METABOLISM AND ENDOCRINE SYSTEM PATHOPHYSIOLOGY

1. Which of the tissues are insulin-dependent and why are they called insulin-dependent? Insulin dependent tissue: - striated muscle - adipose tissue Involve in synthesis of glycogen to glucose.

2. Which of the tissue are insulin-independent and why are they called insulin-independent?

Insulin independent tissue:

- brain - endothelial cell - red blood cell Dont involve in gluconeogenesis. Receive glucose.

3. Point out the counter-regulatory insulin hormones. Glucagon Epinephrine Glucocorticoids Growth hormones

4. Point out the main differences of Diabetes Mellitus Type 1 and 2 Clinical weight insulin cells Type 1 Children > adults Ketoacidosis common Normal / loss weight absence Autoimmune dzs, Severe cells depletion Type 2 Adults > children Ketoacidosis rare Obese Initially insulin, Eventually insulin resistance Mild cells depletion

5. Describe the mechanism of glucosuria in DM. lack of insulin plasma glucose levels are above normal ( > 11 mmol/L) saturation of receptors in the kidneys due to improper functioning of the renal tubules glucosuria ( excretion of glucose in urine)

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6. Describe the mechanism of hyperketonemia in insulin-dependent diabetes mellitus Hyperketonemia: The presence of elevated concentrations of ketone bodies in the blood. Mechanism: Insulin deficiency causes excessive breakdown of adipose stores, resulting increase levels of free fatty acids (FFA's) Oxidation of FFA's through acetyl-CoA produces ketone bodies (acetoacetic acids and Bhydroxybutyric acid) Glucagon accelerates its oxidation The rate at which ketone bodies formed accelerates rate which acetoacetic acid and Bhydroxybutyric acid can be utilized by muscles and other tissues ketonemia Diabetic patient have susceptibility to infection and stress of infection increase insulin requirements, infection will always precipitate diabetic ketoacidosis

7. What symptoms are typical of ketoacidotic coma in diabetes mellitus? Ketoacidosis:acidosis with an accumulation of ketone bodies; occurs primarily in diabetes mellitus Diabetic Ketoacidosis Symptoms & Signs Frequent urination or frequent thirst for a day or more Fatigue Nausea Vomiting Muscular stiffness or aching Mental stupor that can progress to coma Rapid deep breathing Fruity breath (breath odor) Additional symptoms that may be associated with this disease: Headache Consciousness - decreased Breathing - rapid Breathing difficulty - lying down Blood pressure - low Appetite - loss Abdominal pain

8. Name causes of development of insulin resistance Insulin resistance: lack of ability of the body to respond to insulin appropriately - Usually related to type DM type 2 The metabolic syndrome Obesity Pregnancy Infection or severe illness Stress During steroid use 9. What syndromes are typical of hyperosmotic coma? (4) Weakness Increased thirst Nausea Lethargy

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 Confusion Convulsions Coma 10. What are remote complications of diabetes mellitus conditioned by? The most complications of diabetes result from metabolic disarrangements, hyperglycemia and severe dehydration. 11. Point out remote complications of diabetes mellitus Microangiopathy Retinopathy Nephropathy Neuropathy Accelerated atherosclerosis

mainly

12. Indicate possible cause of hypoglycemia Islet cell tumors Insulin sensitivity Diffuse liver disease Inherited glycogenoses Secretion of insulin-like growth factor 2 ( igf-2 ) by certain retroperitoneal fibromas and fibromas Self injection insulin 13. Describe the main manifestation of hypoglycemia Pallor, coldness, clamminess Hunger Nausea, vomiting, abdominal discomfort Fatigue, weakness, apathy, lethargy Confusion, dizziness Anxiety, tremor Blurred vision Difficulty speaking

14. Point out the main group of etiological factors of the development of DM type 1 Genetic predisposition Virus infection ex. Measles Chemical factors

15. Point out the causes of development of hyperlipidemias The defects in various components of lipoprotein metabolism lead to changes in plasma lipoprotein levels and to disorder known as hyperlipidemias or dyslipidemias.

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Causes: Genetics :

Disturbance in lipid digestion and absorption in GIT Bad transport of lipid in the blood Intensive splitting of lipid in fat tissue Retention of lipid in blood - Decreased of albumin lipoprotein lipase 16. Name the risk factors of development of atherosclerosis Risk factors: - Age - Male - Family predisposition Other risk factors: - Hypertension - Hyperlipidemias - Smoking - Diabetes mellitus

17. Indicate types of obesity according to etiology (3) Genetic Environmental Psychological factors

18. For what disease obesity is a risk factor? Diabetes mellitus type 2 19. Name the syndromes developing in case of adenomas of: Zona fasciculate - causing Cushing's syndrome Zona glomerulata - causing Conn's syndrome Zona reticulate - causing hyperandrogenism

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20. What changes in blood concentrations of ACTH and cortisol are typical of: Cushings disease ACTH excess production of ACTH from a pituitary gland adenoma cortisol high cortisol levels. Cushings syndrome ACTH decreases the amount of ACTH released from the pituitary gland. cortisol excesses of cortisol that secreting adenoma in the cortex of the adrenal gland

21. Describe the mechanism of the development of steroid diabetes mellitus. Caused by corticosteroids, sometimes known as steroid diabetes. Complication from renal transplantation. 23. What is a)primary aldosteronism b)secondary aldosteronism

Primary aldosteronism - About mineralcorticoid - Lyse in subscapular adenoma of adrenal gland cortex - Due to heart,kidney/liver disease - Disturbance by RAAS in ECF flow - Accumulation of sodium,lack of calsium and H - Hyperplasia in congenital Conns syndrome Secondary aldosteronism - Chronic heart insufficiency - Kidney,liver disease - Disturbance of liver impaired of aldosterone in liver

24. Point out possible causes of development of Addisons disease. (3)

Autoimmune process only in adrenal cortex Tuberculosis of adrenal gland(total injury) AIDS and meningitis Blood supply disturbance

25. Point out the manifestations of Conns symdrome (5) High blood pressure Headache Muscle weakness Fatigue Intermittent paralysis Numbness 26. Describe the main manifestations of chronic insufficiency of the adrenal gland. Skin hyperpigmentation - due to increased level ACTH stimulate melanocytes. Weaknesses, easily fatigue - due to decrease muscle mass as result of decrease androgen. Gastrointestinal disease

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- anorexia, nausea, vomiting, weight loss & diarrhea. Decreased Aldosterone (mineralocorticoid,) - result in K retention and Na loss. - consequently, hyperkalemia, hyponatremia, vol depletion & hypotension. Decreased Hypoglycemia - due to decreased glucocorticoid. Smaller heart - due to chronic hypovolumia.

27. What is Waterhouse-Friderichsen syndrome? Type of acute adrenal insufficiency Massive, usually bilateral, hemorrhage into the adrenal glands caused by meningococcemia characterised by: An overwhelming bacterial infection Rapidly progressive hypotension leading to shock DIC (disseminated intravascular coagulation) with widespread purpura , particularly of the skin Rapidly developing adrenocortical insufficiency associated with massive bilateral adrenal hemorrhage This type of meningitis occurs most commonly in children and young adults. Can also be caused by other organisms, including Pseudomonas and pneumococci.

28. Describe the main manifestations of acute insufficiency of the adrenal gland. Triad: Prostration( loss of consciousness , but not completely) -patient cant estimate time, space, etc. Cardiovascular shock -result of hypotension Hemorrhagic purpura -due to DIC syndrome.

29. Name possible cause of acute insufficiency of the adrenal gland Addison disease Septic shock Discontinuing corticosteroid without tapering dosage Trauma Stress Complication of chronic adrenal gland insufficiency

30. Why doesn't the introduction of adrenalin on the background of insufficiency of the adrenal gland cause increasing of the arterial pressure? Insufficiency of adrenal gland will cause hypoproduction of all hormones of adrenal gland ( aldosteron, glucocorticoids, androgens, catecholamines)

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Glucocorticoids deficiency will cause decrease sensitivity of tissue / cell to catecholamines (adrenaline) So, the administration of adrenaline will have no effect because the tissue is not sensitive to it not increase art. pressure.

31. What diseases (syndromes) are accompanied by: Increase in the production of the hormone of the thyroid gland Graves disease Toxic nodular struma etc wikipedia

Reduction in production of hormone thyroid gland Myxederma Kretinism Endemic goiter

32. What is LATS factor? What roles does it plays in the pathogenesis of Graves dzs? LATS-long acting thyroid stimulator Role-act as an IgG that fits into TSH receptor on thyroid gland then proliferation of the gland and hormone secretions 33. What syndromes develop in a) innate and b) acquired hypofunction of the thyroid gland? Innate Hashimoto thyroiditis Cretinism Acquired Weakness,fatigue,insomnia,apathy Slowed speech & slow thinking Cold,dry skin Shortness of breath Sluggish reflexes Myxedema

34. What are the effects of excess and deficit of the hormone of the thyroid gland on the function of the sympathetic nervous system? Excess thyroid hormone : increase sympathetic activity, hypermetabolism, hypermotility in GIT (malabsorption and diarrhea), palpitation , tachycardia, nervousness, tremor , irritability Deficit thyroid hormone : decrease sympathetic activity 35. How does the production of TTH and thyroxin change on the background of a) immune forms of Graves disease, b) endemic goiter? decrease of TTH , increase of thyroxin (negative feedback) increase of TTH , decrease of thyroxin (positive feedback)

36. Name the manifestations of innate hypothyroidism Cretinism: severe mental retardation, short stature, impaired CNS and muscle, umbilical, umbilical hernia, wide eyes, protruding tongue 37. Indicate the main manifestations of myxedema

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Typically by localized area of thickening and hyperpigmentations of the skin over the anterior aspect of the feet and lower legs.

38. Describe the pathogenic factors leading to goiter formation in deficit of iodine in food.
The presence of goiter reflects impaired synthesis of thyroid hormone most often cause by dietary iodine deficiency. Impairment of thyroid hormone synthesis leads to compensatory rise in the serum TSH level, which in turn causes hypertrophy and hyperplasia of thyroid follicular cell and ultimately gross enlargement of thyroid gland. 39. Syndromes developed in growth hormone a) Excess: gigantism - Increased in body size, disproportional long arms and legs - May develop acromegaly (swelling of hands and feet with soft tissue) - Separation of teeth because enlargement of jaw b) Deficit: dwarfism - Growth retardation with proportional constitution of body - Normal intellectuality 40. Defects of hormones which are typical for Simmonds disease Refers to panhypopituitarism caused by the destruction of the pituitary gland due to infiltrative processes (e.g. lymphocytic), tumours (pituitary adenomas or craniopharyngiomas) or trauma (cranial injury or following surgery). The deficiency of all anterior pituitary hormones is termed panhypopituitarism prolactin (PRL) - stimulates milk production in the breast growth hormone (GH) - growth and glucose homeostasis luteinizing hormone (LH) - menstrual cycle and reproduction follicle stimulating hormone (FSH) same thyroid stimulating hormone (TSH) - stimulates thyroxine production in the thyroid adrenocorticotropic hormone (ACTH) - stimulates glucocorticoid production in the adrenal gland

41. Indicate the main consequences of hypofunction of the parathyroid gland.

Hypocalcemia is the only real result of parathyroid dysfunction and low PTH levels Muscular irritability (muscle spasm, tetany, tingling) Cardiac arrhythmias Seizures Hypoparathyroidism does not have consequences for bone

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