approach to anemia and jaundice

Approach to Anaemia and Jaundice

IV Term- Introductory Lecture Series

Dept of Medicine

Dr Khati

Learning Objectives

• To be able to list steps in hemoglobin degradation

• Learn definitions and meanings of terms

• To list the broad types of anaemia

• To list the broad types of jaundice

• To identify common causes of anaemia and jaundice

Learning Objectives

List steps in clinical evaluation of anaemia and jaundice-

• Patient details

• History

• General Physical Examination

• Systemic Examination

Learning Objectives

• List steps in lab evaluation of anaemia and jaundice

Steps in Hemoglobin Metabolism

• Hb Biosynthesis • Hb Catabolism

http://www.google.co.in/imgres?imgurl=http://diaglab.vet.cornell.edu/clinpath/modules/rbcmorph/images/n-goat.jpg&imgrefurl=http://diaglab.vet.cornell.edu/clinpath/modules/rbcmorph/caprine.htm&h=300&w=400&sz=26&tbnid=7EYXkYeXk4_uzM:&tbnh=93&tbnw=124&prev=/images?q=Poikilocytosis+images&hl=en&usg=__6oovbr32nKoSOkC1FCaiDgww0A8=&ei=AQmvS7_wKZiekQWp_4mjDQ&sa=X&oi=image_result&resnum=2&ct=image&ved=0CAsQ9QEwAQ




http://www.google.co.in/imgres?imgurl=http://path.upmc.edu/cases/case159/images/micro8.jpg&imgrefurl=http://path.upmc.edu/cases/case159/micro.html&h=408&w=547&sz=24&tbnid=3dvs0QyPrEWQwM:&tbnh=99&tbnw=133&prev=/images?q=Poikilocytosis+images&hl=en&usg=__1OIZn3zRwqTSnYUMoH7y_-WXQcs=&ei=AQmvS7_wKZiekQWp_4mjDQ&sa=X&oi=image_result&resnum=3&ct=image&ved=0CA0Q9QEwAg






Biosynthesis

Heme

• Mitochondria & Cytosol

• porphyrin ring consists of four pyrrolemolecules cyclically linked together with the iron ion bound in the centre.

Globin

• Ribosomes

• Two distinct globin chains (each with its individual heme molecule) combine to form hemoglobin.

• One of the chains is designated alpha. The second chain is called "non-alpha".



Hb degradation

Anemia Jaundice

Hb degradation in RE System

• Denaturation, removal &recycling of protein globin

• Oxidation and opening of the tetrapyrrole ring

• Removal of iron to form the green pigment -biliverdin

• Reduction to bilirubin (+H, insoluble, lipophilic)

• Albumin bound transportation to liver

Hb degradation in the liver

• Conjugated into mono- and diglucuronides (+S, water-soluble)

• Bilirubin glucuronide is passed through the liver cells into the bile caniculi and then into the intestines

Hb degradation in the intestines

• Converted to urobilinogen (colourless) by gut flora

• Urobilinogen is converted to stercobilinogenand stercobilin (excreted in stool)

• Some is converted to urobilin (excreted in stool)

Fate of Urobilinogen

• Converted to stercobilinogen and stercobilin

• Partial reabsoption in the small intestine and recirculation back to the liver - enterohepaticcirculation

• Resorption into blood and passage to kidney for excretion

• Oxidised to urobilin on exposure

Urobilinogen- normal component of urine

Increase in urinary urobilinogen

• hepato-cellular dysfunction

• increased bilirubin formation- haemolysis

In intrahepatic obstruction there is no urobilinogen in the urine.

Definitions- Anaemia

• Anaemia is a state in which the level of hemoglobin in the blood is below the normal range appropriate for age and sex (pregnancy and altitude also should be taken into account). DAVIDSON


• Anaemia is recognised in the lab when a patientshemoglobin level or hematocrit is reduced belowan expected value (the normal range).

• The likelihood and severity of anaemia are definedbased on the deviation of the patient’s hemoglobinor hematocrit, from values expected for age andsex matched normal subjects.

• Hematocrit • For males 47% + SD7

• For females 42% + SD5

• HARRISON


• A reduction in the number of circulating erythrocytes CECIL


• Anaemia results from a reduction in the number of red cells or of the hemoglobin concentration within the cells

• The term anaemia simply means a reduced hemoglobin concentration (adjusted for age and sex) with no specific cause implied. HUTCHISON.

Normal red cell values in adults-Hutchison

Males Females

Table 26.1 Table A 1.2 Table 26.1 Table A 1.2

Hb (g/dl) 13.3 – 16.7 13.5 – 17.5 11.8 – 14.8 11.5 – 16.5

RBC (X10 12

/L)4.32 – 5.66 4.5 – 6.5 3.88 – 4.99 3.8 – 5.8

PCV/Hct % 0.39 – 0.5 0.4 – 0.54 0.36 – 0.44 0.37 -0.47

MCV (fL) 76 - 96 80 - 96 76 - 96 80 - 96

Different Criteria for AnaemiaMen g/dL

Women g/dL

% normal below cut -off

Effect of race

WHO (Blanc et al)

13 12 Not provided Not provided

Jandl 14.2 12.2 2.5 Discussed

Williams (Beutler et al)

14.0 12.3 2.5 Not provided

Wintrobe (Lee et al)

13.2 11.6 Not provided Not provided

Rappaport 14 12 Not provided Not provided Goyette 13.2 11.7 5 hemoglobin 0.5 g/dL

lower- Blacks' Tietz 13.2 11.7 Not provided Not provided Hoffman et al 13.5 12.0 2.5 Not provided

WHO Criteria for the diagnosis of anaemia

• In detecting and evaluating an anemia problem ina country reference standards are necessary eventhough they may be somewhat arbitrary.

• The report of the 1958 WHO Study grouprecommends these values below which anaemiawould be considered to exist.

• These figures were chosen arbitrarily and it is stillnot possible to define normality precisely,however more recent data indicate that thevalues given previously should be modified.

WHO Criteria for the diagnosis of anaemia

• It is recommended that in future studies anemia should be considered to exist in those whose levels are lower than the figures given below.

Indian Criteria cannot be very different from those of WHO

Infant 6-12 months & children 1-5 years <11 gm%

Adolescent girls <12 gm%

Women in reproductive age group < 12 gm%

Pregnant women < 11 gm%

Lactating women < 12 gm%

Adult men <13mg%

Mild to moderate anaemia 7-10.5 gm%

Severe anaemia < 7 gm%

We need to look at-

• Hemoglobin

• Hematocrit

• RBC Count

RBC Indices

• MCV

• MCHC

• MCH

• RDW

Hemoglobin

• Hemoglobin is a pigment in RBCs.

• It is the carries the oxygen from the lungs to cells throughout the body.

• Unit: grams/deciliter of whole blood.(1 dl =100 ml).

• The normal ranges for hemoglobin depend on the age and gender of the person.

Hutchison- Reference Range forHemoglobin (Hb)

• Normal range for females: 11.5 – 16.5

• Normal range for males:13.5 – 17.5

WHO Criteria for the diagnosis of anaemia ( below - g/ dl)

• Children 6 months to 6 years- 11

• Children 6 to 14 years- 12

• Adult males- 13

• Adult females (non pregnant)- 12

• Adult females (pregnant)- 11

Definition/ Meaning- Hematocrit

• The hematocrit is the proportion, by volume, of the blood that consists of red blood cells.

• The hematocrit is expressed as a percentage.

• The percentage by volume of packed red blood cells in a given sample of blood after centrifugation.

Definition/ Meaning- Hematocrit ranges vary with age and gender

• Newborns: 55-68%

• One (1) week of age: 47-65%

• One (1) month of age: 37-49%

• Three (3) months of age: 30-36%

• One (1) year of age: 29-41%

• Ten (10) years of age: 36-40%

• Adult males: 42-54%

• Adult women: 38-46%

Hutchison- Reference Range forHematocrit (HCT/ PCV)

The percentage of (red blood) cells in the blood.

• Normal range for females: 37% - 47%

• Normal range for males: 40% - 54%

Definition/ Meaning- Total RBC Count (TRBC) 1,2,3,4,1000, 5million

• It is a count of the number of RBCs per unitvolume of blood.

• Dependent on hormone Erthyropoietin,

• Normal red blood cells counts at various ages are: – Newborns: 4.8 - 7.2 million

– Adults: (males): 4.6 - 6.0 million

– (Females): 4.2-5.0 million

– Pregnancy: slightly lower than normal adult values

– Children: 3.8 – 5.5 million

Hutchison- Reference Range for Total RBC Count (TRBC)

• 4.5-6.5x106/µL or 1012 L (Male)

• 3.8-5.8x106/µL or 1012 L (Female)

Definition/ Meanings: RBC Indices

• Red blood cell indices are measurementsthat describe the size and oxygen-carrying protein (hemoglobin) content ofred blood cells.


• Red blood cell indices are measurementsthat describe the size and oxygen-carrying protein (hemoglobin) content ofred blood cells.

• The indices are used to help in thedifferential diagnosis of anemia. They arealso called red cell absolute values orerythrocyte indices.


• mean corpuscular volume (MCV)

• mean corpuscular hemoglobin (MCH)

• mean corpuscular hemoglobin concentration(MCHC)

• red cell distribution width (RDW).

Definition/ Meaning- Mean

corpuscular volume (MCV)- Size



• It measures the average volume of a red blood cell by dividing the hematocrit by the RBC count (PCV/TRBC)




• Normocytic anaemias

• Microcytic anaemias

• Macrocytic anaemias




• Normocytic anaemias- normal size

• Microcytic anaemias- small size

• Macrocytic anaemias- large size

Definition/ Meaning- Mean corpuscular hemoglobin concentration

(MCHC) Colour.


(MCHC) Colour• The MCHC measures the average

concentration of hemoglobin in a red blood cell.




• This index is calculated by dividing the hemoglobin by the hematocrit. (Hb/ PCV)




• This index is calculated by dividing the hemoglobin by the hematocrit.

• The MCHC categorizes red blood cells according to their concentration of hemoglobin.


(MCHC) Colour

– normochromic;

– hypochromic.

– there is no hyperchromic category.

Definition/Meaning-Mean corpuscular hemoglobin(MCH)

http://images.clipartof.com/small/12017-Balancing-Weighing-Scale-Clipart-Illustration.jpg


Definition/Meaning-Mean corpuscular hemoglobin(MCH)• The average weight of hemoglobin in an RBC

is measured by the MCH.





• The formula for this index is the value of hemoglobin multiplied by 10 and divided by the TRBC. (Hb X 10/ TRBC)





• MCH values usually rise or fall as the MCV is increased or decreased.



Definition/ Meaning-RDW

• The red blood cell distribution width

(RDW), is a measure of the variation of RBC size (MCV).

http://en.wikipedia.org/wiki/File:Rainbow-diagram-ROYGBIV.svg




(RDW), is a measure of the variation of RBC size (MCV).Higher RDW values indicate greater variation in size.

.






RDW = (standard deviation of MCV÷ mean MCV) × 100

Normal- 11 to 15%

• .






• It is mainly used to differentiate an anemia of mixed causes from an anemia of a single cause.




• An elevated RDW, that is red blood cells of

unequal sizes, is known as anisocytosis.

• High RDW

http://www.drdavidmarquis.com/marquis_images/bloodcellimages/clip_image008.jpg

http://www.drdavidmarquis.com/marquis_images/bloodcellimages/clip_image008.jpg

• Poikilocytosis- unequal shapes







http://www.google.co.in/imgres?imgurl=http://meds.queensu.ca/medicine/deptmed/hemonc/anemia/poikilo.gif&imgrefurl=http://meds.queensu.ca/medicine/deptmed/hemonc/anemia/poikilo.htm&h=288&w=384&sz=80&tbnid=UAhQUpWgSEXcvM:&tbnh=92&tbnw=123&prev=/images?q=Poikilocytosis+images&hl=en&usg=__Lyg1uWa2QNk0Jp8xKl2B-Ifo-hM=&ei=AQmvS7_wKZiekQWp_4mjDQ&sa=X&oi=image_result&resnum=1&ct=image&ved=0CAkQ9QEwAA




http://path.upmc.edu/cases/case159/images/micro8.jpg

http://path.upmc.edu/cases/case159/images/micro8.jpg

Definition/ Meaning- Reticulocytes

These slightly immature cells are called reticulocytes, and are characterized by a network of filaments and granules. Reticulocytes normally make up 1% of

http://diaglab.vet.cornell.edu/clinpath/modules/rbcmorph/images/catregcp.jpg

http://diaglab.vet.cornell.edu/clinpath/modules/rbcmorph/images/catregcp.jpg

http://www.marvistavet.com/assets/images/red_blood_cells_with_reticulocytes.gif

http://www.marvistavet.com/assets/images/red_blood_cells_with_reticulocytes.gif

Definition/ Meaning- Reticulocyte count


• The number of reticulocytes (young red blood cells) circulating in blood, usually less than 1% of the total number of the red blood cells.


• The number of reticulocytes (young red blood cells) circulating in blood, usually less than 1% of the total number of the red blood cells.

• Elevation of the reticulocyte count above 1% (reticulocytosis) is a sign of rapid red blood cell production.

Definition/ Meaning- Reticulocytecount

• Reticulocyte (%) = [Number of Reticulocytes / Number of Red Blood Cells] X 100

• Reticulocyte Index = Reticulocyte count (%) X [Measured hematocrit / Normal hematocrit]


• Decreased reticulocyte percentages are seen in-

• Iron Defeciency Anemia

• Pernicious Anemia

• Folic acid deficiency

• Aplastic anemia

• Radiation therapy

• Bone marrow failure caused by infection or cancer

http://www.labtestsonline.org/understanding/conditions/vitaminb12.html



http://www.labtestsonline.org/understanding/conditions/anemia-4.html


• Where would increased reticulocyte counts be found?

Definition/ Meaning- Ferretin

• Ferritin is a protein that stores iron and releases it in a controlled fashion

• Male: 12-300 ng/mL

• Female: 12-150 ng/mL

Where do you think these levels would be low/ high???

Definition/ Meaning- Ferretin

• Ferritin is a protein that stores iron and releases it in a controlled fashion

• Male: 12-300 ng/mL

• Female: 12-150 ng/mL

Low Ferretin: Iron deficiency, loss, poor absorbtion

High Ferretin: Multiple transfusions, hemochromatosis, hemolytic anemias,

Definition/ Meaning- Serum Iron and TIBC

• Iron is carried in the blood attached to the protein transferrin.


IronFree

Transferrin

Iron transferrin

complex


TIBCSerum

Iron



• Serum iron is a test that measures the amount of circulating iron that is bound to transferrin



• Serum iron is a test that measures the amount of circulating iron that is bound to transferrin

• Total iron binding capacity (TIBC) is a blood test which measures the capacity to bind iron with transferrin (free transferrin)

Definition/ Meaning: Jaundice

• Yellow staining of the skin and sclerae (the whites of the eyes) by abnormally high blood levels of the bile pigment bilirubin.

• The yellowing extends to other tissues and body fluids.

• Jaundice was once called the "morbus regius" (the regal disease) in the belief that only the touch of a king could cure it.



Classification of Anaemias

• Morphological Approach(appearance)

MCV based

• Kinetic approach (production, destruction & loss)

Reticulocyte count based

Morphological Types of Anaemia

• MCV• Microcytic

• Normocytic

• Macrocytic

• MCH & MCHC• Hypochromic

• Normochromic

Morphologic Approach

Normal MCV Low MCV High MCV

Acute blood loss

Iron Deficiency B12 Deficiency

Anaemia of chronic disease

Thallassemia FolateDeficiency

Kinetic Types of Anaemia

• Hypoproliferative- Low reticulocyte count

• Hyperproliferative- high reticulocyte count

Kinetic Approach

Decreased Marrow Production

Peripheral Causes

Fe, B12, Folate Deficiency Blood loss

Hypoplasia Hemolysis

Anemia of chronic disease Hypersplenism

Invasion by Malignant cells

Renal Failure

Types of JaundiceHemolytic Hepatocellular Obstructive

Low Hb V V

Low PCV A A

Reticulocytosis R R

RBC indices I I

Anisopoikilocytosis ABLE ABLE

UnconjugatedHyperbilirubinemia

Conjugated and unconjugatedHyperbilirubinemia

Conjugated and unconjugatedHyperbilirubinemia

Urinary urobilinogen Urinary urobilinogen No Urinary Urobilin

Causes of Anaemia and Jaundice

• Hemolytic States

• Hemorrhage within the body

• Chronic diseases-

• Disseminated Infections- Malaria, TB, Typhoid

• Myeloproliferative disorders

• Pancreato- biliary malignancy

• Drugs

Steps in clinical evaluation of anaemia and jaundice

Clinical Approach must be wide ranging


• Patient details

steps in clinical evaluation of anaemia and jaundice

• Patient details

• Age

• Gender

• Race

• Resident of

• Dietary habits


Chief Complaints:

• Non specific complaints

• Complaints pointing to underlying disease


Non specific Complaints:

• Weakness, fatigability, lassitude

• Dull headaches

• Palpitations, ringing in the ears

• Postural dizziness, fainting, syncope,

• Breathlessness

• Chest pain

• Swelling of face/ feet


Specific Complaints:

• Yellow colouration/ paleness• Colour changes in urine and stool• Fever• GI Disturbances• Itching• Bleeding• Weight loss• Lump

Steps in clinical evaluation of anemia and jaundice

• Personal, Family and Treatment History:

• Nutritional History


• Patient details

• Chief Complaints

• History



• Patient details


• History


• Systemic Examination


• Patient details


• History


• Systemic Examination: GI evaluation is Most Important in unexplained anemia

Lab evaluation of anaemia and jaundice

• Hematology- routine

• Urine- routine

• Biochemistry

• Imaging

• Hematology special tests

• Others

25 year old soldier on exercise in jungles of Nagaland

• Irregular fever with headache X 7 days

• Easy fatigability and palpitations X 5 days

• Yellow discoloration of eyes X 2 days

• Coco cola coloured urine X 1 day

• How will you evaluate ?

30 year old lady, victim of domestic violence 3 days back

• Postural dizziness

• Pain right side of abdomen

• Multiple bruises

• Jaundice

• How will you proceed

15 year old girl, looks pale

• Progressive weakness X 6 months

• Palpitations and breathlessness on exertion X 1 month

• How will you evaluate?

50 year old man went to donate blood

• He was told that he could not donate blood because he had anemia


35 year old man

• Dyspepsia off and on X several years

• Easy fatiguability X 2 months

• Looks pale


6 year old boy

• Failure to thrive since the age of 6 months

• Intermittent pain abdomen and fever since infancy

• Lump in abdomen X 2 years

• Yellowish discoloration of eyes X 2 years

• How will you evaluate ?

approach to anemia and jaundice

Health & Medicine

level of hemoglobin

patients hemoglobin

lab evaluation of anaemia

urobilinogen colourless

liver hb degradation

severity of anaemia

designated alpha

clinical evaluation