Introduction to Paediatric Pathology

Question 1

List the pathogenetic mechanisms leading to paediatric pathologies.

Answer 1

(a) Defects of pregenesis — intrinsic defects within gametes, aneuploidy [atypical number of chromosomes]
(b) Defects of blastogenesis — mutations, teratogens, infections [usually severe]
(c) Defects of organogenesis — mutations, teratogens, infections, physical factors
(d) Defects of phenogenesis — mutations, teratogens, infections, physical factors

Further notes:
👶 Defects of organogenesis are abnormalities that occur during the formation and development of organs in the embryonic stage. They typically occur during the first trimester of pregnancy when the major organs are forming. Examples: congenital heart defects, neural tube defects, limb malformations.

👶 Defects of phenogenesis are abnormalities that occur during the differentiation and growth of tissues and organs after the initial formation.
They occur later in pregnancy, during the fetal period, when organs and tissues are maturing and growing.

Question 2

Briefly discuss causes of defects of pregenesis.

Answer 2

👶 Defects of spermatogenesis e.g. low sperm count, poor motility, or abnormal morphology affect fertility.
👶 Defects of oogenesis may result in aneuploidy, leading to conditions like Down syndrome.
👶 Fertilization defects e.g. fertilization by more than one sperm can result in an abnormal zygote with extra sets of chromosomes, usually leading to early embryonic loss.
👶 Cleavage Abnormalities: Irregularities in the initial cell divisions can result in uneven cell sizes or failed implantation.
👶 Genetic Mutations: Inherited or spontaneous mutations can disrupt normal development.
👶 Environmental factors like radiation, toxins, and infections can interfere with early embryonic development.

Further notes:
Pregenesis refers to the early stages of embryonic development, including gametogenesis, fertilization, and the initial stages of cell division.

Question 3

Aneuploidy and disruptions result in defects of blastogenesis and phenogenesis. What are causes of disruptions?

Answer 3

(a) Problems with vascular development
(b) Anoxia (lack of oxygen)
(c) Infection
(d) Radiation
(e) Amniotic entanglement
(f) Teratogenic drugs

Question 4

What is spontaneous abortion?

Answer 4

Spontaneous abortion refers to the natural loss of a pregnancy before the fetus is viable (able to survive outside the womb). It’s estimated to affect 70-80% of all pregnancies.

Question 5

What are the stages of pregnancy loss before recognition?

Answer 5

👶 Before implantation: Approximately 30% of pregnancies are lost before the embryo implants in the uterus.

👶 After implantation but before recognition: Another 30% of pregnancies are lost after implantation but before the mother realizes she is pregnant.

Question 6

What is the difference between early and late spontaneous abortion?

Answer 6

👶 Early spontaneous abortion: Pregnancy loss in the embryonic period (first 8 weeks).

👶 Late spontaneous abortion: Pregnancy loss between 9-18 weeks.

Question 7

List causes of abortion.

Answer 7

👶 Aneuploidy/Polyploidy: abnormal number of chromosomes or multiple sets of chromosomes
👶 Infections
👶 Luteal phase deficiency: This is a condition where the luteal phase of the menstrual cycle is shorter than normal, leading to insufficient production of progesterone, which is crucial for maintaining pregnancy.
👶 Thrombophilias: These are disorders that increase the risk of blood clots, which can affect the placenta and lead to pregnancy loss.
👶 Anomalies of uterine development: Structural abnormalities in the uterus can interfere with the implantation and growth of the embryo.
👶 Poor maternal nutrition: Deficiencies in essential nutrients like zinc and folate can impact fetal development and increase the risk of abortion.
👶 Increasing maternal age: As maternal age increases, the risk of chromosomal abnormalities and other complications that can lead to pregnancy loss also increases.

Question 8

Growth Disorganisation (GD) describes various stages of developmental abnormalities in embryos. Briefly describe each of the four stages of Growth Disorganisation.

Answer 8

👶 GD 1: An intact chorionic sac with no evidence of an embryo. [Compare Image 1 (abnormal) with Image 2 normal.]

👶 GD 2: A chorionic sac with an embryo (1-4 mm) that has no recognizable external features and lacks retinal pigment.

👶 GD 3: Elongated, smooth embryos (less than 10 mm) without distinct morphological hallmarks but with retinal pigment.

👶 GD 4: An embryo with recognizable head, trunk, and limb buds, but with severe developmental inconsistencies.

Question 9

Discuss conditions that may result in late spontaneous abortions.

Answer 9

(1) Neural tube defects: These are severe birth defects of the brain and spine that occur when the neural tube does not close properly during early pregnancy.

(2) Amnion rupture sequence: This is a rare condition where the amniotic sac ruptures early in pregnancy, leading to complex fetal anomalies.

(3) Posterior cervical cystic hygroma: This is a fluid-filled sac that forms on a baby’s neck due to a blockage in the lymphatic system. It can be associated with genetic conditions and can lead to complications. [Image 1] [Image 2]

Question 10

Molar pregnancies are a type of gestational trophoblastic disease. Compare complete and incomplete molar pregnancies.

Answer 10

👶 Complete Hydatidiform Mole
A complete hydatidiform mole occurs when an egg that has lost its genetic material is fertilized by one or two sperm. As a result, all the genetic material comes from the father. This leads to the formation of abnormal placental tissue that swells and forms fluid-filled cysts, resembling a cluster of grapes. In this type of molar pregnancy, there is no fetus.
[Image 1] [Image 2] [Image 3] [Image 4]

👶 Partial Hydatidiform Mole
A partial hydatidiform mole happens when an egg is fertilized by two sperm, resulting in an embryo with an extra set of chromosomes (69 instead of the normal 46). This leads to the development of both normal and abnormal placental tissue. There may be a fetus, but it is typically malformed and cannot survive.
[Image 5] [Image 6] [Image 7] [Image 8]

Further notes:
[6-minute video]: Normal Histology of the Placenta

Question 11

List five types of developmental defects.

Answer 11

(1) Malformations: A structural defect resulting from an intrinsic problem during embryonic development, caused by failure of embryonic cell proliferation and/or differentiation.

(2) Disruptions: Structural anomalies caused by extrinsic factors that interfere with normal development. Example: amniotic band syndrome, where bands of amniotic tissue constrict parts of the fetus.

(3) Dysplasias: Abnormal cellular organization leading to structural anomalies.

(4) Deformations: Structural anomalies caused by mechanical forces. Example: clubfoot, where the position of the fetus in the womb causes abnormal foot positioning.

(5) Sequences: a series of developmental anomalies that result from a single initial defect or mechanical factor. Example: Potter sequence - oligohydramnios results in compression of the fetus, leading to facial deformities, limb contractures and underdeveloped lungs.

Question 12

List physical agents that can be teratogenic.

Answer 12

Radiation, hypoxia, hyperthermia, mechanical forces, environmental pollutants

Question 13

List infectious agents that can be teratogenic.

Answer 13

👶 rubella
👶 HHV [6, 7]
👶 Zika Virus
👶 parvovirus
👶 syphillis
👶 toxoplasmosis

Question 14

List heavy metals that can be teratogenic.

Answer 14

lead, methylmercury, lithium, cadmium, arsenic, chromium

Question 15

List maternal diseases that can be teratogenic.

Answer 15

diabetes, starvation, myasthenia gravis, endocrinopathies, systemic lupus erythematosus (SLE)

Question 16

List drugs that can be teratogenic.

Answer 16

cannabis, alcohol, heroin, cocaine, antineoplastics, cigarette smoking, anticonvulsants, antihypertensives, caffeine

Question 17

Vascular disruptions during intrauterine development will result in developmental defects. Outline various mechanisms of vascular disruptions.

Answer 17

(1) Disruption of embryonic capillary plexus: This occurs during the early stages of embryonic development and can lead to the early amnion disruption sequence. The capillary plexus is a network of small vessels that form in early development.

(2) Persistence of embryonic vessels: Normally, certain embryonic vessels regress as development progresses. However, if these vessels persist, it can lead to limb abnormalities such as clubfoot. This persistence can interfere with normal limb development and function.

(3) Premature ablation of embryonic vessels: This refers to the early loss of blood vessels that are supposed to persist longer during development. Premature ablation can result in conditions like horseshoe kidney and Poland sequence, where there is an abnormal fusion or development of organs.

(4) Failure of maturation of vessels: When blood vessels fail to mature properly, it can lead to conditions such as capillary hemangioma and Berry aneurysms. These conditions are characterized by abnormal blood vessel growth and can lead to various complications.

(5) Occlusion (external compression) of vessels: This occurs when blood vessels are compressed by external factors, such as amniotic bands, a bicornuate uterus, or fibroids. This compression can restrict blood flow and lead to conditions like amniotic band syndrome, where limbs or other body parts are constricted and malformed

Question 19

Compare symmetric Fetal Growth Restriction (FGR) and asymmetric FGR using the following criteria:
(a) onset
(b) etiology
(c) pathophysiology

Answer 19

(a) onset
👶 symmetric: early in utero
👶 asymmetric: later onset

(b) etiology
👶 symmetric: congenital infections, genetic disorders
👶 asymmetric: utero-placental insufficiency, maternal malnutriiton, hypertension

(c) pathophysiology
👶 symmetric: impaired cell division, decreased cell number, irreversible
👶 asymmetric: impaired cellular hypertrophy, decreased cell size, reversible

Question 20

Compare symmetric Fetal Growth Restriction (FGR) [type 1] and asymmetric FGR [type 2] using the following criteria:
(a) clinical features
(b) prognosis

Answer 20

(a) clinical features
symmetric: inadequate growth of head and body, head:abdomen ratio may be normal
asymmetric: brain is spared, therefore head:abdomen ratio is increased
[Diagram]

(b) prognosis
symmetric: poor prognosis
asymmetric: more favourable prognosis

Question 21

What is fetal hydrops?

Answer 21

Fetal hydrops, also known as hydrops fetalis, is a serious condition characterized by abnormal accumulation of fluid in two or more fetal compartments, such as the skin, abdomen, chest, or around the heart or lungs. [This condition can be life-threatening and is typically a symptom of an underlying issue rather than a disease itself.]

Question 22

State are two types of fetal hydrops and state the causes of each.

Answer 22

(a) Immune hydrops: Occurs when there is an incompatibility between the blood types of the mother and fetus, such as Rh incompatibility. The mother’s immune system attacks the fetal red blood cells, leading to severe anemia and fluid accumulation. This type is less common today due to preventive treatments.

(b) Non-immune hydrops:
👶 severe anemia (e.g. thalassemia)
👶 infections e.g. Parvovirus B19, Cytomegalovirus
👶 heart or lung defects
👶 chromosomal abnormalities (e.g., Turner syndrome, Down syndrome)
👶 metabolic disorders
👶 vascular malformations

Hydrops fetalis gallery: [Image 1] [Image 2] [Image 3]