Major Electrolytes

1. Major Electrolytes

2. Iron

4. Serum Iron Total Iron Binding Capacity (TIBC) Unsaturated Iron Binding Capacity (UIBC) Serum ferritin transferrin Laboratory tests for investigation of iron disorder

5. Three stages of Iron deficiency anemia • Stage I depletion of serum ferritin (↓) with no functional impairment • Stage II deficient erythropoiesis, RBC protoporphyrin↑, transferrin ↑, UIBC↑BUTHb normal) • Stage III Iron deficiency anemia (serum iron↓) →Hb↓→microcytic hypochromic anemia (only in the late stage, low concentration of serum iron can be observed)

7. Hemochromatosis

9. Calcium

10. Normal daily calcium balance

11. Hormonal regulation of plasma calcium

12. Serum calcium and albumin

14. Cause of hypocalcaemia • Hypoparathyroidism (magnesium deficiency or neck surgery) • Vitamin D deficiency • Renal failure (fail to synthesize vit D) • Pseudohypoparathyroidism (lake of receptor) • Clinical features • Neurologic (tingling and tetany) • Cardiovascular (abnormal ECG)

16. Case study

17. Cause of hypercalcaemia • Hyperparathyroidism (adenoma) • Malignancy ( tumors secrete parathyroid hormone related protein(PTHrP) • Vitamin D overload • Familial hypocalciurichypercalcemia • Thyrotoxicosis (bone resorption) • Immobilization especially Pajet’s disease) • Long-standing → Hyperparathyroidism • Calcium therapy • Antacid poisoning • Clinical features • Neurologic and psychiatric (lethargy, confusion, irritability and depression) • Cardiovascular (arrhythmias) • Renal ( thirst, polyuria, renal calculi) • Gastrointestinal (anorexia, nausea, vomiting and constipation)

20. Calcium measurement

21. Phosphate

23. Cause of hyperphosphatemia • Impaired renal excretion (commonest cause) • hypoparathyroidism • Hemolysis • Clinical features • Deposition of calcium phosphate in soft tissues • Cause of hypophosphatemia • hyperparathyroidism • Genetic disorder of phosphate reabsorption • Antacid ingestion • Treatment of diabetes ketoacidosis which enter phosphate to the cell • Dietary deficiency • Clinical features • Muscle weakness and respiratory impairment

24. Phosphate measurement (colorimetric)

25. Phosphate measurement(enzymatic) In the presence of Pi, the substrate 2-amino-6-mercapto-7-methylpurine riboside (MESG) is converted enzymatically by purine nucleoside phosphorylase (PNP) to ribose 1-phosphate and 2-amino-6-mercapto-7-methylpurine Enzymatic conversion of MESG results in a spectrophotometric shift in maximum absorbance from 330 nm for the substrate to 360 nm for the product.

26. Magnesium

29. Cause of hypermagnesaemia • renal failure • Antacid ingestion • Cause of hypomagnesaemia • Malabsorbtion, sever vomiting, diarrhea • Osmotic diuresis such as in diabetes • Diuretic therapy • Cisplatinum that impairs renal reabsorption • Clinical features • Very similar to hypocalcemia including; impaired neuromuscular function such as tetany, hyperirritability, tremor, convulsion, muscle weakness

30. Magnesium measurement

31. 4. Enzymatic: Based on the specific requirement of glycerol kinase for Mg+2. An enzyme linked reaction leads to formation of an intensely colored (λmax = 450nm) product whose formation is proportional to Mg+2 concentration.

32. Copper

33. Copper • Biochemical role (as a cofactor for metaloenzymes, ceruloplasmin, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase and tyrosinase • Absorption: stomach and intestine • Transport: to the liver by Alb and then ceruloplasmin • Distribution: liver, kidney, muscle and bone • Excretion: bile and urine

35. Laboratory tests • Serum copper (Under acid environment, copper present in the sample reacts, with the chromogen Di-Br-PAESA forming a colored blue complex. The intensity of the colored complex is proportional to the copper concentration in the sample.) • Ceruloplasmin (ELISA and emzymatic based on oxidase activity of ceruloplasmin on synthetic substrate . • Urinary copper

36. Copper deficiency (in infants and intestinal bypass surgery or parenteral nutrition) signs: • mental retardation, depigmentation, anemia, hypotonia and scorbutic changes in bone, Iron-resistant microcytic hypochromic anemia. • Copper toxicity • By administration of copper sulfate solutions, • Renal tubular damage • Damage to tissues • Treatment • Penicillamine

37. Wilson’s disease in response to rising concentrations of copper in the intestine, an enzyme called ATP7A releases copper into the portal vein to the liver. In Liver cells ATP7B links copper to ceruloplasmin and releases it into the bloodstream, as well as removing excess copper by secreting it into bile. Both functions of ATP7B are impaired in Wilson's disease. Copper accumulates in the liver tissue; ceruloplasmin is still secreted, but in a form that lacks copper (termed apoceruloplasmin) and is rapidly degraded in the bloodstream. The liver also releases copper into the bloodstream that is not bound to ceruloplasmin. This free copper precipitates throughout the body but particularly in the kidneys, eyes and brain.

38. Kayser–Fleischer ring

40. Menkes syndrome • Low serum copper and seruloplasmin • Mutations in the ATP7A gene • The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system. • Signs: kinky hair; failure to gain weight and grow at the expected rate (failure to thrive); and deterioration of the nervous system; weak muscle tone (hypotonia), seizures and intellectual disability.

42. Zinc

43. Zinc is a co-factor in DNA and protein synthesis and cell division • In plasma it is bound to albumin (90%) and α2-macroglobulin • Located mainly in muscle and bone • Excretion: urine, bile, pancreatic fluid and milk in lactating mothers • Deficiency a result of low intake or cadmium poisoning: hair loss, skin rash, wound breakdown and delayed healing; Anorexia

45. Sodium

46. Hyponatremia • عرق زياد, استفراغ, اسهال, استفاده از ديورتيكها ، كمبود آلدوسترون و ديگر مينرالوكورتيكوئيدها ، پلي‌اوري، اسيدوزمتابوليك(دفع كاتيونها به همراه آنيونهاي آلي)، هيپوناترمي ثانويه (ادم,‌ اختلال مزمن قلبي، سندرم نفروتيك، سندرم ترشح نامناسب هورمون آنتي ديورتيك • Pseudohyponatremia • اختلال آناليزي در نمونه‌هاي ليپميك • Clinical features • اختلال عصبي ضعف, فلج

47. Hypernatremia • تزریق محلول های سالین • انسولین درمانی، • هیپرآلدوسترونیسم • Hypernatriuria • هيپرناتری اورياي فيزيولوژيك در مواقع افزايش جذب و • پس از دیورز قاعدگي ديده مي‌شود. • Hyponatriuria • در نتيجه كاهش دريافت سدیم و يا احتباس آب و سدیم قبل از GFRقاعدگي ايجاد مي‌گردد, هيپرآلدوسترونيسم وكاهش

48. Potassium

49. كاتيون عمده داخل سلولي • بازجذب در توبولهای پروکسیمال می گردد و ترشح در دیستال

50. Hypokalemia • ،كاهش دريافتورود پتاسيم خارج سلولي به داخل سلولي • افزايش دفع مايعات، انسولين درماني • آلكالوز (توقف آنتی پورت پتاسیم- پروتون) • استفراغ, اسهال • اسيدوز توبولهاي كليه • آلدوسترونيسم • دفع پتاسیم از کلیه←خروج پتاسیم از سلول ← ورود پروتون به سلول ← آلکالوز