OUT of veins
16	Affects of Hypotonic Solution on Cell The [solute] outside the cell is lower than inside. Water moves from low [solute] to high [solute]. The cell swells and eventually bursts!
17	Affects of Hypertonic Solution on Cell The [solute] outside the cell is higher than inside. Water moves from low [solute] to high [solute]. The cell shrinks!
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19	Ion Distribution
20	Example of Role of Electrolytes Nervous System Propagation of Action Potential Cardiovascular System Cardiac conduction & contraction
21	Cardiac Conduction / Contraction
22	Composition of Blood 8% of total body weight Plasma: 55% Water: 90% Solutes: 10% Formed elements: 45% Platelets Erythrocytes
23	Hematrocrit % of RBC in blood Normal: 37% - 47% (Female) 40% - 54% (Male)
24	Blood Components Plasma: liquid portion of blood Contains Proteins Albumin (60%) contribute to osmotic pressure Globulin (36%): lipid transport and antibodies Fibrinogen (4%): blood clotting
25	Blood Components Formed Elements Erythrocytes Leukocytes Thrombocytes
26	Erythrocytes ‘biconcave’ disc 7-8 mcm diameter Packed with hemoglobin 4.5 - 6 million RBC/mm³(males) 120 day life span 2 million replaced per second!
27	Leukocytes Most work done in tissues 5,000 - 6,000/mm³ Neutrophils (60-70%) Basophils (Mast Cells) (<1%) Eosinophils (2-4%) Lymphocytes (20-25%) Monocytes (Macrophages) (3-8%)
28	Thrombocytes Platelets Cell fragments 250,000 - 500,000/mm³ Form platelet plugs
29	Hemostasis The stoppage of bleeding. Three methods Vascular constriction Platelet plug formation Coagulation
30	Coagulation Formation of blood clots Prothrombin activator Prothrombin Þ Thrombin Fibrinogen Þ Fibrin Clot retraction
31	Coagulation
32	Fibrinolysis Plasminogen tissue plasminogen activator (tPA) Plasmin
33	Blood Types Agglutinogens (Blood Antigens) Agglutinins (Blood Antibodies) Agglutination (RBC clumping) ABO Rh Antigens
34	Type A Blood
35	Type B Blood
36	Type AB Blood
37	Type O Blood
38	Rh Antigens
39	Capillary Network Blood enters capillary network from arterioles Flows through capillary network into venules Arteriolar capillaries Venous capillaries True capillaries Thoroughfare channels Capillary sphincters
40	Sympathetic Innervation Sympathetic fibers innervate all blood vessels except: Capillaries Capillary sphincters Most metarterioles Vasoconstrictor and vasodilator fibers
41	Diffusion across Capillary Wall Capillary flow Hydrostatic pressure Osmotic pressure Oncotic pressure Capillary and membrane permeability
42	Edema Fluid accumulation in the interstitial compartment Causes: Lymphatic ‘leakage’ Excessive hydrostatic pressure Inadequate osmotic pressure
43	Alterations in Water Movement Edema Fluid accumulation in interstitial spaces Due to any condition that leads to: Net movement of fluid out of capillaries into interstitial tissues
44	Pathophysiology of Edema Normal interstitial space fluid depends on: Capillary hydrostatic pressure Oncotic pressure by blood plasma proteins Capillary permeability Lymphatic channels collect fluid forced from capillaries by blood hydrostatic pressure and return it to circulation
45	Mechanisms Responsible for Edema Increased hydrostatic pressure Decreased plasma oncotic pressure Increased capillary permeability Lymphatic obstruction Increased capillary hydrostatic pressure Venous obstruction Sodium and water retention
46	Electrolyte Imbalances In addition to water and sodium imbalances, other electrolyte imbalances may occur Potassium Calcium Magnesium
47	Potassium Major intracellular cation Needed for nerve, cardiac, skeletal function Excess excreted by kidneys Imbalance can cause sudden death
48	Hypokalemia Poor absorption, vomiting, diarrhea, renal disease, diuretics Malaise, weakness, dysrhythmias, decreased reflexes, faint heart sounds, hypotension, anorexia, vomiting Hospital treatment Oral or IV potassium
49	Hyperkalemia Renal failure, burns, crush injuries, infections, excessive use, acidosis Dysrhythmias, irritability, abdominal distention, nausea, diarrhea, oliguria, weakness, paralysis Treatment Life threats – calcium, glucose, insulin IV, albuterol Hospital – K+ restriction, exchange resins, dialysis
50	Calcium Essential for: Neuromuscular transmission Cell membrane permeability Hormone secretion Bone growth Muscle contraction
51	Hypocalcemia Endocrine dysfunction, renal disease, malabsorption Paresthesia, tetany, cramps, neural excitability, seizure, abnormal behavior Treatment Calcium administration in hospital
52	Hypercalcemia Tumors, endocrine dysfunction, diuretics, excess vitamin D Muscle weakness, renal stones, altered mental status, seizures, bone pain, arrhythmias Treatment Underlying problem Diuresis with furosemide and NS
53	Magnesium Activates enzymes 50% in bone Excreted by kidneys CNS effect similar to calcium
54	Hypomagnesemia Alcoholism, diabetes, malabsorption, starvation, diarrhea, diuresis, disease with hypocalcemia, hypokalemia Tremors, nausea, vomiting, diarrhea, hyperactive reflexes, confusion, seizures, dysrhythmias Treatment Magnesium sulfate
55	Hypermagnesemia Patients with chronic renal insufficiency Ingestion of magnesium-containing compounds CNS depression, dysrhythmias, muscle weakness, confusion, sedation, respiratory paralysis Most effective treatment: hemodialysis Also IV glucose and insulin
56	ACID BASE BALANCE
57	Bottom line of Acid-Base Regulation of [H+] normally about 1/3.5 million that of [Na⁺] 0.00004 mEq/L (4 x 10^-8Eq/L) Dependent upon Kidneys Chemical Buffers Precise regulation necessary for peak enzyme activity
58	pH Effects on Enzyme Activity
59	Acid Base Acids release H⁺ example: HCl -> H⁺ + Cl^- Bases absorb H⁺ example: HCO₃^- + H⁺ -> H₂CO₃
60	pH is logarithmic pH = log 1/[H⁺] = - log [H⁺] = - log 0.00000004 Eq/L pH = 7.4 Think of pH as ‘power of [H⁺]
61	pH is Logarithmic
62	Buffers Resist pH Changes Weak acid & conjugate base pair H₂CO₃ Û HCO₃^- + H⁺ Conjugate Acid Û conjugate base + acid
63	Henderson-Hasselbalch Equation pH = pK_a + log [base]/[acid] Ex: = 6.1 + log 20/1 = 6.1 + 1.3 = 7.4 Key ratio is base: acid HCO₃^- : CO₂(standing in for H₂CO₃)
64	pH Scale 0 : Hydrochloric Acid 1: Gastric Acid 2: Lemon Juice 3: Vinegar, Beer 4: Tomatoes 5: Black Coffee 6: Urine 6.5: Saliva 7: Blood 8: Sea Water 9: Baking Soda 10: Great Salt Lake 11: Ammonia 12: Bicarbonate 13: Oven Cleaner 14: NaOH
65	Acid Base Compensation Buffer System Respiratory System Renal System
66	Buffer System Immediate CO₂ + H₂0 Û H₂CO₃ Û H⁺ + HCO₃^- Equilibrium: 20 HCO₃^- to 1 CO₂ (H₂CO₃) Excessive CO₂ Þ acidosis Excessive HCO₃^- Þ alkalosis
67	Question... Is the average pH of the blood lower in: a) arteries b) veins
68	Respiratory System Minutes CO₂ Û H⁺ Respiration Ý: CO₂ ß: H⁺ ß Respiration ß: CO₂ Ý: H⁺ Ý
69	Renal System Hours to days Recovery of Bicarbonate Excretion of H⁺ Excretion of ammonium
70	Disorders Respiratory Acidosis Respiratory Alkalosis Metabolic Acidosis Metabolic Alkalosis
71	Respiratory Acidosis Ý CO₂ + H₂0 Û Ý H₂CO₃ Û Ý H⁺ + HCO₃
72	Respiratory Alkalosis ß CO₂ + H₂0 Û ß H₂CO₃ Û ß H⁺ + HCO₃
73	Metabolic Acidosis Ý H⁺ + HCO₃ Û Ý H₂CO₃ Û H₂0 + Ý CO₂
74	Metabolic Alkalosis ß H⁺ + HCO₃ Û ß H₂CO₃ Û H₂0 + ß CO₂
75	Normal Values pH: 7.35 - 7.45 PCO₂: 35 - 45
76	Abnormal Values
77	All Roads Lead to Rome!
78	Example: pH = 7.25 PCO₂ = 60
79	Example: pH = 7.50 PCO₂ = 35
80	Example: pH = 7.60 PCO₂ = 20
81	Example: pH = 7.28 PCO₂ = 38
82	Resources A Continuing Education article on Acid-Base disturbances is available on our web site at: http://www.templejc.edu/ems/resource.htm A great online tutorial at: http://www.tmc.tulane.edu/departments/anesthesiology/acid/acid.html