Interpretation ofRoutine Laboratory Investigationsin General PracticeDr.Jithesh.K,MD (General Medicine)

Senior Consultant Physician

STARCARE HOSPITAL,KOZHIKODE

We were taught and

there are evidences,

which show that a good

Case History and a

thorough Clinical

examination usually

reveals most ,if not all of

clinically relevant data.

BUT…..

There remains a need to confirm/document our clinical

impression though, due to present trends of EBM and the

Medico-Legal environment.

Lab investigations supplement rather than replace other methods

for gathering information.

It is a known fact that with the help of lab investigations, some

underlying systemic conditions of which the patients(or even

doctors) are unaware of, are often identified in General practice

for the first time.

Is there a ROUTINE for

Laboratory investigations in all patients ?

NO,BUT THE LAB TEST YOU SELECT IN YOURCLINICALPRACTICE SHOULD HELP TO…

Confirm or reject your clinical diagnosis.

Provide suitable guidelines in your patient management.

Provide prognostic information of the diseases under your

consideration.

Detect diseases through case-finding screening methods.

Establish normal baseline values before treatment.

Monitor follow up therapy.

Provide information for Medico-Legal consultations.

On what basis should I select my Routine lab investigations in my General

practice?

Accuracy

Cost effectiveness

Interfering factors

Morbidity

Reference Range

Specimen collection

Sensitivity

Specificity

SENSITIVITY

(SCREENING)

The probability that a patient with disease has positive test

SPECIFICITY

(DIAGNOSTIC)

The probability that a healthy patient has a negative test

Is Blood routine examination and

Urine routine examination a

ROUTINE laboratory

investigation?

NO

• Hb

• RBC

• TC

• DC

• PLATELET COUNTBlood routine examination is better called Complete blood count(CBC).

• Urine macroscopy

• Urine microscopy

• Urine chemical tests

Urine routine examination is better called urine analaysis.

What are the Routine Laboratory investigations used by a General Practitioner that are going to be discussed here ?

Primary discussion

Complete Blood Count(CBC)

ESR

Blood Sugars

Urine analysis

Renal Function Tests(RFTs)

Liver Function Tests(LFTs)

Addendums

Peripheral smear

CRP

HBA1C

Uric acid

Prothrombin time

Why ?

Correct interpretation of these routine laboratory investigations usually directs the General practitioner to the right diagnosis in daily practice!!

RIGHT DIAGNOSIS

COMPLETE BLOOD COUNTS (CBC) or HEMOGRAM

+PERIPHERAL SMEAR

(Treasure trove for diagnosis of so many Hematological and Non hematological diseases)

Hemoglobin(Hb)

RBC counts

Total WBC counts(TC)

Differential WBC counts(DC)

Platelet counts(Plt)

Hematocrit(PCV, Packed cell volume)

Mean corpuscular volume(MCV)

Mean Corpuscular Hemoglobin(MCH)

Mean Corpuscular Hemoglobin concentration(MCHC)

COMPLETE BLOOD COUNT (CBC)

Normal Values

HEMOGLOBIN(12-15gm/dl)

IF LOW HEMOGLOBIN (ANAEMIA)

MCV

LOW (MICROCYTIC)(<85fl)

NORMAL (NORMOCYTIC)(85-100fl)

HIGH (MACROCYTIC)(>100fl)

IF HIGH HEMOGLOBIN(POLYCYTHAEMIA)

ERYTHROPOETIN

LOW (POLYCYTHAEMIA-VERA)

HIGH(SECONDARY POLYCYTHAEMIA)

CAUSES OF ANAEMIA BASED ON MCV

CAUSES OF POLYCYTHAEMIA(PCV/HEMATOCRIT >55%)

NORMAL ERYTHROPOEITIN

Total WBC count (TC)(5,000-10,000/mm3)

>10,000/mm3 <5,000/mm3

Differential count (DC)

Neutrophils(60-70%) or (3000-

7000/mm3)

Lymphocytes(20-30%) or (1000-

4000/mm3)

Eosinophils(1-3%) or (50-400/mm3)

Basophils (0.3-0.5%)and

Monocytes(3-8%)

Interpretation of the Neutrophil count

Interpretation of Neutrophil count

Interpretation of Lymphocytic count

The ALC can then be calculated by multiplying the WBC and the percentage of lymphocytes:

ALC (cells/microL) = WBC (cells/microL) x percent lymphocytes ÷ 100

Reactive/clonal/malignant — Lymphocytosis can be either a reactive polyclonal proliferation or a clonal expansion.

Causes of Lymphocytosis

Reactive

Acute viral infections (e.g., hepatitis, chicken pox, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes, rubella)

Certain bacterial infections (e.g., Enteric fever, pertussis (whooping cough), tuberculosis (TB))

Clonal

Acute/Chronic Lymphocytic Leukemias

Lymphomas

Causes of Lymphocytop-enia

Autoimmune disorders (e.g., lupus, rheumatoid arthritis)

Infections (e.g., HIV, TB, hepatitis, influenza)

Bone marrow damage (e.g., chemotherapy, radiation therapy)

Immune deficiency

Interpreting Eosinophil,Monocyte and Basophil counts

Interpretation of Platelet counts

Thrombocytopenia-<1lakh/mm3Thrombocytosis->4.5Lakhs/mm3

Interpretation of ESR

ESR vs CRP

Interpretation of Blood sugars

GLUCOMETER(LESS RELIABLE/EMERGENCIES/HOME USE)

GLUCOSE OXIDASE METHOD

MANUAL/AUTOANALYSER)(LABORATORY/DEPENDABLE/TAKES TIME)

Interpretation of Blood sugar levels

HYPERGLYCAEMIA / DIABETES MELLITUS

HYPOGLYCAEMIA

MILD HYPOGLYCA

EMIA-<70mg/dl

SEVERE HYPOGLYC

AEMIA-<45mg/dl

Causes of Glucose level variations

Hyperglycaemia

Diabetes Mellitus

Drugs(eg Steroids)

IV fluids

Infections

Stress

Pancreatitis

Hypoglycaemia

Starvation

OHAs/Insulin overdose

Alcohol

CKD

Liver diseases

Malignancy

Hypothyrodism

Infections

Interpretation of Renal function tests(RFTs)

Urine Analysis

Blood urea

Serum creatinine

Serum uric acid

GFR(wont be discussed here)

Tubular function test (Wont be discussed here)

Cystatin C (Novel marker,wont be discussed here)

Urine Analysis

Color- Pale yellow Normally, Cloudy appearance suggest infection

Urine Analysis

Urine Analysis

Urine Analysis

Urine Analysis

Urine Analysis

Urine Analysis

Urine Analysis

Urine Analysis

RFTs

RFTs

RFTs

RFTs

RFTs

RFTs

RFTs

Interpreting LFTs

Bilirubin:

• Total Bilirubin

• Direct Bilirubin (conjugated bilirubin)

Serum aminotransferases

• Aspartate aminotransferase (AST/SGOT)

• Alanine aminotransferase (ALT/SGPT)

Total Proteins

Albumin

Globulin

A/G Ratio

Alkaline Phosphatase

Prothrombin time

TOTAL BILIRUBIN(REPORTED IN LFT)

Used to determine liver’s ability to clear endogenous/exogenous substances from the circulation

Derived mainly from hemoglobin (95%)

Continuous production (300 mg daily)

Normal values of “Total” bilirubin = 0.1-1.0 mg/dL

Jaundice usually develops with a bilirubin ≥ 3 mg/dL

SUBTYPES OF BILIRUBIN

DIRECT BILIRUBIN

Reported in LFT

0.0-0.2mg%

Conjugated hyperbilirubinaemia >15% T.Bilirubin

Rarely exceeds >6mg% in the absence of renal dysfunction

Conjugated

Water soluble

Polar

Seen in urine

Elevated with biliary obstruction and hepatocellular disease.

INDIRECT BILIRUBIN

CALCULATED

Total Bilirubin- Conjugated bilirubin

If >85% of total bilirubin-Unconjugated hyperbilirubinemia

Lipid soluble/Water insoluble

Non-polar

Not in urine

Elevated with Gilberts syndrome,hemolysis, hepatic disease

LIVER ENZYMES or AMINOTRANSFERASES

Hepatic enzymes that are usually intracellular, but are released from hepatocytes with hepatocellular injury.

Catalyze -amino group transfers

• aspartate or alanine ketoglutarate

AST/ALT ratio

• Normal is 0.8

• In alcoholic hepatitis, is usually > 2

Liver Enzymes or Aminotransferases

Elevated in nearly all liver diseases (ALT > AST)

Markedly usually in hepatocellular disease

Levels may/may not reflect extent of damage

Do not correlate with eventual outcome

Usually <500 in obstructive jaundice

Exception: acute phase of biliary obstruction by the passage of a gallstone into the common bile duct. In this, the aminotransferases can briefly be in the 1000–2000 IU/L range. However, levels decrease quickly, and the LFT rapidly evolve into typical of cholestasis

Usually parallel each other

AST > ALT with EtOH, fulminant, and pregnancy

AMINOTRANSFERASES

Aspartate aminotransferase (AST/SGOT)

In cytosol and mitochondria

Liver > heart > skeletal muscle > kidneys > brain > pancreas > lungs > WBCs > RBCs

Half-life 17hrs

Alanine aminotransferase (ALT/SGPT)

In cytosol Predominantly

liver More sensitive

and specific than AST

Half-life 47hrs

Liver Enzymes

Acute hepatocellular disordersALT is higher than or equal to the AST.

C/c viral hepatitis and NAFLDAST:ALT ratio is typically <1 (but as cirrhosis develops, this

ratio rises to >1)

Alcoholic liver disease AST:ALT ratio >2:1 . The AST in alcoholic liver disease is rarely >300 IU/L, and the

ALT is often normal. A low level of ALT in the serum is due to an alcohol-

induced deficiency of pyridoxal phosphate

Alkaline Phosphatase

Enzymes that catalyze hydrolysis of large number of organic phosphate esters.

ALP mainly comes from surface of bile duct epithelial cells. Cholestasis enhances synthesis and release of ALP

Since half life is 1week ; ALP rise late in bile obstruction and decrease slowly after resolution

Found in: Liver Bone intestine 3rd trimester placenta Kidney

Alkaline Phosphatase

Increases seen with cell injury or

obstruction

Slight to moderate (1-2x) – usually

hepatocellular

Large increases (3-10x) –

obstruction or cholestasis

Alkaline phosphatase

GAMMA-GLUTAMYL TRANSPEPTIDASE (GGT)

To confirm hepatic source of ALP Elevated ALP of Liver origin: Elevated GGT

Elevated ALP of Bone origin: Normal GGT Normal levels=0-45 IU/L

Non specific as Causes of elevations includeLiver disease » Pancreatic

diseaseAlcohol » Renal diseaseCardiac disease » ObesityRadiotherapy » DiabetesDrugs – GGT is “inducible”

phenobarbital anticoagulants dilantin oral contraceptives acetaminophen tricyclic antidepressants

Usually normal in pregnancy

GAMMA-GLUTAMYL TRANSPEPTIDASE (GGT)

Prothrombin Time (PT)

Normal range PT is:11 to 13.5 seconds (Test)

INR of 0.8 to 1.1

Liver is in charge of the synthesis of many clotting factors :

Factor I (fibrinogen) , II (prothrombin) ,V ,VII , IX , X , XII and XIII

PT measures the rate of conversion of prothrombin to thrombin (requiring factors II, V, VII, and X) and thus reflects a vital synthetic function of the liver

Elevated PT may be reflection of decreased synthetic activity of liver.

Prothrombin Time (PT)

Other causes of prolongation:

congenital deficienciesconsumptive coagulopathies (i.e., DIC)drugs (i.e., warfarin)vitamin K deficiency (i.e., dietary, bile output)

Prothrombin Time (PT)