1. 1. The Lipid Profile Lipid Profile is ordered in the following types of patients, who have a family history of high cholesterol or heart disease are obese are diabetic are hypertensive (high B.P) In short, the patients who have high risk of developing atherosclerotic diseases of blood vessels.
2. 2. The Lipid Profile A complete cholesterol test, referred to as a lipid panel or lipid profile, includes the calculation of four types of fats (lipids): Total cholesterol Low-density lipoprotein (LDL) cholesterol High-density lipoprotein (HDL) cholesterol Triglycerides
3. 3. Structure of Lipoproteins The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). composed of a neutral lipid core (containing triacylglycerol and cholesteryl esters) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified (free) cholesterol They serve to transport lipids in the aqueous environment of blood.
4. 4. Size and density of lipoprotein particles: Chylomicrons are the lipoprotein particles lowest in density and largest in size, and contain the highest percentage of lipid and the lowest percentage of protein. VLDLs and LDLs are successively denser, having higher ratios of protein to lipid. HDL particles are the densest having the most protein and least amount of lipids
5. 5. LDL- Cholesterol LDL-Cholesterol is one of the major culprits in the development of atherosclerotic heart disease The function of LDL is to deliver cholesterol synthesized in the liver to other cells, where it is used in membranes, or for the synthesis of steroid hormones. Cells take up cholesterol by receptor-mediated endocytosis. LDL binds to a specific LDL receptor and is internalized in an endocytic vesicle. Receptors are recycled to the cell surface, while hydrolysis in an endolysosome releases cholesterol for use in the cell.
6. 6. LDL- Cholesterol LDL cholesterol is the major cholesterol found in the plaques formed in coronary and other atherosclerotic vascular diseases. Levels of LDL- cholesterol below 1o0 mg./dl are recommended for patients with a history of risk factor for heart disease.
7. 7. HDL- Cholesterol HDL-Cholesterol is called good cholesterol because it is inversely related with the incidence of atherosclerosis HDL is involved in reverse cholesterol transport. Excess cholesterol from cells is brought back to the liver by HDL in a process known as reverse cholesterol transport HDL travels in the circulation where it gathers cholesterol and returns the cholesterol to the liver via various pathways. The HDL-Cholesterol level above 40 mg/dL in men and above 50 mg/dL in women is desirable.
8. 8. Background Uric acid is the final product of purine catabolism in human beings. Approximately two thirds of total body urate is produced endogenously, while the remaining one third is accounted for by dietary purines.
9. 9. Background Approximately 70% of the urate produced daily is excreted by the kidneys, while the rest is eliminated by the intestines. The blood levels of uric acid are a function of the balance between the breakdown of purines and the rate of uric acid excretion. Alterations in this balance may account for hyperuricemia.
10. 10. Mechanism of Hyperuricemia Therefore, there are two main mechanisms of hyperuricemia: 1. Under excretion e.g chronic kidney disease 2. Overproduction e.g rapid cell death such as in cancer chemotherapy or a combination of these two mechanisms!!
11. 11. Effects of Hyperuricemia Gouty Arthritis, Gouty Tophi Uric acid calculi in urinary tract.
12. 12. Gout Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in joints most commonly in the great toe and less frequently in the tarsal joint, knee, and other joints Results in intesnse pain, redness and swelling of the affected joint. polarized light microscopy of the joint aspirate show the presence of needle-shaped mono -sodium urate crystals
13. 13. LABORATORY STUDIES Serum uric acid CBC count: Values may be abnormal in patients with hemolytic anemia, hematologic malignancies, or lead poisoning. Electrolytes, Urea, and serum creatinine values: These are abnormal in patients with acidosis or renal disease. Urinary uric acid excretion
14. 14. KIDNEY DISORDERS and ASSESSMENT OF RENAL FUNCTION The kidneys have many functions, most notably: excretion of waste such as urea and creatinine maintenance of extracellular fluid (ECF) volume and homeostasis Acid Base homeostasis hormone synthesis such as erythropoeitin and vitamin D
15. 15. THE NEPHRON The functional unit of the kidney is a nephron. Each kidney contains approximately 1 to 1.5 million nephrons. A nephron is in fact a long microscopic tubule, consisting of different anatomic and functional units and supplied by a rich blood supply.
16. 16. Urine formation requiers : Urine Formation Glomerular Filtration Due to differences in pressure water, small molecules move from the glomerulus capillaries into the glomerular capsule Tubular reabsorption many molecules are reabsorbed from the nephron into the capillary (diffusion, facilitated diffusion, osmosis, and active transport) i.e. Glucose is actively reabsorbed with transport carriers. If the carriers are overwhelmed glucose appears in the urine indicating diabetes Tubular secretion Substances are actively removed from blood and added to tubular fluid (active transport) ie. H+, creatinine, and some drugs are moved by active transport from the blood into the distal convoluted tubule a) b) c)
17. 17. The structure of the nephron and the processes of urine formation. (Source: Pearson Education/PH College) 03/05/2011 21
18. 18. The glomerular filtrate is an ultra filtrate of plasma; that is, it has a similar composition to plasma except that it is almost free of proteins. Proteins with molecular weights lower than that of albumin (68 kDa) are filterable; negatively charged molecules are less easily filtered than those bearing a positive charge. . The volume of plasma fluid filtered from glomerular capillaries into the Bowmans capsule per unit time is called Glomerular Filtration Rate (GFR).
19. 19. The normal glomerular filtration rate (GFR) is approximately 120 mL/min, equivalent to a volume of about 170 L/24 h. However, urine production is only 1-2 L/24 h, depending on fluid intake; the bulk of the filtrate is reabsorbed further along the nephron
20. 20. Laboratory Investigations in renal DIseases The most routinely ordered tests in suspected kidney diseases are: Blood urea Serum creatinine and Urinary albumin Increased blood urea and creatinine levels in a patient of renal failure may be a sign of decreased GFR However, urea and creatinine levels may be normal in the initial stages of the kidney diseases due to the great ability of the healthier parts of the kidney to compensate and maintain adequate GFR.
21. 21. Therefore, in many patients an estimate of GFR is made to gauge the true extent of kidney damage. Creatinine clearance is measured to estimate the GFR. Creatinine clearance is defined as the volume of plasma which is cleared of creatinine per unit time. Creatinine clearance is a good estimate of GFR because it is freely filtered and only minutely secreted with no reabsorption.
22. 22. Creatinine clearance is calculated from the formula: U urinary creatinine concentration (mol/L) V urine flow rate (mL/min or (L/24 h) P plasma creatinine concentration (mol/L)
23. 23. Assessment of glomerular integrity Impairment of glomerular integrity results in the filtration of large molecules that are normally retained and is manifest as proteinuria. Proteinuria can, however, occur for other reasons.
24. 24. Classification of Proteinuria Albumin excretion below 30 mg/day ( less than 20 mcg/ min) : normoalbuminuria Persistent albumin excretion between 30 and 300 mg/day (20 to 200 mcg/min) OR albumin (g)/creatinine (mg) ratio, ACR>30 g/mg): high albuminemia (formerly called microalbuminuria) Albumin excretion > 300 mg/day (200 mcg/min; (ACR 300 g/mg)): overt proteinuria or very high albuminuria (formerly called macroalbuminuria)
25. 25. The liver INTRODUCTION The liver is of vital importance in intermediary metabolism and in the detoxification and elimination of toxic substances.
26. 26. What does the liver do? Temporary nutrient storage (glucose- glycogen) Remove toxins from blood Remove old/damaged RBCs Secrete Bilirubin synthesized from breakdown of hemoglobin and other heme containing proteins. Regulate nutrient or metabolite levels in bloodkeep constant supply of sugars, fats, amino acids, nucleotides (including cholesterol) Multi-function, blood-processing factory
27. 27. What does the liver do? Secrete bile via bile ducts and gall bladder into small intestines. Secrete and synthesize Albumin which maintains plasma fluid levels Synthesize proteins of the blood clotting system. Removes ammonia from blood and synthesize urea to be excreted in urine. Multi-function, blood-processing factory
28. 28. What targets the Liver? Toxins Alcohol Medications Tylenol Mushrooms Tumors, most frequently secondary; Viral Hepatitis A/B/C/D/E EBV/HSV/CMV Autoimmune
29. 29. What targets the Liver? Metabolic Glycogen storage diseases Wilsons Disease Ischemia Severe hypotension Vasoconstriction Sepsis Deficiency diseases Alpha-1 antitrypsin deficiency
30. 30. LIVER FUNCTION TESTS ALT : Alanine Transaminase AST : Aspartate Transaminase ALP: Alkaline Phosphatase GGT: Gamma Glutamyl Transferase Albumin reflects protein synthetic function PT, aPTT and INR reflect clotting factor synthesis Ammonia: An increase in serum ammonia reflects decreased synthesis of urea.
31. 31. Liver Function Tests and Markers of liver cell injury. Damage to the liver may not obviously affect its activity since the liver has considerable functional reserve, As a consequence, simple tests of liver function (e.g. plasma bilirubin and albumin concentrations) may not become abnormal until a significant damage to liver has occurred. Therefore, they are insensitive indicators of liver disease.
32. 32. However, even a little damage to the hepatocytes will result in increased tissue release of hepatic enzymes: acting as a marker of liver cell injury. Therefore these enzyme assays are sometimes, rightly called as Markers of Liver Cell Injury to differentiate them from the TRUE Liver Function Tests
33. 33. ALT and AST Enzymes, found in Hepatocytes Released when liver cells damaged ALT is specific for liver injury AST (SGOT) is also found in skeletal and cardiac muscle
34. 34. Jaundice or Scleral Icterus Jaundice is a sign of many hepatic diseases. Jaundice is defined as the yellowish discoloration of skin and sclera of the eye. Elevated bilirubin levels in blood (>2.5-3 mg/dL) cause jaundice. Bilirubin is the end product of haem breakdown from hemoglobin and other haem containing proteins Apart from hepatic diseases, jaundice may also result from increased bilirubin formation such as hemolytic anemia and biliary channel obstruction such as gall stones.
35. 35. Thyroid Gland The thyroid gland produces three hormones: Triiodothyronine or T3 Tetraiodothyronine, also called thyroxine, or T4 Calcitonin Strictly speaking, only T3 and T4 are proper thyroid hormones. They are produced in what are known as the follicular epithelial cells of the thyroid, with iodine being one of the main components of both hormones
36. 36. Their most obvious overall effect on metabolism is to stimulate the basal metabolic rate, oxygen consumption and heat production, through actions that include stimulating Na+,K+-ATPases involved in ion transport and increasing the availability of energy substrates. Thyroid hormone can thus be considered as the Tuning Switch of body metabolism. Thyroid Hormones Physiological Functions
37. 37. Thyroid Hormones Physiological Functions Body temperature maintenance Increased heart rate and contractility. Lipolysis, proteolysis, Glycolysis Mobilization of energy storage Brain maturation in children Growth promotion in children.
38. 38. Thyroxine synthesis and release are stimulated by the pituitary trophic hormone, thyroid- stimulating hormone (TSH). The secretion of TSH is controlled by negative feedback by the thyroid hormones, which modulate the response of the pituitary to the hypothalamic hormone, thyrotropin-releasing hormone (TRH). REGULATION OF THYROID SECRETION
39. 39. This feedback is mediated primarily by T3 produced by the action of iodothyronine deiodinase on T4 in the thyrotroph cells of the anterior pituitary. Glucocorticoids, dopamine and somatostatin inhibit TSH secretion.
40. 40. Thyroid function tests The tests used to investigate thyroid function can be grouped into: Tests that establish whether there is thyroid dysfunction Tests to know the cause of thyroid dysfunction
41. 41. Tests that establish whether there is thyroid dysfunction TSH, T4 and T3 measurements Thyroid function tests
42. 42. Tests to know the cause of thyroid dysfunction thyroid auto-antibody and serum thyroglobulin measurements, thyroid enzyme activities, biopsy of the thyroid, ultrasound and isotopic thyroid scanning Thyroid function tests
43. 43. TSH : - The single most sensitive, specific and reliable test of thyroid status . - In primary hypothyroidism, [TSH] is increased. - In primary hyperthyroidism, [TSH] is decrease or undetectable
44. 44. Total T4 and Total T3 : - More than 99% of T4 and T3 circulate in plasma bound to protein - Both [total T4] and [total T3] change if [TBG] alters, e.g. in pregnancy Free T4 and Free T3 Free thyroid hormone concentrations are independent of changes in the concentration of thyroid-hormone binding proteins more reliable for diagnosis of thyroid dysfunction
45. 45. Hyperthyroidism Clinical Features Palpitations Heat intolerance Nervousness Insomnia Breathlessness Increased bowel movements Light or absent menstrual periods Tachycardia Tremors Weight loss Muscle weakness Warm moist skin Hair loss Staring gaze In short everything speeds up and everything becomes hyperactive
46. 46. Hypothyroidism Clinical Features Dry skin Brittle and lustreless hair Weight gain Tiredness Constipation Muscle aches Bradycardia Cold intolarance Depression Memory Loss Menstrual irregularities (menorrhagia) In short, everything slows down and everything becomes dull.
47. 47. The major causes and clinical features of hyperthyroidism. Hyperthyroidism