1 / 131

Pathology of Diabetes

Presentation about 'Pathology of Diabetes'

vmshashi
Download Presentation

Pathology of Diabetes

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Pathology of Diabetes More people would learn from their mistakes if they weren't so busy denying them. -Harold J. Smith

  2. <ul><li>Molly is a 15 year old Y10 student comes to ED with her Aunty Ada, community health worker. Ada says Molly has ‘wee’ problem. </li></ul><ul><li>Molly : ‘I’m going to the toilet often to pass wee and it is sore and itchy afterwards’ </li></ul><ul><li>Problem Analysis: </li></ul><ul><ul><li>? Key points: </li></ul></ul><ul><ul><li>? Differential Diagnosis: </li></ul></ul><ul><ul><li>? Further questions: </li></ul></ul> <ul><li>Molly is a 15 year old Y10 student comes to ED with her Aunty Ada, community health worker. Ada says Molly has ‘wee’ problem. </li></ul><ul><li>Molly : ‘I’m going to the toilet often to pass wee and it is sore and itchy afterwards’ </li></ul><ul><li>Problem Analysis: </li></ul><ul><ul><li>? Key points: </li></ul></ul><ul><ul><li>? Differential Diagnosis: </li></ul></ul><ul><ul><li>? Further questions: </li></ul></ul>

  3. CPC4.3.2 – Molly. <ul><ul><li>Frequency: Passing urine every 2 – 3 hours. </li></ul></ul><ul><ul><li>Duration: ‘ long time ’ </li></ul></ul><ul><ul><li>Dysuria: terminal </li></ul></ul><ul><ul><li>Duration: one day –‘Aunty brought me here’ </li></ul></ul><ul><ul><li>Haematuria: no </li></ul></ul><ul><ul><li>Itch: all the time, ‘quite sore from scratching’ </li></ul></ul><ul><ul><li>Duration: ‘has been there on and off for long time, worse in last three days’ </li></ul></ul><ul><ul><li>Menstrual hx: menarche age 12 years; irregular K </li></ul></ul><ul><ul><li>LMP: 3/52 ago, normal K </li></ul></ul><ul><ul><li>Pelvic pain: no </li></ul></ul><ul><ul><li>Vaginal discharge: whitish </li></ul></ul><ul><ul><li>Sexual history : never been sexually active </li></ul></ul> CPC4.3.2 – Molly. <ul><ul><li>Frequency: Passing urine every 2 – 3 hours. </li></ul></ul><ul><ul><li>Duration: ‘ long time ’ </li></ul></ul><ul><ul><li>Dysuria: terminal </li></ul></ul><ul><ul><li>Duration: one day –‘Aunty brought me here’ </li></ul></ul><ul><ul><li>Haematuria: no </li></ul></ul><ul><ul><li>Itch: all the time, ‘quite sore from scratching’ </li></ul></ul><ul><ul><li>Duration: ‘has been there on and off for long time, worse in last three days’ </li></ul></ul><ul><ul><li>Menstrual hx: menarche age 12 years; irregular K </li></ul></ul><ul><ul><li>LMP: 3/52 ago, normal K </li></ul></ul><ul><ul><li>Pelvic pain: no </li></ul></ul><ul><ul><li>Vaginal discharge: whitish </li></ul></ul><ul><ul><li>Sexual history : never been sexually active </li></ul></ul>

  4. CPC4.3.2 – Molly. <ul><li>Thirst: Aunty Ada: Molly always seems to drinking ’ </li></ul><ul><li>Appetite: normal </li></ul><ul><li>Weight: Ada : ‘Since she has put on a lot of weight ’ </li></ul><ul><li>Bowels: No change/normal </li></ul><ul><li>All other systems questions : negative </li></ul><ul><li>SH Lives with Aunty Ada; mum on TI with rest of family. Doing well at school, plans to study nursing. Non smoker, no alcohol </li></ul><ul><li>PMH 2005 recurrent boils axilla + groin , settled with antibiotics; Ear infection as a young child </li></ul><ul><li>PSH nil </li></ul><ul><li>Meds nil </li></ul><ul><li>Immunisations up to date </li></ul> CPC4.3.2 – Molly. <ul><li>Thirst: Aunty Ada: Molly always seems to drinking ’ </li></ul><ul><li>Appetite: normal </li></ul><ul><li>Weight: Ada : ‘Since she has put on a lot of weight ’ </li></ul><ul><li>Bowels: No change/normal </li></ul><ul><li>All other systems questions : negative </li></ul><ul><li>SH Lives with Aunty Ada; mum on TI with rest of family. Doing well at school, plans to study nursing. Non smoker, no alcohol </li></ul><ul><li>PMH 2005 recurrent boils axilla + groin , settled with antibiotics; Ear infection as a young child </li></ul><ul><li>PSH nil </li></ul><ul><li>Meds nil </li></ul><ul><li>Immunisations up to date </li></ul>

  5. CPC4.3.2 – Molly. <ul><li>? Key points, ? DD, Pathogenesis / importance of, </li></ul><ul><ul><li>Polyuria, Polydipsia, Polyphagia? </li></ul></ul><ul><ul><li>Recurrent Infections? </li></ul></ul><ul><ul><li>Weight gain? </li></ul></ul><ul><li>DM What type? </li></ul><ul><li>How to confirm? Investigations? </li></ul><ul><li>Complications? Prognosis? </li></ul><ul><li>Management – advice / therapy ? </li></ul> CPC4.3.2 – Molly. <ul><li>? Key points, ? DD, Pathogenesis / importance of, </li></ul><ul><ul><li>Polyuria, Polydipsia, Polyphagia? </li></ul></ul><ul><ul><li>Recurrent Infections? </li></ul></ul><ul><ul><li>Weight gain? </li></ul></ul><ul><li>DM What type? </li></ul><ul><li>How to confirm? Investigations? </li></ul><ul><li>Complications? Prognosis? </li></ul><ul><li>Management – advice / therapy ? </li></ul>

  6. Diagnostic points (for DM type) ? <ul><li>On & off for long time. </li></ul><ul><li>Always drinking. </li></ul><ul><li>Put on weight. </li></ul><ul><li>Recurrent boils. </li></ul><ul><li>Mom has DM type 2 </li></ul> Diagnostic points (for DM type) ? <ul><li>On & off for long time. </li></ul><ul><li>Always drinking. </li></ul><ul><li>Put on weight. </li></ul><ul><li>Recurrent boils. </li></ul><ul><li>Mom has DM type 2 </li></ul>

  7. ?Pathogenesis: “ recurrent multisite infections” <ul><li>Associated AIDS </li></ul><ul><li>Hyperglycemia </li></ul><ul><li>Ischemia </li></ul><ul><li>Immunodeficiency </li></ul><ul><li>Multifactorial </li></ul> ?Pathogenesis: “ recurrent multisite infections” <ul><li>Associated AIDS </li></ul><ul><li>Hyperglycemia </li></ul><ul><li>Ischemia </li></ul><ul><li>Immunodeficiency </li></ul><ul><li>Multifactorial </li></ul>

  8. Miss ML: Most likely diagnosis: <ul><li>DM Type 1 </li></ul><ul><li>DM Type 2 </li></ul><ul><li>MODY 1 </li></ul><ul><li>MODY 2 </li></ul><ul><li>Gestational DM </li></ul> Miss ML: Most likely diagnosis: <ul><li>DM Type 1 </li></ul><ul><li>DM Type 2 </li></ul><ul><li>MODY 1 </li></ul><ul><li>MODY 2 </li></ul><ul><li>Gestational DM </li></ul>

  9. ?Pathogenesis: Whitish vaginal discharge. <ul><li>Proteinuria </li></ul><ul><li>Bacterial infection </li></ul><ul><li>Glycosuria </li></ul><ul><li>Trichomoniasis </li></ul><ul><li>Candidiasis </li></ul> ?Pathogenesis: Whitish vaginal discharge. <ul><li>Proteinuria </li></ul><ul><li>Bacterial infection </li></ul><ul><li>Glycosuria </li></ul><ul><li>Trichomoniasis </li></ul><ul><li>Candidiasis </li></ul>

  10. . Most likely .. What type of DM ? <ul><li>56 year male obese </li></ul><ul><li>30 year female following pregnancy </li></ul><ul><li>8 year old boy, poor growth. </li></ul><ul><li>24 year female Cushing’s sy </li></ul><ul><li>68 Year male following Ca. pancreas. </li></ul><ul><li>34 year male, extensive tuberculosis. </li></ul><ul><li>12 year old female following viral fever </li></ul><ul><li>. </li></ul><ul><li>II NIDDM </li></ul><ul><li>II GDM </li></ul><ul><li>I IDDM </li></ul><ul><li>Sec IDDM </li></ul><ul><li>Sec IDDM </li></ul><ul><li>Sec IDDM </li></ul><ul><li>I IDDM </li></ul>

  11. . In this world, Be like the tongue in the midst of the teeth, carefully, confidently & courageously going about its task, without getting bitten..! - Baba Divine Discourse on the Bhagavad Gita, 1984

  12. . “ Nothing great in the world has ever been accomplished without passion” - - CHRISTIAN FRIEDRICH HEBBEL

  13. . Pathology of Diabetes Dr. Venkatesh M. Shashidhar Assoc. Prof. & Head of Pathology

  14. . <ul><li>What is Diabetes? </li></ul><ul><li>“… .a wonderful but not very frequent affection among men, being a melting down of the flesh and limbs into urine …Life is short, offensive, and distressing, thirst unquenchable, death inevitable…” </li></ul><ul><li>-- Aretaeus of Cappadocia (AD 81-3) </li></ul><ul><li>150 AD – Aretaeus, named &quot;diabetes“ Greek word for &quot;siphon” </li></ul><ul><li>1788 – Cawley – damaged pancreas in DM. </li></ul><ul><li>1921 – Banting & Best, Insulin </li></ul>

  15. . Introduction <ul><li>Diabetes mellitus (sweet urine) </li></ul><ul><li>3% of world population, 100m. </li></ul><ul><li>Incidence increasing alarmingly (259m  2025) </li></ul><ul><li>Most Common non communicable disease. </li></ul><ul><li>High Morbidity & mortality. </li></ul><ul><li>DM shortens life span by 15 years. </li></ul><ul><li>Leading cause of blindness and Kidney dis. </li></ul><ul><li>Pacific Islands – leaders in DM & Obesity…! </li></ul><ul><li>Aus: 7 th leading cause of death, 1M.. half of whom may be unaware of their disease. </li></ul>

  16. . World Statistics:

  17. . Diabetes Mellitus - Definition <ul><li>2 nd Century, Greek physician, Aretus named Diabetes from diabainein, “to flow through or siphon & Mellitus meaning sweet/Honey . </li></ul><ul><ul><li>* insipidus  tasteless – dilute urine. </li></ul></ul><ul><li>Disorder of metabolism (Carb, Prot & Fat) </li></ul><ul><li>Absolute/Relative deficiency of insulin. </li></ul><ul><li>Characterized by hyperglycemia. </li></ul><ul><li>P olyuria, P olydypsia, P olyphagia. </li></ul>

  18. . Criteria for the Diagnosis of Diabetes <ul><li>Symptoms + unexplained weight loss </li></ul><ul><li>+ RBS > 11.1 mmol/L. OR </li></ul><ul><li>Fasting(>8h) pl.glucose > 7.0 mmol/L OR </li></ul><ul><li>2h pl.glucose > 11.1 mmol/L during an 75g oral glucose tolerance test (OGTT). </li></ul>

  19. . Pancreas Normal Anatomy:

  20. . Normal Pancreas:

  21. . Normal Pancreas: Islet of Langerhans (Endocrine Pancreas) Pancreatic acini (Exocrine Pancreas) Duct

  22. . Normal Pancreatic Islet: (ipx stain) α cells 20% (Glucagon) ß cells 70% (Insulin) δ cells (Somatostatin) pp Cells (pan prot) ß α

  23. . Blood Glucose & Hormones <ul><li>Hormones </li></ul><ul><li>Insulin </li></ul><ul><li>Glucortocoids </li></ul><ul><li>Glucagon </li></ul><ul><li>Growth Hormone </li></ul><ul><li>Epinephrine </li></ul><ul><li>Action </li></ul><ul><li> Glucose </li></ul><ul><li> Glucose </li></ul><ul><li> Glucose </li></ul><ul><li> Glucose </li></ul><ul><li> Glucose </li></ul>Maintained within 3.5-6.5 mmol/l .

  24. . Normal Insulin secretion:

  25. . Insulin - Anabolic Steroid <ul><li>Transmembrane transport of glucose (Liver, muscle & adipose tissue. Maintain metabolism: </li></ul><ul><ul><li>Skeletal Muscle glucose uptake </li></ul></ul><ul><ul><li>Adipose tissue lipolysis </li></ul></ul><ul><ul><li>Hepatic gluconeogenesis. </li></ul></ul><ul><li> glycogen &  gluconeogenesis. </li></ul><ul><li> lipolysis  Lipogenesis. </li></ul><ul><li> Protein & triglyceride synthesis </li></ul><ul><li> Nucleic acid & Protein synthesis </li></ul><ul><li>Diabetes   glucose   catabolism </li></ul>

  26. . Insulin Functions:

  27. . Cellular Glucose Uptake <ul><li>Insulin Requiring </li></ul><ul><li>Striated Muscle </li></ul><ul><li>Cardiac Muscle </li></ul><ul><li>Liver </li></ul><ul><li>Adipose Tissue </li></ul><ul><li>Glucose deficiency </li></ul><ul><li>Low glucose: </li></ul><ul><li>Liver: Gluconeogenesis </li></ul><ul><li>Adipose: Lipolysis  FFA </li></ul><ul><li>Muscle: depressed metabolism. </li></ul><ul><li>Non-Insulin Requiring </li></ul><ul><li>Blood Vessels </li></ul><ul><li>Nerves </li></ul><ul><li>Kidney </li></ul><ul><li>Eye Lens </li></ul><ul><li>Polyol damage </li></ul><ul><li>Excess glucose: </li></ul><ul><li>Glucose  Aldehyde dehydrogenase  Sorbitol </li></ul>

  28. . Diabetes Classification : (not a single disease) <ul><li>Primary DM </li></ul><ul><ul><li>Type I – IDDM / Juvenile – 10%. </li></ul></ul><ul><ul><li>Type II – NIDDM /Adult onset – 80%. </li></ul></ul><ul><ul><li>MODY – 5% Maturity Onset Diabetes of Youth </li></ul></ul><ul><ul><ul><li>Genetic, sub types MODY 1 – MODY 11, </li></ul></ul></ul><ul><ul><li>Gestational Diabetes Mellitus. </li></ul></ul><ul><ul><li>Type 1.5 – latent autoimmune DM in adults (LADA ) </li></ul></ul><ul><ul><li>Other. </li></ul></ul><ul><li>Secondary DM </li></ul><ul><ul><li>Excess hyperglycemic stimulus. </li></ul></ul><ul><ul><ul><li>Cushings, Phaeochromocytoma, acromegaly, Steroid therapy. </li></ul></ul></ul><ul><ul><li>Beta cell destruction: </li></ul></ul><ul><ul><ul><li>Pancreatitis/tumors/Hemochromatosis </li></ul></ul></ul><ul><ul><ul><li>Infectious – congenital rubella, CMV, TB, </li></ul></ul></ul><ul><ul><ul><li>Endocrinopathy, Downs Sy. </li></ul></ul></ul>

  29. . Metabolic Syndrome (X) - IDF criteria <ul><li>Central Obesity </li></ul><ul><ul><li>>90cm male, >80 fem – Asian, chinese, Jap. </li></ul></ul><ul><ul><li>>94cm male, >80 fem – Europ, Africa, Arab. </li></ul></ul><ul><li>+ Any two of the following. </li></ul><ul><ul><li>Raised triglycerides >1.7mmol/l or treat. </li></ul></ul><ul><ul><li>Reduled HDL-C <1.03mmol/l or treat. </li></ul></ul><ul><ul><li>Hypertension 130/85 or treat. </li></ul></ul><ul><ul><li>Fasting plasma glucose >5.6mmol/l or DM2. </li></ul></ul><ul><li>Australia prevalence 2005 – 30.7% </li></ul><ul><li>10 Year CVD risk - 23.4% </li></ul>

  30. . LADA: Late onset Autoimmune DM <ul><li>Features of both type 1 and type 2. Younger, Rapid onset & progression to insulin dependency. Immune markers like type 1 diabetes, may lack ketoacidosis symptoms. </li></ul><ul><li>Incidence: - 6-10% (UK). </li></ul><ul><li>Diagnosis: Elevated pancreatic autoantibodies </li></ul><ul><li>Risk factors: Metabolic Syndrome </li></ul><ul><li>LADA + Metabolic syndrome = DM Type 1.5. </li></ul><ul><li>Complications of both type 1 & 2. (metabolic, Macro & Microangiopathy etc). </li></ul>

  31. . Your life should rest on morality and truth. Base your life on truth & love for all. - Sai - Summer Showers, 1973 Money and goes but morality comes and grows.

  32. . Pathogenesis of Type I DM Genetic HLA-DR3/4 Environment Viral infe..? Insulin deficiency Autoimmune Insulitis Ab to ß cells/insulin ß cell Destruction <ul><li>Other Autoimmune disorders: </li></ul><ul><li>PS Glomerulonephritis </li></ul><ul><li>Graves, Hashimoto thyroiditis. </li></ul><ul><li>Rheumatic heart disease </li></ul><ul><li>SLE, Collagen vascular disease </li></ul><ul><li>Rheumatoid arthritis. </li></ul>Secondary DM Inflammation, Tumor, Infection Trauma Pancreatitis Antibodies: Islet cell Ab - ICA Insulin Auto Ab - IAA Glut. Acid Decarb - GAD65

  33. . Insulitis – Type I Lymphocytes.

  34. . DM1 Course:

  35. . Progression of Type II Years ..

  36. . Pathogenesis of Type II DM Relative Insulin Def. ß cell Exhaustion (IDDM)

  37. . DM2 Islets: Normal early  amyloid late:  Normal. Loss of ß cells ( only in late stage ) replaced by Amyloid protein deposit (hyalinization).

  38. . Type-I Type-II <ul><li>Less common (10%) </li></ul><ul><li>Children < 25 Years </li></ul><ul><li>Insulin- Dependent </li></ul><ul><li>Duration: Weeks </li></ul><ul><li>Acute Metabolic complications </li></ul><ul><li>Autoantibody: Yes </li></ul><ul><li>Family History: No </li></ul><ul><li>Insulin levels: low </li></ul><ul><li>Islets: Insulitis </li></ul><ul><li>50% in twins </li></ul><ul><li>More common (90%) </li></ul><ul><li>Adult >25 Years </li></ul><ul><li>NIDDM* </li></ul><ul><li>Months to years </li></ul><ul><li>Chronic Vascular complications. </li></ul><ul><li>No </li></ul><ul><li>Yes </li></ul><ul><li>Normal or high * </li></ul><ul><li>Normal / Exhaustion </li></ul><ul><li>~100% in twins </li></ul>

  39. . Type-I Type-II Insulitis: Lymphocytic infiltrate within islets. Islet Hyalinization: Central hyaline deposits replacing dead beta cells

  40. . Diagnosis: (WHO)

  41. . New in DM: Incretins. <ul><li>Incretin harmones by enteroendocrine cells of intestine in response to glucose. </li></ul><ul><ul><li>G lucagon- l ike p eptide-1 (GLP-1) </li></ul></ul><ul><ul><li>G lucose-dependent I nsulinotropic P olypeptide (GIP) </li></ul></ul><ul><li>Inhibit α cells, stimulate β cells  Insulin. </li></ul><ul><li>Destroyed by dipeptidyl peptidase (DPP). </li></ul><ul><li>Dysregulation of these in DM2. </li></ul><ul><li>Two new drugs, exenatide (GLP-1 mimetic) and sitagliptin [DPP 4 inhibitor] – Approved for PBS. </li></ul><ul><li>Medscape online video: </li></ul><ul><li>http://www.medscape.com/infosite/dia/article-3 </li></ul>

  42. . Being true human is maintaining complete harmony between thought, word and deed. Divergence between thought, word and deed is the cause of all our problems…! - BABA.

  43. . DM Complications: <ul><li>Glucose is highly reactive - damages tissues. </li></ul><ul><li>Glucose absorption, storage & use – Timely Insulin release - critical. </li></ul><ul><li>Diabetes is state of insulin deficiency. </li></ul><ul><li>Absolute/Delayed/inappropriate insulin response </li></ul><ul><li>Glucose excess – Hyperglycemia. </li></ul><ul><li>Neo-glucogenesis – Proteolysis, lipolysis </li></ul><ul><li>Clinical symptoms & signs are mainly due to complications. </li></ul><ul><li>Complications: </li></ul><ul><ul><li>Acute Metabolic & Chronic Vascular. </li></ul></ul><ul><ul><li>Damage to BV, Kidney, CNS & immune system. </li></ul></ul>

  44. . Diabetes Complications: <ul><li>Short term Complications: (metabolic) </li></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><li>Diabetic Ketoacidosis </li></ul></ul><ul><ul><li>Non Ketotic hyperosmolar diabetic coma </li></ul></ul><ul><ul><li>Lactic acidosis </li></ul></ul><ul><li>Long term Complications : (Angiopathy) </li></ul><ul><ul><li>Microngiopathy - Retinopathy, Nephropathy, Neurophathy, dermatopathy. </li></ul></ul><ul><ul><li>Macroangiopathy – Atherosclerosis. </li></ul></ul>

  45. . Pathogenesis of complications: <ul><li>Insulin dependant tissue: </li></ul><ul><li>Skeletal muscle, adipose tissue </li></ul><ul><li>Low glucose inside cell </li></ul><ul><ul><li>decreased cell metabolism </li></ul></ul><ul><li>High glucose outside </li></ul><ul><ul><li>Glycosylation damage (AGE) - * </li></ul></ul><ul><li>Insulin independent tissue: </li></ul><ul><ul><li>BV, nerve, (kidney, eye, CNS) </li></ul></ul><ul><ul><li>Excess glucose  Polyol  osmotic damage* </li></ul></ul>

  46. 47. DM: Complications:

  47. 48. The best gift of Nature to man is the briefness of his life…! Latin quote

  48. 49. Microangiopathy Pathogenesis: <ul><li>Hyperglycemia chronic. </li></ul><ul><li>Glycosylation of basement membrane proteins  Leaky blood vessels. </li></ul><ul><li>Excess deposition of proteins – glycosylation cycle. </li></ul><ul><li>Thick and Leaky blood vessels. </li></ul><ul><li>Narrow lumen </li></ul><ul><li>Ischemic Organ damage... </li></ul>

  49. 50. Diabetic Microangiopathy Normal Diabetic <ul><li>Glucose </li></ul><ul><li>Glycosylation </li></ul><ul><li>BM damage leak </li></ul><ul><li>‘ AGE’ deposition </li></ul>

  50. 51. Neuropathy <ul><li>Sensory  Motor (myelin) </li></ul><ul><li>Peripheral Neuropathy </li></ul><ul><ul><li>Bilateral, symmetric </li></ul></ul><ul><ul><li>Progressive, irreversible </li></ul></ul><ul><ul><li>Paraesthesia, pain, muscle atrophy </li></ul></ul><ul><li>Visceral neuropathy </li></ul><ul><ul><li>Cranial nerve – diplopia, Bells palsy </li></ul></ul><ul><ul><li>GIT- constipation, diarrhoea </li></ul></ul><ul><ul><li>CVS – orthostatic hypotension </li></ul></ul>

More Related