CASE PRESENTATION

IRON DEFICIENCY ANEMIA IN CHILDREN

Supervisor:
dr. Ulynar Marpaung, Sp. A

Written by:
Muhammad Haekal Fadhilah
1102014168

Departement of Pediatric

Bhayangkara Tk.I Raden Said Sukanto Hospital

Faculty of Medicine YARSI University

2018
 TABLE OF CONTENT

Preface……………………………………………………………………....2
Section I - Case Report ............................................................................... 3
Identity ......................................................................................................... 3
History taking ................................................................................................ 3
Physical Examination ................................................................................... 5
Laboratory Findings ..................................................................................... 8
Working Diagnosis ....................................................................................... 10
Differential Diagnosis………………………………………………………..10
Management ................................................................................................. 10
Prognosis ...................................................................................................... 11
Follow Up ..................................................................................................... 11
Section II –Literature of Review Iron Deficiency Anemia ..................... 17
Definition ..................................................................................................... 17
Etiology ........................................................................................................ 17
Epidemiology………………………………………………………………...18
Pathophysiology ........................................................................................... 21
Clinical Manifestations ................................................................................. 25
Diagnostic Approach ..................................................................................... 25
Therapeutic Approach .................................................................................. 30
Prevention Approach ..................................................................................... 34
Section III—Literature Review Urinary Tract Infection ........................ 37
Definition ...................................................................................................... 37
Etiology ......................................................................................................... 37
Pathophysiology ............................................................................................ 37
Clinical Manifestations ................................................................................. 39
Diagnostic Approach…………………………………………………………40
Differential Diagnosis………………………………………………………..45
Therapeutic Approach………………………………………………………..45
Prevention Approach…………………………………………………………46
Bibliography…………………………………………………………………48
CDC Growth Chart…………………………………………………………49

1
 PREFACE

Iron deficiency is the most widespread and common nutritional disorder in the world. It is
estimated that 30% of the global population suffers from iron-deficiency anemia, and most of
them live in developing countries. In the USA, 9% of children ages 12-36 months are iron
deficient, and 30% of this group have progressed to iron-deficiency anemia.

The incidence of iron-deficiency relates to basic aspects of iron metabolism and nutrition.
The body of a full-term newborn infant contains about 0.5 g of iron, compared to 5 g of iron in
adults. This change in quantity of iron from birth to adulthood means that an average of 0.8 mg
of iron, must be absorbed each day during the first 15 years of life. A small additional amount is
necessary to balance normal losses of iron by shedding of cells. It is therefore necessary to absorb
approximately 1 mg daily to maintain positive iron balance in childhood. Because <10% of
dietary iron usually is absorbed, a dietary intake of 8-10 mg of iron daily is necessary to maintain
iron levels.

During infancy, when growth is most rapid, the approximately 1 mg/L of iron in bovine
and breast milk makes it difficult to maintain body iron. Breast-fed infants have an advantage
because they absorb iron 2-3 times more efficiently than infants fed bovine milk.

2
 CASE REPORT
IRON DEFICIENCY ANEMIA

Patient’s Identity
Name : Child E
Birthdate : 29st Oct 2017
Age : 11 months
Gender : Male
Nationality : Indonesian
Race : Javanese
Religion : Islam
Address : Pasar Rebo
Date of Admission : 22nd October 2018

Parents’ Identity
Father Mother
Name Mr. R Mrs. N
Age 35 years old 27 years old
Gender Male Female
Nationality Indonesian Indonesian
Religion Islam Islam
Occupation Officer Housewife
Last Education Bachelor Degree High school

Relationship with patient: Biological parents

PERSONAL HISTORY
The information was given by the patient’s mother on the 17th of May 2018.
 Chief Complaint: fever in the last 3 days prior to admission
 Additional Complaint: Pallor skin, nausea

3
Patient’ History of Present Illness:
A 11 months old male infant was admitted to the emergency care unit with a chief complaint of
fever 3 days prior to hospital admission. His mother stated that her baby was healthy before she
noticed the raise in temperature. According to the mother, he gradually developed fever, which
was insidious in onset, initially low grade on and off and gradually progressed to high grade and
was continuous. The mother stated that the temperature reached the peak of 41oC. She brought
him to the nearest clinic and was prescribed sanmol. Fever was not associated with chills or
rigors. The mother gives history of fever subsiding early in the morning and after intake of
paracetamol.

The mother also gave history of nausea but no history of diarrhoea, vomiting, belching or
bloating were reported.

According to his mother, there were no symptoms of increased work of breathing or cough.
However, the mother did say that Child E was slightly more irritable and lethargic in the past
few days.

Past Medical History: No past medical history to date. Mother denied any sickness, accidents
and injuries.

Allergy History: No known allergies were reported.

Birth History:
Child E was born at 39 weeks of gestation by normal labor to a 27-year-old mother G2P2, whose
first prenatal visit at was in the first trimester. His birth weight was 3000 grams and length of 48
cm. There were no complications at delivery, APGAR score was unknown but the mother said
Child A breathed spontaneously at birth and he did not require any respiratory support or
phototherapy.

Developmental History

- Social Personality
 Smile : 3 months
 Reaching toys : 6 months
 Drinking from cup :-
 Clapping hands : 6 months
- Psychomotor development

4
  Slant : 5 months
 Speech initiation : 5 months
 Prone position :-
 Sitting : 8 months
 Crawling : 8 months
 Standing : 9 months
 Walking :-
- Language
 Screaming :-
 Laughing : 6 months
 Turn one’s head : 3 months
 Papa/Mama :-
- Conclusion: developmental is within the normal limits and appropriate according to
the patient’s age.

Feeding History
- Breast milk : Exclusively 6 months
- Formula milk : None were given
- Baby biscuit : Milna and cerelac
- Fruit and vegetables : Banana and papaya

Immunization History: Up to date

PHYSICAL EXAMINATION
General
 Patient is a well-developed, well-nourished infant in no apparent distress. Appears to be
well hydrated.
Vital Sign
 Body Temperature : 37.7oC
 Respiratory Rate : 24 breaths per minute
 Heart Rate : 110 beats per minute
Growth Parameter
 Weight : 7 kg
 Height

5
  Standing height : 71 cm
 Sitting height : 39 cm
 Head Circumference :
 CDC Growth Chart
 Weight for age : 9.1/10.2 x 100% = 89% (Normal range)
 Height for age : 71/75 x 100% = 94% (Normal range)
 Weight for height : 9.1/8.8 x 100% = 103% (Normal range)

Head
 Normocephalic, atraumatic with thin hair. Anterior fontanelle measured 2 cm x 1.5 cm,
soft and flat within normal pulsation.
Eyes
 Pupils equal, round and reactive to light. Extraocular muscle appeared intact but the
patient was too young to cooperate with the examination. No discharges, conjunctivitis
or scleral icterus. No ptosis. Pallor were detected for both eyes.
Ears
 Clear external auditory canals. Pinnae shape and contour was normal. No pre-auricular
pits or skin tags. No erythema or bulging.
Nose
 Normal pink mucosa, no discharge or blood visible. Normal midline septum.
Mouth
 Moist mucous membrane.
Pharynx
 Unable to visualise tonsils. Pharynx shows no erythema or ulcerations.
Neck
 Grossly non-swollen. No tracheal deviation. No decrease in ROM. No lymphadenopathy,
goitre or masses detected.
Chest
 No increase of accessory muscles (no evidence of increased work of breathing).
Lungs
 Lungs are clear to auscultation bilaterally. No stridor, wheezes, crackles or rubs.
 Good air movement.

6
Cor
 Normal S1-S2 rate and rhythm. No murmurs, gallops or rubs.
Abdomen
 Soft, non-tender, non-distended. Bowel signs present. No noted splenomegaly. No
masses.
Extremities
 Warm, no cyanosis or oedema. No gross deformities. Good skin turgor with no tenting.

Neurogical Examination
Meningeal Sign
- Nuchal rigidity (-)
- Kernig sign (-)
- Lasegue sign (-)
- Brudzinski I (-)
- Brudzinski II (-)

Motoric Examination

Power
- Hand 5555/5555
- Feet 5555/5555
Tones
- Hand Normotonus/ Normotonus
- Feet Normotonus / Normotonus
Trophy
- Hand Normotrophy / Normotrophy
- Feet Normotrophy / Normotrophy
Physiologic Reflex
Upper extremities
- Biceps +2 / +2
- Triceps +2 / +2
Lower extremities
- Patella +2 / +2

7
 - Achilles +2 / +2
Pathologic Reflex
Upper extremities
- Hoffman -/-
- Trommer -/-
Lower extremities
- Babinsky -/-
- Chaddock -/-
- Oppenheim -/-
- Gordon -/-
- Schaeffer -/-
Clonus
- Patella -/-
- Achilles -/-

LABORATORY FINDINGS
Hematology (Oct 22nd, 2018)
Results Normal Value
Hemoglobin 4 13 – 16 g/dl
White blood cells 8.100 5.000 – 10.000 u/l
Hematocrit 15 40 – 48 %
Platelet count 321.000 150.000 –400.000 /ul

Hematology (Oct 23th,2018)

Results Normal Value
Blood Type O/+
Hemoglobin 4,5 13 – 16 g/dl
White blood cells 8.000 5.000 – 10.000 u/l
Hematocrit 16 40 – 48 %
Platelet count 340.000 150.000 –400.000 /ul
Leukocyte count
Basophil 0 0–1%

8
 Eosinophil 0 1–3%
Rod Neutrophil 0 2–6%
Segmented Neutrophil 45 50 – 70 %
Lymphocyte 48 20 – 40 %
Monocyte 7 2–8%
Erythrocyte Sedimentation
4 < 15 mm/jam
Rate (ESR)
Erythrocyte 3.38 4.5 – 5.5 juta/ul
Erythrocyte
MCV 48 82 – 92 %
MCH 13 27 – 31 fL
MCHC 28 32 – 36 g/dl
Reticulocyte count 1.43 0.8 – 1.5 %
Reticulocyte absolute
71,100 20.000 – 100,000 /uL
count

Peripheral Blood Smear (Oct, 23th, 2018)

 HB: Moderate Anaemia
 RBC: Microcytic hypochromic with anisopoikilocytosis, pencil cell (++), tear drop
cell (++), Fragmentocyt(++)
 WBC: Normal range
 Platelets: Normal range
 Impression: Microcytic Anaemia, possible causes due to Iron Deficiency Anaemia.
 Suggestion: Check Serum Iron, TIBC, Ferritin Serum, Transferrin saturation
Hematology (Oct 23th, 2018)
Results Normal Value
Serum Iron 15 60 – 150 ug/dl
TIBC 378 250 – 400 ug/dl
Ferritin 12 30 – 400 ng/dl

9
Urinalysis (Oct 23th, 2018)
Results Normal Value
Colour Light yellow
Appearance Cloudy
Specific Gravity 1.010 1.000 – 1.030
pH 7.0 5 – 8.5
Protein - Negative
Bilirubin - Negative
Glucose - Negative
Ketone - Negative
Occult Blood - Negative
Nitrite - Negative
Urobilinogen - Negative
Leukocyte - Negative
Leukocyte sediment 0–1 0–5
Erythrocyte sediment 1–2 1-3
Epithelial cell +
Cast -
Crystal -
Bacteria + Negative

Hematology (Oct 25th,2018)

Results Normal Value
Hemoglobin 10,6 13 – 16 g/dl
White blood cells 3400 5.000 – 10.000 u/l
Hematocrit 37 40 – 48 %
Platelet count 246.000 150.000 –400.000 /ul

WORKING DIAGNOSIS
 Iron Deficiency Anaemia
 Urinary Tract Infection
 Good Nutritional State

10
DIFFERENTIAL DIAGNOSIS
 Anemia of inflammation disease
 Thalassemia

MANAGEMENT
 Fluid Maintenance
 Intravenous hydration: Ringer Lactate 900 ml for 24h.
 Symptomatic drugs
 Acetaminophen syrup 90-135 mg every 6 hours.
 Antibiotics
 Cefotaxime intravenous 500 mg twice daily.
 Fe Supplementation
 Iron supplementation drop 0.5 ml once daily (1mg/kg/day) for 4 months.

PROGNOSIS
- Quo ad vitam : Bonam
- Quo ad functionam : Dubia ad bonam
- Quo ad sanationam : Dubia ad bonam

FOLLOW UP

Oct 22nd 2018, first day of admission, 3th day of illness

S Mild fever (+),
Consciousness : Compos Mentis
General condition : Midly ill
O
Temperature : 37,8 °C
Pulse :120 x/min
Respiratory rate : 24 x/min

11
Head
 Normocephalic, atraumatic with thin hair. Anterior fontanelle
measured 2 cm x 1.5 cm, soft and flat within normal pulsation.
Eyes
 Pupils equal, round and reactive to light. Extraocular muscle
appeared intact but the patient was too young to cooperate with the
examination. No discharges, conjunctivitis or scleral icterus. No
ptosis. Pallor were detected for both eyes.
Ears
 Clear external auditory canals. Pinnae shape and contour was
normal. No pre-auricular pits or skin tags. No erythema or bulging.
Nose
 Normal pink mucosa, no discharge or blood visible. Normal
midline septum.
Mouth
 Moist mucous membrane.
Pharynx
 Unable to visualise tonsils. Pharynx shows no erythema or
ulcerations.
Neck
 Grossly non-swollen. No tracheal deviation. No decrease in ROM.
No lymphadenopathy, goitre or masses detected.
Chest
 No increase of accessory muscles (no evidence of increased work
of breathing).
Lungs
 Lungs are clear to auscultation bilaterally. No stridor, wheezes,
crackles or rubs.
 Good air movement.
Cor
 Normal S1-S2 rate and rhythm. No murmurs, gallops or rubs.
Abdomen

12
  Soft, non-tender, non-distended. Bowel signs present. No noted
splenomegaly. No masses.
Extremities
 Warm, no cyanosis or oedema. No gross deformities. Good skin
turgor with no tenting.
Anemia
A Normal Growth development
Good nutritional state
- IVFD D5 ½ NS 7 tpm
P - Paracetamol 4 x 0,8cc
- Apialys drop 1 x 0,5cc.

Oct 23th 2018, second day of admission, 4th day of illness

S Mild fever (+)
Consciousness : Compos Mentis
General condition : Midly ill
Temperature : 37,8 °C
Pulse :120 x/min
Respiratory rate : 24 x/min
Head
 Normocephalic, atraumatic with thin hair. Anterior fontanelle
measured 2 cm x 1.5 cm, soft and flat within normal pulsation.
Eyes
 Pupils equal, round and reactive to light. Extraocular muscle
appeared intact but the patient was too young to cooperate with the
examination. No discharges, conjunctivitis or scleral icterus. No
ptosis. Pallor were detected for both eyes.
Ears
 Clear external auditory canals. Pinnae shape and contour was
normal. No pre-auricular pits or skin tags. No erythema or bulging.

13
 Nose
 Normal pink mucosa, no discharge or blood visible. Normal
midline septum.
Mouth
 Moist mucous membrane.
Pharynx
 Unable to visualise tonsils. Pharynx shows no erythema or
ulcerations.
Neck
 Grossly non-swollen. No tracheal deviation. No decrease in ROM.
No lymphadenopathy, goitre or masses detected.
Chest
 No increase of accessory muscles (no evidence of increased work
of breathing).
Lungs
 Lungs are clear to auscultation bilaterally. No stridor, wheezes,
crackles or rubs.
 Good air movement.
Cor
 Normal S1-S2 rate and rhythm. No murmurs, gallops or rubs.
Abdomen
 Soft, non-tender, non-distended. Bowel signs present. No noted
splenomegaly. No masses.
Extremities
 Warm, no cyanosis or oedema. No gross deformities. Good skin
turgor with no tenting.
Iron Deficiency Anemia
Urinary Tract Infection
A
Normal Growth development
Good nutritional state
- IVFD D5 ½ NS 7 tpm
P - Trf PRC 224 cc ( 100cc/day)
- Inj Lasix 5mg (while tranfussion)

14
 - Paracetamol 4 x 0,8cc
- Apialys drop 1 x 0,5cc

Oct 24th 2018, Third day of admission, 5th day of illness

Liquid defecation 4 times, greenish, acidic smell
S
Cough (+)
Consciousness : Compos Mentis
General condition : Midly ill
Temperature : 36.7 °C
Pulse :116 x/min
Respiratory rate : 24 x/min
Head
 Normocephalic, atraumatic with thin hair. Anterior fontanelle
measured 2 cm x 1.5 cm, soft and flat within normal pulsation.
Eyes
 Pupils equal, round and reactive to light. Extraocular muscle
appeared intact but the patient was too young to cooperate with the
examination. No discharges, conjunctivitis or scleral icterus. No
ptosis. Pallor were detected for both eyes.

Ears
 Clear external auditory canals. Pinnae shape and contour was
normal. No pre-auricular pits or skin tags. No erythema or bulging.
Nose
 Normal pink mucosa, no discharge or blood visible. Normal
midline septum.
Mouth
 Moist mucous membrane.
Pharynx
 Unable to visualise tonsils. Pharynx shows no erythema or
ulcerations.
Neck

15
  Grossly non-swollen. No tracheal deviation. No decrease in ROM.
No lymphadenopathy, goitre or masses detected.
Chest
 No increase of accessory muscles (no evidence of increased work
of breathing).
Lungs
 Lungs are clear to auscultation bilaterally. No stridor, wheezes,
crackles or rubs.
 Good air movement.
Cor
 Normal S1-S2 rate and rhythm. No murmurs, gallops or rubs.
Abdomen
 Soft, non-tender, non-distended. Bowel signs present. No noted
splenomegaly. No masses.
Extremities
Warm, no cyanosis or oedema. No gross deformities. Good skin turgor
with no tenting.
Iron Deficiency Anemia
Urinary Tract Infection
A
Normal Growth development
Good nutritional state
- IVFD D5 ½ NS 7 tpm
- Trf PRC 224 cc ( 100cc/day)
P - Inj Lasix 5mg (while tranfussion)
- Paracetamol 4 x 0,8cc
- Apialys drop 1 x 0,5cc

16
Oct 25th 2018, Fourth day of admission, 6th day of illness
Liquid defecation 1 time, greenish, acidic smell
S
Cough (+)
Consciousness : Compos Mentis
General condition : Midly ill
Temperature : 36.7 °C
Pulse :116 x/min
Respiratory rate : 24 x/min
Head
 Normocephalic, atraumatic with thin hair. Anterior fontanelle
measured 2 cm x 1.5 cm, soft and flat within normal pulsation.
Eyes
 Pupils equal, round and reactive to light. Extraocular muscle
appeared intact but the patient was too young to cooperate with the
examination. No discharges, conjunctivitis or scleral icterus. No
ptosis. Pallor were not detected for both eyes.

Ears
 Clear external auditory canals. Pinnae shape and contour was
normal. No pre-auricular pits or skin tags. No erythema or bulging.
Nose
 Normal pink mucosa, no discharge or blood visible. Normal
midline septum.
Mouth
 Moist mucous membrane.
Pharynx
 Unable to visualise tonsils. Pharynx shows no erythema or
ulcerations.
Neck
 Grossly non-swollen. No tracheal deviation. No decrease in ROM.
No lymphadenopathy, goitre or masses detected.
Chest

17
  No increase of accessory muscles (no evidence of increased work
of breathing).
Lungs
 Lungs are clear to auscultation bilaterally. No stridor, wheezes,
crackles or rubs.
 Good air movement.
Cor
 Normal S1-S2 rate and rhythm. No murmurs, gallops or rubs.
Abdomen
 Soft, non-tender, non-distended. Bowel signs present. No noted
splenomegaly. No masses.
Extremities
Warm, no cyanosis or oedema. No gross deformities. Good skin turgor
with no tenting.
Iron Deficiency Anemia
Urinary Tract Infection
A
Normal Growth development
Good nutritional state
- IVFD D5 ½ NS 7 tpm
- Paracetamol 4 x 0,8cc
P
- Apialys drop 1 x 0,5cc
- Dexamethason 2 mg

18
Oct 26th 2018, Fifth day of admission, 7th day of illness
Liquid defecation (-)
S
Cough (+)
Consciousness : Compos Mentis
General condition : Midly ill
Temperature : 36.7 °C
Pulse :116 x/min
Respiratory rate : 24 x/min
Head
 Normocephalic, atraumatic with thin hair. Anterior fontanelle
measured 2 cm x 1.5 cm, soft and flat within normal pulsation.
Eyes
 Pupils equal, round and reactive to light. Extraocular muscle
appeared intact but the patient was too young to cooperate with the
examination. No discharges, conjunctivitis or scleral icterus. No
ptosis. Pallor were not detected for both eyes.

Ears
 Clear external auditory canals. Pinnae shape and contour was
normal. No pre-auricular pits or skin tags. No erythema or bulging.
Nose
 Normal pink mucosa, no discharge or blood visible. Normal
midline septum.
Mouth
 Moist mucous membrane.
Pharynx
 Unable to visualise tonsils. Pharynx shows no erythema or
ulcerations.
Neck
 Grossly non-swollen. No tracheal deviation. No decrease in ROM.
No lymphadenopathy, goitre or masses detected.
Chest

19
  No increase of accessory muscles (no evidence of increased work
of breathing).
Lungs
 Lungs are clear to auscultation bilaterally. No stridor, wheezes,
crackles or rubs.
 Good air movement.
Cor
 Normal S1-S2 rate and rhythm. No murmurs, gallops or rubs.
Abdomen
 Soft, non-tender, non-distended. Bowel signs present. No noted
splenomegaly. No masses.
Extremities
Warm, no cyanosis or oedema. No gross deformities. Good skin turgor
with no tenting.
Iron Deficiency Anemia
Urinary Tract Infection
A
Normal Growth development
Good nutritional state
- IVFD D5 ½ NS 7 tpm
- Paracetamol 4 x 0,8cc
P
- Apialys drop 1 x 0,5cc
- Dexamethason 2 mg

20
 LITERATURE REVIEW
IRON-DEFICIENCY ANEMIA

Iron deficiency is the most widespread and common nutritional disorder in the world. It is
estimated that 30% of the global population suffers from iron-deficiency anemia, and most of
them live in developing countries. In the USA, 9% of children ages 12-36 months are iron
deficient, and 30% of this group have progressed to iron-deficiency anemia.

The incidence of iron-deficiency relates to basic aspects of iron metabolism and nutrition.
The body of a full-term newborn infant contains about 0.5 g of iron, compared to 5 g of iron in
adults. This change in quantity of iron from birth to adulthood means that an average of 0.8 mg
of iron, must be absorbed each day during the first 15 years of life. A small additional amount is
necessary to balance normal losses of iron by shedding of cells. It is therefore necessary to absorb
approximately 1 mg daily to maintain positive iron balance in childhood. Because <10% of
dietary iron usually is absorbed, a dietary intake of 8-10 mg of iron daily is necessary to maintain
iron levels.

During infancy, when growth is most rapid, the approximately 1 mg/L of iron in bovine
and breast milk makes it difficult to maintain body iron. Breast-fed infants have an advantage
because they absorb iron 2-3 times more efficiently than infants fed bovine milk.

DEFINITION
Anemia (pronounced /əˈniːmiə/, also spelled anaemia or anæmia; from Ancient Greek ἀναιμία
anaimia, meaning "lack of blood") is a decrease in normal number of red blood cells (RBCs) or
less than the normal quantity of haemoglobin in the blood. However, it can include decreased
oxygen-binding ability of each haemoglobin molecule due to deformity or lack in numerical
development as in some other types of haemoglobin deficiency.

ETIOLOGY
Most iron in neonates is in circulating haemoglobin. As the relatively high haemoglobin
concentration of the newborn infant falls during the first 2-3 months of life, considerable iron is
reclaimed and stored. These reclaimed stores usually are sufficient for blood formation in the
first 6-9 months of life in term infants. Stores are depleted sooner in low birthweight infants with
perinatal blood loss because their iron stores are smaller. Delayed clamping of the umbilical cord
can improve iron status and reduce the risk of iron deficiency.

21
Dietary source of irons is especially important in these infants. In term infants, anemia caused
solely by inadequate dietary iron usually occurs at 9-24 months of age and is relatively
uncommon thereafter. The usual dietary pattern observed in infants and toddlers with nutritional
iron-deficiency anemia in developed countries in excessive consumption of bovine milk (low
iron content, blood loss from milk protein colitis) is a child who is often overweight. Worldwide,
undernutrition is usually responsible for iron deficiency.
Blood loss must be considered as a possible cause in every case of iron deficiency anemia,
particularly in older children. Chronic iron deficiency anemia from occult bleeding may be
caused by a lesion of the gastrointestinal (GI) tract, such as peptic ulcer, Meckel diverticulum,
polyp, hemangioma, or inflammatory bowel disease. Infants can have chronic intestinal blood
loss induced by exposure to a heat-labile protein in whole bovine milk. This GI reaction is not
related to enzymatic abnormalities in the mucosa, such as lactase deficiency, or to a typical milk
allergy.
Involved infants characteristically develop anemia that is more severe and occurs earlier than
would be expected simply from an inadequate intake of iron. The ongoing loss of blood in the
stools can be prevented either by breast-feeding or by delaying the introduction of whole bovine
milk in the first year of life and then limiting the quantity of whole bovine milk to <24 oz/24 hr.
Unrecognised blood loss also can be associated with chronic diarrhoea and rarely with
pulmonary hemosiderosis. In developing countries, infections with hookworm, Trichuris
trichuria, Plasmodium, and Helicobacter pylori often contribute to iron deficiency.
About 2% of adolescent girls have iron-deficiency anemia, due in large part to their adolescent
growth spurt and menstrual blood loss. The highest risk of iron deficiency is among teenagers
who are or have been pregnant; 30% of these girls have iron-deficiency anemia.

EPIDEMIOLOGY
In 2010, global anemia prevalence was 32·9% (ie, more than 2·2 billion people were affected);
iron deficiency was the most common cause. WHO estimated that, between 1993 and 2005,
worldwide prevalence of anemia was 24∙8% in the general population—from 12∙7% in men to
47∙4% in children aged 0–5 years. Prevalence was 30∙2% in women, and 41∙8% in pregnancy.
23∙9% of people older than 60 years were anemic. Between 1995 and 2011, worldwide
prevalence of anemia decreased by 4–5% in children aged 0–5 years, non-pregnant women, and
pregnant women aged 15–49 years. Prevalence of anemia varies hugely around the world.

Iron deficiency is the most common nutritional deficiency, but robust, population-based studies

22
are few. Thus, in US studies prevalence of iron deficiency ranges from 4∙5% to 18∙0%. But at a
global level, the lowest burden of anemia associated with iron deficiency was noted in the USA
and Canada (2·9% of envelope). In several regions—including central Asia (64·7%), south Asia
(54·8%), and Andean Latin America (62·3%)—a very high proportion of the anemia burden was
caused by iron deficiency.

Data for the epidemiology of iron deficiency anemia are unreliable, especially because anemia
is often ascribed to iron deficiency, irrespective of its cause (table 1). WHO estimates that 50%
of cases worldwide are due to iron deficiency, but regional and subgroup disparities exist. In two
studies from the past 3 years, prevalence of iron deficiency anemia was roughly 20%.

In North America and Europe, iron deficiency is most common in women of childbearing age
and as a manifestation of hemorrhage. Iron deficiency caused solely by diet is uncommon in
adults in countries where meat is an important part of the diet. Depending upon the criteria used
for the diagnosis of iron deficiency, approximately 4-8% of premenopausal women are iron
deficient. In men and postmenopausal women, iron deficiency is uncommon in the absence of
bleeding.

International statistics
A study of national primary care database for Italy, Belgium, Germany, and Spain determined
that annual incidence rates of iron deficiency anemia ranged from 7.2 to 13.96 per 1,000 person-
years. Higher rates were found in females, younger and older persons, patients with
gastrointestinal diseases, pregnant women and women with a history of menometrorhagia, and
users of aspirin and/or antacids.

In countries where little meat is in the diet, iron deficiency anemia is 6-8 times more prevalent
than in North America and Europe. This occurs despite consumption of a diet that contains an
equivalent amount of total dietary iron; the reason is that heme iron is absorbed better from the
diet than non-heme iron. In studies of children and adolescents from Sudan and Nepal, iron
deficiency anemia was found in as many as two thirds of subjects. In certain geographic areas,
intestinal parasites, particularly hookworm, worsen the iron deficiency because of blood loss
from the GI tract. Anemia is more profound among children and premenopausal women in these
environs.

23
Age-related demographics
Healthy newborn infants have a total body iron of 250 mg (80 ppm), which is obtained from
maternal sources. This decreases to approximately 60 ppm in the first 6 months of life, while the
baby consumes an iron-deficient milk diet. Infants consuming cow milk have a greater incidence
of iron deficiency because bovine milk has a higher concentration of calcium, which competes
with iron for absorption. Subsequently, growing children must obtain approximately 0.5 mg
more iron daily than is lost in order to maintain a normal body concentration of 60 ppm.

During adult life, equilibrium between body loss and gain is maintained. Children are more likely
to develop iron deficiency anemia. In certain geographic areas, hookworm adds to the problem.
Children are more likely to walk in soil without shoes and develop heavy infestations.
During childbearing years, women have a high incidence of iron deficiency anemia because of
iron losses sustained with pregnancies and menses.

Gastrointestinal neoplasms become increasingly more prevalent with each decade of life. They
frequently present with GI bleeding that may remain occult for long intervals before it is
detected. Usually, bleeding from neoplasms in other organs is not occult, prompting the patient
to seek medical attention before developing severe iron depletion. Investigate the etiology of the
iron deficiency anemia to evaluate for a neoplasm.

Sex-related demographics
An adult male absorbs and loses about 1 mg of iron from a diet containing 10-20 mg daily.
During childbearing years, an adult female loses an average of 2 mg of iron daily and must
absorb a similar quantity of iron in order to maintain equilibrium. Because the average woman
eats less than the average man does, she must be more than twice as efficient in absorbing dietary
iron in order to maintain equilibrium and avoid developing iron deficiency anemia.

Healthy males lose body iron in sloughed epithelium, in secretions from the skin and gut lining,
and from small daily losses of blood from the GI tract (0.7 mL daily). Cumulatively, this amounts
to 1 mg of iron. Males with severe siderosis from blood transfusions can lose a maximum of 4
mg daily via these routes without additional blood loss.

A woman loses about 500 mg of iron with each pregnancy. Menstrual losses are highly variable,
ranging from 10 to 250 mL (4-100 mg of iron) per period. These iron losses in women double

24
their need to absorb iron in comparison to males. A special effort should be made to identify and
treat iron deficiency during pregnancy and early childhood because of the effects of severe iron
deficiency upon learning capability, growth, and development.
Race-related demographics
Race probably has no significant effect upon the occurrence of iron deficiency anemia; however,
because diet and socioeconomic factors play a role in the prevalence of iron deficiency, it more
frequently is observed in people of various racial backgrounds living in poorer areas of the world.

PATHOPHYSIOLOGY
Iron metabolism and homeostasis - Iron in the form of heme is vital to many metabolic
functions including oxygen transportation in hemoglobin. Iron is also a component of multiple
enzymes, including cytochromes, necessary for energy generation and drug metabolism.
Through the donation or acceptance of an electron, iron exists in either a reduced ferrous (Fe2+)
or an oxidative ferric (Fe3+) state. The majority of functional iron is contained in hemoglobin,
with smaller quantities found in myoglobin and cytochromes.

The liver, which is the site of production of iron transport proteins, contains the largest non-
functional iron stores either as ferritin or hemosiderin. Ferritin is both diffuse and soluble, and
is the primary iron storage protein. Hemosiderin is similar in structure, but has more iron relative
to protein and is insoluble. Iron is also stored in reticuloendothelial cells of the bone marrow and
spleen, but is not commonly stored in the bone marrow of cats.

Dietary iron is absorbed mainly in the duodenum. Only ferrous iron is absorbed, and it is
transported across the apical membrane of the enterocyte by divalent metal transporter 1. It is
then transferred across the enterocyte to the basolateral membrane by an unknown mechanism.
Iron is exported across the basolateral membrane of enterocytes by ferroportin, then bound to
transferrin in the plasma and transported for use in target organs and/or storage.

Body stores of iron are tightly regulated to provide adequate iron for cellular needs without
developing toxicity from excess. Because the body lacks a mechanism to excrete excessive iron,
homeostasis is tightly controlled by limiting enteric iron uptake through impaired efflux from
enterocytes. Iron efflux is regulated by hepcidin, a recently discovered hormone produced by
hepatocytes.

25
When iron stores are adequate or high, hepcidin is released and binds to intestinal ferroportin
causing internalization and destruction of ferroportin. The reduction in ferroportin causes
absorbed dietary iron to remain in the enterocyte, where it is lost by enterocyte shedding.
Conversely, when iron stores are low, hepcidin production and secretion are suppressed,
increasing iron efflux from enterocytes into the blood (Figure 1).

Tight homeostasis of iron is critical, as excessive iron accumulation in hepatocytes can cause
pathologic damage, termed hemochromatosis. Subsequently, increased fibrosis and cirrhosis can
occur. In contrast, iron deficiency leads to depletion of body iron stores, and ultimately, iron
deficiency anemia and other metabolic dysfunctions. The duodenum’s ability to absorb dietary
iron is very limited, but can be upregulated. However, the upregulation in iron absorption
secondary to chronic blood loss and resulting iron deficiency may be insufficient to restore
adequate iron homeostasis, even after blood loss has been arrested.

Pathophysiology - Iron is an essential component of haemoglobin in red blood cells and of

myoglobin in muscles, which contain around 60% of total body iron. It is also necessary for the
functioning of various cellular mechanisms, including enzymatic processes, DNA synthesis, and
mitochondrial energy generation. In adults, the body contains 3–5 g of iron; 20–25 mg is needed
daily for production of red blood cells and cellular metabolism. Because dietary intake is limited
(1–2 mg per day), other sources are needed for iron homoeostasis—eg, recycling of ageing

26
erythrocytes in macrophages, exchange of iron in iron-containing enzymes, and iron stores.
About 1–2 mg of iron is lost daily as a result of menstrual bleeding, sweating, skin desquamation,
and urinary excretion. Because iron does not have an excretion regulation pathway, dietary
intake, intestinal absorption, and iron recycling have to be finely regulated.

Dietary iron is available in two forms: haem and non-haem iron. Iron is complexed as Fe2+
(ferrous iron) in haemoglobin in the haem form, which is present in animal food sources, such

as meat, poultry, and seafood. Non-haem iron (Fe3+ or ferric iron) is present in the vegetarian
diet (black tea, cacao, cereals, dried fruit, etc). Haem iron is estimated to contribute 10–15% of
total iron intake in meat-eating populations, but because it is generally better absorbed—with a
rate of absorption estimated at 15–35%—than non-haem iron, it can account for more than 40%
of total absorbed iron.

In iron homoeostasis, a small peptide called hepcidin, which is mainly secreted by hepatocytes
and was first described in 2001 in mice with iron overload, has a crucial role in the control of
iron availability to tissues. Outside the liver, other cell types and organs, such as macrophages,
adipocytes, the heart, and the kidneys, can produce hepcidin. In plasma, hepcidin is bound to α2-
macroglobulin and albumin, and can be cleared via the kidney. The main role of hepcidin is to
control surface expression of FPN1 by binding to the protein, which is then internalised and
degraded by lysosomes. FPN1 is the only known iron-exporting protein, so after its degradation
enterocytes, macrophages, and hepatocytes can no longer export iron, which is sequestrated in
these cells.

High expression of hepcidin decreases plasma iron concentrations; low expression increases
concentrations. Hepcidin expression is upregulated by high concentrations of iron in the liver
and plasma, inflammation, and physical activity whereas it is downregulated by iron deficiency,
erythropoiesis, hypoxia, and endocrine signals (testosterone, oestrogen, and growth factors). A
new hormone called erythroferrone was identified in 2014. It is produced by erythroblasts in
response to erythropoietin, and mediates hepcidin suppression during stress erythropoiesis.

Iron deficiency anemia may be classified into 3 stages: storage iron deficiency, iron deficient
erythropoiesis, and iron deficiency anemia. Initially during blood loss, iron body stores are
preferentially utilized for accelerated erythropoiesis. After depletion of body iron stores,
erythropoiesis and production of other iron-containing proteins (such as myoglobin) become
limited, leading to an overt iron deficiency anemia. Anemia is exacerbated as iron-deficient

27
erythrocytes have a shortened survival due to their fragility, which accelerates
reticuloendothelial cell sequestration and destruction. The observed erythrocyte morphologic
changes with the underlying iron deficiency reflect the severely hampered hemoglobin synthesis
and are characterized by hypochromasia and microcytosis. Furthermore, the hemoglobin-
deficient erythroid precursors are thought to undergo additional mitoses while attempting to
achieve ideal cytoplasmic hemoglobin levels, thereby exaggerating the microcytosis.

While normocytic normochromic erythrocytes contain approximately 1/3 hemoglobin, red blood
cell indices of animals with iron deficiency anemia demonstrate progressive decreases in mean
corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular
volume. Early iron deficiency states may not be suspected as the anemia may be initially
normocytic and normochromic. However, evaluation of the erythrogram and reticulocyte count,
along with novel parameters such as reticulocyte hemoglobin content, may provide an earlier
indication of iron deficiency anemia once these assays are available in canine and feline
commercial laboratories. Initially, reticulocytosis is present due to increased production and
release of reticulocytes secondary to anemia. However, as iron stores are depleted and the iron
deficiency becomes more severe, the absolute reticulocyte count becomes inadequate for the
degree of anemia. Furthermore, due to the lack of heme and reduced hemoglobin synthesis, the
red blood cells become more fragile which can result in mild hemolysis, worsening the anemia.

Disease states with functional iron deficiency can occur when iron is not available for heme
synthesis despite normal to increased body stores of iron. One example is anemia of
inflammatory disease, which can be mistaken for iron deficiency anemia based on the
hemogram. In this condition, serum iron levels are decreased secondary to iron sequestration in
the liver, spleen, and bone marrow, which results in a functional iron deficiency, defective heme
synthesis, and the formation of some microcytic and possibly hypochromic erythrocytes despite
adequate body iron stores. Animals with chronic renal disease develop anemia, which is most
commonly normocytic, normochromic, and non-regenerative. This anemia is mostly due to
decreased renal erythropoietin synthesis, but chronic low-grade gastrointestinal hemorrhage
with loss of iron and anemia of inflammatory disease can also contribute. Following treatment
with recombinant human erythropoietin, the iron reserves can become limited and thus impair
erythropoietin-induced erythropoiesis. Microcytosis, hypochromasia, and low serum iron
concentrations have been reported in dogs with congenital portosystemic shunts but no other
hepatic diseases. The pathogenesis of this apparent functional iron deficiency is not well

28
understood, but thought likely to be a direct consequence of the portosystemic shunt as these
features normalize following surgical intervention. Rare genetic defects in ferroportin and
hepcidin regulation have been reported to cause iron refractory iron deficiency anemia in humans
but these have not been reported in animals. However, a single currently unpublished case of
iron refractory iron deficiency anemia in a cocker spaniel has recently been identified by the
authors involving a defect in the hepcidin regulator.

CLINICAL MANIFESTATION
Patients with iron deficiency anaemia can present with symptoms that are associated with all
anaemias, which are sometimes associated with specific signs due to iron deficiency. Pallor of
the skin, conjunctivae, and nail beds are common. The diagnostic usefulness of these signs is
increased when clinicians can ascertain whether their presence is a change from normal in the
patient. Other symptoms and signs result from hypoxic functioning: fatigue, exertional dyspnoea
progressing to breathlessness at rest, vertigo, syncope, headache, tachycardia, and a cardiac
systolic flow murmur.

29
In severe cases patients might have dyspnoea at rest, angina pectoris, and haemodynamic
instability. Clinical features of iron deficiency anaemia depend on the severity of the anaemia,
age, comorbidities, and chronicity and speed of onset. In some cases, anaemia is asymptomatic
and diagnosed only after laboratory measurement of haemoglobin concentrations.

Iron deficiency especially affects epithelial cells with a rapid turnover, causing dryness and
roughness of the skin, dry and damaged hair, diffuse and moderate alopecia, and koilonychia
(spoon-shaped finger nails). Loss of tongue papillae occurs in patients with mild-to-moderate
iron deficiency and is a good gauge of length of deficiency.

Atrophic glossitis is noted in severe cases. Iron deficiency has been reported to be associated
with restless legs syndrome. However, in a meta-analysis evidence was insufficient to determine
whether iron therapy is beneficial for restless legs syndrome.

Whatever its cause, anaemia can negatively affect physical performance, particularly work
productivity, in adults, as a result of both the reduced oxygen transport associated with anaemia
and the reduced cellular oxidative capacity associated with iron deficiency. In a 2013 systematic
review, a positive association was noted in older people (aged ≥65 years) between anaemia and
global cognitive decline and incidence of dementia. Perinatal iron deficiency is associated with
delayed neurocognitive development and psychiatric illness. Even after iron repletion in infancy,
cognitive abnormalities can persist at age 10 years.

DIAGNOSTIC APPROACH

The diagnostic approach to iron deficiency anemia includes identifying the underlying disease
or trigger with a thorough history, physical examination, and diagnostic evaluation. The history
should include a thorough review of medications, diet, concurrent medical conditions, fecal
characteristics, flea and tick exposure, and careful questioning of the owner for possible sources
of blood loss.

Minimum diagnostics, such as fecal examination for color and endoparasites, microscopic blood
smear evaluation, packed cell volume, and total protein may be sufficient in juvenile anemic
animals with suspected ectoparasite and/or endoparasite infestation. However, in many cases,
further diagnostic evaluation is necessary, including complete blood (cell) count (CBC) with
reticulocyte count, fecal occult blood test, serum iron parameters, coagulation parameters,

30
biochemical profile (including albumin, globulins, and hepatic and renal parameters), urinalysis
and abdominal imaging. Animals with chronic blood loss frequently have a marked reactive
thrombocytosis which may exceed; the mechanism causing the thrombocytosis is still
undetermined. Furthermore, decreased neutrophil production due to iron deficiency may lead to
neutropenia; the mechanism for this is also unknown.

If melena or hematochezia is not evident and no blood loss can be identified, fecal occult blood
tests should be performed. Various commercial tests are available to detect occult blood in feces

31
that may not be visible on visual inspection. However false positive results are possible with oral
iron supplementation, meat diets, and much less likely with commercial animal diets due to the
presence of dietary myoglobin, hemoglobin, or plant peroxidases. Withdrawal of iron
supplementation and meat-based diet for 3 d may be required to accurately interpret results.
Fecal occult blood test may also be negative if gastrointestinal hemorrhage occurs intermittently.
Thus, repeated testing and color assessment by the owner are indicated in cases with elusive iron
deficiency anemia. In some cases, the serum total protein values are also low due to the
concomitant loss of plasma.

Iron status is further investigated by measuring serum iron parameters. Typically, serum iron
concentration is very low in animals with iron deficiency anemia. However, mildly low to low
normal serum iron values can also be observed with anemia of inflammatory disease. Serum iron
can be transiently elevated by intravascular red blood cell lysis, recent blood transfusion, and
iron supplementation, which can complicate interpretation of laboratory data. Exogenously
administered corticosteroids have also been shown to increase serum iron levels by an
undetermined mechanism.

The total iron binding capacity (TIBC) is a measure of the plasma’s ability to carry iron and
represents the maximum concentration of iron that can be bound by plasma transferrin. This test
is often performed as part of an iron panel, but is of limited clinical value in small animals, as it
does not assess serum or tissue iron levels and does not change dramatically in disease. Iron
saturation (IS) reflects the amount of iron bound to transferrin and is low (20%) in cases of iron

32
deficiency anemia. Finally, the unsaturated iron binding capacity (UIBC) measures transferrin’s
open iron binding sites and is elevated in iron deficiency anemia.

Ferritin can be detected in serum and correlates well with body iron stores. However, the assay
for ferritin is species-specific and therefore not widely available. Ferritin is decreased with iron
deficiency anemia and is increased with elevated total body stores of iron. Ferritin is also an
acute phase protein, and hyperferritinemia can occur with underlying disease, such as
inflammatory disease, neoplasia, liver disease, or hemolytic disease. Nevertheless, low serum
ferritin concentrations can be helpful in differentiating iron deficiency anemia from anemia of
inflammatory disease.

Body iron stores can be qualitatively assessed by staining aspirates, impression smears, or biopsy
sections of liver, spleen or bone marrow (or both) with Prussian blue stain. Iron con- centration
can be quantified in biopsied tissues such as liver and spleen. These methods are invasive and
usually not performed in cases of known iron deficiency anemia. If iron is visualized in these
samples, iron deficiency can be ruled out. It should, however, be noted that healthy, non-anemic
cats with adequate iron homeostasis normally lack stainable iron in their bone marrow.

33
Diagnostic imaging may be warranted to further investigate iron deficiency anemia. Abdominal
ultrasonography is recommended to visualize abdominal organs and to assess the gastro
intestinal tract for evidence of ulceration, wall thickening, or masses. Examples of typical
gastrointestinal tumors that can cause ulceration and chronic blood loss include leiomyoma,
leiomyosarcoma, carcinoma, and round cell tumors. If primary gastrointestinal disease is
suspected, and no abnormalities are noted with abdominal imaging, gastroduodenal or colonic
endoscopy (or both), or exploratory laparotomy may be indicated to assess for ulceration and to
obtain biopsies.

THERAPEUTIC APPROACH

Initial Evaluation - Most infants and children with mild anemia do not exhibit overt clinical
signs and symptoms. Initial evaluation should include a thorough history, such as questions to
determine prematurity, low birth weight, diet, chronic diseases, family history of anemia, and
ethnic background. A complete blood count is the most common initial diagnostic test used to
evaluate for anemia, and it allows for differentiating microcytic, normocytic, and macrocytic
anemia based on the mean corpuscular volume.

Diagnosis of iron deficiency anemia - Microcytic anemia due to iron deficiency is the most
common type of anemia in children. The U.S. prevalence of iron deficiency anemia in children
one to twelve years of age is estimated to be 1% to 2%. A child with microcytic anemia and a
history of poor dietary iron intake should receive a trial of iron supplementation and dietary
counseling. Iron deficiency anemia is likely if the hemoglobin level increases by more than 1.0
g per dL (10 g per L) after one month of presumptive treatment.

Although iron deficiency anemia is usually microcytic, some patients may have normocytic red
blood cells. Further testing may also be necessary if suspected iron deficiency anemia does not
respond to treatment. Ferritin measurement is the most sensitive test for diagnosing iron
deficiency anemia. Ferritin is a good reflection of total iron storage and is also the first laboratory
index to decline with iron deficiency. It may be less accurate in children with infectious or
inflammatory conditions because ferritin is also an acute phase reactant.

34
An elevated red blood cell distribution width index can also be a sensitive test to differentiate
iron deficiency anemia from other types of microcytic anemia if ferritin and iron studies are not
available.

35
The general principles of treating animals with iron deficiency anemia include preventing further
blood loss, correcting the anemia if severe, initiating iron supplementation, and addressing the
underlying disease. Animals with severe anemia may not show significant clinical signs but may
rapidly decompensate shortly after presentation in the clinic, thus they should be handled
carefully.

A blood transfusion may be necessary prior to receiving results from diagnostic evaluation if the
animal is severely anemic and demonstrating signs of hypoxemia. Blood samples for CBC, and
ideally serum biochemical profile, coagulation profile, and iron parameters should be obtained
prior to the administration of a blood transfusion. Ideally stored compatible packed red blood
cell products are slowly administered but fresh or stored whole blood may also be slowly
transfused. Fluid overload secondary to rapid or overzealous blood transfusion or intravenous
fluid administration can readily occur in these animals as they are usually normovolemic or even
hypervolemic. This is in contrast to patients with acute to peracute blood loss anemia, where
fluid resuscitation is appropriate.

Transfusion with red blood cell products addresses the anemia and provides an excellent source
of bioavailable iron. There is no specific transfusion trigger and in comparison, to many other
causes of anemia, iron deficient animals tolerate even severe anemia well unless challenged or
stressed. Thus, blood transfusions are only indicated in cases of severe anemia with resulting
tissue hypoxia, to stabilize a decompensated patient, or prior to performing general anesthesia
and surgery on an animal with moderate to severe anemia. The amount of packed red blood cells
transfused may be calculated as:

volume to be transfused (mL) = desired packed cell volume (PCV) increase x body weight
(kg) x 2
with an approximate target packed cell volume of 20%. Blood transfusions bear inherent risks
including acute hemolytic and hypersensitivity reactions, hemolysis, infectious disease trans-
mission, and volume overload. Prior to a first transfusion, dog erythrocyte antigen (DEA) 1.1 or
AB blood typing should be performed in dogs and cats, respectively, and appropriate blood type
compatible donors should be selected. If the animal has previously been transfused, a major and
minor blood crossmatch test should also be performed to assure blood compatibility. There are
no specific guidelines that indicate when a transfusion is appropriate; clinical and laboratory
assessments of the patient are used to make that decision.

36
Iron supplementation is generally needed to restore iron homeostasis and should be based on the
degree of anemia, underlying pathology, red blood cell count, serum iron panel, and erythrocyte
morphology. These same parameters are used to monitor further iron supplementation needs.
Supplemental iron is beneficial in treating iron deficiency anemia but is not recommended for
other forms of anemia and in fact may be harmful, as iron overload may occur. Iron can be
delivered to animals through supplemental iron products administered either orally or
parenterally, including blood transfusions.

In stable patients, oral iron therapy is usually preferred over parenteral iron administration in
small animals due to its low cost and higher safety. Both ferrous and ferric forms are available
but only the ferrous form is recommended due to superior absorption. Ferrous sulfate is used
most frequently but ferrous gluconate and fumarate can also be used. Care must be taken when
determining the dosage to be administered, as published doses are expressed as either milligrams
of iron salt or elemental iron.

Ferrous sulfate can be administered at a dose of 15 mg iron salt per kg body weight (5 mg
elemental iron per kg) divided every 8 to 12 h. One of the more common side effects of oral iron
supplementation is gastrointestinal irritation, which can be minimized by dividing the dose
several times a day. Interaction with other drugs is recognized and should be avoided. For
instance, iron can bind tetracycline and other drugs thereby decreasing the efficacy of both; these
and other drugs should be administered several hours apart if given concurrently. Moreover, the
bioavailability of iron is decreased if administered concurrently with antacids, eggs, or milk.

Parenteral forms of iron other than red blood cell products can be administered if oral
supplementation causes side effects, is ineffective due to malabsorption, if the animal is
vomiting, or if compliance is poor. A single dose of iron can also be administered parenterally

37
prior to initiation of oral supplementation. Iron dextran is absorbed primarily by the lymphatic
system following intramuscular administration, and approximately 70% of the iron is absorbed
from the injection site within days.

Iron dextran can be given at a dose of 10 mg elemental iron per kg body weight weekly to dogs,
and at a dose of 50 mg per cat once every 3 to 4 wk. A small dose should be administered first
as hypersensitivity reactions can occur. Other side effects of intramuscular iron include irritation
and pain at the injection site.

Several months of iron supplementation may be necessary for red blood cell parameters to return
to normal, and therapy should be continued beyond normalization of red blood cell parameters
as body iron stores take much longer to be replenished. While serum iron would be expected to
be normal or even high when being actively supplemented with iron, red blood cell indices
should be monitored closely to gauge response to therapy and resolution of functional iron
deficiency. Body iron stores are rarely assessed post-treatment, but measurement of serum
ferritin and other iron parameters is warranted after termination of iron supplementation to
ensure normalization.

PREVENTION APPROACH

During Pregnancy and Delivery. Up to 42% of pregnant women worldwide will have anemia,
with a prevalence of 6% in North America. The iron requirement increases with each trimester
and should be supported by higher maternal iron intake. Between 60% and 80% of the iron
storage in a newborn occurs during the third trimester, but it is unclear whether treatment of

38
maternal anemia prevents anemia in newborns and infants. The USPSTF found insufficient
evidence to recommend screening for or treating iron deficiency anemia in pregnant women to
improve maternal or neo- natal outcomes. Although two Cochrane reviews found that maternal
hemoglobin levels improve with antepartum iron supplementation, studies have not
demonstrated statistically significant benefits in clinical outcomes (e.g., low birth weight,
preterm birth, infection, postpartum hemorrhage) for mothers or newborns.

Delayed umbilical cord clamping (approximately 120 to 180 seconds after delivery) is associated
with improved iron status (ferritin levels) at two to six months of age. This benefit may be
especially important in those vulnerable to iron deficiency, such as infants who were premature
or small for gestational age. A Cochrane review looking at the effects of the timing of cord
clamping during preterm births showed a reduction of blood transfusions when clamping was
delayed (24% vs. 36%). The effects of delayed cord clamping do not appear to persist beyond
the first 12 months.

Iron Supplementation During Infancy. Iron is the most common single-nutrient deficiency.
Preterm infants (born at less than 37 weeks’ gestation) who are exclusively breast-fed should
receive 2 mg per kg per day of elemental iron supplementation from one to 12 months of age,
except for those who have had multiple blood transfusions. In healthy full-term infants, iron
storage from in utero is adequate for the first four to six months of life. The AAP recommends
that full-term, exclusively breastfed infants start 1 mg per kg per day of elemental iron
supplementation at four months of age until appropriate iron-containing foods are introduced.
Formula-fed infants often receive adequate amounts of iron (average formula contains 10 to 12
mg per L of iron) and thus rarely require further supplementation.

Ideally, the estimated 7-mg daily iron requirement for children one to three years of age should
be met through consumption of iron-rich foods. Consumption of large quantities of non–iron-
fortified cow’s milk increases the risk of iron deficiency. Although iron supplementation may
achieve more significant improvements in hemoglobin concentration, children are more likely
to tolerate iron-fortified foods, if achieving daily iron supplementation is difficult, intermittent
iron supplementation still improves hemoglobin concentration and reduces the risk of iron
deficiency.

39
40
 LITERATURE REVIEW
URINARY TRACT INFECTION

DEFINITION
A urinary tract infection (UTI) is a common type of infection that occurs in the urinary
tract which includes the kidneys, the ureters, the bladder and the urethra. The symptoms of a
UTI include pain or a burning sensation during urination (dysuria), a frequent need to urinate,
and lower abdominal pain.

PREVALENCE AND ETIOLOGY

Urinary tract infections occur in 1 – 3% of girls and 1 % of boys. In girls, the first UTI
usually occurs by the age of 5 yr, with peaks during infancy and toilet training. In boys, most
UTIs occur during first year of life. The prevalence of UTIs varies with age. During the first year
of life, the male : female ratio is 2.8 – 5.4 : 1. Beyond 1 – 2 yr, there is a female preponderance,
with a male : female ratio of 1 : 10.
UTIs are caused mainly by colonic bacteria. In girls, 75 – 90% of all infections are
caused by Escherichia coli, followed by Klebsiella spp and Proteus spp. Some series report that
in boys > 1 yr of age, Proteus is as common a cause as E.coli; others report a preponderance of
gram-positive organisms in boys. Staphylococcus saprophyticus and enterococcus are pathogens
in both sexes. Adenovirus and other viral infections also can occur, especially as a cause of
cystitis.
Historically, UTIs have been considered a risk factor for the development of renal
insufficiency or end-stage renal disease in children. Some researchers have questioned the
importance of UTI as a risk factor, because only 2% of children with renal insufficiency report
a history of UTI. This paradox may be secondary to better recognition of the risks of UTI and
prompt diagnosis and therapy. Furthermore, many children receive antibiotics for fever without
a focus resulting in a partially treated UTI.

PATHOGENESIS AND PATHOLOGY

Most UTIs are ascending infections. The bacteria arise from the fecal flora, colonize
the perineum, and enter the bladder via the urethra. In uncircumcised boys, the bacterial
pathogens arise from the flora beneath the prepuce. In some cases, the bacteria causing cystitis

41
ascend to the kidney to cause pyelonephritis. Rarely, renal infection occurs by haematogenous
spread, as in endocarditis or in some neonates.
If bacteria ascend from the bladder to the kidney, acute pyelonephritis can occur.
Normally the simple and compound papillae in the kidney have an anti-reflux mechanism that
prevents urine in the renal pelvis from entering the collecting tubules. However, some compound
papillae, typically in the upper and lower poles of the kidney, allow intrarenal reflux. Infected
urine then stimulates an immunologic and inflammatory response. The result can cause renal
injury and scarring. Children of any age with a febrile UTI can have UTI can have acute
pyelonephritis and subsequent renal scarring, but the risk is highest in those <2 years of age.
In girls, UTIs often occur at the onset of toilet training because voiding dysfunction that
occurs at that age. The child is trying to retain urine to stay dry, yet the bladder may have
uninhibited contractions forcing urine out. The result may be high-pressure, turbulent urine flow
or incomplete bladder emptying, both of which increase the likehood of bacteria. Voiding
dysfunction can occur in the toilet-trained child who voids infrequently. Similar problems can
arise in school-age children who refuse to use the school bathroom. Obstructive uropathy
resulting in hydronephrosis increases the risk of UTI because of urinary stasis. Urethral
catheterization for urine output monitoring or during a voiding cystourethrogram or non-sterile
catheterization can infect the bladder with a pathogen. Constipation with fecal impaction can
increase the risk of UTI because it can cause voiding dysfunction.
The pathogenesis of UTI is based in part on the presence of bacterial pili or fimbriae on
the bacterial surface. There are two types of fimbriae, type I and type II. Type I fimbriae are
found on most strains of E. coli. Because attachment to target cells can be blocked by d-mannose,
these fimbriae are referred to as man- nose-sensitive. They have no role in pyelonephritis. The
attachment of type II fimbriae is not inhibited by mannose, and these are known as mannose-
resistant. These fimbriae are expressed by only certain strains of E. coli. The receptor for type
II fimbriae is a glycosphingolipid that is present on both the uroepithelial cell membrane and red
blood cells. The Gal 1-4 Gal oligosaccharide fraction is the specific receptor. Because these
fimbriae can agglutinate by P blood group erythrocytes, they are known as P fimbriae. Bacteria
with P fimbriae are more likely to cause pyelonephritis. Between 76-94% of pyelonephritogenic
strains of E. coli have P fimbriae, compared with 19-23% of cystitis strains. Other host factors
for UTI include anatomic abnormalities precluding normal micturition, such as a labial adhesion.

This lesion acts as a barrier and causes vaginal voiding. A neuropathic bladder can
predispose to UTIs if there is incomplete bladder emptying and/or detrusor-sphincter dys-

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synergia. Sexual activity is associated with UTIs in girls, in part because of incomplete bladder
emptying. From 4-7% of pregnant women have asymptomatic bacteriuria, which can develop
into a symptomatic UTI. The incidence of UTI in infants who are breast-fed is lower than in
those fed with formula.

CLINICAL MANIFESTATION
The 3 basic forms of UTI are pyelonephritis, cystitis, and asymptomatic bacteriuria. Focal
pyelonephritis (nephronia) and renal abscesses are less common.

Clinical pyelonephritis is characterized by any or all of the following: abdominal, back, or flank
pain; fever; malaise; nausea; vomiting; and, occasionally, diarrhea. Fever may be the only
manifestation. Newborns can show nonspecific symptoms such as poor feeding, irritability,
jaundice, and weight loss. Pyelonephritis is the most common serious bacterial infection in
infants <24 mo of age who have fever without an obvious focus. These symptoms are an
indication that there is bacterial involvement of the upper urinary tract. Involvement of the renal
parenchyma is termed acute pyelonephritis, whereas if there is no parenchymal involvement, the
condition may be termed pyelitis. Acute pyelonephritis can result in renal injury, termed pyelone-
phritic scarring.

Acute lobar nephronia (acute lobar nephritis) is a renal mass caused by acute focal infection
without liquefaction. It may be an early stage in the development of a renal abscess.
Manifestations are identical to pyelonephritis; renal imaging demonstrates the abnormality.
Renal abscess can occur following a pyelonephritic infection due to the usual uropathogens or
may be secondary to a primary bacteremia (S. aureus). Perinephric abscess can occur secondary
to contiguous infection in the perirenal area (e.g., vertebral osteomyelitis, psoas abscess) or
pyelonephritis that dissects to the renal capsule.

Xanthogranulomatous pyelonephritis is a rare type of renal infection characterized by

granulomatous inflammation with giant cells and foamy histiocytes. It can manifest clinically as
a renal mass or an acute or chronic infection. Renal calculi, obstruction, and infection with
Proteus spp or E. coli contribute to the development of this lesion, which usually requires total
or partial nephrectomy.

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DIAGNOSIS

UTI may be suspected based on symptoms or findings on urinalysis, or both; a urine culture is
necessary for confirmation and appropriate therapy. There are several ways to obtain a urine
sample; some are more accurate than others. In toilet-trained children, a midstream urine sample
usually is satisfactory; the introitus should be cleaned before obtaining the specimen. In
uncircumcised boys, the prepuce must be retracted; if the prepuce is not retractable, a voided
sample may be unreliable and contaminated with skin flora. In children who are not toilet trained,
a catheterized urine sample should be obtained. Alternatively, the application of an adhesive,
sealed, sterile collection bag after disinfection of the skin of the genitals can be useful only if the
culture is negative or if a single uropathogen is identified. However, a positive culture can result
from skin contamination, particularly in girls and uncircumcised boys. If treatment is planned
immediately after obtaining the urine culture, a bagged specimen should not be the method
because of a high rate of contamination often with mixed organisms. A suprapubic aspirate
generally is unnecessary.

Pyuria (leukocytes in the urine) suggests infection, but infection can occur in the absence of
pyuria; this finding is more confirmatory than diagnostic. Conversely, pyuria can be present
without UTI.

Sterile pyuria (positive leukocytes, negative culture) occurs in partially treated bacterial UTIs,
viral infections, renal tuberculosis, renal abscess, UTI in the presence of urinary obstruction,
urethritis due to a sexually transmitted infection (STI), inflammation near the ureter or bladder
(appendicitis, Crohn disease), and interstitial nephritis (eosinophils). Nitrites and leukocyte
esterase usually are positive in infected urine. Microscopic hematuria is common in acute
cystitis, but microhematuria alone does not suggest UTI. White blood cell casts in the urinary
sediment suggest renal involvement, but in practice these are rarely seen. If the child is
asymptomatic and the urinalysis result is normal, it is unlikely that there is a UTI. However, if
the child is symptomatic, a UTI is possible, even if the urinalysis result is negative.

Prompt plating of the urine sample for culture is important, because if the urine sits at room
temperature for more than 60 min, overgrowth of a minor contaminant can suggest a UTI when
the urine might not be infected. Refrigeration is a reliable method of storing the urine until it can
be cultured.

If the culture shows >100,000 colonies of a single pathogen, or if there are 10,000 colonies and

44
the child is symptomatic, the child is considered to have a UTI. In a bag sample, if the urinalysis
result is positive, the patient is symptomatic, and there is a single organism cultured with a
colony count >100,000, there is a presumed UTI. If any of these criteria are not met, confirmation
of infection with a catheterized sample is recommended.

With acute renal infection, leukocytosis, neutrophilia, and elevated serum erythrocyte
sedimentation rate and C-reactive protein are common. The latter 2 are nonspecific markers of
bacterial infection, and their elevation does not prove that the child has acute pyelonephritis.

With a renal abscess, the white blood cell count is markedly elevated to >20,000-25,000/mm3.
Because sepsis is common in pyelonephritis, particularly in infants and in any child with
obstructive uropathy, blood cultures should be considered before starting antibiotics if possible.

History and physical examination – Clinical signs and symptoms of a UTI depend on the age
of the child. Newborns with UTI may present with jaundice, sepsis, failure to thrive, vomiting,
or fever. In infants and young children, typical signs and symptoms include fever, strong-
smelling urine, hematuria, abdominal or flank pain, and new-onset urinary incontinence. School-
aged children may have symptoms similar to adults, including dysuria, frequency, or urgency.
Boys are at increased risk of UTI if younger than six months, or if younger than 12 months and
uncircumcised. Girls are generally at an increased risk of UTI, particularly if younger than one
year. Physical examination findings can be nonspecific but may include suprapubic tenderness
or costovertebral angle tenderness.

Diagnostic tests – Dipstick tests for UTI include leukocyte esterase, nitrite, blood, and protein.
Leukocyte esterase is the most sensitive single test in children with a suspected UTI. The test
for nitrite is more specific but less sensitive. A negative leukocyte esterase result greatly reduces

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the likelihood of UTI, whereas a positive nitrite result makes it much more likely; the converse
is not true, however. Dipstick tests for blood and protein have poor sensitivity and specificity in
the detection of UTI and may be misleading. Accuracy of positive findings is as follows
(assumes a 10 percent pretest probability):

 Nitrite: 53 percent sensitivity, 98 percent specificity, 75 percent probability of UTI.

 Bacteria on microscopy: 81 percent sensitivity, 83 percent specificity, 35 percent
probability of UTI.
 Leukocytes on microscopy: 73 percent sensitivity, 81 percent specificity, 30 percent
probability of UTI.
 Leukocyte esterase: 83 percent sensitivity, 78 percent specificity, 30 percent probability
of UTI.
 Leukocyte esterase or nitrite: 93 percent sensitivity, 72 percent specificity, 27 percent
probability of UTI.
 Blood: 47 percent sensitivity, 78 percent specificity, 19 percent probability of UTI.
 Protein: 50 percent sensitivity, 76 percent specificity, 19 percent probability of UTI.

All febrile children between two and 24 months of age with no obvious cause of infection should
be evaluated for UTI, with the exception of circumcised boys older than 12 months. Older
children should be evaluated if the clinical presentation points toward a urinary source. The
National Institute for Health and Clinical Excellence in the United Kingdom endorses
incorporating specific strategies for urine testing based on the child’s age. In this model,
microscopy and urine culture should be performed in children younger than three years instead
of dipstick testing.

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The presence of pyuria of at least 10 white blood cells per high-power field and bacteriuria are
recommended as the criteria for diagnosing UTI with microscopy. In young children, urine
samples collected with a bag are unreliable compared with samples collected with a catheter.

Therefore, in a child who is unable to provide a clean-catch specimen, catheterization should be

considered. If urine cannot be cultured within four hours of collection, the sample should be
refrigerated. Imaging procedures with the highest ratings from the American College of
Radiology Appropriateness Criteria for further evaluation of select children with UTIs are renal
and bladder ultrasonography, radionuclide cystography or voiding cystourethrography, and renal
cortical scan. Renal and bladder ultrasonography is effective for evaluating anatomy, but is
unreliable for detecting vesicoureteral reflux.

Radionuclide cystography or voiding cystourethrography is effective for screening and grading

vesicoureteral reflux, but involves radiation exposure and catheterization. Although voiding
cystourethrography is suggested for either girls or boys, radionuclide cystography is suggested
only for girls because voiding cystourethrography is needed for adequate anatomic imaging of

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the urethra and bladder in boys. A renal cortical scan (also called scintigraphy or DMSA scan)
uses technetium and is effective for assessing renal scarring, but requires intravenous injection
of radioisotope.

DIFFERENTIAL DIAGNOSIS

Although fever may be the sole presenting symptom in children younger than 24 months,
physical examination findings may point toward an alternative diagnosis, including otitis media,
gastroenteritis, or upper respiratory tract infection. Occult bacteremia should always be
considered, although the probability of this diagnosis is much lower than UTI (less than 1 versus
7 percent) in fully immunized children with no other identifiable potential source for fever on
physical examination. Urinary calculi, urethritis (including a sexually transmitted infection),
dysfunctional elimination, and diabetes mellitus must be considered in verbal children with
urinary tract problems.

TREATMENT

Although amoxicillin has traditionally been a first-line antibiotic for UTI, increased rates of E.
coli resistance have made it a less acceptable choice, and studies have found higher cure rates
with trimethoprim/sulfamethoxazole (Bactrim, Septra). Other choices include
amoxicillin/clavulanate (Augmentin) or cephalosporins, such as cefixime (Suprax),
cefpodoxime, cefprozil (Cefzil), or cephalexin (Ke ex).

When the presenting symptoms are non-specific for a UTI or the urine dipstick test is non-
diagnostic, there may be a delay in treatment while culture results are pending. Parents can be
reassured that antibiotics initiated 24 hours after the onset of fever are not associated with a
higher risk of parenchymal defects than immediate antibiotics in children younger than two
years. However, delaying antibiotics by four days or more may increase the risk of renal scarring.

Fluoroquinolones are not usually used in children because of potential concerns about sustained
injury to developing joints, although there is no compelling evidence supporting the occurrence
of this phenomenon. Fluoroquinolones may be useful when infection is caused by multidrug-
resistant pathogens for which there is no safe and effective alternative, parenteral therapy is not
feasible, and no other effective oral agent is available.

Guidelines from the American Academy of Pediatrics recommend limiting fluoroquinolone

therapy to patients with UTIs caused by Pseudomonas aeruginosa or other multidrug-resistant,

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gram-negative bacteria. Ciprofloxacin (Cipro) is approved by the U.S. Food and Drug
Administration for complicated UTIs and pyelonephritis attributable to E. coli in patients one to
17 years of age.

PREVENTION

In an observational study of otherwise healthy children with a first UTI, antibiotic prophylaxis
was not associated with a reduced risk of recurrent UTI and increased the risk of treatment-
resistant pathogens. A randomized controlled trial of children two months to seven years of age
found that prophylactic antibiotics for 12 months following a febrile UTI did not reduce the risk
of subsequent UTI, even in children with mild to moderate vesicoureteral reflux.

Another randomized controlled trial of children and adolescents with pyelonephritis found that
antibiotic prophylaxis did not prevent subsequent UTIs in patients with no documented
vesicoureteral reflux or with mild to moderate vesicoureteral reflux. Antibiotic prophylaxis may
be more beneficial in children with more severe vesicoureteral reflux, however. The most recent
Cochrane review on the subject concluded that large, properly randomized, double-blind studies
are needed to determine the effectiveness of long-term antibiotics for the prevention of UTI in
susceptible children. Additionally, continuous antibiotic prophylaxis in children younger than
two and a half years with vesicoureteral reflux may not decrease the risk of pyelonephritis or
renal damage.

Constipation should be addressed in infants and children who have had a UTI to help prevent
subsequent infections. There is some evidence that cranberry juice decreases symptomatic UTIs
over 12-months, particularly in women with recurrent UTIs. The effectiveness of cranberry juice

49
in children is less certain, and the high dropout rate in studies indicates that cranberry juice may
not be acceptable for long-term prevention. A systematic review concluded that routine
circumcision in boys does not reduce the risk of UTI enough to justify the risk of surgical
complications.

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 BIBLIOGRAPHY

 Anthony L, Patrice C, Macdougal C, Lauren PB,et al. Iron Deficiency Anemia. The
Lancet. 2015 Aug. 6736 (15):1-10.
 Mary Wang MD, et al. Iron Deficiency and Other Types of Anemia in Infants and
Children. American Academy of Family Physician. 2016 Feb. Vol 93(4): 270-8.
 Robert DB, Frank R, et al. Clinical Report: Diagnosis and Prevention in Iron Deficiency
and Iron Deficiency Anemia in Infants and Young Children (0-3 years of age). 2018
April. Vol 126 (5): 1040-50.
 Manfred N, Igor T, Dominik W, Gunter W, et al. Iron Deficiency or Anemia of
Inflammation: Differential and Diagnosis. Wien Med Worchenschr. 2016 Aug. Vol 166:
411-23.
 Naveed A, Aamir I, Tariq R, Zujaja H, et al. Diagnostic Accuracy of Serum Iron and
Total Iron Binding Capacity (TIBC) in Iron Deficiency State. Journal of the College of
Physicians and Surgeons Pakistan. 2016. Vol.26 (12) 958-61.
 Jacquelyn M, George R, et al. Effect of Low Dose Ferrous Sulfate vs Iron Polysaccharide
Complex on Hemoglobin Concentration in Young Children with Nutritional Iron
Deficiency Anemia: A Randomized Clinical Trial. American Medical Association. 2017
June.Vol.317 (22): 2297-305.
 Jian S, Lei Z, Shanshan L, Hongting L, et al. Effect of Dietary Intervention Treatment
on Children with Iron Deficiency Anemia in China: A Meta-Analysis. Lipids in Health
and Disease. 2018 Jan. Vol.17:108.
 Mark H, Christopher C, Alastair H, et al. Diagnosis of Urinary Tract Infection in
Children. American Academy of Family Physicians. 2018. Vol.97 (4).
 Sherry R, Hans P, et al. Urinary Tract Infection in Children. Current Medicine Group.
2011. Vol.9: 165-71.
 Brett White, et al. Diagnosis and Treatment of Urinary Tract Infections in Children.
American Academy of Family Physicians. 2011 Feb. Vol.83 (4): 409-15.

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