blood patophysiology anemia

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