RBCs & Its Clinical Implications

Dr. Amit T. SuryawanshiOral and Maxillofacial Surgeon

Pune, India

Contact details :Email ID - amitsuryawanshi999@gmail.com

Mobile No - 9405622455

Contents

1. Introduction. 2. History. 3. Erythropoiesis. 4. Morphology of RBCs. 5. Properties of RBCs. 6. Functions of RBCs. 7. Lifespan & Fate of RBCs. 8. Hemoglobin & Iron Metabolism. 9. Blood tests & Blood indices .10. Clinical implications of RBCs.11. Conclusion.

Introduction

• Blood is connective tissue of the body in fluid form.

• Blood  is a specialized  body fluid in  humans  that delivers oxygen and  nutrients   to the  cells and transports carbon dioxide and metabolic waste products away from the cells. Hence it is called as a “ River of Life ”

• Blood and Blood related disorders has got very much importance in patients life ,making it mandatory to learn for Oral Surgeons .

Composition of Blood

Blood Cells 45.7 % Plasma 54.3%

Solid6-7%

Water92-93 %

Gases <1 %

Organic Substances

Inorganic Substances

Erythrocytes45 %

Leucocytes0.6 %

Thrombocytes0.1 %

Blood is considered as a fluid of life. Because it

carries Oxygen from lungs to all parts of the body

and Carbon dioxide from all parts of the body to the

lungs.

This function of the blood is performed by RBCs.

i.e. Red blood Cells which are also known as

Erythrocytes . ( Erythros - Red , Cytes – Cells )

Introduction of RBCs

• RBCs- Red Blood Cells .They are also known as Erythrocytes.

• Red colour of RBCs is due to presence of coloring pigment Hemoglobin.

• RBCs play important role in transport of Oxygen from lungs to the tissues and carbon dioxide from tissues to lungs.

History

• The first person to describe red blood cells was the young Dutch biologist Jan Swammerdam, who had used an early microscope in 1658 to study the blood.

• In 1959, Dr. Max Perutz was able to reveal the structure of hemoglobin .

Normal RBC Count -

• Avrg RBC count = 4 - 5.5 millions / mm3

• RBC count in adults male – 5- 5.5 millions /mm3

• RBC count in adults female – 4 – 4.5 millions /mm3

• RBC count in infants - 6-7 million/mm3

Erythropoiesis• Haematopoiesis is the process which includes

origin, development & maturation of all blood cells.

• Whereas the process by which origin , development and maturation of erythrocytes occur is known as Erythropoiesis.

Stages & Sites of Erythropoiesis

• In Fetal life -

Mesoblastic stage

•First 2 months of i.u.•From mesenchyme of yolk sac

Hepatic stage

•From 2-6 months•Liver, spleen & lymphoid organs

Myeloid stage

•From 7-9 month•Red bone marrow, Liver

In post natal life

• Upto 5-6 years : Red bone marrow of all bones.

• From 6-20 years : Red bone marrow of long bones & all flat bones .

• After 20th year : almost red bone marrow of all the long bones is replaced by yellow bone marrow.

In post natal life

• Only the upper ends of the femur & humerus contain red bone marrow.

• Vertebras , ribs, sternum scapula ,iliac bone also produce red cells continuously.

• In case of Bone disorders, RBCs are produced in

spleen, liver

Erythropoiesis -o Blood cells are derived from Pluripotent

Hemopoetic Stem Cells (PHSC)

o Growth inducers (GI) like interleukin-3 and differentiation inducers (DI) play an important role.

o Few PHSC are retained throughout life as they are.

Erythropoietin dependent stages

Iron dependent stagesCELL DIAMETER

NUCLEUS CYTOPLASM

15-20 µm Big Very Scanty & basophilic. No Hb

11-16µm Smaller Still Scanty & basophilic.No Hb

10-12µm Smaller & denser

Hb starts to appear, cytoplasm polychromatic

8-10µm Ink spot nucleus Plentiful, eosinophilic cytoplasm. Increase in Hb

8-10µm Absent Some RNA still present

7.2 µm Absent Hb is present in large amount .

RBC Maturation factors

1. Vitamin B12 (Extrinsic factor) –• Essential for maturation of RBCs• Deficiency of Vitamin B12 causes Pernicious Anemia. So it is also called as antipernicious factor .

2. Intrisic Factor of castle-• Produced in Gastric mucosa• Essential for absorption of Vit.B 12

3. Folic acid –• Essential for synthesis of DNA in RBCs.• Absence of folic acid causes failure of

maturation of cells leading to Megaloblastic anemia.

Morphology

• Size : 7.2 µ

• Shape : Circular , Biconcave

• Thickness : 2.2 µ, 1 µ

• Surface area : 120 µm2

• Volume : 85-90 µm3

Advantages of bi-concave shape:

1. provides large surface area for

absorption and removal of

respiratory gases and other

substances.

2. Cells can easily squeeze through

while passing through capillaries

Composition

• Water - 62.5%

• Hemoglobin - 35%

• Others - 2.5% (glucose, lipids,

proteins, enzymes, vitamin, ions)

otherswaterhaemoglobin

Properties of RBCsRouleaux formation Packed cell volume

Specific gravity-

1.092 – 1.101

Suspension stability

Functions of RBCs -

1. Transport of OXYGEN from lungs to the tissues

2. Transport of CARBON DIOXIDE from tissues to the lung

3. Buffering action in blood

5. Blood group determination.

6. Help to maintain the viscosity of blood.

LIFE SPAN AND FATE OF RBC’S

• Average life span -- 100-120 days. • Spleen -- Graveyard of red blood cells.

• Daily 10% red blood cells, which are senile, get destroyed in normal young healthy adults.

Hemoglobin

• Hemoglobin is an oxygen carrying pigment of the RBCs.

• It is a conjugated protein which consists of protein combined with an iron containing pigment.

Functions of Hemoglobin

1. Transport of OXYGEN from lungs to the tissues

2. Transport of CARBON DIOXIDE from tissues to the lung

3. Buffering action in blood

HAEMOGLOBIN

NORMAL VALUES• Average hemoglobin (Hb) -- 14 to 16 gm%.

• At different ages:

–At birth : 22 – 25 gm%

–After 3 months : 18 – 20 gm%

–After1 year : 17 gm%

– In adult males : 14 – 17 gm%

– In adult females : 12 – 16 gm%

Iron Metabolism-• Iron is absorbed for small intestine and

transported to blood .

• In blood , Iron combines with β globulin

to form Transferrin

• Iron is stored in large quantities in

RE cells and Hepatocytes as Ferritin.

• In RBCs , Iron is stored in Fe++ form .

Synthesis of hemoglobin

A. 2 succinyl-CoA + 2 glycine Pyrole compund

B. 4 pyrrole compunds Protoporphyrin IX

C. Protoporphyrin IX + Fe++ Heme

D. Heme + globin Hemoglobin

Factors for Hemoglobin synthesis

• Proteins • Iron • Vitamin C, Riboflavin ,Nicotinic acid , Pyridoxine• Copper• Cobalt and nickel

Structure of Hemoglobin

• It is a conjugated protein • It consists of 1. Heme - An Iron containing pigment. 2. Globin- Protein

Heme part- Structure

• It consists of 1. Iron – Ferrous form(Fe++) 2. Porphyrin – Pigment part

Globin -Structure

It consists of 4 polypeptide chains 1. Two α chains 2. Two β chains

Types of Normal Hemoglobin

• There are 2 types of hemoglobin . 1. Adult Hemoglobin (HbA)- - It contains 2 α and 2 β chains

2. Fetal Hemoglbin (HbF)- -It contains 2 α and 2 γ chains

DESTRUCTION OF HEMOGLOBIN

– Occurs in Phagocytes of Spleen.

– Globin is broken into amino acid and

reused.

– Heme – Its tetrapyrrole ring is opened up

to form BILIVERDIN.

– Its oxidation produces BILIRUBIN

CLINICAL IMPLICATIONS OF RBC

Clinical disorders related to RBCsBroadly classified into

1. Anemia – Decrease in RBC count and

Hemoglobin level.

2. Polycythemia – Increase in RBC count and

Hemoglobin level.

ANEMIA

• It is defined as a blood cell disorder characterized by decreased oxygen carrying capacity of blood caused by reduction in red blood cell count or hemoglobin content or both.

ClassificationEtiological (Whidby's) classification

A. Deficiency anemias -

1. Iron deficiency anemia

2. Megaloblastic anemia

3. Pernicious anemia

B. Blood loss anemias -

1. Acute post- hemorrhagic anemia (accidents)

2.Chronic post- hemorrhagic anemia

C. Haemolytic anemias ( increased destruction of rbc)

1. Hereditary heamolytic anemias

a. Thalassemia

b. Sickle cell anemia

c. Hereditary spherocytosis

d. Glucose 6-phosphate dehydrogenase

deficiency (G6PD)

• Acquired haemolytic anemias

- Due to direct toxic effect ( eg snake venom, drugs , chemicals, etc)

- In splenomegaly

- In paroxysmal nocturnal haemoglobinuria( PNH)

D. APLASTIC ANEMIA (failure of bone marrow)

E. Anemia due to chronic diseases

(tuberculosis, chronic infections, malignancies )

Morphological (Wintrobe’s) classification1.Normocytic normochromic anemias• Acute post-haemorrhagic anemia• Haemolytic anemias• Aplastic anemia• Anemia in chronic diseses.

2.Macrocytic normochromic anemia • Pernicious anemia (Addison’s anemia)

3. Macrocytic hypochromic anemias-• Protein deficiency anemia • Megaloblastic anemia

2.Microcytic hypochromic anemias• Iron deficiency anemia• Chronic post-haemorrhagic anemia• Thalassemias

SIGN & SYMPTOMS

Considered in two broad categories:

1. Clinical features common to all anemias.

2. Certain special clinical features for different types of anemias.

Common Clinical features• Typically none in early stages

• General lassitude

Cardio-respiratory -1. Dyspnoea

2. Tachycardia

3. Murmurs

4. Palpitations

5. Angina Pectoris

Oral –1. Sore mouth

2. Oral ulceration

3. Angular stomatitis

4. Glossitis

5. Burning mouth syndrome

Cutaneous -6. Pallor

7. Brittle Nails

8. Koilonychia

Iron deficiency anemia

• Most common type of anemia • It Develops due to inadequate availibity for

iron for hemoglobin synthesis .

• Causes –1. Loss of blood 2. Decreased intake or poor absorption of iron3. Increased demand in conditions like growth

and pregnancy

Clinical featuresPALLOR KOILONYCHIA

ANGULAR CHEILITIS PAPILLARY ATROPHY OF TONGUE

Megaloblastic anemia

• Megaloblastic anemia is due to deficiency of Maturation factor of RBC i.e. folic acid.

• DNA synthesis is impaired so cells are megaloblastic but immature .

Oral manifestations

1. Atrophic glossitis 2. Patchy erythema 3. Taste alterations 4. Dysphagia 5. Burning mouth

Atrophic glossitis

Pernicious anemia

• Cause –• It occurs due to atrophy of gastric mucosa

because of autoimmune destruction of parietal calls.

• Hence , it leads to decreased production of intrinisic factor and poor absorption of vitamin B12 .( Maturation factor )

Oral manifestations

1. Atrophic glossitis 2. Patchy erythema 3. Taste alterations 4. Dysphagia 5. Burning mouth

Atrophic glossitis

SICKLE CELL ANEMIA•It is a congenital anamaly occurs due to abnotmal Hb called Hb–S.

•Molecules of Hb-S polymerize into long chains and precipitate inside the cell.

•Hence RBCs attain “ Sickle” or “Crescent” shape & become more fragile leading to hemolysis

Hemolysis in Sickle cell anemia

OralManifestations

Pallar of mucosa Delayed erruption of teeth

Other clinical features -

Jaundice Hand & Foot syndrome

• It is also known as “Cooley’s anemia” .• It is caused by inherited anomalies of hemoglobin• It is of 2 types 1. α thalesemia 2. Β thalesemia

THALASSEMIA

Clinical features

1. Saddled nose2. Prominent malar

bone3. Retracted upper

lip4. Bimaxillary

protrusion5. Chipmunk facies

Radiographic feature

HAIR ON END APPEARENCE

• Aplastic anemia is due to failure of red bone marrow .

• Red bone marrow is replaced by fatty tissues

• Causes –1. Repeated exposure to X-rays & Gamma rays 2. Due to bacterial toxins , quinine , gold salts

APLASTIC ANEMIA

Oral manifestations

ORAL PETECHIAE

GINGIVAL HYPERPLASIA

Blood Tests

Blood testsThe routine blood tests are 1. Complete blood count I. RBC count II. Blood indices – PCV , MCV, MCH, MCHC 2. ESR3. Blood smear4. Retuculocyte count

ERYTHROCYTE SEDIMENTATION RATE

• It is commonly used blood test and is also called as a sed rate or BIERNACKI’s REACTION.

• Procedure –

1. Blood is mixed with an anticoagulant and allowed to stand on a vertical tube.

2. RBCs settle down due to gravity leaving supernatant layer of clear plasma above .And the rate at which RBCs settle down is called as ESR .

• It is the length of clear supernatant plasma measured in mm at the end of 1 hr.

• Determination by

1. Westergreen’s Method

2. Wintrobe’ s Method

• Normal Values of ESR

–Westergreen's Method

• Adult Males = 0

– 15 mm in 1 hr

• Adult Females=

0 - 20 mm in 1 hr

• Variations of ESR

Pathological -• ESR increases in -– All Anemias,

except sickle cell anemia .• ESR decreases in -– Polycythemia– Sickle cell anemia

BLOOD INDICES• Importance – Help in diagnosis & typing of Anemias.

• Different Blood Indices

1. Packed Cell Volume (PCV)

2. Mean Corpuscular Volume (MCV)

3. Mean Corpuscular Hemoglobin (MCH)

4. Mean Corpuscular Hemoglobin Concentration

(MCHC)

PACKED CELL VOLUME

• Also called as HEMATOCRIT value • It is the fraction of blood composed of RBC• Procedure-• Blood is mixed with anticoagulant & filled in

wintrobe’s tube upto 100mm mark .• And tube is typically centrifuged at 3000 RPM

for 30 minutes OR at 10,000 rpm for 1 minute

• NORMAL VALUES OF PCV –

Males = 40 to 45%. Females = 38 to 42%

• VARIATIONS IN PCV

1. PCV increases in - Polycythemia2. PCV decreases in -All types of anemia.

HEMATOCRIT VALUES

MEAN CORPUSCULAR VOLUME (MCV)

Average volume of a single red blood cell

– Normal MCV = 85 - 90 µm3 .

– VARIATIONS IN MCV-

• Increases in (Macrocyte anemia ) -

1. Pernicious anemia

2. Megaloblastic anemia

• Decreases in (Microcyte anemia )1. Iron deficiency anemia

2. Chronic post-haemorrhagic anemia

3. Thalassemias

MEAN CORPUSCULAR HEMOGLOBIN

(MCH)

• Quantity or amount of Hb present in one RBC

– Normal value of MCH is 30 pg (27 -32pg)

–Increases or remains normal in

1. Pernicious anemia

• Decreases in (Hypochromic anemia). 1. Protein deficiency anemia

2. Megaloblastic anemia

3. Iron deficiency anemia

4. Thalassemia

MEAN CORPUSCULAR HEMOGLOBIN CONCENTRATION (MCHC)

• It is the amont of Hb expressed in relation to volume of single RBC .

• Normal value of MCHC is 30 %

• Increases in (Macrocyte anemia ) -

1. Megaloblastic anemia

• Decreases in ( Microcyte anemia )1. Iron deficiency anemia

2. Chronic post-haemorrhagic anemia

3. Thalassemias

Peripheral blood smear (PBS)

o A well prepared & correctly read smear gives vast amount of information of RBC morphology.

o They are stained by polychromatic stain such as Wright’s stain

o Variation in shape, size & Hb concentration & the presence of abnormal cells is noted

Management of anemia

Oral Surgeon’s Perspective

Pre operative – When patient has to undergo surgery , following

preoperative measures should be carried out.

1. Complete blood count with differential

2. Consultation with physician if lower values of Hb

are obtained . (<10gm/dL )

3. Severity of anemia & its correction should be

evaluated before surgical intervention.

4. Possible blood tranfusions , if severe.

5. Drugs that induce Hemolysis should be avoided.

6. Avoidance of elective surgical treatment in patients in “crisis” (sickle cell anemia)

7. Elimination of oral sources of infection should be done.

8. Administration of antibiotic prophylaxis , if necessary

9. GA should be administered only when Hb is 10 gm/dL or more .

10. Short appointments should be given and that too in the morning (Sickle cell anemia)

11. Thorough oral examination of teeth ,

periodontium ,soft tissues should be conducted

to correct the cause of infection .(Aplastic

anemia )

12. Oral rinses with chlorhexidene 0.2% in aquous solution will reduce the chances of infection.

1. Gingival bleeding , if present , can be controlled with antifibrinolytic agents.

2. Intramuscular inj. and Nerve blocks should be avoided because of risk of bleeding.

3. Intraligamantary anesthesia can be used safely in extraction procedures .

Intra operative -

4. GA should be used in caution

Mostly N2 O + O2 is safe to use.

(Sickle cell anemia & vitamin B12 deficiency ).

5. Prevent dehydration using Normal saline I.V.

during operation.

Primary closure

1. Avoidance of drugs that can cause hemolysis in patients with hemolytic anemias

2. Oral hygiene techniques have to be done.

3. Recommendation of prophylactic antibiotics if poor wound healing

4. Prescribe Acetaminophen , codein , oxycodone as an analgesics because salicylates can induce acidosis.

Post operative -

Treatment of Anemia

Physician’s perspective

Treatment of Anemia1. Exclude the possibility of hemoglobinopathy

2. Correct any identified cause of blood loss

3. Give oral iron therapy

4. Correct identified vitamin deficiency with oral folic acid & Vit. B12 by injection.

5. Treat malaria with effective antimalarial drugs( in sickle cell anemia & thalessemia )

6. If evidence of hemolysis, review the drug treatment, & stop the drugs if possible

7. Check if the patient is on marrow suppressing drugs and stop if possible

Polycythemia

• It is a general term used for

1. Increased red blood cell count

2. Increased Hb level.

Causes-1. chronic hypoxia

2. smoking

3. fluid loss

4. hypertension & obesity

• Classified as

1. Primary polycythemia (Polycythemia vera)

2. Secondary Polycythemia

Signs & symptoms

1. Lassitude 2. Dyspnoea3. Dizziness4. Headache ,Body

ache 5. Itching ,numbnes

s, burning and weakness in hands, feet.

• Urticaria

Facial plethora

Oral manifestations

Purplish mucosa Edematous gingiva

Treatment of Polycythemia

1. Oral surgical procedures in patients with polycythemia, should be avoided.

2. Patient should have CBC with differential before surgery.

3. If Hb levels are found increased , Physician’s concern should be taken and

patient should undergo treatment for the same.

1. Before performing surgery , threshold levels should be obtained ..

a. Hb = < 16 g/ dL b. Hematocrit value = < 47%

2. Intraoperatively, patients require special attention to hemostasis.

3. If emergency surgery is required venesection is performed & blood is replaced with equal amount of colloid until a satisfactory hematocrit is reached.

It is necessary for the oral surgeon to have knowledge about RBC related disorders .

Because , it is mandatory to find the etiology of the RBC disorders by letting the patient undergo Blood tests or by consulting with General physician for medicinal treatments before performing any surgical procedure to prevent further complications during & after surgery .

Conclusion

References• Medical Physiology : 11th edition GYTON & HALL.• Davidson : General Medicine .• Burket’s Principle of medicine .• Articles- 1. Dental managemenotf idiopathic aplastic anemia:

report of a case .2. Managing the dental patient with sickle cell

anemia: a review of the literature• Tuft university manual – Rx of Medically

compromised patients

Thank you