The rest of medicine in six hours

1. The rest of medicine in six hours Dr. Alan McLeod (F2)

2. The Plan Day One • A systematic approach • Chest Pain • Palpitations • Acute sob • Chronic sob • Haemoptysis • Painful Limb Day Two • TATT • Swallowing • Change in bowel habits • Hepatomegaly • Abdo pain • Pregnancy • Congenital abnormality • Head Injury • Emergency Management • Maximising your marks

3. I GET VINO…

4. 2 Minutes 10 Reasons to be Tired All The Time

5. TATT? Wine? For Me? Why Not?

6. Anaemia Erythrocytes • Deformable biconcave discs Each carries • 250 MILLION Hb mols • 1 billion O2 molecules

7. Anaemia – two classifications Three basic causes • Blood loss • Reduced erythrocyte production • Increased erythrocyte destruction Three basic cell sizes • Microcytic • Normocytic • Macrocytic

9. Protein Basics

10. Protein Basics

11. Protein Basics Primary Structure • Amino acid sequence Secondary Structure • Folded primary structure • Alpha helix • Beta pleated sheet Tertiary Structure • Complex of secondary structures Quaternary structure • Associated tertiary structures • e.g. Haemoglobin

12. Tissues Lungs 1.0 Fractual Concentration Myoglobin Haemoglobin 0 100 pO2 (torr)

13. Bohr effect and 2,3-BPG 100% Right Shift Easier to release O2 pH (e.g. lactic acid) pCO2 (e.g. COPD) temp (e.g. exercise) 2,3-BPG (e.g. altitude training) Left Shift Reverse of these [oxyhaemoglobin] 10kPa 0 pO2 Bohr effect: CO2pH

14. Haemoglobin is Allosteric T-Form • Bloomin’ – 2,3-BPG can bind • Tired – has no O2 R-Form • Has enough O2 to Run 2,3-BPG

15. Thallasaemia • One gene encodes the alpha globin • Two genes encode the beta globin • Beta thallasaemia minor = one gene faulty • Beta thallasaemia major = both genes faulty

16. Comparison of Inheritance Modes

17. Iron Uptake & Storage Iron is a vital element for life • Humans have no active way of excreting iron • 1-3 g stored • 80% in haemoglobin • 1 g lost / day from skin / mucosal shedding • 1 g lost / day extra in menstruation Absorbed • Duodenum + upper jejunum • Exact mech unknown • About 10% of intake • Lead toxicity reduces • Vit C increases

18. Important Molecules • Transferrin • Small • Extracellular • Transporter • Holds 1 or 2 iron • Ferritin • Large • Intracellular • Storage molecule • Up to 45,000 iron

19. CKD and EPO Erythropoietin • Glycoprotein • 10% from liver • 90% from kidneys • Renal cortex • Peritubular capillary endothelium • Responds to low O2 • Acts at bone marrow • Promotes erythrocyte production • Promotes haemoglobin synthesis • Chronic Kidney Disease • Erythropoietin  • Vitamin D  • Renin 

20. B12 and Folate Involved in • RBC production • Reduced RBC numbers • Increased size • Reduceed O2 carrying • DNA Sythesis • Tissue regeneration Pernicious Anaemia • B12 deficiency • B12 absorbed via intrinsic factor • IF produced by Parietal cells in stomach

21. B12 from food R R: Non-specific B12 binding protein IF: Intrinsic factor TC: Transcobalamin R.B12 R IF IF.B12 Parietal cells Terminal Ileum B12 TC TC Brush border TC.B12 TC.B12 IF Tissue Cell IF.B12 Blood

22. Diabetes • Pancreatic Islets • 60% beta cells • Secrete insulin • 25% alpha cells • Secrete glucagon • Reciprocal action of hormones • Not usually present together • Secretions enter pancreatic vein into portal system

23. Diabetes Type 1 • Childhood • Failure insulin prod. • Insulin dependent Type 2 • Traditionally older • Insulin resistance • Lifestyle/drugs/insulin

24. Insulin Peptide hormone • Alpha chain • Species specific • Beta chain • Biologic activity • C-peptoid joins chains

25. Packaging and Release Insulin production • Increased by glucose • Transcription • Translation • Pre-proinsulin • Signal peptide cleaved • Proinsulin • Disulphide links • Excision of C-peptide • Insulin • Packaged in Golgi into secretory granules • Insulin • C-peptide • Insulin forms hexamers • Secreted via exocytosis

26. Describe the modifications that transform proinsulin into insulin

27. Insulin ‘C’ Peptide ‘B’ Chain ‘A’ Chain S S S S S S

28. Insulin ‘C’ Peptide ‘B’ Chain ‘A’ Chain S S S S S S

29. Insulin ‘B’ Chain ‘A’ Chain S S S S S S

30. Release of Insulin • GLUT-2 admits glucose • Keeps intracellular conc same as interstitial fluid • ATP prod stimulated • ATP:ADP ratio changes • ATP binds to K+ channel • Channel closes • Cell depolarisation • Depolarisation • Opening of voltage gated Ca++ channels • Increased [Ca++] • Exocytosis • Release of insulin

31. Insulin Stimulated Glucose Uptake A B

32. Glucose Transporters

33. Functions of Insulin Anabolic • Promotes glucose uptake • Promotes use of glucose as a fuel • Promotes K+ uptake • Used to treat hyperkalaemia • Protein synthesis • Blood proteins • Muscle tissue • TAG synthesis • Glycogen synthesis • Decreased proteolysis • Decreased lipolysis • Decr. gluconeogenesis

34. Sulphonylureas Insulin Vesicle Beta Cell K+ K+ SUR1 SUR1

35. Insulin Vesicle Sulphonylurea Molecules K+ K+ SUR1 SUR1

36. Insulin Vesicle Sulphonylurea Molecules Rising K+ SUR1 SUR1

37. Insulin Vesicle Sulphonylurea Molecules Depolarisation Ca++ Ca++ Ca++ Ca++ Ca++ Ca++ SUR1 Ca++ Ca++ Ca++ SUR1 Ca++ Ca++

38. Insulin Vesicle Sulphonylurea Molecules Ca++ Ca++ Ca++ Insulin Ca++ Ca++ SUR1 Ca++ Ca++ Ca++ SUR1 Ca++ Ca++

39. Other Drugs Metformin • Unknown mechanism •  Gluconeogenesis •  Insulin sensitivity • No weight gain • Epigastric discomfort • Diarrhoea • Anorexia Glitazones • Alpha ketoglutarase inhibitor •  carbohydrate breakdown in gut • Abdominal discomfort • Diarrhoea • Flatulence

40. 2 Minutes 10 Causes of Abdo Pain

41. Phases of swallowing The nerves involved in swallowing are: • CN IX: Glossopharyngeal • CNX: Vagus • CNXII: Hypoglossal

42. Dysphagia: difficulty in swallowing By location • Inside lumen • Foreign body • Tumour • Within wall: • Stricture • Achalasia • Outside oesophagus • Lymphoma • Lung cancer By Mechanism • Motor causes: • Achalasia • Mechanical causes: • Tumour • Stricture • Foreign body • Neurological: • Bulbar palsy • Myasthenia gravis

43. Achalasia • Damage to myenteric plexus • Loss of peristalsis • Inability of lower oesophageal sphincter to relax • Barium swallow • Balloon dilatation

45. Myasthenia Gravis • Acquired autoimmune • Thymic hyperplasia 75% • Thymoma 15% • Non-thymoma • Two peaks • 10-30 yrs F>M • 60-70 yrs M>F • Thymoma • 40-50 yrs Features • Muscle weakness and fatigueability, esp: • Periocular • Facial • Bulbar • Girdle

46. Normal Signal Myasthenia Gravis Cholinergic Neurone Cholinergic Neurone Normal Response Response Blocked ACh receptor Acetylcholine Anti AChR

47. Mass movement into rectum If critical mass of stool in rectum  distension of rectal walls: Defecation sensation Defecation reflex Contraction rectum Relaxation int sphincter Contr. Ext sphincter If convenient Increased pressure in rectum  relaxation of ext sphincter + expulsion of faeces. If not convenient Override by higher centres  no relaxation of external anal sphincter Prolonged distension  reverse peristalsis Defecation

48. 2 Minutes 5 Causes of Diarrhoea 5 Causes of Constipation

49. Diarrhoea? Waiter! More Wine…

50. Change in Bowel Habit Diarrhoea • Passage of an excess volume of stool • Usually increased frequency and liquidity • May be: • Abdo / rectal pain • Urgency / incontinence • Pus / blood Treatment • Usually not antibiotics • Oral / IV rehydration • Opiates: codeine / loperamide • Pancreatic enzymes if deficient