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3) Αιμοποιητικό Σύστημα
3) Αιμοποιητικό Σύστημα
3) Αιμοποιητικό Σύστημα
Φυσιολογική αιμοποίηση
Παθήσεις ερυθρού αιμοσφαιρίου
Απαραίτητες ουσίες για την αιμοποίηση
Αναιμία
Blood Components
Blood Components: Cells
• Erythrocytes
– Red Blood Cells (RBC)
– O2 & CO2 transport
• White Blood Cells (WBC)
– Immune defense
– Phagocytosis
• Platelets: clotting
Normal Peripheral Smear
SITES OF HEMOPOIESIS
• Active Hemopoietic – Appendicular skeleton:
marrow is found, in • Bones of the Upper &
Lower limbs
children throughout the:
• In Adults active
– Axial skeleton:
• Cranium
hemopoietic marrow is
• Ribs. found only in:
• Sternum – The axial skeleton
• Vertebrae – The proximal ends of
• Pelvis the appendicular
skeleton.
The hematopoietic hierarchy and phenotypic markers associated with
HSCs
Stimulates CFU – E
An
Proerythroblasts example
ERYTHROPOIETIN Mature Erythrocytes of a
Negative
Decreases feed back
Tissue Oxygenation mechanis
Factors decreasing: m
• Hypovolemia
» Anemia
• Poor blood flow
• Pulmonary Disease
ERYTHROPOIESIS
PROERYTHROBLAST
BASOPHILIC
ERYTHROBLAST
POLYCHROMATOPHILIC
ERYTHROBLAST
ORTHOCHROMATIC
ERYTHROBLAST
RETICULOCYTE
MATURE ERYTHROCYTES
Reticulocytes: Elevated Count
ΔΙΚΤΥΟΕΡΥΘΡΟΚΥΤΤΑΡΑ
Απύρηνα πολυχρωματόφιλα
ερυθροκύτταρα
http://www.mfi.ku.dk/PPaulev/chapter8/images/8-3.jpg
Oxygen Dissociation Curve
18
11_02.jpg
Globin Chain Synthesis
t
r io e n
on ain
p e opm
d
mp c h
b t
en
cluster - chromosome 16
H g ad u l
l
ve
e
co bin
am
De
o
of
bn
Gl
2 1
%
Hg
22 Gower 1
22 Gower II
22 A2 1.5-3.5%
Adult
22 A > 95%
G A
cluster - chromosome 11
Body Iron Distribution and Storage
Duodenum Dietary iron
(average, 1 - 2 mg
Utilization Utilization
per day)
Plasma
transferrin (TIBC)
(3 mg)
Bone
Muscle marrow
(myoglobin) Circulating (300 mg)
(300 mg) erythrocytes
Storage
iron (hemoglobin)
(Ferritin) (1,800 mg)
Η απορρόφηση σιδήρου
γίνεται κυρίως στο
12δάκτυλο
Iron Transfer Between Cells and Tissues:
Mediated by Hepcidin
Hepcidin
Iron overload
Anemia of chronic disease
Iron deficiency
Increased iron demand
(hemolysis)
• Causes
– Decreased production
– Blood loss
– Hemolysis
Symptoms of Anemia
• Decreased oxygenation
– Exertional dyspnea
– Dyspnea at rest
– Fatigue
– Bounding pulses
– Lethargy, confusion
• Decreased volume
– Fatigue
– Muscle cramps
– Postural dizziness
– syncope
Classification of Anemia
• Clinical findings
– Acute
– Chronic
MCV
μικροκυτταρικά ερυθρά
MCV
μακροκυτταρικά ερυθρά
MCH
(Mean corpuscular hemoglobin)
μέση περιεκτικότητα Hb, 30±2 pg
MCH=Hb/RBC
MCHC
(Mean corpuscular hemoglobin concentration)
μέση πυκνότητα Hb, 30±4 %
MCHC=Hb/Ht
MCH, MCHC κ.φ.
ορθόχρωμα ερυθρά
MCH, MCHC
υπόχρωμα ερυθρά
MCH, MCHC
υπέρχρωμα ερυθρά
Classification of Anemia Based on RBC
Kinetics and Size
MCV
Microcytic Normocytic Macrocytic
(<80 fl) (80-97 fl) (>98 fl)
• Storage
– Iron storage 0-1000 mg
• Transit
– Serum iron 3 mg
• Total 3000-4000 mg
Causes of Iron Deficiency
Iron deficiency is a symptom, not a disease
• Increased iron requirements • Inadequate iron supply
– Blood loss – Insufficient dietary iron
• Gastrointestinal tract – Impaired iron absorption
• Genitourinary tract • Gastric surgery
• Blood donation • Intestinal malabsorption
– Pregnancy and lactation • Celiac disease
Ferritin: The Best
Marker for
Iron Deficiency
Ferriti
n µg/l
• Pica (pagophagia)
• Angular stomatitis
• Koilonychia
• Glossitis
AITIOΛΟΓΙΑ
Beta Thalassemia: Clinical Manifestations
• Skeletal
– Osteoporosis due to bone marrow expansion
– Pneumatization of the sinuses is delayed by
expanded hematopoiesis
• Dilated cardiomyopathy secondary to severe
anemia
β-Μεσογειακή αναιμία
ΘΑΛΑΣΣΑΙΜΙΕΣ
β-Μεσογειακή αναιμία
ΘΑΛΑΣΣΑΙΜΙΕΣ
Μορφολογία
Επίχρισμα αίματος σε ομόζυγη β-ΜΑ
α-Μεσογεακή αναιμία
Alpha Thalassemia: Clinical Features
• Absence of 1-2 alpha chains
– Common X
X
– Asymptomatic XX
– Does not require therapy
X
– Splenomegaly
• Absence of 4 alpha chains
– Hydrops fetalis (non-viable) XX
XX
Alpha Thalassemia: Laboratory Findings
Hemoglobin
Chains Hgb (g/dl) MCV (fl) Analysis
X X
Blocked in
Anemia of chronic disease
• Etiology
– Insufficient production of erythropoietin
Pure Red Cell Aplasia
• Normocytic anemia with reticulocyte count < 0.5%
• Clinical setting
– Immunocompetent patients with chronic hemolysis
– Immunodeficient patients with persistent viremia
Macrocytic Anemia with Low Reticulocyte
Count
• Megaloblastic anemia
– Vitamin B12 deficiency
– Folate deficiency
Diet
Vitamin B12
(Cobalamin) Folate
Source Animal products Widespread
Body stores 5 mg 5 mg
Daily requirement 2-5 µg 50-200 µg
Daily intake 10-20 µg 400-800 µg
Dietary deficiency Rare Common
Cofactor Activities of Folate and Cobalamin
Methionine
synthetase
Homocysteine Methionine
CH3-Cobalamin Cobalamin
THF THF-CH3
MMA-CoA
mutase
Methylmalonic acid (MMA) Succinyl-CoA
Adenosyl- Cobalamin
Cobalamin
Enteric Processing and Absorption of
Cobalamin
Stomach Food-Cbl
H + Peptic
digestion
Cbl + R-binder
R-Cbl
Duodenum
Pancreatic
enzymes R-Cbl Cbl-TC complex
IF + Cb OH -
Cbl-IF
Distal ileum IF receptor Cbl + TC
Cbl-IF
Metabolic Testing for the Diagnosis of
Vitamin B12 and Folate Deficiency
• Susceptible to infection
– S. pneumoniae
– Osteomyelitis
– Staphylococcal infections
• Vaso-occlusion
ΔΡΕΠΑΝΟΚΥΤΤΑΡΙΚΑ ΣΥΝΔΡΟΜΑ
Κλινική εικόνα
1. Αγγειοαποφρακτικές επώδυνες κρίσεις
2. Απλαστικές κρίσεις
3. Κρίσεις εγκλωβισμού στα σπλάχνα (σπλήνα)
4. Χολολιθίαση
5. Λοιμώξεις
6. Οστά. Νέκρωση κεφαλής μηριαίου
7. Δρεπανοκυτταρικό πνεύμονα
8. Ατονα έλκη κνημών
9. Πριαπισμό
10. Αδυναμία συμπύκνωσης ούρων
11. Καρδιακή ανεπάρκεια
12. κ.ά
Sickle Cell Trait
• Genitourinary complications
• Hyposthenuria
• Painless hematuria
• UTI during pregnancy
Sickle cell trait areas shown in
• Vaso-occlusive complications orange stripes
• Splenic infarction with hypoxia
• Sudden death during extreme
exertion
• Rhabdomyalysis
Glucose-6-Phosphate Dehydrogenase
Deficiency
• G-6-PD - reduces NADP/oxidizes glucose-6-phosphate
– Detoxifies free radicals and peroxides
• Sex-linked disorder
• Effects > 200 million people
• Hemolytic anemia occurs in the presence of stress
(infection or drugs)
– African form - mild hemolysis
– Mediterranean form - more severe
• Unique sensitivity to fava beans
Hereditary Spherocytosis
• Autosomal dominant disorder
• Abnormality in RBC membrane
protein
• Clinical and laboratory findings
– Splenomegaly
– Chronic hemolytic anemia
– Spherocytes on peripheral smear
• Treatment
– Splenectomy
Acquired Hemolytic Diseases
• Immune mediated hemolytic anemia
• Non-immune mediated
Autoimmune Hemolytic Anemia
• Warm antibodies (IgG-mediated)
– Primary 45%
– Secondary 40%
• Lymphoproliferative disease
• Connective tissue disease
• Infectious disease
– Drug-induced 15%
• Laboratory testing
– Normocytic/macrocytic anemia
– Peripheral smear - spherocytosis
Αυτοάνοση αιμολυτική
αναιμία από θερμό αντίσωμα
Anti-Globulin (Coombs) Testing
Direct antiglobulin testing
+
Anti-C3d
Patients RBCs Anti-IgG
+ +
Patients serum RBCs Anti-IgG
Επίκτητη αιμολυτική αναιμία
Non- Immune
Μικροαγγειοπαθητική ΜικροαγγειοπαθητικήΕλονοσία
Παροξυντική νυχτερινή αιμοσφαιρινουρία