Blood 1

Good Morning

BLOOD AND ITS COMPONENTS

Dr. Nitika Jain

04/12/2023BLOOD AND ITS COMPONENTS 3

CONTENTS Introduction Properties of blood Composition of blood Functions of blood Red blood cells Erythropoiesis


Erythrocyte sedimentation rate White blood cells Platelets


Coagulation of blood

Test for clottingBleeding timeClotting timeProthrombin timePartial Prothrombin timeThrombin time

Bleeding disorders


INTRODUCTION Connective tissue in fluid form

Fluid of lifeFluid of growthFluid of health


PROPERTIES OF BLOOD Color Volume Reaction and pH Specific gravity Viscosity


COMPOSITION OF BLOOD Blood cells

RBCWBC

Platelets Plasma Serum



Plasma – Straw colored clear liquid part of the bloodContains 91-92% water and 8-9% solids

Serum – Clear straw colored fluid that is left after

blood has been clotted.Serum is same as plasma but only

difference serum is devoid of fibrinogen ( its absent because fibrinogen is converted into fibrin during blood clotting).


COMPOSITION OF PLASMA MOLECULAR WEIGHT:-

Albumin:69,000 Globulin:1,56,000 Fibrinogen:4,00,000

ONCOTIC PRESSURE – The plasma proteins are responsible for the

oncotic or osmotic pressure. Normally it is about 25 mm Hg.

SPECIFIC GRAVITY- The specific gravity plasma proteins is

1.026. BUFFER ACTION – Hydrogen ions is responsible for buffer

action. The plasma protein have 1/6th of total buffering action of blood.


FUNCTIONS OF BLOOD Nutrient function Respiratory function Excretory function Transport of hormones and enzymes Regulation of water balance Regulation of acid – base balance Regulation of body temperature Storage function Defensive function


RED BLOOD CELLS Non – nucleated cells Normal value

4 and 5.5 millions per cu mm of bloodMales – 5 millions/ Cu mmFemales – 4.5 millions/ Cu mm


MORPHOLOGY OF RBC Morphology of RBC

Disk shaped and biconcave Advantages of biconcave shape of RBC Normal size

Diameter – 6.9 – 7.4µThickness – Periphery – 2.2µ and centre - 1µSurface area – 120 sq. µVolume – 85 - 90 cu.µ


PROPERTIES OF RBC Rouleaux formation Specific gravity

1.092 to 1.101 Packed cell volume Suspension stability Lifespan of RBC – 120 days. After the

lifetime the senile RBC are destroyed in reticuloendothelial system.


FUNCTIONS OF RBC Transport of oxygen from lungs to the

tissues Transport of CO2 from tissues to the

lungs Buffering action in blood – Hb acts as

buffer In blood group determination



VARIATION IN NUMBER OF RBC

Physiological variations Increase in RBC count

Age Gender High altitude Muscular exercise Emotional conditions Increased environmental temp. After meals

Decrease in RBC count High barometric pressure During sleep – all the activities decreases Pregnancy – decrease in ECF vol. – increase in

plasma vol. resulting in hemodilution.


Birth – 8 to10 millions/cc

Count decreases causing physiological jaundice

Infants and growing children have increased count


Before puberty and menopause count is same as males

During reproductive age the count is less than that of males


Temporary increase in RBC count after exercise

mild hypoxia and contraction of spleen. Spleen stores RBC.

Hypoxia increases the sympathetic activity resulting in secretion of adrenaline. Adrenaline contracts the spleen and hence RBC are produced


High altitude

hypoxia

Stimulation of kidney

Production of erythrpotein

Stimulation of bone marrow

Production of RBC

Emotional conditions

Increased sympathetic activity

Increased secretion of adrenaline

Contraction of spleen

Release of RBC


Pathological variationsPathological polycythemia

RBC count increases 7millions/cc of bloodTwo types:1.Primary2.Secondary


PRIMARY POLYCYTHEMIA Persistent increase in RBC count above

14 millions/cc of blood. Always associated with increased white

blood cell count above 24ooo/cc of blood.

Occurs in myeloproliferative disorders like malignancy of red bone marrow


SECONDARY POLYCYTHEMIA Secondary to some of the pathological

conditions:Respiratory disorders like emphysemaCongenital heart diseaseAyerza’s disease – hypertrophy of right

ventricle and obstruction of blood flow to lungs.

Chronic carbon monoxide poisoningPoisoning by chemicals like phosphorus,

and arsenicRepeated mild hemorrahages


ERYTHROPOIESIS Process of origin, development and

maturation of erythrocytes.



Changes during ErythropoiesisReduction in size of RBCDisappearance of nucleoli and nucleusAppearance of hemoglobinChange in the cytoplasm properties of the

cytoplasm


STAGES OF ERYTHROPOIESISThe various stages between stem cells

and matured red blood cell are; Proerythroblasts Early normoblasts Intermediate normoblasts Late normoblasts Reticulocytes Matured erythrocytes




RBCs after 120 days

Fragile

Membranes of RBC rupture

Phagocytized by Reticulo endothelial

system

Tissue macrophages Kupffer cells

SpleenFATE OF RBC


HEMOGLOBIN SPLIT

Heme Globin Amino acid

pool- reuse

Free Iron Straight chain of 4 pyrole nuclei

Transported in blood by transferrin

Reused


Straight chain of 4 pyrole nuclei

Biliverdin

Free Bilirubin (released by Macrophages)

Combination with plasma Albumin

Blood Interstitial

fluids

Liver kidney-- Nil

Free Bilirubin

HEME OXYGENASE

BILIVERDIN REDUCTASE


ERYTHROCYTE SEDIMENTATION RATE The rate at which the erythrocytes

settle down. Methods:

Westergren’s methodWintrobe’s method


Normal values:Westergren's method

Males – 3 to 7 mm Females – 5 to 9 mm Infants – 0 to 2 mm

Wintrobe’s method Males – 0 to 9 mm Females – 0 to 15 mm Infants – 0 to 5 mm


VARIATION IN ESR Physiological variation

Age – less in children and infantsGender – more in females than in malesMenstruation – increases because of loss of

bloodPregnancy – from 3rd to paturition ESR

increases because of hemodilution


Pathological variation Increased in

Tuberculosis All types of anemia except sickle cell anemia Malignant tumors Rheumatoid arthritis Rheumatic fever Liver diseases

Decreased in Allergic conditions Sickle cell anemia Polycythemia Severe leukocytosis


SIGNIFICANCE OF DETERMINING ESR ESR is an easy, inexpensive and non

specific test , which helps in diagnosis as well as in prognosis.

Certain disorders like:Pulmonary TBRheumatoid arthritisPolymyalgia rheumaticaTemporal arteritis


FACTORS EFFECTING ESR Specific gravity of RBC – Increases so

ESR also increases Rouleaux formation – increases the ESR Increase in size of RBC – increases so

ESR also increases Viscosity of blood – increases so ESR

decreases RBC count – increases so viscosity

increases so ESR decreases.


GOOD MORNING


HEMOGLOBIN


HEMOGLOBIN Hb is the iron containing coloring matter

of RBC The main function of red cells is to carry

O2 to the tissues and to return carbon dioxide (CO2) from tissues to the lungs.

In order to achieve this gaseous exchange the red cells contain the specialized protein haemoglobin.

Each red cell contains approximately 640 million Hb molecules.


NORMAL HEMOGLOBIN CONTENT Average Hb in blood is 14 to 16g/dL Age

At birth – 25g/dLAfter 3rd month – 20g/dLAfter 1 year – 17g/dLFrom puberty onwards – 14 – 16g/dL

Gender In adult males – 15g/dL In adult females – 14.5g/dL


FUNCTIONS OF HB Transport of gases

Oxygen Oxygen + Hb known as oxygenation occurs

resulting in the formation of oxyHb Iron in this state remains as ferrous Its an unstable compound and the combination

is reversibleCarbon dioxide

Carboxyhaemoglobin is formed Unstable and reversible Hb has 250 times affinity for Co2 as compared

to oxygen


STRUCTURE OF HB


IRON In ferrous form, unstable and loose form In some abnormal conditions gets

converted into ferric form – stable form Porphyrin

Pigment partFormed by 4 pyrrole ringsAttached by methane bridges

Globin 4 polypeptide chains2 alpha and 2 beta



B

B

A

A

heme

HEMOGLOBIN STRUCTURE



Hb A Hb A2 Hb F

structure a2b2 a2d2 a2g2

Normal % 96-98 % 1.5-3.2 % 0.5-0.8 %

ADULT HAEMOBLOBIN

04/12/2023 BLOOD AND ITS COMPONENTS 52

HAEMOGLOBIN SYNTHESIS Haem synthesis starts

with the condensation of glycine and succinyl coenzyme A under the action of a rate limiting enzyme d-aminolaevulinic acid synthase.

d-ALA will be formed. Pyridoxal phosphate

(vit. B6) is a coenzyme for this reaction.


HAEMOGLOBIN SYNTHESIS A series of biochemical

reactions will follow. Two molecules of d-ALA

condense to form a pyrrole called porphobilinogen (PBG)

Four PBG condense to form a tetrapyrrole uroporphyrinogen III.

UPG III is then converted to coproporphyrinogen.


HAEMOGLOBIN SYNTHESIS CPG then changes to

protoporphyrin which ultimately combines with iron in the ferrous state (Fe2+) to form haem.

Iron is brought to the developing red cells by a carrier protein ( transferrin) which attaches to special binding sites on the surface of these cells.

Transferrin releases iron and returns back to circulation.


HAEMOGLOBIN SYNTHESIS Each molecule of

haem combines with a globin chain.

A tetramer of four globin chains each with its own haem group in a pocket is formed to make up a haemoglobin molecule.


HEMOGLOBIN SPLIT

Heme Globin Amino acid

pool- reuse

Free Iron Straight chain of 4 pyrole nuclei

Transported in blood by transferrin

Reused


Straight chain of 4 pyrole nuclei

Biliverdin

Free Bilirubin (released by Macrophages)

Combination with plasma Albumin

Blood Interstitial

fluids

Liver kidney-- Nil

Free Bilirubin

HEME OXYGENASE

BILIVERDIN REDUCTASE


BILE PIGMENTS AND JAUNDICE












ABNORMAL HB Hemoglobinopathies Hemoglobin in thalassemia and related

disorders


HEMOGLOBINOPATHIES Hemoglobin S –

Found in SC anemia Alpha chains are normal and beta chains are

abnormal Hemoglobin C –

Beta chains are abnormal In people with HB C diseases characterized by mild

hemolytic anemia and splenomegaly Hemoglobin E

Beta chains are abnormal Hemoglobin M

Abnormal Hb present in the form of methHB Occurs due to mutation Blue baby syndrome


HB in thalessemia and related disordersAbnormal Hb are presentPolypeptide chains are decreased


THALASSEMIA


WHAT IS THALASSEMIA? Thalassemia is an inherited blood

disorder that causes mild or severe anemia.

The anemia is due to reduced hemoglobin and fewer red blood cells than normal. Hemoglobin is the protein in red blood cells that carries oxygen to all parts of the body.

http://www.nhlbi.nih.gov/health/dci/Diseases/anemia/anemia_whatis.html


In people with thalassemia, the genes that code for hemoglobin are missing or variant (different than the normal genes). Severe forms of thalassemia are usually diagnosed in early childhood and are lifelong conditions.


THE TWO MAIN TYPES OF THALASSEMIA Alpha and beta, are named for the two

protein chains that make up normal hemoglobin.

The genes for each type of thalassemia are passed from parents to their children. Alpha and beta thalassemias have both mild and severe forms.


ALPHA THALASSEMIA Four genes are involved in making the

alpha globin part of hemoglobin—two from each parent.

Alpha thalassemia occurs when one or more of these genes is variant or missing.


People with only one gene affected are called silent carriers and have no sign of illness.

People with two genes affected (called alpha thalassemia trait, or alpha thalassemia minor) have mild anemia and are considered carriers.

People with three genes affected have moderate to severe anemia, or hemoglobin H disease.

Babies with all four genes affected (a condition called alpha thalassemia major, or hydrops fetalis) usually die before or shortly after birth.


If two people with alpha thalassemia trait (carriers) have a child, the baby could have a mild or severe form of alpha thalassemia or could be healthy.


BETA THALASSEMIA Two genes are involved in making the

beta globin part of hemoglobin—one from each parent. Beta thalassemia occurs when one or both of the two genes are variant.


If one gene is affected, a person is a carrier and has mild anemia. This condition is called beta thalassemia trait, or beta thalassemia minor.

If both genes are variant, a person may have moderate anemia (beta thalassemia intermedia, or mild Cooley’s anemia) or severe anemia (beta thalassemia major, or Cooley’s anemia).

Cooley’s anemia, or beta thalassemia major, is a rare condition. A survey in 1993 found 518 Cooley’s anemia patients in the United States. Most of these persons had the severe form of the illness, but there may be more who are not diagnosed.


WHO IS AT RISK FOR THALASSEMIA? 1. Thalassemia is passed from parents

to children through their genes. 2. Thalassemia affects both males and

females. 3. Beta thalassemias affect people of

Mediterranean origin or ancestry (Greek, Italian, Middle Eastern) and people of Asian and African descent.

4. Alpha thalassemias mostly affect people of Southeast Asian, Indian, Chinese, or Filipino origin or ancestry.


WHAT ARE THE SIGNS AND SYMPTOMS OF THALASSEMIA? The symptoms of thalassemia depend

on the type and severity of the disease. Symptoms occur when not enough

oxygen gets to various parts of the body due to low hemoglobin and a shortage of red blood cells in the blood (anemia).



IN MORE SEVERE TYPES OF THALASSEMIA, SUCH AS COOLEY’S ANEMIA, SIGNS OF THE SEVERE ANEMIA

ARE SEEN IN EARLY CHILDHOOD AND MAY INCLUDE: 1. Fatigue (feeling tired) and weakness 2. Pale skin or jaundice (yellowing of the skin) 3. Protruding abdomen, with enlarged spleen

and liver 4. Dark urine 5. Abnormal facial bones and poor growth

Babies with all four genes affected (a condition called alpha thalassemia major, or hydrops fetalis) usually die before or shortly after birth

http://www.cooleysanemia.org/




HOW IS THALASSEMIA DIAGNOSED?

1. Thalassemia is diagnosed using blood tests, including a complete blood count (CBC) and special hemoglobin studies.

2. A CBC provides information about the amount of hemoglobin and the different kinds of blood cells, such as red blood cells, in a sample of blood. People with thalassemia have fewer red blood cells than normal and less hemoglobin than normal in their blood. Carriers of the trait may have slightly small red blood cells as their only sign.

3. Hemoglobin studies measure the types of hemoglobin in a blood sample.


COOLEY’S ANEMIA

is usually diagnosed in early childhood because of signs and symptoms, including severe anemia. Some people with milder forms of thalassemia may be diagnosed after a routine blood test shows that they have anemia.

Doctors suspect thalassemia if a child has anemia and is a member of an ethnic group that is at risk for thalassemia.




http://www.nhlbi.nih.gov/health/dci/Diseases/Thalassemia/Thalassemia_Signs.html



To distinguish anemia caused by iron deficiency from anemia caused by thalassemia, tests of the amount of iron in the blood may be done.

Iron-deficiency anemia occurs because the body doesn’t have enough iron for making hemoglobin.

The anemia in thalassemia occurs not because of a lack of iron, but because of a problem with either the alpha globin chain or the beta globin chain of hemoglobin. Iron supplements do nothing to improve the anemia of thalassemia, because missing iron is not the problem.

http://www.nhlbi.nih.gov/health/dci/Diseases/ida/ida_whatis.html

http://www.nhlbi.nih.gov/health/dci/Diseases/ida/ida_whatis.html


Family genetic studies are also helpful in diagnosing thalassemia. This involves taking a family history and doing blood tests on family members.

Prenatal testing can determine if an unborn baby has thalassemia and how severe it is likely to be.


HOW IS THALASSEMIA TREATED?

Treatment for thalassemia depends on the type and severity of the disease.

People who are carriers (they have thalassemia trait) usually have no symptoms and need no treatment.


Those with moderate forms of thalassemia (for example, thalassemia intermedia) may need blood transfusions occasionally, such as when they are experiencing stress due to an infection.

If a person with thalassemia intermedia worsens and needs regular transfusions, he or she is no longer considered to have thalassemia intermedia; instead, the person is said to have thalassemia major, or Cooley’s anemia.





1. Those with severe thalassemia have a serious and life-threatening illness.

2. They are treated with regular blood transfusions, iron chelation therapy, and bone marrow transplants.

3. Without treatment, children with severe thalassemia do not live beyond early childhood.


BLOOD TRANSFUSIONS Severe forms of thalassemia are treated by

regular blood transfusions. A blood transfusion, given through a

needle in a vein, provides blood containing normal red blood cells from healthy donors. In thalassemia treatment, blood transfusions are done on a schedule (often every 2–4 weeks) to keep hemoglobin levels and red blood cell numbers at normal levels. Transfusion therapy can allow a person with severe thalassemia to feel better, enjoy normal activities, and live longer.


Transfusion therapy, while lifesaving, is expensive and carries a risk of transmitting viral and bacterial diseases (for example, hepatitis). Transfusion also leads to excess iron in the blood (iron overload), which can damage the liver, heart, and other parts of the body. To prevent damage, iron chelation therapy is needed to remove excess iron from the body.


IRON CHELATION THERAPY

Iron chelation therapy uses medicine to remove the excess iron that builds up in the body when a person has frequent blood transfusions. If the iron is not removed, it damages body organs, such as the heart and liver.


The medicine, deferoxamine, works best when given slowly under the skin, usually with a small portable pump overnight.

This therapy is demanding and sometimes is mildly painful, so some people stop chelation therapy. A pill form of iron chelation therapy, deferasirox, was approved in November 2005 for use in the United States.

People who have iron overload should not take vitamins or other supplements that contain iron.


SURGERY Surgery may be needed if body organs,

such as the spleen or gall bladder, are affected.

For example, if the spleen becomes inflamed and enlarged, it may be removed.

If gallstones develop, the gall bladder may be removed.


BONE MARROW OR STEM CELL TRANSPLANTS Bone marrow or stem cell transplants

have been used successfully in some children with severe thalassemia. This is a risky procedure, but it offers a cure for those children who qualify.


OTHER TREATMENTS People with severe thalassemia are more

likely to get infections that can worsen their anemia. They should get an annual flu shot and the pneumonia vaccine to help prevent infections.

Folic acid is a B vitamin that helps build red blood cells. People with thalassemia should take folic acid supplements.

Researchers are also studying other treatments, such as gene therapy and fetal hemoglobin.


RED BLOOD CELL INDICES AND PACKED CELL VOLUME


They are the measurements that describe the size and oxygen carrying protein (hemoglobin) content of red blood cells. The indices are used to help in the differential diagnosis of anemia.

The relationships between the hematocrit, the hemoglobin level, and the RBC are converted to red blood cell indices through mathematical formulas.

The indices include these measurements: mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); and mean corpuscular hemoglobin concentration (MCHC).


MEAN CORPUSCULAR VOLUME The MCV is the average volume of the RBC in cubic

microns

MCV = Hct (%) X 10 / RBC count (10-12/L).

Example: Hct = 45%, RBC count = 5.0x1012/L; therefore,

MCV = 45.0x10 / 5.0 = 90fL

Cells of normal size (MCV is 80-100cu. microns) are called normocytic, smaller cells are microcytic, and larger cells are macrocytic.


Microcytic cells are found in:Patients with iron deficiency anemia.Thalassemia.

Macrocytic cells are found in:Patients with liver disease or hypothyroidismWhen there is asynchrony in RBC maturation (termed

megaloblastic anemia's).Folate and vitamin B12 deficiencies.


MEAN CORPUSCULAR HEMOGLOBIN (MCH) The MCH is the average weight of Hb in an RBC,

expressed in the units of picograms (pg), or 10-12g:

MCH = Hb (g/dL) X 10 / RBC count (1012/L).

The reference range for adults is 28-32pg. The MCH is not generally considered in the

classification of anemia's. Example:

Hb=16.0 g/fl.RBC count=5.0x1012/l.

MCH=16.0x10 / 5.0 = 32.0pg


MEAN CORPUSCULAR HEMOGLOBIN CONCENTRATION (MCHC) The MCHC is the average concentration of Hb

in each individual erythrocyte. The units used are gram per deciliter (formerly

referred to as a percentage). MCHC = Hb (g/dL) X 100 / Hct (%).

Example: Hb =16 g /dl, Hct = 48%; MCHC=16 X 100 / 48 = 33.3g/dL


Values of normochromic cells range from 32 to 37g/dL.

Hypochromic cells are less than 32g/dL, and those of hyperchromic cells are greater than 37g/dL.

Hypochromic erythrocytes occur in thalassemia and iron deficiency.

Because there is a physical limit to the amount of hemoglobin that can fit in a cell, there is no hyperchromic category, a cell does not really contain more than 37g/dL of Hb, but its shape may have become spherocytic, making the cell appear full.


PACKED CELL VOLUME OF WHOLE BLOOD

Hematocrit is defined as the volume occupied by erythrocytes in a given volume of blood and is usually expressed as a percentage of the volume of the whole blood sample.

The hematocrit may also be referred to as Packed Cell Volume (PCV).


Principle:• The hematocrit is usually determined by spinning a blood-

filled capillary tube in a centrifuge.

Specimen:• Venous blood anticoagulated with EDTA or capillary blood

collected directly into heparinized capillary tubes can be used. Specimens should be centrifuged within 6 hours of collection.

• Hemolyzed samples cannot be used for testing.


Reagents and equipment:

• Capillary tubes, heparinized for finger sticks (red tip) or plain for anticoagulated blood (blue tip)

• Clay-type tube sealant• Microhematocrit centrifuge• Microhematocrit reader• Kimwipes or gauze


Procedure:1. Fill two capillary tubes approximately three quarters

full with blood anti-coagulated with EDTA or heparin. Alternatively, blood for heparinized capillary tubes may be collected by capillary puncture. Wipe any excess blood from the outside of the tube.

2. Seal the end of the tube with the colored ring with nonabsorbent clay


3. Balance the tubes in the centrifuge with the clay ends facing the outside away from the center, touching the rubber gasket.

4. Tighten the head cover on the centrifuge and close the top. Activate the centrifuge for 5 minutes between 10,000 and 15,000 rpm

5. Determine the HCT by using a microhematocrit reading device Read the level of RBC packing.

6. The values of the two Hcts should agree within 2% (0.02).


HEMATOCRITE READER

Reference ranges:

• Newborn 53-65%

• Infant/child 30-43%

• Adult male 42-52%

• Adult female 37-47%


ANEMIA




MORPHOLOGICAL CLASSIFICATION

Normocytic normochromic anemiaEg. Hemolytic anemia, anemia of chronic disease, aplastic anemia

Macrocytic normochromic anemia

Eg. Vitt B12

Macrocytic hypochromic anemia

Eg. Protein deficiency

Microcytic and hypochromic anemia

Eg iron deficiency anemia



ETIOLOGICAL CLASSIFICATION

Hemorrhagic anemia

Hemolytic anemia

Nutrition deficiency anemia

Aplastic anemia

Anemia of chronic disease


HEMORRHAGIC ANEMIA Excessive loss of blood Acute and chronic

Acute Accident Decreased RBC count causes hypoxia which

stimulates the bone marrow to produce more no. of RBC.

Chronic Internal or external bleeding over a long period

of time Like peptic ulcer, purpura, hemophilia and

menorrhagia


HEMOLYTIC ANEMIA Excessive destruction of RBC Two types:

Extrinsic Liver failure Renal disorder Hypersplenism Burns Infections

Intrinsic Generally inherited like sickle cell anemia and

thalassemia


Sickle cell anemia/ SS disease/ Sickle cell disease inherited blood disorderAlpha chains normal beta chains abnormal

Mainly seen in black race and in central Africa where

falciparum malaria is endemic


CLINICAL FEATURES Anemia – severe hemolytic anemia. Vaso – occlusive phenomenon –

recurrent vaso – occlusive due to obstruction to capillary blood flow by sickled cells upon deoxygenation or dehydration Micro infarcts – abdomen, chest , and jointsMacro infarcts – bones, liver, kidney, spleen

Other symptoms like impaired growth and development and increased susceptibility to infection due to markedly impaired splenic function.


PATHO PHYSIOLOGY OF SICKLE CELL ANEMIA


NUTRITION DEFICIENCY ANEMIA Iron deficiency anemia Pernicious anemia/ Addison’s anemia Megaloblastic anemia


IRON DEFICIENCY ANEMIA


IRON DEFICIENCY ANEMIAPREVALENCE

Country Men (%) Women(%)

PregnantWomen (%)

S. India 6 35 56N. India 64 80Latin America 4 17 38Israel 14 29 47Poland 22Sweden 7USA 1 13


IRON Functions as electron transporter; vital

for life Must be in ferrous (Fe+2) state for activity In anaerobic conditions, easy to maintain

ferrous state Iron readily donates electrons to oxygen

Ferric (Fe+3) ions cannot transport electrons or O2

Organisms able to limit exposure to iron had major survival advantage


CAUSES OF IRON DEFICIENCY ANEMIA Blood Loss

Gastrointestinal Tract Menstrual Blood Loss Urinary Blood Loss (Rare) Blood in Sputum (Rarer)

Increased Iron Utilization Pregnancy Infancy Adolescence Polycythemia Vera

Malabsorption Tropical Sprue Gastrectomy Chronic atrophic gastritis

Dietary inadequacy (almost never sole cause) Combinations of above


IRON DEFICIENCY ANEMIAPROGRESSION OF FINDINGS

Stainable Iron, Bone Marrow Aspirate Serum Ferritin - Low in Iron Deficiency Desaturation of transferrin Serum Iron drops Transferrin (Iron Binding Capacity)

Increases Blood Smear - Microcytic, Hypochromic;

Aniso- & Poikilocytosis Anemia


IRON DEFICIENCYSYMPTOMS

Fatigue - Sometimes out of proportion to anemia

Atrophic glossitis Pica Koilonychia (Nail spooning) Esophageal Web


MANAGEMENT OF IDA Correction of the disorder Correction of iron deficiencyOral therapy

Ferrous sulphate – 6omg TIDFerrous gluconate – 37mg

Parenteral therapy Dose is calculated by multiplying the

grams of Hb below normal with 250.Given as single IM iron dextran(interferon)Repeated inj. Of iron sorbitol citrate

(jectofer)


PREVENTION OF IDADietary modification

Food fortification

Iron supplementation


PREVENTION OF IDA Diet & nutrition education

eat more fruits and vegetable no coffee or tea with meals programmes should be targeted to at risk groups reduce phytic content of cereals and legumes by fermentation


PREVENTION OF IDA Short term approach:

supplementation with iron tablets.Long-term approach:

food fortification with iron either for the whole population (blanket fortification) or for specific target groups like infants. It requires no cooperation from users unlike taking iron supplements.


FOOD FORTIFICATION Iron compounds used in food

fortification can be divided into 4 groupsFreely water soluble (ferrous sulphate, gluconate, lactate & ferric ammonium citrate).Poorly water soluble (ferrous fumarate, succinate & saccharate).Water insoluble (ferric pyrophosphate, ferric orthophosphate & elemental iron).


WHICH IRON FORM TO USE? The major factors governing the choice

of iron compound include:BioavailabilityOrganoleptic problemsCostSafety

Ideally we should go for a safe, cheap, highly bioavailable iron, which causes no organoleptic side-effects


WHICH IRON FORM TO USE? Freely water soluble iron are the most

bio-available, but causes unacceptable colour & flavour change in many foods.

Insoluble iron compounds are inert with no organoleptic effects but it is poorly absorbed

Cost-wise elemental iron is the cheapest, ferrous sulphate costs 10 times more, but most expensive is EDTA

Safety is of concern with EDTA & Bovine Hb only because of potential problems


MEGALOBLASTIC ANEMIA


MEGALOBLASTIC ANEMIAS - CAUSES

1. Vit. B12 deficiency

2. Folic acid deficiency3. Other causes like drugs which interfere with

DNA synthesis, acquired defects of hemopoietic stem cells and congenital enzyme deficiency.


VITAMIN B12 AND FOLIC ACID-PHYSIOLOGIC CONSIDERATIONS

Vitamin B12 Folic acid

Sources meat, fish green vegetables, yeast

Daily requirement 2-5 ug 50-100 ug

Body stores 3-5 mg (liver) 10-12mg

(liver)Places of absorption ileum duodenum

and proxymalsegment of small intestine


PERNICIOUS ANEMIA


PERNICIOUS ANEMIA First described by Addison in 1855 as a

chronic disorder of middle aged and elderly individual of either sex in which intrinsic factor secretion ceases owing to atrophy of the gastric mucosa.

Average age is 60yrs. Bur rarely can be seen in children

( juvenile pernicious anemia) Mostly seen in northern European

descent and American blacks and is uncommon in South European.


CLINICAL FEATURES Insidious onset and progress slowly Mainly due to Vit. B12 deficiency Anemia, Glossitis, Neurological

abnormalities ( neuropathy, subacute combined degeneration of the spinal cord, retrobulbar neuritis) GIT manifestation ( diarrhoea, anorexia, weight loss, dyspepsia), hepatospleenomegaly, congestive heart failure and hemorrhagic manifestation


LAB. FINDINGS Hypergastrinaemia Pentagastrinaemia Haematologic findings - Rise in serum bilirubin, LDH,

haptoglobin, ferrritin and iron. Chromosomal abnormalities are

frequently present in bone marrow cells which disappear after therapy.


TREATMENT Replacement therapy with vitamin B12 Vitamin B12 administration intramuscular in dose 1000 (100) μg

per day for a week , then 100 μg 2x per week for 2 weeks, 1 x per week 100μg for month

Reticulocytosis begins 2 or 3 days after therapy started and maximal number reached on day 5 to 8.

Serum iron monitoring, after 7-10 days of vit.B12 treatment, If Fe deficiency is diagnosed we should start iron substitution

100 ug vit.B12 i.m. every month, regimen that must be maintained for the rest on the patients life.

Physiotherapy for neurologic deficits and occasionally blood transfusion

Follow up early detection of cancer of the stomach


FOLIC ACID DEFICIENCY ANEMIA


CAUSES OF FOLIC ACID DEFICIENCY

1. Inadequate intake

- diet lacking fresh, slightly cook food; chronic alcoholism, total parenteral nutrition,

2. Malabsorption

- small bowel disease (sprue, celiac disease,)

- alcoholism

3. Increased requirements:

- pregnancy and lactation

- infancy

- chronic hemolysis

- malignancy

- hemodialysis

4. Defective utilisation

Drugs:folate antagonists(methotrexate, trimethoprim, triamteren), purine analogs (azathioprine), primidine analogs (zidovudine), RNA reductase inhibitor (hydroxyurea), miscellaneous (phenytoin, N2)


MEGALOBLASTIC ANEMIAS CLINICAL FEATURES

1. Symptoms of anemia2. Symptoms associated with vit. B12 or Folic acid

deficiencyneurologic manifestations (exclusivly in wit. B12

deficiency) - megaloblastic madness or psychosis, - subacute, combined degeneration of the

spinal cord (proprioceptive and vibratory sensation, spinal ataxia)gastrointestinal compraints (vit.B12 and folic acid deficiency)

- loss of appetite - glosstis (red, sore, smooth tongue) - diarrhea or constipation


MEGALOBLASTIC ANEMIAS DIAGNOSIS1. Blood cell count:

macrocytic anemiathrombocytopenialeucopenia (granulocytopenia)low reticulocyte count

2. Blood smear:

hypersegmentation of granulocytesmacroovalocytes , anisocytosis, poikilocytosis


MEGALOBLASTIC ANEMIAS DIAGNOSIS

3. Laboratory featuresindirect hyperbilirubinemia elevation of lactate dehrogenase (LDH)serum iron concentration- normal or increased

4. Bone marrow smearhypercellularincreased erythroid /myeloid ratio erythroid cell changes (megaloblasts, RBC precursor a

abnormally large with nuclear- cytoplasmic asynchrony) myeloid cell changes (giant bands and metamyelocytes ,

hypertsegmentation) megakariocytes are decreased and show abnormal

morphology


FOLIC ACID DEFICIENCY ANEMIA DIAGNOSIS

1. Establishing megaloblastic anemia 2. History: causes of folate deficiency3. Absence neurologic symptoms 4. Low serum and red blood cell folic acid


MEGALOBLASTIC ANEMIAS TREATMENT

FOLIC ACID DEFICIENCY ANEMIA

1. Oral administration of Ac. folicum 1 (5) mg per day, for 3 months, and maintenance therapy if it’s necessary.

2. Reticulocytosis after 5-7 days 3. Correction of anemia is over after 1-2

months therapy4. Maintenance therapy if necessary

Health & Medicine

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