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Biochemistry and Foundations of Western Medical Sciences. FALL 2011 Dr. Megan Gonzales ND, LAc. Introductions. Name What you were doing this time last year What was the best part of your summer before grad school Why you are here. BE SPECIFIC
Biochemistry and Foundations of Western Medical Sciences • FALL 2011 • Dr. Megan Gonzales ND, LAc
Introductions • Name • What you were doing this time last year • What was the best part of your summer before grad school • Why you are here. BE SPECIFIC • What is your favorite biochemical concept/construct
Course Outline • Break it down by week in pairs or trio • Each team has 10 minutes to prepare and 2 minutes to tell the class what they think the class is about the week they are assigned • Cohort has 2 minutes to ask questions
Basic SCIENCES SIOM • 1.Biochemistry and Foundations of Western Medical (clinical) Sciences • 2. Immunology/Hematology and Microbiology / Infectious Disease (Foundations of Western disease) and Malignant Neoplasms: This includes the HIV/AIDS 7-hr required course - Introduce antimicrobials here • 3. Systems I: changes with what is presented in Chinese Medicine course designed to coincide in content to provide a basic understanding of the western diagnosis and treatment at the same time as being presented Chinese illness interpretations. • 4. Systems II: • 5. Systems III: • 6. Systems IV:
Systems View (versus reductionist view) • Article: The Clinical Application of a Systems Approach • Citation: Ahn AC, Tewari M, Poon C-S, Phillips RS (2006) The Clinical Applications of a Systems Approach. PLoS Med 3(7): e209. doi:10.1371/journal.pmed.0030209
The Problem • The primary side effect of a reductionist approach is that the act of reduction (from larger to smaller) disregards component–component interactions and the dynamics that result from them. Therefore, as a general rule, reductionism is less helpful for systems where interactions between components dominate the components themselves in shaping the system-wide behavior
Reductionist versus systems • Big Difference
When to use which... • In clinical medicine, complex, chronic diseases such as diabetes, coronary artery disease, or asthma are examples where this rule may apply. In these examples, a single factor is rarely implicated as solely responsible for disease development or presentation. Rather, multiple factors are often identified, and the disease evolves through complex interactions between them.
continued • Consequently, a perspective in which the interactions and dynamics are centrally integrated into the analytical methods may be better suited. Systems perspectives, unlike reductionisms, focus on these interrelationships and therefore may be the optimal method for complex chronic diseases.
What do you mean? • Where reductionism is helpful, when a systems approach is not, is when one or several components overwhelmingly influence the systems behavior. Diseases such as urinary tract infection, acute appendicitis, or aortic dissection are driven primarily by a single pathology amenable to a specific intervention. Arguably, these conditions would do poorly under a systems approach, where lengthy analysis and comprehensive data acquisition are often required.
Bottom line: • Reductionism works best when an isolatable problem exists and where a quick and effective solution is needed. For that reason, reductionism may generally be most effective for acute and simple diseases, whereas a systems approach may be most applicable to chronic and complex diseases.
The example of diabetes • Given that a systems approach is likely applicable to complex chronic diseases, how might it influence the treatment of a complex disease such as diabetes? Research has shown that diabetes is a multidimensional disorder. Factors such as genetics, inflammation , PPAR-gamma, leptin, cortisol, diet, and body mass index, among others, have been implicated in some form with its pathogenesis.
The role of systems medicine • The fundamental distinctiveness of systems medicine is not just the recognition that these complex factors are important in disease management, but that they need to be incorporated in some meaningful way to treatment selection and delivery.
Conclusions • The challenges of incorporating systems science into medicine are difficult but not insurmountable. The specific task to be faced is the system-level understanding of human health and disease at the organ, organism, and community level. This effort has great potential for the advancement of medicine.
Questions on Systems thought? • Logical?
Acid-Base Biochemistry & Unit ONE • WEEK 2 SIOM
Acid-Base Biochemistry • Definitions • Methods • Physiology • Pathology
Acid-Base BiochemistryDefinitions • What is an acid? • What is a base?
Acid-Base BiochemistryDefinitions • Definitions of an acid • Taste • Boyle • Arrhenius • Bronsted-Lowry • Lewis
Acid-Base BiochemistryDefinitions • Taste • – tasting sour • Lemon juice • Vinegar • Definition - Thousands of years old
Acid-Base BiochemistryDefinitions • Robert Boyle 17th century scientist • Acids taste sour, are corrosive to metals, change litmus (a dye extracted from lichens) red, and become less acidic when mixed with bases (Alkali). • Bases (Alkali) feel slippery, change litmus blue, and become less basic (alkaline) when mixed with acids.
Acid-Base BiochemistryDefinitions • Arrhenius (swedish scientist) • Arrhenius suggested that acids are compounds that contain hydrogen and can dissolve in water to release hydrogen ions into solution. For example, hydrochloric acid (HCl) dissolves in water as follows: • H2O • HCl (g)→ H+ (aq) + Cl-(aq)
Acid-Base BiochemistryDefinitions • Arrhenius defined bases as substances that dissolve in water to release hydroxide ions (OH-) into solution. For example, a typical base according to the Arrhenius definition is sodium hydroxide (NaOH): • H2O • NaOH (s)→ Na+ (aq) + OH-(aq)
Acid-Base BiochemistryDefinitions • The Arrhenius definition of acids and bases explains a number of things. Arrhenius's theory explains why all acids have similar properties to each other (and, conversely, why all bases are similar): because all acids release H+ into solution (and all bases release OH-).
Acid-Base BiochemistryDefinitions • The Arrhenius definition also explains Boyle's observation that acids and bases counteract each other. This idea, that a base can make an acid weaker, and vice versa, is called neutralization.
Acid-Base BiochemistryDefinitions • Neutralization: As you can see from the equations, acids release H+ into solution and bases release OH-. If we were to mix an acid and base together, the H+ion would combine with the OH- ion to make the molecule H2O, or plain water: • H+ (aq) + OH-(aq) → H2O
Acid-Base BiochemistryDefinitions • The neutralization reaction of an acid with a base will always produce water and a salt, as shown below: • Acid Base Water Salt • HCl + NaOH → H2O + NaCl • HBr + KOH → H2O + KBr
Acid-Base BiochemistryDefinitions • Limitations of Arrhenius • The Arrhenius definition does not explain why some substances, such as common baking soda (NaHCO3), can act like a base even though they do not contain hydroxide ions.
Acid-Base BiochemistryDefinitions • Brǿnsted-Lowry 1923 • An acid is any chemical species that donates a proton to another chemical species (proton donor) • A base is any chemical species that accepts a proton from another chemical species (Proton acceptor)
Acid-Base BiochemistryDefinitions • The Brønsted-Lowry definition of acids is very similar to the Arrhenius definition, any substance that can donate a hydrogen ion is an acid (under the Brønsted definition, acids are often referred to as proton donors because an H+ ion, hydrogen minus its electron, is simply a proton).
Acid-Base BiochemistryDefinitions • The Brønsted definition of bases is, however, quite different from the Arrhenius definition. Arrhenius base releases hydroxyl ions whereas the Brønsted base is defined as any substance that can accept a hydrogen ion.
Acid-Base BiochemistryDefinitions • The Brønsted-Lowry definition includes the Arrhenius bases so • NaOH and KOH, as we saw above, would still be considered bases because they can accept an H+ from an acid to form water. • But it extends the concept of a base and introduces the concept of conjugate acid-base pairs
Acid-Base BiochemistryDefinitions • The removal of a proton (hydrogen ion) from an acid produces itsconjugate base, which is the acid with a hydrogen ion removed, and the reception of a proton by a base produces its conjugate acid, which is the base with a hydrogen ion added
Acid-Base BiochemistryDefinitions • The Brønsted-Lowry definition also explains why substances that do not contain OH- ions can act like bases. • Baking soda (NaHCO3), for example, acts like a base by accepting a hydrogen ion from an acid as illustrated below: • Acid Base Salt • HCl + NaHCO3→ H2CO3 + NaCl
Acid-Base BiochemistryDefinitions • Lewis definition 1923 • A substance that can accept an electron pair from a base is an acid. • The Lewis theory defines an acid as a species that can accept an electron pair from another atom, and a base as a species that can donate an electron pair to complete the valence shell of another atom
Acid-Base BiochemistryDefinitions • pHUnder the Brønsted-Lowry definition, both acids and bases are related to the concentration of hydrogen ions present. Acids increase the concentration of hydrogen ions, while bases decrease the concentration of hydrogen ions (by accepting them). The acidity or basicity of something therefore can be measured by its hydrogen ion concentration.
Acid-Base BiochemistryDefinitions • In 1909, the Danish biochemist Sören Sörensen invented the pH scale for measuring acidity. The pH scale is described by the formula: • pH = -log [H+] • Note: concentration is commonly abbreviated by using square brackets, thus [H+] = hydrogen ion concentration. When measuring pH, [H+] is in units of moles of H+ per litre of solution.
Acid-Base BiochemistryPhysiology • What is Physiological pH range?
Acid-Base BiochemistryPhysiology • Extracellular fluid • pH 7.35 – 7.46 (35-45 nmol/L) • Does this apply to whole body • ?any different pH ranges elsewhere
Acid-Base BiochemistryPhysiology • More extreme/variable pH range • Digestive tract • Gastric Juice 1.0-3.0 • Pancreatic Juice 8.0-8.3 • Intercellular organelles • Lysosomal pH 4-5 • Digestive and lysosomal enzymes are function optimally at these pH ranges
ph examples • 7.4 blood
Acid-Base BiochemistryPhysiology • WHAT ARE THE SOURCES OF ACID IN THE BODY?
Acid-Base BiochemistryPhysiology • Sources of acid • Metabolism of food • Metabolism of drugs • Inborn errors of metabolism
Acid-Base BiochemistryPhysiology • Acid production from metabolism of food • Sulphuric acid from metabolism of sulphur-containing amino acids of proteins • Lactic acid from sugars • Ketoacids from fats