ANIMIAS. Anemia Defined as a reduction in one or more of the major RBC measurements: Hgb: measures...

ANIMIAS

Anemia

Defined as a reduction in one or more of the major RBC measurements: Hgb: measures the concentration of the major

oxygen carrying pigment in whole blood Hct: percent of a sample of whole blood

occupied by intact RBCs RBC Count: number of RBCs contained in a

specified volume of whole blood All factors are dependent on the RBC mass

and the plasma volume

Signs and Symptoms of Anemia Dependent on the degree of anemia, the

rate at it evolved, and the oxygen demand Normally, RBCs carry oxygen linked to Hgb

from the lung to tissue capillaries, where oxygen is released

Symptoms result from decreased oxygen delivery or acute blood loss (hypovolemia)

Compensatory mechanisms allow one to tolerated lower levels of Hgb/Hct Increase in stroke volume, HR (

increased CO) Enhanced oxygen extraction by the

tissues

Anemia: History

Is the patient bleeding? NSAIDs, ASA

Past medical history of anemia? Family history?

Alcohol, nutritional questions Liver, renal diseases Menstrual history if applicable Ethnicity Environmental/work toxins (ie lead)

Symptoms of Anemia

Decreased O2 delivery Hypovolemia if acute loss Exertional dyspnea, fatigue, palpitations,

“bounding pulses” Severe: heart failure, angina, MI “Pica”– craving for paper products Pagophagia– craving for ice

Signs of Anemia

Tachycardia, Pallor Jaundice Koilonychia or “Spoon nails” Splenomegaly, lymphadenopathy Petechiae, ecchymoses Atrophy of tongue papillae Guaiac

Koilonychia or “Spoon nailsPallor

Approach to Anemia

Classification: Kinetic Approach –mechanism responsible

Decreased RBC production Increased RBC destruction Blood Loss

Morphologic Approach – alteration in RBC size Macrocytic Normocytic Microcytic

Kinetic Approach

• Decreased RBC Production– Lack of nutrients (Fe, B12, Folate) due to diet,

malabsorbtion– Bone Marrow Disorders– Bone Marrow Suppression– Drugs, chemotherapy, radiation

– Low levels of trophic hormone levels which stimulate RBC production– Epo, Thyroid Hormone, Androgens

– Chronic disease/inflammation– Causes decreased Fe absorbtion from GIT, decreased

Fe release from macrophages, reduction of Epo

Kinetic Approach

• Increased RBC Destruction• Inherited and acquired hemolytic anemias• Inherited: Hereditary Spherocytosis, sickle cell

disease, thalassemia• Acquired:

• Blood Loss• One of the most common causes of anemia• Not only lose RBCs, but also the Fe in these

cells, which leads to Fe deficiency

Morphologic Approach

• Macrocytic– Reticulocytosis– Drugs interfering with nucleic acid synthesis– Abnormal nucleic acid metabolism of erythroid

precursors– Abnormal RBC Maturation– liver disease, hypothyroidism

• Normocytic• Microcytic

– Reduced iron availability– Reduced Heme synthesis– Reduced globin production

Lab Evaluation

• CBC• Reticulocyte Count:

– High: hemolysis or blood loss– Low: deficient production of RBCs (reduced

marrow response to anemia)• RBC Indices:

• MCV – mean corpuscular volume (Hct/RBC)• MCH – mean corpuscular Hgb (Hgb/RBC)• MCHC – mean corpuscular Hgb concentration

(Hgb/Hct)

Hemolytic Anemia

Hemolytic Anemia

• Anemia due to shortened survival of circulating RBCs (Normal: 110-120 days)– Hemolysis <100 days

• With intact bone marrow:• Anemia Compensatory increase in Epo

secretion Enhances RBC production (reticulocytosis) Reduces degree of anemia

• This is most commonly seen with hemolytic anemia, but not specific to hemolysis (can also be seen with acute blood loss)

Reticulocyte Count

Relative reticulocyte count % of all RBC (normal 0.8-1.5%)

Absolute reticulocyte count Relative reticulocyte count x RBC count Normal 50,000-75,000/µl Examples:

1.1% x 4.96 x106 = 55,000/ml

12..2% x 2.05 x106 = 250,000/ml

Causes of Hemolysis - Intrinsic• Generally, a hereditary disorder• Intrinsic hemolysis is caused by defects

in Hgb, RBC membrane or metabolic factors needed to generate ATP

• Examples• Thalassemia (defect in alpha or beta globin

chains)• Spherocytosis (missing RBC membrane proteins)• G6PD deficiency (abnormality in reducing power

(NADPH))

Causes of Hemolysis - Extrinsic• Acquired disorder• Causes include:

• Ab directed against RBC membrane components • AIHA (Auto Immune Hemolytic Anemia), delayed transfusion

reaction

• Stasis/trapping/destruction in spleen (hypersplenism)• Trauma• Prosthetic heart valve

• Exposure to compounds with oxidant potential• Sulfonamide in those with G6PD

• Destruction of RBC by pathogens• Malaria, babesiosis

Site of Hemolysis

Dependant on the severity and type of cell alteration (alteration in RBC membrane)

Severe damage immediate lysis in the circulation (INTRAVASCULAR)

Less severe damage cell destruction is via the monocyte-macrophage system in the liver, spleen, BM, lymph node (EXTRAVASCULAR)

Intravascular Hemolysis

• Intravascular hemolysis Release of Hgb into the plasma

• Free Hgb binds to haptoglobin Hgb-haptoglobin complex is taken up by liver Decrease in plasma haptoglobin

• Free Hgb breaks down to alpha-beta dimers filtered by glomerulus Hemoglobinuria

Intravascular Hemolysis

• Causes:• Shear stress– Mechanical heart valve

• Heat damage• Complement-induced lysis– Paroxysmal cold hemoglobinuria

• Osmotic lysis• Lysis from bacterial toxins• Clostridium

Extravascular Hemolysis

Damaged RBCs are destroyed by liver and spleen

Features of Hemolysis

Rapid fall in Hgb Increased LDH, decreased Haptoglobin Jaundice (elevated indirect bilirubin) Splenomegaly H/o pigmented gallstones Abnormally shaped RBCs Reticulocytosis

Labs

LDH: elevated Indirect bilirubin: elevated (due to catabolism of

Hgb) Haptoglobin: decreased

Binds to Hgb and taken up by liver In a series of reports:

Elevated LDH, low Haptoglobin was 90% specific Normal LDH, Haptoglobin >25 was 92% sensitive for ruling out

hemolysis

Reticulocyte Count: elevated Normal is 0.5-1.5% Anemia leads to increase Epo production leading to a

reticulocytosis (4-5% increase above baseline)

Iron deficiency anemia

role of iron in the body

Iron have several vital functions Carrier of oxygen from lung to tissues Transport of electrons within cells Co-factor of essential enzymatic

reactions:NeurotransmissionSynthesis of steroid hormonesSynthesis of bile saltsDetoxification processes in the liver

IRON METABOLISM

Iron is present in the diet in many forms. Haem is the most important source.

Vegans may need to supplement their dietary intake with non-organic iron.

A normal adult requires 15-20 mg of iron per day to remain in balance.

Iron is normally absorbed by active transport across the wall of the duodenum and upper part of the jejunum.

If large amounts of iron are ingested the active transport mechanism is overtaken by passive diffusion..

Disease of the upper small gut can lead to malabsorption of iron, e.g. coeliac disease or tropical sprue.

Iron is best absorbed in the ferrous (reduced) form (Fe++).

Absorption is improved by reducing substances, e.g. ascorbic acid (vitamin C).

Absorption is also increased by certain iron chelators and by alcohol.

Iron absorption is normally relative to the needs of the body.

About 10% of dietary iron is usually taken up by the body but this can increase several-fold in iron deficiency, or reduce if the body has a surplus.

Most iron in the body is in the form of haem; present in large amounts in red cells, muscle and liver where it is essential for oxygen supply.

Iron is also present in many enzyme systems, e.g. electron transport systems.

The transport and storage of iron mainly involves three proteins: transferrin

transferrin receptor (TfR)ferritin

Transferrin actively binds and transports iron in the body and can be estimated by measuring the serum total iron binding capacity (TIBC).

Transferrin increases in iron deficiency and decreases with iron overload, liver disease, infection, malignancy and protein deficiency.

Excess iron is stored mainly in macrophages as haemosiderin; an insoluble protein-iron complex formed by lysosomal degeneration of ferritin.

Ferritin is the water soluble protein-iron complex formed when iron combines with apoferritin. Iron in ferritin is in the ferric form (Fe+++) and must be reduced before it can be utilised.

LABORATORY INVESTIGATION OF IRON

DEFICIENCY ANAEMIA

Full Blood Count Serum Ferritin Serum Iron & Total Iron Binding

Capacity Serum Transferrin Bone Marrow

FULL BLOOD COUNT can be suggestive but not diagnostic of iron deficiency.

Negative iron balance produces microcytosis (low MCV) and hypochromasia (low MCH).

Red cell morphology varies from mild anisocytosis to marked anisopoikilocytosis.

Thrombocytosis is common.

Leucocytes are usually normal.

SERUM FERRITIN is now a standard diagnostic test for IDA;

only iron deficiency will give a low result.

Normally the level of serum ferritin reflects the body iron stores (100 μg/L = 800 mg of iron).

A value <15 μg/L is diagnostic of IDA.

Circumstances in which the serum ferritin is normal or high in the presence of IDA:

· Liver dysfunction; ferritin is released when hepatocytes are damaged

· Increased haem turnover; haemolysis and trauma (including surgery)

· Inflammatory lesions; malignancy, infection and inflammation

SERUM IRON (SI) and TOTAL IRON BINDING CAPACITY (TIBC)

In iron deficiency the SI is low (<10 μmol/L) and the TIBC is usually raised (>70 μmol/L).

The SI shows marked diurnal variation. It may also be low in the presence of infection or inflammation.

The TIBC is also affected by nutrition and may be low in malnourished persons despite iron deficiency. For these reasons the serum ferritin is now preferred.

SI and TIBC are useful when the ferritin is falsely high, e.g. liver damage.

In the plasma, iron is bound to transferrin and the TIBC depends on the concentration of this protein.

The transferrin to which iron is not bound is known as the unsaturated iron-binding capacity (UIBC).

SI + UIBC = TIBC

Iron in the bodyThe total body

iron in a 70-kg man is about 4 g. This is maintained by a balance between absorption and body losses in the proximal small intestine (duodenum)

10-20% 5-15%

75%

•At physiological pH, ferrous iron (Fe2+) is rapidly oxidized to the insoluble ferric (Fe3+) form

•Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron

•If iron are low•hepcidin in the duodenal epithelium is decreased•causes an increase in ferroportin activity•stimulating iron uptake

Laboratory findings

1. CBC; WBC and differential cell count normal or

variable depend on patient condition,

Hb, Hct

RBC morphology => hypochromic microcytic cells

platelet => adequate or depend on patient condition

2. RBC indices => MCV, MCH, MCHC

3. Reticulocyte count => low related to degree of anemia

4. Serum iron (SI) , Total iron binding capacity (TIBC)

5. Serum ferritin

6. Serum transferrin receptor (sTfR)

7. % Transferrin saturation

Laboratory diagnosis

Hypochromic microcytic anemia

Low Si and ferritin

Raised TIBC and sTfR

Investigation of cause

Suspicious

Lab. diagnosis

1. For female

-Menorrhagia

-Pregnancy

2. For male or

female (1. not found)

-GI bleeding

-Stool occult blood test

-GI endoscopy

-Investigation of other causes

Treat cause and iron uptake

Anemia of Chronic Disease

Anemia of Chronic Disease

A normocytic, normochromic chronic anemia due to chronic infections (TB) or chronic inflammations (RA, neoplatic conditions) as well as chronic illnesses (diabetes, liver disease)

Usually mild, progressive and asymptomatic

Anemia of Chronic Disease

Etiology disruption of iron metabolism defect in red cell production shortening of erythrocyte life span

Incidencesecond most common to iron deficiency

Diagnostics

Normal to increased iron stores with concurrent low serum iron

serum iron-decreased TIBC-decreased serum ferritin-increased Hemoglobin-decreased Hematocrit- decreased MCV? normal Reticulocytes-decreased

Lab. Parameter

Iron deficiency

Chronic diseases

Thalassemia

MCV

MCH

MCHC

Reduced in related to severity of anemia

Normal or mild reduction

Reduced; very low for degree of anemia

Serum iron

Reduced Reduced Normal

TIBC Raised Reduced Normal

TfR Raised Normal/low

variable

Serum ferritin

Reduced Normal/

Raised

Normal

Thalassemia