HEMATOLOGY

FANER, Ned DenebeLACANILAO, Sunshine

NUCUM, Billie KimPAGADUAN, Maribec

PUA, Monalisa

BLOOD

Monocyte

Platelets

Smalllymphocyte

Neutrophil

LargeLymphocyte

Basophil

Smalllymphocyte

Neutrophil

Eosinophil

Erythrocyte

Young (band)neutrophilMonocyteNeutrophil

Red Blood Cells

small,biconcave disks that lack a nucleus when mature. 4 to 6 million red blood cells per mm3 of whole blood.

Red blood cells transport oxygen, and each contains about 200 million molecules of hemoglobin, the respiratory pigment.

Make ATP by anaerobic metabolism

HEMOGLOBIN

lungsHb + O2 HbO2

tissues

The cytoplasm of an RBC consists mainly of a 33%solution of hemoglobin (Hb), the red pigment that gives the RBC its color and name.

HEMOGLOBIN

Hemoglobin consists of four protein chains.

βα

β α

Each chain isconjugated with a nonprotein moiety called the hemegroup, which binds oxygen to a ferrous ion(Fe2) at its center

Hypoxemia(inadequate O2 transport

Sensed by liver and kidneys

Secretion oferythropoietin

Stimulation ofred bone marrow

Acceleratederythropoiesis

IncreasedRBC count

IncreasedO2 transport

The kidneys release increased

amounts of erythropoietin whenever

the oxygen capacity of the blood is

reduced. Erythropoietin stimulates the red bone marrow to speed up itsproduction of red blood

cells, which carry oxygen. Once the

oxygen-carryingcapacity of the blood is

sufficient to support normal cellular activity,

thekidneys cut back on their

production of erythropoietin.

RBC PRODUCTION AND REGULATION

↓ proliferation

Decreased erythropoietin effect

Marrow damage or defect

Impaired erythropoietin production

Impaired cellular response to erythropoietin (e.g. anemia of chronic diseases)

By external agents, physical or chemical (e.g. ionizing radiation, marrow toxins

Hereditary or acquired aplastic anemia

Intrinsic marrow replacement (e.g. myelofibrosis

ANEMIA

Maturation

defect

Microcytic

(hypochromic

Megaloblastic

macrocytic

Vit B12 deficiency

Folate deficiency

Iron deficiency and the anemia of chronic disease

Impaired globin chain synthesis

(thalassemias)

Impaired porphyrin synthesis

ANEMIA

Accelerated

Hemolysis

Phagocytosis by reticuloendothelial cells

Membrane defects (e.g. hereditary spherocytosis)

Heinz body associate (e.g. G6PD deficiency)

Hemoglobin discorders (e.g. sickle cell)

Red cell fragmentation syndromes

DIC

Vasculitis syndromes

Sickle cell

Intravascular hemolysis

Osmotic and physical injury

ANEMIA

ANEMIASType Morphologic

characteristicsCauses Underlying

Pathophysiology

Microcytic: Iron deficiency; chronic blood loss

Microcytic; hypochromic

Inadequate diet

Blood loss, chronic

Insufficient iron stores lead to a depleted RBC mass with subnormal hgb conc, and in turn, subnormal O2 carrying capacity of the blood

Macrocytic or megaloblastic; pernicious or folic acid

Macrocytic with variation in size, shape of RBCs

Inadequate diet, lack of intrinsic factor for pernicious anemia, impaired absorption

Vit B12 deficiency Inhibits cell growth; deformed RBCs with poor O2 carrying capacityNeuro damage occurs bec VB12 impairs myelin formationDeficiency of folic acid results in inhibits cell growth, which have shortened life span

ANEMIASType Morphologic

CharacteristicsCauses Underlying

Pathophysiology

Aplastic Normocytic, normochromic RBCs, depletion of leukocytes and platelets

drug toxicity, genetic failure, radiation, chemicals, infections

Damage of destroyed stem cells inhibit blood cell production

Hemolytic Normocytic, normochromic, inc number of reticulocytes

Mechanical injury, RBC antigen-antibody reaction, chemical reactions

Reduced RBC survival

Post hemorrhagic; acute hemorrhage

Normocytic, normochromic, inc number of reticulocytes within 48-72 h

Internal or external hemorrhage

Reduced circulating blood volume

POLYCYTHEMIA VERA

Uncontrolled and rapid cellular reproduction and maturation cause proliferation or hyperplasia of all bone marrow cells (panmyelosis)

↑ RBC mass, ↑ blood viscosity, inhibits blood flow to microcirculation

↓ blood flow and thrombocytosis set the stage for intravascular thrombosis

SICKLE CELL ANEMIA

OVERVIEW

Sickle-cell disease is a general term for a group of genetic disorders caused by sickle hemoglobin (Hgb S or Hb S).

Erythrocytes become elongated and crescent shaped (sickled) removed from the circulation and destroyed at

increased rates, leading to anemia.

OVERVIEW

An autosomal recessive inherited defect

The disease is chronic and lifelong.

Lifespan is often shortened with sufferers living to an average of 40 years.

OVERVIEW

The polymerization of deoxygenated HbS is the primary indispensable event in the molecular pathogenesis of sickle cell disease

HbS polymerization is associated with increased red cell density (dense erythrocytes) as well as red cell membrane damage favoring the generation of distorted rigid sickle cells and contributing to vaso-occlusion and premature red cell destruction (hemolytic anemia).

OVERVIEW

The gene defect is a known mutation of a single nucleotide polymorphism (SNP) (A to T) of the β-globin gene, which results in glutamic acid to be substituted by valine at position 6.

GAG to GUG codon mutation = LEADING TO HbS FORMATION

OVERVIEW

Fetal hemoglobin contains a gamma, not a beta chain, the disease usually will not result in clinical symptoms until the child’s hemoglobin changes from the fetal to the adult form at approximately 6 months.

Sickle-Cell Trait

Both parents with the disease will have both normal adult and hemoglobin S and be carriers (heterozygous) of the SICKLE-CELL TRAIT. 25% - 50% of hemoglobin is abnormal.

No symptoms

Diagnosis

Can be diagnose prenatally by chorionic villi sampling or from cord blood during amniocentesis

Attacks are diagnosed clinically Abnormal hemoglobin forms are detected on

hemoglobin electrophoresis, a form of gel electrophoresis on which the various types of hemoglobin move at varying speed

sickledex

Characteristics of Sickled Cells

Normal RBC Sickled Cells

120-day life span 30- to 40- day life span

Hgb has normal O2 carrying

capacity

Hb has decreased O2 carrying capacity

12 to 14 g/ml of Hb

6 to 9 g/ml of Hb

RBC destroyed at normal rate

RBCs destroyed at accelerated rate

CRISES

1. Vaso-occlusive— “painful episode”

2. Acute splenic sequestration-- pooling of blood

3. Aplastic– diminished RBC production

4. Hyperhemolytic– accelerated rate of RBC destruction

5. Cerebrovascular accident– blockage of major blood vessels

6. Acute Chest syndrome– similar to pneumonia

7. Infection

Enlargement of spleen

Concentration of sickle-shaped cells in the spleen

Impaired blood supply to various organs

Change in one base-pair in DNA molecule

Valine produced instead of glutamic acid at position, 6 in β-chain

Abnormal hemoglobin molecule

Sickling of RBC

Clumping of sickle shaped cells interferes with circulation

Impaired mental function

Weakness and lassitude

Proliferation of bone marrow

Anemia

Desctruction of many sickle cells

Enlargement of heart

Slowed physical development

Fibrosis of spleen

DEATHDEATH

paralysis Kidney failure

Heart Failure

Abd pain

pneumoniaRheumatism

Damage to heart muscle

Damge to lungs

Damage to muscles and joints

Brain damage Kidney

damage

Damage to abd organs

NURSING PROBLEMS

Impaired gas exchange Dyspnea Use of accessory

muscle Cyanosis Hypoxia restlessness

Ineffective tissue perfusion paralysis Tissue infarction Bone pain

NURSING PROBLEMS

Acute/ Chronic pain Localized/

generalized joint and/ or abdominal/ back pain

Guarding Crying, restlessness Facial grimacing

• Delayed growth and development

-Altered physical growth

-Delay and difficulty performing skills

Sickle cell anemia as an inflammatory disease

Orah S. PlattHarvard Medical School, Children’s Hospital,

300 Longwood Avenue, Boston, Massachusetts 02115, USA.

Sickle cell anemia as an inflammatory disease

Classical view---“primary genetic defect”: abnormal Hgb

Holistic view---abnormal hgb interacts with, damages, and stimulates the vascular endothelium “irritant”

“. . .reperfusion injury plays a major role in sickle pathophysiology. . .”

Sickle cell anemia as an inflammatory disease

high base-line leukocyte count

ongoing base-line chronic inflammation

major risk factor for severity in sickle cell anemia

References

Andreoli & Bennett etal; Cecil Essential of Medicine, 4th Edition, 1997, WB Saunders Co

Bullock: Pathophysiolgy: Adaptations and Alterations in Function, 4th Edition; 1996, Lippincott

Fauci et al: Harrison’s Principle of Internal Medicine, 17th Edition: McGraw Hill Companies, Inc

Mader: Understanding Human Anatomy Physiology, Fifth Edition, The McGraw−Hill Companies, 2004

Marieb: Essentials of Human Anatomy and Physiology, 6th Edition, 2002, Pearson Education Asia Pte, Ltd

McPhee at al: Pathophysiology: An Introduction to Clinical Medicine, 2nd Edition, 1997, Prentice Hall, ltd

Rifknd et al: Fundamentals of Hematology, 2nd Edition; 1980; Year Book Medical Publishers, Inc

Straight A’s in Pathophysiology: A Review Series; Lippincott Williams & Wilkins