Term
| Explain DIABETES INSIPIDUS |
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Definition
- NOT AT ALL RELATED OR A SUB TYPE OF DIABETES MELLITUS
- However, both diseases (mellitus and insipidus) share something in common; they both cause PU/PD
> PU = Polyuria (excessive urination)
> PD = Polydipsia (excessive thirst)
- DIABETES INSIPIDUS IS DUE TO AN ADH (anti-diuretic hormone) DEFICIENCY IN THE PITUITARY GLAND. |
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Term
| Explain DIABETES MELLITUS |
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Definition
- It is a CHRONIC disorder that affects the METABOLISM of CARBOHYDRATES, FATS, AND PROTEINS.
> A defective or deficiency of insulin secretory response IMPAIRS carbohydrates use as energy.
> The result is HYPERGLYCEMIA.
- This is a group of disorders that all have HYPERGLYCEMIA as a common feature:
> PRIMARY: Type 1 and Type 2 diabetes
> SECONDARY: Chronic pancreatitis, hormonal tumors, corticosteroid drugs |
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Term
Explain NORMAL INSULIN PHYSIOLOGY
(slide 1) |
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Definition
- The insulin gene is expressed in BETA cells of the PANCREATIC ISLETS.
- BETA CELLS SYNTHESIZE insulin and STORE it in granules. (Alpha cells --> glucagon)
- GLUCOSE is a strong TRIGGER for insulin release:
> a rise in blood glucose causes an immediate release of insulin
> if glucose blood levels still remain high, ACTIVE SYNTHESIS of INSULIN will continue. |
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Term
Explain NORMAL INSULIN PHYSIOLOGY
(slide 2) |
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Definition
- Insulin enables GLUCOSE and AMINO ACIDS across (MOST) cell membranes.
- Insulin DECREASES the level of serum glucose by promoting its influx into the LIVER and SKELETAL MUSCLES where glucose now becomes GLYCOGEN.
- Insulin stimulates:
> The influx of glucose into SKELETAL, and CARDIAC muscle cells, FIBROBLASTS, and FAT CELLS.
> the CONVERSION of glucose into TRYGLYCERIDES in FAT CELLS
> The SYNTHESIS of PROTEINS from AMINO ACIDS. |
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Term
Explain NORMAL INSULIN PHYSIOLOGY
(slide 3) |
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Definition
- Insulin first binds to it's target cells INSULIN RECEPTORS.
> The NUMBER and FUNCTION of the INSULIN RECEPTORS are important in regulating the ACTION of the insulin.
- This stimulates GLUTs (glucose transport units) in the target cells to move from the golgi apparatus to the plasma membrane.
- This facilitates glucose uptake by the target cell. |
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Term
| Explain DIABETES MELLITUS TYPE 1 and TYPE 2 |
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Definition
- The pathogenic mechanisms and metabolic characteristics are different between the types.
- However, the LONG TERM COMPLICATIONS in BLOOD VESSELS, KIDNEYS, EYES, and NERVES occur in BOTH types.
- Affects about 13 million people in the USA
> annual mortality rate is 35,000
> 7th leading cause of death in the USA |
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Term
| Explain CHARACTERISTICS of Type 1 diabetes |
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Definition
- Insulin dependent
- Onset < 20 years
- normal weight
- autoimmune
- Severely insulin deficient
- ketoacidosis is common
- decreased blood insulin
- 10-20% of DM cases |
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Term
| Explain characteristics of Type 2 diabetes |
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Definition
- NON-insulin dependent
- Onset > 40 years
- Obesity
- Ketoacidosis is rare
- Normal or increased levels of blood insulin
- Insulin RESISTANCE
- Relative insulin deficiency
- 80-90% of DM cases |
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Term
| Explain the PATHOGENESIS OF TYPE 1 DIABETES |
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Definition
- This results from a severe, or ABSOLUTE LACK of insulin caused by BETA-CELL MASS reduction.
- Paitnets depend on insulin injections for survival.
- Three mechanisms WORKING together for are responsible for pancreatic islet cell destruction:
> GENETIC SUSCEPTIBILITY
> AUTOIMMUNITY
> AN ENVIRONMENTAL INSULT (USUALLY VIRAL) |
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Term
| Explain the GENETIC SUSCEPTIBILITY factor of TYPE 1 DM |
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Definition
- Occurs most commonly in people of northern european descent
- Type 1 not common in blacks, native americans, and asians
- seems to be a familial inheritance pattern
- method of inheritance is UNKOWN (idiopathic)
- CONCORDANCE RATE amongst IDENTICAL TWINS is 40%. |
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Term
| Explain the AUTOIMMUNE factor of type 1 diabetes |
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Definition
- A chronic autoimmune attack on beta cells may begin years before the onset of disease (even though signs may seem to start abruptly)
- Don't display clinical manifestations of type 1 diabetes until 90% of beta cells have been destroyed.
- 70-80% of patients with type 1 diabetes have ISLET CELL ANTIBODIES when tested 1 year after diagnosis. |
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Term
| Explain ENVIRONMENTAL FACTORS in TYPE 1 DM |
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Definition
- What triggers the autoimmune response?
- One theory is that a VIRAL PROTEIN shares the SAME AMINO ACID SEQUENCE as that of a BETA CELL PROTEIN (MOLECULAR MIMICRY)
- Another theory is that an environmental insult DAMAGES THE BETA CELLS stimulating an autoimmune response.
- IMPLICATED VIRUSES: Coxsackievirus B, mumps, measles, rubella, and infectious mononucleosis |
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Term
| What is the most likely scenario in the development of type 1 diabetes? |
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Definition
| - The most likely scenario is a person is hit with a common viral infection which causes an alteration of beta cells, followed by an autoimmune reaction to the altered (damaged) beta cells in people who are genetically susceptible. |
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Term
| Explain the PATHOGENESIS OF TYPE 2 DM |
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Definition
- NO EVIDENCE FOR AUTOIMMUNE DISORDERS
- GENETIC FACTORS play an even bigger role in Type 2 diabetes than in type 1
> Concordance rate in identical twins is 60-80%
>risk in general population is 5-7%
> risk in relatives is 20-40%
> appears to be a collection of multiple genetic defects
- *** TWO METABOLIC DEFECTS that characterize type 2 diabetes ***
- Derangement of insulin secretion by beta cells
- Peripheral tissues don't respond to insulin (insulin resistance) |
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Term
| Explain DERANGED BETA CELL STIMULATION IN TYPE 2 DIABETES |
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Definition
- People AT RISK of developing TYPE 2 DM will often show a moderate HYPERINSULINEMIA.
- As the disease continues on in development the NORMAL OSCILLATING pattern of insulin secretion is lost.
- Later on in the disease a mild to moderate DEFICEINCY of Insulin is present.
- Chronic hyperglycemia and persistent beta cell stimulation can lead to the EXHAUSTION OF THE BETA CELL FUNCTION. |
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Term
| Explain INSULIN RESISTANCE |
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Definition
- Insulin SENSITIVTY in target tissues DECREASES causing an INCREASE in insulin serum levels.
> a decrease in the number of insulin receptors
> binding of insulin to its receptor does not result in GLUT facilitating glucose transport
- Insulin resistance results in:
> the inability of circulating insulin to properly direct the disposition of glucose
> a more persistent HYPERGLYCEMIA
> a more PROLONGED STIMULATION OF BETA CELLS
> Early in the disease --> hyperinsulinemia |
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Term
| Explain the OBESITY FACTOR of type 2 diabetes |
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Definition
- 80% of type 2 diabetics are obese
- ** NONDIABETIC OBESE individuals exhibit insulin resistance and hypERinsulinemia
- ** DIABETIC OBESE individuals will exhibit insulin resistance and hypOinsulinemia
- Weight loss in the early stages can reverse impaired glucose tolerance |
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Term
| Explain the PATHOGENESIS of TYPE 2 DM |
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Definition
- Type 2 DM is a complex, multifactorial disease including impaired insulin release as well as end organ insulin sensitivity.
- Insulin resistance (often associated with obesity) puts a lot of stress on the beta cells, which may cause them to fail.
- A genetic factor is definitely involved. |
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Term
| Explain the COMPLICATIONS OF DIABETES MELLITUS (TYPE 1 OR TYPE 2) |
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Definition
- UNCONTROLLED OR INADEQUATELY controlled diabetes can result in a variety of complications.
- Most research shows that the complications associated with DM results from HYPERGLYCEMIA.
> * NONENZYMATIC GLYCOSYLATION: glucose becomes chemically attached to free amino group of proteins (ex. collagen in blood vessel walls)
> * INTRACELLULAR HYPERGLYCEMIA: Chemical disturbance in cells make it so that insulin isn't required for glucose transport |
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Term
* What are the insulin INDEPENDENT cells?
( Never Let Rich Kids Gamble ) |
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Definition
- Neurons
- Lens
- RBC's
- Kidneys
- Gut lining
- All other cells are insulin DEPENDENT |
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Term
| Explain the CARDIOVASCULAR COMPLICATIONS of DM |
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Definition
- Diabetes promotes the development of ATHEROSCLEROTIC LESIONS in the LARGE arteries
- Cerobrovascular accidents: CVA, strokes
- Development of atherosclerosis in the aorta with aneurysm
- Coronary artery disease --> MI
- Gangrene in toes or feet due to ischemia
- MICROANGIOPATHY: due to nonenzymatic glycosylation
- Diabetics also have an increased incidence in HYPERTENSION |
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Term
| Explain RENAL COMPLICATIONS of diabetes |
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Definition
- GLOMERULOSCLEROSIS: sclerotic lesions of the glomeruli which destroys renal function.
- MICROANGIOPATHY: (diffuse thickening of blood vessel basement membrane) --> RENAL ISCHEMIA
> tubular atrophy (disinigration of tubules) and interstitial fibrosis
> may cause infarcts and papillary necrosis
- Kidneys become PRONE to PYELONEPHRITIS
> UTI's (urinary tract infections), Cystitis (inflammation of the urinary bladder) |
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Term
| Explain COMPLICATIONS INVOLVING EYES |
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Definition
- Diabetes is the LEADING cause of BLINDNESS in the USA.
- RETINOPATHIES:
> microaneurysmal dilations in the retinal vessels.
> microinfarcts that occur with hemorrhage
- GLAUCOMA:
> Due to vascular changes, there's an obstruction of aqueous outflow
- CATARACTS:
> Sugars in the lens matrix, increased osmotic swelling |
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Term
| Explain Nervous System Complications from diabetes |
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Definition
- MICROANGIOPATHY: Causes widespread focal damage
- STROKES: Due to atherosclerosis of the cerebral arteries
- PERIPHERAL NEUROPATHY:
> Diabetes affects the sensory and autonomic nerves
> Symptoms vary from mild loss of sensation to urinary incontinence
> Partly due to microangiopathy and partly due to sugar build up in axons and myelin sheaths |
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Term
Explain the Clinical Features of Diabetes (both type 1 and type 2)
4 "P's" |
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Definition
- PU: POLYURIA
> The kidneys have a TRANSPORT MAXIMUM past which they cannot save glucose. (AKA Renal threshold = 180 mg/dl)
> Glucosuria causes osmotic diuresis (lots of peeing)
- PD: POLYDIPSIA
> Thirst trying to compensate for the PU.
- POLYPHAGIA
> Body breaking down fats and proteins for energy.
- PREDISPOSITION to infections
> Impaired WBC function
> poor blood supply |
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