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Pathology lectures for 4th year medical students on Diabetes

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Pathology of Diabetes


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    pathology of diabetes

    Pathology of Diabetes

    Always do your best. What you plant now, you will harvest later.- - OgMandino<br />

    cpc 3 2 ms ml 18y thrush br recurrent thrush

    CPC 3.2: Ms. ML, 18y, Thrush.<br />Recurrent thrush*, boils*, tired*, <br />Obese*, junk food, no exercise*, <br />polyuria, polydipsia* , Abd. Striae*, <br />Mom DM2*, smoker, social drinker.<br />Dipstick: Nitrate +, WCC 3+, Blood 2+, Prot. 2+, Glucose 2+ <br />MSU: Ecoli >108, swab: Candida 4+, RBGL 35.<br />? Key points: <br />? Differential Diagnosis: Thrush, UTI, STI, Pregn, DM<br />? Further questions:<br /> CPC 3.2: Ms. ML, 18y, Thrush.<br />Recurrent thrush*, boils*, tired*, <br />Obese*, junk food, no exercise*, <br />polyuria, polydipsia* , Abd. Striae*, <br />Mom DM2*, smoker, social drinker.<br />Dipstick: Nitrate +, WCC 3+, Blood 2+, Prot. 2+, Glucose 2+ <br />MSU: Ecoli >108, swab: Candida 4+, RBGL 35.<br />? Key points: <br />? Differential Diagnosis: Thrush, UTI, STI, Pregn, DM<br />? Further questions:<br />

    cpc 3 1 molly 15y wee problem br molly

    CPC 3.1: Molly 15y.. Wee problem.<br />Molly is a 15 year old Y10 student comes to ED with her Aunty Ada, community health worker. Ada says Molly has ‘wee’ problem.<br />Molly : ‘I’m going to the toilet often to pass wee and it is sore and itchy afterwards’<br />? Key points: <br />? Differential Diagnosis: <br />? Further questions<br />? DM type <br />? How to confirm Investigations?<br />? Complications Prognosis? <br />? Management<br /> CPC 3.1: Molly 15y.. Wee problem.<br />Molly is a 15 year old Y10 student comes to ED with her Aunty Ada, community health worker. Ada says Molly has ‘wee’ problem.<br />Molly : ‘I’m going to the toilet often to pass wee and it is sore and itchy afterwards’<br />? Key points: <br />? Differential Diagnosis: <br />? Further questions<br />? DM type <br />? How to confirm Investigations?<br />? Complications Prognosis? <br />? Management<br />

    pathogenesis recurrent multisite infections

    ?Pathogenesis: “recurrent multisite infections”<br />Associated AIDS<br />Hyperglycemia<br />Ischemia<br />Immunodeficiency<br />Multifactorial<br /> ?Pathogenesis: “recurrent multisite infections”<br />Associated AIDS<br />Hyperglycemia<br />Ischemia<br />Immunodeficiency<br />Multifactorial<br />

    specific features for diagnosis

    Specific features for diagnosis of DM2?<br />On & off for long time.<br />Always drinking.<br />Obesity.<br />Recurrent boils.<br />Mom has DM2<br /> Specific features for diagnosis of DM2?<br />On & off for long time.<br />Always drinking.<br />Obesity.<br />Recurrent boils.<br />Mom has DM2<br />

    miss ml most likely diagnosis br dm type

    Miss ML: Most likely diagnosis:<br />DM Type 1<br />DM Type 2<br />MODY 1<br />MODY 2<br />LADA<br /> Miss ML: Most likely diagnosis:<br />DM Type 1<br />DM Type 2<br />MODY 1<br />MODY 2<br />LADA<br />

    pathogenesis whitish vaginal discharge

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

    nothing great in the world has ever been

    “Nothing great in the world has ever been accomplished without passion”<br />- - CHRISTIAN FRIEDRICH HEBBEL<br /> “Nothing great in the world has ever been accomplished without passion”<br />- - CHRISTIAN FRIEDRICH HEBBEL<br />

    most likely what type of dm br 56 year male obese

    Most likely .. What type of DM ? <br />56 year male obese<br />30 year female following pregnancy<br />8 year old boy, poor growth, DKA.<br />24 year female Cushing’s sy<br />68 Year male following Ca. pancreas.<br />32 male, DM, BMI 18, Anti-GAD +ve.<br />34 year male, extensive tuberculosis.<br />12 year old female following viral fever<br />41y DM2, BMI 17.1, HbA1c 14.1, DKA<br />15y male, BMI 16.2, recurrent infect.<br />II NIDDM<br />II GDM<br />I IDDM<br />Sec IDDM<br />Sec IDDM<br />I LADA<br />Sec IDDM<br />I IDDM<br />LADA<br />MODY<br /> Most likely .. What type of DM ? <br />56 year male obese<br />30 year female following pregnancy<br />8 year old boy, poor growth, DKA.<br />24 year female Cushing’s sy<br />68 Year male following Ca. pancreas.<br />32 male, DM, BMI 18, Anti-GAD +ve.<br />34 year male, extensive tuberculosis.<br />12 year old female following viral fever<br />41y DM2, BMI 17.1, HbA1c 14.1, DKA<br />15y male, BMI 16.2, recurrent infect.<br />II NIDDM<br />II GDM<br />I IDDM<br />Sec IDDM<br />Sec IDDM<br />I LADA<br />Sec IDDM<br />I IDDM<br />LADA<br />MODY<br />

    the foundation of lasting self confidence

    . The foundation of lasting self-confidence and self esteem is excellence, mastery of your work.- Brian Tracy<br />

    pathology of diabetes br dr venkatesh

    . Pathology of Diabetes<br />Dr. Venkatesh M. Shashidhar<br />Assoc. Prof. & Head of Pathology<br />

    what is diabetes br a wonderful but not very

    . What is Diabetes?<br />“….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…”<br />-- Aretaeus of Cappadocia (AD 81-3)<br /><ul><li>150 AD – Aretaeus, named "diabetes“ Greek word for "siphon”

    1921 banting best insulin

    . 1921 – Banting & Best, Insulin</li></li></ul><li>Introduction<br />Diabetes mellitus (sweet urine)<br />3% of world population, 100m.<br />Incidence increasing alarmingly (259m 2025)<br />Most Common non communicable disease.<br />High Morbidity & mortality.<br />DM shortens life span by 15 years. <br />Leading cause of blindness and Kidney dis.<br />Pacific Islands – leaders in DM & Obesity…!<br />Aus: 7th leading cause of death, 1M.. half of whom may be unaware of their disease.<br />

    diabetes mellitus definition br 2nd century greek

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

    criteria for the diagnosis of diabetes

    . Criteria for the Diagnosis of Diabetes<br />A random blood glucose concentration of 11mmol/L or higher, with classical signs and symptoms. or<br />A fasting glucose concentration of 7mmol/L or higher on more than one occasion. or<br />An abnormal oral glucose tolerance test (OGTT, done for borderline 5.5-6.9 mmol/L ), in which the glucose concentration is >11mmol/L at 2 hours after a standard carbohydrate load (75 gm of glucose).<br />

    normal pancreas br duct br islet of langerhans

    . Normal Pancreas:<br />Duct<br /> Islet of Langerhans (Endocrine Pancreas)<br />Pancreatic acini (Exocrine Pancreas)<br />

    normal pancreatic islet ipx stain br br br cells

    . Normal Pancreatic Islet: (ipx stain)<br />ß<br />α<br />αcells 20%(Glucagon) ß cells 70%(Insulin)<br />Other Cells in Islets: δ cells - Somatostatin<br /> PP Cells - pancreatic polypeptide<br />D1 cells – Vasoactive Intestinal Polypeptide<br />Enterochromaffin – Seratonin.<br />

    blood glucose hormones br hormones br insulin

    . Blood Glucose & Hormones<br />Hormones<br />Insulin<br />Glucortocoids<br />Glucagon<br />Growth Hormone<br />Epinephrine<br />Action<br /> Glucose<br /> Glucose<br /> Glucose<br /> Glucose<br /> Glucose<br />Maintained within 3.5-5.5mmol/l. <br />

    insulin anabolic steroid br transmembrane

    . Insulin - Anabolic Steroid<br />Transmembrane transport of glucose (Liver, muscle & adipose tissue. Maintain metabolism: <br />Striated Muscle glucose uptake<br />Adipose tissue lipogenesis<br />Hepatic gluconeogenesis. <br /> glycogen & gluco-neogenesis.<br /> lipolysis  Lipogenesis.<br /> Protein & triglyceride synthesis<br /> Nucleic acid & Protein synthesis<br />In DM  Insulin   glucose &  catabolism<br />

    insulinanabolic steroidglut4 br only these tissue

    . InsulinAnabolic SteroidGLUT4*<br />only these tissue….!<br />

    dm2 pathogenesis 3 mechanism br non insulin

    . DM2: Pathogenesis – 3 mechanism.<br />Non-Insulin Requiring Cells<br />Blood Vessels<br />Nerves & Brain<br />Kidney, Eye Lens<br />Intracellular Hyperglycemia<br />Glucose polymers “Polyol” damage<br />Excess glucose:<br />Glucose  Aldosereductase Sorbitol (Polyol)  Osmotic cell swelling and dysfunction.<br />Insulin Requiring Cells<br />Striated Muscle<br />Liver<br />Adipose Tissue<br />Intra cellular hypoglycemia<br />Low glucose:<br />Liver: Gluconeogenesis<br />Adipose: Lipolysis  FFA<br />Extracellular hyperglycemia<br />Vascular & tissue damage…*<br />

    dm2 pathogenesis br liver skeletal muscle insulin

    . DM2: Pathogenesis<br />Liver & skeletal muscle insulin resistance<br />β-cell hypersecretion β-cell failure<br />Lipotoxicity<br />decreased incretin secretion<br />increased glucagon secretion<br />increased renal glucose re-absorption<br />appetite dysregulation<br />

    new in dm pathogenesis incretins br insulin

    . New in DM Pathogenesis: Incretins.<br />Insulin release through Incretins (from intestine) in response to glucose intake. <br />Glucagon-like Peptide-1 (GLP-1) <br />Glucose-dependent InsulinotropicPolypeptide (GIP)<br />stimulate βcells (Insulin) & Inhibit α (glucagon)<br />Destroyed by dipeptidyl peptidase (DPP).<br />Dysregulation in DM2 (early breakdown).<br />Two new drugs, exenatide (GLP-1 mimetic) and sitagliptin [DPP 4 inhibitor] – Approved for PBS.<br />http://www.medscape.com/infosite/dia/article-3<br />http://video.medscape.com/pi/editorial/cmecircle/2004/3418/flash/beaser/index.html<br />

    diabetes classification not a single disease

    . Diabetes Classification: (not a single disease)<br />Primary DM<br />Type I – IDDM / Juvenile – 5-10%.<br />Type II – NIDDM /Adult onset – 90-95%.<br />MODY – 5% Maturity Onset Diabetes of Youth<br />Genetic, sub types MODY 1–6,<br />LADA – Latent Autoimmune Diabetes in Adults (LADA)<br />Gestational Diabetes Mellitus.<br />Other.<br />Secondary DM<br />Excess hyperglycemic stimulus.<br />Cushings, Phaeochromocytoma, acromegaly, Steroid therapy.<br />Beta cell destruction:<br />Pancreatitis/tumors/Hemochromatosis<br />Infectious – congenital rubella, CMV, TB, <br />Endocrinopathy, Downs Sy.<br />

    metabolic syndrome x idf criteria br central

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

    lada late onset autoimmune dm br features of both

    . LADA: Late onset Autoimmune DM<br />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. <br />Incidence: - 6-10% (UK). <br />Diagnosis: Elevated pancreatic autoantibodies<br />Risk factors: Metabolic Syndrome <br />LADA + Metabolic syndrome = DM Type 1.5.<br />Complications of both type 1 & 2. (metabolic, Macro & Microangiopathy etc).<br />

    mody maturity onset diabetes of young

    . MODY: Maturity Onset Diabetes of Young.<br />5% of DM, Young*, non obese, insulin release defect*<br />Like DM2, non-ketotichyperglycemia, no DM Antibodies.<br />Auto. Dom. - Monogenic – Genetic testing*.<br />Treatment is specific to type. Unline type 1 or 2 <br />Also known as Type 1.5 (MODY + LADA)<br />Subtypes: 1,2,3,4,5,6 – type 3 & 2 common.<br />1,3,4,5,6 – Insulin transcription defect  HNF.<br />Type 2 – Enzyme glucokinase, defective β cell response.<br />

    one machine can do the work of fifty ordinary

    . One machine can do the work of fifty ordinary men. No machine can do the work of one extraordinary man.- - Elbert Hubbard<br />

    pathogenesis of type i dm br other autoimmune

    . Pathogenesis of Type I DM<br />Other Autoimmune disorders:<br /><ul><li>PS Glomerulonephritis

    rheumatoid arthritis li ul insulin deficiency

    . Rheumatoid arthritis.</li></ul>Insulin deficiency<br />ß cell <br />Destruction<br />Antibodies:<br />Islet cell Ab - ICA<br />Insulin Auto Ab - IAA<br />Glut. Acid Decarb - GAD65<br />Autoimmune Insulitis<br />Ab to ß cells/insulin <br />Secondary DM<br />Inflammation, <br />Tumor, <br />Infection<br />Trauma<br />Pancreatitis<br />Environment<br />Viral infe..?<br />Genetic <br />HLA-DR3/4<br />

    relative br insulin def br pathogenesis of type

    . Relative <br />Insulin Def.<br />Pathogenesis of Type II DM<br />ß cell <br />Exhaustion<br />(IDDM)<br />

    dm2 islets normal early amyloid late br normal

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

    type i type ii br less common 10 br children

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

    type i type ii br insulitis br lymphocytic

    . Type-I Type-II<br />Insulitis:<br />Lymphocytic infiltrate within islets.<br />Islet Hyalinization:<br />Central hyaline deposits replacing dead beta cells<br />(only in late stage…!)<br />

    being a good human is maintaining complete

    . Being a good human is maintaining complete harmony between thought, word and deed. Divergence between thought, word and deed is the cause of all our problems…!- BABA.<br />

    dm complications br glucose is highly reactive

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

    diabetes complications br short term

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

    pathogenesis of complications br insulin

    . Pathogenesis of complications:<br />Insulin dependant tissue:<br /> Striated muscle, adipose tissue & Liver.<br />Low glucose inside cell <br />decreased cell metabolism.<br />High glucose outside <br />Glycosylation damage (AGE), cross linking, trap plasma proteins, LDL, cholesterol, - *<br />Insulin independent tissue:<br />BV, nerve, (kidney, eye, CNS)<br />Excess glucose  Sorbitol, Polyol osmotic damage*<br />Excess glucose  Diacylglycerol (DAG)Activation of Protein Kinase C  angiogenesis, BM matrix.<br />

    the best gift of nature to man is the briefness

    . The best gift of Nature to man is the briefness of his life…!Latin quote<br />

    microangiopathy pathogenesis br ul li chronic

    . Microangiopathy Pathogenesis:<br /><ul><li>Chronic Hyperglycemia.

    glycosylation of basement membrane proteins leaky

    . Glycosylation of basement membrane proteins  Leaky blood vessels.

    atherosclerosis li li ul li diabetic

    . Atherosclerosis.</li></li></ul><li>Diabetic Microangiopathy<br />Normal<br /><ul><li>Glucose

    neuropathy br sensory motor myelin br peripheral

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

    dm neuropathy myelin stain br myelin loss

    . DM-Neuropathy – Myelin stain<br />Myelin loss in nerve<br />Normal<br />

    neuropathic ulcer br etiology br ul li peripheral

    . Neuropathic ulcer<br />Etiology:<br /><ul><li>peripheral sensory neuropathy, Trauma & deformity.</li></ul>Factors:<br /><ul><li>Ischemia, callus formation, and edema.</li></li></ul><li>Neuropathic ulcers<br />FEATURES:<br />Painless, surrounded by callus <br />At pressure points. <br />associated with good foot pulses<br />May not be associated with gangrene<br />

    nephropathy br nodular glomerulo sclerosis

    . Nephropathy<br />Nodular Glomerulo Sclerosis.<br />Common morbidity & mortality.<br />Deposition of ‘AGE’ Advanced Glycosylation End-products as nodules.<br />Nephrotic syndrome<br />Pyelonephritis<br />End stage renal failure<br />

    diabetic nephropathy br microangiopathy

    . Diabetic Nephropathy<br />Microangiopathy, atherosclerosis & infections:<br />Diffuse or nodular diabetic glomerulosclerosis (Kimmelstiel Wilson Sy)<br />Renal arteriolosclerosis & atherosclerosis<br />Necrotizing renal papillitis.<br />Pyelonephritis.<br />End stage kidney.<br />

    diabetic glomerulosclerosis

    . Diabetic Glomerulosclerosis<br />A<br />B<br />A: Nodular glomerulosclerosis. <br />B: Hyaline Arteriolosclerosis. <br /> What is the pathogenesis?<br />

    dm kidney advanced kw lesion br a br b br

    . DM Kidney: advanced (KW Lesion)<br />A<br />B<br />

    dm kidney thickening

    . DM Kidney: thickening of BM (PCT)<br />DCT<br />PCT<br />PCT: Proximal Convoluted Tubule, DCT: Distal Convoluted Tubule<br />

    dm with infarction br papillary necrosis br

    . DM with Infarction:<br />Papillary necrosis<br />

    retinopathy br non proliferative

    . Retinopathy:<br />Non Proliferative<br />Microaneurysms, <br />Dots & blots<br />Hard and soft exudates<br />Cotton wool – infarcts<br />Macular edema.<br />Proliferative.<br />Neovascularization<br />Large hemorrhages<br />Retinal detachment.<br />

    non proliferative retinopathy br venous dilation

    . Non Proliferative Retinopathy<br />Venous dilation and small red dots posterior retinal pole - capillary micro-aneurysms.<br />Dot and blot retinal hemorrhages and deep-lying edema and lipid exudates impair macular function. <br />Cotton-wool spots (soft exudates) - microinfarcts due to ischemia. They are white and obscure underlying vessels. Hardexudates are caused by chronic edema. They are yellow and generally deep to retinal vessels.<br />Late generalized diminution of vision due to ischemia and macular edema - common cause of visual defect (best detected by fluorescein angiography)<br />

    proliferative retinopathy br neovascularization

    . Proliferative Retinopathy<br />Neovascularization – new capillaries grow into the vitreous cavity. <br />hemorrhages may lead to sudden severe loss of vision. <br />In advanced disease, neovascular membranes can occur, resulting in a traction & retinal detachment. Leading to permanent blindness. <br />Panretinal photocoagulation may diminish or eliminate proliferative retinopathy <br />

    diabetic retinopathy br fluorescein angiogram

    . Diabetic Retinopathy<br />Fluorescein angiogram of the eye of a diabetic patient. Note the numerous, small, dot-like capillary microaneurysms.<br />

    diabetic retinopathy br pre retinal hemorrhage

    . Diabetic Retinopathy<br />Pre retinal Hemorrhage - detachment<br />

    you must learn to distinguish between good

    . You must learn to distinguish between good and bad, truth and untruth. You must use your education for the purpose of serving community. - Sai - Summer Showers, 1973.<br />

    macroangiopathy atherosclerosis br dyslipidemia

    . Macroangiopathy Atherosclerosis<br />Dyslipidemia<br /> HDL<br />Non-Enzymatic Glycosylation<br /> Platelet Adhesiveness<br /> Thromboxane A2<br /> Prostacyclin<br />Endothelial damage  Atherosclerosis<br />MI, CVA, Gangrene of Leg (PVD), Renal Insufficiency<br />

    blood vessel calcification br in digital arteries

    . Blood vessel calcification:<br />In digital arteries in DM<br />Amputated Toe<br />Calcified BV<br />

    cataract sorbitol polyol osmotic br lens

    . Cataract – Sorbitol.. Polyol..osmotic..<br />Lens epithelium (Insulin independent) is exposed to Hyperglycaemia, excessive flux of glucose to sorbitol by the polyol pathway. The accumulation of intracellular sorbitol exerts osmoprotection and prevents cell shrinkage. The excessive accumulation of sorbitol, causes an increased osmotic load within the lens causing swelling, fibre breakdown, and opacification (the osmotic hypothesis). Other mechanisms, including glycation and oxidative stress, may also be responsible for lens opacification. <br />

    acanthosis nigricans br ul li insulin resistance

    . Acanthosis Nigricans<br /><ul><li>Insulin resistance…</li></li></ul><li>ComplicationsSummary:<br />

    pathogenesis of infections

    . Pathogenesis of Infections in DM:<br />Multifactorial:<br />Impaired inflammation – BV thickening – <br />Decreased immune function: WBC, chemical mediator glycosylation.<br />Glycosylation of immune mediators. Abs.<br />Tissue damage: Ischemia & infarctions.<br />Decreased metabolism – low immunity.<br />Increased glucose (alone is not the cause*) <br />

    laboratory diagnosis br urine glucose dip stick

    . Laboratory Diagnosis:<br />Urine glucose - dip-stick –Screening<br />Fasting > 7mmol, Random >11mmol<br />If Fasting level is 5.5 to 7  OGTT<br />HbA1c - for follow-up, not for diagnosis<br />Fructosamine – similar to HbA1c - long term maintenance.<br />Antibodies – Type-1<br />Gene testing: MODY<br />

    it s not that i m so smart it s just that i stay

    . “It's not that I'm so smart, it's just that I stay with problems longer”…!<br />--Albert Einstein<br />

    cpc 3 2 end dm2 br pathology major core learning

    . CPC-3.2– END–DM2<br />Pathology – Major Core Learning Issues: <br />Pathology of Diabetes Overview & Classification. Pathological basis of clinical features. <br />Details of Type 1 & 2 (Etiology, pathogenesis, morphology, clinical features) <br />Complications of Diabetes: Micro & Macroangiopathy. Retinopathy, nephropathy, neuropathy, dermatopathy.. etc.. & <br />Metabolic complications (ketoacidosis, coma etc) <br />Laboratory diagnosis of diabetes. (GTT, HBA1c,  etc)<br />Pathology – Minor CLI: <br />Metabolic Syndrome (Syndrome X). <br />MODY, LADA, Gestational, childhood type 2, <br />Secondary diabetes, Bronze diabetes.<br />Hyperglycemia Syndromes: Cushings, drugs, etc.<br />Hypoglycemia syndromes, Insulinoma. <br />New research & developments<br />

    case 1 br a 29y woman bmi 33 kg m2 complains

    . Case 1<br />A 29y woman BMI = 33 kg/m2. complains of declining visual acuity since 6 months. Fundoscopic examination shows peripheral retinal microaneurysms. Urinalysis reveals 3+ proteinuria and 3+ glucosuria. Serum albumin is low & cholesterol is high. <br />These clinicopathologic findings are best explained by which of the following pathologic mechanisms of disease <br />

    0 pathologic mechanism br anti insulin antibodies

    0. Pathologic mechanism?<br />Anti-insulin antibodies.<br />Increased insulin uptake.<br />Irregular insulin secretion.<br />Peripheral insulin resistance.<br />Serum Anti GAD-67 antibodies.<br />

    1 dm pancreatic islet feature shown by arrow

    1. DM– Pancreatic Islet- ? Feature shown by arrow?<br />Β cell exhaution.<br />Amyloid deposits<br />Lymphocytic Insulitis<br />Pancreatic acinus<br />Chronic Pancreatitis<br />

    2 50y male dm2 kidney biopsy likely nature

    2. 50y, male DM2, kidney biopsy. Likely nature of feature shown by arrow?<br />Amyloid protein.<br />AGE protein<br />Basement mem protein.<br />Fibrinoid necrosis.<br />Inflammatory cells.<br />

    3 47y f dm2 foot ulcer diagnosis br fungal

    3. 47y F, DM2 - foot ulcer: ? Diagnosis<br />Fungal infection<br />Neuropathic ulcer<br />Venous ulcer<br />Arterial ulcer<br />Atypical TB in AIDS<br />

    4 thickening of small bv in this patient is most

    4. Thickening of small BV in this patient is most likely related which pathologic mechansim?<br />Glycosylation of hemoglobin.<br />Inadequate inflammtion resp.<br />Insulin resistance in tissues.<br />Increased Atherosclersis.<br />Microvascular disease.<br />

    5 57y m dm2 gross kidney arrow feature br benign

    5. 57y M, DM2: Gross Kidney- arrow ? feature<br />Benign nephrosclerosis.<br />Glomerulonephritis<br />Papillary necrosis<br />Nodular glomerulosclerosis<br />Renal artery Atherosclerosis<br />

    6 dm pancreatic islet feature shown by arrow

    6. DM– Pancreatic Islet- ? Feature shown by arrow?<br />Β cell exhaution.<br />Amyloid deposits<br />Lymphocytic Insulitis<br />Pancreatic acinus<br />Chronic Pancreatitis<br />

    7 47y f dm2 kidney arrow feature br nodular

    7. 47y F, DM2 – Kidney- arrow ? feature<br />Nodular glomerulosclerosis.<br />Artereolosclerosis<br />Atherosclerosis<br />AGE deposition<br />Diffuse glomerulosclerosis<br />

    8 dm kidney microscopy feature arrow b br nodular

    8. DM Kidney.Microscopy. ? Feature Arrow B<br />Nodular sclerosis<br />Artereolosclerosis<br />Diffuse sclerosis<br />Pyelonephritis<br />Abscess formation<br />A<br />B<br />

    9 dm kidney microscopy feature arrow a br nodular

    9. DM Kidney.Microscopy. ? Feature Arrow A<br />Nodular sclerosis<br />Artereolosclerosis<br />Diffuse sclerosis<br />Pyelonephritis<br />Abscess formation<br />A<br />B<br />

    0 57y m dm2 kidney arrow feature

    0. 57y M, DM2 – Kidney- arrow ? feature<br />Dot hemorrhage<br />Hard exudate<br />Soft cotton wool exudate<br />Neovascularization<br />Micro Aneurysm<br />

    1 57y m dm2 eye pathogenesis br age deposition

    1. 57y M, DM2 – Eye ? Pathogenesis<br />AGE deposition<br />Glycosylation<br />Collagen deposition<br />Osmotic Polyol damage<br />Artereolosclerosis<br />

    2 47y f dm2 foot ulcer diagnosis br fungal

    2. 47y F, DM2 - foot ulcer: ? Diagnosis<br />Fungal infection<br />Neuropathic ulcer<br />Venous ulcer<br />Arterial ulcer<br />Atypical TB in AIDS<br />

    3 56y fem anterior wall mi 3 proteinuria

    3. 56y Fem, Anterior wall MI. 3+ proteinuria & FBG 19mmol/L. Image shows her pancreas. What complication she may develop?<br />Gall stones.<br />Chronic pancreatitis.<br />Uric acid stones.<br />Gangrene of foot.<br />Pancreatic carcinoma<br />

    4 a 65y man bmi 40 peripheral neuropathy

    4. A 65y man, BMI 40, peripheral neuropathy, retinopathy and abdominal aortic aneurysm is now developing renal failure. His FBS is 18.3 mmol/L, microscopic examination of his renal biopsy. What is the microscopic feature shown?<br />Renal papillary necrosis.<br />Nodular glomerulosclerosis.<br />Hyaline artereolosclerosis.<br />Atrophy + Amyloid deposition.<br />Diffuse glomerular sclerosis.<br />What is the chemical nature of nodular deposit within glomerulus?<br />Briefly describe steps in the Pathogenesis of nodular glomerulosclerosis?<br />What other renal pathology are commonly seen in diabetic patients?<br />

    5 a 47 year old man hypertensive dm2 since

    5. A 47 year old man, Hypertensive & DM2 since 6 years for checkup. Complains of his vision as spectacles recently made does not seem to help. Image shows his fundoscopy. What is the most likely diagnosis ?<br />Normal fundus.<br />Mild Hypertensive retinopathy.<br />Non proliferative retinopathy.<br />Proliferative retinopathy.<br />Retinal detachment.<br />Retinopathy – Differences between Hypertensive & Diabetic retinopathy?<br />Briefly describe steps in the Pathogenesis of diabetic retinopathy?<br />Differentiate soft & hard exudates, dots & blots, proliferative & non-proliferative.?<br />

    6 a 65y man bmi 40 diabetes since 18 years

    6. A 65y man, BMI 40, Diabetes since 18 years. His FBS is 18.3 mmol/L, is now developing hypertension since 3 years (BP 186/98 mm of Hg) . Image shows microscopic appearance of his renal biopsy. What microscopic feature shows pathogenesis of high blood pressure?<br />Hyperplasticartereosclerosis<br />Protein cast within tubule.<br />Artereolosclerosis.<br />Nodular glomerulosclerosis.<br />Both A & C.<br />What is the pathogenesis of feature A (hyperplasticarterosclerosis) in the image?<br />Briefly describe feature B and its clinical presentation?<br />What is seen in the interstitium of this kidney? Pathogenesis? Clinical feature?<br />

    7 a 42 year female presents with recent onset

    7. A 42 year female presents with recent onset polyuria, polydypsia and decreasing vision. HbA1c was 16.1%. She is chronic alcoholic with past history of jaundice. Image shows her pancreatic biopsy compared with normal. What is the most likely diagnosis ?<br />Secondary diabetes.<br />Late onset Type 2 diabetes.<br />Chronic cholecystitis.<br />Cushing’s syndrome.<br />Type 1 diabetes.<br />Normal Patient<br />Briefly describe features of LADA?<br />What further investigations can be done to confirm the diagnosis?<br />List & briefly describe other types of Diabetes ?<br />

    8 70y man brought from nursing home with

    8. 70y man brought from nursing home with progressive confused & disoriented status since 2 weeks. Not eating or drinking well. On steroid therapy for COPD.<br />What is the most likely diagnosis ?<br />Diabetic ketoacidosis.<br />Non-ketotichyperosmolar coma.<br />Diabetic lactic acidosis.<br />Respiratory acidosis.<br />Diabetic nephropathy.<br />Lab tests:<br />List & briefly discuss common metabolic complications of Diabetes?<br />?<br />?<br />

    9 the most splendid achievement

    9. The most splendid achievement of all is the constant striving to surpass yourself and to be worthy of your own approval.- - Denis Waitley<br />

    4 cotton wool soft

    4. Cotton wool / soft dep.</li></ul>1.<br />2.<br />3.<br />4.<br />5.<br />

    5 label the diagram

    5. Label the diagram.<br />1.<br />2.<br />3.<br />4.<br />Capillary<br />Nodule – AGE<br />Bowman cap.<br />Hyaline arteriolo sclerosis in arteriole.<br />

    6 diabetic retinopathy br dot hem br blot

    6. Diabetic Retinopathy<br />Dot hem<br />Blot hem<br />Neovascul. <br />Cotton wool<br />Cotton wool<br />

    7 neuropathic arthropathy charcot s foot br acute

    7. Neuropathic Arthropathy: Charcot’s foot.<br />Acute, swollen, red, warm<br />Minimal or no pain. <br />No or minimal h/o trauma.<br />Pathogenesis:<br />Neuropathyosteoporosis#<br />Chronic - Foot deformity.<br />Normal Charcot<br />

    8 dm amyotrophy painful muscle wasting br pain

    8. DM Amyotrophy- Painful muscle wasting<br />Pain & weakness of lower limb muscles.<br />Neuropathy.<br />Muscle wasting.<br />Minimal sensory loss.<br />Loss of knee reflex.<br />Inflammation in spinal cord. <br />

    9 chronic polyneuropathy br claw foot dermopathy

    9. Chronic Polyneuropathy<br />Claw foot – Dermopathy & Neuropathy<br />Pathophysiology: (unknown)<br />Polyol  Sorbitol  damage.<br />Ishcemic injuty.<br />Impaired Nerve growth factor.<br />Autoimmune damage.<br />

    0 diabetic amyotrophy br ul li painful proximal

    0. Diabetic Amyotrophy<br /><ul><li>Painful, proximal Asymmetrical, motor neuropathy.

    1 poor diabetic control hyperglycemia age

    1. Poor diabetic control – hyperglycemia – AGE.

    2 occlusion of capillaries of proximal lumbar

    2. Occlusion of capillaries of proximal lumbar plexus  nerve damage. (no myelin degeneration*)

    3 it is multiple mononeuropathy li li ul li your

    3. It is multiple mononeuropathy </li></li></ul><li>Your life should rest on morality and truth. Base your life on truth & love for all. - Sai - Summer Showers, 1973Money and goes but morality comes and grows. <br />

    4 case 2 58y fem asymptomatic

    4. Case 2 – 58y Fem Asymptomatic.<br />She has a BMI of 29 and is on enalapril for hypertension. She has no symptoms of diabetes. A fasting glucose is 6.5mmol/L. Mother had DM type2.<br />Should she be tested for DM? Indications?<br />Yes. (IGTT, IFG, Aboriginals, High risk immig, Obese fem+, cardiac event, >45y+ BMI>30, FH of DM2 or HPTN).<br />Diagnosis? next investigation for this patient?<br />IFG, oGTT (FG 5.5-7, RG 7-11 mmol/L)<br />How do you manage a IGT patient?<br />Advice about Diet & excercise.<br />

    5 cpc 3 2 kfp questions br dm definition

    5. CPC-3.2– KFP Questions:<br />DM – Definition, epidemiology<br />Type I,II, NIDDM, IDDM, GDM, MODY.<br />Etiology, Risk factors<br />Pathogenesis of Clinical features – PPP<br />Complications <br />Acute – metabolic – ketoacidosis, coma<br />Chronic – vascular – Micro/Macro<br />Glycosylation, AGE, Polyols<br />Lab Diagnosis – FBS, GTT, KFT, Lipids.<br />

    6 summary br abnormal metabolic state

    6. Summary<br />Abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action.<br />Type I (juvenile onset) Autoimmune destruction of β-cells (Genetic + ? Virus + Autoimmunity); insulin-dependent – Treat by Insulin.<br />Type II (maturity onset) - defective insulin action – peripheral resistance to insulin. treatment by life style change & oral hypoglycaemic agents.<br />Complications: accelerated atherosclerosis, susceptibility to infections, and microangiopathy (retinopathy, neuropathy, dermatopathy, nephrophathy)<br />

    7 points to remember review br diabetes

    7. Points to remember/review:<br />Diabetes is a state of hyper ketabolism.<br />Increased fat & protein breakdown, wt loss.<br />Blood vessel damage – arteriosclerosis is central to chronic complications.<br />Increased Infections – why?.<br />Glucose control is critical * why?<br />Hypoglycemia is more dangerous. Not hyper<br />FBS, GTT & HbA1C – interpretation.<br />