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New final lft,rft,tft. Presentation Transcript

  • 1. 1
  • 2. 1.LIVER FUNCTION TESTS1.LIVER FUNCTION TESTS 2.RENAL FUNCTIONS TESTS2.RENAL FUNCTIONS TESTS 3.THYROID FUNCTION TESTS3.THYROID FUNCTION TESTS 2
  • 3. Entero hepatic Circulation 3
  • 4. Portal Hypertension 4
  • 5. 5
  • 6. Jaundice ∗ Bilirubin > 2mg/dl 6
  • 7. ∗ Usually accompanied by jaundice & pruritis ∗ Due to ∗ primary liver disease ∗ drug interference with bile secretion ∗ pregnancy ∗ Elevated blood cholesterol ∗ Xanthomas ∗ Increased ALKP Cholestasis 7
  • 8. Anatomic Types of Cirrhosis ∗ Portal ∗ caused by diffuse liver cell injury ∗ repeated episodes of necrosis followed by regeneration & growth of fibrous tissue from portal triad area ∗ most common type ∗ usually due to alcoholic liver disease or chronic viral hepatits ∗ Biliary ∗ caused by chronic disease of the biliary tree ∗ chronic inflammation of bile ducts due to ∗ autoimmune disease ∗ obstruction by gallstones ∗ sclerosing cholangitis 8
  • 9. Cirrhosis ∗ Final, common end- stage for a variety of chronic liver diseases 9
  • 10. ∗ Final & irreversible stage of alcoholic liver disease ∗ Only about 15% of alcoholics develop ∗ One of the leading causes of liver transplantation Alcoholic Cirrhosis 10
  • 11. 11
  • 12. 12
  • 13. 13
  • 14. Hepatitis B ∗ HBV ∗ Infects hundreds of millions worldwide ∗ Incubation varies from a few weeks to 6 months 14
  • 15. 15
  • 16. Hepatitis C ∗ Major cause of chronic liver disease ∗ Incubation varies from a few weeks to 6 months ∗ About 40,000 new cases/ yr 16
  • 17. 17
  • 18. ∗ Autosomal recessive disorder ∗ Toxic accumulation of copper mainly in brain & liver ∗ Copper absorbed in GI tract & excreted in bile ∗ albumin transports to liver ∗ bound to ceruloplasmin then secreted ∗ if biliary excretion decreases, accumulates in liver & brain ∗ Manifests as behavioral oddities, psychosis, tremors, abnormal gait ∗ Diagnosis confirmed by liver biopsy ∗ Early diagnosis critical ∗ Chelation therapy Wilson Disease 18
  • 19. Primary Biliary Cirrhosis ∗ Autoimmune disease ∗ Usually have another autoimmune disease ∗ Evolves from inflammatory destruction of intrahepatic bile ducts ∗ Early on see accumulation of lymphocytes around bile ducts ∗ Death due to hepatic failure & portal HTN 19
  • 20. Obstruction of the Extrahepatic Bile Ducts 20
  • 21. ∗ Gallstones in the gallbladder or biliary tree ∗ Form in gallbladder ∗ Usually have multiple stones ∗ About 1 million new cases/yr ∗50% require surgery Cholelithiasis 21
  • 22. ∗ Cholesterol gallstones ∗ 80% of cases ∗ Bile saturated with cholesterol ∗ Conditions associated with their development ∗ age & gender ∗ weight ∗ ethnic, hereditary, & geographic factors ∗ drugs ∗ acquired conditions 22
  • 23. ∗ Pigment gallstones ∗ 20% of cases ∗ Form in gallbladder & in biliary tree ∗ Composed of bilirubin & bile substances other than cholesterol 23
  • 24. Acute Cholecystitis ∗ Most common major complication of gallstones ∗ 90% associated with obstruction of the neck ∗ Gallbladder is enlarged, tense, & inflamed ∗ Persistent rather mild RUQ pain to very severe pain 24
  • 25. Chronic Cholecystitis ∗ Do not have to have a history of acute attacks ∗ Almost always associated with gallstones , ∗ Mild to moderate RUQ pain ∗ Nausea/vomiting ∗ Intolerance of fatty foods 25
  • 26. ∗ Die within a few weeks or months ∗ May be sudden injury or chronic injury ∗ Loss of 90% of function ∗ Clinically ∗ jaundice ∗ ascites ∗ fetor hepaticas ∗ hypoalbuminemia ∗ hypoglycemia ∗ palmar erythema ∗ spider angiomata ∗ testicular atrophy ∗ balding ∗ gynecomastia ∗ bleeding disorders ∗ hepatorenal syndrome ∗ hepatic encephalopathy Hepatic Failure 26
  • 27. Hepatocellular Carcinoma ∗ Usually related to HBV & HCV ∗ Hematogenous metastases are common ∗ High levels of alpha fetoprotein ∗ Prognosis is grim 27
  • 28. Metastatic Carcinoma ∗ Most common neoplasm in the liver ∗ Usually from colon, lung, breast 28
  • 29. Fulminant Hepatic Failure ∗ Acute liver disease that progresses to hepatic failure or encephalopathy in just a few weeks ∗ More than ½ of the cases are fulminant hepatitis usually involving HAV or HBV ∗ Other causes include drugs, heat stroke 29
  • 30. ∗ Liver is largest organ of the body ∗ Weight: ∗ 1–1.5 kg(1.5–2.5% of the lean body mass) ∗ Located in the right upper quadrant of abd ∗ Under the right lower rib cage. ∗ Dual blood supply ∗ ~20% oxygen rich blood from the hepatic artery ∗ 80% is nutrient rich blood from the portal vein. 30
  • 31. ∗ Two lobes: Right & Left ∗ Anatomical division ∗ By line joining gall bladder fossa to IVC ∗ Histology: ∗ Hepatocytes ∗ Kupffer cells ∗ Ito cell ∗ Cannalicular cells. 31
  • 32. ∗ Synthesis of serum proteins ∗ Albumin, Carrier proteins ∗ Coagulation factors synthesis ∗ Production of bile and its carriers ∗ Bile acids, Cholesterol, Phospholipids ∗ Regulation of nutrients ∗ Glucose, Glycogen ∗ Metabolism & conjugation ∗ Lipophilic compounds (Bilirubin, Drugs) ∗ For excretion in the bile or urine. Functions of Liver 32
  • 33. ∗ Serum Bilirubin (Conjugation) ∗ Urine Bilirubin (Conjugation) ∗ Blood Ammonia ∗ Serum enzymes reflect hepatocytes damage: ∗ ASpartate amino- Transferase (AST) (SGOT) ∗ Alanine amino- Transferase (ALT) (SGPT) ∗ Serum enzymes reflecting cholestasis: ∗ Alkaline phosphatase (AP) ∗ 5 - nucleotidase′ ∗ Gamma glutamyl trans peptidase (GGT) Detoxification or excretory functions 33
  • 34. 34
  • 35. ∗ Context of the patient’s risk factors ∗ Symptoms ∗ Concomitant conditions ∗ Medications ∗ Physical findings ∗ It rarely provide specific Diagnosis ∗ Suggest general category of liver disease ∗ Different Labs give different N values Functions of Liver Interpretation of results 35
  • 36. ∗ Bilirubin is a breakdown product ∗ Porphyrin ring of heme -containing proteins ∗ With van den Bergh method ∗ Unconjugated (indirect) ∗ 0.7mg/dl ∗ Insoluble in water & bound to albumin in blood ∗ Conjugated (direct) ∗ 0.3 mg/dl ∗ Water soluble & excreted by kidney ∗ With Newer test methods ∗ 100% serum Bilirubin = Unconjugated !! ∗ Normal total serum Bilirubin = 1.2-1.4 mg/dl Serum bilirubin 36
  • 37. ∗ Increased Production ∗ Hemolytic Disorders (not > 5 mg/dl) ∗ Spherocytosis, G6PD Def, Sickle Anaenia (inherited) ∗ PNH (Paroxysmal Nocturnal Haemaglobinuria) ∗ Immune Hemolysis, Microangiopathic Haemolysis ∗ Ineffective Erythropoiesis ∗ Cobalamin, Folate, Thalassemia, Severe Iron def ∗ Drugs (Rifampicin, Probenecid, Ribavirin) ∗ Resolving large haematoma ∗ Defective uptake / conjugation (Inherited) ∗ Crigler Najjar (Type I - II) ∗ Gilbert’s Syndrome Indirect hyper- bilirubinaemia 37
  • 38. ∗ Direct Bilirubin > 50% of total Bilirubin ∗ in Obstruction / Parenchymal disease ∗ Rarely > 30 mg/dl ∗ Filtered at the glomerulus ∗ Majority reabsorbed by the proximal tubules ∗ Small fraction appears in Urine ∗ All conjugated Direct hyper- bilirubinaemia 38
  • 39. Direct hyper- bilirubinaemia ∗ Bile duct obstruction ∗ Hepatitis ∗ Cirrhosis All ∗ Primary biliary cirrhosis ∗ Medications / Toxins ∗ Primary Sclerosing Cholangitis ∗ Sepsis ∗ Intrahepatic Cholestasis of Pregnancy ∗ Benign recurrent Cholestasis ∗ Dubin-Johnson syndrome ∗ Rotor syndrome 39
  • 40. ∗ Unconjugated Bilirubin ∗ Always binds to albumin in the serum ∗ Not filtered by kidney ∗ Only Conjugated Bilirubin found in urine ∗ Implies presence of Liver disease OR ∗ Outflow obstruction ∗ Detected by urine dipstick test Urine bilirubin 40
  • 41. ∗ Family of isoenzyme ∗ For hydrolysis of many P esters at alkaline pH ∗ Require Zn for activity ∗ Present in all tissues ∗ Liver, Bone, Gut, Placenta, Kidney ∗ Initial evaluation ∗ determine hepatic or nonhepatic origin ∗ Concomitant rise of other serum Enzymes ∗ Levels NOT reliable indicators ∗ Of severity of liver disease OR ∗ To distinguish intra / extra hepatic disease Alkaline phosphatase 41
  • 42. ∗ ALP > 1000 (normal 33-96 u/l) ∗ Malignant Biliary obstruction ∗ Sepsis ∗ AIDS with systemic infection ∗ Decrease : ∗ Hypothyroidism ∗ Pernicious anemia, ∗ Zn deficiency ∗ Wilson’s disease ∗ Severe hepatic insufficiency Alkaline phosphatase 42
  • 43. ∗ Major plasma protein ∗ Responsible for osmotic pressure of plasma ∗ Synthesized by Liver ∗ Half life 20 days ∗ Normal value 3.5 to 5.5 gm/dl ∗ Decreased in ∗ Chronic liver disease ∗ Other Causes ∗ Malnutrition ∗ Nephrotic Syndrome ∗ Protein Losing Enteropathy Serum albumin 43
  • 44. Hypoalbuminemia 44
  • 45. ∗ Produced by stimulated B lymphocyte ∗ Serum Globulin elevation in ∗ Chronic Liver Disease ∗ Chronic Inflammation and ∗ Malignant Disease ∗ Normal value 1.5 – 3.5 gm/dl ∗ Normal Albumin & Globulin Ratio 2 – 2.5 : 1 ∗ Reversal seen in ∗ Chronic Liver Disease (Cirrhosis) ∗ Late Feature Serum Globulin 45
  • 46. ∗ Reflect damage to hepatocytes (Necrosis) ∗ ASpartate amino-Transferase (AST) (SGOT) ∗ Alanine amino- Transferase (ALT) (SGPT) ∗ Located inside hepatocytes ∗ Released after hepatocyte damage ∗ Not specific to liver ∗ Found in many body tissues ∗ Elevation > 3 X normal is significant Serum enzymes: liver damage 46
  • 47. ∗ Serum enzymes that reflect cholestasis / Obstruction : ∗ Alkaline phosphatase (AP) ∗ 5 -nucleotidase′ ∗ Gamma Glutamyl Transpeptidase (GGT) ∗ Located near bile cannaliculi ∗ Released after obstruction and Cannalicular damage Serum enzymes cholestasis / obstruction 47
  • 48. ∗ < 1 : Majority of liver disease ∗ >2 ∗ Extra hepatic source ∗ Alcoholic Hepatitis ∗ Ischemic and Toxin ∗ Acute Wilson’s disease : hemolysis ∗ Cirrhosis ∗ >4 : fulminant Wilson’s disease Ast /alt ratio 48
  • 49. ∗ Acute viral hepatitis (A-E, herpes) ∗ Medications / toxins ∗ Ischemic hepatitis ∗ Heat stroke ∗ Autoimmune hepatitis ∗ Acute Budd- Chiari syndrome ∗ Wilson’s disease ∗ Acute bile duct obstruction (rare) ∗ Hepatic artery ligation >75 times = Ischemic & Toxic hepatitis AST> ALT = Ischemic & Toxic hepatitis Alt & ast > 15 times 49
  • 50. ∗ Catalyzes transfer of - glutamyl groups of peptides to other amino acid ∗ Abundant in liver, kidney, pancreas, intestine, and prostate, spleen, heart, brain ∗ But not in bone ∗ T1/2 ∗ 7-10 days ∗ 28 days in alcohol-associated liver injury Gamma glutamyl transferase (GGT) 50
  • 51. ∗ Increased in ∗ Alcohol ∗ Drug ∗Anticonvulsant (CBZ, phenytoin, and barbiturate), warfarin, Oral Contraceptives ∗ Almost all type of liver diseases ∗ COPD, Renal failure, DM, Hyperthyroidism, RA, AMI, Pancreatic disease Gamma glutamyl transferase (GGT) 51
  • 52. ∗ Non specific ∗ Rhabdomyolysis ∗ Myocardial Infarction ∗ Haemolysis, Cerebral Stroke ∗ Acute or Chronic liver disease ∗ Useful in ,Ischemic hepatitis ∗Transient, massive elevation ∗ Malignant infiltration of liver ∗Sustained elevation with ALP LDH 52
  • 53. ∗ During protein metabolism ∗ Produced in body by intestinal bacteria ∗ Liver detoxifies Ammonia ∗ By converting to urea (excreted by kidneys) ∗ Blood ammonia level ∗ Detecting Encephalopathy ∗ For monitoring Hepatic synthetic function (Urea) ∗ Very poor correlation with, Severity of acute encephalopathy Blood ammonia 53
  • 54. Initial approach History ∗ Symptoms ∗ Risk factors for Liver disease ∗ Concomitant conditions ∗ Medications ∗ Occupational exposure to hepatotoxins ∗ Physical Exam ∗ Splenomegaly ∗ Ascites ∗ Cutaneous stigmata of chronic liver disease History & physical examination Algorithm approach useful when no clinical clues 54
  • 55. ∗ Alpha-fetoprotein ∗ Ultrasound ∗ Ultrsound guided FNAC ∗ liverbiopsy 55
  • 56. ∗ Several tests for diagnosis ∗ Immunological tests ∗ Enzymes tests ∗ Biopsy- hepatomegaly, splenomegaly jaundice cirrhosis, hepatitis. 56
  • 57. 57
  • 58.  Based on Kidney Function & Clinical Utility 58 Classification – Kidney Function Test Group I Overall functioning of kidneys Complete urine analysis Measurement of non-protein nitrogenous substances in blood Measurement of serum electrolytes Group II Markers of glomerular filtration rate Clearance tests Group III Markers of glomerular permeability Microalbuminuria Proteinuria Group IV Markers of tubular dysfunction Osmolality – plasma & urine Concentration and dilution tests Tests to assess renal acidification
  • 59.  Test for glomerular filtration rate (GFR)  Useful index for the assessment of severity of kidney damage  Definition: ‘Clearance is defined as the quantity of blood or plasma that is completely cleared of a substance per unit time’  Units: ml/min 59 Clearance tests
  • 60.  Creatinine clearance: - Otto Folin: estimated it in 1904 - formation of creatinine is continuous, spontaneous and non-enzymatic - dependent on muscle mass of the body - Reference range: 85 to 125 ml/min  Inulin clearance: - polysaccharide of fructose - neither absorbed nor secreted by tubules - Reference value: 125ml/min 60 Clearance tests
  • 61.  Volume  Polyuria: ↑Urine output → > 2.5 litres/day  Oliguria: ↓ Urine outout → 300 to 500 ml/day  Anuria: ↓↓↓ Urine output → < 50 ml/day 61 Urine Analysis – Physical Characteristics Normal Range Conditions increased Conditions decreased 1000 – 1800 ml/day Diuretic therapy Diabetes insipidus Diabetes mellitus Excess sweating Dehydration Acute renal failure
  • 62. Appearance: Clear and transparent  Turbid → Excess phosphates, Urinary tract infection  Odour: Aromatic  Smell of acetone: Diabetic ketoacidosis  Fishy: Presence of blood Colour: Amber-yellow  High colour → Jaundice  Red colour → Blood  pH: 6.0 (Range: 5.5 to 7.5)  ↓ → Metabolic acidosis, ↑ → Metabolic alkalosis 62 Urine Analysis – Physical Characteristics
  • 63. Specific gravity  Instrument: ‘ Urinometer’  Fixed specific gravity of 1.010: Chronic renal failure 63 Urine Analysis – Physical Characteristics Normal Range Conditions increased Conditions decreased 1.016 to 1.022 Diabetes mellitus Nephrosis Excessive sweating Excess water intake Chronic nephritis Diabetes insipidus
  • 64. Abnormal Constituent Name of the Test Associated Clinical Conditions Characteristics Reducing Sugar or substance Benedict’s test Diabetes mellitus Gestational Diabetes Renal glycosuria Essential Pentosuria Galactosemia Hereditary fructose intolerance Essential fructosuria Lactosuria Homogentisicaciduria Ketone bodies Rothera’s test Gerhad’s test Diabetic ketoacidosis Starvation ketoacidosis Von Gierke’s disease 64 Urine analysis – Chemical Characteristics
  • 65. 65 Urine analysis – Chemical Characteristics Abnormal Constituent Name of the Test Associated Clinical Conditions Characteristics Proteins Heat & Acetic acid test Sulphosalicyli c acid test Heller’s test Glomerulonephritis Pyelonephritis Nephrotic syndrome Blood Benzidine test Stones in ureter Glomerulonephritis Renal tuberculosis Trauma to genito- urinary tract Carcinoma urinary bladder Urinary tract infection
  • 66. Abnormal Constituent Name of the Test Associated Clinical Conditions Characteristics Bile salts Hay’s test Viral hepatitis Alcoholic hepatitis Toxic hepatitis Drug induced hepatitis Obstructive jaundice Bile pigments Fouchet’s test Urine analysis – Chemical Characteristics 66
  • 67.  Major route of excretion → Urine  ↑ levels is seen in kidney dysfunction  Blood Urea: (normal 20-40 gm%/dl)  End product of protein metabolism  Serum Uric acid: (normal )  End product of purine metabolism  Serum Creatinine ( normal 0.6 to 1.2 mg/dl)  Anhydride form of c reatine formed in muscles NPN Substances measurement 67
  • 68. Segment of Nephron Substance reabsorbed Substance secreted Proximal Convoluted Tubule (PCT) Sodium Chloride Bicarbonate Water (Obligatory) H+ Organic acids and bases NH4 + Loop of Henle Sodium Chloride Calcium Magnesium --- Distal Convoluted Tubule (DCT) Sodium Chloride Water (Facultative) H+ K+ NH4 + 68 Serum Electrolytes Reabsorption and secretion of electrolytes is essential for the maintenance of body’s acid-base balance
  • 69.  Microalbuminuria  Syn: Minimal albuminuria/ pauci-albuminuria  Small quantity of albumin in urine  30 to 300 mg/day  Cause: abnormally high permeability for albumin in the renal glomerulus  Use: early marker for nephropathy in patients with diabetes and hypertensiom  Markers of Glomerular Permeability 69
  • 70.  Specific gravity  Instrument: ‘Urinometer’  earliest manifestation of renal disease → difficulty in concentrating the urine → alterations in specific gravity  Renal biopsy : Tests for renal tubular function 70
  • 71. ∗Chronic renal failure with normal sized kidney ∗Unexplained acute renal failure ∗Nephrotic syndrome in children's ∗Glomerular proteinuria in adults ∗Isolated haematuria/ proteinuria. Renal biopsy 71
  • 72. 72 Kidney Function Test - Summary Measurement of GFR Clearance tests Endogenous substance used for clearance tests Creatinine Exogenous substance used for clearance testes Inulin Volume, Appearance, Colour, Odour, Specific gravity Physical Characteristics Measurement of specific gravity Urinometer Reducing substance, Ketone bodies, Proteins, Blood, Bile salts and Bile pigments Abnormal chemical constituents Early detection of Diabetic and hypertensive nephropathy Microalbumine Specific gravity, Concentration test, Urine volume, Osmolality, Dilution test, Acidification Renal tubular function
  • 73. 73
  • 74. 74
  • 75. ∗ SCREENING FOR THYROID DYSFUNCTION ∗ SURVILENCE ∗ MONITERING. INTRODUCTION 75
  • 76. ∗ Neonates for congenital hypothyroidism ∗ Patients With Autoimmune Disease. ∗ Strong family history of family disease ∗ Patients with suspected hyperthyroidism/hypothyroidism 76
  • 77. ∗ Postpartum thyroiditis ∗ Post neck irradiation ∗ Post destructive treatment for thyrotoxicosis ∗ Monitoring treatment for hyperthyroidism with antithyroid drugs ∗ Patients with primary hypothyroidism 77
  • 78.  Based on Thyroid Function & Clinical Utility 78 Classification – Thyroid Function Test Group I Primary function of thyroid Radio-iodine uptake T3 – suppression test TSH – stimulation test TRH stimulation test Group II Measurement of blood levels of thyroid hormones Total T3 and T4 levels Free T3 and Free T4 levels Circulating TSH level Plasma tyrosine level Group III Metabolic effects of Thyroid hormones Basal Metabolic Rate Serum cholesterol level Serum creatine level Serum uric acid level Serum creatine kinase level Group IV Immunological tests for auto-immune disorders Agar gel diffusion test Complement fixation test
  • 79.  Radioactive ‘Uptake’ studies  I131 → ‘tracer’ used for thyroid studies  Normal: 20 to 40%  TSH – stimulation test  Basal levels of thyroid hormones is measured  3 injections of TSH each of 5 USP units is given 8 hourly  Failure to produce thyroid hormones → Primary hypothyroidism  Stimulation of gland by production of thyroid hormones → secondary hypothyroidism Tests based on primary function of thyroid 79
  • 80. Hormone Method Reference Range Total T4 ELISA Chemiluminescence Radioimmunoassay 5 to 12 µg/dl Total T3 120 to 190 ng/dl TSH 0.5 to 4.5 mIU/ml Free T3 Chemiluminescence 0.2 to 0.5 ng/dl Free T4 0.7 to 1.8 ng/dl Plasma Tyrosine 60 to 70 µ Mol/L MEASUREMENT OF BLOOD LEVELS OF THYROID HORMONES 80
  • 81. Disorder Causes Thyroid profile Levels Primary Hypothyroidism Congenital Radiation damage Surgical removal Viral infection Auto-immune T3 T4 TSH ↓ ↓ ↑ Secondary Hypothyroidism Damage to the pituitary gland T3 T4 TSH ↓ ↓ ↓ Hyperthyroidis m Graves disease Toxic adenoma Multi-nodular goitre Thyroid hormone overdose T3 T4 TSH ↑ ↑ ↓ Clinical Application of Thyroid Hormone Measurement 81
  • 82. Thyroid Function Test - Summary Primary function of thyroid assessment Radioactive iodine – I131 Decrease in T3, Decrease in T4 & Increase in TSH Primary hypothyroidism Increase in T3, Increase in T4 & Decrease in TSH Hyperthyroidism Anti-thyroid antibodies Hashimoto’s Thyroiditis 82
  • 83. Thyroid nodule History& physical examination TSHLow TSH High or normal scintigraphy coldhot Perform FNAC benign U/S guided FNAC Benign- ve Malignant +ve SuspiciousInadequate Repeat FNAC Surgery Surgery Observe and repeat FNAC 1 year Or levothroxin
  • 84. 84