anemias (sickle cell anemia with pathophysiology)
DESCRIPTION
this presentation is made for Medical Surgical Nursing 1 (Pathophysiology) University of Santo Tomas -Graduate School.TRANSCRIPT
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