IASM Notes (1) PDF - Introduction to the Art and Science of Medicine

**[INTRODUCTION TO THE ART AND SCIENCE OF MEDICINE (IASM 1)]** +-----------------------+-----------------------+-----------------------+ | **CONTENT** |..................... | p\. 2 | | |..................... | | | 1. 1. 2. 3....

**[INTRODUCTION TO THE ART AND SCIENCE OF MEDICINE (IASM 1)]** +-----------------------+-----------------------+-----------------------+ | **CONTENT** |..................... | p\. 2 | | |..................... | | | 1. 1. 2. 3. 4. |......... | p\. 7 | | | | | | 2. 5. 6. 7. 8. 9 |..................... | p\. 10 | |. 10. |..................... | | | |......... | p\. 21 | | 3. 11. 12. 13. 14. | | | | |..................... | p\. 30 | | 4. 15. 16. 17. 18. 1 |..................... | | | 9. 20. 21. |......... | p\. 31 | | | | | | |..................... | p\. 32 | | |..................... | | | |......... | p\. 37 | | | | | | |..................... | p\. 40 | | |..................... | | | |......... | p\. 41 | | | | | | |..................... | p\. 43 | | |..................... | | | |......... | p\. 52 | | | | | | |..................... | p\. 61 | | |..................... | | | |......... | p\. 66 | | | | | | |..................... | p\. 73 | | |..................... | | | |......... | p\. 86 | | | | | | |..................... | p\. 96 | | |..................... | | | |......... | p\. 105 | | | | | | |..................... | p\. 114 | | |..................... | | | |......... | p\. 120 | | | | | | |..................... | p\. 127 | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | | | | | | |..................... | | | |..................... | | | |......... | | +-----------------------+-----------------------+-----------------------+ **1. MOLECULES OF MEDICINE** **1.1. DNA** **1.1.1. STRUCTURE OF B-DNA** - - - - - - - - - - - - - - - - - - - - -  - - - - - - - - **1.1.2. ORDER OF DNA STRUCTURE** - - - - - - - LEVEL EQUIVALENT --------------------------------------- --------------- Chromatids (x2) 10 coils each Coil 30 rosettes Rosette 6 loops Loop \~75,000 bp 30 nm fibre / "Beads-on-a-string" form of chromatin / DNA **1.1.3. DNA EXPRESSION AND GENE REGULATION** - - - 1. 2. 3. - - - - - - - - - **1.1.4. THE CENTRAL DOGMA** - - - - - - - - - - - - - - - **1.1.5. TRANSCRIPTION** - A. - - - - B. - - C. - - - - - - - - - - - - - - - - - - - - - **1.2. RNA** **1.2.1. RNA VARIETIES AND FUNCTIONS** - - - - - - - - - - - - - - - - - - **1.2.2. TRANSLATION** - A. B. C. D. - - - - - - - - - - - - - -  **1.3. PROTEINS** **1.3.1. FUNCTION OF PROTEINS** - 1. 2. 3. 4. 5. - - - - - - - - - - - - - **1.3.2. AMINO ACIDS AND THEIR PROPERTIES** - - - - \[Gamma amino acid here is GABA.\] - -  - - - - - -   +-----------------------------------+-----------------------------------+ | | Note: | | | | | | - - | | | | | | | | | | | | - | | | | | | | | | | | | - | +-----------------------------------+-----------------------------------+ **1.3.3. PROTEIN BONDS AND STRUCTURES** - - - -  - 1. - - 2. - - - - - - - - - - - - - 3. - - - 4. - - **1.3.4. CLASSIFICATION OF PROTEINS** 1. - - A. - - - - - -  - - - - - - - B. - - - - - - - - - - 2. - A. - - - - - - - - - - - - - - - - 1. 2.  +-----------------------------------+-----------------------------------+ | Positive cooperativity of | | | haemoglobin and myoglobin: | | | | | | - - - | | | | | | \[protein crystallography -- | | | structure of proteins\] | | | | | | - - - | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | Oxygen-haemoglobin dissociation |  | | curve: | | | | x-axis: pO~2~, the partial | | High affinity state: | pressure of oxygen in the | | | surrounding atmosphere | | - | | | | y-axis: 𝜃, the proportion of | | Low affinity state: | sites which are filled (with | | | oxygen) | | - | | | | | | Sigmoid curve: | | | | | | - - | | +-----------------------------------+-----------------------------------+ - - - - - +-----------------------------------+-----------------------------------+ | - - - - - | | +-----------------------------------+-----------------------------------+ **1.3.5. PROTEIN FOLDING** - - - - - - - - - - - - - - -  **1.3.6. PROTEIN-RELATED PATHOLOGIES** 1. A. - - B. - - - - - - - +-----------------------------------+-----------------------------------+ | 2\. Related to protein folding | | | -- prion diseases: | | | | | | - | | | | | | | | | | | | - | | | | | | | | | | | | - - - - | | | | | | | | | | | | - | | +-----------------------------------+-----------------------------------+ A. - - - B. - C. - D. - E. - - - - - - - -  **1.4. ENZYMES** **1.4.1. OVERVIEW OF ENZYMES** - - - - - - - - - - **1.4.2. CATEGORISATION OF ENZYMES**  - - - - - - - - - - 1. - - 2. - - - - - - **1.4.3. THE MICHAELIS-MENTEN EQUATION** - - - - - - - - **1.4.4. BISUBSTRATE ENZYMATIC REACTIONS** - - - - - 1. - -  2. - - **1.4.5. FACTORS AFFECTING ENZYME CATALYSIS** +-----------------------------------+-----------------------------------+ | 1. |  | | | | | - - - |  | | | | | 2. 3. | | | | | | - - | | | | | | | | | | | | - | | | | | | | | | | | | - - - | | | | | | | | | | | | - | | | | | | | | | | | | - - - | | +-----------------------------------+-----------------------------------+ 4.  **1.4.6. REGULATION OF ENZYME ACTIVITY** - - - - - - - - - 1. 2. 3. 1. - - - A. B. C. +-----------------------------------+-----------------------------------+ | B. | | | | | | - - - | | +===================================+===================================+ | A. |  | | | | | - - - | | | | | | \[End-product inhibition: | | | | | | - - - | | +-----------------------------------+-----------------------------------+ 2. - - A. B. C. D. A. - - 1. 2. 3. 4. +-----------------------------------+-----------------------------------+ | B. |  | | | | | - - - | | +-----------------------------------+-----------------------------------+ - - - C. - - - - -  +-----------------------------------+-----------------------------------+ | - - - - | | | | | | 3. | | | | | | - - - | | +-----------------------------------+-----------------------------------+ **2. PRECISION MEDICINE** **2.1. KEY CONCEPTS** - - - - - - - - - - - - - - - - - - - - - - - - - **2.2. EXAMPLES OF THE APPLICATION OF PRECISION MEDICINE** 1. - - -  - - - - - 2. - - - - - 3. - - - - - - - - - - **2.3. THE HUMAN GENOME** **2.3.1. HUMAN GENETIC INFORMATION** - - - - - - - - - - - - - - - - - - - - - - - - - - - **2.3.2. GENETIC VARIATION** - - - - - 1. - - - - - 2. - - - - - - - - 3. - - - - - - - - - - - - - - **2.3.3. OTHER GENETIC-RELATED PATHOLOGIES** - - - - - - - - - - - - 1. - - - - - - - - - - - - - - - - - 2. - - - - - - - - 3. - - - - - - - - - - - - - - 4. - - - - - - - - **2.3.4. GENE REGULATION IN MEDICINE** - - - - - - - - -  **2.4. GENE SEQUENCING** **2.4.1. OVERVIEW OF GENE SEQUENCING** - - - - - - - - - - - **2.4.2. SANGER METHOD** - - - - - - - - - - - - - **2.4.3. MODERN DNA SEQUENCING** - - - - - - - - - - - - - - - - - - - - - - - - **2.4.4. SEQUENCING-BY-SYNTHESIS** - - - 1. - 2. - - - 3. - - 1. 2. 3. - 1. - - - - **2.4.5. HKU CENTRE FOR GENOMIC SCIENCES** - - - - - - - - - - - - - - - - - - - - - **2.5. GENE EDITING -- CRISPR CAS9** **2.5.1. MECHANISM OF CRISPR CAS9** - - - - - - - - - - - - - **2.5.2. NEW APPLICATIONS OF CRISPR** 1. - - - 2. - - - - 3. - - - - - \[Chromothripsis may be a potential challenge to the use of CRISPR: - **2.6. FURTHER INFORMATION ON PRECISION MEDICINE** **2.6.1. DIGITAL HEALTH ECOSYSTEM** - - - - - - - - - - - - - -  **2.6.2. ETHICAL AND LEGAL ISSUES OF DIGITAL HEALTH** - - - - - - - - - - - **3. NUTRITION AND METABOLISM** **3.1. HUMAN NUTRITION** **3.1.1. OVERVIEW NUTRITION AND METABOLISM** - - - +-----------------------------------+-----------------------------------+ | - | | | | | | | | | | | | - - | | | | | | | | | | | | - | | | | | | 1. a. b. | | | | | | 2. | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | - |  | | | | | | | | | | | - - - - - - - - - | | | - | | | | | | - | | +-----------------------------------+-----------------------------------+ **3.1.2. INTRODUCTION TO NUTRIENTS** - - - - - - - - - - - - - - - - - - - 1. - - - - - - - - - - - - - - - - 2. - - - 3. - - - - 4. 5. - - - - - - - - - - - - - - - - - - - - - - - - - - 1. 2. 3. - - **3.1.3. CLASSIFICATION OF NUTRIENTS** 1. - - - - 2. - - - 3. - - - 4. - 5. - - - - - - 6. - - - **3.1.4. TOTAL DAILY ENERGY EXPENDITURE (TEE)** - - - - - - - - - - - - - 1. - - - 2. - - 3. - - - - - 1. - - - 2. - - 3. - - - - - - - - - - - -  **3.1.5. NUTRITIONAL RECOMMENDATIONS AND ASSESSMENT** - - - - 1. 2. 3. 4. - - - - - - - - - - - - - - - 1. 2. 3. 4. 5. - - - - - - - - - - - - - - - - - - - - - - - **3.2. VITAMINS** **3.2.1. OVERVIEW OF MICRONUTRIENTS** - - - - - - 1. 2. 3. - - - -  - - - - - - - - - **3.2.2. FAT-SOLUBLE VITAMINS -- VITAMIN A**  - 1. 2. - - - - - 3. - - - - 4. - - - - - - - - - - - - - - - - - - **3.2.3. FAT-SOLUBLE VITAMINS -- VITAMIN D** - - - +-----------------------------------+-----------------------------------+ |  | | | | | | Hypovitaminosis D: | | | | | | - - - - - | | | | | | Hypervitaminosis D: | | | | | | - - - | | +-----------------------------------+-----------------------------------+ **3.2.4. FAT-SOLUBLE VITAMINS -- VITAMIN E** - - - - - - - - - - - - - - - **3.2.5. FAT-SOLUBLE VITAMINS -- VITAMIN K** - - - - -  \[Glutamic acid residues in prothrombin → thrombin, fibrinogen → fibrin\] \[Warfarin -- good for treating thrombosis, reduce clotting\] Hypovitaminosis K: - - - - - - - - - Hypervitaminosis K: - - **3.2.6. WATER-SOLUBLE VITAMINS -- VITAMIN B** - - - - - -  \[A coenzyme is an organic compound that binds with an enzyme to catalyse a reaction. They are often vitamins, or derivatives of vitamins.\] - - - - - - - - - - - - - - - - - - - - - - - - - - - +-----------------------------------+-----------------------------------+ | - |  | | | | | | | | | | | - - - | | | | | | | | | | | | - | | +===================================+===================================+ | - | | | | | | | | | | | | - - - - - - - | | +-----------------------------------+-----------------------------------+ **3.2.7. WATER-SOLUBLE VITAMINS -- VITAMIN C** - - - - - - - - - - - - - - - - - - - - - - - **3.3. MINERALS** **3.3.1. OVERVIEW OF MINERALS**  - - - - - - **3.3.2. SODIUM, CHLORIDE, POTASSIUM** - - - - - - - - - **3.3.3. CALCIUM, MAGNESIUM, PHOSPHATE** - - - - - - - - - - +-----------------------------------+-----------------------------------+ | - - |  | | | | | - - - | | | | | | | | | | | | - - | | | | | | | | | | | | - - | | +-----------------------------------+-----------------------------------+ **3.3.4. IRON, ZINC, COPPER** - - - - - - - - - -  - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **3.4. NUTRITION-RELATED PATHOLOGIES** **3.4.1. OVERVIEW OF UNDERNUTRITION** - 1. - 2. - - - - - - - - - - - - - - **3.4.2. TYPES OF PEM** - 1. - - - - - 2. - - - - - - \[Marasmus and kwashiorkor are terms *rarely* used in hospital *practice in developed countries*\] **3.4.3. SYNDROME AND EFFECTS OF UNDERNUTRITION** - 1. - - a. - - - b. - 2. - - - 3. - - - - - - - - - - - - - - - - - - - -  **3.4.4. OVERNUTRITION AND OBESITY** - - - - - - - - - **3.4.5. EFFECTS OF OVERNUTRITION** - - - - - - - - - - - - **3.4.6. SPECIFIC DIETARY REQUIREMENTS** - - - - - - - - - - - 1. - - - - - 2. - - 3. - - - - - - - **3.4.6. PERSONALISED NUTRITION** -  A. - - - - - - B. - - - - - - - - - - - - - - - - - - - - - - **4. METABOLISM** **4.1. GLUCOSE METABOLISM** **4.1.1. COMMON STRUCTURES OF DIETARY CARBOHYDRATES** - - - - - - -  - - - - - **4.1.2. DIGESTION OF DIETARY CARBOHYDRATES** - - - - - - - - - - - - Sucrose -- 𝛼-1,2 linkage between fructose and glucose  - 1. 2. 3. 4. - - \[Trehalose: - - - - +-----------------------------------+-----------------------------------+ | - | | | | | | | | | | | | - - - | | | | | | | | | | | | - - - | | | | | | | | | | | | - - - | | +-----------------------------------+-----------------------------------+ - - - - - - - - - **4.1.3. GLUCOSE TRANSPORTERS** - -  - - - - - - - - - a. b. - - - Subjected to modulation of glucose's presence in blood -- excess amounts are removed for storage\] - - - - -  - - - - - 1. 2. 3. 1. - - - 2. - - +-----------------------------------+-----------------------------------+ | 3. | | | | | | - - - | | | | | | 1. 2. | | | | | | \[LPL, ACC, DGAT are enzymes\] | | | | | | \[Pathway on the left shows lipid | | | uptake by adipocytes\] | | +-----------------------------------+-----------------------------------+ -  - - - - - - **4.1.4. ANAEROBIC GLYCOLYSIS** - - - +-----------------------------------+-----------------------------------+ | - | | | | | | 1. | | | | | | - - - | | | | | | | | | | | | - - - | | | | | | 2. | | | | | | - - - - | | +-----------------------------------+-----------------------------------+ - - - -  - - - - **4.1.5. AEROBIC RESPIRATION**  - - - - - - 1. - - 2. - - a. b. **4.1.5. CLINICAL CONNECTIONS OF GLUCOSE METABOLISM** +-----------------------------------+-----------------------------------+ | Clinical connections: | | | | | | - - - | | | | | | Lactose intolerance: | | | | | | - - - | | +-----------------------------------+-----------------------------------+ Positron emission tomography (PET) scan: - - - - - - -  - - - - - **4.1.6. ABNORMAL GLUCOSE METABOLISM** - 1. - - - 2. - 3. - \[No insulin induction → GLUT4 go back inside cells\] -  \[Exercise alone can lead to increased GLUT4 on the cell surface independent of GLUT4 induction\] - - - - - - - - - - - - - ------------------------- ---------------------------------------------------------------------------------------------  In diabetic patient, the plasma glucose level sustains high over a prolonged period of time ------------------------- --------------------------------------------------------------------------------------------- +-----------------------------------+-----------------------------------+ | | \(IV) glucose tolerance test: | | | | | | - - - | +-----------------------------------+-----------------------------------+ - - - **4.2. LIPID METABOLISM** **4.2.1. LIPIDS** - - - - - - - - - - -  \[Arachidonic acids: 20-carbon long polyunsaturated fatty acids\] - - - - - - - - - - - - - - \[In humans, fatty acids are generally saturated or monounsaturated\] - - - - - - - - - - +-----------------------------------+-----------------------------------+ | - - - - |  | | | | | - - | | | | | | - - | | | | | | | | | | | | - - - | | +-----------------------------------+-----------------------------------+ **4.2.2. TRIACYLGLYCEROLS AND TRANSPORTED FATS** - - - - - - - - - - - - - - - -  **4.2.3. TRIACYLGLYCEROL DIGESTION AND ABSORPTION**  - - - - - - - - - - - - - - - 1. - - - - - - 2. - - - 3. - - - - 4. - - - - - - - - - - - - 5. **4.2.4. FATE OF TRIACYLGLYCEROL AND FATTY ACIDS** A. - - - - - - - - - - B. - - - - - - - - - - - - - - - - C. - - - -  - - - - - - - -  - - - - - - - - - - - - - **4.2.5. CLINICAL CONNECTIONS OF LIPID METABOLISM** - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - **4.3. AMINO ACID METABOLISM** **4.3.1. METABOLISM OF EXOGENOUS AMINO ACIDS** - - - - - - - - - - - - - - - - -  - - - - - - - - - - **4.3.2. METABOLISM OF ENDOGENOUS AMINO ACIDS** - - - - - 1. - - - - 2. - - - +-----------------------------------+-----------------------------------+ | A. |  | | | | | - - | | | | | | | | | | | | - - - - | | | | | | - | | +-----------------------------------+-----------------------------------+ - - - B.  - - - - - - - - - 1. 2. - Urea Cycle: - - - - - - - - **4.3.3. NITROGEN TRANSPORTATION BY ALANINE AND GLUTAMINE** - - - - - - - - - - - a. b. - - -  -  - - - - - - - - - \[Glutamate forms urea and 𝛼-ketoglutarate\] **4.3.4. SUMMARY** 1. 2. 3. 4. 5. 6. -  - - - - 1. - - - - - - 2. - - +-----------------------------------+-----------------------------------+ | - - - - |  | +-----------------------------------+-----------------------------------+ **4.4. SYNTHESIS OF OTHER BIOMOLECULES** - - - - - - - **4.4.1. SYNTHESIS OF NEUROTRANSMITTERS** - - - - 1. - a. - b. - c. - 2. - 3. - 4. - - - **4.4.2. SYNTHESIS OF PORPHYRINS** +-----------------------------------+-----------------------------------+ | - |  | | | | | | | | | | | - - - | | +-----------------------------------+-----------------------------------+ - 1. 2. 3. 4.  - - - - - - - - - - 1. 2. - - - - +-----------------------------------+-----------------------------------+ | - | | | | | | | | | | | | - - - - - | | | | | | | | | | | | - | | +-----------------------------------+-----------------------------------+ **4.4.2. SYNTHESIS OF NUCLEOTIDES** - - - - - 1. 2. +-----------------------------------+-----------------------------------+ | - - - - | -  | +-----------------------------------+-----------------------------------+ - - - - - - - - - A. 1. - - -  - - - -  \[Note: - - - - 2. - - - - 3. - - - - +-----------------------------------+-----------------------------------+ | Excess uric acid -- Gout: | | | | | | - - - | | | | | |  | | +-----------------------------------+-----------------------------------+ B. 1. - - - - - - - - - - - - - -  +-----------------------------------+-----------------------------------+ | - | - | | | | | | | | | | | - - - - | | +-----------------------------------+-----------------------------------+ 2. - - - 1.  2. 3. - - - - - **4.5. GENERATION OF ATP** **4.5.1. OVERVIEW OF ATP AND BIOGENETICS** - - - - - - -  - - - - - \[Case 1: Reasons: - - - - **4.5.2. THE TCA CYCLE** - - - - - - - - - -  \[Succinyl CoA → Succinate: ADP → ATP (or GDP → GTP)\] \[Isocitrate dehydrogenase is the rate limiting enzyme\] \[ADP will stimulate TCA cycle; ATP will inhibit TCA cycle; NADH will inhibit TCA cycle\] **4.5.3. OXIDATIVE PHOSPHORYLATION** - - - - - A. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. B. 1. 2. 3. 4. 5. 6. ATP yield:  **4.5.4. CLINICAL CONNECTIONS OF ATP GENERATION** A. - - - - 1. - - - 2. - - 3. - - - - - 4. - - - - - - - - - - 5. - - B. - - - - - - - C. - - - - - - \[Case 2: Reasons: - - - **4.6. SUMMARY** **4.6.1. ANABOLISM AND CATABOLISM** - - - - - - -  +-----------------------------------+-----------------------------------+ | - | | | | | | | | | | | | - - - | | | | | | \[Acetyl group is released as | | | CO~2~ during respiration\] | | +-----------------------------------+-----------------------------------+ **4.6.2. LINKAGE BETWEEN DIFFERENT METABOLIC PATHWAYS** - - - - - - - - - -  - - - - - - - - - - - - - - **4.6.3. REGULATION OF METABOLISM** - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 1. 2. - - - - - - - +-----------------------------------+-----------------------------------+ | - - - - - - - | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | - - - - - |  | | | | | | | | | | | - | | +-----------------------------------+-----------------------------------+ Other regulatory hormones: - - - - - - - - - - -  **4.7. CLINICAL RELEVANCE** **4.7.1. OVERVIEW OF SPECIFIC METABOLIC FUNCTIONS OF TISSUES** - - - - - - - - - - - - - - - - - - - **4.7.2. METABOLISM IN THE LIVER** A. - 1. 2. 3. 4. 5. B. 1. 2. 3. 4. - - 5. 6. 7. 8. 9. 10. C. 1. 2. 3. 4. 5. 6. 7. 8. - - - - - - -  Liver in the fasting state: - - - - - - **4.7.3. MORE ON FAT TISSUES** - 1. - - - 2. - - - - -  - - - - - - - - **4.7.4. METABOLISM IN MUSCLES** +-----------------------------------+-----------------------------------+ | - | | | | | | 1. | | | | | | - - | | | | | | 2. | | | | | | - - - | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | - |  | | | | | | | | | | | - - | | | | | | | | | | | | - | | | | | | | | | | | | - - - - | | +-----------------------------------+-----------------------------------+ **4.7.5. METABOLISM IN BRAIN** +-----------------------------------+-----------------------------------+ | - | | | | | | | | | | | | - - - | | | | | | | | | | | | - | | +-----------------------------------+-----------------------------------+ **4.7.6. MORE ON PROLONGED FASTING AND DIABETES** - 1. 2. 3. 4. 5. 6. 7. 8. 9.  - - - - - - - - - - - - - - - - - - - - - - - - - - - -