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Gynecology Medical Knowledge Readiness

Scientific Affairs – Sylvia AzizCycle Meeting December 2016

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By the End of this Training You should be able to :• Explain Iron absorption physiology and regulation• Define IDA and it’s etiology and complications • Explain the relation between Preeclampsia and oxidative stress . • Understand lipid peroxidation.• Explain Preterm Delivery and what risks lead to this.• Know Bacterial infections from E.Coli , Shigella , Salmonella , H.Pylori • Understand Giardia Colonization• Understand Infertility Problems and IVF • Understand Apoptosis and breast cancer• Explain what is Lactoferrin and what are its’ major roles

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Iron absorption physiology and regulation

4https://www.youtube.com/watch?v=ahCy97FVUpM&t=3s

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IDA and it’s etiology and complications 

Iron-deficiency anemia

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• Is anemia caused by a lack of iron. • RBCs tend to be microcytic and hypochromic, and iron

stores are low as shown by low serum ferritin and low serum iron levels with high serum total iron binding capacity.

Table 1: Recommended Dietary Allowances (RDAs) for Iron

Age Male Female Pregnancy Lactation

Birth to 6 months 0.27 mg* 0.27 mg*    

7–12 months 11 mg 11 mg    

1–3 years 7 mg 7 mg    

4–8 years 10 mg 10 mg    

9–13 years 8 mg 8 mg    

14–18 years 11 mg 15 mg 27 mg 10 mg

19–50 years 8 mg 18 mg 27 mg 9 mg

51+ years 8 mg 8 mg    7

1-Parasitic disease• Helminthiasis caused by infestation with parasitic worms

(helminths) such as tapeworms, flukes, and roundworms).• The World Health Organization estimates that

"approximately two billion people are infected with soil-transmitted helminths worldwide.

• Parasitic worms cause both inflammation and chronic blood loss.

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Causes of iron deficiency anemia

Causes of iron deficiency anemia

2-Blood loss• Women with menorrhagia (heavy menstrual periods). • Peptic ulcer, angiodysplasia, a colon polyp or

gastrointestinal cancer.• Gastrointestinal bleeding can result from regular use of

some groups of medication.

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3-Diet• Examples of iron-rich foods include meat, eggs, leafy

green vegetables and iron-fortified foods.

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4-Iron absorption• Inflammatory bowel disease.• Post surgical resection.• If there is an insufficient production of hydrochloric acid in

the stomach, often due to chronic H. pylori infections or long-term proton pump inhibitor therapy. Ferrous and Ferric iron salts will precipitate out of solution in the bowel which are poorly absorbed.

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3-Iron absorption• In cases where systemic inflammation is present, iron will

be absorbed into enterocytes, but due to the reduction in basolateral ferroportin molecules which allow iron to pass into the systemic circulation, iron is trapped in the enterocytes and is lost from the body when the enterocytes are sloughed off. Depending on the disease state, one or more mechanisms may occur.

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5-PregnancyWithout iron supplementation, iron deficiency anemia occurs in many pregnant women because their iron stores need to serve their own increased blood volume as well as be a source of hemoglobin for the growing fetus, and for placental development.

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WHO definition Of Anaemia in Pregnancy• For diagnosis of anaemia in Pregnancy when HB concentration is < 11 gm%

( 7.45mmol/ L)and a haematocrit of < 0.33. • Mild------------ 8 – 10 gm % • Moderate ---- 5 –< 8 gm %• Severe---------- < 5 gm % During Pregnancy there is increase in total blood volume (1500 ml = 30 - 40%), plasma

volume(250 ml = 40-50 %) as well as the EBC volume (350ml = 20 -30 % ) also , But increment in plasma volume is more than the increased total hemoglobin(15-20 % ).

Hence there is dilution of blood, resulting in physiological anaemia( upper limit for normal / 100% Hb level in pregnancy is brought down to 11gm % ) .

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Complications in Pregnancy• Hb < 6 g/dL may cause:

– Reduced amniotic fluid volume– Fetal cerebral vasodilation.– Nonreassuring FHR patterns. – Increased risks of:

• Prematurity• Spontaneous abortion• Low birth weight• Fetal death• Maternal mortality.

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The relation between Preeclampsia and oxidative stress

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Iron leads to formation of Free radicals

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Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, often the kidneys. Preeclampsia usually begins after 20 weeks of pregnancy in a woman whose blood pressure had been normal. Even a slight rise in blood pressure may be a sign of preeclampsia.Left untreated, preeclampsia can lead to serious — even fatal — complications for both the mother and her baby. If she has preeclampsia, the only cure is delivery of her baby.

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Lipid Peroxidation

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Preterm Delivery and what risks lead to it

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Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age. These babies are known as preemies or premmies.  Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes or the leaking of fluid from the vagina.  Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems, and sight problems. `

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Bacterial Infections from E.Coli , Shigella , Salmonella , H.Pylori

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Salmonella species are facultative intracellular pathogens. Many infections are due to ingestion of contaminated food. Salmonella serovars can be divided into two main groups—typhoidal and non typhoidal Salmonella. Non typhoidal serovars are more common, and usually cause self-limiting gastrointestinal disease.

Shigella  is one of the leading bacterial causes of diarrhea worldwide

Most E. coli strains do not cause disease, but virulent strains can cause gastroenteritis, urinary tract infections, and neonatal meningitis.

Helicobacter pylori  found usually in the stomach. It was present in a person with chronic gastritis and gastric ulcers, conditions not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer

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Giardia Colonization

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Giardiasis is a major diarrheal disease found throughout the world. The flagellate protozoan Giardia intestinalis  (previously known as G lamblia), its causative agent, is the most commonly identified intestinal parasite in the United States and the most common protozoal intestinal parasite isolated worldwide.  Infection is more common in children than in adults. G intestinalis can cause asymptomatic colonization or acute or chronic diarrheal illness. It is a common cause of chronic diarrhea and growth retardation in children in developing countries.

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Infertility and IVF

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IVF : In vitro Fertilization

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Sperm Capacitation

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Apoptosis and Necrosis

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Lactoferrin structure and roles

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What is Lactoferrin ?

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30% Fe+3 iron saturation 70% unsaturated

The most crucial part of mechanism of action

Glycoprotein similar structurally and chemically to serum transferrin but

with affinity to iron 300 times higher

Highly abundant in colostrum and milk, but is also present in other extracellular excretions

Lactoferrin contains 2 high affinity binding sites for iron.

The red spheres denote ferric ions (Fe3+).

The N-terminal moietyof lactoferrinis of particular

affinity for the anti-microbial and

immune-modulating actions of lactoferrin.

It is involved in several physiological functions, related to:

Iron binding Immunity

Regulation of iron absorption in the bowel

1. Immune response

2. Antioxidant, anticarcinogenic and anti-inflammatory properties

3. Protection against microbial infection, which is the most widely studied function to date.

Regulation of iron absorption in the bowel

• LF plays a key role in maintaining iron levels in the body (demonstrated in several studies).

• Several decades ago it was shown that breast-fed infants have no iron deficiencies.

• supporting the involvement of LF in this function is the discovery of LF receptors in the enterocytes of various species.

Gram-negative bacteria• LF damages the external membrane of Gram -ve bacteria

through interaction with lipopolysaccharide (LPS):-

– the interaction between LPS and the bacterial cations (Ca2+ and Mg2+) inhibited by +ve charged LF, causing a release of LPS from the cell wall and increase the membrane permeability.

– The interaction of LF and LPS also potentiates the action of natural antibacterials such as lysozyme,which is secreted from the mucosa at elevated concentrations along with LF.

Gram positive bacteria

• LF’s mechanism of action against Gram +ve bacteria is based on binding:-

• due to its net +ve charge to anionic molecules on the bacterial surface, resulting in a reduction of -ve charge on the cell wall and thus favouring contact between lysozyme and the cell membrane.