L4-Iron deficiency anaemia - PowerPoint Presentation

Slide1

L4-Iron deficiency anaemia

Ass.prof

.

Abeer

Anwer

Ahmed

Slide2

Sequence of events

Depletion of

iron stores

When the body is in a state of negative iron balance, the

first

event is depletion of body stores, which are mobilized for

haemoglobin

production.

Iron absorption is increased when

stores are

reduced

, before

anaemia

develops and even when the serum

iron level is still normal,

although

the serum

ferritin

will

have already

fallen.

Slide3

Iron - deficient erythropoiesis

With further iron

depletion,manifested

by

:

a

serum

ferritin

below

15 μ g/L

and

fall in serum

transferrin

aturation

to

less than

15

%,

iron - deficient

erythropoiesis

develops

with increasing concentrations of serum

transferrin

receptor and red cell

protoporphyrin

.

At this stage, the

haemoglobin

, mean corpuscular

volume (MCV) and MCH may still be

within the reference

srange

,

although

they may rise

significantly

when iron therapy

is given.

Slide4

Iron

deficiency

anaemia

If

the negative balance continues, frank iron

deficiency

anaemia

develops

.

The

red cells become obviously

microcytic

and

hypochromic

and

poikilocytosis

becomes

more marked

.

The

MCV and MCH are reduced, and target cells

may be

present.

The

reticulocyte

count is low for the degree

of

anaemia

.

The

serum TIBC rises and the serum iron falls, so

that the

percentage saturation of TIBC is usually less than 10

%.

Slide5

B.M

The number of erythroblasts containing

cytoplasmic

iron (

sideroblasts

) is reduced at an early stage in the development of deficiency, and

siderotic

granules are entirely absent from these cells when iron deficiency

anaemia

is established.

The erythroblasts have a ragged vacuolated cytoplasm and relatively

pyknotic

nuclei. The bone marrow macrophages show a total absence of iron, except where very rapid blood loss outstrips the ability to mobilize the storage iron.

Platelets are frequently increased

Slide6

Slide7

Tissue effects of iron deficiency

When

iron

deficiency

is severe and chronic, widespread tissue

changes may be present,

including:

koilonychia

(ridged

nails, breaking

easily), hair thinning, angular

stomatitis

(especially

in

those

with badly

fitting

dentures),

glossitis

and pharyngeal

webs (Paterson

– Kelly syndrome

).

Partial villous atrophy, with

minor degrees

of

malabsorption

of

xylose

and fat, reversible by

iron therapy

, has been described in infants suffering from iron

deficiency

, but not in adults.

Pica

is sometimes present; in

some who

eat clay or chalk, this may be the cause rather than

the result

of iron

deficiency

.

Slide8

Iron - dependent enzymes in the tissues are usually better preserved than other iron - containing compounds.

In severe iron deficiency, however, these enzymes are not inviolate and their levels may fall.

This may be partly responsible for the general tissue changes, with mitochondrial swelling in many different

cells (including, in the experimental animal, hepatic and myocardial cells), poor lymphocyte transformation and diminished cell - mediated immunity, and impaired intracellular killing of bacteria by

neutrophils

.

Slide9

A particular concern has been the finding that infants with iron deficiency

anaemia

may have impaired mental development and function, and that this deficit may not be completely restored by iron therapy.

There is recent evidence that premature

labour

is more frequent in mothers with iron deficiency

anaemia

.

It remains controversial whether impaired work performance

seen in adults results from the

anaemia

or from depletion

of mitochondrial iron - containing enzymes. It is also

unclear to what extent some of the other tissue effects of iron

deficiency can occur even in the absence of

anaemia

.

Slide10

Causes of iron deficiency

Blood loss

Uterine:

menorrhagia

, post- menopausal bleeding, parturition ,

Gastrointestinal

:

oesophageal

varices

, hiatus hernia,

Helicobacter pylori , peptic ulcer, aspirin ingestion, hookworm, hereditary

telangiectasia

, carcinoma of the stomach,

caecum

or colon, ulcerative colitis,

angiodysplasia

,

Meckel

diverticulum

,

diverticulosis

,

haemorrhoids

, etc.

Renal tract:

haematuria

(e.g. renal or bladder lesion),

haemoglobinuria

(e.g. paroxysmal nocturnal

haemoglobinuria

)

Pulmonary tract

: overt

haemoptysis

, idiopathic pulmonary

haemosiderosis

Widespread bleeding disorders Self - inflicted

Malabsorption

Gluten - induced

enteropathy

(child or adult),

gastrectomy

,

atrophic gastritis, chronic inflammation, clay eating, etc.

Dietary

Especially vegetarian diet

Slide11

Diet

Defective intake of iron is rarely the sole or major cause of iron deficiency in adults in Western communities. The diet may contain insufficient or poorly available iron as a result of poverty, religious tenets or food faddism.

Iron deficiency is more likely to develop in subjects taking a largely vegetarian diet the majority of the world ’ s population – who also have

increased physiological demands for iron

Slide12

Increased physiological iron requirements

Iron

deficiency

is common in infancy, when demands for growth may be greater than dietary supplies.

It is aggravated by prematurity, infections and delay in mixed feeding.

It is also frequent in adolescence, in females and in pregnancy

The fetus acquires about 280 mg of iron and a further 400 – 500 mg is required for the temporary expansion of maternal red cell mass. Another 200 mg of iron is lost with the placenta and with bleeding at delivery.

Although iron absorption increases throughout pregnancy and increased requirements are partly offset by

amenorrhoea

, this may not be sufficient to meet the resultant net maternal outlay of over600 mg iron.

Slide13

Blood loss

Blood loss is the most common cause of iron deficiency in adults.

A loss of more than about 6 – 8

mL

of blood (3 – 4 mg iron) daily becomes of importance, as this equals the maximum amount of iron that can be absorbed from a normal diet.

Slide14

loss is usually from the genital tract in women or from the

gastrointestinal tract in either sex.

The most common cause on a worldwide basis is infestation with hookworm, in which

anaemia

is related to the degree of infestation. In the UK,

menorrhagia

,

haemorrhoids

and peptic ulceration are common, as well as gastric bleeding because of

salicylates

or other non - steroidal anti-

infl

ammatory

drugs, hiatus hernia, colonic

diverticulosis

and bowel

tumours

.

Some unusual causes of blood loss deserve mention. Cow ’ s milk intolerance in infants may lead to gastrointestinal

haemorrhage

. Self - induced

haemorrhage

may occur.

Chronic intravascular

haemolysis

, such as that in paroxysmal nocturnal

haemoglobinuria

or mechanical

haemolytic

anaemia

, may be a serious source of urinary iron loss.

Slide15

Malabsorption

Malabsorption

may be the primary cause of iron deficiency or

it may prevent the body adjusting to iron deficiency from other

causes.

Dietary iron is poorly absorbed in gluten - induced

enteropathy

,

in both children and adults.

Gluten - induced

enteropathy

is encountered in about 5% of patients presenting with unexplained iron deficiency

anaemia

and, conversely, about

50% of patients with newly diagnosed

coeliac

disease have coexistent

iron deficiency

anaemia

.

Patients with this disease often show decreased or no response to oral therapy with inorganic iron.

Slide16

Helicobacter pylori gastritis appears to be a common cause of

iron deficiency, responding

favourably

to eradication with triple therapy.

Helicobacter pylori gastritis inhibits gastric hydrochloric

acid secretion, interfering with the

solubilization

and

absorption of inorganic food iron but it is also possible that gastrointestinal blood loss plays a

signifi

cant role in the causation of iron

defi

ciency

associated with

H. pylori infection

Slide17

achlorhydria

associated with autoimmune gastritis, an entity

preceding and closely related to pernicious

anaemia

, is an

important cause of iron

malabsorption

due to impaired food

iron

solubilization

.

It is encountered in about 20% of patients with unexplained or refractory iron deficiency

anaemia

, mostly

women of fertile age in whom

achlorhydria

aggravates the consequences of menstrual blood loss.

Slide18

Management of iron deficiency

(

i

)

identification

and treatment of the

underlying cause and (ii) correction of the

defi

ciency

by therapy

with inorganic iron. Iron

defi

ciency

is commonly due to blood

loss and, wherever possible, the site of this must be

identifi

ed

and the lesion treated.

Slide19

Oral therapy

In most patients, body stores of iron can be restored by oral

iron therapy.

ferrous

sulphate

is the cheapest, this is

the drug of first choice – 200 mg of ferrous

sulphate

contains

67 mg of iron.

Where smaller doses are required, 300 mg of

ferrous

gluconate

provides 36 mg of iron.

It is usual to give 100 – 200 mg of elemental iron each day to adults and about

3 mg/kg per day as a liquid iron preparation to infants and

children.

The side - effects of oral iron, such as nausea,

epigastric

pain,

diarrhoea

and constipation, are related to the amount of

available iron they contain.

Slide20

The minimum rate of response should be a 20 g/L rise in

haemoglobin

every 3 weeks, and the usual rate is 1.5 – 2.0 g/L daily.

This will be slower when the dose tolerated is less than

100 mg/day, but this is seldom of clinical importance.

It is usually necessary to give iron for 3 – 6 months to correct the deficit of iron in circulating

haemoglobin

and in stores (shown by a rise in serum

ferritin

to normal)

Slide21

Positive response in

reticulocytosis

is seen in

few days

of oral therapy

Hb

should reach to normal level after

2 months

A

Hb

response of <20 g/L over a 3-week period warrants therapy evaluation

Day-14

Hb

may be a useful tool for clinicians in determining whether and when to

transition patients from oral to IV iron.

an increase of 1.0 g/

dL

or more over baseline is an accurate predictor of longer-term and sustained response to continued oral therapy

Slide22

Iron profile

should be measure in the

first week

for oral therapy and

2 weeks

after large intravenous doses

Complete therapeutic response requires iron supplementation for up to 2-6 months

, however, symptoms may improve within few days after oral therapy

Slide23

Failure to respond to oral iron

most commonly due to :

-patient not taking it

-continued

haemorrhage

or

malabsorption

.

-other causes of

microcytic

anaemia

such as iron - loading

anaemias

. For instance, many patients with, bone marrow examination or other tests have revealed the co

thalassaemia

trait,

sideroblastic

anaemia

or other

anaemias

have been treated with iron before

haemoglobin

studies ,bone marrow examination or other tests have revealed the correct diagnosis.

-patient has an infection, renal or hepatic failure, an underlying malignant disease or

anaemia

of inflammation due to high

hepcidin

levels (which inhibits absorption of therapeutic oral iron) and any other cause of

anaemia

in addition to iron deficiency

Slide24

Parenteral i ron t herapy

This is usually unnecessary, but it may be given if subjects

-cannot tolerate oral iron, particularly if gastrointestinal

disease, such as inflammatory bowel disease, is present.

It is also occasionally necessary in gluten - induced

enteropathy

-it is essential to replete body stores rapidly (e.g. where

severe iron deficiency

anaemia

is first diagnosed in late pregnancy)

- when oral iron cannot keep pace with continuing

haemorrhage

(e.g. in patients with hereditary

haemorrhagic

telangiectasia

).

-Patients with chronic renal failure who are being

treated with recombinant erythropoietin are also likely to

require

parenteral

iron therapy.

Slide25

From all parenteral

preparations, the iron complex is taken up by macrophages of the

reticuloendothelial

system, from which iron is released to circulating

transferrin

, which then transports it to the marrow

Slide26

three preparations areavailable

. Iron

dextran

(

CosmoFer

) is given intravenously by slow injection or infusion or deep intramuscularly into the

gluteal

muscle.

An iron – sucrose complex,

Venofer

, is given by slow intravenous infusion or injection.

The deficit in body iron

should be calculated from the degree of

anaemia

; it is usually1 – 2 g. In patients receiving erythropoietin treatment in chronic renal failure, smaller intravenous doses of

Venofer

(25 – 150 mg/ week) may be used, with regular monitoring of serum

ferritin

to avoid iron overload.

Ferrinject

is a macromolecular iron(III) -hydroxide carbohydrate complex (molecular weight approximately 150 000). It can be administered as an intravenous bolus (maximum single dose 200 mg) or slow infusion (maximum single dose 1000 mg).

Newer intravenous preparations including

ferumoxytol

and ferrous

gluconate

(

Ferrlecit

) may become

available.

Slide27

Iron refractory iron deficiency anaemia

Homozygous or doubly heterozygous

germline

frameshift

,

splice junction or

missense

mutations of

matriptase

- 2(

TMPRSS6 )

are a cause of iron refractory iron deficiency

anaemia

..

The patients show a

microcytic

hypochromic

anaemia

with

normal or raised serum and urine

hepcidin

levels and

Low serum iron and percentage saturation of iron –

binding capacity

The patients absorb iron poorly and are refractory to oral iron

therapy but are partially responsive to

parenteral

iron.

Slide28

the 

TMPRSS6

 gene

encoding Matriptase-2

Matriptase-2

(MT-2).

.

 is a

transmembrane

serine protease that cleaves

Hemojuvelin

, a major regulator of

hepcidin

expression and plays an essential role in down-regulating

hepcidin

,

the key regulator of iron homeostasis.

Slide29

mutations of DMT1

.

A

microcytic

hypochromic

anaemia

with liver iron overload

has also been described in a few patients with homozygous or

doubly heterozygous

mutations of DMT1

Liver iron stores are increased but

erythroid

iron utilization is impaired and

Serum

hepcidin

levels are low for the degree of iron overload. These

patients may respond to erythropoietin injections.

The patients are susceptible to infections.

Slide30

Deficiency of serum

transferrin

due to mutations of the

transferrin

gene causes a

hypochromic

microcytic

anaemia

with tissue iron overload caused by increased plasma non -

transferrin

- bound iron and low

hepcidin

levels. Treatment

hasbeen

with infusions of fresh frozen plasma or

apotransferrin

.

Deficiency of

caeruloplasmin

also causes a mild

hypochromic

microcytic

anaemia

with iron overload in the liver and progressive

neurodegeneration

. There is failure of

ferroxidase

activity, which impairs iron mobilization from stores.

Slide31

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