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1.LIVER FUNCTION TESTS1.LIVER FUNCTION TESTS

2.RENAL FUNCTIONS TESTS2.RENAL FUNCTIONS TESTS

3.THYROID FUNCTION TESTS3.THYROID FUNCTION TESTS

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Entero hepatic Circulation

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Portal Hypertension

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Jaundice

Bilirubin > 2mg/dl

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Usually accompanied by jaundice & pruritis

Due to primary liver disease drug interference with bile secretion pregnancy

Elevated blood cholesterol Xanthomas Increased ALKP

Cholestasis

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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

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Cirrhosis

Final, common end-stage for a variety of chronic liver diseases

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Final & irreversible stage of alcoholic liver disease

Only about 15% of alcoholics develop

One of the leading causes of liver transplantation

Alcoholic Cirrhosis

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Hepatitis B HBV Infects hundreds of millions worldwide Incubation varies from a few weeks to 6 months

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Hepatitis C Major cause of chronic liver disease Incubation varies from a few weeks to 6

months About 40,000 new cases/ yr

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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

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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

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Obstruction of the Extrahepatic Bile Ducts

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Gallstones in the gallbladder or biliary tree

Form in gallbladder Usually have multiple stones About 1 million new cases/yr

50% require surgery

Cholelithiasis

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Cholesterol gallstones 80% of cases Bile saturated with

cholesterol Conditions associated

with their development age & gender weight ethnic, hereditary, &

geographic factors drugs acquired conditions

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Pigment gallstones 20% of cases Form in gallbladder & in biliary tree Composed of bilirubin & bile substances

other than cholesterol23

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

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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 foods25

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

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Hepatocellular Carcinoma

Usually related to HBV & HCV Hematogenous metastases are common High levels of alpha fetoprotein Prognosis is grim 27

Metastatic Carcinoma

Most common neoplasm in the liver Usually from colon, lung, breast

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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

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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.

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Two lobes: Right & Left Anatomical division

By line joining gall bladder fossa to IVC Histology:

Hepatocytes Kupffer cells Ito cell Cannalicular cells.

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Hypoalbuminemia

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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

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Reflect damage to hepatocytes (Necrosis) ASpartate amino-Transferase (AST) (SGOT)

Alanine amino- Transferase (ALT) (SGPT)

Located inside hepatocytesReleased after hepatocyte damageNot specific to liver

Found in many body tissuesElevation > 3 X normal is significant

Serum enzymes: liver damage

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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 enzymescholestasis / obstruction

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< 1 : Majority of liver disease>2

Extra hepatic sourceAlcoholic Hepatitis Ischemic and Toxin Acute Wilson’s disease : hemolysis

Cirrhosis>4 : fulminant Wilson’s disease

Ast /alt ratio

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Acute viral hepatitis (A-E, herpes)Medications / toxins Ischemic hepatitisHeat strokeAutoimmune hepatitisAcute Budd- Chiari syndrome Wilson’s diseaseAcute bile duct obstruction (rare) Hepatic artery ligation

>75 times = Ischemic & Toxic hepatitisAST> ALT = Ischemic & Toxic hepatitis

Alt & ast > 15 times

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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 days28 days in alcohol-associated liver injury

Gamma glutamyl transferase (GGT)

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Increased inAlcohol 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)

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Non specificRhabdomyolysisMyocardial InfarctionHaemolysis, Cerebral StrokeAcute or Chronic liver disease

Useful in ,Ischemic hepatitisTransient, massive elevation

Malignant infiltration of liverSustained elevation with ALP

LDH

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During protein metabolism Produced in body by intestinal bacteria

Liver detoxifies Ammonia By converting to urea (excreted by kidneys)

Blood ammonia level Detecting EncephalopathyFor monitoring Hepatic synthetic function (Urea)

Very poor correlation with, Severity of acute encephalopathy

Blood ammonia

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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 examinationAlgorithm approach useful when no clinical clues

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Alpha-fetoprotein Ultrasound Ultrsound guided FNAC liverbiopsy

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Several tests for diagnosis Immunological tests Enzymes tests Biopsy- hepatomegaly,

splenomegaly jaundice cirrhosis, hepatitis.

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Based on Kidney Function & Clinical Utility

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Classification – Kidney Function Test

Group I Overall functioning of kidneys

Complete urine analysisMeasurement of non-protein nitrogenous substances in bloodMeasurement 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 & urineConcentration and dilution testsTests to assess renal acidification

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

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Clearance tests

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

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Clearance tests

Volume

Polyuria: Urine output > 2.5 litres/day

Oliguria: Urine outout 300 to 500 ml/day

Anuria: Urine output < 50 ml/day61

Urine Analysis – Physical Characteristics

Normal Range Conditions increased

Conditions decreased

1000 – 1800 ml/day

Diuretic therapyDiabetes insipidusDiabetes mellitus

Excess sweatingDehydrationAcute renal failure

Appearance: Clear and transparent Turbid Excess phosphates, Urinary tract infection Odour: Aromatic Smell of acetone: Diabetic ketoacidosis Fishy: Presence of bloodColour: Amber-yellow High colour Jaundice Red colour Blood pH: 6.0 (Range: 5.5 to 7.5)

Metabolic acidosis, Metabolic alkalosis

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Specific gravity Instrument: ‘ Urinometer’

Fixed specific gravity of 1.010: Chronic renal failure

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Normal Range Conditions increased

Conditions decreased

1.016 to 1.022 Diabetes mellitusNephrosisExcessive sweating

Excess water intakeChronic nephritisDiabetes insipidus

Abnormal Constituent

Name of the Test

Associated Clinical Conditions

Characteristics

Reducing Sugar or substance

Benedict’s test

Diabetes mellitusGestational DiabetesRenal glycosuriaEssential PentosuriaGalactosemiaHereditary fructose intoleranceEssential fructosuriaLactosuriaHomogentisicaciduria

Ketone bodies

Rothera’s testGerhad’s test

Diabetic ketoacidosisStarvation ketoacidosisVon Gierke’s disease

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Urine analysis – Chemical Characteristics

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Urine analysis – Chemical CharacteristicsAbnormal

Constituent

Name of the Test


Characteristics

Proteins Heat & Acetic acid testSulphosalicylic acid testHeller’s test

GlomerulonephritisPyelonephritisNephrotic syndrome

Blood Benzidine test

Stones in ureterGlomerulonephritisRenal tuberculosisTrauma to genito-urinary tractCarcinoma urinary bladderUrinary tract infection

Abnormal Constituent

Name of the Test


Characteristics

Bile salts Hay’s test

Viral hepatitisAlcoholic hepatitis Toxic hepatitisDrug induced hepatitisObstructive jaundice

Bile pigments

Fouchet’s test

Urine analysis – Chemical Characteristics

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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

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Segment of Nephron Substance reabsorbed

Substance secreted

Proximal Convoluted Tubule (PCT)

SodiumChlorideBicarbonateWater (Obligatory)

H+

Organic acids and basesNH4

+

Loop of Henle SodiumChlorideCalciumMagnesium

---

Distal Convoluted Tubule (DCT)

SodiumChlorideWater (Facultative)

H+

K+

NH4+

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Serum Electrolytes

Reabsorption and secretion of electrolytes is essential for the maintenance of body’s acid-base balance

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

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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

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Chronic renal failure with normal sized kidney

Unexplained acute renal failureNephrotic syndrome in children'sGlomerular proteinuria in adultsIsolated haematuria/ proteinuria.

Renal biopsy

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Kidney Function Test - SummaryMeasurement 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

SCREENING FOR THYROID DYSFUNCTION

SURVILENCE

MONITERING.

INTRODUCTION

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Neonates for congenital hypothyroidism

Patients With Autoimmune Disease.

Strong family history of family disease

Patients with suspected hyperthyroidism/hypothyroidism

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Postpartum thyroiditisPost neck irradiationPost destructive treatment for thyrotoxicosis

Monitoring treatment for hyperthyroidism with antithyroid drugs

Patients with primary hypothyroidism77

Based on Thyroid Function & Clinical Utility

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Classification – Thyroid Function Test

Group I Primary function of thyroid

Radio-iodine uptake T3 – suppression testTSH – stimulation testTRH stimulation test

Group II Measurement of blood levels of thyroid hormones

Total T3 and T4 levelsFree T3 and Free T4 levelsCirculating TSH levelPlasma tyrosine level

Group III

Metabolic effects of Thyroid hormones

Basal Metabolic RateSerum cholesterol levelSerum creatine levelSerum uric acid levelSerum creatine kinase level

Group IV

Immunological tests for auto-immune disorders

Agar gel diffusion testComplement fixation test

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

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Hormone Method Reference Range

Total T4 ELISAChemiluminescenceRadioimmunoassay

5 to 12 g/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 Mol/L

MEASUREMENT OF BLOOD LEVELS OF THYROID HORMONES

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Disorder Causes Thyroid profile

Levels

Primary Hypothyroidism

CongenitalRadiation damageSurgical removalViral infectionAuto-immune

T3T4

TSH

Secondary Hypothyroidism

Damage to the pituitary gland

T3T4

TSH

Hyperthyroidism

Graves diseaseToxic adenomaMulti-nodular goitreThyroid hormone overdose

T3T4

TSH

Clinical Application of Thyroid Hormone Measurement

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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

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Thyroid nodule

History& physical examination

TSHLow TSH

High or

normal

scintigraphy

coldhot

Perform

FNACbenign

U/S guided FNAC

Benign- ve

Malignant +ve

Suspicious

Inadequate

Repeat FNAC

Surgery Surgery Observe

and repeat FNAC 1 year

Or levothroxin

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