blood patophysiology anemia
TRANSCRIPT
BLOOD
PATOPHYSIOLOGY
ANEMIA
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A N E M I A - DEFINITION
Anemia is defined as a reduction in one ore more of the
major red blood cell measurements:
Hb concentration
Hematocrit
RBC count
WHO criteria for anemia is:
Hb < 13 g/dl in men
< 12 g/dl in women
CAUSES OF ANEMIA
1. Decrease RBC production
2. Increase RBC destruction
3. Blood loss
1. DECREASE RBC PRODUCTION
Lack of nutrients: iron, B12, folate (dietary lack, malabsorbtion, blood loss )
Low levels of throphic hormones (EPO, thyroid hormone, androgens)
Anemia of chronic disease (inflammation, malignant disorders)
Bone marrow disorders (aplastic anemia, tumor infiltration, leukaemia, irradiation, chemioteraphy)
2. INCREASED RBC DESTRUCTION
( H E M O L Y S I S )
RBC life span below 100 days (as little as several days)
(definition of hemolysis)
CORPUSCULAR HEMOLYTIC ANEMIA (MAINLY INHERITED)
EXTRACORPUSCULAR HEMOLYTIC ANEMIA (MAINLY ACQIRED)
3. BLOOD LOSS
Bleeding (trauma, surgical procedures)
Occult bleeding (slowly bleeding from gastric
ulcers, duodenal ulcers, genitourinary bleeding)
Bleeding during or after surgical procedures
Blood donation
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RED BLOOD CELLS
morphology
MEAN CORPUSCULAR VOLUME ( MCV)
80-94 fL (m3)
< 80 fL microcitic; > 100 fL macrocytic
MEAN CELL HEMOGLOBIN in RBC ( MCH)
26-36 pg
<26pg hypochromic; < 36pg hyperchromic
MEAN CELL HEMOGLOBIN CONCENTRATION
(MCHC)
31-37g/dL
CLINICAL CONSEQENCES OF
ANEMIA I
S y p t o m s a r e d u e t o h y p o x i a
NORMAL Hb CONCENTRATION:
women: 12-16 g/dL
men: 13-18 g/dL
optimum oxygen delivery occurs with Hb 15 g/dL
CLINICAL CONSEQENCES OF
ANEMIA II
Fatigue
Somnolence (sleepiness)
Iintolerance to cold
Pallor of skin and mucous membranes
Hypotension
Tachycardia (angina, arrhythmia, palpitation)
Ringing in the ears
Headache
Dispnea & dyspnea at rest
Lethargy
Confusion
Dizziness
MICROCYTIC ANEMIA
MCV < 80fL
Reduced hem synthesis (syderoblastic anemia):
iron deficiency anemia (IDA)
porphyria (deficency of certain enzymes in hem synthesis)
Reduce globin production (thalassemia)
Hemolytic anemia (e.g. hemoglobinopathies, erythrocyte membrane defects)
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IRON DEFICIENCY ANEMIA
Iron deficiency anemia is the most
common anemia, particularly in women
and children
Approximately 20% of all women have
anemia
IRON – DAILY INTAKE
Women – 20 mg
Men – 10 mg
Pregnant women – 30 mg
Infant- 10 mg
Children (1-6 year) – 5-8 mg
Youth (13-19 year) – 15 mg
IRON METABOLISM
ABSORPTION
most iron comes from the breakdown of
hemoglobin in liver and spleen
5-10% of daily intake is only absorbed
Iron is absorbed in the mucosa of the
proximal small intestine, mainly duodenum
(HCl)
IRON METABOLISM –TRANSPORT
T R A N S F E R R I N
major iron transport protein in blood (95%)
about 30% saturated with iron (up to 50% - IDA)
test that measures the blood's capacity to bind iron
with transferrin = TOTAL IRON-BINDING
CAPACITY (TIBC)
IRON METABOLISM - STORAGE
MAJOR STORAGE DEPOT IS THE LIVER
Stored as ferritin and hemosyderin
F E R R I T I N
primary storage, stored in cell cytoplasm
release for heme synthesis
H E M O S Y D E R I N
major long term storage form of iron in lysosomes
slow release
IRON LOSS OF THE BODY
Daily exfoliation of intestinal mucosa
Menstruation
Nails and hair cut
IRON METABOLISM
Parameters that need to be checked in order to
diagnose IDA:
Iron level: 55-180 μg/dL
Transferin : 200-400 mg/dL
TIBC: 250-500 μg/dl
Ferritin: 150-1200 ng/dl
IRON RICH FOOD
Fe 2+
Liver
Beef
Lamb
Pork
Veal
Chicken
Fish
Fe 3+
Green leafy
vegetables
Beetroot
Carrot
Tomato
IRON DEFICENCY - SYMPTOMS
brittle nails and hair
spoon nails (koilonychia)
mucosal atrophy: glossitis (smooth
erythematous tongue), dysphagia, cheilitis
ETIOLOGY OF IDA
Blood loss (80%)
Dietary deficiency
- cause in developing countries
- infants, pregnancy, adolescence
Malabsorbtion
Chronic inflammatory disorders
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ANEMIA OF CHRONIC DISEASE
CAUSES
-chronic infections (often in children)
- chronic inflammatory disorders (obesity, uremia, autoimmune diseases,
etc.)
-chronic inflammation (elder people)
- neoplastic disorders
PATHOMECHANISM
1. Decreased iron absorption from GI tract
2. Decreased release of iron from macrophages from RE system (cytokines)
3. Relative reduction in EPO (cytokines) and impaired marrow response
4. Shortened RBC survival
MACROCYTIC ANEMIA
MCV > 100fL
Abnormalities of DNA metabolism
- vitamin B12 deficiency (pernicious anemia)
- folate deficiency
- drugs (metothrexate, contraceptives)
Lipid abnormalities
- liver disease
Alcohol abuse
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MEGALOBLASTIC ANEMIA I
Abnormalities in the absorption or metabolism of folate
or cobalamine (vit.B12).
The result is that DNA synthesis is inhibited and the cell
cycle is slowed down during erythropoesis.
Hemoglobin synthesis in cytoplasm is unchanged but
erythriblasts increase in size (megaloblasts; MCV>100 fL)
and oval erythrocythes pass into the blood.
There is normal cytoplasm synthesis but, nucleus
synthesis is delayed.
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MEGALOBLASTIC ANEMIA II
The formation of granulocytes and
megacaryocytes (platelets) is also disturbed
There is premature destruction of mgaloblasts in
bone marrow (inefficient erythropoesis) and
shortened life-span (premature hemolysis)
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COBALAMINE (VITAMIN B12) I
Must be taken up by humans in their food (animal
food: meat, eggs, milk, fish).
Daily requirement 1-5g
Main storage – liver (3 years)
Normal absorption of vit B12 needs intrinsic
factor, produced by the gastric mucous (parietal cells).
Autoimmune disorder- antibodies vs. intrinsic factor
or parietal cells is called pernicious anemia
Site of absorption - ileum
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COBALAMINE ( VITAMIN B12) II
METABOLIC FUNCTION
DNA synthesis
Fatty acids synthesis
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COBALAMINE ( VITAMIN B12) III
DEFICIENCY
Intrinsic factor deficiency (pernicious anemia)
Too little uptake with food (strict vegetarian diet)
Competition for cobalamine (broad fish tapeworms-
Diphyllobothrium latum in the intestinal lumen)
The symptoms of cobalamine deficiency may occur only
after years of blocked supply (great liver storage)
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FOLATE I
Necessary for the synthesis of DNA
Folate deficiency inhibits the rate of formation of
rapidly proliferating cells for example during
erythropoesis and tumor formation.
Daily intake - 50g
Food source – leafy fresh green vegetables
(overcooking food destroys folate), red meats ( liver);
must be provided by dietary sources
Absorption – duodenum, upper jejunum
Main storage – liver (2-3 months)
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FOLATE II
DEFICIENCY
Too little folate uptake with food or too long
cooking of vegetables
Increased requirement (pregnancy)
Malabsorbtion ( diseases of the small intestine e.g.
Celiac disease)
Inhibition of folate synthesis caused by cytostatic
chemotherapeutics (methotrexat, fluorouracil,
aminopterin)
Low absorption (contraceptive pills)
Folate deficiency is more commonly
encountered in clinical practice
Megaloblastic anemia is often seen
as malnutrition in the elderly,
alcoholics, teenagers and in
pregnancy
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MEGALOBLASTIC ANEMIA - SYMPTOMS
H E M A T O L O G I C A L
Megaloblasts MCV>100
G A S T R O I N T E S T I N A L
Severe glossitis (inflamed, red, painful tongue)
Diarrhea
N E U R O N A L (only vit.B12 deficiency)
Dementia
Ataxic gait (unsteady)
Psycholgical disturbances
Feeling disorders
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NORMOCYTIC ANEMIA
MCV 80-100fL
Acute blood loss
Aplastic anemia
Chronic renal failure (EPO)
Hemolytic anemia (normocytic & microcytic)
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APLASTIC ANEMIA
Aplastic anemia is a condition where bone
marrow does not produce sufficient new cells to
replenish blood
The etiology is considered to be idiopatic
(without a known cause), but one known cause is
an autoimmune disorders in which white blood
cells attack the bone marrow.
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APLASTIC ANEMIA
This is the insufficient production of blood cells
It is life-threatening disorders of the stem cell in
bone marrow.
There are deficiencies in erythrocytes, lekocytes
and thrombocytes in blood (pancytopenia)
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APLASTIC ANEMIA
PREDICTABLE CAUSES
1.Antineoplastic
- Cyclophosphamide
- Vincristine
- Metotrexate
2.Radiation therapy (ionizing radiation)
3.Certain antibiotics (Chloramphenicol)
4.Miscellaneous drugs
- Anticonvulsant : Diphenylhydantoina, Phenobarbital
- Anti-inflammatory: Phenylobutazone, gold compounds
- Thyroid medication
5. Benzene
6. Viral infection (especially the viral hepatitis )
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APLASTIC ANEMIA - SYMPTOMS
The complex of symptoms in aplastic anemia relates to
PANCYTOPENIA
ERYTHROCYTES
Anemia
Hypoxia
WHITE BLOOD CELLS
Increased susceptibility to infection
PLATELTS
Ecchymosis (subcutaneous purpura larger than 1 centimeter or a
hematoma) and bleeding into the skin (petachiae)
Epistaxis (nosebleeding)
Gastrointestinal, genitourinary and central nervous system bleeding
HEMOLITIC ANEMIA
Hemolytic anemia is a form of anemia due to hemolysis.
Hemolysis is the rupturing of erythrocytes and the release of their contents (Hb) into surrounding fluid (blood plasma).
The abnormal breakdown of (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular).
RBC life span below 100 days (as little as several days = definition of hemolysis)
HEMOLITIC ANEMIA
CORPUSCULAR HEMOLYTIC ANEMIA
(MAINLY INHERITED). RBCs are removed from peripheral blood by extravascular hemolysis
• spherocytosis, ovalocytosis, sicle cell anemia, talasemia
EXTRACORPUSCULAR HEMOLYTIC ANEMIA (MAINLY ACQIRED). RBCs are removed from peripheral blood by intravascular hemolysis.
• blood group mismatches, malaria, snake poisoning, mechanical cause (e.g. artificial heart valves), viral infection
EXTRAVASCULAR HEMOLYSIS
INTRAVASCULAR HEMOLYSIS
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JAUNDICE
Jaundice is an excess of bilirubin in blood
Bilirubin is a breakdown product of hemoglobin that it is
normally excreted into the bile
In hemolytic anemia increased red blood cell
destruction leads to the increased release of free Hb
and increased production of bilirubin
The liver is not able to remove bilirubin so fast,
leading to pigmented skin and the whites of the eyes with
the characteristic yellowish color indicative of jaundice
1. CENTRAL MECHANISMS
Increased cardiac output
Increased heart rate (tachycardia)
2. PERIPHERAL MECHANISMS
Vasodilation (reduced peripheral resistance)
Lowering blood viscosity
Increased blood flow through the heart and brain (activation of the sympathetic
nervous system →vasopresin→ relaxation of cerebral and coronary arteries and constriction other
artheries)
Decreased blood flow through the kidneys, muscles, skin
Increased erythropoetin synthesis
3. ERYTHROCYTE MECHANISM :
Increased synthesis of 2,3 - DPG (bifosfoglicerynian) →easier oxygen transfer to the
tissues
4. TISSUE MECHANISMS :
Increased extraction of oxygen
Increased anaerobic methabolism
ANEMIA – COMPENSATORY MECHANISMS